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 PRACTICAL HORMONE THERAPY 
 
 UNIVERSITY OF CALIFORNIA 
 
 CALIFORNIA COLLEGE OF MEDICINE 
 
 LIBRARY 
 
 OCT ^ y iy/0 
 
 IRVINE, CALIFORNIA 92664
 
 PRACTICAL 
 HORMONE THERAPY 
 
 A MANUAL OF ORGANOTHERAPY 
 FOR GENERAL PRACTITIONERS 
 
 \ 
 
 ,, \) BY 
 
 HENRY R. HARROWER. M.D. 
 
 SOMETIME PROFESSOR OF CLINICAL DIAGNOSIS, LOYOLA UNIVERSITY, CHICAGO ; 
 
 FELLOW OF THE ROYAL SOCIETY OF MEDICINE; FELLOW OF 
 
 THE AMERICAN MEDICAL ASSOCIATION 
 
 WITH FOREWORD BY 
 
 PROFESSOR DR. ARTUR BIEDL 
 
 LONDON 
 
 BAILLIERE, TINDALL AND COX 
 
 8, HENRIETTA STREET, COVENT GARDEN 
 
 1914 
 
 [Ai! rights reserved]

 
 FOREWORD 
 
 My dear Colleague, — 
 
 I feel greatly honoured in being asked to write a 
 few words of introduction to your book, " Practical 
 Hormone Therapy " 
 
 On looking through the proof sheets, I was at once 
 struck with the excellent manner in which you had 
 succeeded in laying before your readers this new branch 
 of therapeutics in a concise and easily understood form. 
 
 Hormone Therapy, although its beginnings can be 
 traced back to ancient times, is actually a most recent 
 acquisition, a practical deduction from that new sphere 
 of biological inquiry which is concerned with the Theory 
 of Internal Secretions. 
 
 Smce I have myself worked on this subject, and have 
 endeavoured to give a clear and concise account of its 
 present state m my own book, you will readily understand 
 that I am perhaps somewhat prejudiced in its favour 
 when I emphasize the importance of internal secretions 
 for the purpose of obtainmg a correct insight into the 
 normal and pathological processes. Medical practitioners 
 will have to decide finally whether the deductions drawn 
 from our theoretical observations can be tm-ned to
 
 vi Foreword 
 
 good account in the diagnosis of diverse complicated 
 pathological conditions, and whether they can be reduced 
 to rational therapeutic methods. 
 
 You have now placed in their hands a guide which 
 will enable them to collaborate with us in workmg out 
 this problem. All those concerned, whether theorists or 
 medical practitioners, will be grateful to you for your 
 labours. 
 
 Allow me, my dear colleague, to congratulate you on 
 your work, and to sign myself, 
 
 Yours very truly, 
 
 PEOFESSOR DR. ARTUR BIEDL. 
 Prague, 
 
 May, 1914.
 
 CONTENTS 
 
 PAGE 
 
 FOREWORD --.... V 
 
 INTRODUCTION - - - - - ix 
 
 SECTION A 
 PRELIMINARY CONSIDERATIONS 
 
 CHAPTER 
 
 I. HORMONES: THEIR DISCOVERT, [PRODUCTION, AND 
 
 ACTION ...... 1 
 
 II. THE FUNDAMENTAL PRINCIPLES OF HORMONE 
 
 THERAPY - - - . . - 18 
 
 III. THE HORMONE BALANCE . - - - 28 
 
 SECTION B 
 THE HORMONES OF THE DIGESTIVE SYSTEM 
 
 IV. DO THE SALIVARY GLANDS PRODUCE A HORMONE J - 49 
 
 V. THE SECRETINS AND PTLORO-DUODENAL EXTRACTS - 54 
 
 VI. OTHER EXTRACTS OF ALIMENTARY ORIGIN - - 82 
 
 VII. THE PANCREAS AND ITS HORMONE - - - 91 
 
 VIII. THE INFLUENCE OF THE PANCREAS AND EXTRACTS 
 
 THEREOF ON RESISTANCE TO INFECTION . .112 
 
 IX. THE FUNCTION OF THE SPLEEN AND THE VALUE OF 
 
 ITS EXTRACTS - - - . .121 
 
 X. THE PERISTALTIC HORMONE OF ZUELZER . . 144 
 
 XI. THE VALUE OF LIVER EXTRACTS - . - 155 
 
 XII. THE THERAPEUTICS OF BILE PREPARATIONS - 171 
 
 SECTION C 
 THE METABOLIC GLANDS 
 
 XIII. THE THYROID GLAND AND THE TREATMENT OP ITS 
 
 INSUFFICIENCIES ..... 180 
 
 XIV. THE CURATIVE PROPERTIES OF PARATHYROID EX- 
 
 TRACTS ---... 215 
 
 XV. THE THYMUS ..... 232 
 
 XVI. RENAL OPOTHERAPr ..... 244 
 
 XVII. ARE THE TONSILS ENDOCRINOUS ORGANS i - - 254 
 
 vii
 
 VllI 
 
 Contents 
 
 SECTION D 
 THE NERVOUS SYSTEM 
 
 CHAPTER 
 
 XVIII. THE CHROMAFFIN SYSTEM ADKENAL THERAPY 
 
 THE HYPOPHYSIS OR PITUITARY BODY 
 
 THE EPIPHYSIS OR PINEAL BODY - 
 
 XIX. 
 
 XX. 
 
 XXI. 
 
 PAGE 
 
 257 
 
 287 
 320 
 
 THE THERAPEUTIC PRODUCTS OF BRAIN AND NERVE 
 
 SUBSTANCE ... - - 328 
 
 SECTION E 
 THE REPRODUCTIVE SYSTEM 
 
 XXII. THE TESTES — ORCHITIC EXTRACTS - - - 334 
 
 XXIII. THE ACTION OF PROSTATIC EXTRACTS - - 343 
 
 XXIV. THE OVARIES AND CORPORA LUTEA - - 347 
 XXV. THE THERAPEUTIC VALUE OF MAMMARY EXTRACTS 368 
 
 XXVI. THE PLACENTAL HORMONE- - - - 382 
 
 SECTION F 
 THE VASCULAR SYSTEM 
 
 XXVII. PULMONARY OPOTHERAPY - 
 XXVIII. THE CAROTID GLAND 
 XXIX. LYMPHATIC GLAND EXTRACTS 
 
 391 
 395 
 397 
 
 SECTION G 
 MISCELLANEOUS 
 
 XXX. THE USE OF PLURIGLANDULAR EXTRACTS - 
 
 XXXI. THE CONTROL OF HYPERENDOCRINISM 
 
 XXXII. MISCELLANEOUS EXTRACTS OF MINOR VALUE 
 
 XXXIII. THE PREPARATION OF ANIMAL EXTRACTS 
 
 THERAPEUTIC PURPOSES 
 
 XXXIV. THE LIPOIDS . - - - 
 
 FOR 
 
 404 
 
 428 
 434 
 
 438 
 446 
 
 SECTION H 
 APPENDIX 
 
 XXXV. A GLOSSARY OF TERMS ... - 455 
 
 XXXVI. AN ORGANOTHERAPEUTIC DOSE-TABLE - - 465 
 
 XXXVII. A LIST OF BOOKS ON THE INTERNAL SECRETIONS, 
 
 ETC. --..-- 470 
 
 INDEX 
 
 476
 
 INTRODUCTION 
 
 The introduction into therapeutics of preparations con- 
 taining the active principles of the internal secretions is 
 one of the greatest achievements of modern medicine ; and 
 the increasing applicability of the hormones as useful 
 factors in the general practice of medicine suggests the 
 collation of much practical information which will 
 epitomize the position of this rapidly advancing branch 
 of therapeutics. 
 
 The Title. — -With regard to the title of this book, I feel 
 that some explanation is necessary. It is fully admitted 
 that the activity of animal extracts is not due entirely to 
 their hormone content ; but at the same time most of this 
 activity is undoubtedly brought about by such bodies, and 
 the title " Hormone Therapy " is concise and convenient. 
 It is gradually being recognized in medical literature as a 
 ready form of expression for the more cumbrous one of 
 "therapeutics of the ductless glands and internal secre- 
 tions." At the same time I do not propose to limit the 
 scope of the book strictly to its title, for it is proposed to 
 consider several closely allied subjects (bile, the lipoids, 
 etc.). 
 
 In the blood there are countless substances of the 
 nature of hormones, related to one another and performing 
 innumerable functions. We have but to think of such 
 phenomena as the production of digestive fluids, the regu- 
 lation of the nervous system, the change from puberty to 
 
 ix
 
 X Introduction 
 
 manhood or womanhood, the menopause, the gradual 
 onset of senility, and many other well-known phenomena, 
 to understand why the blood should carry within it 
 countless "chemical messengers," each with a specific 
 object. The fmidamental principle of hormone thera- 
 peutics, and certainly a most reasonable one, is to supply 
 to the body a certain hormone or combination of hormones 
 which through disease has been diminished or lost. 
 
 Some of the statements regarding the therapeutic 
 apphcation of endocrinous preparations are strange, to 
 say the least, for whoever would imagine the use of 
 placental extract as a remedy for alopecia, or of adrenal 
 extract as a cure for seasickness. The story of these and 
 many other remarkable things is to be found in the follow- 
 ing pages, and whether these ideas are in everyday use or 
 not does not alter the fact that the hormones are perfectly 
 wonderful therapeutic agents, exceeding in range and 
 activity any drugs at present known. 
 
 Medical Scepticism. — As has been the case with practi- 
 cally every new discovery of import, there is still a tendency 
 to look askance upon the use of animal extracts in thera- 
 peutics. A few are becoming generally used, but as yet 
 only a few. We all remember the storm of hilarious 
 incredulity with which the first announcement of Roent- 
 gen's discovery was received less than twenty years ago. 
 The idea that a living man's skeleton could be photo- 
 graphed seemed too absurd to be considered. 
 
 The position of the medical profession is well outlined 
 in the following sentence, requoted from the preface to 
 Sajous's work on the "Internal Secretions": "If any 
 daring member has introduced a subject bearing on 
 medical treatment, it has been with an apologetic air and 
 humble mien, weU knowing that if his remarks had any 
 reference to the utility of drugs in the treatment of disease
 
 Introdiiction xi 
 
 they would be subjected to good-humoured banter, and 
 received by those sitting in the seat of the scornful with 
 amused incredulity." 
 
 The only valid test in the case of hormones, of course, is 
 clinical experience, which may be carried out under con- 
 ditions which can be repeated by others with compara- 
 tively similar results. It is not difficult to find cases suit- 
 able for this purpose, nor, for that matter, trustworthy 
 preparations with which to make the tests. We must 
 separate ourselves from those who are satisfied only with 
 extraordinary results from any new remedy or method of 
 treatment, and be content with frequent encouragements 
 and occasional failures. 
 
 There is still a widespread tendency on the part of 
 some medical men, at least among those in general 
 practice, to consider that the functions of various organs 
 are controlled principally by the nervous system, and when 
 disorganization of these functions is found, to treat it 
 with remedies and methods calculated to influence them 
 through nervous channels.* Our ideas need broadening, 
 and the study of the hormones and their diverse activities 
 will effect this very quicldy. 
 
 No subject will prove more enthralling to the interested 
 reader than the possibihties of hormone therapy, not only 
 in the obvious disorders of the endocrinous glands, but 
 in many other diseases evidently amenable to treatment 
 with their products. Nor will the interest wane when 
 plausible theories have become tangible results; for the 
 possibilities of this method are almost limitless and its 
 study not confined to laboratory experiments, nor is its 
 chemical basis dependent on the unsupported experiences 
 of a few enthusiastic investigators. 
 
 * This is illustrated liy our everyday use of strychnia in conditions 
 requiring stimulation, and morphia where an opposite etl'ect is desired.
 
 xii Introduction 
 
 Personally, I believe that " opotherapie," as the French 
 have named it — that is to say, the use of organic prepara- 
 tions, the activity of which is dependent npon their 
 contained hormones — is deserving of considerably greater 
 study and application than it has hitherto received, and 
 it seems that in this phase of medicine, at least. British 
 and American physicians are behind their European 
 confreres. 
 
 The Present Limited Application of Hormone Therapy. — • 
 At present the application of hormone therapy in general 
 practice is the exception rather than the rule, and the 
 exhibition of endocrinous preparations as remedies is, in 
 this country at least, practically confined to the use of 
 preparations from the thyroid, pituitary, and adrenal 
 glands. 
 
 It is admitted that much has been accomplished in the 
 past ten years to estabhsh the therapeutic usefulness of 
 certain secretions of the digestive glands, the renroductive 
 glands, and the spleen; but the proportion of general 
 practitioners who avail themselves of remedies of this 
 character is very small, possibly not five per cent. 
 
 As a part of my investigation of this subject, I have 
 looked into the frequency, or, rather, the infrequency, of 
 the use of preparations of this character, and if the data 
 obtained from the limited hundreds from whom informa- 
 tion has been secured may serve as a criterion, the per- 
 centage mentioned above is none too small. On the other 
 hand, in the Continental countries, especially in France, 
 Italy, and Germany (probably in the order mentioned), 
 the whole subject is considered in a much more familiar 
 manner. 
 
 There is, then, much truth in the statement that the 
 use of hormones in general practice is terra incognita to 
 the majority of medical men, and for this reason a review
 
 Introduction xiii 
 
 of the important advances in certain of these fields may 
 lead to more successful practice through the more thorough 
 control of those conditions which are either directly due 
 to, or at least indirectly associated with, disorganized 
 metabolism. 
 
 The Scope of this Book. — The principal object of this 
 book is to broaden the therapeutic horizon and to stimu- 
 late the reader to include in his armamentarium such of 
 the hormones as are of proved utihty. This work is not 
 a study of the internal secretory organs and their products, 
 but rather an attempt to collate such knowledge as will 
 be useful in practical therapeutics. The scope of its con- 
 tents, therefore, must be limited to a consideration of the 
 remedial value, actual and prospective, of these varied 
 substances. Anatomy, comparative anatomy, physiology 
 (except such as may be essential clearly to set before the 
 reader the philosophy of a certain procedure), pathology 
 (save only where reference to pathologic changes lays 
 emphasis upon a corresponding therapeutic deduction), 
 and biochemistry are left to numerous other books, 
 which already thoroughly cover this part of the subject. 
 Readers who desire further information on this subject 
 are referred to several most excellent and exhaustive 
 works, notably those of Biedl, Beebe, Sajous, and Swale 
 Vincent. Professor Biedl's book — especially the second 
 German edition — is a masterpiece, and is the most com- 
 plete piece of literature on this subject in any language. 
 To read it through is a postgraduate course in the study 
 of the internal secretory organs. It is true that numerous 
 books are devoted to the internal secretions, and practi- 
 cally every one of them in French, German, Italian, and, 
 of course, English, is in my library. So greatly do I prize 
 these works of reference that it seems advisable to include 
 a list of the more important of them in the appendix, and
 
 xiv Introduction 
 
 opportunity is taken here to recommend them highly and 
 to make due acknowledgment of the assistance they have 
 afforded me in the preparation of this book. 
 
 On the other hand, so far as information regarding the 
 practical application of the knowledge gained by physiol- 
 ogists in their experimentation with animal extracts is 
 concerned, it is felt that the English hterature is lack- 
 ing. With one or two exceptions, there are no books 
 published on this subject, either in England or the United 
 States, and the exceptions are incomplete and already 
 quite out of date. (An admirable resume of the subject 
 appeared in the Prescriber, a British journal which 
 devoted an entire double number to a review of Hormone 
 Therapy down to the time of issue, April, 1913. I under- 
 stand that copies of this number are still available.) As 
 a result, one must look to foreign literature or to the 
 literature of manufacturers who specialize in organo- 
 therapeutic preparations for information concerning the 
 practical results which have been achieved by such patient 
 experimentation. 
 
 The Manufacturer's Position. — A word about the manu- 
 facturer may not be amiss. When physiology proves the 
 definite importance of any substance produced bj^ the 
 endocrinous organs, pharmacy immediately attempts to 
 isolate it or at least to prepare it for suitable administra- 
 tion, while therapeutics proceeds to put it to the test and 
 prove or disprove its efficacy in a disease in which it is 
 presumably of service. 
 
 Unfortunately there is a tendency on the part of the 
 profession to discount any statements that may be made 
 by those who are avowedly working in this field for their 
 own financial advantage. The other day a prominent 
 professor of medicine in one of the largest English pro- 
 vincial medical colleges assured me that all that the
 
 Introduction xv 
 
 manufacturers were after was the doctor's money, and 
 he intimated that their interest in science was merely a 
 pretence to cover their mercenary motives. It is un- 
 doubtedly true that many ill-considered ideas have been 
 foisted upon the profession, and that many highly 
 coloured and even untrue statements have been made 
 with reference to the ingredients and effectiveness of 
 certain pharmaceutical "specialities"; but in spite of 
 these one cannot deny that medicine is a debtor to the 
 commercialism of those who have deliberately set them- 
 selves to discover something new, and thus to add to their 
 prestige in scientific reputation as well as to their pros- 
 perity in business. After all, there is a more or less 
 evident mercenary motive beneath all good work, not 
 excepting that of the physician. Ought manufacturers, 
 therefore, to be blamed for considering the bread-and- 
 butter side as well as that which is purely altruistic ? 
 
 This is not a record of personal clinical experiences. I 
 cannot even lay claim to great originality in the matter 
 presented. Part of it has been drawn from numerous 
 French works. A majority of the facts have come from 
 technical and medical journals and appear in book form 
 here for the first time. I am aware that in the collection 
 of information from such scattered and polyglot sources, 
 important omissions and even contradictory statements 
 may have crept in. It may easily also have happened 
 that emphasis has been laid on certain points to the 
 exclusion of others of equal importance. My experience 
 with the well-known hormone-bearing preparations is that 
 of an average physician, and my use of such preparations 
 as thymus, kidney, and parathyroid extracts is very 
 limited, while I have never once used extracts of lung, 
 tonsil, prostate, or brain. I am frank to admit that some 
 of the statements which have been incorporated in the
 
 xvi Introduction 
 
 following pages are not yet generally accepted, and some 
 possibl}^ may ultimately prove erroneous; but I am con- 
 vinced that they have a greater or less degree of warrant 
 of clinical usefulness, and therefore deserve the considera- 
 tion suggested long since: " Prove all things ; hold fast to 
 that which is good." 
 
 The Subdivisions of the Book have not been made upon 
 any arbitrary basis. While the recognized anatomical 
 classifications have been followed, the standpoint of con- 
 venience has not been ignored. There is still some contro- 
 versy regarding the actual status of some of the organs of 
 interest to us, and the chromaffin organs are classed in 
 " the nervous system " for want of a better place, while 
 the pituitary gland comes under the same classification, 
 although it is not so long since it was considered a vascular 
 organ. The classification of the spleen with the digestive 
 system may not be in harmony with the ideas of all, 
 especially of those who are wont to consider it as a purely 
 haemopoietic organ, but the text will explain why this has 
 been done. 
 
 The grouping of the thyi^oids, parathyroids, thymus, 
 kidneys, and tonsils in one class — " the metabohc 
 glands " — may seem incongruous, but it has been adopted 
 for lack of a better way ; and because all these organs are 
 certainly closely concerned with the metabohsm, even 
 though the principal function of the kidneys may not be 
 of an internal secretory character. 
 
 Bibliographic References. — The bibliographies accom- 
 panying each chapter are far from complete. It is 
 useless to dupHcate, and those who are desirous of studying 
 the subject are reminded that the total of the references 
 in the library books already referred to mounts up into the 
 thousands. In Biedl's English edition the bibhography 
 covers 140 octavo pages; in Swale Vincent's book there
 
 Introduction xvii 
 
 are 2, 1 64 references ; while in "Hormone Therapy, 1913" 
 — the special number of the Prescriber already referred 
 to — there are 467 references to articles, most of which 
 appeared in 1911-1913, and 177 brief abstracts of recent 
 hterature. The bibhographies in this book, therefore, are 
 not extensive, especially those connected with the chapters 
 upon comparatively well-known subjects, such as the 
 thyroid, adrenals, etc. On the other hand, where the 
 reference books seem to me not to have done justice to 
 certain subjects, my bibliographies are more extensive. 
 This is particularly true of the pancreas, spleen, para- 
 thyroid, secretin, and pluriglandular extracts. I have 
 dealt with these subjects in original articles published 
 elsewhere. 
 
 In verifying several of the references quite a number of 
 additional references were found. The most important of 
 these have been added for the convenience of the inter- 
 ested student. 
 
 The l7idex. — There are numerous works in which the 
 therapeutic indications of various disorders are alpha- 
 betically enumerated, and not a few medical men smile 
 when they see, for example, over fifty drugs and combina- 
 tions specified in Weilcome's " Excerpta Therapeutica " 
 as being useful in tonsillitis. In spite of this tendency to 
 deprecate therapeutic tables — it is admitted that effica- 
 cious treatment is dependent on broad, general knowledge 
 and experience, and that a novice cannot expect to be 
 successful simply by selecting a certain table of thera- 
 peutic indications and applying them, hit or miss — it has 
 seemed advisable to incorporate with the index a brief 
 and suggestive list in alphabetical order of the commoner 
 diseases with their opotherapeutic indications. An 
 attempt has been made to refer to the particular page in 
 which the general considerations, and so on, are to be
 
 xviii Introduction 
 
 found, thus making an index, as well as a therapeutic 
 index. It must be understood, though, that I have no 
 intention of being arbitrary, and that the main reason 
 for preparing this index has been that it may perhaps 
 stimulate a new train of thought, and the interested 
 investigator may thus be led into certain lines of study, 
 which, without the index, he possibly might have over- 
 looked. 
 
 The Author's Acknowledgments. — I have an especially 
 large number of acknowledgments to make. In order 
 that my enthusiasm might not lead me astray I conceived 
 the idea of submitting several of the units which form 
 this book to authorities for criticism. I am under con- 
 siderable obligations to a number of prominent men, whose 
 names are well known to medical readers. 
 
 First and foremost I have to thank Professor Biedl of 
 Vienna for the benefits that have accrued from reading his 
 book, and also for the honour he does me in writing the 
 preface, and in criticizing the three preliminary chapters. 
 To the following gentlemen I am indebted for their having 
 read and criticized the chapters the numbers of which 
 immediately follow each name: Dr. Ch. Bayle of Cannes 
 (IX.) ; Prof. S. P. Beebe (V.) and Dr. W. N. Berkeley of New 
 York (XIV. and XX.); Prof. Paul Carnot of Paris (XL); 
 Prof. C. A. Ewald of Berhn (V.); Dr. E. Hertoghe of 
 Antwerp (XIII.); Prof. Howard A. Kelly of Baltimore 
 (XXIV.); Prof. R. Lepine of Lyons (VII.); Prof. G. R. 
 Murray of Manchester (XIII. ); Dr. C. E. de M. Sajous 
 of Philadelphia (XVIII.) ; Sir Edward A. Schafer of 
 Edinburgh (XIX.); Prof. E. H. Starhng (V.) and 
 Dr. Leonard Williams of London (XIII.) ; and Dr. G. 
 Zuelzer of BerUn (X.). 
 
 Finally, to Dr. Kemieth W. Millican I must express my 
 thanks for his helpful revision of the manuscript, and to
 
 Introduction xix 
 
 Mr. Thomas Stephenson, editor of the Prescriber (Edin- 
 burgh), for assistance with the proofs and make-up of 
 the book. 
 
 In presenting this book to the profession it is with the 
 sincere hope that the information gathered in the pages 
 which follow may serve to lead many to a fuller appre- 
 ciation of the therapeutic possibilities of hormones in the 
 routine work of the average medical man, 
 
 H. R. H. 
 
 London, 
 
 J/«?/, 1914.
 
 PRACTICAL 
 
 HORMONE THERAPY 
 
 CHAPTER I 
 
 HORMONES : THEIR DISCOVERY, PRODUCTION, 
 AND ACTION 
 
 The Ayitiquity of Animal Therapy — The Origi7i of Scientific 
 Endocrinology — The Application of this Knowledge in 
 Therapeutics — A Recent Estimate of the Basis of Internal 
 Secretory Therajjeutics — Charlatanism and Animal Therapy 
 — The Scientific Establishment of Hormone Action — 
 Starling's Conception of the Hormones — Definitions of the 
 Term '''Hormone" — A Classification of Hormones — The 
 Present List of Known Hormones — A Comparison of Hor- 
 mones and Enzymes — The Selective Action of the Hormones — 
 The Role of the Blood-Plasma. 
 
 Medicine, like every branch of science, is constantly 
 changing. Our knowledge is being increased at such a 
 rate that the advance of a single decade suffices entirely 
 to revolutionize our conceptions. Nowhere has this 
 transition been more apparent than in therapeutics. 
 What would om^ present -day therapists do if they had to 
 revert to the methods of, say, twenty-five years ago ?. 
 What should we do without the X ray, the numerous 
 synthetics, the sterilisans magna of Ehrlich, the bacterins, 
 or the internal secretions ? The rise and development of 
 " hormone therapy " is a great achievement, and the 
 facts of the present are destined to be outshone by the 
 prospects of the future, empirical though they still may 
 
 1
 
 2 Praciical li or) none Therapg 
 
 seem to be. " Hormones are to physiology what radium 
 is to che7nistry.^^ 
 
 The Antiquity of Animal Therapy. — The use of animal 
 organs in the treatment of disease is as old as medicine 
 itself. It is recorded that the ancient Egyptians treated 
 various diseases by means of animal organs or secretions, 
 and in the Ayurvedic writings of Susruta, who lived some 
 time between 400 and 500 B.C., mention is made of the 
 use of orchitic substance in the treatment of impotence. 
 This is probably the earliest specific reference to organo- 
 therapy, and from that time it has never been long 
 absent from the literature relating to " medicine " or the 
 healing art. The works of Pliny and Galen show that 
 both those writers had vague notions of the possible 
 presence in certain organs of substances having a regu- 
 lating action on the functions of similar organs, and 
 contain numerous references to the employment of 
 various animal preparations in the treatment of disease. 
 
 From the writings of Hippocrates it is clear that he 
 considered many diseases a result of various " humomrs," 
 and looked to the corresponding healthy organs of animals 
 for a means of relief. It was natural, then, that organo- 
 therapy should be a prominent part of medical practice 
 as it was then. 
 
 But the more recent discovery of the wonderful power 
 of control of the body found to reside in the central 
 nervous system quickly overshadowed the crude and 
 absiu:d notions of the ancients, and from that time the 
 " humoral theory " was quite discarded. Now, however, 
 the pendulum is swinging back, for it has been discovered 
 that the nervous system is not alone in its direction of the 
 functions of the body. 
 
 The principle of aimilia similibus curantur, which is the 
 basis of Hahnemann's system of homoeopathy, has a like-
 
 Hormones : Discovery, Production^ and Action 3 
 
 ness to the principles of organotherapy which have come 
 to us down through the centuries, and, to say the least, it 
 is considerably more pleasant so far as the palate is 
 concerned. The animal therapy of the past is not nice 
 to think of, and the more repulsive forms of animal 
 preparations long held sway. Even at the present day 
 we have such unsavoury animal products as cod-liver oil 
 still enjoying the full benefit of ofhcial recognition. 
 
 Of course the use of all these remedies is empirical. 
 Indeed, there was a tinge of superstition in many of the 
 cures — that superstition which allows the ignorant to 
 attain by intuition what the learned can arrive at only 
 after years of toil and study. 
 
 The Origin of Scientific Endocrinology. — The beginning 
 of the scientific study of the endocrinous organs dates 
 from 1849 or 1850, when Berthold^ first hinted at the 
 fundamental position of the ductless glands. About five 
 years later the famous Claude Bernard, ^ whose centenary 
 has just been (1913) celebrated, substantiated this sug- 
 gestion, and by his well-directed enthusiasm laid the 
 foundation of an entirely new science. This celebrated 
 French scholar is generally conceded to have been the 
 first exponent of the physiologic influence of the internal 
 secretions. As a result of his labours our knowledge of 
 human chemistry, and of the influence of the internal 
 secretions upon it, has become by no means inconsider- 
 able; and, if one can judge by the Uterature devoted to 
 this subject, it is advancing " at a rate which even the 
 most sanguine advocates of this line of research could not 
 but deem astounding." 
 
 The Application of this Knowledge in Therapeutics. — 
 Some twenty or twenty-two years ago a new phase of 
 so-called rational therapeutics sprang up — a system 
 wherein gland substances were administered in cases
 
 4 Practical Hormone Therapy 
 
 where disease was believed to be due to deficient secretion 
 of that particular organ. This doctrine was first put to a 
 practical test by Brown-Sequard,^ also of Paris, and his 
 experiences with testicular extracts upon his own person 
 were the real foundation of the modern science of internal 
 secretory therapeutics. For years information on the 
 numerous phases of the subject was indefinite and dis- 
 associated. What the gland secreted and how the 
 deficiency affected the disease was then but imperfectly 
 known; still the adrenals and the thyroid and other 
 organs gradually began to have a responsibility in regard 
 to morbid conditions placed upon them, and these glands, 
 obtained from animals, were used empuically in almost 
 every conceivable condition. 
 
 Then followed what might be called a craze for organo- 
 therapy. Almost every internal organ of the sheep or 
 ox, from the brain to the testes, was removed and served 
 with pharmaceutical skill in the form of desiccated 
 powder, compressed tablets, or glycerine extracts. Doubt- 
 less benefit was derived from the treatment, but soon 
 much of it was discarded, although in France opotherapie 
 is to-day as popular as ever it was. 
 
 A Recent Estimate of the Basis of Internal Secretory 
 Therapeutics. — Italian physicians, next perhaps to the 
 French in the activity of their investigations of this 
 subject, have contributed much valuable information to 
 the sum of our present knowledge. At a recent Italian 
 congress* an official report was made and adopted, in 
 which it is deemed established that the " endocrinous 
 system "f — the internal secretory system — exerts an in- 
 
 * The Italian Society of Mediciue at a special meeting held in Rome, 
 October, 1912. 
 
 f The word "endocrinous" is incorrect. It should be "endocritic," but 
 in deference to general usage the former term will be used throughout. See 
 Glossary.
 
 Hormones : Discovery, Production, and Action 5 
 
 fluence on anomalies of growth, morphogenesia, and 
 organic metabolism, on nutrition and inherent excita- 
 bility of the nervous system, and on resistance to infec- 
 tions and intoxications, and also that it has a prepondera- 
 ting influence on the causation of dyscrasias and morbid 
 temperaments. The equilibrium of the nervous system, 
 the sympathetic in particular, is also regarded as main- 
 tained by the internal secretions. In nervous diseases 
 per se they act probably as indirect or predisposing factors. 
 
 In commenting editorially upon this report the New 
 York Medical Journal says'^: "One cannot but be im- 
 pressed by the vast field which the ductless glands have 
 steadily invaded, in keeping with the conclusions an- 
 nounced nearly ten years ago in this country, that these 
 organs were second to none in the body in their bearing 
 upon physiology, pathology, and clinical medicine. . . . 
 The array of disorders enumerated in the report in which 
 the internal secretions are now known to take part is 
 such that pathology bids fair to require a complete 
 readjustment if its tenets are to harmonize with all 
 established facts." 
 
 Charlatanism and Animal Therapy. — There is, un- 
 happily, a tendency on the part of many physicians to 
 look askance on the use of animal preparations other 
 than those so well known and already mentioned. To 
 many it still savours of quackery, for did not the im- 
 mortal Pliny advocate the use of some fifty or more 
 preparations from the hyeena for as many human ailments? 
 and if so, why not limitless preparations from the whole 
 animal kingdom for practically all the ills to which the 
 flesh is heir ? And do not many Chinese " physicians," 
 whose ideas we scorn, still use such animal preparations 
 as powdered deer's horn, hoof of a white horse, thigli of 
 a grey horse, eyes of a tiger, etc. ?
 
 6 Practical Hormone Therapy 
 
 Unfortunately for the progress of scientific organo- 
 therapy, the important work of Brown-Sequard with 
 testicular extract was immediately taken up with avidity 
 by many astute quacks, and his suggested treatment was 
 lauded to the world as the one sure cure for impotence 
 and other conditions which are of such a nature as not 
 only to influence the organs concerned, but also the 
 credulity of the unfortunate sufferer. Thus the funda- 
 mental value of Brown-Sequard's work was in a measure 
 discredited, although the professional reputation of those 
 among the first to use this new method should not be 
 permitted to belittle the fact that these medicaments 
 have a very wide and increasing range of usefulness, that 
 our knowledge of the subject is being put on a scientific 
 basis, and that those physicians who do not appreciate 
 this to the full are separating themselves from means to 
 very encouraging ends. 
 
 The Scientific Establishment of Hormone Action. — As a 
 result of the stimulus given by this pioneer work, how- 
 ever, many set themselves to unravel the intricacies of 
 various phases of this vast subject, and among many 
 important discoveries one stands out as epoch-making. 
 This was the chemical isolation of the first endocrinous 
 active principle in 1901, when the hormone of the adrenal 
 medulla was given to the world by Takamine^ of Detroit. 
 How this substance brought about its remarkable action 
 was only hinted, and it was left to Starling and his co- 
 workers to determine the basis of the actual relations of 
 the internal secretions in physiology. 
 
 The discovery of the principle of hormone action M^as 
 brought about by the experiments of Bayliss and Starling^ 
 in the research laboratory of University College, London, 
 in 1902. These gentlemen, in studying the then newly 
 discovered enterokinase, proved that the presence of an
 
 Hormones : Discovery, Production, and Action 7 
 
 acid, or acid stomach contents, in a loop of small intestine 
 was always followed by a secretion of pancreatic juice, and 
 that this took place notwithstanding the careful destruc- 
 tion of all nerve channels. The details of the study and 
 the action of the first-named hormone — secretin — will be 
 found in Chapter V. 
 
 About this time, in the same laboratories, the so-called 
 " mamma hormone " was demonstrated by Starling and 
 his assistant, Miss Lane ClayfDon,'^ and it seemed necessary 
 to propose a term to cover these chemical agents, or 
 messengers, which, when carried by the blood, serve to 
 co-ordinate the activities of certain remote organs. 
 Starling therefore proposed the term " hormone," from 
 the Greek 6p/u,d(o, " I arouse or excite," and in the decade 
 that has passed the innumerable experiments have 
 proved the soundness of this premise, and have estab- 
 lished the hormones in therapeutics as well as in physi- 
 ology. 
 
 Hormones are evidently definite chemical substances 
 produced either with a special predestined action or as 
 by-products in the normal cell catabolism, which serve 
 to unite the complex of activities of the body into a 
 functional harmony, both by means of chemical regulation 
 effected through humoral channels, as well as, in certain 
 cases, by means of reflex control exerted by the nervous 
 system . 
 
 Starling's Conception of the Hormones. — One of Star- 
 ling's earliest pronouncements on the subject is to be 
 found in profoundly interesting and illuminating con- 
 sideration of the chemical co-ordination of the activities 
 of the body.^ In this article the author refers to the 
 excitatory substances (Reizstoffe), long familiar to botan- 
 ists, which have a decided dynamic effect on the living 
 cell. In this respect they present a close analogy to the
 
 8 Practical Hormone Therapy 
 
 substances that form the ordinary drugs of our pharma- 
 copoeias. One cannot do better here than quote Starhng's 
 own words: " Since in the normal fmictioning of the body 
 they [the hormones] have to be discharged at frequent 
 intervals into the blood-stream, and carried onward by 
 this to the organ on which they exercise their specific 
 effect, they cannot belong to that class of complex bodies, 
 which include the toxins, of animal or vegetable origin. 
 We must therefore conceive the latter as substances, 
 produced often in the normal metabolism of certain cells, 
 of definite chemical composition, and comparable in their 
 chemical nature and mode of action to drugs of specific 
 action such as the alkaloids. This conclusion is borne 
 out by the few investigations which have been made as 
 to the nature of the chemical messengers in the case of 
 certain well-marked correlations of function in the higher 
 animals. In consequence of the distinctive features of 
 this class of bodies, and the important functions played 
 by them in the higher organisms, I have proposed to give 
 a special name to the class — viz., hormones, from opfidco, 
 ' I arouse or excite.' " 
 
 This, then, is the beginning of hormone therapy, the 
 scientific explanation of that system of animal medication 
 so steadfastly believed in throughout the ages. The body, 
 it would appear, manufactures its own drugs. These are 
 supplied by the glands of internal secretion ; and not only 
 have they the power to correlate and co-ordinate the 
 various bodily functions — such as pregnancy and mam- 
 mary secretion, growth and sexual development, and so 
 forth — but they also destroy toxins, and, further still, 
 these hormones control one another. The essential im- 
 portance of this will be emphasized more thoroughly in 
 later chapters. 
 
 How close the earlier students were to the essentials of
 
 Hormones : Discovery, Production, and Action 9 
 
 the action of hormones is shown in a paper by Brown- 
 Sequard and his assistant d'Arsonval,^ published in 1891. 
 They refer to these chemical substances in the following 
 terms: " These special soluble products [of the living cell] 
 enter into the blood and serve to influence, with this 
 liquid as the intermediary, other cells or anatomical 
 elements of the organism. As a result, the diversified 
 cells of the economy are thus correlated with one another 
 by means of a mechanism other than the influence of the 
 nervous system." 
 
 Definitions of the Term "Hormone." — In a paper 
 published nearly twenty years later, HowelP° of Johns 
 Hopkins University defines hormones as " those sub- 
 stances in solution which, conveyed from one organ to 
 another through any of the liquid media of the body, 
 effect a correlation between the activities of the organ of 
 origin and the organ on which they exert their specific 
 effect." 
 
 Starling's most recent statement embodying a defini- 
 tion of hormones was given in a discussion on the thera- 
 peutic value of hormones held by the Royal Society of 
 Medicine. 11 He says : " By the term ' hormone ' I under- 
 stand any substance normally produced in the cells of 
 some part of the body and carried by the blood-stream to 
 distant parts, which it affects for the good of the organism 
 as a whole. The hormones are thus the chemical means 
 of correlation of the activities of different parts of the 
 body. Their action may be either the increase or diminu- 
 tion of function, or the alteration of nutrition or rate of 
 growth." He then proceeds to classify the hormonic 
 actions into two classes, which he terms " the acute " 
 and " the chronic." Typical examples of the former are 
 secretin, carbonic acid, and adrenaline; of the latter, the 
 thyroid, anterior pituitary, and luteal hormones. Star-
 
 10 Practical Hormone Therapy 
 
 ling believes that the " chronic " class of hormonic reac- 
 tions offers the best chances for therapeutic interference, 
 as it includes the only definite instance of successful 
 substitution therapy at present known — e.g., the use of 
 thyroid extract. 
 
 It seems quite evident that all the glands of internal 
 secretion are active principally through the influence of 
 the hormonic content of their secretion, and while several 
 of these hormones have been extracted (secretin, hypo- 
 physin, adrenalin, etc.), it is still necessary to presume 
 that they are present in suitably prepared extracts of 
 the various organs; and that, because of their general 
 stability and the fact that they are active in animals 
 other than those in which they are produced, they 
 may be used to bring about, in part at least, in man 
 those co-ordinative activities which are their specific 
 duties. 
 
 A Classification of Hormones. — Of course the action of 
 the various substances usually called " hormones " is 
 widely divergent, and, strictly speaking, they are not all 
 entitled to be included in this class. Recently a sugges- 
 tion was made with a view to the classification of these 
 chemical messengers. At the Section of Physiology of 
 the Seventeenth International Congress of Medicine a 
 noteworthy paper on "A Proposed Classification of 
 Hormones " was read by Sir E. A. Schafer. He considers 
 the term " hormone " not strictly applicable to every 
 principle of the internal secretions, for the word implies 
 excitation, while many of these principles really relax or 
 inhibit rather than excite. He therefore suggested a 
 generic name indicative of their drug-like action, and 
 proposed the term " autacoid " (from avr6<i and aKo<i, 
 " a remedy ") for the entire group, subdividing these 
 into "hormones," those that excite, and " chalones "
 
 Hormones : Discovery, Production, and Action 11 
 
 (;j^aXaft), " to relax "), those whose action is of an antag- 
 onist nature or inhibitory. 
 
 This tentative nomenclature has not yet been generally 
 accepted, and it is likely that, just as the incorrect and 
 inappropriate term " vaccine," to indicate a certain 
 bacillary emulsion, is in everyday usage, so the word 
 " hormone " will continue to indicate the active principles 
 of the internal secretory glands which serve as chemical 
 messengers to correlate the activities of the body, irre- 
 spective of whether they are excitants of positive activity 
 — e.g., stimulators — or excitors of negative activity — 
 e.g., inhibitors. Howell very rightly said in 1909 that it 
 was likely that the term " hormone," like some ot the 
 useful nomenclature of immunology, will be overworked. 
 
 The Present List of Known Hormones.* — By "known 
 hormones " are intimated those principles the presence 
 of which is presumed because of definite action caused 
 by the organ producing them; they are not necessarily 
 capable of isolation or even of standardization. 
 
 " The substances of known composition which may be 
 regarded as playing the role of hormones are few in 
 number, three or four at most, as follows: First, the 
 carbon dioxide formed in the tissues, particularly in 
 muscle during contraction. It seems agreed now that the 
 carbon dioxide acts as the normal stimulus to the respira- 
 tory centre. When produced in the working muscles in 
 such quantities as to raise perceptibly the carbon dioxide 
 tension in the alveoli of the lungs and the blood of the 
 pulmonary veins, the respiratory centre is excited to 
 greater activity, and the excess above the normal contents 
 is thereby removed; second, the adrenalin of the adrenal 
 
 * This list is taken from Howell's address before the Section of Physiology 
 and Experimental Medicine, American Association for the Advancement of 
 Science. 1910.
 
 12 Practical Hormone Therapy 
 
 glands, which in some way, directly or indirectly, makes 
 possible the full fimctional activity of the involuntary 
 musculature of the body; third, the hydrochloric acid 
 produced in the stomach, which stimulates the formation 
 of secretin in the duodenal epithelium ; and fourth, possibly 
 the iodothyrin of the thjrroid gland with its dynamogenic 
 effect upon the neuromuscular apparatus of the body. 
 In addition, there are a number of hormones of unknown 
 composition which have been either proved or assumed 
 to exist, and which are held responsible for certain well- 
 known correlations of function. The pancreatic secretin 
 formed in the epithelium of the duodenum or jejunum, 
 which stimulates the flow of pancreatic secretion ; the gas- 
 tric secretin formed in the pyloric mucous membrane, 
 which gives rise to the chemical secretion of gastric juice; 
 a secretin formed in the duodenal epithelium, which 
 stimulates the formation of intestinal juice in the following 
 segments of the intestine ; unknown hormones of pancreatic 
 origin, which determine the absorption activity of the 
 intestinal epithelium; vaso-dilator hormones formed in 
 tissues in functional activity, and which have a specific 
 effect upon the vessels of the functioning organ; a vaso- 
 constricting and diuretic hormone formed in the posterior 
 lobe of the pituitary body; a hormone controlling the 
 growth of the bones and connective tissues produced in the 
 anterior lobe of the pituitary body ; a hormone controlling 
 the oxidation of sugar in the body and produced in the 
 cells of the islands of Langerhans in the pancreas; a 
 hormone produced in the thymus, which controls possibly 
 in some way the development of the reproductive organs ; 
 a vaso-constricting hormone formed in the kidneys; a 
 hormone in the salivary glands, which controls the flow 
 of water from the blood-capillaries in the glands ; a hor- 
 mone produced in the foetus in utero, which stimulates the 
 
 I
 
 Hormo7ies : Discovery, Production, and Action 13 
 
 growth of the mammary glands ; a hormone in the ovary, 
 which controls the growth of the uterus and the processes 
 of menstruation; a hormone in the ovary, which controls 
 the implantation of the fertilized ovum and the growth 
 of placental tissue; a hormone in the testis, which initiates 
 the development of the secondary sexual characteristics 
 in the male ; hormones of an indefinite number, produced 
 in all the tissues and acting specifically upon the deter- 
 minants in the gametes in such a way as to make possible 
 the transmission of acquired characteristics." 
 
 A Comparison of Hormones and Enzymes. — The impor- 
 tance of the difference between hormones and ferments 
 or enzymes must be emphasized. Enzymes are com- 
 plicated chemical substances — miorganized ferments — 
 which are capable of causing chemical changes in certain 
 other substances without themselves being permanently 
 changed in the process. Among these are such well- 
 known substances as diastase, pepsin, trypsin, etc. These 
 are invariably destroyed* by heat, and are capable of 
 performing their function outside of the tissues. Hor 
 mones, on the other hand, are complex but evidently 
 quite definite chemical substances produced in various 
 cell-groups ; their function is to provoke the production 
 of enzymes and ferment action, and generally to act as 
 excitants to numerous manifestations of physiologic 
 activity. Hormones are carried directly into the blood, 
 are quite stable, and can withstand a much greater degree 
 of heat. A ferment consists of the product of the cell 
 
 * This is tlie general impression obtained from the cuirent literature, but 
 it seems that not all enzymes, at least, are "destroyed" by heat. Rather 
 should we say that they arc rendered inert, by lieat. Kxpcriniental (^(Wi- 
 lirmation of this is found in the consideiiiti;in of the salixary glands in 
 Chapter IV. It has been stated that enzymes are more stable tlian hormones, 
 for they are not "used up" as are tlie hormones, but are "virtually inde- 
 struetible, " being used and re-used indefinitely. More proof of this is 
 needed.
 
 14 Practical Hormone Therapy 
 
 producing it, the proferment, plus the hormone. The 
 proferment is not active until it has been influenced by 
 the hormone, while the hormone itself is not influenced 
 save only as it serves its work as a chemical messenger. 
 (The reader's attention is directed to the glossary which 
 forms Chapter XXXV. in the Appendix, in which the 
 numerous terms directly or indirectly related to this 
 subject have been explained.) 
 
 Starling has indicated that hormones belong to the 
 crystalloid rather than to the colloid class of substances, 
 and that they are therefore thermo-stable, and do not act 
 as antigens when injected into the living animal. The 
 stability of these substances and their resisting powers 
 against ordinary heat differentiate them entirely from 
 ferments and enzymes. 
 
 It must also be remembered that since there is an 
 absence of antigen action when they are used in thera- 
 peutics, the body does not immediately attempt to destroy 
 them as it would foreign substances; but as soon as they 
 enter the blood-stream they are appropriated by the 
 organ which they specifically excite, just as are those 
 similar substances which it is desirable to replace or 
 augment. 
 
 The Selective Action of the Hormones. — Perhaps more 
 experimental work has been done with the first hormone 
 — secretin — than with any other, because of the perfec- 
 tion of the present methods for separating it, and the com- 
 parative ease with which it is separated from the duodenal 
 cells (see chapter on Secretin). It is quite reasonable to 
 presume that the action of the hormones as a class is 
 uniform, and, without offending the physiologists, we 
 can take it for granted that the various hormones com- 
 bine with certain uniform substances in the cells to 
 produce the stimulus or substance which it is their func-
 
 Hormones : Discovery, Production, and Action 15 
 
 tion to produce. It seems to be well established that 
 secretin is used up in the reaction that takes place between 
 it and the proferments of the pancreas, stomach, Uver, 
 etc., and the present idea is that these enzyme precursors 
 are activated by actual combination with the secretin, 
 and that the hormone is a component part of the com- 
 pleted ferment. 
 
 The general action of hormones has already been 
 briefly intimated. Undoubtedly a specific selective at- 
 traction is manifested by certain organs for the hormones 
 which activate them ; and it is quite reasonable to imagine 
 the blood-serum as a far more complex solution than has 
 hitherto been presumed, containing, in addition to its 
 cells, salts, opsonins, and other related substances, scores 
 of hormones at one time, each of which is appropriated 
 by the cells of those organs which are specifically stimu- 
 lated by it. 
 
 The Role of the Blood-Plasma. — Much of intense in- 
 terest will be found in a series of articles by Harry Camp- 
 bell, entitled "The Role of the Blood-Plasma in Disease," 
 and published in the Lancet during the early part of 
 1907.^^ Campbell has very lucidly outlined the impor- 
 tant part played by the blood-plasma, not only in every 
 function of health, but practically in every condition of 
 disease. He has very forcibly emphasized the importance 
 of the work of the individual cell, and for convenience 
 divides its activities into two parts — egoistic and altru- 
 istic. The former consists in the maintenance of the 
 individual cell vitality; while the latter, possibly an 
 entirely secondary function, consists in supplying the 
 organism as a whole with certain service, such as control 
 by the nerve cells, the production of ferments or hormones, 
 and the elimination of toxins by gland cells, and the 
 causation of motion as with muscle cells. This author
 
 16 Practical Hormone Therapy 
 
 points out that the cell itself may be to all intents and 
 purposes quite healthy and still gravely fail in its altru- 
 istic functions — a failure which, small though it may be, 
 may suffice to disorganize the delicate hormonic balance 
 of the body, either by permitting the presence of an excess 
 of a certain substance, as, for example, is generally con- 
 sidered to be the case in Graves's disease, or by the lack 
 of it, as in myxoedema. 
 
 With these facts in mind, we can consistently pass to 
 a consideration of the fundamental principles of hormone 
 therapy. 
 
 BIBLIOGRAPHY 
 
 ^ Berthold ( — ): Transplantation der Hoden, Arch. f. Anat. 
 Physiol, u. iviss. Med. (Berlin), 1849, 42. 
 
 - Bernard (Cl.): Lecons de physiol. ex-per. (Paris), 1855, i, 96. 
 
 ^ Brown-Sequard (C. E.): Reclierches expevimentales sur la 
 physiologie et la pathologie des capsules siirrenales, C. r. 
 Acad. d. Sci. (Paris), 1856, xliii, 422. 
 
 * Editorial: The clinical relations of the internal secretions, 
 N. Y. Med. J., 1912, xcvi, 1183. 
 
 ^ Takamine (J.): The blood-pressure-raising principle of the 
 suprarenal glands; a preliminary report, Ther. Gaz. (Detroit), 
 1901, xvi, 221. 
 
 ^ Bayliss (W. M.) and Starling (E. H.): Preliminary com- 
 munication on the so-called " peripheral reflex secretion " 
 of the pancreas. Lancet (London), 1902, i, 813. 
 
 ' Lane-Claypon (J. E.) and Starling (E. H.): An experimental 
 inquiry into the factors which determine the growth and 
 activity of the mammary glands, Proc. Boy. Sac. (B), 
 (London), 1905-06, Ixxvii, 505. 
 
 8 Starling (E. H.): The chemical co-ordination of the activities 
 of the body, Science Progr. (Loudon), 1906-07, i, 557. 
 
 '•' Brown-Sequard (C. E.) and d'Arsonval (A.): Faits mon- 
 trant combien est grande et variee I'influence du systemc 
 nerveuse sur la nutrition et les secretions; Influence cm-ativc 
 du liquide testiculaire, Arch. d. physiol. norm, el path. (Paris), 
 1891, xxiii, 747. 
 1^0 Howell (W. IL): The chemical regulation of the body by 
 means of activators, kinases, and hormones, Science (Xew 
 York), 1910, xxxi, 93.
 
 Hormones : Discovery, Production^ and Action 17 
 
 1* Starling (E. H.): Discussion on the therapeutic value of 
 hormones, Froc. Boy. Soe. Med. (Sec. Ther.), (London), 1914, 
 vii, 29. 
 
 '- Campbell (H.): The role of the blood-plasma in disease. 
 Lancet (London), 1907, i, 313 et seq. 
 
 PoPiELSKi (L.): Der Theorie der Hormone und innere Sekre- 
 tion, Kl. ther. Wchnschr. (Berlin), 1913, xx, 1133. 
 
 DuTOiT (A.): Der gegenwartige Stand der Hormonenlehre, 
 Aertd. Bund. (Munich), 1912, xxii, 265, 313, 325, 337. 
 
 KoHLER (H.): Der gegenwartige Stand der Hormonologie, 
 Dent. med-aeHsl. Ztschr. (Berlin), 1912, xli, 254.
 
 CHAPTER II 
 
 THE FUNDAMENTAL PRINCIPLES OF HORMONE 
 THERAPY 
 
 The Importance of the Metabolism in Disease — The Value of Hor- 
 mones in Indefinite Metabolic Disorders — A Study Fruitful 
 in Promise — The Range of Hormone Action — The Outside 
 Control of Hormone Production — The Homostimulant Action 
 of Organic Extracts — On the Dosage of Hormone Prepara- 
 tions — The Prospects of Hormone Therapy. 
 
 The study of hormones and their use as factors in the 
 stimulation or inhibition of certain functions of the body 
 has arrived at a stage which reaches well beyond the 
 laboratory of the physiologist; and although experimental 
 physiology is destined to throw much more light on this 
 subject, in certain phases of it, at least, its application in 
 clinical therapeutics is already established on a firm 
 basis. 
 
 The Importance of the Metabolism in Disease.— To apply 
 these fundamentals successfully in general practice, it is 
 essential to appreciate to the full the importance of the 
 role that metabolism plays. We have been accustomed 
 to consider certain diseases in a class by themselves, and 
 to call them "disorders of metabolism," and by this 
 segregation we have been led to overlook the fact that 
 the chemistry of the body is of equal importance in prac- 
 tically every other disease. One should also have a fair 
 knowledge of pathologic anatomy, or, if this is not feasible, 
 at least of the pathologic physiology of various glandular 
 organs in certain diseases. 
 
 18
 
 Fundamental Principles of Hormone Therapy 19 
 
 Fortunately, the extensive experimental work neces- 
 sary to secure such information has been well clone by 
 numerous interested investigators of unquestioned repu- 
 tation and excellent standing. One need only refer to 
 the voluminous literature published during the past few 
 years to become fully convinced that not only are many 
 diseases accompanied by changes in structure and func- 
 tion of certain secretory organs, but also that the adminis- 
 tration of corresponding gland substances has proved 
 well worthy of further study and clinical application. 
 It must be emphasized that one cannot always expect a 
 definite disease picture to respond favom*ably to a corre- 
 spondingly definite organotherapeutic remedy ; but among 
 a number of quite definite disease entities which have 
 been shown by experience to be influenced by hormones 
 are apepsia and the indigestions generally, pancreatic 
 insufficiency, asthma, intestinal stasis and atonia, utero- 
 ovarian disorders, as well as the numerous conditions 
 amenable to thyroid, pituitary, and adrenal medication. 
 
 The Value of Hormones in Indefinite Metabolic Dis- 
 orders. — On the other hand, there are not a few very in- 
 definite, but none the less well-marked, symptoms- 
 complex which have been found to be amenable to this 
 form of therapeutics, and among them we must not 
 overlook neurasthenia, suboxidation, certain mental dis- 
 orders, malnutrition, and tuberculosis. In numerous 
 other states not strictly classed as "disease," hormones 
 may form a useful adjunct method of treatment and a 
 means of increasing the necessary normal stimuli. Among 
 these are pernicious vomiting of pregnancy, the act of 
 parturition, lactation, uterine involution, suboxidation, 
 obesity, deficiency in gastro-intestinal function, etc. 
 
 The value of thjn'oid extract in myxoedema is beyond 
 question. It is a specific. This being the case, now that
 
 20 Practical Hormone Therapy 
 
 we can really augment a diminished, or can supply an 
 absent, hormone, have we not accomphshed a direct cura- 
 tive service that stands high above our usually indirect 
 and more or less haphazard methods of treatment ? If, 
 then, it is possible to secure from animals those substances 
 which in the normal course of events would have accom- 
 plished certain physiologic services in these animals, and 
 by introducing them into the human system, thus accom- 
 plish for the patient what they were intended to do 
 for the animal, is there not a very good ground for a 
 more general study of hormone therapy, and a broader 
 application of this idea in every phase of general 
 practice ? 
 
 Unfortunately, not every hormone-bearing preparation 
 is as uniform in its action as thyroid extract is in myx- 
 cedema, and where in one case excellent results may be 
 obtained from a product of this character, in another we 
 find very mediocre changes. We are still in the dark 
 as to the explanation of many facts regarding these 
 matters. We cannot tell exactly why the results vary so 
 greatly, but it seems clear that the effects of a hormone 
 given as a therapeutic agent are in proportion to its 
 power to stimulate or inhibit the corresponding parts of 
 the endocrinous system, and evidently the responsiveness 
 of these various organs differs greatly in different indi- 
 viduals. " It is also probable that one hormone may, to 
 a certain extent, be able to supplement or replace another 
 of similar but not identical properties. These points serve 
 to illustrate how much less we know about the hormones 
 than we do about the ferments secreted by the digestive 
 glands, and how further knowledge of the physiological 
 action of the hormones will enlarge their sphere of action 
 as therapeutic agents."^ 
 
 Furthermore, we now have a class called " diseases of
 
 Fundamental Princi'ples of Hormone Therapy 21 
 
 the internal secretory organs " in which definite patho- 
 logic changes have been found in certain of these glands, 
 as in Addison's disease, goitre, acromegaly, etc. We 
 must not allow ourselves to overlook the minor and in- 
 tangible disorders of the internal secretory organs, which, 
 because of their insidiousness, often escape attention, 
 although, because of their comparatively greater frequency, 
 they are of equal or even greater importance to the general 
 practitioner than are the major conditions, the presence 
 of which is patent. 
 
 This is at once the most promising and most complex 
 of the prospects before us, and the more it is studied the 
 greater will be the encouragement to delve deeper into 
 the mysteries of this fathomless subject. 
 
 We have already seen how for over fifty years it has 
 been known that certain glands have a direct as well as 
 a remote influence upon other glands and upon numerous 
 functions of the body, but until very recently the sub- 
 stances responsible for this influence have been quite 
 hypothetic. They had not been isolated and named, 
 although evidence of their presence was plentiful. Con- 
 sequently, when the practice of opotherapy was first 
 begun, the glands themselves were administered in toto ; 
 later glycerine extracts and dried extracts were used. 
 Naturally much therapeutically useless material was 
 given in this way, and not infrequently such extracts 
 contained antagonistic substances which interfered in a 
 varying degree with the desired therapeutic action. As 
 yet we have learned little of the methods of preparing 
 hormones in a pure state. Some have been isolated, and 
 of these at least two — the adrenal and posterior pituitary 
 hormones — are now of known chemical form, the former 
 even having been made synthetically. Our knowledge, 
 however, has increased our capacity to produce active
 
 22 Practical Hormone Therapy 
 
 preparations, and recourse to the vacuum-drier has facili- 
 tated tliis work very much. 
 
 A Study Fruitful in Promise. — While the hormones are 
 still on the verge of our knowledge, many do not appre- 
 ciate their value through quite pardonable ignorance. 
 Since their range of activity is as yet known only in part, 
 the part is undervalued by many because our knowledge 
 of it is admittedly incomplete. At a new departure that 
 revolutionizes our present methods we hesitate, because 
 we are loath to let go the notions so thoroughly ingrained 
 in our medical constitutions. 
 
 No one who has used hormones for any length of time, 
 and who is in a position to appreciate their specificity 
 and value, can deny the extreme importance of this phase 
 of therapeutics. Surely, as Dr. Leonard Williams has 
 so well said^: " This is a subject of inquiry as fascinating 
 as any in the whole range of medicine, and as fruitful in 
 promise as any in the whole range of therapeutics." 
 
 The Range of Hormone Action. — To the student of 
 practical therapeutics an outline of the availability of 
 hormone action will be of interest. There are several 
 different ways in which the hormones may render thera- 
 peutic service: 
 
 1. Substitution therapy: by supplying missing hor- 
 mones the definite loss of which is known to be due to 
 destructive lesions or congenital absence of an organ. 
 For example, as in hypothyroidism, where the thyroid 
 treatment actually replaces a secretion. 
 
 2. Supplementary therapy: by augmenting directly or 
 reflexly a presumed deficiency, due either to an increased 
 physiological demand or to a decreased hormone output. 
 This includes both the hormone and the chalone action, 
 as exempUfied respectively by the luteal treatment of 
 amenorrhoea and the pancreas treatment of glycosuria.
 
 Fundamental Princi'ples of Hormone Therapy 23 
 
 3. Specific physiological therapy: by producing a defi- 
 nite physiological influence which is indicated, but is not 
 due to any change in the normal hormone-production 
 of the patient, as in the use of infundibular extract for 
 stimulating uterine contractions during labour, or of the 
 angiotonic and styptic action of adrenaline. 
 
 4. Empirical application: a strictly unscientific but 
 nevertheless sufficiently useful phase of hormone therapy, 
 which produces results in a manner which is clinically 
 evident but more or less unexplainable from the strictly 
 scientific basis, as in the pituitary treatment of functional 
 ovarian disorders, the parathyroid treatment of paralysis 
 agitans, the thjrroid treatment of rheumatic arthritis, or 
 the pluriglandular treatment of "run-down conditions," 
 etc. 
 
 The Outside Control of Hormone Production. — Another 
 most important feature of the broad usefulness of hor- 
 mones in normal physiology, as well as in their therapeutic 
 application, is the fact that, in addition to their specific 
 activating powers, hormones control their own production 
 as well as one another. It is equally true, although bj^ 
 no means as extended in its possibilities of application, 
 that the inhibitory or antagonistic action of certain 
 hormones — or the " chalones," as they may yet be called 
 — is available in the control of certain conditions in which 
 the production of hormones by an organ is an excess of 
 the needs of the body, and is hence a deterrent to the 
 physiological harmony. This is best illustrated by the 
 conditions known as " hyperthyroidism " and "hyper- 
 ovaria." 
 
 This is a most important phase of hormone therapy; 
 for we must remember that when a certain secretion is 
 deficient, not only have we the results of this deficiency to 
 deal with, but we have also the baneful effects of an un-
 
 24 
 
 Practical Hormone Therapy 
 
 controlled antagonistic secretion. This " hormone 
 balance " is a most important factor in medical treat- 
 ment, and one that is Yevy frequently overlooked. It 
 seems advisable to lay special emphasis on the intricacies 
 of these interactions, and the subject is therefore con- 
 sidered in a chapter by itself. 
 
 The Homostimulant Action of Organic Extracts. — One 
 of the most important advantages of hormone therapy is 
 dependent upon the influence which hormone-bearing 
 extracts have upon the organs to which they correspond. 
 This is so general that it seems to be an invariable occur- 
 rence. HaUion^ was apparently the first to refer to this influ- 
 ence, and the following axiom has been called " Hallion's 
 law ": Extracts of an organ exert on the same organ an 
 exciting influence which lasts for a longer or shorter time. 
 When the organ is insufficient, it is conceivable that this 
 influence augments its action, and, when it is injured, 
 that it favours its restoration. 
 
 Here, then, is one of the fundamentals of this method 
 of treatment; and while it is manifestly useless to hope 
 to regenerate an organ which is totally destroyed, it has 
 been proved, again and again, entirely possible to re- 
 generate that part of the gland which is not yet beyond 
 the hormone stimuli, and even to cause a hypertrophy of 
 the tissue thus regenerated, thereby restoring a measure 
 of its former usefulness. 
 
 On the Dosage of Hormone Preparations. — Since hor- 
 mones are beginning to be used extensively as drugs, the 
 subject of dosage is naturally an important one. As the 
 manifest service of a hormone is not to supply nutritive 
 material to the cells, but to stimulate them to certain 
 functions, a very small amount suffices to cause the de- 
 sired results. The majority of hormones are innocuous, 
 and the inert material frequently associated with them
 
 Fundamental Principles of Hormone Therapy 25 
 
 when used in the form of animal extracts is non-toxic. 
 There are, however, several exceptions to this rule; the 
 dose of thyroid extract must be very carefully regulated, 
 and extract of the prostate gland is quite toxic. Very 
 minute doses of adrenaline and infundibulin are used, 
 and their influence should be always carefully watched; 
 but, generally speaking, extracts of such organs as the 
 duodenum, spleen, liver, pancreas, ovary, testicle, mam- 
 mse, etc., are not dangerous, and the dosage is based 
 rather upon experience than upon careful toxicologic 
 experiments. 
 
 The Prospects of Hormone Therapy. — If, then, it is 
 possible successfully to influence the cell-workings of 
 various organs by means of substances procured from 
 other animals, the possibilities open to us are immense, 
 and progress to the ultimate control of many complicated 
 conditions is limited only by the capacity of the pharma- 
 cist to produce, in convenient form and at a reasonable 
 price, satisfactory preparations from those various animal 
 organs. 
 
 There is a genuineness in the enthusiasm of many 
 students of this subject that many less interested indi- 
 viduals have not appreciated. The prospect of results 
 in this field of research are positively enormous, and as 
 our knowledge broadens and the facts become more 
 generally known, many of these possibilities will become 
 actualities, and available in the everyday routine of any 
 physician who is willing to apply them. 
 
 This, all too briefly outlined, is the present position of 
 hormone therapy. That it opens up a new pathway in 
 therapeutics is undoubted. It explains in many respects 
 the action of the older drugs, and affords a solid ground- 
 work for future methods of treatment. It would seem of 
 the utmost importance, then, that practitioners should
 
 26 Practical Hormone Therapy 
 
 become thoroughly acquainted with its many ramifications^ 
 and with this object the author has collated here many 
 recent opinions and findings on this highly important 
 subject. 
 
 BIBLIOGRAPHY 
 
 ^ Murray (G, R.): Discussion on tlio therapeutic value of 
 
 hormones, Proe. Boy. Soc. Med. (Sec. Therap.), (London), 
 
 1914, vii, 23. 
 - AViLLiAMS (L.): The therapeutic promise of the internal 
 
 secretions, Pract. (Loudon), 1911, Ixxxviii, 605. 
 "* Halliox (L.): Sur le mecanisme d'action de Topotherapie, 
 
 Jour. d. mid. d. Paris, 1914, xxxiv, 71. See also id.: Les 
 
 hormones, Pr. med. (Paris), 1912, xx, 433. 
 
 McFadden (W. G.): The antiquity and fallacy of animal 
 
 extract therapy, Lancet-Clinic (Cincinnati), 1906, Ivi, 35. 
 Jacob Y (M.) : Die Lehre von der Hormonen und die Moglichkeit 
 
 der praktischen Verwertung, Zusammenfassenden Ueberblick 
 
 Dent. med. Wehnschr. (Leipzig), 1911, xxxvii, 2123. 
 Park (R.): Isopathy in the twentieth century, Post-Grad. 
 
 (Xew York), 1912, xxvii, 855. 
 BoRCHARDT (L.): Die Bedeutung der Hormone fiir die innere 
 
 Medizin, Beih. z. Med. Klin. (Berlin), 1911, vii, 123. 
 Gley (E.): Correlations fonctionelles et inteiTelations humo- 
 
 rales, liev. gen. d. sc. pares et apj)l. (Paris), 1913, xxiv, 537. 
 Beebe (S. p.): Glandular therapy, in Hare's "Modern Treat- 
 ment " (Philadelphia), i, 551-572. 
 Sajous (C. E. de M.): True versus false opotherapy, N. Y. 
 
 Med. J., 1909, xc, 437. 
 Id.: The ductless glands in surgical therapeutics. Mo. Cycl. 
 
 and Med. Bull. (Pliiladelphia), 1912, v, 219. 
 Id.: Physiology of the ductless glands in their relations to 
 
 obstetrics. Am. Jour. Obs. (New York), 1912, Ixvi, 509. 
 Hare (II. A.): The therapeutic application of the ductless 
 
 glands, ibid., 514. 
 Murray (G. R.): Some aspects of internal secretion in disease, 
 
 Br. Med. J. (London), 1913, ii, 157, 212. 
 Denison (H. S.): Ilormonic equilibrium of the glands of 
 
 internal secretion, Colo. Med. (Denver), 1912, ix, 68. 
 MoRAT (J. P.): Les 86cr6tions internes et le systeme nerveux, 
 
 Lyon med., 1911, ex vii, 617. 
 Meltzer (S. J.): Animal experimentation in relation to our 
 
 knowledge of secretions, especially internal secretions, J. 
 
 Am. Med. Assn. (Chicago), 1910, liv, 1430.
 
 Fu7idamental Principles of Hormone Tlierapy 27 
 
 Dardel (J.): The present status of organotherapy, Praet. 
 
 (London), 1912, Ixxxviii, 852. 
 Osborne (0. T.): Disturbances of the internal secretions 
 
 clinically considered, J. Am. Med. Assn. (Chicago), 1910, liv, 
 
 670. 
 Browning (W.): A brief consideration of internal secretions 
 
 and animal therapy, N. Y. State J. 2Ied. (New York), 1909, 
 
 ix, 350. 
 Berkeley (W. N.): How far have we got with the clinical use 
 
 of the internal secretions ? Old Dom. J. lied, and Surg. 
 
 (Richmond), 1913, xvi, 213. 
 Leslie (R. M.): Internal glandular secretions and their 
 
 influence on the causation and treatment of disease, Clin. J. 
 
 (London), 1913, xlii, 289. 
 Strubell (A.): Pharmako-dyuamische Probleme. III. Der 
 
 Einfluss der Hormone auf den opsonischen Index, Berl. hi. 
 
 Wchnschr., 1912, xlix, 2350. 
 Serrallach (M.): Fundamentos biologicos de la opoterapia, 
 
 Bev. d. med. y cirurg. (Barcelona), 1912, xxvi, 289. 
 Chvostek (F.): Konstitution und Blutdriisen, Wien. kl. 
 
 Wchnschr., 1912, xxv, 6. 
 Morris (M.): The internal secretions in relation to derma- 
 tology, Br. Med. J. (London), 1913, i, 1037. 
 MuNZER (A.): Ueber die atiologische Bedeutung psychischer 
 
 insulte bei Erkraukungen der Blutdriisen, Berl. kl. Wchnschr., 
 
 1912, xlix, i, 1165. 
 Starr (M. A.): Neui'oses dependent upon errors of internal 
 
 secretion of the ductless glands, N. ¥. Med. J., 1912, Ixxxi, 
 
 1217. 
 Kranz (P.): Inuere Sekretion, Kieferbildung und Dentition, 
 
 Beitr. z. kl. Chir. (Tiibingen), 1913, Ixxxii, 180. 
 Editorial: Lesions of the ductless glands and disease, N. Y. 
 
 3Ied. J., 1914, xcix, 389. 
 Levi (L.): Dissociation et instabilite pilaires par dysendo- 
 
 crinie, Sem. med. (Paris), 1914, xxxiv, 8.
 
 CHAPTER III 
 
 THE HORMONE BALANCE 
 
 The Intercellular Equilibrium — The Control of Nutrition — A 
 Possible Relation of the Internal Secretions to Cancer — Gly- 
 cosuria : An Illustration of a Disturbed Hormone Balance — 
 The Hormone Control of Carbohydrate Metabolism — The 
 Thyroid Control of the Hormone Balance — The Influence of 
 the Ovaries — The Kinetic System — Hormone Stimulation of 
 Muscular Activity — A Diagram showing the Relations of the 
 Endocrinous Organs — The Psychic Control of Endocrinous 
 Action — A New Idea in Organotherapeutic Preparations — 
 The Loss of the Hormone Balance — The Modification of Dis- 
 orders of the Hormone Balance. 
 
 The Intercellular Equilibrium. — In the body every 
 motive force is balanced by a retarding force, and this 
 nice equilibrium is quite essential to the proper regulation 
 of the numerous cellular functions. Should one or other 
 of two factors gain the ascendency, disorganization may 
 be expected at once, and the extent of this disturbance 
 can hardly be confined to the single area in which it is 
 initiated. This is evidently what happens in diabetes, 
 myxcedema, acromegaly, ovarian insufficiency, and 
 numerous other conditions related to the internal secre- 
 tory system. If we are able partly or wholly to restore 
 that balance by the addition of a suitable agent in the 
 form of an animal extract or hormone, we shall have 
 assisted Nature in a very effective and helpful manner. 
 
 Numerous writers have considered the close interrela- 
 tion between the internal secretions, and have demon- 
 strated that certain of these secretions are synergists, 
 
 28
 
 The Hormone Balance 29 
 
 while others are antagonists.^ Bearing in mind the 
 altruistic function of the cell mentioned in the first chapter 
 — that function which influences its near or remote neigh- 
 bours — the importance of the hormone equilibrium may- 
 be faintly appreciated. 
 
 The Control of Nutrition. — The principal function of the 
 hormones is the maintenance of cellular activity of the 
 control of bodily nutrition. As the subject becomes more 
 thoroughly studied, we may expect to find out more defi- 
 nitely how this influence is exerted. At present we must 
 be satisfied to believe that the hormones are far more 
 important factors than the trophic nerves, although 
 doubtless a combination of their activities is essential. 
 
 This fact is an important underlying reason for the 
 variations in susceptibility to disease, and it is not too 
 much to state that the condition of the hormone 
 balance is of paramount importance in the maintenance 
 of health. It is quite likely, moreover, that the modifi- 
 cation of certain chronic dyscrasias by dietetic and 
 hygienic measures is specifically caused by the influence 
 of these measures upon the activities of the ductless 
 glands. Some interesting experimental work gives weight 
 to this suggestion, and seems to show a connection be- 
 tween the internal secretory activities and cancer. 
 
 A Possible Relation of the Internal Secretions to Cancer. 
 — Following the experiments of Hunt^ in the Govern- 
 ment laboratories in Washington, which showed that 
 certain drugs and diets were capable of equally stimulating 
 or repressing the activities of the thyroid gland, it has 
 seemed that dietetic regulation may influence the growth 
 of certain tumours. Some very interesting work has been 
 done in this connection by Osborne and Mendel,"^ which, 
 while beside this subject, bears a certain relation to some 
 interesting experiments at the American Oncologic Hos-
 
 30 
 
 PracMcal Hormone Therapy 
 
 pital in Philadelphia. Sweet, Corson-White, and Saxon^ 
 have shown that the diets suggested by Osborne and 
 Mendel have a decided influence upon the development 
 of transplanted tumours in animals ; and still more inter- 
 esting than this is the fact that tumours transplanted into 
 animals which had previously been deprived of certain 
 internal secretions, such as that of the gonads, showed 
 that the animal was rendered more susceptible since the 
 frequency of the establishment of the tumour growth 
 and the rapidity of its growth was noticeable. In this 
 connection it is interesting to recall that cancer is essen- 
 tially a disease of that period of life when certain of the 
 ductless glands lose their normal function, this loss en- 
 tailing related changes in the whole chain of interrelated 
 functions of the ductless glands.^ Perhaps it is suggesting 
 too much to say that the ductless glands are responsible 
 for the condition of the body which permits the growth 
 of cancer cells, or that by applying the fundamentals of 
 organotherapy we are likely to be able to control this 
 disease ; but such facts as these seem very pregnant, and 
 it is by no means impossible that future study will show 
 that the hormones may be very intimately concerned in 
 the prevention and cure of this dread disease. 
 
 Glycosuria : An Illustration of a Disturbed Hormone 
 Balance. — Much has been added to our knowledge of the 
 hormone balance by the study of several diseases in which 
 hormone action and interaction are intimately concerned. 
 Prominent among these is diabetes, one form of which 
 now seems definitely to be classed as a disorder of certain 
 of the organs concerned in the maintenance of the hor- 
 mone balance. From the numerous experiments which 
 have been made, we know that there is a close relation- 
 ship between the internal secretions of the pancreas and 
 thyroid. They oppose one another, and it seems to be
 
 The Hormone Balance 31 
 
 established that " in hyperthyroidism the function of 
 the pancreas is depressed and ahinentary glycosuria is 
 easily brought about. On the other hand, in atrophy or 
 hyperplasia of the thyroid gland, the pancreatic powers 
 are increased, and patients suffering from these disorders 
 — -for instance, myxoedema — can take large quantities of 
 glucose without the slightest glycosuria. . . . The 
 thyroid also can be influenced by the pancreas, and so we 
 are not surprised to find that the moment the pancreas is 
 ablated, the thyroid function gains the upper hand."^ 
 
 The pancreas also " acts as a brake upon the sugar- 
 producing mechanism." This was first emphasized by 
 Opie, whose work and its importance is more fully re- 
 ferred to in the chapter devoted to the pancreatic hor- 
 mone, and later quite conclusively proved by Eppinger, 
 Rudinger, and Falta. They also showed that the adrenal 
 bodies play an important part in the glycosuric-complex, 
 as the chromaffin hormone — the hormone produced in 
 the adrenal chromic-acid-staining cells — -regulates the ex- 
 citability of the sugar-producing mechanism of the liver. 
 This is directly antagonistic to the work of the pancreas, 
 as it is one of stimulation. Von Noorden'^ says: " Adre- 
 nalin gives a rapid expulsion of glycogen from the liver, 
 and glycosuria results. ... A moderate dose of adre- 
 nalin produces a glycosuria lasting for some hours; after 
 that, normal conditions are restored. ... If injections 
 are repeated several times, glycosuria does not reappear. 
 A much larger dose of adrenalin is required to produce 
 sugar in the urine. . . . An inhibition of the action of 
 adrenalin may be explained by supposing that the pan- 
 creas was taken by surprise by the first stimulating dose, 
 and consequently could not prevent the disturbances of 
 sugar control ; but the repetition of the stimulus puts the 
 pancreas into a strong defensive position, and a stop is
 
 32 Practical Hormone Therapy 
 
 put to the disturbance in the regulating mechanism pro- 
 duced by the adrenahn."^ 
 
 The pituitary evidently is concerned in the metabolism 
 of carbohydrates, for disturbances of pituitary fmiction 
 have frequently, as one of the associated symptoms, the 
 presence of a greater or less degree of glycosuria. The 
 parathyroids also stand in a metabolic relation to the 
 pancreas, and certain experiments have been made to 
 show that they are related to a number of the other 
 internal secretory organs. It may be stated here that 
 parathyroid ablation weakens the functions of the pan- 
 creas and favours glycosuria, proving that their action is 
 antagonistic to that of the thyroids. 
 
 The Hormone Control of Carbohydrate Metabolism. — 
 Von Noorden^ has illustrated his views regarding the 
 control exercised by the various hormones upon one 
 another in the intricacies of carbohydrate metabolism by 
 a diagram, which, with the permission of this distinguished 
 authority, is reproduced on p. 33. 
 
 His own description of this diagram follows : 
 
 The dotted lines indicate " nervous paths," the continuous 
 lines "blood paths"; the arrows show the direction of the 
 stimulus; and the plus or minus signs behind them show whether 
 the stimulus increases or inhibits the power of the organ which 
 is influenced. 
 
 The normal metabolism of the carbohydrates is concerned only 
 with Paths I,, II., and III. Path I. shows that material, inciting 
 an increased activity of the sugar-forming mechanism, streams 
 up from the intestine to the liver. This path in diabetes corre- 
 sponds to the " alimentary factor " in glycosmia. We can, at 
 will, control the stimuli passing up by this way. The conscien- 
 tious carrying out of this is the aim and object of diabetic cures. 
 
 Paths II. and III. show the action of the metabolic processes 
 as a whole. Along Path II. are transmitted the requirements 
 of the tissues (especially tlie muscles), and their extent corre- 
 sponds to the amount of sugar formed and exported by the 
 blood (Path III., hepatic vein, heart, and arteries). The total 
 stimulus transmissal by Path II. can also, to a certain extent, 
 be voluntarily controlled. It can be diminished by excluding 
 everything which markedly increases the total production of
 
 The Hormone Balance 
 
 33 
 
 calories (such as heavy muscular work, loss of heat, abundant 
 food, high protein diet). That these are the factors which 
 increase the production of calories and at the same time the 
 formation of sugar has already been noted; and we make us^i 
 of this knowledge to achieve our aims in the treatment of diabetes. 
 By Paths A and B the influences are sent from the two most 
 important and powerful controllers, which govern the sugar 
 factory, the sensitizing suprarenals (A), and the calming pancreas 
 
 ^Central Nervous 
 System 
 
 Farat/iyrobds 
 
 ChrGma/fub 
 SysterrL 
 
 Pamrtsas 
 
 Fig. 1. 
 
 (B). Along TatJis a and h indicate the active influences by which 
 the functions of the controlling organs can be increased or dimin- 
 ished. Along Path a pass the nervous impulses. It is along this 
 path that the piqiire of Claude Bernard exerts its effects, and 
 psychical distvirbances obtain their influence over the sugar pro- 
 duction of diabetes. There may also exist other paths which 
 influence the production of adrenaline, and consequently that of 
 sugar also; I refer to the over-activity of the suprarenals and the 
 
 3
 
 34 Practical Hormone Therapy 
 
 hypertension developed in chronic nephritis. But there is so 
 much uncertainty surrounding this and other questions that I have 
 only suggested in the diagram the possibility of other paths than 
 that of the sympathetic. 
 
 Path b indicates the certain relationship between the thyroid 
 and the pancreas. The indicator on this path canies a negative 
 sign to show that the internal secretion of the pancreas is not 
 increased, but inhibited by the thyroid. A path from the para- 
 thyroids to the pancreas (V) is also shown on the diagram. The 
 indicator carries a positive sign. Up to the present the prob- 
 ability of the existence of this path is only supported by certain 
 experimental facts. There is no clinical evidence for it in 
 diabetes. It is, however, only of subordinate importance. 
 The impulses passing to the pancreas from the hypophysis 
 appear to be more far-reaching. I may refer to the extraordinary 
 frequency of diabetes in acromegaly compared with the astonish- 
 ing tolerance of carbohydrates shown in cases of fatty degenera- 
 tion of the so-called " dystrophia adipose -genitalis." The influ- 
 ence of the pituitary gland is identical with that of the thyroid. 
 
 Paths a and b are secondary. When the functions of the two 
 principal organs (pancreas and suprarenals) are normal, the 
 extent of the stimuli they originate is of no great or immediate 
 importance. When, however, there is any morbid predisposition 
 (such as anatomical changes, functional debility, or diminished 
 excitability of the pancreas, or increased excitability of the 
 suprarenals), the more distant organs can exert a distinct influ- 
 ence on sugar production. 
 
 The Thyroid Control of the Hormone Balance. — It is 
 difficult to imagine an organ more intimately related to the 
 numerous hormone-producing glands than the thyroid. 
 Reference to several of the clinical and experimental 
 findings associated with the study of the various forms of 
 goitre will quickly show how complex are its lines of 
 communication. This evidence is more thoroughly 
 worked out and more extensive than is the case with any 
 of the other endocrinous organs. ^° 
 
 As we have just seen, the thjrroid is an antagonist to 
 the pancreas, and in this direction, at least, a complement 
 to the adrenals. FrankeP^ has shown that in Graves's 
 disease the amount of adrenaline in the blood is increased 
 several hundred per cent., and others have concluded 
 that the thyroid stimulates the adrenal medulla. Ep-
 
 The Hormone Balance 
 
 35 
 
 pinger, Rudinger, and Falta^- have performed numerous 
 experiments involving excision of the thyroid and of the 
 pancreas, as well as the administration of glandular 
 preparations, and, in addition to their conclusion regarding 
 the antagonism of the pancreas to the thyroid and 
 adrenals just mentioned, they also found that the adrenals 
 and thyroids mutually stimulate one another, and that 
 these glands mutually antagonize the pancreas.* These 
 writers have illustrated this by means of the accompany- 
 ing diagram : 
 
 This has also been schematically represented by 
 Cammidge^^ in slightly modified form. He uses a quadri- 
 lateral figure with the pancreas, thyroid, parathyroids, 
 and chromaffin tissue at the four angles (see Fig. 3). 
 
 The findings at autopsy of many myxcedematous indi- 
 viduals have shown that thjnroid atrophy is very frequently 
 accompanied by pituitary hypertrophy, and the general 
 consensus of opinion favours the view that the thyroid 
 normally has an inhibitory influence upon the pituitary, 
 
 * This may be a reason wliy tlie pancreas is said to be six or seven times 
 larger than the necessities of its normal production of external enzyme- 
 bearing secretion actually require — it has such a vital position as a check to 
 these important endocrinous glands. It may also be an explanation of tlie 
 frequency of alimentary disorders in conditions of thyroid or adrenal excess.
 
 36 
 
 Practical Hormone Therapy 
 
 especially its posterior lobe, and that the hypertrophy 
 just mentioned is due to a partial or complete removal of 
 this check. 
 
 More remarkable still is the relation of the thyroid to 
 the gonads. Chief among the clinical manifestations of 
 hypo- and hyper-thyroidism are disturbances in the repro- 
 ductive glands. In myxoedema sex depression is very 
 frequent, in men lack of development or impotence being 
 the result. In women amenorrhoea and ovarian atrophy 
 are common, while thyroid therapy is found to cause a 
 remarkable regeneration in the growth and activity of 
 the gonads. In hyperthyroidism ovarian disturbances are 
 
 PANCREAS 
 
 PARATHYROIDS, 
 
 CHROMAFFIN TISSUE. 
 Fig. 3. 
 
 almost invariably found, Rogers" believing that " dis- 
 turbances of menstruation with large and tender ovaries 
 always occur in Basedow's disease." All ovarian involve- 
 ments, however, are not identical, for in some cases 
 amenorrhcea has been found, but dysmenorrhcea and 
 menorrhagia are much more frequent. It is generally 
 conceded that the thyroid stimulates the gonads and is 
 an important factor in the establishment and furtherance 
 of sexual activity. 
 
 Two other glands, or sets of glands — the thymus and 
 the parathyroids — are unquestionably intimately con- 
 nected with the thyroid. Their relationship is discussed 
 in the chapters dealing with these respective subjects.
 
 The Hormone Balance 37 
 
 The Influence of the Ovaries. — Ott^° has stated that: 
 "Just as glands with an external secretion concur in 
 taking up the work not accomplished by the others and 
 unite in the perfection of the products to be brought 
 forth, in a similar way the glands with an internal secre- 
 tion concur in the metabolites to be produced; a sort of 
 physiological balance is maintained between the activities 
 of the different glands in the wilderness of metabolism." 
 There are several hormones produced by the reproductive 
 organs, and they have a close interrelationship with one 
 another and with many of the other internal secretory 
 organs. It is supposed that the luteal hormone antago- 
 nizes the thyroid. This is evidenced by the enlargement 
 of the thyroid, which often occurs during pregnancy ; and 
 the fact that Graves's disease is essentially a disease of 
 women is possibly also due to this relation. 
 
 Mannaberg^^ is convinced that the ovaries play some 
 part in the clinical picture of exophthalmic goitre. This 
 may be due to some substance formed in the ovaries in 
 such a way that the goitre results. By exposures to the 
 Rontgen rays, the source of this substance in the ovaries 
 is dried up, and the thyroid is permitted to resume its 
 normal activity. In ten cases in which he has applied 
 this measure a favourable influence was manifest on all 
 the symptoms except enlargement of the gland. He does 
 not call it a cure in any case, as the pulse is stiU usually 
 unstable. It is possible that a course of thyroid treat- 
 ment might advantageously supplement the radio- 
 therapy. In eight of the ten cases the patients gained 
 from 23 to 21 per cent, in weight. In one case the exoph- 
 thalmos completely subsided, and in the others there was 
 no change. The most striking improvement was subjec- 
 tive ; nearly all the patients felt entirely well. 
 
 This same hormone is in relation with both the adrenals
 
 38 Practical Hormone Therapy 
 
 and pituitary body, for Schenk has shown that the re- 
 moval of the ovaries in rabbits causes adrenal hyper- 
 trophy, and Mayer, Alquier, and others note that ovari- 
 otomy causes an increased pituitary function. The sexual 
 glands are also closely related to the thymus, as evidenced 
 by the fact that persistent thymus is usually found in 
 individuals in which the sexual organs are undeveloped, 
 and, further, the thymus is persistent in eunuchs. On 
 the contrary, removal of the thymus in certain animals 
 retards the growth of the generative glands. 
 
 The hormone produced in the mammae is in close rela- 
 tionship with the generative organs, and the " mamma 
 hormone " produced in the foetus and placenta stimulates 
 the growth and functioning powers of the breast. The 
 production of the ovarian hormone at the commencement 
 of menstruation serves a similar but less complete pur- 
 pose. On the other hand, the hormone produced in the 
 mammae has a reserve action upon the ovaries and uterus, 
 as will be evidenced in the clinical experiments with 
 extracts of this organ, referred to in greater detail in 
 the chapter devoted to this subject. 
 
 The Kinetic System. — As a result of his assiduous study 
 of shock, blood-pressure, energy production, and the 
 mechanism of the regulation of the functions of the body, 
 Crile,^^ of Cleveland, has recently summarized his con- 
 clusions in a communication to the Cleveland Academy 
 of Medicine. He brings evidence to support his view that 
 there is a " kinetic system " which controls the produc- 
 tion, storage, and output of energy. 
 
 How intimately this department of the bodily activities 
 is connected with the hormone-producing organs, and 
 how dependent it is upon the hormone balance, will be 
 evident from the following paragraphs, which are taken 
 from the introduction to Crile's most interesting mono- 
 
 I
 
 The Hormone Balance 39 
 
 graph: "The self-preservation of man and kindred 
 animals is effected through mechanisms which transform 
 latent energy into kinetic energy to accomplish adaptive 
 ends. Man appropriates from environment the energy 
 he requires, in the form of crude food, which is refined by 
 the digestive system; oxygen is taken to the blood and 
 carbon dioxide is taken from it by the respiratory system ; 
 to and from the myriads of working cells of the body 
 food and oxygen and waste are carried by the circulatory 
 system; the body is cleared of waste by the urinary 
 system; procreation is accomplished through the genital 
 system ; but none of these systems are evolved primarily 
 for the pm-pose of transforming potential energy into 
 kinetic energy for specific ends. Each system transforms 
 such amounts of potential into kinetic energy as are 
 required to perform its specific work; but they do not 
 transform latent into kinetic energy for the purposes of 
 escaping, fighting, pursuing, nor for combating infection. 
 The stomach, the kidneys, the lungs, the heart strike no 
 physical blow ; their role is to do certain work, to the end 
 that the blow may be struck by another system evolved 
 for that purpose. I propose to offer evidence that there 
 is in the body a system evolved primarily for the trans- 
 formation of latent energy into motion and into heat. 
 This system I propose to designate The Kinetic System. 
 
 " The kinetic system does not directly circulate the 
 blood, nor does it exchange oxygen and carbon dioxide, 
 nor does it perform the functions of digestion, urinary 
 elimination, procreation; but though the kinetic system 
 does not directly perform these functions, yet it does play 
 indirectly an important role in each — just as the kinetic 
 system itself is aided indirectly by all the other systems, 
 
 " Among the organs in the kinetic system arc the brain, 
 the thyroid, the adrenals, the liver, the pancreas, and the
 
 40 Practical Hormone TTierajnf 
 
 muscles. The brain is the great central battery which 
 drives the body; the thyroid governs the conditions 
 favouring tissue oxidation; the adrenals govern imme- 
 diate oxidation processes; and the muscles are the great 
 converters of latent energy into motion and heat. . . . 
 Adrenalin alone, and thyroid extract alone, and brain 
 activity alone, and muscular activity alone, are capable 
 of causing the body temperature to rise above normal. 
 The functional activity of no other gland of the body 
 alone, and the secretion of no other gland alone, can cause 
 a comparable rise in body temperature — that is, increase 
 functional activity; and no active principle derived from 
 the kidney, liver, stomach, pancreas, hypophysis, para- 
 thyroid, spleen, intestines, thymus, lymphatic glands, or 
 bones can, per se, cause a rise in temperature comparable 
 to the rise that may be caused by the activity of the brain, 
 or the muscles, or by the injection of adrenalin or thyroid 
 extract. Then, too, when the brain, thjrroid, adrenals, 
 or muscles are eliminated, the power of the body to 
 convert latent into kinetic energy is impaired or lost. I 
 shall offer evidence tending to show that an excess of 
 either internal or external environmental stimuli may 
 modify one or more organs of the kinetic chain, and that 
 this modification may cause certain diseases. For ex- 
 ample, alterations in the efficiency of the cerebral link 
 yields neurasthenia, mania, dementia ; of the thyroid link 
 — Graves's disease, myxoedema; of the adrenal link — 
 Addison's disease, cardiovascular disease." 
 
 Without a doubt this theory will be assailed, as all 
 theories have been and will be ; but there seems to be no 
 ground for disputing the breadth of what was termed, 
 and not so long since either, the " hormone theory," nor 
 can one deny the extent and reasonableness of the system 
 of therapeutics which has been built upon this "theory."
 
 The Hormone Balance 41 
 
 Hormone Stimulation of Muscular Activity.— Elsewhere 
 reference will be found to the frequency of myasthenia 
 as a symptom of endocrinous disturbances, and from the 
 observation by Brown-Sequard of the dynamogenic effect 
 of testicular extract, not a few experimental and occa- 
 sional clinical investigators have demonstrated to what 
 an extent the ductless glands influence the neuromuscular 
 system. Markeloff^ has carried out numerous experi- 
 ments on dogs, and has determined the comparative 
 effects of various endocrinous extracts. In addition to 
 a number of commercial preparations he used freshly 
 made glycerin extracts, and as a result of his deductions 
 he has grouped the more important ductless glands into 
 two classes — viz., those which stimulate muscular ac- 
 tivity — the thyroid, testicles, pituitary body and adrenals ; 
 and those which depress muscular action — the parathy- 
 roids, pancreas, and thymus. 
 
 This information has been turned to good therapeutic 
 advantage, and is more fuUy discussed in the study of 
 pluriglandular extracts (Chapter XXX.). 
 
 The Relations of the Endocrinous Organs. — It is ahnost 
 impossible to portray in an inflexible diagram or state- 
 ment a mind-picture of the hormone actions and inter- 
 actions. Not always does a hormone act identically 
 under different conditions ; and many factors control the 
 influences exerted by the ductless glands upon themselves 
 and the body as a whole. 
 
 One can, however, roughly show the generally accepted 
 and principal action of the various endocrinous organs, 
 and the accompanying diagram concentrates much in- 
 formation on this subject. It has been called " good," 
 but in the author's opinion might be considerably better.* 
 
 • Criticisms ol' this diagram with a view to rcudciing it more complete 
 and less complex will be appreciated by the author, who may be addressed in 
 care of the publishers.
 
 The Relations oFTimENDOcRimus Organs 
 
 ( Sclif^maucaily arranged, ) 
 
 /^ — ^ 
 
 -.IrdatJifi. 
 
 ^— O.y— ^^ — — '"Swrmck. 
 
 y.5jL_ /^~N SU^ ' 
 
 =^ ■ CoopcraUort Stuvjzlatiarh ^ Anla^OJUsm, 
 
 Fia. 4.
 
 The Hormone Balance 43 
 
 KEY TO THE DIAGRAM OPPOSITE. 
 
 The Adrenals seem to work in harmony with, and are stimu- 
 lated by, the thyroid (2) and hypophysis (3), and are antagonists 
 to the pancreas (4), especially in the control of sugar combustion. 
 They also inhibit the thymus (5), and, perhaps, secretin (29). 
 The cortex stimulates the gonads (I). 
 
 The Thyroid stimulates the gonads (8), but may be also re- 
 ciprocally stimulated by them. It has a co-operative relation 
 with the hypophysis (7), and is closely but indefinitely associated 
 with the thymus (9) and the parathyroids (10). It stimulates 
 the adrenals (2), inhibits the pancreas slightly (6), and an exces- 
 sive secretion stimulates the intestine (11). 
 
 The Htpophysis (posterior lobe), experimentally at least, 
 stimulates the smooth muscle of the uterus (15) and intestine (13). 
 It is co-operative with the thyroid (7), and is said by some to 
 act vicariously for it. It stimulates the mammae (16), but is 
 slightly antagonized by the gonads (17) and the pineal (18). 
 There is a mutual antagonism between it and the pancreas (12), 
 and it also supplements, in a degree, the adrenals (3). 
 
 The Gonads check the pituitary (17), pregnancy (ovarian rest) 
 or castration causing increased pituitary activity. They depress 
 the thymus (19), for by their commencing action cause thymus 
 retrogression. They are reciprocal with the adrenal cortex (I), 
 are intimately related with the thyroid (8), being usually stimu- 
 lated by it, stimulate the uterus (23) and mammae (21), and, 
 paradoxically, are during mammary activity antagonized by 
 them (22). 
 
 The Pancreas controls (and is controlled by) the adrenals (4), 
 and in this connection is assisted by the parathyroids (24). It 
 seems to be inhibited by the thyroid (6) and the hypophysis (12). 
 Its stimuli come from the duodenum (secretin) (25), and, per- 
 haps, the intestine (26). 
 
 The Pineal inhibits the development of the gonads (20), and 
 there is a degree of antagonism between it and the hypophysis (18). 
 
 The Thymus inhibits the gonads (19), and vice versa. The 
 evidence regarding its relation to the thyroid is somewhat con- 
 tradictory ; it is often stimulated by hyperthyroidism, and thyroid- 
 ectomy often causes thymus hypertrophy (9). It is also inhibited 
 by the adrenals (5). 
 
 The Parathyroids are said to co-operate with the pancreas 
 (24) and the liver (27). In a rather indefinite manner they are 
 intimate with the thyroid (10). 
 
 The Mamm^ are stimulated by the hypophysis (16) and corpora 
 lutea (21), but they antagonize the ovaries proper (22) and the 
 uterus (28). 
 
 The Uterus is not generally conceded to be an endocrinous 
 organ, but it may bo experimentally stimulated by the hypoph- 
 ysis (15). The gonads stimulate its growth (23), and it is 
 inhibited by the mammuc (28).
 
 44 Practical Hormone Therapy 
 
 The Liver is stimulated by the duodenum (secretin) (30) and 
 intestine (36), and is stated to work in harmony with the para- 
 thyi-oids (27). 
 
 The Duodenum (secretin) activates the pancreas (25), the 
 liver (30), the intestine (31), and perhaps the stomach (32). Its 
 work is inhibited by the adrenals (29) and hypophysis (14). 
 
 The Intestine stimulates the liver slightly (36) and pancreas 
 (26). Its muscular activities may be stimulated by the spleen 
 (35), the hypophysis (13), and slightly by the thyroid (11). It 
 may be assisted by the stomach (33). 
 
 The Spleen is stated to have an activating power upon the 
 work of the stomach (34) and digestion generally. It is also 
 supposed to furnish a stimulant to the intestine musculature (35). 
 
 The Stomach may activate the intestine (33) and, in turn, 
 is stimulated by the duodenal secretin (32). Its work is also 
 enhanced by the spleen (34). 
 
 The Psychic Control of Endocrinous Action. — The pro- 
 duction of the secretions of the ductless glands is not 
 under the control of the will, but the mind evidently has 
 an influence upon certain phases of endosecretory activity. 
 Such psychic states as fear, rage, or pain, have been defi- 
 nitely proved to stimulate the production of adrenaline. 
 Cannon's experiments, which prove this, are referred to 
 more fully in Chapter XVIII. 
 
 A New Idea in Organotherapeutic Preparations. — 
 Miinzer^^, in commenting on the well-established fact that 
 the ductless glands seem to work in pairs, one of each pair 
 stimulating and the other checking certain functions, 
 has made a suggestion well worth considering. Since, by 
 the operative removal of the gland that does the checking, 
 the stimulating gland is left in full control, and the func- 
 tion of which it has charge receives only the stimulating 
 activation, one arrives at the logical conclusion that, 
 before utilizing glands for organotherapeutic purposes, 
 their antagonists should be removed. Miinzer cites as 
 an example Cushing's recent research on carbohydrate 
 tolerance before and after removal or exclusion of the 
 posterior lobe of the hypophysis. His experiments all 
 demonstrate that the posterior lobe has an inhibiting
 
 The Hormone Balance 45 
 
 action on the oxidation of carbohydrates, and is thus an 
 antagonist to the pancreas, which, as we know, is con- 
 cerned in the oxidation of carbohydrates. For organo- 
 therapy, therefore, a pancreas should be used which has 
 been previously activated by removal of its antagonist, 
 the infundibulum. This writer goes so far as to state 
 that only in this way will organotherapy accomplish what 
 has been hoped from it, and its use be extended. 
 
 This is a difficult suggestion to carry out, not merely 
 from financial considerations, but because of the com- 
 plexity of the relations of the hormone-producing organs. 
 The example referred to proves this, for we have already 
 seen that pancreas antagonism is not confined to the 
 pituitary, but that the thyroid and adrenals also have a 
 similar restraining action. 
 
 The Loss of the Hormone Balance. — It will be seen 
 that there is abundant opportunity for the blood-plasma 
 to become deficient in respect of its hormonic constituents. 
 The hormone balance may be very easily disturbed. 
 There may be too much, too little, or a perversion of any 
 single hormone, and these defects may be combined in 
 numerous ways, causing many disturbances, each of 
 which has its own peculiar effect upon metaboHsm. From 
 the above, it is evident that the intricacies of the hormone 
 balance are fully as complicated as those of the nervous 
 system, and it does not seem to be an overstatement to 
 say that they are fully as important. The importance, 
 then, of a knowledge of the antagonisms and sjniergisms 
 of the various hormones must be clear. With a knowledge 
 of these facts, it is possible to give a physiologic reason 
 for many organotherapeutic procedures. 
 
 The loss of the hormonic balance is written large in the 
 morbid phenomena of the human body, and its restoration 
 forms a main principle of modern therapy. The part
 
 46 Practical Hormone Therapy 
 
 played by the hormones in the destruction of toxins is 
 another important function. There is undoubtedly a 
 great future before hormone therapy, and a knowledge 
 of its present application is essential to all who practise 
 the art of medicine. ^^ 
 
 The Modification of Disorders of the Hormone Balance. 
 — Two statements may well be added as a final touch to 
 this chapter. One by Ott^^ reads thus: "In deficiency 
 or loss of internal secretions we substitute by giving the 
 gland by the mouth. In excessive internal secretion of 
 the gland we can overcome it by its antagonistic gland." 
 The other, by Blair Bell, 22 is as follows : " No experimental 
 finding in regard to the interrelationship of the internal 
 secretions can be regarded as of real or practical value 
 unless it be supported by clinical evidence." Hence it is 
 for the practical clinician to apply himself to the task of 
 establishing or refuting the large and ever-increasing 
 number of suggestions made by the experimentalists. 
 Much of the clinical experimentation, no doubt, will be 
 contradictory and unsatisfactory, but much will be of the 
 most encouraging nature; for, as an editorial writer in 
 the Medical Press and Circular^^ says: "In some cases 
 [referring to those treated by pluriglandular therapy] it 
 must be admitted that the results obtained seem to be 
 little short of miraculous "; and we must persist in our 
 attempts regardless of failure, for, as this same writer 
 continues: " On the other hand, the many failures point 
 to the fact that there is a great deal yet to be understood 
 and many difficulties to be overcome before hormone 
 therapy can be said to rest on an absolutely scientific 
 basis." 
 
 All of which goes to show the vital importance of a 
 knowledge of the hormone balance, as well as to lay the 
 foundation for a method of treatment which will it is
 
 The Hormone Balance 47 
 
 confidently believed, eventually revolutionize medical 
 practice. In the sections which follow, an attempt has 
 been made to bring into review a part of what has been 
 done in this direction, in order that the ways in which 
 an aggressive study of hormone action and therapy the 
 more conveniently may be made clear. 
 
 BIBLIOGRAPHY 
 
 1 Batliss (W. M.) and Starling (E. H.): Die kemische Koordi- 
 
 nation der Funktionen des Korpers, Ergebn. d. Physiol. 
 (Wiesbaden), 1906, v, 664. 
 
 2 Hunt (R.): Bull. Hyg. Lab. U.S. Pub. H. Serv., 1910, No. 69. 
 
 3 Osborne (T. B.) and Mendel (L. B.): Beobachtungen ueber 
 
 Wachstum bei Fiitterungsversuchen mit isolierten Nahrungs- 
 
 substanzen, Ztschr. f. physiol. Chem. (Strassburg), 1912, Ixxx, 
 
 307. 
 * Sweet (J. E.), Corson- White (E. P.), and Saxon (G. J.): 
 
 The relation of diets and of castration to the transmissible 
 
 tumours of rats and mice, J. Biol. Chem. (Baltimore), 1913, 
 
 XV, 181. 
 ^ Editorial: Diet, ductless glands, and tumours, J. Am. Med. 
 
 Assn. (Chicago), 1913, Ixi, 1460. 
 ^ Von NooRDEN:*pp. 40-41. 
 ' Id.: p. 51. 
 « Id. .-p. 52. 
 9 Id; pp. 60-63. 
 ^" See HosKiNS (R. G.): The interrelation of the organs of internal 
 
 secretion, Am. J. Med. 8ci. (Philadelphia), 1911, cxlii, 374, 
 
 and 535. 
 " Fraenkel (A.): Ueber den Gehalt des Blutes an Adrenalin bei 
 
 chronischer Nephritis und Morbus Basedowii, Arch. f. exp. 
 
 Path. u. Pharm. (Leipzig), 1909, Ix, 395. 
 " Eppinger (H.), Falta (W.), and Rudinger (C): Ueber die 
 
 Wechselwirkungen der Driisen mit innerer Sekretion, Ztschr. 
 
 f. kl. Med. (Berlin), 1908, Ixvi, 1; and 1909, Ixvii, 386. 
 *3 Cammidge:* p. 150. 
 ^* Rogers (C. C): Symptoms and treatment of exophthalmic 
 
 goitre, J. Am. Med. Assn. (Chicago), 1910, liv, 1893. 
 15 Ott (I.): The correlation of the glands with an internal secre- 
 tion, in " Internal Secretions," p. 108. 
 " Mannaberg (J.): Ueber Versuche die Basedow'sche Krankheit 
 
 mittels Rontgenbestrahlung der Ovarien zu beeinfluasen, 
 
 Wien. kl. Wehnschr., 1913, xxvi, 693.
 
 48 Practical Hormone Therapy 
 
 ^^ Crile (G. W.): Tlie kinetic system, Cleve. Med. J., 1913, xii, 
 
 665. 
 1* Makkeloff (G. L): [Influence of extracts of ductless glands 
 
 upon the ergographic curve (Russian)] Oboss. psichiat. nevrol., 
 
 etc. (St. Petersburg), 1912, xvii, 350; see also Eoiissky Vratch 
 
 (St. Petersburg), 1913, xii, 1140. 
 ^^ MuNZER (A.): Zur prinzipiellen Begriindung der Organothera- 
 
 pie, Berl M. Wchnschr., 1912, xlix, ii, 2022. 
 
 20 Editorial: Hormone therapy, Med. Pr. and Circ. (London), 
 
 1914, cxlvii, 83. 
 
 21 Ott:* p. 129. 
 
 22 Blair Bell (W.): The genital functions of the ductless glands 
 
 in the female. Lancet (London), 1913, i, 809, 937. 
 
 23 Editorial: Hormone therapy, Med. Pr. and Circ. (London), 
 
 1914, cxlvii, 83. 
 
 Okintschitz (L.): Ueber die gegenseitigen Beziehimgen einiger 
 Driisen mit innerer Sekretion, Arch.f. Gyn. (Berl.), 1914, cii, 
 333. (Extensive bibliography.)
 
 CHAPTER IV 
 
 DO THE SALIVARY GLANDS PRODUCE A 
 HORMONE ? 
 
 Salivary Digestion in the Stomach — Certain Heat-Stable Active 
 Principles — The Saliva activates Pancreatic Digestion — 
 The Relation of the Salivary Glands to other Endocrinous 
 Organs — The Relation of the Parotids to the Gonads — Parotid 
 Therapy in Ovarian Disorders. 
 
 The function of the salivary glands is generally con- 
 sidered to be limited to the production of saliva, a slightly 
 alkaline watery fluid whose principal function is to facili- 
 tate mastication and deglutition by moistening the food. 
 
 A secondary, or perhaps equally important, function is 
 that of producing a starch-splitting ferment — ptyalin — 
 which, however, has not so much opportunity to accom- 
 plish its task as it should have, because of the usually brief 
 contact with food in the mouth or its neutralization by the 
 gastric acid ; for ptyalin is active only in an alkaline medium , 
 
 Salivary Digestion in the Stomach. — According to Star- 
 ling,^ however, the food mass, on reaching the stomach, 
 is penetrated only with difficulty by the acid gastric juice, 
 which is secreted by the mucous membrane of the stomach 
 within five minutes of the taking of the food. Even half 
 an hour after a meal the interior of the mass of food in 
 the stomach may be still found to be neutral or slightly 
 alkaline. The food, therefore, thoroughly moistened by 
 and mixed with saliva, remains in the stomach for thirty 
 to forty minutes before the salivary ferment is destroyed 
 
 19 4
 
 50 Practical Hormone Therapy 
 
 by the penetration of the acid gastric juice. During this 
 time the ptyahn continues to exert its eflfect, so that we 
 may say that the chief part of the sahvary digestion occurs 
 actually in the stomach, and may result in the almost 
 c omplete alteration of the starch into dextrin and maltose 
 Certain Heat-Stable Active Principles. — Several investi- 
 gators have shown that the activity of the saliva is evi- 
 dently not limited to its contained ptyalin. It is well 
 known that this ferment is destroyed by heat, yet Roger^ 
 has shown that saliva submitted to a heat of 85° to 100° C. 
 for some time, is not completely inactive, for when mixed 
 with fresh saliva it notably augments the diastatic power. 
 Roger's figures are interesting. He found that if one 
 allows 0*05 c.c. of saliva to act upon 10 c.c. of a 1 per cent, 
 starch solution for half an hour, there will be obtained 
 0-007 gramme of sugar; but if one adds to the mixture 
 2 c.c. of heated saliva, the quantity of sugar is multiplied 
 five times, the figure recorded in exactly similar experi- 
 ments being 0-031 gramme. A material reduction in 
 the amount of heated saliva was made, and even then more 
 than three times the amount of sugar was produced — 
 0-025 gramme. According to this authority, one can re- 
 activate heated saliva with a mere trace of the fresh liquid, 
 and this seems to be a point of possible therapeutic worth. 
 The Saliva activates Pancreatic Digestion. — In a later 
 commmiication Roger and Simon^ have sliown that the 
 saliva has an energizing action upon the starch-splitting 
 powers of the pancreatic juice. If the acid contents of 
 the stomach are secured, then slightly alkalinized, and a 
 trace of fresh saliva is added, the digestive action imme- 
 diately reappears. With this in mind, an attempt was 
 made to show that this same activating power was a 
 factor in starch digestion in the intestine. In another 
 series of experiments saliva ^\as mixed with a starch
 
 Do the Salivary Glands produce a Hormone ? 51 
 
 solution. Sugar-splitting immediately commenced, and 
 then gastric juice was added and the process arrested. 
 Upon rendering the mixture alkaline, sugar-splitting did 
 not continue, but seemed to be definitely arrested; but 
 on the addition of a trace of pancreatic juice — a mere 
 fraction of a drop — the salivary activity was started 
 again, and the amount of sugar produced was multiplied 
 from four to five times. 
 
 Evidently, then, the saliva contains a substance which 
 is not a ferment, but which either activates the starch- 
 splitting powers of the pancreatic juice or is activated by it, 
 and hence the digestive powers of the saliva are not totally 
 lost because of its passage through the stomach. This is 
 not a hormone, although it is not improbable that the 
 parotid and submaxillary glands are infiuenced by 
 humoral channels, just as we have learned that the 
 majority of the other secretory glands are controlled; 
 and while some work has been done in France with prep- 
 arations of the parotid in the reactivation of starch 
 digestion, the advantage to be gained from such medica- 
 tion is not likely to be so great as the simple regulation 
 of diet and the physiologic stimulation of these glands 
 by giving foods that require much mastication, etc. 
 Hence salivary opotherapy as a means of stimulating the 
 activity of the salivary glands is not generally practised. 
 
 The Relation of the Salivary Glands to other Endocrinous 
 Organs. — A number of facts seem to indicate that the 
 salivary glands are a part of the endocrinous system. 
 For example, Sprinzles^ noted that in thirty-tliree cases 
 of obesity there was an enlargement of the parotid gland, 
 and suggests that this is more than a mere coincidence. 
 He notes that this hypertrophy is not found in persons 
 who are merely corpulent or well nourished, but in those 
 suffering from a type of obesity in which fat is evidently
 
 52 Practical Hormone Therapy fl 
 
 pathologic and found mostly upon the face, breasts, and 
 abdomen. It is inferred that this finding may be an 
 evidence of some more or less intimate connection with the 
 disordered metabolism responsible for the obesity. 
 
 Another endocrinous relationship of the parotid gland 
 has been mentioned — e.g., with the pancreas. Allegri,'' 
 in a recent communication, tells of three cases of acute 
 parotitis {"' orrechioni '''') which he believed to be the 
 cause of a severe inflammation of the pancreas, which 
 supervened in every case. It is entirely probable that 
 other similar connections may have been noticed, and that 
 the salivary glands are an integral part of the system of 
 glands of internal secretion. 
 
 The Relation of the Parotids to the Gonads. — There is 
 also an obvious connection between the parotid glands 
 and the gonads, for clinical experience with mumps very 
 frequently shows a " sympathetic " inflammation of the 
 testicles, which inust be considered as of humoral trans- 
 mission. Ovarian disorder, while not nearly so common, 
 has been occasionally seen as a sequel of acute parotitis. 
 
 BelP believes that the parotids have a considerable 
 influence upon the ovaries, but it is not likely that changes 
 in the normal activity of the parotids cause or prevent 
 ovarian disease. This writer, however, has used an ex- 
 tract of the parotid glands of sheep with what he con- 
 sidered good results in ovarian disorder, and reports 
 sixty cases of enlargement and pain in the ovaries in 
 which he was able by parotid treatment to avoid operative 
 interference and to obtain a complete cure. 
 
 Parotid Therapy in Ovarian Disorders. — Parotid ex- 
 tracts have been used in the control of dysmenorrhcea 
 with success. Mallett'' has convinced himself that they 
 relieve the pains with far more certainty than any uterine 
 sedative. Other associated pelvic disorders, such as local
 
 Do the Salivary Glands produce a Hormone ? 53 
 
 infiltrations, ovarian hypersemia, and the persistent reflex 
 headaches of ovarian origin, are considerably benefited 
 by this treatment. 
 
 Shober^ confirms the value of parotid extracts in the 
 treatment of ovaritis, ovarian dysmenorrhoea, and 
 neuralgia, and urges that the treatment be used more 
 frequently, and continued in each case for a minimum 
 period of two months in doses of 3 to 5 grammes of a 
 powdered extract three times a day. 
 
 At present no further use has been found for this 
 method of treatment, and it has "gone out of fashion," 
 due undoubtedly to the immense progress made in the 
 study of other organic preparations, which have been 
 found more suitable in this class of cases. 
 
 It seems, nevertheless, that the salivary glands, and 
 especially the parotid, are not entirely inert, either in 
 that part of their physiological action which is related to 
 hormone influences, or, for that matter, in organotherapy. 
 
 BIBLIOGRAPHY 
 
 1 Starling:* p. 741. 
 
 2 Roger (H.): Action de la salive chanff^e, C. r. Soe. Biol. (Paris), 
 
 1907, Ixii, 833. 
 ^ Roger (H.) and Simon (L. G.): Action syn^rgiquo de la salivo 
 et du -sue pancr^atique, 0. r. Soc. Biol. (Paris), 1907, Ixii, 
 1070. 
 
 * Sprinzles (H.): Parotisvergrosserung bei Fettleibigen, Wien. 
 
 Id. Wchnschr., 1912, xxv, 1901. 
 '> Allegri (A.): Pancreatite da orreehioni, Polid. (Rome), 1913, 
 
 XX (P.), 1538. 
 ^ Bell (R.): The treatment of carcinoma of the uterus; certain 
 
 forms of ovarian disease and fibroids of the uterus by means 
 
 of thyroid, parotid, and mammary gland extracts, Med. 
 
 Times and Hosp. Gas. (London), 1897, xxv, 398. 
 ■^ Mallett (E. p.): The use of parotid gland extract in the 
 
 treatment of ovarian disease, Am. Gyn. and Obs. Jour. (New 
 
 York), 1899, xv, 12. 
 
 * SiiOBER (.T. B.): Parotid gland therapy in ovarian disea^se. 
 
 Am. J. Obst. (New York), 1899, xi, 368.
 
 CHAPTER V 
 
 THE SECRETINS AND PYLORO-DUODENAL 
 EXTRACTS 
 
 The Discovery of Hormone Action — A Therapeutic Agent of 
 Promise — The Specificity of Secretin Action — The Gastric 
 Secretin — The Broader Activities of Secretin — The Estab- 
 lishment of the ''Secretin Theory" — The Physiology of 
 Secretin Action — Stimulating the Production of Secretin in 
 Constipation — The Bacillus Bulgaricus and Secretin Pro- 
 duction — The Preparation of Secretin — Secretin in Gastro- 
 intestinal Therapeutics — Methods of Administration — The 
 Treatment of Digestive Insufficiencies — Possibilities in In- 
 fantile Diarrhoeas — Secretin in Malnutrition and Cachexia — 
 Experiences with Secretin in Diabetes Mellitus — The Rela- 
 tion of Secretin to the Hormone Balance— Dosage and Ad- 
 ministration. 
 
 The orthodox treatment of certain forms of indiges- 
 tion has for many years included preparations of animal 
 origin. The use of pepsin and pancreatin has been estab- 
 lished on a firm basis, although at times dissentient 
 voices are heard to the effect that the continued use of 
 such preparations tends to induce laziness on the part of 
 the organs in question, for the preparations simply serve 
 as digestants and do not actually facilitate a regeneration 
 of the disordered alimentary function. Our conception 
 of the treatment of the indigestions has in the past few 
 years been very materially modified by the discovery of 
 certain other substances, also of animal origin, and a 
 revolution has begun, not only in our conception of the 
 physiology of the digestive glands, but in the treatment 
 of their functional insufficiencies. 
 
 54
 
 The Secretins and Pyloro-Diiodenal Extracts 55 
 
 The Discovery of Hormone Action. — The first dis- 
 covery which led up to this was when Dolinski and 
 Gottlieb^ noted that the introduction of dihite hydro- 
 chloric acid into the digestive canal is followed by a 
 remarkable increase of the secretion of pancreatic juice. 
 The researches of Popielski, Wertheimer, and Le Page 
 established the fact that this hypersecretion was pro- 
 duced when the acid came into contact with the duodeno- 
 jejunal mucosa; in other words, the contact of acid 
 solutions with the duodenal mucosa is the physiologic 
 excitant of pancreatic secretion. 
 
 Then came the crucial monograph of Bayliss and 
 Starling, 2 which gave proof that this action was not 
 simply the so-called " acid reflex " referred to by Pavlov, 
 and that the acid did not act by itself, but by the inter- 
 mediary of a hitherto unknown substance, which could 
 be produced in vitro as well as in vivo. 
 
 This was the hormone " secretin " first isolated by 
 t]iese investigators in the research laboratories of Uni- 
 versity College, London, in 1902. 
 
 This proved to be one of the most important discoveries 
 in physiological research, for it firmly established the 
 position of the "chemical messengers," and, as we have 
 already seen, brought into being the whole subject of 
 hormones and their essential role in the functions of the 
 body. 
 
 A Therapeutic Agent of Promise. — More than ten years 
 have passed since the initial reports were published, and 
 in that time scores of tests have been carried out, which 
 have established very definitely the important part that 
 secretin plays. For a number of years the author has 
 been interested in the application of this idea in thera- 
 peutics, and has studied the relation of secretin and ex- 
 tracts of the duodenum to gastro- intestinal therapeutics.
 
 56 Practical Hormone Therapy 
 
 In the matter which follows, an attempt will be made, 
 first, to explain the mechanism of secretin action and to 
 give sufficient proof of its powers, and then to recapitu- 
 late the fundamental facts already published, so that 
 their relation to therapeutics may be fully evidenced; in 
 other words, an attempt will be made here to prove that 
 a new and revolutionary therapeutic procedure is avail- 
 able for the treatment of functional insufficiencies of the 
 alimentary tract, and to further the introduction of what, 
 because of the limited amount of literature on its use, 
 can still consistently be called " a new method." 
 
 Hitherto the use of secretin has been mainly limited 
 to the experimental investigators, and these, usually, 
 have not applied it in clinical work. It is still the ex- 
 ception to find physicians using secretin as a therapeutic 
 agent. 
 
 The Specificity of Secretin Action. — Secretin is a definite 
 chemical product of the mucous membrane of the duo- 
 denum — the principal alimentary hormone. We know 
 its chief physiological qualities, but as yet practically 
 nothing of its chemical structure. 
 
 It has been extracted from the human duodenum after 
 autopsy, and is found in many animals. There is no speci- 
 ficity of secretin for any genus — that is to say that it is 
 presumably identical, irrespective of its source — hence, 
 secretin procured from animals is active in man, and vice 
 versa. According to Sweet and Pemberton^ the activity 
 of secretin-bearing preparations for laboratory testing 
 varies greatly. The extracts generally used in experi- 
 mental work are made from the dog. They found that 
 sheep extract is the most active of any that they have 
 used, and also state that the human intestine is not only 
 relatively, but actually lower in its content of prosecretin 
 than is the intestine of some lower animals. This is in
 
 The Secretins and Pyloro-Diiodenal Extracts 57 
 
 harmony with the fact that the digestive activities in 
 man are not so great as in other animals — e.g., as the dog 
 or pig. 
 
 The Discovery of Secretin. — The story of the discovery 
 of secretin may be briefly recalled. In the investigation 
 of the properties of enterokinase, that remarkable tryptic 
 activator first discovered by Chepovalnikov^ in Pavlov's 
 laboratories at St. Petersburg, Bajdiss and Starling noted 
 the phenomenon already mentioned — viz., that the in- 
 jection of acid or acid chyme into a loop of small intestine 
 was followed by a secretion of pancreatic juice. They 
 fiu-ther found that this occurred even when all nerve 
 channels had been destroyed. These investigators were 
 convinced that the message from the intestine to the 
 pancreas was carried not by the nervous system, but by 
 the blood; they concluded, therefore, that the activating 
 substance was produced in the duodenal walls under the 
 influence of the acid, and that it was then absorbed into 
 the blood and served to excite pancreatic function. A 
 portion of the intestinal mucous membrane was accord- 
 ingly scraped, pounded up with dilute hydrochloric acid, 
 and filtered. Injection of a portion of the neutralized 
 filtrate into the blood of an animal resulted in a copious 
 flow of pancreatic juice, and the chemical messenger, or 
 hormone, responsible for this action was named " secre- 
 tin." Later it was called " pancreatic secretin," to dis- 
 tinguish it from other similar substances which excited 
 other glands.* 
 
 The Gastric Secretin. — Since this epoch-making an- 
 nouncement was made, other investigators, notably 
 Edkins,^ have shown that the gastric walls near the pylorus 
 produce a similar hormone, which has been called " gas- 
 
 * Further interesting references to this whole subject will be fouufl in 
 Starling's '■ Principles of Human Physiology," 1912, \^. 797.
 
 58 Practical Hormone Therapy 
 
 trin " or " gastric secretin." For all we know there may 
 be no essential difference between the gastric and duodenal 
 secretins, save only in the cells which they activate. Its 
 action is through the blood and upon the peptic and 
 oxyntic glands of the stomach. 
 
 In a recent editorial reference^ to the gastric secre- 
 tin the results of this work are concisely outlined as 
 follows: " Edkins has carried out experiments to see 
 whether such a chemical mechanism, in distinction from 
 the nervous control which is usually called on to elucidate 
 the phenomena of secretion, may not also serve to ex- 
 plain the secretion of the gastric juice when food is intro- 
 duced into the stomach. He finds that substances such 
 as peptones, broths, dextrin, etc., which are known to 
 induce gastric secretion when ingested, are without in- 
 fluence on the secretory act if they are injected directly 
 into the blood-stream ; but when such known excitants of 
 secretion are allowed to stay with the pyloric mucous 
 membrane, and a decoction of this is then injected into 
 the circulation, a secretion of both acid and peptic enzyme 
 into the stomach ensues. Infusions of the cardiac portion 
 of the stomach or of other organs do not act in this secre- 
 tion-producing manner. Edkins concludes that this 
 typical secretion of gastric juice is determined by a 
 chemical mechanism. The first products of digestion 
 act on the pyloric mucous membrane, in which they 
 produce a substance which, entering the blood-stream, is 
 carried to the gland-cells of the stomach, where it acts as 
 a specific excitant of their secretory activity; this is the 
 gastric hormone — 'gastric secretin.' " 
 
 As will shortly be shown, just as secretin is not com- 
 pletely formed in the duodenal cells, but is changed from 
 its precursor prosecretin into secretin by contact with 
 an acid, so the gastric secretin — gastrin — remains in the
 
 The Secretins and Pyloro-Duodenal Extracts 59 
 
 orm of a precursor — progastrin — until either the products 
 of digestion or the psychic stimulus of food changes this 
 inert substance into the chemical activator — gastrin — 
 which is not secreted into the stomach, but which, by 
 humoral channels, is brought back to the secreting cells 
 of the stomach. The following diagram may make this 
 clear. (Fig. 5.) 
 
 Prosecretin and Secretin. — Secretin is evidently not 
 preformed in the duodenal walls and stored up there in 
 quantities ready for use; it is made as needed, and the 
 precursor of secretin, or "prosecretin," as it has been 
 called, was thought by Bayliss and Starling to be changed 
 by the acid contact into the active hormone. This has 
 
 FoocL or 
 F^ycluo ^ Stanu Zi Progastrinj 
 
 (in. sWrruiJch. walls ) 
 Prope psirvogen. — GASTRIN ^==^HC1 Brecursors 
 
 PEPSIN lici ^ 
 
 Fio. n.— The FAcrims concet.xed in Pepsix PrioDrcTiox. 
 
 been the subject of considerable controversy, and Dele- 
 zenne and Pozerski'^ seem to have proved that secretin 
 may be extracted from the duodenum without recourse 
 to acids, and state that it is simply liberated by the acid 
 contact. These writers bring indisputable evidence to 
 show that secretin pre-exists in a definite form in the 
 mucosa, and that there is a hindering substance which 
 prevents its liberation. This substance is rendered inert 
 by the acid (and by other means), and the secretin is 
 permitted to be passed into the blood. They relate 
 numerous methods of extracting it, and state that, irre- 
 spective of the method of extraction, the product — secre- 
 tin — is always the same.
 
 60 Practical Hormone Therapy 
 
 Whether or not this is correct is too technical a question 
 to interest us. It suffices that it passes into the blood 
 when intestinal digestion is about to begin, and excites 
 the three organs concerned — the pancreas, liver, and 
 intestine — as we shall now see. 
 
 The Broader Activities of Secretin. — Some of the French 
 physiologists have proved that secretin not only influ- 
 ences the gastric and pancreatic glands, but also stimu- 
 lates the production in the duodenal walls of the same 
 substance. Shortly after Starling's announcement, Dele- 
 zenne and Frouin,^ working at the Institut Pasteur in 
 Paris, confirmed his statements and demonstrated that 
 the action of secretin was broader than had been sup- 
 posed; for it did not exert itself solely on the pancreas, 
 but its activities apparently extended to the ileum, and 
 it was concerned also in the stimulation of the production 
 of succus entericus. Bottazzi and Gabrieli^ have shown 
 that secretin preparations (acid extracts of the intestinal 
 mucosa) contain a substance which provokes the normal 
 flow of intestinal juice; it has clearly been sho\\^l by a 
 number of experimenters that secretin also stimulates 
 the functional activity of the liver. Clinically, too, it is 
 evident that secretin preparations do not influence the 
 stomacli and pancreas alone, for it will be frequently 
 noted that acholic clay - coloured stools resume their 
 normal colour following a few doses of this remedy. 
 Hallion^^ notes that secretin has also a distinct influence 
 upon the liver and the motor functions of the bowel. In 
 his experiments, in which he was associated with En~ 
 riquez,^^ he noted that secretin also increases in a great 
 measure the secretion of bile. These writers observed 
 that almost invariably during experiments on animals 
 injections of secretin were shortly followed by evacuation 
 of the bowels. This fact has been put to good use in the
 
 The Secretins and Pyloro-Duodeiial Extracts 61 
 
 treatment of certain forms of constipation, and is fully 
 considered in Bregeon's thesis, and has been carefullj'^ 
 confirmed by Portier, Falloise,^^ and others. 
 
 The Establishment of the "Secretin Theory."— The 
 St. Petersburg School has long opposed the " secretin 
 theory." Bylina,^^ as late as in 1911, intimated that 
 secretin was not quite what Bayliss and Starling had 
 made out, stating that the pancreas possesses a constant 
 secreting function for which nervous influences are prin- 
 cipally responsible. In a later paper^"* he admits that 
 the pancreatic secretion to a certain extent is dependent 
 upon a humoral mechanism; but he still asserts that 
 nervous influences are concerned in the excitation of 
 pancreatic secretion, and, indeed, determine the chemical 
 character of the juice. Popielski^*^ insisted similarly that 
 secretin played a minor part in the stimulation of pan- 
 ci'eatic secretion, and that the results purporting to be due 
 to its influence were obtainable in other ways. In Italy, 
 Luciani^*^ and his colleagues have agreed with this posi- 
 tion, and bring forward experiments which are supposed 
 to prove the fallacy of Starling's position. 
 
 Experiments seem to discount these statements, how- 
 ever, and the most conclusive proof of the error of Bylina's 
 idea is to be found in a 100 page thesis, ^^ which gives the 
 details and deductions of Hustin's interesting studies of 
 the mechanism of the external secretion of the pancreas, 
 carried out at the Institut Pare Leopold, in Brussels. 
 The subject is very thoroughly discussed, the importance 
 of secretin being emphasized in a most convincing 
 manner, and certain of the experiments being apparently 
 decisive. Among other things Hustin has demonstrated 
 that the pancreatic secretion cannot be stimulated by 
 secretin alone; he has proved that a certain element in 
 the blood must be associated with the secretin. His
 
 62 Practical Hormone Therapy 
 
 method consisted in taking the pancreas from an animal, 
 placing it in a bath of liquid paraffin, overlaying water 
 at 38^C., and then irrigating it with liquids, which were 
 introduced by means of a cannula through the pan- 
 creatico-duodenal artery, and were conveyed away by 
 another cannula in the portal vein. A third cannula 
 was introduced into the duct of Wirsung, to lead off the 
 pancreatic juice. As a result of numerous experiments 
 Hustin established the important fact that a gland 
 irrigated indej)endently with Locke's physiological 
 serum, blood, or secretin solution gives no secretion, but 
 irrigation with a mixture of blood and secretin gives an 
 abundant secretion of clear liquid containing trypsinogen^ 
 lipase, and amylase — results that can hardly be gainsaid. 
 The author further states that secretin is used up in the 
 gland in the impregnation of the pancreatic cell, in a 
 manner that renders it sensible to the action of certain 
 substances in the blood. The presence of calcium elec- 
 trolytes is stated to be a third essential (see diagram on 
 p. 64). For convenience Husti'i compares this action 
 with the side-chain theory of Ehrlich — viz., that living 
 protoplasm carries certain chemoreceptors or contains 
 chemoreceptive substances, and it is by combination 
 with these that drugs, etc., induce their specific effects. 
 
 Recent reports from 8t. Petersburg seem to indicate 
 that at last there is a tendency to admit that the "secre- 
 tin theory," so long discounted by certain Russian and 
 Italian physiologists, is no longer so mitenable. Sawitch 
 and Zeliony,^* reporting a series of experiments which 
 were carried out in the physiological laboratory of the 
 Military Medical Academy in St. Petersburg, have estab- 
 lished the essential accuracy of Edkins's contention that 
 normal gastric secretion is due to the co-operation of at 
 least two factors — the one a nervous element induced by
 
 The Secretins and Pyloro-Duodenal Extracts 63 
 
 the stimulation of the mucosa of the mouth or by the 
 awakening of the appetite through psychic chamiels, and 
 the other a chemical factor dependent on the elaboration 
 of a hormone which acts as a chemical messenger to all 
 parts of the stomach through humoral paths, and whose 
 effects linger long after the psychic stimulus has dis- 
 appeared. 
 
 In his book on " The Action of Medicines,"* Brunton 
 illustrates his statements by means of a diagram (Fig. 6). 
 This diagram (for permission to use which I have cordially 
 
 No^O 
 
 orX 
 
 Fig. 6.— Di.^gram to illustkatb the Chemicwl Ch.a.xges dckin-g 
 Gastuic Secketiox. 
 
 to thank this distinguished therapeutist) shows that it 
 was hardly possible, before the discovery of the hormones, 
 to explain the phenomena of gastric digestion without 
 presupposing the presence of an indefinite entity. It is 
 evident that in this diagram, which is intended to illus- 
 trate the chemical changes during secretion, the unknown 
 quantity, or X, is no other than secretin, or, rather, in 
 this particular case, gastrin, or gastric secretin. 
 
 A very similar, and perhaps identical, hormone is 
 probably produced by the spleen, the function of which 
 
 * Kdiliuu dl' 18'J7, \\ 50.
 
 64 
 
 Practical Hormone Therapy 
 
 is to stimulate the digestive glands to do their normal 
 work. This splenic hormone has been proved by numer- 
 ous physiologists to have a part in the activation of 
 trypsinogen. 
 
 The Physiology of Secretin Action. — Dixon and Hamill^'^ 
 made a series of experiments at the pharmacological 
 laboratory of Cambridge University, to test the hypoth- 
 esis of Ehrlich (which has been referred to above). 
 This is also illustrated by Hustin's deductions, which are 
 
 Blood 
 eLerri/iTtti 
 
 ?/japf/7ph/)rei 
 
 Fig. 7. — Schematic Rei'uesentatiox of Secretix Action (based ox 
 Eurlich's Hypothesis). 
 
 explained in Fig. 7, which is a modification of that of 
 Hustin. Secretin was investigated first, as its marked 
 action on the pancreas was already known. As a result 
 of this work, the physiology of secretin action is now 
 better understood. The prosecretin of the duodenal 
 wall is first changed into secretin by contact with hydro- 
 chloric acid ; it is then carried in the blood-stream to the 
 pancreas, where, as a result of chemical change, its char- 
 acteristic features are lost, secretin combining with
 
 The Secretins and Pyloro- Duodenal Extracts 65 
 
 amylopsinogen and steapsinogen, to form the ferments 
 amylopsin and steapsin, and, with the precursor protryp- 
 sinogen, to form trypsinogen.* This last becomes the 
 ferment trypsin only after it has come into contact with 
 enterokinase in the intestinal canal. The action of 
 secretin, then, may be conveniently expressed by the 
 following equation : 
 
 Prosecreliny tx: HCl 
 
 ( i/h dimdeihoL avails) 
 PfotrypsTJtogen. = SECRETIN 
 
 iirv pancj'eas cells) 
 
 Trypsmogen. x Enter oldruxse' 
 
 (i/h duodemzm.) 
 TRYPSIN 
 
 Fig. 8. — The Factors concerned in Tryi'sin Production. 
 
 {Note. — The := indicates hj humoral channels, and X iy direct contact.) 
 
 Hallion believes that secretin is not totally lost or de- 
 stroyed during its action, and suggests that the whole 
 part of the molecule may be utilized again, as some 
 authorities are now beginning to suppose is the case with 
 the ferments. Hallion, at least, reports that subcutaneous 
 injections of secretin, which had no secretory influence, 
 were not without some effect, for the duodenal mucosa 
 of the animals thus treated showed considerable redness 
 and a special richness in secretin precursors, producing, 
 when influenced by acids, an abundant internal secretion 
 of secretin. 2" This is in harmony with the statement of 
 this same investigator regarding the specific action of the 
 
 * Professor Starling, in an annotation u[)on the manuscript of this chapter, 
 writes: "I could not confirm these experiments, nor could Mellanby. I 
 do not believe they 'are correct." There can be no doubt, however, of the 
 stimulating,' action of secretin, tlic rather indefinite point \w\\v^ just how this 
 is broufrht about.
 
 66 Practical Hormone Therapy 
 
 hormones upon the internal secretory capacity of the 
 corresponding hormone-producing tissues, and also with 
 a statement attributed to Starling: "Secretin not only 
 causes the outpouring of the digestive secretion, but at 
 the same time brings about the formation of new enzyme 
 material." 
 
 Stimulating the Production of Secretin in Constipation. — 
 At present there is a paucity of literature on the clinical 
 use of secretin. There are numerous references to its 
 physiology, and in French literature there are several 
 interesting papers. In one of these Enriquez brings up 
 a very important point. In a communication to the 
 Paris Academic de Medicine he writes i^^ " Based on the 
 greater importance of normal digestion of the production 
 of secretin in the duodenmn, why should not, clinically, 
 a large number of dyspepsias be secondary to a disturb- 
 ance in the highly specialized function of the duodenal 
 mucosa ? " " When it is remembered, ' ' he continues, ' ' that 
 secretin also possesses an incontestable influence upon 
 intestinal motility, one of the first and most constant signs 
 of secretin insufficiency must, without doubt, be clinically 
 represented by constipation. Thus, guided by our ex- 
 perimental research, we have found a means of stimulating 
 this function in certain constipated dyspeptics." En- 
 riquez prepared keratin-coated capsules of gluten, con- 
 taining an active and harmless acid (tartaric), which was 
 proved experimentally to be stable in the stomach and 
 easily destroyed in the duodenum. 
 
 The results of this form of medication were most inter- 
 esting. All the patients showed a more or less noticeable 
 constipation, and in seven of the cases it was the dominat- 
 ing symptom, inconveniencing the patients as much by 
 its persistence as by its obstinacy. In these seven cases 
 acid medication of the duodenum brought about, with
 
 The Secretins and Pyloro-Duodefial Extracts 67 
 
 varying ease according to the dose, a stimulation of the 
 secretory and motor functions of the intestine and a 
 regulation of the stools. Two cases were of special 
 interest. One was that of a person suffering from 
 localized sclerosis (sclerose en plaques) for many years, 
 with intractable constipated periods lasting from six to 
 eight days and resisting many kinds of purgatives, enemas 
 alone having any action. Under this treatment the stools 
 were immediately regulated, giving way again to con- 
 stipation as soon as the treatment ceased, and this 
 occurred several times. In five of the observations 
 muco-membranous colitis was complicated alternately 
 with constipation and painful abdominal crises, terminat- 
 ing by the passage of glairy mucous and membranous 
 casts. In four of the cases the oolitic symptoms were 
 much relieved at the same time as the constipation. 
 
 It will be noted that Enriquez did not administer a 
 preparation of secretin; but, of course, the principal 
 value of this method depends upon the production of 
 secretin, which is artificially stimulated by replacing the 
 evidently missing HCl with another equally efficacious 
 acid. There may be cases in which the duodenal cells 
 will not be stimulated, and here it would seem that secre- 
 tin itself could be used to good advantage. 
 
 The author has personally noticed, and his experience 
 has been confirmed by several correspondents, that the 
 administration of preparations of secretin is followed 
 quite constantly by the rehef of fermentation in the upper 
 bowel, and the reason for this is not far to seek. Gastric 
 and intestinal fermentations are mainly due to a de- 
 ficiency in the amount and activity of the digestive 
 juices, as it has long been known that the administration 
 of hydrochloric acid not only favours the digestive action 
 in the stomach, but also tends to increase the amount of
 
 68 Practical Hormone Therapy 
 
 pancreatic ferments in the duodenum, and only since the 
 discovery of secretin has it been clear how this is brought 
 about. 
 
 The Bacillus Bulgariciis and Secretin Production. — An 
 interesting fact has been established by Beveridge of 
 New York regarding a possible relation between soiu:- 
 milk therapy and the production of secretin. It is well 
 known that normal secretin production is caused by a 
 stimulus to the duodenal mucosa by an acid — usually 
 the acid chyme passing from the stomach. Beveridge 
 has secured some excellent results in the treatment of 
 diabetes with cultures of the B. bulgaricus, and in his 
 article^^ he wTites : 
 
 "The power exerted through the stimulation of acid 
 digestion in producing secretin, so necessary to the 
 normal functioning of the pancreas, has never, until now, 
 been brought forward as a factor in glycosuria; hence, 
 one can readily perceive that when chronic conditions 
 arise to change the acidity of the gastric contents, a 
 corresponding response will be noted in the production 
 of secretin. According as an increased acidity or lowered 
 acidity of the gastric chyme is apparent while passing 
 through the duodenum and upper portion of the small 
 intestine, the amount of secretin manufactured is either 
 increased or diminished, and, reflexly, the pancreatic 
 secretions will also be increased or diminished. Should 
 this abnormal chemical reaction continue, whereby the 
 pancreas receives inadequate stimulation during digestion, 
 serious chemical and metabolic changes will in time 
 manifest themselves, which may eventually combine and 
 prevent complete carbohydrate metabolism. 
 
 " The other causes interfering with a normal produc- 
 tion of secretin are intestinal putrefaction, ulcer of the 
 duodenum or pylorus, and any lesion involving the mucosa
 
 The Secretins and Pyloro- Duodenal Extracts 69 
 
 of the duodenum and upper portion of the small intes- 
 tine." 
 
 The value of Beveridge's treatment, then, does not lie 
 only in the favourable influence of the B. hulgarictis upon 
 intestinal putrefaction, but is due also to the acid stimu- 
 lus to secretin production caused by the lactic acid, 
 which is a normal product of these micro-organisms This 
 subject is deserving of much wider study and application. 
 
 The Preparation of Secretin. — Secretin is not particu- 
 larly difficult to obtain. As already mentioned. Starling 
 secured it by pounding up duodenal scrapings with hydro- 
 chloric acid. Various methods of extracting secretin are 
 outlined in articles by Bayliss and Starling.^^ Stepp,^^ 
 Gley,25 ^j^(j Launoy.2^ Aqueous solutions of secretin are 
 easily made, but they must be used while fresh, for, if 
 left unstoppered, they lose their activity in about twenty- 
 four hours. If, however, they are preserved in sterile 
 ampoules and kept in the dark, they remain active for 
 some time. Sweet and Pemberton^ have found that 
 sterile preparations keep for as long as nine weeks, but 
 gradually lose their excito-secretory powers. 
 
 Fortunately, dried extracts of duodenal mucous mem- 
 brane keep well, and from them potent solutions are now 
 made in America, France, and England. Provided that 
 in this manner one can stimulate the production of hydro- 
 chloric acid in the stomach, the rest is simple. The 
 passage of the acid gastric contents into the intestine 
 will be a natural stimulus to the production of secretin, 
 so that the administration of such a remedy serves a 
 double purpose; it will stimulate the pancreas directly, 
 and also indirectly, by the production of an additional 
 supply of this important activator. 
 
 Secretin in Gastro-Intestinal Therapeutics. — From the 
 foregoing experimental facts it will be seen that in this
 
 70 Practical Hormone Therapy 
 
 remarkable substance, or series of substances, we should 
 have a therapeutic weapon with vast possibilities. This 
 is especially true when we remember Starling's^'^ own 
 statement: "It is now a demonstrated fact that a large 
 share of the wonderful co-ordination of the activities of 
 different parts of the body, which determine their mutual 
 co-operation for the common weal of the organism, is 
 played by the production and circulation of chemical 
 substances which are strictly analogous to the drugs 
 emploj^ed during countless ages by mankind in the treat- 
 ment of his diseases." It does not seem that the analogy 
 is as thorough as the foregoing quotation would indicate, 
 for the use of secretin and other hormones is infinitely 
 more reasonable, and its stimulating effect far more nearty 
 physiological, than that of other means to the same ends. 
 
 Before proceeding to the consideration of the clinical 
 possibilities of secretin preparations, a few facts concern- 
 ing the stability of secretin as a remedy and its administra- 
 tion deserve to be referred to. 
 
 Methods of Administration. — In practically all animal 
 experiments with secretin, this substance has been ad- 
 ministered by the intravenous method, and it has been 
 stated more than once that secretin given by other methods 
 — e.g., when taken into the stomach — is not active 
 (Starling). 23 We have already seen that Hallion found 
 that hypodermic injections had a marked influence upon 
 the duodenum, although they did not give a secretory 
 response comparable to the intravenous injections. 
 
 Some experiments have been made, the results of which 
 indicate that in animals secretin is not absorbed when 
 introduced, even in large doses, into the digestive canal; 
 but clinical tests, covering a period of several years, have 
 proved that neither the conditions in the stomach during 
 digestion nor those in the intestine, prevent secretin from
 
 The Secretins and Pyloro- Duodenal Extracts 71 
 
 entering intact into the circulation, and while the rapidity 
 is not so great, otherwise it is just as it is given direct in 
 the experimental work. It is therefore available as a 
 chemical excitant of the various cell units which respond 
 to its activation. 
 
 Of considerable importance in this connection is the 
 fact that Camus and Gley^^ have secured secretin from 
 the mucosa of the stomach (thus amplifying Edkin's 
 work on gastrin), and have shown that secretin in neutral 
 solutions is slightly weakened by the alkaline pancreatic 
 secretions, but that it remains the same in acid solutions. 
 It is only necessary, then, to give a preparation of secre- 
 tin containing sufficient acid, when its properties are 
 preserved. It has been supposed that the alkalinity of 
 the intestinal juice would destroy the secretory powers of 
 this hormone, but the work of Delezenne and Pozerski 
 has shown that this fear is unfounded. If, in effect, the 
 intestinal extract in solution destroys secretin, this de- 
 structive action does not manifest itself with acid extracts ; 
 thus, in order to paralyze the opposing substance, or 
 antisecretin, which destroys its action, it is necessary 
 only to insure an acid medium. 
 
 Undoubtedly a comparison between the results of the 
 intravenous injection of secretin solutions and the oral 
 administration of solid or liquid extracts of the duodenal 
 mucosa would give evidence in favour of the direct method 
 — intravenous medication for obvious reasons is more 
 rapid, active, and pronounced than any other method 
 of giving drugs — but any statements to the contrary not- 
 withstanding, one cannot overlook the noticeable influ- 
 ence on digestion and nutrition which follows the ad- 
 ministration of secretin by mouth; this will be still more 
 apparent when all the evidence is considered. It must 
 also be remembered that, in the preparation of secretin,
 
 72 Practical Hormone Therapy 
 
 boiling with dilute HCl is a part of the process, and any 
 conditions compared with this which might be found in 
 the stomach would seem theoretically to be negligible; 
 in fact, in practice the oral administration of secretin 
 accomplishes definite results which are sometimes nothing 
 short of marvellous. 
 
 The Treatment of Digestive Insufficiencies. — Very little 
 clinical work seems to have been done with secretin in 
 the English-speaking countries. The only articles re- 
 ferring to secretin-containing preparations that have been 
 found in a very careful search of English and American 
 medical literature are those on its possible use in diabetes 
 (q.v.), those by the present author, ^° and one from the 
 pen of Boardman Reed.^^ In this article he compares 
 his standard pepsin-hydrochloric mixtures, referred to in 
 his excellent book,* with an elixir containing gastric and 
 pancreatic secretins, and finds that these organic prin- 
 ciples are considerably more active, rapidly bringing the 
 work of the stomach to the normal, and usually at the 
 same time improving the intestinal indigestion and 
 assimilation. Reed states that " secretogen is appar- 
 ently the most powerful excitant of gastro-intestinal 
 secretion so far tried by me," and refers to a number of 
 cases, one of which is mentioned in an addendimi to his 
 paper, which follows: " Since the foregoing was written, 
 I have examined chemically the stomach contents of one 
 of the patients referred to, in which none of the secretogen 
 has been taken for a month, and the proportions of both 
 the free and combined hydrochloric acid were foimd still 
 a little above normal, though, before the remedy was 
 taken, there had been no free hydrochloric acid at all, and 
 the proportions of both the combined hydrochloric acid 
 and of the total acidity had been decidedly below normal." 
 
 * "Diseases of the Stomach and Intestines," third edition, New York, 
 1911.
 
 The Secretins and Pyloro-Duodenal Extracts 73 
 
 Possibilities in Infantile Diarrhoeas. — Personal experi- 
 ences fully confirm Reed's statements, and attention has 
 been called by Harrower^^ ^q the encouraging possibilities 
 of this preparation in the treatment of the gastro-intes- 
 tinal disorders of small children, especially those preva- 
 lent in the summer. Two paragraphs from this paper 
 will give the gist of the idea: "Since secretin exerts a 
 very effective stimulus to the gastro-intestinal function, 
 this stimulation is normal and physiologic, and usually 
 followed by no reaction. Flatulence and fermentation 
 seem to be controlled very effectively, and limited experi- 
 ence with infantile indigestions, and especially the summer 
 tjrpes, shows that this is a means of treatment worthy of 
 further study and consideration. 
 
 " It cannot be denied that by far the best antiseptics 
 for the reduction of toxic conditions in the intestine are 
 its natural juices. Secretin plays the most important 
 part in their production, and its influence is not limited 
 to the stomach or pancreas ; but including these important 
 organs, it also influences the production of bile and the 
 intestinal juices from the pylorus to the ileum. The 
 augmentation of the amount and activity of the normal 
 digestive secretions is the most reasonable means of check- 
 ing the intestinal fermentations so common in children, 
 and it is well to remember that the administration of 
 secretin does not in the least interfere with the hydro- 
 therapeutic and even the present-day drug treatment of 
 these conditions." 
 
 It may seem paradoxical to suggest the same remedy 
 for constipation and diarrhoea, but the facts show 
 that secretin - bearing preparations are valuable for 
 both. 
 
 Secretin in Malnutrition and Cachexia. — It is well 
 known that there is practically always a complete ab-
 
 74 Practical Hormone Therapy 
 
 sence of hydrochloric acid production in cancer and 
 gastric cancer, and the lack of hydrochloric acid — the 
 physiological stimulus to normal secretin production in 
 the duodenal walls — results in a marked decrease in the 
 amount and efficacy of the pancreatic ferments, as well 
 as of the whole digestive cycle. This nearly suffices to 
 account for the nutritional disorders which are pathogno- 
 monic of carcinoma. With the foregoing in mind, it can 
 be readily appreciated that secretin may be used in 
 cancer and cachexias generally, not to influence the 
 disease per se, but rather as a means of increasing the 
 digestive activities and nutrition; the same ideas natur- 
 ally hold good in other conditions, where toxaemias, super- 
 function, or asthenia, have lessened the digestive capacity. 
 In no disease is this influence more desirable than in 
 tuberculosis, and attention is already being turned to the 
 possibilities of this new adjunct remedy for the digestive 
 disorders of the tuberculous.'^^ 
 
 Secretin in Diabetes Mellitus. — Since the numerous con- 
 firmatory reports of the action of secretin on the external 
 secretion of the pancreas, as well as upon the intimate 
 relation between pancreatic activity and carbohydrate 
 metabolism, secretin has been recommended as a means of 
 treating diabetes.^ Much was expected from its use, 
 because several very good results occasionally followed 
 its early administration in this disease. There seemed 
 to be good reasons to anticipate success, for the basis of 
 this application of secretin therapy was the clear physio- 
 logical evidence of a connection between pancreatic 
 activity and diabetes, as well as between secretin and 
 pancreatic activity ; and where functional disorder of the 
 pancreas was present, it was presumed that advantage 
 might follow the stimulus caused by the secretin. 
 
 In their first communication on this subject, Moore.
 
 The Secretins and Pyloro-Duodenal Extracts 75 
 
 Edie, and Abram^^ described three cases of diabetes in 
 which improvement followed the oral administration of 
 an acid extract of duodenal mucosa. As a result of this 
 treatment, the sugar diminished gradually, and finally 
 disappeared. Later these same authors,^^ whose work 
 in the meantime had been augmented by the discovery 
 by Bainbridge and Beddard,^"^ that in many diabetics 
 prosecretin is absent from the duodenum,* admit that 
 the majority of cases treated in this manner showed no 
 appreciable change in the sugar output. They call atten- 
 tion, however, to the fact that " in some of these negative 
 cases there has been noticed an improvement in the 
 digestion, and in certain cases the patient's weight has 
 increased." In one case in particular this incidental 
 influence on digestion was very decided. " Almost at 
 once the dyspepsia from which he was sufl'ering was re- 
 lieved, and his general nutrition improved to such an 
 extent that he regained over 18 pounds in weight, and 
 this improvement was accompanied by a complete re- 
 covery of his mental and physical energies." ^^ Crofton^^ 
 of Dublin also recommends secretin as useful in diabetes, 
 and Beveridge,22 in his experiences with the Bacillus hul- 
 garicus treatment of this disease, infers that deficient 
 secretin action is concerned in the disorders of metabolism 
 that characterize diabetes mellitus. 
 
 Unfortunately there have been too many failures to 
 stimulate a really extensive series of clinical tests. It 
 
 * It is interesting to note that Evans^^ made a series of experiments at 
 the Institute of Physiology, University College, London, to ascertain the fate 
 of prosecretin in depancreatized dogs. The information thus gained shows 
 that total extirpation of the pancreas is rapidly followed by complete dis- 
 appearance of the precursor of secretin in the duodenal walls ; but if a 
 small portion of the pancreas is left (to preserve a sufficient amount of tlie 
 pancreatic hormone for the prevention of glycosuria) there is no appreciable 
 diminution in prosecretin. It is suggested that the loss of secretin in 
 pancreatic diabetes is simply one symptom in the general train of metabolic 
 disturbances consequent on loss of the internal secretion of the pancreas.
 
 76 Practical Hormone Therapy 
 
 seems, however, that the failures that have been reported 
 are due, not to lack of activity in the secretin preparation 
 or to its administration, but rather to the fact that the 
 external secretion of the pancreas plays a very minor 
 part in the carbohydrate metabolism. The internal 
 secretion, on the other hand, has a specific influence on 
 sugar combustion, due, in all probability, to the so-called 
 " Langerhansian hormone," which is now lmo^\^l to 
 antagonize the chromaffin hormone produced by the 
 adrenal system (see Chapter VII.), and that the influence 
 of secretin on the production of the pancreatic internal 
 secretion is almost negligible, or, at least, decidedly less 
 than upon the digestive, or external, secretion. 
 
 There seems to be a good field for clinical research in 
 the application of a combination of the duodenal and 
 pancreatic internal secretions in the treatment of diabetes, 
 for this disease at first is essentially a form of indigestion, 
 or, at least, very commonly associated with digestive 
 disturbances, and, as we have seen, secretin does favour 
 the digestive processes of the upper bowel. 
 
 The Relation of Secretin to the Hormone Balance. — If 
 the duodenum is a part of the endocrinous system, and 
 everything points to the correctness of this assumption, 
 it would seem that in some way it should be related to 
 other endocrinous organs; this is undoubtedly the case. 
 
 With the essential antagonism of the pancreas to certain 
 other glands (adrenals, pituitary, etc.) in mind, we may 
 at least look in this direction for evidence of a similar 
 antagonism to secretin. Some experimental evidence to 
 prove an antagonism by the adrenals and pituitary has 
 been brought forward by Sweet and Pemberton,'^° who 
 show that the removal of the adrenals induces a flow of 
 pancreatic juice which " has been equalled in duration 
 and activity only by the processes which depend on
 
 The Secretins and Pyloro-Duodenal Extracts 77 
 
 activation by duodenal secretin." These same investi- 
 gators previously^ ^ showed that " the suprarenal glands 
 and the nervous moiety of the pituitary body in dogs 
 contain something which, on extraction with salt solution 
 and intravenous injection into dogs, cuts short the flow 
 of pancreatic juice, after the administration of secretin; 
 it also prevents the stimulation of the gland by secretin 
 if its injection precedes the secretin." 
 
 This may be a part of the reason why secretin has been 
 of some value in diabetes, since it is well known that both 
 the chromaffin and posterior pituitary hormones favour 
 glycosuria and occasionally may cause glycosm'ia. 
 
 Dosage and Administration. — It has been shown that 
 secretin cannot be obtained in a pm'e state, at least, for 
 pharmaceutical pinposes; but that very active secretin- 
 bearing extracts can be made from the duodenum and 
 pylorus. 
 
 We have also learned that, since the hormones act in 
 very minute quantities, and an important part of their 
 action is to cause an increased product of the correspond- 
 ing hormone in the body, small doses are very efficacious. 
 It must also be remembered that hormones are activators, 
 and many experiments have proved that a trace of a 
 hormone (see the experiences with saliva in Chapter IV.) 
 causes a very marked result, and they cannot be compared 
 with, let us say, strychnine or the hypophosphites ; hence 
 large dosage is not necessary. 
 
 From 1 to 3 grains of secretin-bearing extract is a 
 sufficient and active dose, and it may be repeated every 
 fifteen to twenty minutes for an hour or even two, and 
 the dosage will regulate itself after a few days. It should 
 be added that this medication is most effective when 
 continued in small (but sufficient) dosage for several 
 weeks or even longer.
 
 78 Practical Hormone Therapy 
 
 It is not harmful, although there are certain contra- 
 indications, chief among which is functional hyperactivity, 
 such as hyperchlorhydria, gastric and duodenal ulcer, 
 etc. Reed^^ gives a word of caution regarding large 
 doses: "I take issue decidedly with those who advise 
 much larger doses on the theory that we should approxi- 
 mate the dose as nearly as practicable to the quantity 
 which Nature secretes normally. I am sure that the 
 large doses often fail when smaller ones would succeed, 
 and explain this observed fact by the principle frequently 
 insisted upon by me, that all active drugs are capable of 
 exerting two opposite effects, according to the size of the 
 dose. ... It should be added, and strongly emphasized, 
 that we should never prescribe an active stimulant of any 
 of the digestive glands, or permit in the diet any condi- 
 ment having a like effect, without a knowledge of what 
 glands are at fault. ..." 
 
 Readers who are interested in the study of the pan- 
 creatic secretion are referred to a valuable 132-page 
 monograph by Terroine,"*^ which considers every phase 
 of the subject. The bibliography is very complete, 
 especially as regards secretin. 
 
 BIBLIOGRAPHY 
 
 * GoiTLiEB (R.)- Beitriige zur PJiysiologie uud Pliaimakologin 
 
 der Paukreas Sekretion, Arch. f. exp. Path. u. Pharm. 
 (Heidelberg), 1894, xxxiii, 261. 
 
 2 Bayliss (W. M.) and Starling (E. H.): Preliminaiy com- 
 
 muaication oa the causation of the so-called " peripheral 
 reflex secretion " of the pancreas, Lancet (Loudon), 1902, 
 i, 813. 
 
 3 Sweet (J. E.) and Pemberton (R.): Experimental observa- 
 
 tions on secretin. Arch. Int. Med. (Chicago), 1908, i, 231. 
 
 * See Pavlov (I. P.): "The Work of the Digestive Glands," 
 
 London, second edition, 160.
 
 The Secretins and Pyloro-Duodenal Extracts 79 
 
 ° Edkins (J. S.) AND TwEEDT (M.): The natural channels of 
 absorption evoking the chemical mechanism of gastric 
 secretion, J. Physiol. (London), 1909, xxxviii, 263. 
 
 * Editorial: The gastric secretin, J. Am. Med. Assn. (Chicago), 
 1913, Ix, 305. 
 
 " Delezenne (C.) and Pozerski (E.): Sur la preexistence de la 
 s6cretino dans la muqueuse intestinale et sur les differents 
 proc6d6s d'extraction de cette substance, C. r. 8oc. Biol. 
 (Paris), 1912, Ixii, 560. 
 
 ^ Delezenne (C.) and Frouin (A.): La secretion physiologique 
 du sue intestinal. Action de I'acide chlorhydrique sur la 
 secretion duod^nale, C. r. Sac. Biol. (Paris), 1904, Ivi, 319. 
 
 ® BoTTAzzi (F.) AND Gabrieli (L.): Reclicrches sur la secretion 
 du sue ent^rique, Areh. Int. d. Physiol. (Liege), 1905, cxi, 156. 
 
 10 Hallion:* p. 19. 
 
 11 Enriquez (E.) and Hallion (L.): Rappel de nos recherches 
 
 experimentales et cliniques sur les proprietes excito-peri- 
 staltiques de certains extraits d'organes, Bull. gen. d. Ther. 
 (Paris), 1911, clxii, 702. 
 
 12 Falloise (A.): Contribution a I'etude do la secr6tine. Bull. d. 
 
 VAcad. Boy. d. Belg. (Brussels), 1902, v, 945. 
 '^ Bylina (A. Z.): Normale Pankreassekretion als Synthese von 
 
 uervosen und humoralen Einfluss, Arch. f. d. ges. Physiol. 
 
 (Bonn), 1911, cxlii, 531. 
 1* Id.: Le s6cr6tion pancreatique normale est la synthese des 
 
 influences nerveuses et humorales. Arch. d. Sci. Biol. (St. 
 
 Petersburg), 1912, xvii, 139. 
 1^ PopiELSKi (L.): Ueber den Charakter der Sekretionstatigkeit 
 
 des Pankreas unter deni Einfluss von Salzsaure und Dar- 
 
 mextrakt. Arch. f. d. ges. Physiol. (Bonn), 1908, cxxi, 239; 
 
 see also G. r. 8oc. Biol. (Paris), 1911, Ixxi, 656, lor other 
 
 references. 
 18 LuciANi:*pp. 90-91. 
 1' HusTiN (A.): Contribution a I'etude du mecanisme de la 
 
 secretion externe du pancr6as. Arch. Int. d. Physiol. (Liege), 
 
 1913, xiii, 318. 
 1^ Sawitch (W. W.) AND Zeliony (G.): Zur Physiologie des 
 
 Pylorus, Arch. f. d. ges. Physiol. (Bonn), 1913, cl, 128. 
 " Dixon (W. E.) and Hamill (P.): The mode of action of specific 
 
 substances with specific reference to secretin, -/. Physiol. 
 
 (London), 1909, xxxviii, 314. 
 '" Hallion (L.): Les hormones, Pr. Mid. (Paris), 1912, xx, 433. 
 21 Enriquez (E.): La 86cr6tine; medication acide duodenalo; 
 
 stimulation des fonctions secretiniques chez F horn me, Rev. d. 
 
 ther. med.-chir. (Paris), 1904, Ixxi, 187. 
 2- Beveridge (J. VV.): Diabetes mellitus: treatment with B. 
 
 bulgaricus ctJtures, N. T. Med. J., 1913, xcviii, 70.
 
 80 Practical Hormone Tlierapy 
 
 23 Bayliss (W. M.) and Stakling (E. H.): The mechanism of 
 pancreatic secretion, J. Physiol. (London), 1902, xxviii, 325. 
 
 -* Stepp (W.): On the preparation of secretin, J. Physiol. 
 (London), 1912, xliii, 441. 
 
 -5 Glet (E.): Des modes d'extraction de la seoretine, C. r. Acad. 
 Sci. (Paris), 1910, cU, 345. 
 
 26 Launot (L.) and CEchslin (K.): Sur une methode de prepara- 
 tion de la s6cretine, C. r. Soc. Biol. (Paris), 1913, Ixxiv, 338. 
 
 -' Starling (E. H.): The chemical control of the body, J. Am. 
 Med. Assn. (Chicago), 1908, 1, 835. 
 
 -** Id.: Discussion on the therapeutic value of hormones, Proc. 
 Boy. Soc. lied. (Sec. Ther.), (London), 1914, vii, 29. 
 
 23 Camus (L.) and GtLEY (E.): S6cr6tine pancreatique active et 
 s6cr6tine inactive, C. r. Soc. Biol. (Paris), 1902, liv, 241; 
 and also ibid., p. 895. 
 
 30 Hakrower (H. E.): Secretin in gas tro -intestinal disorders, 
 
 N. Y. Med. J., 1913, xcviii, 315. 
 
 31 Reed (B.): The indigestions. Am. J. G astro -enterol. (P.hila- 
 
 delpliia), 1912, ii, 5. 
 3- Harrower (H. R.): Secretin in the gastro-iutestinal diseases 
 
 of children, Pediatries (New York), 1913, xxv, 430. 
 33 Id.: The adjunct treatment of tuberculosis with certain 
 
 organic extracts, Br. J. Tuber. (London), 1913, vii, 170. 
 31 Editorial: The treatment of diabetes with extracts of the 
 
 mucosa of the duodenum, J. Am. Med. Assn. (Chicago), 1907, 
 
 xlviii, 698. 
 
 35 Moore (B.), Edie (E. S.), and Abram (J. H.): On the treat- 
 
 ment of diabetes mellitus by acid extract of duodenal mucous 
 membrane, Biochem. J. (Liverpool), 1906, i, 28. 
 
 36 Id.: Further observations on the treatment of diabetes 
 
 mellitus by acid extract of duodenal mucous membrane, 
 ibid., 1906, i, 446. 
 
 3' Bainbridge (F. a.) and Beddard {A. P.): Secretin in relation 
 to diabetes mellitus, Gay's Hosp. Eep. (London), 1907, Ixi, 
 161. 
 
 3^* Evans (C. L.): Note on the fate of secretin in pancreatic 
 diabetes, J. Physiol. (London), 1912, xliv, 461. 
 
 ^^ Crofton (W. M.): Pancreatic secretion in the treatment of 
 diabetes, Lancet (London), 1909, i, 607. 
 
 1° Pemberton (R.) and Sweet (J. E.): The induction of pan- 
 creatic activity by the removal of the adrenals, Arch. Int. 
 Med. (Chicago), 1910, vi, 536. 
 
 *i Id.: The inhibition of pancreatic activity by extracts of supra- 
 renal and pituitary bodies. Arch. Int. Med. (Chicago), 1908, 
 i, 628; and also ii, 295. 
 
 *2 Terroine:* La Secretion Pancreatique.
 
 The Secretins and Pyloro- Duodenal Extracts 81 
 
 Enbiquez (E.) and Hallion (L,): Recherches nouvelles sur la 
 
 s^cr^tine; action sux le foie, Pr. Med. (Paris), 1903, xi, 105. 
 Hallion (L.)= Les notions uouvellcs sur le role de la muqueuse 
 
 duod6nale dans la digestion ; leurs corrolaires pour la patho- 
 
 logie et pour la tli6rapeutique, J. d. mid. d. Par., 1903, xv, 
 
 53; see also Bepeiioire d. ther. (Paris), 1903, xx, 49. 
 Simon (L. G.): Sur quelques effets des injections de secretine, 
 
 J. d. physiol. et path. gen. (Paris), 1907, ix, 78. 
 Foster (N. B.): Beobachtungen iiber die Wirkung des Sekre- 
 
 tins bei Diabetes und Betrachtungen iiber seine Anwendung., 
 
 3Ied. Klin. (Berlin), 1907, iii, 446. 
 Von FtJRTH (0.) and Schwartz (C): Zur Keuntnis der " Sekre- 
 
 tine," Arch.f. d. ges. Physiol. (Bonn), 1908, cxxiv, 427. 
 PoPiELSKi (L.): tJber die physiologische Wirkung und cliemische 
 
 Natur des Sekretins, Zentr. f. Physiol. (Leipzig), 1905-06, 
 
 xix, 801. 
 Alessandra (F.): Influenza della macerazione acide di mucosa 
 
 duodeno-digiunale (contenente secretina) sulla secrezione 
 
 lagi'imale, sulla prodvizione dell' umore acqueo e sulla circo- 
 
 lazione del fondo dell' occhio. Arch, di ottal. (Naples), 
 
 1907-08, XV, 85. 
 Gley (E.): Sur I'antagonisme de I'adrenaline et de la s6cretine, 
 
 G. r. Sac. Biol. (Paris), 1911, Ixx, 866. 
 Tomaszewski (Z.): Ueber die sekretorische Tatigkeit der 
 
 Magendriisen unter dem Einflusse von Organextrakten, 
 
 Zentr. f. Physiol. (Leipzig), 1913, xxvii, 630.
 
 CHAPTER VI 
 OTHER EXTRACTS OF ALIMENTARY ORIGIN 
 
 Extracts of the Gastric Mucosa — The Activities of Extracts of 
 the Intestine — ^.4 Motor Excitant in Intestinal Extract — 
 The Depressor Action of Intestinal Extract — A Bemarkdble 
 Uterine Stimulant — The Detoxicating Power of Intestinal 
 Extract — -The Hormone Influence of the Appendix. 
 
 As we have seen, a very important hormone is elabor- 
 ated in the duodenal walls, and is obtainable for thera- 
 peutic purposes in extracts of this part of the intestine. 
 In the previous chapter reference was also made to the 
 hormone activity of extracts of the pyloric end of the 
 stomach. Here it is proposed briefly to consider the 
 therapeutic possibilities of other extracts of the stomach, 
 certain parts of the intestine, and the vermiform ap- 
 pendix. 
 
 The chief characteristic of a hormone consists in corre- 
 lating the activities of the body, the product of one organ 
 inducing activity of another more or less remote from it. 
 It has been noted by Aarons^ that "it is an essential 
 peculiarity of most hormones that they act on other 
 organs of the body, whereas the hormones of the gastro- 
 intestinal tract have no influence on the general system. 
 The hormones of the digestive apparatus act on the 
 digestive secretion." 
 
 It will be clear, then, that the principal usefulness of 
 hormone-bearing extracts of the various parts of the 
 digestive tract will be confined to their influence upon 
 
 82
 
 Other Extracts of Alimentary Origin 83 
 
 the digestive activities ; and their capacity in this direction 
 deserves to be studied more extensively and applied more 
 frequently in cUnical therapeutics. 
 
 Extracts of the Gastric Mucosa. — There is no doubt that 
 preparations of the gastric mucosa have a therapeutic 
 influence, probably due to their hormone content. It is 
 not unlikely that the gastric secretin discovered by 
 Edkins, or other similar substances, are produced in 
 parts of the stomach other than the pylorus, and hence 
 extracts of the stomach might be supposed to have a 
 therapeutic influence in stimulating this organ to greater 
 physiologic activity. Gilbert^ has stated that the 
 powdered extract of the gastric mucosa possesses a more 
 active and comprehensive influence than pepsin, and has 
 the advantage of being much easier to obtain; it is also 
 considerably more convenient and stable than natiural 
 gastric juice obtained through the fistula. Its action, of 
 course, is different from that of pepsin in that it manifests 
 only a limited degree of digestive activity ; but it is none 
 the less valuable, because it serves to stimulate the lagging 
 cells to more satisfactory service. 
 
 It will shortly be seen that Zuelzer and his collaborators 
 procured an extract of stomach walls which, when given 
 intravenously, caused a considerable increase in peristalsis, 
 and it is quite possible that preparations of this character 
 might be used to advantage in the treatment of con- 
 stipation. 
 
 According to Byla,^ a preparation called exo-gastrine, 
 which is a substitute for natural animal gastric juice, as 
 well as for the commonly used pepsin-HCl mixture, is 
 used in France. It is obtained by extraction by exolysis 
 of the macerated scrapings of the stomach walls of pigs 
 in the presence of glycerine. This is said to be an ex- 
 cellent substitute for the normal juice, since it is always
 
 84 Practical Hormone Therapy 
 
 active and easily preserved. Three or four teaspoonfuls 
 are given in carbonated water before or during meals. 
 
 The Activities of Extracts of the Intestine. — In addition 
 to the secretin-bearing product procured from the duo- 
 denum, extracts of the jejunum and ileum have been 
 made, and considerable experimental work has been done 
 towards establishing their position as therapeutic agents. 
 Enteric opotherapy is available in the treatment of in- 
 testinal indigestion, and several preparations are active, 
 especially because of their content of enterokinase. In 
 addition to the trypsin-activating powers of this substance, 
 it has been shown that preparations of this character 
 have a stimulating influence upon the intestinal walls, 
 augmenting the production of the intestinal hormones 
 and kinases, stimulating the production of the succus 
 entericus, and also increasing peristalsis. The addition 
 of extracts of this character to secretin-bearing prepara- 
 tions might be of advantage in the treatment of chronic 
 dyspepsia associated with atonic conditions in the intestine. 
 
 Masson"* believes that there is a series of endocrinous 
 glands in the intestinal wall of man homologous to the 
 islands of Langerhans in the pancreas. At present it is 
 not yet decided as to the physiologic influence of these 
 hypothetical gland areas, but he believes that in path- 
 ology these glands may be especially subject to neoplastic 
 growths, particularly the so-called " atypical small-celled 
 carcinomata." 
 
 A Motor Excitant in Intestinal Extract. — In their study 
 of secretin-bearing extracts of the duodenal mucosa, in 
 1904, Enriquez and Hallion^ noted that during the experi- 
 ments there was a considerable stimulation of the bowels 
 following injections of these extracts, and that almost 
 invariably after a brief period the bowels were moved and 
 the fseces were often of a liquid nature.
 
 Other Extracts of Alimentary Origin 85 
 
 They concluded that the enterokinetic element in the 
 aqueous extract was not identical with secretin, and made 
 a number of attempts to isolate it. They succeeded in 
 securing an active product, but not in definitely isolating 
 the actual active principle. Because of its marked 
 excito-motor action, they called this substance " moti- 
 line." It has not been made in commerce, although 
 intestinal extracts, suitably combined, are frequently 
 used to stimulate muscular tone and increase the motor 
 activity of the intestines. 
 
 In a later communication these same authors® contend 
 that the motiline, which they assert is to be found in 
 intestinal extract, " is the same substance which Zuelzer, 
 ignoring our own researches, has called ' the peristaltic 
 hormone.' " This may be true; but, as will be seen in 
 Chapter X., Zuelzer's hormone is procured from the 
 spleen. 
 
 Wieland" has since made a series of tests to show the 
 pharmacological comparison between the active principle 
 in intestinal extract and hormonal. He is convinced that 
 while these substances undoubtedly have several proper- 
 ties in common, they are by no means identical. 
 
 The Depressor Action of Intestinal Extracts. — The char- 
 acteristic depressor action of intestinal extracts upon 
 blood- pressure has been emphasized by Popielski,^ and a 
 hypothetical substance, named by him " vasodilatin, " is 
 credited with the responsibihty for this hypotensive 
 action. 
 
 A number of investigators are at work on this and other 
 subjects, and it seems as though a purified hypotensive 
 drug may yet be made from intestinal extracts and used 
 as an antagonist to hypertension. Launoy and (Echslin^ 
 have isolated an element with a marked hypotensive 
 action, and have called it " depressine." Very small
 
 86 Practical Hormone Therapy 
 
 doses suffice to cause a material reduction in blood- 
 pressure. Heretofore most of the clinical tests have been 
 upon animals. 
 
 More recently these authors have reported a new 
 method of preparing depressine from the intestinal mucosa 
 in crystalline and very active form.^*^ It may be that this 
 is identical with the /3-iminazolylethylamine of Dale and 
 Laidlaw, which will now be briefly considered. 
 
 A Remarkable Uterine Stimulant. — A similar, if not 
 identical, substance to the hypothetical " motiline " is 
 the definite chemical product, /S-iminazolylethylamine, 
 which may be prepared from intestinal extract, being 
 formed from histidine by the action of certain putrefactive 
 bacteria. This depressor substance has been isolated 
 from intestinal extract by Barger and Dale,^^ who suggest 
 that it is a part of Popielski's hypothetical " vaso-dilatin " 
 (which is supposed to be obtainable from all animal ex- 
 tracts), but differs in that it has no influence upon the 
 coagulability of the blood. 
 
 /3-iminazolylethylamine has been carefully studied in 
 the Wellcome Research Laboratories by Dale and Laid- 
 law,^- who have outhned its principal physiological action. 
 This, in brief, consists of a characteristic depressor action 
 and a stimulating effect upon plain muscle — in particular 
 that of the uterus. 
 
 From the statements of these investigators this action 
 seems to be even more marked than that of the extract 
 of the posterior lobe of the pituitary gland, for it is said 
 to be evident in dilutions as high as 1 in 250,000,000, 
 
 This substance is more easily made synthetically, and 
 such a product is now obtainable in commerce under the 
 name ergamine. The indications for its use are quite 
 similar to those of ergot, and it may be given with advan- 
 tage where prompt uterine contraction is desired, as in
 
 Other Extracts of Alimentary Origin 87 
 
 postpartum haemorrhage, etc. The dose (hypodermic) 
 recommended is gr. ^V (0 001 gramme). 
 
 The Detoxicating Power of Intestinal Extract.— It has 
 been shown experimentally at least that intestinal ex- 
 tract, under certain conditions, exerts a noticeable de- 
 toxicating effect. 
 
 In 1905, VidaP^ made an interesting experimental 
 demonstration, before the French Congress of Surgery, on 
 the influence of preparations of the intestinal wall upon 
 the faecal poisons. A dog injected with very active fsecal 
 extracts died in a few moments, while a second animal 
 survived the same dose of the same poison, to which had 
 been added an extract of the intestinal mucosa. From 
 this experience, Vidal suggested a clinical indication for 
 the treatment of various forms of intestinal occlusion 
 before surgical intervention is made. In this manner, by 
 the destruction of the absorbed poisons resulting from 
 the reflex action of this extract, operative procedures, if 
 absolutely necessary, are made under more favourable 
 circumstances. 
 
 Although numerous experiments have been made with 
 intestinal extracts, this therapeutic promise seems to be 
 very limited, and the application of this idea has not 
 been tried in more than one or two clinical cases. 
 
 The Hormone Influence of the Appendix. — In our 
 present broadening knowledge of the internal secretory 
 activity of various parts of the body, we are beginning to 
 appreciate the frequent dual activities of various organs. 
 In the literature of the past half-century many references 
 have been made to the function of the vermiform appen- 
 dix, and these ideas have varied from the suggestion that 
 it is a vestigial remnant of an organ which at one time 
 was useful, to the statement that the appendix is a 
 superfluous, useless organ, the principal value of which is
 
 88 Practical Hormone Therapy 
 
 in the removal ! Several studies on the subject have been 
 made, and Salvini^* has performed a number of experi- 
 ments which lead him to believe that the appendix 
 normally produces a substance that stimulates the intes- 
 tinal musculature. This may be a possible explanation 
 of the common clinical observation that appendiceoto- 
 mized individuals are very commonly sufferers from 
 chronic constipation. Quimby^^ of New York, in his 
 radiographic studies, has made some observations which 
 seem to emphasize this position, and one of the conclu- 
 sions of a recent paper by him intimates that when there 
 is chronic constipation due to delayed or inhibitory action 
 of the bowel, the appendix is usually diseased. 
 
 Robert believes that the appendix has an important 
 function in normal digestion, and has found that in certain 
 fish the removal of the appendix materially interferes 
 with digestion. The present author's experiences with 
 an extract of the appendix of pigs indicate that the ap- 
 pendix may also contain an antiperistaltic principle, as 
 the administration of this preparation in several cases 
 had a constipating effect. Experiments are being made 
 with a view to establishing whether or not there are two 
 active principles, the one exercising a stimulating influ- 
 ence on, and the other inhibiting, the motor activities of 
 the bowel. 
 
 The whole subject of the regulation of the complex 
 mechanism of digestion has been made intensely interest- 
 ing by the establishment of the " hormone theory," and 
 it is believed that as the experimental work in this field 
 is standardized and the subject is more fully known, we 
 shall be able to secure a series of very valuable therapeutic 
 agents from various parts of the intestine, to augment or 
 inhibit, as the case may be, corresponding deficiencies or 
 excess on the part of the digestive tract in medical prac-
 
 other Extracts of Alimentary Origin 89 
 
 tice. In the meantime we must be very satisfied to be 
 able to use with such obvious advantage extracts of the 
 pylorus and duodenum, and hope that later other equally 
 valuable preparations may be made available. 
 
 BIBLIOGRAPHY 
 
 ^ Aakons (C. D.): The hormones with special reference to peri- 
 staltic hormone, J. Am. Med. Assn. (Chicago), 1912, Iviii, 
 407. 
 
 2 Gilbert (A.) and Chassevant (A.): Sur une nouvelle classi- 
 
 fication chimique des dyspepsies, C. r. Soc. Biol. (Paris), 
 1900, Ivii, 463. 
 
 3 Byla (P.) AND Delaunat (R.):* P- 293. 
 
 * Masson (P.): La glande endocrine de I'intestin chez I'homme, 
 
 G. r. Acad. d. Sci. (Paris), 1914, clviii, 69. 
 ^ Hallion (L.): Discussion de la communication de MM. Dele- 
 zenne et Frouin sur " La secretion physiologique du sue 
 intestinal," G. r. Soc. Biol. (Paris), 1904, Ivi, 322. 
 
 * Enriquez (E.) and Hallion (L.): Rappel de nos recherches 
 
 experimeutales et cliuiques sur les propri6tes excito-p6ri- 
 staltiques de certains extraits d'organes, Bull. gen. d. Ther. 
 (Paris), 1911, clxii, 702; see also Hallion (L.): Les hor- 
 mones, Pr. med. (Paris), 1912, xx, 433. 
 ' Wieland (W.): Zur Kenntniss des Entstehung der Darmbe- 
 wegung, Arch. f. d. ges. Physiol. (Bonn), 1912, cxlvii, 171. 
 
 * PopiELSKi (L.): Ueber die physiologische Wirkung von Ex- 
 
 trakten aus samtlichen Teilen des Verdauungskauales 
 
 (Magen, Dick- und Dunndarm) sowie des Gehirms, Pankreas 
 
 und Blutes, und ueber die chemischen Eigenschaften des 
 
 darin wirkenden Korper, Arch. f. d. ges. Physiol. (Bonn), 
 
 1909, cxxviii, 191. 
 ^ Launot (L.) and (Echslin (K.): A propos de la secretine 
 
 (Bayliss et Starling) et la vasodilatiue (Popielski). G. r. 
 
 Acad. d. Sci. (Paris), 1913, clvi, 962. 
 ^° Id.: Nouvelle contribution a I'dtude de la depressine, G. r. 
 
 Soc, 1914, Ixxvi, 79. 
 " Barger (G.) and Dale (H. H.): /3-Iminazolylethylamine, a 
 
 depressor constituent of intestinal mucosa, J. Physiol. 
 
 (London), 1911, xli, 499. 
 12 Dale (H. H.) and Laidlaw (P. P.): The physiological action 
 
 of ^-Iminazolylethylamine, J. Physiol. (London), 1910, xli, 
 
 31S.
 
 90 Practical Hormoiie Therapy 
 
 ^^ ViDAL (E.): OpotMrapie dans rocclusion intestinale, Trans. 
 
 Cong. FrauQ. de Chir. (Paris), 1905, xviii, 1237. 
 ^* Savini (E.): Sur I'organotherapie appendiculaire. C. r. 8oc. 
 
 Biol. (Paris), 1914, Ixxvi, 106. 
 ^^ QuiMBT (A. J.): Differential diagnosis of tlie appendix by aid 
 
 of the Roentgen ray, N. Y. Med. J., 1913, xcviii, 697. 
 
 Sakdou (Gr.): Le mode souscutan^e d'opotli6rapie gastrique 
 
 Clinique (Paris), 1912, vii, 718. 
 Id.: Note sur les effets tlierapeutiques de I'extrait intestinal 
 
 total dans diverses modalites d'insufl&sance intestinale, Gaz, 
 
 d. Hop. d. Lyon., 1903, iv, 319. 
 LoEPEK (M.) AND EsMONET (C.) : Action vasotonique de 
 
 macerations de muqueuse de I'estomac, Arch. d. med. exper. 
 
 et anal. path. (Paris), 1911, xxiii, 267. 
 Drucbert (J.) AND Dehon (M.): Eecherclies sur Fopotlierapie 
 
 enterique, Gaz. med. de Paris, 1904, iv, 37; see also Id.: 
 
 Echo med. du Nord (Lille), 1904, viii, 74. 
 Roger (H.): Toxicite des extraits d'appendice, G. r. Soc. Biol. 
 
 (Paris), Ixxi, 353.
 
 CHAPTER VII 
 
 THE PANCREAS AND ITS HORMONE 
 
 Is there a Langerhansian Hormone ? — The Discovery of the In- 
 ternal Secretory Function of the Pancreas — The Production 
 of Experimental Diabetes — The Antidiabetic Action of the 
 Pancreas Hormone — von Noorden's Opinioii of Pancreatic 
 Insufficiency — Knowlion and Starling's Perfusion Ex- 
 periment — The Function of the Islands of Langerhans 
 — Layigerhansian Disturbances in Diabetes — Compression 
 of the Islands a Cause of Glycosuria — Dock's Summary 
 of the Relation of the Pancreas to Diabetes Mellitus — The 
 Antagonism of the Adrenals and Pancreas — The Differentia- 
 tion of Pancreatic Diabetes — The Diagnosis of Pancreatic 
 Insufficiency by Adrenalin — The Pancreas Treatment of 
 Diabetes — Clinical Experience with Pancreas Preparations — 
 Pancreas Extract in Hypertension — The Influence of the 
 Pancreas on Phagocytosis. 
 
 Much controversy has surrounded the study of the 
 internal secretion of the pancreas and its physiologic 
 action and therapeutic possibilities. Naturally this has 
 made it difficult to establish the therapeutic application 
 of pancreatic opotherapy upon as broad a basis as its 
 well-known and favourable enzyme action upon digestion. 
 
 Is there a Langerhansian Hormone ? Almost all are 
 now agreed that the " theory " of the dual capacity of 
 the pancreas is a fact, but not all will admit that the term 
 *' Langerhansian hormone " is warranted by the findings; 
 for it is still asserted that, while the pancreas may produce 
 an internal secretion, we have no proof that its activities 
 are due to a hormone, nor have we been able to 
 isolate one, and not all are agreed that the islands of 
 
 91
 
 92 Practical Hormone Therapy 
 
 Langerhans are the seat of the elaboration of the internal 
 secretion. 
 
 The present author, however, is convinced by personal 
 experience and by a study of a large amount of literature 
 — for the Hterature dealing with or related to this subject 
 is extraordinarily voluminous — (1) That the term " Lang- 
 gerhansian hormone " is warranted; (2) that hormone- 
 bearing extracts of the pancreas can be prepared and 
 frequently applied with success in practical therapeutics ; 
 and (3) that the presumed pancreas hormone has little or 
 no direct connection with the external digestive secretion 
 of this organ, and hence practicallj^ no influence upon 
 alimentary disorders or, more strictly, indigestion. 
 
 An attempt will be made to marshal a few of the essen- 
 tial facts which are the basis of the above conclusions, 
 and as the skein is unravelled it wdU appear that different 
 extracts of the pancreas are very useful in the treatment 
 of certain well-defined disorders of metabolism. 
 
 The Discovery of the Internal Secretory Function of the 
 Pancreas. — The internal secretory function of the pan- 
 creas does not seem to have been thought of until 1889, 
 when the memorable work of von Mering and Minkow- 
 ski^ showed that the removal of the pancreas was in- 
 variably followed by the symptom-complex which is 
 called " diabetes mellitus."* 
 
 This was a substantiation of the theory put forward 
 twelve years before by Lancereaux,^ which was based 
 upon his clinical observations in several cases of severe 
 diabetes, in which degeneration of the pancreas was found 
 at autopsy. Lancereaux was the first to use the term 
 "pancreatic diabetes," and, of course, he had to be 
 severely criticized, for others promptly found indubitable 
 
 * The study of the internal secretion of the pancreas is inseparably 
 connected with the stndy of diabetes ; hence the major part of this chapter 
 will be devoted to ii consideration of this disorder.
 
 The Pancreas and its Hormone 93 
 
 cases of diabetes without evident lesions in the pancreas, 
 and still others found grave pancreatic disease with no 
 previous signs of diabetes. Nevertheless Lancereaux's 
 theory is now well established. 
 
 The Production of Experimental Diabetes. — While 
 reference has repeatedly appeared in medical hterature to 
 von Mering and Minkowski's experiments, it seems 
 advisable briefly to outline their epoch-making results. 
 They made many tests upon dogs, thereby establishing 
 the fact that after complete removal of the pancreas, if 
 the animal survives the operation, diabetes, persisting 
 until death, never fails to appear. If one-fourth or one- 
 fifth of the gland remains, diabetes does not follow ; or if 
 a portion of the pancreas containing the islands of Lan- 
 gerhans, and still attached to its arterial supply, is first 
 transplanted under the skin and all the remainder of the 
 pancreas is removed, no glycosuria is produced, but the 
 removal of the transplanted portion is followed by 
 glycosuria. 
 
 In this latter experiment, as the digestive secretions 
 of the pancreas are not discharged into the intestinal 
 tract, it seems to prove that it is neither the digestion of 
 the food in the intestines nor injury to nerve structures 
 that is at fault, but that the cause is evidently lack of an 
 internal secretion, presumably from the transplanted 
 portion which contains the islands of Langerhans.* 
 
 A number of years later Minkowski^ was stimulated to 
 repeat his experiments, modifying his technique by per- 
 forming a two-step operation. He first removed, for 
 later convenience, the splenic portion of the pancreas, 
 
 * The enzymes of the pancreas are, however, undoubtedly of value in the 
 treatment of diabetes, if only for the improvement in nutrition and digestion 
 that they facilitate. They also serve to strengthen the functional powers of 
 the pancreas, both as regards its capacity to produce the external secretion 
 as well as the internal secretion.
 
 94 Practical Hormone Therapy 
 
 and did a gastro-jejunostomy; from this operation the 
 dog recovered and gained 1,450 grammes in the following 
 month. The second part of the operation was then per- 
 formed, at which the pancreas was divided at a distance 
 of 2 or 3 centimetres from its head. The duodenum, to 
 which was attached the head of the pancreas, was then 
 removed, and a cholecystenterostomy performed. Re- 
 covery was complete, and the dog remained in good health, 
 showing sugar in the urine for only two days after the 
 operation. At the end of four weeks after the operation 
 the dog's urine was still sugar - free, even though 
 50 grammes of sugar and 50 to 100 grammes of rice soup 
 formed a part of the daily diet. The remainder of the 
 pancreas was then extirpated, and within a few hours 
 100 c.c. of urine, containing 9 per cent, of sugar, were 
 excreted. 
 
 A similar experiment was performed upon another dog, 
 but a small pancreatic graft was inserted under the skin 
 of the abdomen, with the result that the onset of diabetic 
 symptoms was postponed until the graft was removed. 
 
 The Antidiabetic Action of the Pancreas Hormone. — It 
 would be superfluous to relate the numerous confirmatory 
 experiments, or, for that matter, the inevitable dissenting 
 voices. Biedl, with good authority, says'*: "The results 
 have since been confirmed by means of many hundreds 
 of experiments undertaken by numerous authors, includ- 
 ing Lepine, Hedon, Gley, Thiroloix, Caparelli, Harley, 
 Schabad, Cavazzini, Sandmeyer, Selig, Rumboldt, among 
 others." In the latest of his numerous communications 
 on this subject Hedon^ has conclusively shown that the 
 blood passing from the pancreas has a decided anti- 
 diabetic influence. He removed the pancreas from a dog 
 and kept it alive for a month by means of a pancreatic 
 graft; the graft was then removed and glycosuria q^uickly
 
 The Pancreas and its Hormone 95 
 
 appeared. Transfusion from the inferior pancreatic vein 
 of a healthy dog was arranged, and by careful weighings 
 the amount of blood transfused was known. For three 
 hours transfusion was continued, and 300 grammes of 
 blood was passed. Laboratory estimations of the urine 
 showed that at the commencement of the transfusion 
 the sugar percentage was 65, and shortly reached 
 81 per cent., in spite of the transfusion, but that very 
 soon the sugar disappeared, and after three hours the 
 urine barely reduced Fehling's solution. 
 
 The figures given prove that the pancreatic venous 
 blood has a marked influence on the renal secretion, 
 diminishing the amount of water and its concentration, 
 slightly increasing the urea, and almost completely elimi- 
 nating the sugar. These experiments confirm Hedon's pre- 
 vious work, and are convincing evidence of the presence 
 of an internal secretion of the pancreas and its influence 
 upon glycosuria. 
 
 Von Noorden's Opinion of Pancreatic Insufficiency in 
 Diabetes. — Von Noorden, in his latest book,® says: "I 
 think I shall be voicing the opinion of all pathologists 
 when I say that every individual who has a diminished 
 tolerance for carbohydrates, either permanently or ex- 
 tending at least over a considerable period, and thus 
 exhibits the most important clinical symptom of dia- 
 betes, must be considered as a subject of pancreatic in- 
 sufficiency. We need not always expect to find per- 
 ceptible anatomical evidence, for there may be functional 
 impairment where no macroscopic or microscopic patho- 
 logical appearances can be discovered." 
 
 The pancreas begins the elaboration of its internal 
 secretion before its external secretion is needed. This 
 has been shown by Carlson and Drennan, and later by 
 Lafon,'' who, in a paper read before the Soci6te de
 
 96 Practical Hormone Therapy 
 
 Biologic, Paris, reports having observed that in a preg- 
 nant dog extirpation of the pancreas did not cause 
 glycosuria until the uterine cavity was emptied. It may 
 be reasonably supposed that the production of the internal 
 secretion of the foetal pancreases was diffused into the 
 blood of the mother and supplied the function of the 
 removed pancreas. 
 
 Knowlton and Starling's Perfusion Experiment. — Another 
 most convincing experiment by Kjiowlton and Starling^ 
 justifies the idea that the pancreas influences carbo- 
 hydrate metabolism by an internal secretion rather than 
 by any power which its cells might have of removing or 
 neutralizing toxic substances while the blood is circu- 
 lating through it. They made observations on the rate 
 at which sugar disappeared from blood that was repeatedly 
 perfused through an isolated mammalian heart prepara- 
 tion (dog), and found that the consumption of dextrose 
 per hour and per gramme of heart muscle was usually 
 less than 1 milligramme when the blood and heart were 
 those of a depancreatized dog, as against 5 milligrammes 
 when the heart and blood were from a normal animal. 
 When the heart was taken from a diabetic animal and the 
 blood from a normal one, the consumption of dextrose 
 for the first hour v/as still low, but it increased steadily 
 during the next two hours ; conversely, when the blood of a 
 diabetic animal was perfused through a normal heart, the 
 dextrose consumption, although almost normal during 
 the first hour, fell off markedly during the second and 
 third. 
 
 These results may be interpreted as an indication that 
 a hormone necessary for the utilization of sugar by the 
 tissues is evidently absent in the diabetic blood. This 
 idea is further supported by the observation that the 
 addition of a boiled pancreas extract to the diabetic
 
 The Pancreas and its Hormone 97 
 
 blood used in their experiments restores almost to normal 
 its glycolytic power. 
 
 The Function of the Islands of Langerhans.*— Being 
 now convinced that the pancreas is concerned in sugar 
 combustion, it may be well to establish the fact that the 
 islands of Langerhans are evidently the seat of the elabora- 
 tion of the pancreatic internal secretion, and thus explain 
 the term " Langerhansian hormone." 
 
 It was in 1895 that Schafer^^ first offered the suggestion 
 that the seat of trouble in pancreatic diabetes was in the 
 islands of Langerhans, and the autopsy findings reported 
 by a number of writers have confirmed this. 
 
 One of the conclusions arrived at by Bosanquet^ in 
 his Gouldstonian lecture in 1905 is as follows: " Although 
 it is not yet proved, yet it is becoming increasingly prob- 
 able that the pancreas is diseased in all cases of diabetes 
 melhtus. An increasmg bulk of evidence is also accu- 
 mulating to show that the function of the pancreas, 
 which is in abeyance in diabetes, is normally performed 
 by certain special groups of cells, known as the ' islands of 
 Langerhans,' which are distinct from the ordinary secreting 
 cells of the gland." 
 
 Thoinot and Delamarre^^ state that they "have now 
 examined the closed intrapancreatic glands of 167 subjects, 
 and have been able in 130 cases to discover Langerhansian 
 
 * Professor R. Lepiue, in a personal communication accompanying the manu- 
 script for this chapter which he had just been criticizing, writes : "Unfortu- 
 nately we arc not in accord on one point. I do not admit, and for some time 
 competent authorities do not concede, that the islands of Langerhans are the 
 exclusive organs of the internal secretion (of the pancreas). It is thought 
 even that they secrete very slightly. It is the whole gland which produces 
 the hormone. Please read the reprints which I have marked " — (A),^pp. 429- 
 431, and (B),i<^ pp. 451-459 and 623-624. One must hesitate to contradict so 
 eminent an authority as Professor Lepine, and the facts pro and con must be 
 taken as they stand. It cannot be denied, however, that the pancreatic 
 hormone is a substance with a very definite action, and that it offers thera- 
 peutic possibilities that are not to be gainsaid, 
 
 7
 
 98 Practical Hormone Therapy 
 
 lesions. We are therefore logically led to regard these 
 forms of diabetes as a clinical demonstration of Langer- 
 hansian insufficiency." Lazarus^^ has induced glycosuria 
 and cachexia in guinea-pigs by administering adrenaline 
 and phloridzin during a period of several months. At 
 the autopsies the adrenals and pancreas were enlarged, 
 and the islands of Langerhans had increased both in 
 number and size. He supposes that this Langerhansian 
 hypertrophy is a result of the efforts of the organism to 
 neutralize the excesses of adrenaline that were given. 
 Lombroso could not duplicate these experiments, and 
 contradicts Lazarus's views. 
 
 Langerhansian Disturbance in Diabetes. — Opie's^ ex- 
 periments at the Rockefeller Institute included a series 
 of the most painstaking post-mortem and pathological 
 examinations. As a result of it he states that — " The 
 study of pancreatic diabetes has shown the relationship 
 of diabetes to lesions of the pancreas and to its various 
 histological structures. If the various lesions to which 
 the pancreas is subject are reviewed, it will be found that 
 those which destroy the islands of Langerhans are almost 
 constantly accompanied by diabetes." At Opie's sug- 
 gestion, CeciP® made a series of autopsy examinations in 
 ninety patients who died of diabetes, and concluded that 
 — " Lesions of the pancreas occur in more than seven- 
 eighths of aU cases of diabetes meUitus, and in such cases 
 the islands of Langerhans constantly appear changed, the 
 lesions in some cases being limited to these structures. 
 In half of those cases of diabetes, in which the pancreas 
 shows no changes, the size of the pancreas or the number 
 of islands is less than normal." 
 
 In this connection Cammidge^''' also writes: "It is 
 highly probable that the islands of Langerhans are in 
 some way intimately associated with sugar metabolism,
 
 The Pancreas and its Hormone 99 
 
 and personally I have no doubt that in at any rate the 
 majority of cases of diabetes, lesions of the pancreas, 
 and particularly the islands of Langerhans, are responsible 
 for the disease." Further evidence is available in 
 quantities, and " the case in favour of the islet theory is 
 steadily growing stronger." ^^ The most conclusive evi- 
 dence has been adduced by Weichselbaum,^^ who, after 
 many years of study, has made the most positive state- 
 ment on this subject. He states that in every one of a 
 series of 183 patients who died with diabetes, in his 
 examination of the pancreas he found distinct and charac- 
 teristic lesions in the islets ; while in an even larger series 
 of control cases, representing many different diseases, 
 no corresponding changes were found. The slight dis- 
 crepancy between the findings of Weichselbaum and 
 those of Cecil referred to previously is probably due to 
 the fact mentioned by Weichselbaum, that when lesions 
 of the islets occur in young persons, hydropic degenera- 
 tion is most frequent, and that lesions of this character 
 are easily overlooked, especially if the tissue has not been 
 properly preserved and prepared. This would account 
 for the cases in which the islets have been said to be normal 
 in fatal diabetes, and perhaps may explain why Cecil 
 did not find lesions in the remaining one-eighth of his 
 cases. Weichselbaum 's work seems to establish con- 
 clusively that the majority of cases of diabetes mellitus 
 are not only of pancreatic, but of Langerhansian origin. 
 
 Heiberg^^ has also shown that there is always danger 
 to the island tissue in the pancreas of diabetics. He has 
 studied the islands quantitatively instead of in the usual 
 purely qualitative way. 
 
 Compression of the " Islands " a Cause of Glycosuria. — 
 Morris,^^ of New York, believes that many cases of 
 glycosuria are due to pancreatitis caused by the effects
 
 100 Practical Hormone Therapy 
 
 of bacteria escaping from the duodenum, and conse- 
 quent squeezing of the islands of Langerhans. As soon as 
 the pancreatitis is relieved, the pressure is reduced, and 
 the islands are enabled to resume their functions, and the 
 glycosuria shortly disappears. 
 
 Tiberti^^ has shown that an artificially induced hyper- 
 plasia of connective tissue in the pancreas ultimately 
 destroys the islands of Langerhans, and so glycosuria 
 results; and Lissauer^^ found in twenty-four subjects 
 with gin liver that the pancreas showed more or less 
 similar changes. His findings confirm those of Weichsel- 
 baum in twenty-seven similar cases. The importance of 
 this " gin pancreas " is evident when one remembers the 
 comparative frequency of the development of diabetes 
 mellitus in persons addicted to liquor. 
 
 A report by S. A. Scott ^^ of Oxford University is of 
 particular interest. He tells of a case of cancer of the 
 pancreas with no previous glycosuria or symptoms of 
 pancreatic internal secretory loss. At autopsy it was 
 seen that the growth had effectively obliterated the 
 ducts and destroyed the glandular part of the organ, 
 with the result that only the islands of Langerhans sur- 
 vived. Opie,2^ in his book, describes and illustrates a 
 specimen in a less advanced state than Scott's. 
 
 Dock's Summary of the Relation of the Pancreas to 
 Diabetes Mellitus. — In the Section of Medicine of the 
 Seventeenth International Congress of Medicine, Dock^® 
 makes the following summary of the foregoing facts: 
 " Now that the relation of the pancreas to diabetes has 
 been carried far towards a conclusion, it is worth while 
 remembering how long it has taken us to reach this stage. 
 Bouchardat very early claimed a place for the pancreas 
 in the pathology of diabetes. Lancereaux and his pupil, 
 Lapierre, tried to show the relation more than thirty
 
 The Pancreas and its Hormone 101 
 
 years ago, but sought it in the external secretion. Von 
 Mering and Minkowski looked for it in the internal secre- 
 tions a decade later; Hansemann soon after insisted on a 
 specific anatomical alteration. In 1895 Schafer made 
 the pregnant suggestion that the islands of Langerhans 
 are at fault, and in a few years this was confirmed on a 
 large scale by the work of Opie, Weichselbaum, Salty- 
 koff, Hirschfeld, Russell, Heiberg, and many others. 
 There is no question now as to the existence of the insular 
 lesions in most cases of diabetes. ... It hardly seems 
 necessary here to discuss the meaning of cases of pancreatic 
 disease without diabetes, and of diabetes without pan- 
 creatic disease — at least, disease we can recognize anatom- 
 ically with our present methods." 
 
 The Antagonism oi the Adrenals and Pancreas. — Atten- 
 tion has already been drawn to the supreme importance 
 of the hormone balance in carbohydrate metabolism (see 
 Chapter III.), and further elucidation of the part that 
 the internal secretory organs play in the regulation of 
 carbohydrate metabolism may be found by studying von 
 Noorden's diagram and descriptive text, which appears 
 on pp. 33 and 34. 
 
 A number of experiments have shown that the Langer- 
 hansian hormone antagonizes the power of the chromaffin 
 hormone to " mobilize " sugar, or, in von Noorden's 
 words, " the pancreas acts as a brake upon the sugar 
 factory." 
 
 Zuelzer^" was among the first to discover the fact that 
 adrenaline glycosuria could be suppressed by injections of 
 an albumose-free pancreatic extract. Frugoni^^ then con- 
 firmed this by showing that pancreas extract had the 
 power of destroying adrenaline in vitro. Ghedini^^ (and 
 later other investigators) have shown that a fatal dose of 
 adrenaline, when mixed with pancreas extract, does not
 
 102 Practical Hormone Therapy 
 
 cause death, and is practically innocuous. Pick and 
 GlsGsner have also prevented adrenal glycosuria by adding 
 to the adrenaline solution 4 to 20 c.c. of liquid pancreatic 
 extract. The same result, obtained, however, by a 
 totally different experiment, was secured by Frouin and 
 Andre Mayer,^° who have demonstrated a diminution of 
 the manifestations of experimental pancreatic diabetes 
 by partial or complete removal of the adrenals. 
 
 The Differentiation of Pancreatic Diabetes. — Since the 
 use of hormone -bearing extracts of the pancreas in 
 diabetes is frequently unsuccessful, it is desirable to be 
 able to discern which cases are likely to benefit. Lepine 
 beUeves that in many cases of glycosuria, and occasion- 
 ally in non-diabetic disorders, there is a functional in- 
 sufficiency of the pancreas which is often very difficult to 
 recognize. 
 
 Sometimes this is possible only by making a therapeutic 
 test. However, there are several subjective signs which 
 are frequently seen in these cases : marked loss of weight 
 (the French call pancreatic diabetes h diabete maigre), 
 serious digestive troubles with steatorrhoea, and an in- 
 frequency of soaps in the faeces. These and other tests 
 not mentioned here* are evidence of a general pancreatic 
 disorder, but not necessarily of a deficiency of the pan- 
 creatic internal secretion, although it is likely that the 
 manifestations of severe disease of the pancreas will not 
 be confined to its external secretion alone. There is, 
 however, another important procedure which appears to 
 be of considerable promise. 
 
 The Diagnosis of Pancreatic Insufficiency by Adrenalin. 
 — The relation of the Langerhansian and chromaffin hor- 
 
 * The subject of "the functional diagnosis of pancreatic disease" is 
 exhaustively studied by Pratt^^ in a paper bearing the above title. It is 
 amplified by no less than ninety-six bibliographic references (see also Leech's 
 review), ^2
 
 The Pancreas and its Hormone 103 
 
 mones to pancreatic insufficiency, and particularly to the 
 so-called "pancreatic diabetes," led Loewi^^ to suggest a 
 clinical test, which gives fairly constant and useful results. 
 He showed that the instillation of 3 or 4 drops of adrenalin 
 (1 in 1,000 solution) into the conjunctival sac causes 
 mydriasis in cases suffering from pancreatic disease. 
 Here it is presumed that the Langerhansian hormone, 
 being diminished or absent, there is an increased ex- 
 citability of the sympathetic system, due to an excess of 
 the antagonist adrenal hormone; and the minute amount 
 of adrenalin is capable of influencing mydriasis. Where 
 this does not take place following the instillation, it is 
 presumed that the pancreas hormone is present, and that 
 this is evidence that the disorder of the internal secretory 
 function of the pancreas is negligible. 
 
 This is not an infallible test, however; but as it is 
 quite innocuous and simple, it is recommended in every 
 suspicious case, and especially in all cases of diabetes. 
 
 Gandola Quadrio^"* tried this procedure in twenty-five 
 cases in his medical clinic in Rome. Twenty did not 
 respond, and no other sign of pancreatic disorder was 
 apparent. Of the remaining five, four had definite pan- 
 creatic disease (two diabetes and two pancreatic tumours), 
 while the remaining case was an epileptic, who, however, 
 showed no sign of alteration in the pancreatic function. 
 
 The Pancreas Treatment of Diabetes. — With the for- 
 midable amount of evidence to show that the pancreas, 
 and more specifically the islands of Langerhans, are fre- 
 quently at fault in diabetes, it would seem proper to infer 
 that just as the administration of thyroid extract enables 
 one to replace the lost hormone in athyroidia, etc., so 
 the deficiency of the Langerhansian hormone could be 
 replaced by the administration of extracts of the Lan- 
 gerhansian islets. This is true in a degree; but the
 
 104 Practical Hormone Therapy 
 
 results are not so specific as those that follow thyroid 
 medication in hypothyroidism for several reasons : 
 
 First, not in every case of diabetes is the pancreatic 
 factor present or prominent.* Second, very few prepara- 
 tions of pancreas are made with the object of specifically 
 supplying as much as possible of the islet substance. 
 Third, it is no easy matter to supply the lacking hormone, 
 for it is normally supplied continuously to the blood, and 
 we have no means of knowing how much is elaborated, or, 
 in disease, how much is lacking in each case. Fourth, 
 the antagonism of the chromaffin hormone must be con- 
 sidered, for the diabetes may be due not simply to a 
 deficiency of the pancreatic internal secretion, but to an 
 exaggeration of that of the adrenals or a combination of 
 both. Fifth, evidently several other factors are con- 
 cerned, and hence the hormone treatment of diabetes 
 alone cannot be instituted with hopes of success. 
 
 The exciting cause of the disturbed hormone balance is 
 not to be neglected, and if it cannot definitely be found 
 (and rarely can this be done, much less can it be con- 
 trolled), all one can expect to accomplish in this direc- 
 tion is to favour the restoration of the hormone balance 
 as much as possible. This is best accomplished by — 
 (1) The regulation of obvious elements of disturbance, 
 such as indigestion, anaemia, worry, etc. ; (2) the regula- 
 tion of the dietary, so that a minimum of the deficient 
 hormone will be required; (3) the sedation of adrenal 
 overactivity, if present; and (4) the exhibition of prepara- 
 tions containing a maximum of the Langerhansian hor- 
 mone in doses graded to fit the condition present. 
 
 Clinical Experiences with Pancreas Preparations.— As an 
 adjunct remedy in pancreatic diabetes, this method is 
 
 * By referring to Chapter XI. it will be found that there are undoubtedly 
 cases of diabetes in which the hepatic hypofunction overshadows any possible 
 pancreatic deficiency.
 
 The Pancreas and its Hormone 105 
 
 of encouraging utility. Frequently glycosuria is reduced 
 to a minimum or disappears entirely, and after response 
 to this treatment a wider dietetic range is made possible. 
 
 Therapeutic trials of feeding pancreas have been carried 
 out by several writers. Combe^^ found it of good service 
 in many cases, although it did not suffice completely to 
 cause the disappearance of glycosuria, save only in a few 
 cases. He called special attention to the improvement 
 in the nutrition and general condition which was also 
 brought about. 
 
 Cowles^^ relates an interesting case in which the in- 
 gestion of from one to three raw calves' pancreases daily 
 reduced the daily amount of urine from 7-10 to 2-3 
 quarts, the specific gravity from 1040-1045 to 1028-1030, 
 and the sugar, although the urine was never entirely 
 sugar-free. The weight was materially increased, during 
 one fortnight 16 pounds being gained. Circumstances 
 caused the patient to stop treatment, and some time later 
 he died from sepsis. The pancreas was found to be a mere 
 fibrous cord. Cowles suggests that the numerous failures 
 with this treatment are due to the administration of too 
 little pancreatic substance, as " few people would be able 
 to eat, even if they could get, the amount of uncooked 
 pancreas taken by my patient." 
 
 Zuelzer^"^ has reported good results from his preparation, 
 and believes that it is possible to cause sugar, acetone, 
 and diacetic acid to disappear from the urine of diabetic 
 patients by the injection of a specially prepared pan- 
 creatic extract. In six cases, between six and sixty-five 
 years of age, treated with subcutaneous injections of 
 extracts of pancreas obtained from living animals at the 
 height of digestion, he reports that the results were uni- 
 form and constant, the glucose, acetone, and diacetic acid 
 being always diminished, and usually entirely absent from
 
 106 Practical Hormone Therapy 
 
 the urine in two or three days after injection. In all these 
 cases no change was made in the diet after administration. 
 
 It is evident that the pancreas-ferment preparations 
 may have an excellent influence upon glycosuria. This 
 is probably due to the restorative action on the pancreas 
 caused by the reinforcement of digestion, and the removal, 
 in part or altogether, of the pancreatic disability which 
 is reflected not alone upon its external, but also on its 
 internal secretion. Walko^''' noted a conspicuous effect upon 
 the sugar content of the urine, which was seen in a case of 
 glycosuria in chronic pancreatitis. Under pankreon medica- 
 tion the excretion of sugar ceased entirely after eleven 
 days and did not return, although a gradual increase was 
 made in the quantity of food containing carbohydrates. 
 
 Rennie and Fraser^^ prepared an extract of the islands 
 of Langerhans of the Teleostei (a genus of fish in which 
 Langerhansian islets are sufficiently large to be visible to 
 the naked eye). It was used in five cases of diabetes, 
 with some improvement; but the experiments could not 
 be continued, owing to the limited supply of the extract, 
 and the difficulty of securing it. 
 
 Crofton^^ reports good results in a child of thirteen 
 following the administration of a total extract of the 
 pancreas {holadin), and in a later paper '^^ tells his further 
 experiences. He begins treatment by giving a preparation 
 of secretin*; if no marked improvement is noted, he 
 gives a pancreas extract from which all the coagulable 
 proteins and ferments were removed by heating to 80° C. 
 for three hours. He frequently gives secretin and pan- 
 creatic extract together. As to his results, Crofton 
 
 * Pochoii*^ was probably the first to suggest the combination of sccretin- 
 bearing extracts (duodenal) and pancreas extract in diabetes. He believes 
 tliat by combining these jiroducts one can stimulate both the internal and 
 external secretory powers of the pancreas. He reports two cases in which the 
 sugar fell sharply (from 50 grammes to 3 grammes and from 70 grannnes to 
 45 grammes per litre), and in other ways miprovement was apparent.
 
 The Pancreas and its Hormone 107 
 
 writes: "I have seen a sufficient number which were 
 going to the bad on the several lines of treatment improve 
 and resume their usual mode of life, and this on an 
 ordinary full diet. This encourages me in the idea that 
 I am working on the right lines. The patients soon begin 
 to lose their abnormal thirst and hunger, and the wretched 
 feeUng of weakness and illness. In some cases the amount 
 of sugar and urine decreases rapidly, but I have never 
 yet succeeded in entirely getting rid of the sugar, although 
 the patient has frequently declared himself well and 
 strong and able for his full quantum of arduous work." 
 
 The author's experience has been limited to a prepara- 
 tion of pancreas called trypsogen, which is said to contain 
 the internal secretion, besides the ferments trypsin and 
 amylopsin. In several cases of unmistakable diabetes 
 mellitus (with several or all of the usual symptoms — • 
 glycosuria, polyuria, thirst, emaciation, and asthenia) the 
 weight has been increased, polyuria quite controlled, and 
 sugar reduced. Occasionally the sugar disappears en- 
 tirely and, with no further treatment, does not return. A 
 case has been seen in which sugar would return immedi- 
 ately the dosage of trypsogen was stopped, and another 
 in which glycosuria returned if the dose was reduced below 
 what apparently was the minimum effective for that 
 patient. No cases of gangrene have been met with per- 
 sonally, but several correspondents have reported en- 
 couraging experiences with this treatment, and in the 
 following chapter an excerpt from a paper published by 
 Attix and RommeP^ records the successful treatment of 
 several severe cases of gangrene. 
 
 Certain cases have been found to respond to this treat- 
 ment in a limited degree, and the sugar is reduced, but 
 persists in small amounts; while, again, not infrequently 
 the results are negative. Quite recently Wynter,"*^ in the
 
 108 Practical Hormone Therapy 
 
 discussion on " Glycosuria " at the Britisli Medical Asso- 
 ciation Meeting (1913), reported having seen good results 
 follow the administration of trypsogen in a severe case of 
 glycosuria. 
 
 Conclusions. — The evidence is by no means unanimous, 
 nor are the results constant ; but it is proved beyond all 
 question that such a condition as the " Langerhansian 
 insufficiency " mentioned by Thoinot exists in many cases 
 of diabetes, and that a possible means of controlling this 
 may be found in extracts of these islands. However, this 
 is but one factor in the control of this complex disease. 
 It seems that pancreas, or preferably Langerhansian 
 preparations, should be added as a part of the routine 
 treatment of all cases of diabetes not definitely known 
 to be due to hepatic disorders, as mentioned previously. 
 
 Pancreas Extract in Hypertension. — There are many 
 remedies more active than pancreas preparations for the 
 reduction of blood-pressure, and it must not be inferred 
 from this subheading that the latter are recommended as 
 hypotensive remedies. Occasionally, however, one finds 
 certain cases of hypertension in which there does not 
 seem to be a very marked arterio-sclerosis. The palpa- 
 tion of the usual superficial vessels shows them to be 
 evidently normal, while the sphygmomanometer tells a 
 different tale. In such cases it is quite likely that there 
 is a hyperadrenia, due either to some stimulating action 
 on the adrenals or to a diminution of antagonist hormone 
 from the pancreas. This leads to the suggestion, which 
 has been clinically tried by Ghedini^^ with success, that 
 extracts of the pancreas rich in its internal secretion 
 might advantageously be employed to control these con- 
 ditions, and if the diagnostic premises are correct, the 
 blood-pressure and associated symptoms are very likely 
 to be lessened by this form of hormone therapy.
 
 The Pancreas and its Hormone 109 
 
 The Influence of the Pancreas on Phagocytosis.— It is 
 
 quite possible that there may be in the internal secretion 
 of the pancreas a factor concerned in phagocytosis and 
 bacteriolysis aside from the influence of trypsin upon 
 bacterial disintegration; and chnical experiences, as well 
 as laboratory experiments with the use of extracts of the 
 pancreas, or better still the Langerhansian bodies, may 
 prove this more thoroughly and conclusively. 
 
 In 1913 the author prepared a paper"** which considered 
 this subject, and it seems best to incorporate it as a 
 separate chapter, which immediately follows this one. 
 
 BIBLIOGRAPHY 
 
 ^ Von Mering (J.) and Minkowski (0.) : Diabetes mellitus 
 nach Pankreasextirpation, Centralbl. f. Jcl. Med. (Leipzig), 
 1889, X, 393. 
 
 - Lancereaux (L.): Notes a propos de deux cas de diab^to 
 Sucre avec alteration du pancreas. Bull. Acad. d. Med. (Paris), 
 1877, vi, 1215. 
 
 2 Minkowski (0.): Untersuchungen ueber den Diabetes mellitus 
 nach pankreasextirpation. Arch. f. exp. Path. v. Phar. 
 (Leipzig), 1893, xxxi, 85. 
 
 * Biedl:* p. 413. 
 
 ^ Hbdon (E.): Le sang veineux pancreatique poss6de-t-il une 
 propriete antidiabetique '? C r. Soc. Biol. (Paris), 1913, 
 Ixxiv, 238; see also Id.: Sur la secretion interne du pan- 
 creas et la pathogenese du diabete pancreatique. Arch. int. d. 
 Physiol. (Liege), 1913, xiii, 4. 
 
 ^ Von Noorden : * p. 69. 
 
 • Lafon (G.): Sur le passage de la secretion interne du pancreas 
 du foetus a la mere, C. r. Soc. Biol. (Paris), 1913, Ixxv, 266. 
 
 ® Knowlton (F. p.) and Starling (E. H.): On the nature of 
 pancreatic diabetes. Lancet (London), 1912, ii, 812. 
 
 ^ Lepine (R.): Recents travaux sur le diabete et sur la secretion 
 interne du pancreas, Rev. d. Med. (Paris), 1910, xxx, 420. 
 
 i^" Id. : Sur la pathogenie et le traitement du diabete sucr6, 
 Bev. d. Med. (Paris), 1913, xxxiii, 449, 601, 769. 
 
 11 Schafer (E. a.): The internal secretions. Lancet (London), 
 1895, ii, 321.
 
 110 Practical Hormone TJierapy 
 
 ^2 BosANQUET (W. C): Some considerations on the nature of 
 
 diabetes raellitus, Lancet (London), 1905, i, 977. 
 ^3 Thoinot (M.) and Delamarke (G.): L'insuffisance Langer- 
 
 hansienne, Pr. med. (Paris), 1904, xii, 491. 
 1* Lazarus (P.): Experimentelle Hypertropliie der Langer- 
 
 hans'schen Pankreasinseln bei der Phloridzinglycosurie 
 
 Munch, med. Wchnschr., 1907, liv, 2222. 
 ^5 Opie (E. L.): On the relation of chronic interstitial pancrea- 
 titis to the islands of Langerhans and to diabetes mellitus, 
 
 J. Exp. Med. (New York), 1901, v, 397; see also 527. 
 ^' Cecil (E. L.): A study of the pathological anatomy of the 
 
 pancreas in ninety cases of diabetes mellitus, J. Exp. Med. 
 
 (New York), 1909, xi, 267. 
 " Cammidge (P. J.): The relation of the ductless glands to 
 
 glycosuria, Pract. (London), 1912, Ixxxviii, 237. 
 18 Editorial: The islet theoiy of diabetes, J. Am. Med. Assn, 
 
 (Chicago), 1911, Ivii, 2086. 
 1^ Weichselbaum (A.): Ueber die Yeranderungen des Pankreas 
 
 bei Diabetes mellitus, Wien. hi. Wchnschr., 1911, xxiv, 153. 
 2° Heiberg (K. A.): Zur pathologischen Anatomic des Diabetes 
 
 mellitus, Ceniralhl. f. allg. Path. (Jena), 1910, xxi, 749. 
 -1 Morris (R. T.): Discussion on "The treatment of diabetes 
 
 and pregnancy," J. Am. Med. Assn. (Chicago), 1913, Ix, 1913. 
 -2 TiBERTi (N.): Intorno al modo di compotarsi della isole del 
 
 Langerhans in sequito alia legatura del condotto pancreatico. 
 
 Abs. in Cent.f. Allg. Path. (Jena), 1909, xx, 430. 
 23 LissAUER (M.): Pathologische Yeranderungen des Pankreas 
 
 bei chronischen AlkohoUsmus, Deut. med. Wchnschr. (Leip- 
 zig), 1912, xxxviii, ii, 1972. 
 2* Scott (S. G.): Obstruction atrophy of the pancreas, J. Path. 
 
 and Bad. (Edinburgh), 1905, xi, 459. 
 25 Opie (E. L.): "Diseases of the Pancreas," second edition, 
 
 1910 (Philadelphia), 326. 
 28 Dock (G.): Diabetes mellitus, Trans. XVII Int. Cong. Med. 
 
 (Sec. Med.), (London), 1913, 231. 
 2^ Zuelzer (G.): Ueber Yersuche einer specifischen Fermentthe- 
 
 rapie des Diabetes, Ztschr. f. exp. Path. u. Ther. (Berlin), 
 
 1908, V, 307, 318. 
 
 28 Frugoni (C): Delia glicosuria adrenalinica e dell' influenza su 
 
 di essa esercitata dell' estratto e de succo pancreatico, Gaz. 
 med. Ital. (Turin), 1908, lix, 372. 
 
 29 Ghedini (D. G.): Sul potere anti-adrenalinico dell' estratto 
 
 pancreatico, Gaz. deg. Osped. (Milan), 1908, xxix, 1669. 
 
 30 Mater (A.): Ablation des surr6nales et diabete pancr6atique, 
 
 C. r. Soc. Biol. (Paris), 1908, Ixiv, 219. 
 
 31 Pratt (J. H.): The functional diagnosis of pancreatic disease, 
 
 Am. J. Med. Sei. (Philadelpliia), 1912, cxliii, 313. 
 
 32 Leech (E. B.): Review of recent attempt to judge pancreatic 
 
 activity by clinical tests, Pract. (London), 1911, Ixxxviii, 63X.
 
 The Pa7icreas and its Hormone 111 
 
 23 LoEwi (0.): Ueber eine neue Funktion des Pankreas und ilire 
 
 Beziehung zum Diabetes mellitus. Arch. f. exp. Path. u. 
 
 Pharm. (Leipzig), 1908, lix, 83. 
 3* Gandola Quadrio (R.): Intoruo ad un nuovo segno dell' 
 
 insufficenza pancreatica, PoUcl. (Rome), 1908, xv (M), 933. 
 3^ Combe (A.) : Glandes a secretion interne et leur emploi tliera- 
 
 peutique (organoth6rapie), Bev. med. d. la Suisse Bom. 
 
 (Geneva), 1895, xv, 250; see also Berl. hi. Wchnschr., 1909, 
 
 xlvi, 1209. 
 
 38 CowxES (W. N.): A case of diabetes treated by feeding of 
 
 calves' pancreas, Bost. Med. and Surg. J., 1911, clxiv, 921. 
 3' Walko (K.): Erkennung und Behandlung der Erkrankungen 
 
 des Pankreas, Brag. med. Wchnschr., 1909, xxxiv, 147. 
 3^ Rennie (J.) and Fraser (T.): The islets of Langerhans in 
 
 relation to diabetes, Biochem. J. (Liverpool), 1906, ii, 7. 
 
 39 Crofton (W. M.): Pancreatic secretion in the treatment of 
 
 diabetes. Lancet (London), 1909, i, 607. 
 *<* Id. : The aetiology and treatment of diabetes mellitus, Trans. 
 
 Boy. Acad. lied. Ire. (Dublin), 1911, xxix, 64. 
 *^ PocHON (G.): Action des ferments pancr6atiques et duodenal 
 
 sur la glycosurie, Bull, et Mem. Soc. Med. d. Hop. d. Paris, 
 
 1905, xxiv, 823. 
 
 42 Attix (J. C.) AND Rommel (J. C): The treatment of diabetes, 
 
 Med. World (Philadelphia), 1912, xxx, 431. 
 
 43 Wynter (W. E.): Discussion on "Non-diabetic glycosuria," 
 
 Lancet (London), 1913, ii, 294. 
 ** Harrower (H. R.): Influence of the pancreas and extracts 
 thereof on resistance to infection. Bract. (London), 1913, 
 xci, 289. 
 
 Minkowski (0.): Pankreasschrumpfung bei Diabetes, Berl. 
 M. Wchnschr., 1912, xlix, 39. 
 
 Ballet (G.): Diabete maigre par sclerose atrophique du pan- 
 creas, Br. med. (Paris), 1912, xx, 33. 
 
 UsPENSKi (D. M.) : Pankreatische Organotherapie, Deut. 
 Aerzte Ztg. (Berlin), 1911, 409, 435, 460, 484. 
 
 Farini (A.): Sull rapporto degli estratti di pancreas, Clin, 
 med. Ital. (Milan), 1910, xlix, 259. 
 
 Sew ALL (H.): Is there a specific treatment for diabetes? 
 Trans. Assn. Amer. Bhysic, 1911, xxvi, 267. 
 
 Scott (E. L.): On the influence of intravenous injections of pan- 
 creatic extract in experimental pancreatic diabetes. Am. J. 
 Bhysiol. (Boston), 1911-12, xxix, 306. 
 
 Id. : The relation of pancreatic extract to the sugar of the 
 blood, Proc. Soc. Exp. Biol, and Med. (New York), 1913, 
 X, 101.
 
 CHAPTER VIII 
 
 THE INFLUENCE OF THE PANCREAS AND EXTRACTS 
 THEREOF ON RESISTANCE TO INFECTION* 
 
 The Pancreas is Concerned in the Control of Infections — The Re- 
 lation of Infective Processes to Pancreatic Disorder — The 
 Opsonic Index in Diabetes — The Action of Pancreas Pre- 
 paration on Gangrene, etc. — The Relation of Typhoid Fever 
 to Glycosuria — The Pancreatin Treatment of Tuberculosis — 
 Stimulating Phagocytosis icith Organotherapy. 
 
 The functions of the pancreas are by no means limited 
 to the production of the ferments for the digestion of pro- 
 teids, fats, and carbohydrates. While its position as the 
 most important digestive gland is fully recognized, other 
 very important functions of this organ have, during recent 
 years, come to light. We now know that, in addition to 
 the manufacture of its external digestive secretion, the 
 pancreas produces an internal secretion or hormone, 
 which has a very important influence on carbohydrate 
 combustion; while still another important phase of its 
 service to the body as a whole — that of increasing its re- 
 sistance to bacterial invasion — is now beginning to be 
 admitted. It is to this last that I Avould direct attention. 
 
 The Pancreas is Concerned in the Control of Infections. 
 — That the pancreas plays an important part in preventing 
 or controlling infection has definitely been proved. In 
 the experiments of Hedon,^ as well as those of von Mering, 
 
 * This appeared as an original article in the Practitioner,^ and is reprinted 
 by permission with several new facts which lend additional emphasis to the 
 author's position. 
 
 112
 
 Influence of the Paiicreas and its Extracts 113 
 
 Minkowski,^ and many others — especially those concerned 
 with the production of an artificial diabetes by extirpa- 
 tion of the pancreas — it was found that to remove the 
 pancreas in one step was almost invariably fatal. The 
 animals did not die of shock or loss of the digestive ser- 
 vices of the organ, but from severe sepsis; the wound 
 would not heal. Starling, in his excellent textbook, 
 draws attention to this in the following statement"^: 
 " One of the main difficulties in the operation of excision 
 of the pancreas lies in the fact that the tissues of a diabetic 
 are extremely prone to infection. It is almost impossible, 
 after total excision of the pancreas, when diabetes has been 
 set up, to procure healing of the wounds wdthout suppura- 
 tion." 
 
 This hindrance to the experiments Avas soon obviated 
 by the implantation of a small piece of pancreatic tissue, 
 preferably from the tail of the pancreas, in the abdominal 
 wall, either before or during pancreatectomy. This small 
 graft sufficed to preserve the resisting power against infec- 
 tion, and, it may incidentally be mentioned, at the same 
 time prevented the desired outcome of the experiments — 
 the production of an experimental glycosuria. As soon as 
 the animal recovered from its serious operation, it was an 
 easy matter to remove the graft (an insignificant opera- 
 tion, in which danger from sepsis was negligible), with 
 the result that an experimental diabetes was quickly 
 established. This seems to afford evidence of a relation 
 between the internal secretion of the pancreas and the 
 power to overcome bacterial invasion. 
 
 The Relation of Infective Processes to Pancreatic 
 Disorder. — There are other ways in which mc may give 
 emphasis to this fact. One of the most frequent compli- 
 cations of diabetes, especiall}^ diabetes of pancreatic origin, 
 is tuberculosis, a fact that has impressed not a few
 
 114 Practical Hormone Therapy 
 
 clinicians. Montgomery,^ in a recent paper, gives the 
 results of his study of 117 cases of diabetes, from which 
 he concludes that resistance to the tubercle bacillus is 
 lowered in diabetes, and that a large number of diabetics 
 develop eventually a very acute, extensive, and rapidly 
 fatal form of pulmonary tuberculosis. This investigator 
 notes that when diabetes and tuberculosis occur together, 
 diabetes is usually the primary disease. 
 
 The frequency with which diabetics suffer from concomi- 
 tant infections is well known. Small pimples often rapidly 
 become serious boils, and these in turn sometimes assume 
 the characteristics of carbuncles, and spread with amazing 
 rapidity. Small infections that are considered trivial, or 
 even negligible, may become quite serious in the diabetic, 
 while the frequency of diabetic gangrene is well known. 
 
 The Opsonic Index in Diabetes. — While the author is not 
 convinced that the exact estimation of the opsonic index 
 is possible under ordinary circumstances, there is no 
 doubt that there is an index of opsonic capacity even 
 though we may not be able to estimate it accurately. 
 Comparative estimations are better than none at all, and 
 the work of King^ is of interest in that it shows that the 
 phagocytic capacity is often reduced in diabetes. This 
 writer makes the following statement: " The first exami- 
 nation of ten diabetics to compare the phagocjrtic activity 
 of leucocjrtes, on a twelve hours' growth of Saccharomyces 
 cerevisice, showed their indices to be 0-61, 0-64, 0-68, 0-69, 
 0-73, 0-805, 0-81, 0-87, and 0-99. We found, therefore, 
 in each of these patients a lowering of the resistance, vary- 
 ing to 0*56 of normal. The one with the index 0-64 had 
 one leg amputated for diabetic gangrene four years ago. 
 The one with the index 0-87 had been taking trypsogen 
 tablets for two months, and said he was much better than 
 he had been."
 
 Influence of the Pancreas and its Extracts 115 
 
 In his study of the blood-findings in diabetes mellitus, 
 Caro'^ invariably found a reduction of haemoglobin and a 
 decrease in the number of red cells. Leucocytosis was not 
 present. In twenty- two cases out of twenty-eight there 
 was a lymphocytosis which in fifteen cases was as high as 
 40 to 70 per cent. These patients invariably suffered 
 from gangrene, tuberculosis, etc. 
 
 From this it must be concluded that either the toxicity 
 of the blood in diabetes is the direct cause of the lowered 
 resistance, or that the absence of a certain hormone has 
 a specific influence upon the resistance, in both incidents 
 the trouble being hormonic in origin — iij the former case 
 indirectly, while in the latter directly. 
 
 These facts seem to establish conclusively that when 
 the internal secretion of the pancreas has been lost, or 
 diminished, either experimentally or from pancreatic 
 disease, there is always a noticeable reduction in the 
 power of the individual or animal to destroy bacteria. 
 
 The Action of Pancreas Preparations on Gangrene, etc. — 
 Emphasis of an encouraging nature is lent to these state- 
 ments by the fact that pancreatic preparations have a 
 marked influence upon infections. A very severe case of 
 diabetic gangrene was recently reported by Attix and 
 Rommel,^ in which the extensive osseous destruction was 
 illustrated by radiographs. The clinical record is of 
 especial interest, as the medical treatment consisted 
 solely of a pancreatic preparation [try opsogen), to which 
 was added ^ grain of codeine three times a day. Here 
 follows a brief abstract of two cases reported : 
 
 "Mrs. L., aged sixty-five, had injured a corn on the 
 great toe. It would not heal. The urine, on analysis, 
 showed 4 per cent, of sugar. Under treatment the sugar 
 rapidly disappeared ; but the condition of the toe extended, 
 typical gangrene developed, and eventually the distal half
 
 116 Practical Hormone Therapy 
 
 of the distal phalanx of the toe was picked out with for- 
 ceps. The wound eventually healed and caused no further 
 trouble. About eighteen months afterward she stubbed 
 the great toe, which became inflamed, but not very sore. 
 The urine was examined, and 8 per cent, of sugar was 
 found. She had stopped all treatment for about nine 
 months, believing herself well. The sugar reached 17|- per 
 cent, (the highest we have ever known), and about one- 
 half of the right foot died from dry gangrene. The line 
 of demarcation was well defined, and the foot became very 
 painful. The sugar was controlled, and operation was 
 advised. The classic operation was done, and Bier's 
 treatment, hot-water bags, etc., applied following it. 
 The flaps failed to unite, became gangrenous, and had to 
 be removed. Operation higher up was advised, but 
 refused. The wound gradually granulated, and at one 
 time both bones of the leg protruded |- inch beyond the 
 other tissues. About nine months after the operation, 
 the stump was completely covered with good skin, and 
 caused no trouble thereafter. Three and a half years 
 after the operation the patient died of cancer in the uterus. 
 At no time was there a trace of sugar in the urine. This 
 was a true case of diabetes with many of the classic 
 symptoms, the sugar-content at one time being the 
 highest I [Attix] have met with in many thousands of 
 sugar determinations, but was completely controlled for 
 years. 
 
 "Mrs. L., aged fifty - nine, had injured her heel. 
 Gangrene developed, and three-fourths of the heel sloughed 
 off down to the periosteum. . . . On first examination, 
 the urine showed 7 per cent, sugar, and the leg looked as 
 though a line of demarcation were going to form. Sugar 
 disappeared at the end of six weeks' treatment, and has 
 only been present in traces on a few occasions since; the
 
 hifliience of the Pancreas and its Extracts 117 
 
 heel is now entirely covered with good skin, and the 
 patient is doing her housework." 
 
 These authors intimate that they might cite several 
 similar cases, and add that " a very inexplicable thing is 
 the healing of these gangrenous areas when sugar is 
 removed from the urine." It would appear that the 
 explanation lies in a special function of the pancreas not 
 hitherto fully recognized. The facts gathered in this 
 paper may help to establish this. 
 
 The Relation of Typhoid Fever to Glycosuria.— An 
 interesting phenomenon is occasionally noticed when 
 diabetics suffer from typhoid fever. It is not unusual to 
 find that the sugar may disappear from the urine during 
 the attack. A satisfactory explanation for this is not 
 available, but it may be that in the attempt of the body 
 to re-establish a normal condition in the intestine, the 
 pancreas is stimulated to increased action in order that 
 phagocytosis, notably low in typhoid, may be stimulated, 
 and the infection more thoroughly controlled. At the 
 same time the increased production of the internal secre- 
 tion of the pancreas suffices to neutralize the antagonizing 
 hormones (see the previous chapter), and to control, for 
 the time being, the glycosuria. 
 
 Prendergast,^having this peculiar relation of typhoid fever 
 to glycosuria in mind, was interested to find out whether 
 tjrphoid vaccine would influence glycosuria in diabetes. He 
 gave four patients a dose of typhoid vaccine, varying from 
 50,000,000 to 100,000,000, at intervals of four days, and 
 in each case the sugar output was very markedly reduced. 
 Later, after discontinuance of the injections, the sugar rose, 
 and at the end of four weeks the vaccine treatment was 
 again begun, and the sugar output was checked. 
 
 While this may be of no prospective therapeutic value, 
 it is at least interesting to note the relation between pan-
 
 118 Practical Hormone Therapy 
 
 creatic activity and the production of the opsonins which 
 correspond to the Bacillus typhosus. 
 
 The Pancreatin Treatment of Tuberculosis. — Several 
 German investigators have been studying the use of 
 pancreatic preparations in the treatment of various infec- 
 tions. Brieger for a number of years has been using 
 pancreatin, given by the mouth, in certain serious diseases, 
 as cancer, tuberculosis, and pernicious anaemia. In a 
 recent article, ^° he cites experiences with several severe 
 cases of pernicious anaemia successfully treated with a 
 combination of pancreatin and arsenic. This author also 
 draws attention to the power of pancreatin to lower the 
 antitryptic index of the blood in tuberculosis, and even 
 predicts a combination of tuberculin with pancreatic 
 extracts as the eventual treatment of that disease. 
 
 StrubelP^ of Dresden has shown that the administration 
 of pancreatin in tablet form increased the opsonic index to 
 the staphylococcus, adding that extract of pancreas contains 
 a substance which is concerned in the defences of the body. 
 
 Discussing the " New Aspects of Pancreatic Organo- 
 therapy," the editor of the Medical Record}^ says: " The 
 future may witness the routine use of pancreatin in tuber- 
 culosis, in affections of the internal secretions (in addition 
 to diabetes), and in many chronic affections with lowered 
 opsonic index." 
 
 The work of Baetzner^^ with pancreatic preparations in 
 the treatment of tuberculosis (concerned especially with 
 the local treatment of surgical tuberculosis) seems to 
 indicate that part of the action of the trypsin is general 
 as well as local. In his conclusions he states: "Even 
 previous to the local changes, a general improvement is 
 observed to follow trypsin injections ; lessening and even 
 complete cessation of pain, discharge, and night-sweats, 
 and, chiefly, a very marked improvement of appetite."
 
 Influence of the Pancreas and its Extracts 119 
 
 Stimulating Phagocytosis with Organotherapy. — Bayle 
 of Carxnes has published some remarkable results with 
 spleen extract as a remedy for tuberculosis. This author 
 is perhaps unduly enthusiastic regarding results, which 
 are, after all, mainly empirical; still the nature of these 
 results led the present writer to investigate the matter 
 further. Many statements have been brought to light 
 showing the influenceof the spleen upon tryptic digestion.^'* 
 It was learned that the spleen produces a chemical mes- 
 senger, or hormone, an important function of which is to 
 activate protrypsinogen, thus increasing nutrition and 
 digestion, as well as raising the phagocytic index. Just how 
 this latter is brought about may be explained by Sajous's 
 theory ^^ — viz., that the trypsin in the white blood-cells 
 is activated by the splenic and pancreatic hormones, and 
 the capacity of the white cell to digest ingested micro- 
 organisms is thereby indirectly increased. 
 
 Clinical experience has been gained with the use of a 
 combination of splenic and pancreatic extracts with the 
 idea of combining these important physiological influences. 
 The results have been most encouraging, and the informa- 
 tion so far secured seems to emphasize the facts previously 
 stated. 
 
 Notwithstanding the convincing physiological study, or 
 even the excellent clinical results outlined above, it would 
 seem that the facts gathered here should serve rather as a 
 stimulus to further practical study than to set this down 
 as a cut-and-dried therapeutic method. The advantages 
 to be gained from the use of pancreatic extracts are 
 certainly not confined to their influence upon digestion, 
 and it would be a pity to withhold from sufferers a means 
 of treatment which is quite harmless, easily administered, 
 and by no means ineffective. 
 
 As Leonard Williams has aptly said^®: "It is time we
 
 120 Practical Hormone Therapy 
 
 set ourselves seriously to examine and appraise the side of 
 the account which is presented by the cultivation of the 
 normal process of resistance to bacterial invasion. . . . 
 Not only are the defences there, asking to be studied, but 
 they afford a subject of inquiry as fascinating as any in 
 the whole range of medicine, and as fruitful in promise as 
 any in the whole range of therapeutics." 
 
 BIBLIOGRAPHY 
 
 1 Hakrower (H. R.) : The influence of the pancreas and extracts 
 
 thereof on resistance to infection, Pract. (London), 1913, 
 
 xci, 289. 
 - H^DON (E.): Sur la production du diabete sucre apres Textir- 
 
 pation du pancreas, C. r. Soc. Biol. (Paris), 1890; see also id.: 
 
 GrefEe sous-cutan6e du pancreas, Arch. d. Physiol. (Paris), 
 
 1892, iv, 617. 
 3 Minkowski (0.): Untersuchungen ueber den Diabetes mellitus 
 
 nach Pankreas-extirpation, Areh. f. exp. Path. u. Pharm. 
 
 (Leipzig), 1893, xxii, 271. 
 
 * Starling:* p. 910. 
 
 5 Montgomery (C. M.): Diabetes mellitus and tuberculosis, Am. 
 J. Med. Sci. (Philadelphia), 1912, cxliv, 550. 
 
 * King (A. J.): Treatment of diabetes as an infectious disease, 
 
 J\^. Y. Med. J., 1909, xc, 17. 
 ' Caro (L.): Blutbefunde bei Diabetes mellitus, Berl. Id. 
 Wchnsehr., 1912, xlix, ii, 1514. 
 
 * Attix (J. C.) AND Rommel (J. C): Treatment of diabetes, 
 
 Med. World (Philadelphia), 1912, xxx, 431. 
 ^ Prendergast (F. A.) : The effect of typhoid vaccine on the sugar 
 
 output in diabetes, Med. Record (New York), 1914,lxxxv, 18. 
 ^° Brieger (K.): Kombinationstherapie bei pernizioser Anamie, 
 
 Beut. med. Wchnsehr. (Berlin), 1912, Ixxxiii, 205. 
 ^^ Strubell (A.): Der Einfiuss der Hormone auf den opsonischen 
 
 Index, Berl. kl. Wchnsehr., 1912, xlix, 2350. 
 
 12 Editorial: New aspects of organotherapy, Med. Becord (New 
 
 York), 1913, Ixxxiii, 205. 
 
 13 Baetzner (W.): Trypsin treatment of surgical tuberculosis, 
 
 Pract. (London), 1913, xc, 203. 
 
 " Harrower (H. R.): Therapeutic action of spleen extract, etc., 
 Lancet (London), 1913, i, 524. 
 
 ^^ SajouS:* vol. i., p. 664. 
 
 1® Williams (L.): The therapeutic promise of the internal secre- 
 tions, Pract. (Loudon), 1911, Ixxxviii, 605.
 
 CHAPTER IX 
 
 THE FUNCTION OF THE SPLEEN AND THE VALUE 
 OF ITS EXTRACTS 
 
 The Broader Functions of the Spleen — 7<s the Spleen an hiternal 
 Secretory Organ ? — The Spleen a Factor in the Control of 
 Nutrition — The Spleen a Pancreatic and Gastric Activator — 
 The Metabolism of Iron — Splenic Opotherapy an Adjunct in 
 Infectious Diseases — Malaria and Paludism — Sjjlenic Ex- 
 tract in Diseases of the Spleen — The Influence of Spleen 
 Preparations on the Blood — Increasing Resistance in Tuber- 
 culosis — Further Experiences with Spleen Preparations — 
 Dosage. 
 
 Like numerous other organs, the spleen has undoubtedly 
 a multiple function, and it seems well established that, 
 like the pancreas, liver, or duodenum, it deserves to be 
 classed with the endocrinous organs. 
 
 Histologically, the spleen cannot be included with the 
 glands or ductless glands, as its structure does not consist 
 of epithelial cells. Hutchison, in his Goulstonian lecture,^ 
 mentions the following functions of the spleen: "It is a 
 filter to remove particles from the blood, and also the 
 debris of red and white cells. It is the seat of formation 
 of lymphocytes, and in a lesser degree large mononuclear 
 leucocytes. During intrauterine life it has a part in the 
 formation of red cells, but there is no evidence that this 
 continues after birth." 
 
 The same writer further emphasizes his belief in the 
 limited view of the splenic functions in his excellent little 
 book on physiology, 2 in which he says that " the spleen 
 
 121
 
 122 Practical Hormone Therapy 
 
 is usually classed in textbooks of physiology amongst the 
 ductless glands. If by a ' gland,' however, one means an 
 organ with secretory functions, then the term is hardly 
 applicable, for whatever its part in the economy of the 
 body, the spleen certainly does not secrete." 
 
 The Broader Functions of the Spleen. — An interesting 
 editorial on the functions of the spleen recently appeared 
 in a leading periodical,^ from which several paragraphs 
 may be quoted: "An examination of any textbook of 
 physiology will suffice to indicate how utterly chaotic and 
 uncertain have been the views with respect to the prob- 
 able functions of the spleen. The chief reason for this 
 state of our knowledge lies in the fact that the obvious 
 fundamental experiment designed to test the uses of such 
 an organ has hitherto completely failed to furnish any 
 decisive evidence regarding the real purpose of the 
 spleen." 
 
 This does not seem to be quite in harmony with the 
 recorded facts. The editorial continues: "There are 
 numerous records of its experimental removal in diverse 
 groups of animals as well as its surgical removal in man ; 
 but either the observations made after splenectomy are 
 entirely negative in so far as any observable perversions 
 of function are concerned, or the evidence is conflicting. 
 Removal of the spleen is certainly not incompatible with 
 the maintenance of life, as is the case in so many other 
 instances of prominent organs which are far less con- 
 spicuous in size and apparent importance. There are no 
 detected alterations of metabolism as the consequence of 
 the operation; yet, in spite of all this negative evidence, 
 one cannot help but hesitate to relegate to the pigeon- 
 hole of physiologic obscurity an organ which so evidently 
 obtrudes itself in our consideration whenever the viscera 
 are brought to^light."
 
 The Value of Spleen Extracts 123 
 
 The Question of the Internal Secretion of the Spleen.— 
 
 Besides the generally admitted facts regarding the physi- 
 ology of the spleen, there are clear experimental evidences, 
 supported by work which it is not difficult to repeat if 
 desired, that the function of the spleen is not limited to 
 its relation to haemopoiesis. Some time ago the present 
 author took occasion to make a thorough search of the 
 literature in an attempt to convince himself that there 
 was a previously proven physiological basis for the en- 
 couraging results which he and certain others had been 
 obtaining from the use of spleen extract.* 
 
 Verzar^ and Meyer ^'^ have recently contributed to the 
 discussion two valuable monographs in which is discussed 
 the importance of the position held by this remarkable 
 organ. Meyer's article is referred to again in Chapter X., 
 and is especially helpful because of its extensive biblio- 
 graphy. 
 
 Unfortunately, the most recent books on the internal 
 secretions — notably Biedl's exhaustive monograph — make 
 no reference whatever to an internal secretion of the 
 spleen; and Swale Vincent, in his book, gives this subject 
 only four lines. Possibly these eminent authors have 
 omitted to refer to the spleen because it is not really a 
 glandular organ, and is not presumed to have any other 
 than its well-known hsemopoietic function. Other in- 
 vestigators have expressed their doubt as to the 
 hormone-producing powers of the spleen. Osborne® of 
 Yale says: "From a histological standpoint, and from 
 the standpoint of what is known of the physiology of the 
 spleen, and from the fact that men and animals can live 
 after the spleen has been extirpated, it seems doubtful if 
 this organ furnishes an internal secretion. When the 
 
 * This was published in February, 1913,* and with a considerable number 
 of additional facts forms this chapter.
 
 124 Practical Hormone Therapy 
 
 spleen is removed, the lymph glands do its work. After 
 such removal there is an increase of the l3rmphoc3i:e9 in 
 the blood and a decrease of red corpuscles, as well as a 
 reduction of the haemoglobin, but in a few weeks the 
 blood becomes normal." 
 
 Metzner'^ also contests the internal secretory powers of 
 the spleen, but Lepine,^ in 1914, referring to Metzner's 
 statement, says: " It seems to me, however, that one can 
 hardly contest this action of the spleen." And again: 
 " I have myself made several experiments which appear 
 to me to prove the correctness of this idea." 
 
 Whether the spleen produces a hormone or not, and in 
 spite of the fact that a part of its work may be vicari- 
 ously accomplished by other parts of the body, there is 
 abundant proof that its less evident functions (other than 
 haemopoiesis and haemolysis) are worthy of consideration. 
 There is little doubt that — in part, at least — ^the influence 
 of the spleen is transmitted to suitably prepared extracts, 
 and is therefore available when necessary in the augmen- 
 tation of these particular functions. 
 
 The Spleen a Factor in the Control of Nutrition. — It is 
 evident that in some manner at present little known the 
 spleen exercises a control upon nutrition; but when one 
 sees splenectomized individuals survive, and after several 
 months become quite normal, one is forced to admit that 
 other organs (probably the red bone-marrow and the 
 lymph nodes) supplant the missing organ. Still, it must 
 be admitted that there is not much satisfaction in this 
 conclusion. 
 
 Richet^ indicates that the spleen, by a mechanism 
 which he does not attempt to explain, facilitates the 
 utilization and increases the consumption of foods. Nine 
 dogs were splenectomized, and careful comparative ob- 
 servations were made with nine other dogs as similar as
 
 The Value of Spleen Extracts 125 
 
 possible in age, sex, and disposition. This author gives 
 convincing tables, which make it clear that the splenec- 
 tomized animals ate more and fattened less, and con- 
 cludes that the missing organ plays an important part in 
 the digestion, assimilation, and consumption of food. 
 This is in corroboration of Bellamy's^^ position, which is 
 outlined in the following pages. This writer expressed 
 his conviction that pancreatic digestion is almost com- 
 pletely destroyed as a result of splenectomy, this diges- 
 tion being then carried out by the stomach and intes- 
 tines. The increased need for food in splenectomized 
 animals, and the proof that digestion is not often so 
 perfect with the spleen liors de combat or entirely removed, 
 thus shown by experiment, simply emphasize the fact 
 long kno\Mi to physiologists — that the functions of an 
 organ which becomes diseased or is removed are often 
 taken up by the other organs. All this suggests that the 
 splenic influence on digestion is supplementary. 
 
 The Spleen a Pancreatic and Gastric Activator.— Asher 
 and SoUberger^^ believe that the spleen is intimately con- 
 cerned in the metabolism of proteids, and it will be inter- 
 esting to revert to the original work along this line, which 
 was begun over thirty years ago. The experimental 
 proof of the above premises concerning the method where- 
 by the spleen favours nutrition was first deduced by 
 Schiff,^'^ who contended that the spleen was concerned in 
 the complex function of the pancreas. His original ideas, 
 however, were faulty, and have been disproved, and to 
 his successor, Herzen^'' of Lausanne, must be given the 
 credit of having definite!}^ settled this question. His 
 experiments were most convincing, and prove that the 
 spleen acts as a tryptogene by means of some unknown 
 substance, which it proliferates, and which is carried by 
 the blood to the pancreas. This work has been dupli-
 
 126 Practical Hormone Therapy 
 
 cated by his associate, Bellamy," whose experiments cor- 
 roborated Herzen's ideas of the relations of the spleen 
 and pancreas. He concludes that " the inactive zymogen 
 granules present in the cells [of the pancreas] receive from 
 the spleen in the form of an ' internal secretion ' the agent 
 with which to elaborate . . . trypsin. The blood carries 
 this product to the pancreas in its solid elements. The 
 jejunal mucosa also furnishes a similar activator, which 
 is produced quite independently of the spleen." Bellamy 
 writes further regarding this: " Without any reference to 
 the possible and perhaps equally important manner in 
 which the spleen acts in other departments of the animal 
 economy, I propose to consider the spleen in the light of 
 a powerful and, indeed, essential factor in the pancreatic 
 digestion of proteids"; and he follows this up with a 
 convincing and comprehensive review of his work and 
 that of his colleagues at Lausanne. 
 
 Luciani has caused an extended series of experiments 
 to be carried out in his laboratories at the University of 
 Rome. They demonstrate that the spleen has an influ- 
 ence upon gastric digestion, and as a result of his experi 
 ments, which are outlined and diagrammatically illus- 
 trated in his book,^ he concludes that — (1) After extirpa- 
 tion of the spleen the digestive power of the gastric juice 
 is constantly weakened in a greater or less degree; (2) the 
 administration by the mouth of an infusion of congested 
 spleen eight hours before the experimental meal increased 
 the digestive power again for one, two, or even three 
 days. 
 
 Further work has been done along this line by Soler 
 and Madero,^^ who are of the opinion that the spleen also 
 plays a part in the production of the gastric enz3rmes; 
 and Hedin's'-^ experiments demonstrated the presence in 
 the spleen of two proteolytic ferments easily destroyed by
 
 The Value of Spleen Extracts 127 
 
 heat, the one active in acid media and the other in alka- 
 line. Rettger^^ also has injected directly into the circu- 
 lation of splenectomized dogs an aqueous extract of 
 spleen, and has demonstrated a definite rise in the trypsin 
 coming from the pancreas, and numerous other studies of 
 the relation of the spleen to pancreatic function have 
 been made by other physiologists.* 
 
 The Metabolism of Iron. — In addition to its activation 
 of the digestive juices of the stomach and pancreas, the 
 spleen is said to have a still more extended influence upon 
 digestion and nutrition. Pugliese^^ of Milan has made 
 experiments from which he concludes that the spleen has 
 an influence also upon the composition of the pigments, 
 and is related to the maintenance of the physiologic 
 amounts of iron in the bile as well as in the blood. 
 
 " Pugliese has proceeded with the experimental analysis 
 of this peculiar function of the spleen. Interrelations 
 between the liver and spleen have been asserted to exist. 
 The Italian physiologist has therefore investigated the 
 secretion of bile in the same animal before and after 
 splenectomy. The volume of bile secreted after removal 
 of the organ is, if anything, increased; but the output of 
 iron in the fluid is noticeably diminished thereby. This 
 is explicable in the light of the undue amounts of iron in 
 the faeces. Pugliese has further demonstrated a diminu- 
 tion of the iron in the blood, along with the decrease in 
 erythrocytes and haemoglobin, in the early period after 
 splenectomy. This does not persist very long, however,, 
 before a recovery of normal conditions in the blood ensues. 
 The facts confirm what we have earlier pointed out — • 
 namely, that with a suitable diet the nutritive outcome 
 of splenectomy need not be in any way unfavourable."^ 
 
 * A number of additional bibliographic references will be found in the 
 author's paper ^ quoted iu the bibliography.
 
 128 Practical Hormone Therapy 
 
 This is also the position held by Asher,^^ who believes 
 that the spleen controls the metabolism of iron. He and 
 his pupils at Berne have established the fact that under 
 the most diverse conditions spleenless animals regularly 
 excrete more iron than their normal companions. Evi- 
 dently the spleen enables the body to retain ingested 
 iron, for the removal of this organ causes an augmented 
 and continued loss of iron in the stools. This finding has 
 been confirmed by Bayer-^ on splenectomized men. 
 
 These facts may not be concerned in the consideration 
 of the therapeutic value of spleen extracts, as doubtless 
 the substances which influence iron metabolism may not 
 be present in these extracts ; but they evidently explain 
 the reason why certain dietaries are more suitable than 
 others for splenectomized individuals. " If healthy young 
 dogs are maintained for even considerable periods on an 
 iron-free diet, they do not suffer any anaemia unless the 
 spleen has been removed, whereupon a marked diminu- 
 tion in the content of hsemoglobin and the number of red 
 blood-corpuscles promptly ensues. This deficiency is at 
 once made to disappear if meat — a food abounding in iron 
 — is furnished in the diet. . , . The conflicting evidence 
 in regard to the blood-forming functions of the spleen 
 may thus find their explanation in dietary factors. In 
 any event, the removal of the spleen, which is not a 
 familiar surgical procedure, calls for an abundance of 
 iron. "2"^ 
 
 Another factor which must be added to the extended 
 list of the activities of the spleen was first noted by Ott^"* 
 in 1897. The spleen is evidently concerned in the regula- 
 tion of peristalsis, and extracts of spleen were shown to 
 have a marked effect in exciting the intestinal movements. 
 Considerable time has been devoted to the study of this 
 special action, and the next chapter deals more especially
 
 The Value of Spleen Extracts 129 
 
 with what is now called "the peristaltic hormone." It 
 is quite evident, however, that this substance is not 
 identical with those substances to which we have been 
 referring — i.e., the hormones concerned in digestion and 
 nutrition. 
 
 Splenic Opotherapy. — Having thus added a little to the 
 textbook information regarding the functions of the 
 spleen, let us collate some of the experiences which go to 
 show that preparations of spleen have a place in rational 
 therapeutics. 
 
 An Adjunct in Infectious Diseases. — ^One would naturally 
 suppose that the spleen must be the source of protective 
 substances, since swelling of this organ frequently accom- 
 panies acute infectious disease, and this is considered to 
 be a defensive act on the part of the spleen. 
 
 Carpenter^ has had considerable clinical experience 
 with the use of splenic extract in typhoid fever, and he 
 believes that the good results which he has obtained are 
 due to an influence in restoring the functional activity of 
 the spleen, which, it is well known, is notably disordered 
 in typhoid. Its administration " causes a marked in- 
 crease in leucocytosis, and otherwise restores its [the 
 spleen's] functions to normal." He used 5 grains of 
 splenic extract three times a day in typhoid fever, and 
 states that this was a means of rapidly and steadily 
 reducing the temperature without undue diaphoresis, and 
 that it ameliorates all the symptoms and restores the 
 patient to the normal. 
 
 Malaria and Paludism. — In a more recent article Car- 
 penter^® also advocates splenic extract as a " real remedy 
 for malarial infection," and explains its action in malaria 
 in the same manner as in typhoid, and goes as far as bo 
 state that it produces the beneficial effects of quinine 
 without its bad effects. Incidentally, he also advises the 
 
 9
 
 130 Practical Hormone Therapy 
 
 use of red bone-marrow, which seems to activate the 
 splenic extract in those cases which do not promptly 
 respond to splenic extract alone. This is in corrobora- 
 tion of the experiences of a number of others, who have 
 used spleen in malarial cachexia and paludism with a 
 resultant reduction in the hypertrophy of the spleen, as 
 well as in the other symptoms. 
 
 In malarial cachexia spleen may be used to good 
 advantage. Of course, it does not supersede quinine, and 
 must not be counted as destructive to the parasites. Its 
 value lies in its restitutive effects upon the cachectic spleen 
 and blood, reducing the size of the former and increasing 
 both the red and white cells in the latter. 
 
 Nouveau's^^ thesis brings together facts which show 
 the advantage of spleen substance over quinine, arsenic, 
 iron, hydrotherapy, etc., in the treatment of paludism. 
 He noted the rather interesting fact that there was fre- 
 quently slight pain in the region of the spleen two or 
 three hours after the administration of the extract, but 
 that it was shortly followed by a feeling of general well- 
 being. The results were not limited to the moderate 
 cases, but even in most desperate conditions an appreci- 
 able amelioration was noted. 
 
 Roux and Lacomme^^ showed that extract of spleen 
 increased the resisting power of the blood, and report the 
 disappearance of trypanosomes from the blood following 
 injections of this substance. There does not seem to be 
 any confirmation of this experience. 
 
 Splenic Extract in Diseases of the Spleen. — It is well 
 known that various animal extracts are capable of modi- 
 fying disorders of the corresponding organ. Evidence is 
 adduced elsewhere to show that adrenal extract has been 
 used in Addison's disease, hepatic extract in liver disease, 
 thyroid CxKlract in thyroid disease, etc.; and the results
 
 The Value of Spleen Extracts 131 
 
 are said to be due to the partial replacement of the 
 internal secretions of the organ in question, and to a 
 special action, first emphasized by Hallion, manifested 
 by a regeneration of the sound but functionally inactive 
 tissues. This being so, it was natural that extracts of 
 spleen should be tried in several well-knowTi diseases of 
 that organ. Reference has already been made to the use 
 of splenic extract in malarial conditions. 
 
 The best results have been secured in the application 
 of this idea in the treatment of splenomegaly, and this 
 in spite of the seriousness of this disorder and its intract- 
 able nature. 
 
 In a communication made by Paucot,"^ of the French 
 Army Medical Corps, stationed at Hai-Duong (Indo- 
 China), will be found an almost astounding series of ex- 
 periences. The frequence of splenomegaly in the tropics 
 materially facilitated this writer's tests, and he reports 
 having tried every known method of treatment, including 
 splenectomy. Experiences with this operation lead the 
 author to the conclusion that it is not prudent to remove 
 the spleen. This, however, is a matter for surgeons to 
 discuss. The use of arsenical preparations, iron, ergotine, 
 etc., did not produce either rapid or satisfactory results 
 in the sixty cases so treated. 
 
 Of 252 cases in which the spleen was enlarged and 
 there were typical symptoms of splenomegaly, no less 
 than 251 were cured — that is to say, the spleen, which 
 before treatment measured from 10 to 20 centimetres in 
 height, became normal, and was neither palpable nor per- 
 cussable below the ribs, and the usual symptoms dis- 
 appeared. The sole remaining case was benefited in a 
 degree. 
 
 These results were qualified by a long series of clinical 
 reports from the official Government records, and here
 
 132 Practical Hormone Therapy 
 
 follows as briefly as possible an outline of Paucot's pro- 
 cedure: Fresh beef spleens were reduced to a pulp, and 
 given in doses of 50 grammes each morning; 25 grammes 
 did not give sufficiently rapid results, and more than 
 50 grammes seemed to be too much. This resulted in 
 an increase in appetite, which, however, was lost and a 
 certain repugnance for food ensued if the dose was raised 
 much above 50 grammes. Translating directly from the 
 article in question, we read: " To sum up, this treatment 
 has given me results incomparably superior to those 
 which I have secured from other methods of treatment. 
 It seems to be able to succeed in every case of chronic 
 splenitis, save only where the spleen has acquired a stone - 
 like hardness, and has become adherent to the diaphragm 
 or abdominal wall. Even then, however, there has been 
 amelioration. The general condition is rapidly benefited. 
 The men are so thoroughly cm-ed that they are able to 
 continue their service, thus obviating a considerable 
 expense and loss of men to the Government." 
 
 The Influence of Spleen Preparations on the Blood. — 
 Numerous writers have called attention to the influence 
 of spleen extracts as hsemopoietic reconstructants. All 
 physiologists agree that the spleen is an important part 
 of the hsemopoietic system, although not entirely essential 
 to it. Its influence in the production of leucocytes and 
 its place as an important defensive organ against disease 
 were emphasized by Bezangon^^ in his thesis. Gold- 
 scheider and Jacob^^ in 1893 reported that extracts of 
 spleen and thymus produced decided leucocytosis, and 
 showed that this was evidently not due to the nuclein 
 contained in these extracts, for similar experiments with 
 preparations from the thyroid, liver, and kidney, all of 
 which contain relatively large amounts of nuclein, caused 
 no appreciable influence on the white-cell count.
 
 The Value of Spleen Extracts 133 
 
 In 1894-95 Danilewsky ^^ a^d Selensky made a study 
 of this subject, and as a result of their experiments they 
 announced that the extract of spleen contained a certain 
 definite substance, not destroyed by heat, which, when 
 used hypodermically, caused considerable increase in the 
 haemoglobin index (from 7 to 40 per cent.) as well as in 
 the red-cell count (from 10 to 40 per cent.). 
 
 Simon and Spillman^^ record encouraging experimental 
 findings, which emphasize the value of splenic extract in 
 modifying the blood-count. Injections of 0-20 gramme 
 of fresh spleen extract caused an increase of both red and 
 white cells, and in one of the cases a red count of 2,988,000 
 became 6,816,000, and the white rose from 9,400 to 12,800. 
 The therapeutic application of these facts is interesting. 
 Bayle's experiences with the blood-counts following injec- 
 tions of splenic extract are as follows^"* : "When one injects 
 5 c.c. of splenic extract in a tuberculous individual with 
 a red count of 3,800,000, it will be approximately 5,000,000 
 twenty-four hours after the injection. A second injec- 
 tion twenty-four hours later will bring the figure to almost 
 6,000,000. The number then varies during the period of 
 treatment between 5,000,000 and 6,000,000. ... We 
 have also noted a distinct increase in the number of white 
 cells, the eosinophiles being increased as well as the 
 lymphocytes." 
 
 David^^ has also used an extract of spleen in anaemia, 
 clinically confirming Danilewsky's experimental studies. 
 He also found that not only were the blood-findings 
 changed, but the appetite was increased, and there was 
 a corresponding gain in weight and general resistance. 
 
 Carnot^^ offers an explanation of the manner in which 
 spleen extracts favour haemopoiesis. He writes: "We 
 know that in order to stimulate an organ we may employ 
 the extract or pulp of an organ having a synergistic
 
 134 Practical Hormone Therapy 
 
 action. For instance, we stimulate the ovaries by giving 
 thyroid extract. It is therefore conceivable that the 
 bone-marrow may be stimulated by the administration 
 of splenic extracts, and haemopoiesis thus be regulated." 
 
 It is also believed that the spleen exercises an influence 
 on the coagulability of the blood, and in some manner 
 tends to prevent hsemorrhage. A preparation named 
 stagnin, produced in Germany, is made from the spleen 
 of the horse. It is a liquid preparation, and in its pro- 
 duction the spleen substance has been subjected to autol- 
 ysis. The dose is 1 to 2 c.c. subcutaneously. Landau^"^ 
 has used it with success in various haemorrhages, and 
 reports especially good results in monorrhagia. 
 
 A remarkable coincidence was noticed by Landau, 
 which is worth mentioning. He found that in cases of 
 multiple cancer which came to the autopsy-table, even 
 though several organs — lungs, liver, kidneys, etc. — were 
 studded with miliary carcinomatous nodules, the spleen 
 was invariably free from them. 
 
 Increasing Resistance in Tuberculosis. — It has been 
 proved that the protective powers of the organism are 
 dependent in part upon the presence in the leucocytes of 
 a certain amount of active trypsin. ^^ It is also believed 
 that phagocytosis is virtually digestion of the enveloped 
 bacteria by the white blood-cells, and, further, that 
 trypsinogen passed from the pancreas into the blood is 
 activated by the splenic hormone, and the active secre- 
 tions are then utilized by the white cells. Whether this 
 sequence of events occurs regularly or is brought about 
 by spleen substance is not yet proved, but the literature 
 contains much substantial evidence that resistance to in- 
 fection, especially in tuberculosis, may be facilitated by 
 the administration of preparations of spleen. 
 
 One of the pioneers in this fruitful field of investiga-
 
 The Value of Spleen Extracts 135 
 
 tion is Bayle of Cannes, to whom the author is indebted 
 for the stimulus which has caused him to make clinical 
 tests as well as an exhaustive study of the literature on 
 this subject. 
 
 While clinical reports in the application of this idea 
 are still comparatively few in number, a limited personal 
 experience, coupled with that of several correspondents 
 in Great Britain, the United States, France, Italy, and 
 Russia, convinces me of its importance. Since tuber- 
 culosis is essentially a wasting disease, a vital part of its 
 treatment is the attempt to increase the nourishment of 
 the body, thereby enhancing its resisting powers. It cer- 
 tainly seems as though the facts already brought forward 
 substantiate the value of splenic extract, and one cannot 
 but be convinced that this method of treatment is worthy 
 of much more extended trial. A preparation of the 
 extracts of spleen, liver, and pancreas^® has, to the 
 author's certain knowledge, been a factor in favouring 
 the nutrition of a number of consumptives in whom the 
 nutritional element was the most discouraging feature. 
 
 For nearly twelve years Bayle has used spleen prepara- 
 tions in tuberculosis, and in his communication, read 
 before the International Congress of Tuberculosis at 
 Rome, April, 1912, he concludes: "I feel authorized by 
 my results to call splenic opotherapy a specific treatment 
 for tuberculosis. It is specific from the therapeutic view- 
 point, because it modifies the soil, rendering it less suit- 
 able as a medium for the culture of the bacillus of Koch. 
 It is specific from the practical viewpoint, because it 
 manifests all the function and rapidity of action of a 
 specific medication. Employed in convalescents, it pre- 
 vents tuberculosis by increasing the mineral content of 
 the tissue [en remineralisant le terrain). Employed in 
 confirmed cases of tuberculosis, it cures them."
 
 136 Practical Hormone Therapy 
 
 In an earlier communication Bayle'*^ refers to " 150 
 cases treated by me in which I have noticed 146 showing 
 the unquestionable and rapid effects of the treatment. 
 Among those which I have been able to follow for a 
 length of time sufficient to acquire some conviction. I 
 note 75 per cent, of cures, some of which were in a very 
 advanced stage, and regarding which I had no hope to 
 begin with." 
 
 In no disease have so many and such varied remedies 
 been recommended as in tuberculosis, and the mere 
 number alone is evidence of their unsatisfactory results. 
 Time and again our hopes have been raised, to be as 
 rudely dashed to the ground. One therefore accepts with 
 considerable reserve such enthusiastic statements, no 
 matter how thoroughly they may be backed up by 
 clinical results. While many have considered Bayle's 
 experiences as "too good to be true," there is no doubt 
 that a more general trial of spleen preparations in tuber- 
 culosis wiU be both interesting and profitable. 
 
 Bayle's method is of interest, for he has secured in- 
 dubitable results. He prepares an extract of pig's spleen, 
 which is called colloidogenine, because he believes that its 
 action is connected with a hypothetical capacity of this 
 organ to maintain, by means of an internal secretion, the 
 principal mineral elements of the blood in a colloidal state 
 — the so-called " colloidogenic " function.* 
 
 * Bayle's theory is this : The blood contains the mineral elements in two 
 forms — (1) Those in a colloid state suitable for cellular appropriation, and 
 thus not suited for elimination by the kidneys ; and (2) the mineral cellular 
 wastes, wliich are dissolved in the plasma, and ai-e destined to be eliminated. 
 If the colloid elements lose their colloidal form, they are promptly eliminated, 
 and a condition of demineralization obtains. The capacity to maintain the 
 mineral salts in a colloidal state is evidently of considerable importance, and 
 according to Bayle, seems to belong to the spleen. Bayle states that he has 
 always found that splenic opotherapy quickly reduces an excessive elimination 
 of jihosphates in the urine All of this deserves to be tested experimentally 
 and clinically.
 
 The Value of Spleen Extracts 137. 
 
 He injects the contents of a 5 c.c. ampule into the 
 buttock each day for twelve days. Then, after a rest of 
 eight days, he commences another series of twelve daily 
 injections, followed by another rest of eight days, and so 
 on until the results warrant discontinuance of the treat- 
 ment. He reports having given over 4,000 such treat- 
 ments, with no inconvenience. 
 
 By mouth he gives an elixir, the strength of which 
 corresponds to 25 grammes of fresh spleen to each table- 
 spoonful. Four tablespoonfuls are taken each day, one 
 at each meal. Bayle has also given 100 grammes per 
 day of spleen pulp in jam, and suggests the cruder method 
 as available for the poorer classes, as it is less expensive 
 and just as efficacious. 
 
 Hypodermic and oral administration may be combined, 
 and the dosage above is followed — i.e., 5 c.c. hypodermi- 
 cally and 25 grammes four times a day in elixir, syrup, 
 or raw in jam, etc. — thus obtaining a maximum of ac- 
 tivity and rapidity of response. In his most recent paper 
 at this writing (December, 1913), Bayle concludes^'*: " To 
 date I have treated several hundred cases of tuberculosis — 
 pulmonary, osteo-articular, and glandular. The results 
 have been : 100 per cent, cure in primary pulmonary tuber- 
 culosis, 75 per cent, cure in all cases (including the cachec- 
 tic, advanced cases), remarkably rapid cure of white 
 swellings {tumeurs blanches) (treatment lasting from one 
 to eight months), cure of tuberculous glands in from 
 fifteen days to two months. This treatment, which is 
 perfectly innocuous, gives results comparable for rapidity 
 and constancy to those which follow the so-called speci- 
 fics." 
 
 Further Experiences with Spleen Preparations. — Quite 
 recently van Stockum of Rotterdam^^ has been experi- 
 menting with an extract of spleen which has previously
 
 138 Practical Hormone Therapy 
 
 been exposed to the Rontgen rays. He reports 3,000 
 treatments, which show that the method is harmless, 
 and that it causes an early change for the better in many 
 cases, especially of surgical tuberculosis. He first trans- 
 planted healthy splenic tissue under the abdominal skin, 
 and rayed it daily with encouraging results ; and later, to 
 obviate the necessity of the operation, after several 
 attempts, he obtained a liquid which gave excellent 
 results without producing toxic symptoms when injected 
 daily in doses of 20 c.c. Four patients were treated with 
 the mixture of splenic tissue in a solution of hydrogen 
 peroxide, and then subjected to X-ray treatment. Three 
 of these were cured, and the fourth was improved. 
 Another series of experiments was undertaken with the 
 preparation obtained through repeated precipitation of 
 the fluid above described. The last precipitate contained 
 what van Stockum believes to be the active principle, 
 and this proved more powerful than any of the preceding 
 substances used, causing marked improvement after two 
 injections. This last treatment was applied in seven 
 cases, and has given encouraging results in every one. 
 For five or six days 20 c.c. are injected daily, and van 
 Stockum believes that he has obtained a permanent cure 
 by this method. 
 
 To test the results of van Stockum, Bayle,^"* acting 
 upon the advice of Professor Lepine, made a series of 
 daily blood-counts in a number of cases, half of which 
 were treated with Bayle's aqueous extract {colloidogenine) 
 and the other half with extracts which had been irradiated 
 according to the method of the Dutch writer. The results 
 were the same in both series, and it is concluded that van 
 Stockum 's results were due to the virtues of the splenic 
 extract itself, and not to changes brought about by the 
 influence of the X ray upon it.
 
 The Value of Spleen Extracts 139 
 
 Schr6der,^2 Superintendent of the Neuen Heilanstalt 
 fiir Lungenkrankheiten in Scliomberg, has carried out 
 many tests which show that the spleen is a defence organ 
 against tubercle infections. It was noticed that rabbits 
 and calves show a relatively great resistance to tubercle 
 infection, and Schroder concluded that the spleen of these 
 animals is especially rich in the hypothetical defensive 
 agent, and would increase the resistance if introduced 
 into an infected organism. 
 
 Tuberculous human sputum was administered to guinea- 
 pigs or subcutaneous injections were made of the sputum 
 or of fresh cultures of human tubercle bacillus. An ex- 
 tract was prepared from the spleens of animals immunized 
 to tuberculosis, and was given hypodermically. Some of 
 these animals received injections before and some after 
 the inoculations. The dose of the extract was in all cases 
 regulated by the body weight of the animal. The im- 
 munizing effect of the extract was obvious, insuring a 
 longer duration of life and milder lesions in the animals 
 treated as compared with the control animals, in which 
 the typical lesions of experimental tuberculosis were found. 
 
 In the animals treated with splenic extract the tuber- 
 culous foci in the lungs showed a marked tendency to 
 fibrous healing. Wherever caseation was found, it was 
 in a retrograde state, indicating attempts at healing. 
 
 In a further communication Schroder'*^ and his asso- 
 ciates report that " a certain immunity follows injections 
 of splenic extract, and the resistance to tuberculous infec- 
 tion is manifested by connective-tissue organization of 
 the tuberculous foci. Tubercle bacilli lose their virulence 
 when kept in contact with splenic extract. Direct bac- 
 teriolysis was not observed. Splenic extract does not 
 diminish the antigens of O.T., no antituberculin being 
 found in the serum of animals treated with splenic extract."
 
 140 Practical Hormone Therapy 
 
 Some of Carrers"*^ experimental work at the Rocke- 
 feller Institute seems to give weight to Schroder's re- 
 marks concerning the influence of this treatment upon 
 fibrous encapsulation. Carrel advances the startling view, 
 which is backed up by the most extensive experiment, 
 that certain tissue extracts have the power to activate 
 in vitro the growth of connective tissue. While he found 
 that the extract of chick embryos was the most active 
 preparation, extracts of adult spleen were almost as 
 active, while kidney and heart extracts were much less 
 active, and extracts of connective tissue or blood-cells 
 were almost without influence. Carrel intimates that 
 these discoveries " may be indirectly useful by leading to 
 the discovery of some of the factors determinating the 
 growth of tissues and of the unknowTi laws of cell dyna- 
 mics, and may ultimately throw light on the mechanism 
 of the cicatrization of wounds." 
 
 Strangely enough, spleen preparations have been advo- 
 cated in Great Britain for the treatment of certain phases 
 of insanity. Clarld^ used them in asthenic cases, with 
 good results both on the general and mental condition. 
 Their principal influence was upon the weight and blood- 
 count. Confirmation of this is given by Bois and Kerr,"*® 
 who pointed out that splenic extract is often useful in 
 such cases, especially when associated with thyroid 
 extract, where indicated; but this is not generally ad- 
 mitted. 
 
 Quite a number of other references regarding the influ- 
 ence of the spleen and its hormone may be found, and 
 interested readers are referred to the writings of Patri- 
 celli, Liverato, Grimana, Foa, Maggiore, Salomon and 
 Halvron, Lepine and Lyonnet, and Williams. 
 
 Dosage. — Splenic extract is practically non-toxic. 
 Simon and Spillmann^''^ report that a series of injections
 
 The Value of Spleen Extracts 141 
 
 of 2 to 4 c.c. in frogs varying in weight from 80 to 92 
 grammes were not accompanied by the least trouble. 
 The dose varies considerably, Paucot found, as already 
 noted, that more than 50 grammes of chopped spleen 
 were not well tolerated, while Bayle's dosage is twice 
 this. Dried extracts are not so nauseous, and, according 
 to Carnot, may be given in capsules or tablets containing 
 \^ grains (O'l gramme) or more, four to ten tablets being 
 given daily. 
 
 The statements preceding and a study of the literature 
 referred to in the bibliography should convince even the 
 confirmed sceptic that the splenic functions have an 
 extent and importance far beyond their immediate con- 
 nection with the blood. There can be no reasonable 
 doubt that the spleen has a very important influence upon 
 digestion, nutrition, haemopoiesis, and resistance to infec- 
 tion, and that splenic extract is a valuable remedy in the 
 treatment of those conditions in which malnutrition, 
 anaemia, and infections are important factors. While the 
 author does not for one moment consider splenic extract 
 a panacea, it undoubtedly facilitates an increase in weight 
 and resistance in many cases, and should be regarded as 
 a remedy with a reasonable basis and of considerable 
 therapeutic promise. 
 
 BIBLIOGRAPHY 
 
 ^ Hutchison (R.): On some disorders of the blood-forming 
 organs in early life. Lancet (Loudon), 1904, i, 1323. 
 
 2 Id.: " Applied Physiology " (London), 1908, p. 99. 
 
 3 Editorial: Functions of the spleen, J. Am. Med. Assn. 
 
 (Chicago), 1912, lix, 1546. 
 * Harrower (H. R.): The therapeutic action of splenic extract 
 
 and its application in the treatment of tuberculosis, Lancet 
 
 (London), 1913, i, 524. 
 5 Verzar (F.): Die Grosse dor Milzarboit, Bioclicm. Ztschr. 
 
 (Berlin), 1913, liii. 09.
 
 142 Practical Hormone Therapy 
 
 s^ Meyer (A.): Beitrag zur Kenntnis der Milzfunktion, Centralbl. 
 
 f. d. Grenz. d. Med. u. Chir. (Jena), 1914, xviii, 41 (Biblio- 
 graphy, with 363 references). 
 ^ OsBOKNE (0. T.): Disturbances of the internal secretions clinic- 
 ally considered, J. Am. Med. Assn. (Chicago), 1910, liv, 670. 
 ' Metzner (J.): Chapter on " Innere Sekretion " in " Lehrbuch 
 
 der Physiologie," Zuntz and Loewy (Berlin), 1913, p. 638. 
 ^ Lepine (K..): Nouvelles secretions internes ct nouvelles fonc- 
 
 tions des vaisseaiix, Bev. d. Med. (Paris), 1914, xxxiv, 81. 
 ^ RiCHET (C): Influence de la rate sur la nutrition, C. r. Soc. 
 
 Biol. (Paris), 1913, Ixxi, 635. 
 1° Bellamy (H. F.): The spleen in the digestion of proteids. 
 
 Lancet (London), 1900, ii, 1185. 
 ^^ AsHER (L.) AND SOLLBERGER (H.): Beitrag© zur Lehre von der 
 
 Funktion der Milz als Organ des Eiweisstoftwechsels, Bio- 
 
 chem. Ztschr. (Berlin), 1913, Iv, 13. 
 ^- ScHiFP (M.): Ueber die Funktion der Milz, Ges. Beitr. zur 
 
 PhijsioL, 1862, iv, 167. 
 ^3 Herzen (A.): Ueber den Einfiuss der Milz auf die Bildung des 
 
 Trypsins, Arch. f. d. ges. Physiol. (Bonn), 1883, xxx, 295; see 
 
 also ibid., 1901, Ixxxiv, 115. 
 ^* Bellamy (H. F.): On the agents concerned in the production 
 
 of the tryptic ferment from its zymogen, J. Physiol. (London), 
 
 1901, xxvii, 323. 
 " LuciANi:* pp. 175-176. 
 ^^ SoLER (F. L.) AND Madero (L. F.): Influencia del bazo en la 
 
 formacion de los fermentos gastricos, Semana Med. (Buenos 
 
 Aires), 1912, xix, 641. 
 ^' Hedin (S. G.): Investigations on the proteolytic enzymes of 
 
 the spleen of the ox, J. Physiol. (London), 1903, xxx, 155. 
 ^8 Rettger (L. F.) AND Mendel (L. B.): Experimental observa- 
 tions on pancreatic digestion and the spleen. Am. J. Physiol. 
 
 (Boston), 1902, vii, 387. 
 ^^ PuGLiESE (A.): Neuer Beitrag zur Physiologie der Milz; das 
 
 Eisen der GaUe und des Blutes bei entmilzten Tieren, 
 
 Biochem. Ztschr. (Berlin), 1913, lii, 423. 
 20 Editorial: Splenectomy and the metabolism of iron, J. Am. 
 
 Med. Assn. (Chicago), 1913, Ixi, 777. 
 -^ AsHER (L.): Die Funktion der Milz, Beat. med. Wchnschr. 
 (Leipzig), 1911, xxxvii, 1252. 
 
 22 Bayer (R.): Untersuchung ueber den Eisenstoffwechsel nach 
 
 der Splenektomie, Mitt. a. d. Grenz. d. Med. u. Chir. (Jena), 
 1910, xxi, 335; see also ibid., 1911, xxii, 111, 532. 
 
 23 Editorial: Functions of the spleen, J. Am. Med. Assn. 
 
 (Chicago), 1912, lix, 1546. 
 
 24 OiT (1.): The peristaltic action of the intestine; action of 
 
 certain agents upon it; new function of the spleen, Med. 
 Ball. (Philadelphia), 1897, xix, 376. 
 
 !
 
 The Value of Spleen Extracts 143 
 
 25 Carpenter (C. '&.): Splenic extract and the splenic function, 
 Med. Record (New York), 1900, Ivii, 273. 
 
 2^ Id.: Therapeutic action of splenic extract in malarial infec- 
 tions, lied. Record (New York), 1906, Ixx, 165. 
 
 2^ NouvEAu (M.): Contribution a I'etude de ropoth6rapie splen- 
 ique dans le traitement de la cachexie palustre. These de 
 Montpellier, 1902, No. 43. 
 
 28 Eoux (G.) AND Lacomme (L.): Disparition momentanee des 
 trypanosomes du magana chez les chiens infectes, Progr. 
 mid. (Paris), 1906, xxii, 456. 
 
 2^ Paucot (M.): L'opotherapie de la rate dans la splenomegalie 
 paludique, Nord med. (Lille), 1907, xxii, 53; see also Bull, et 
 mem. Soc. med.-chir. du Nord (Lille), 1907, iii, 29. 
 
 30 Bezan^on (F.): De la rate dans les maladies infectieuses, Gaz. 
 
 d. Hop. (Paris), 1896, Ixix, 39. 
 
 31 GoLDSCHNEiDER (A.) AND JACOB (P.): Ucber die Variationen 
 
 der Leukocytose, Ztschr. f. Id. Med. (Berlin), 1894, xxv, 373 
 
 32 Danilewsky (B.): Ueber die blutbildende Eigenschaft der 
 
 Milz, Arch.f. d. ges. Physiol. (Bonn), 1895, Ixi, 264. 
 
 33 Simon (P.) and Spillmann (L.) : Recherches experimentales sur 
 
 Taction des injections d'extrait do rate; reactions du sang, 
 C. r. Soc. Biol. (Paris), 1906, Ix, 833. 
 3* Bayle (C): Action therapeutique des extraits de rate dans la 
 tuberculose, Progr. mid. (Paris), 1913, xxix, 530. 
 
 35 David (M.) : cf. Merck's Annual Report, 1908, xxi, 68. 
 
 36 Carnot:* p. 120. 
 
 3' Landau (Tli.): Ein neues durch Autolyse der Milz gewonnes 
 Blutstillungsmittel, Berl. Id. Wchnschr., 1904, xli, 577. 
 
 38 Sajous:* vol. i., pp. 731-732. 
 
 39 Harrower (H. R.): The value of the internal secretions in 
 
 tuberculosis, Ind. Med. Bee. (Calcutta), 1913, xxxiii, 293. 
 *" Bayle (C): L'opoth6rapie spl6nique; traitement sp6ciflque 
 
 de la tuberculose, Eev. d. Mid. (Paris), 1911, xxxi, 482. 
 *i Van Stockum (W. J.): Die therapeutische Wirkung der mit 
 
 Rontgen-strahlung vorbehandelten Milz bei Tuberkulose, 
 
 Wien. Id. Wchnschr., 1912, xxv, 1857. 
 *2 Schroder (G.): Ueber die Rolle der Milz als Schutzorgan gegen 
 
 tuberkulose Infektion (I. Teil), Beitr. s. kl. d. TuberTc. (Wurz- 
 
 burg), 1909, xii, 323. 
 *3 Schroder (G.), Kaufmann (H.), and Kogel (H.): See above 
 
 (II. Teil), ibid., 1912, xxiii, 1. 
 ** Carrel (A.): Artificial activation of the growth in vitro of 
 
 connective tissue, J. Exp. Med. (New York), 1913, xvii, 14. 
 *^ Clark (A. C): The therapeutic value of spleen extract, Edinb. 
 
 Med. J., 1898, iii, 152. 
 *® Bois (C. A.) AND Kerr (N. T.): Clinical studies with spleen 
 
 and thyroid extracts, Br. Med. J. (London), 1898, ii, 684.
 
 CHAPTER X 
 
 THE PERISTALTIC HORMONE OF ZUELZER 
 
 The Hormone Control oj EnteroTcinesia — The Action of the Peris- 
 taltic Hormone — The Relation of the Spleen and Intestines — 
 Concerning the Depressor Action of Hormonal — Combining 
 the Peristaltic and Infundibular Hormones — The Treatment 
 of Chronic Constipation — The Control of Intestinal Par- 
 alysis — The By -Effects and Dangers of Hormonal — Neo- 
 hormonal — The Usual Methods of Administration — The Oral 
 Administration of Hormonal. 
 
 As far back as 1897 Ott^ of Philadelphia showed that 
 extracts of the spleen when injected into animals had a 
 decided influence upon intestinal peristalsis. This seems 
 to be the first indication of the presence in this organ 
 of a substance which influences the natural alimentary 
 movements. 
 
 Ott's discovery remained unappropriated by the pro- 
 fession until Zuelzer and his associates rediscovered it in 
 1908,2 and with the unfolding field of hormone action 
 before them, the term "peristaltic hormone " was applied 
 to the organic active principle which is believed to be 
 concerned in establishing normal intestinal peristalsis. 
 
 The Hormone Control of Enterokinesia. — With the facts 
 before him concerning secretin action, and the convincing 
 results of experiments with other substances of similar 
 action, it naturally occurred to Zuelzer that the muscular 
 activities of the intestinal walls were probably not con- 
 trolled solely by nervous impulses. By analogy this 
 investigator's hypothesis was that the presumed " peri- 
 
 144
 
 The Peristaltic Hormone of Zuelzer 145 
 
 staltic hormone " must be found in the stomach. After 
 some time he succeeded in preparing extracts of the gastric 
 mucous membrane that showed a marked action upon 
 the intestinal peristalsis of the animals experimented 
 upon. It was further ascertained that this hormone was 
 produced in the stomach and duodenum in the course 
 of normal digestion, the greatest quantities being made 
 at the height of digestion, carried off by the blood, and 
 stored up in the spleen. It can be extracted from the 
 mucous membrane, but before long the whole of this 
 substance that was used in the numerous experiments was 
 prepared from the spleen of cattle because of the com- 
 paratively greater quantities secured, and to-day this 
 organ is the source of the trade preparation " hormonal,''' 
 which is becoming generally used. 
 
 As a result of animal experimentation it was found that 
 the peristaltic hormone, when introduced into the blood, 
 caused a vigorous stimulation of atonic intestinal walls, 
 and that its influence extended to conditions bordering 
 on paresis — where intestinal motion was practically gone. 
 It was presumed that in this hormone we had a cathartic 
 which, acting through the blood, could be given directly 
 into the circulation, and this surmise has fortunately 
 proved to be well founded. 
 
 The Action of the Peristaltic Hormone. — Just how the 
 peristalsis initiated by this hormone is brought about is 
 not absolutely known. It may be due to an activating 
 influence upon the nerves of the area concerned, similar 
 to the now well-known action of the chromaffin hormone 
 on the sympathetic system. The hypotensive action of 
 hormonal is quite constant, and as likely as not is a factor 
 in bringing about its influence on peristalsis, for evidently 
 the vessels of the intestines are temporarily dilated and 
 gorged with blood, while the superficial vessels are corre- 
 
 10
 
 146 Practical Hormone Therapy 
 
 spondingly depleted with the accompanying, though 
 evanescent, fall of blood-pressure. Zuelzer himself has 
 noted in the records of his experiments that changes in 
 the blood-pressure are a part of the normal physiologic 
 action of the peristaltic hormone, and are accompanied 
 by a very strong flow of blood to the intestine. Probably 
 the action is a combination of both the above, the latter 
 being in the predominance. 
 
 Zuelzer^ suggests two theories in an attempt to account 
 for the effect of this substance: (1) In chronic constipa- 
 tion there is a complete absence or an insuflficient pro- 
 duction of the peristaltic hormone, and its introduction 
 stimulates its normal elaboration; and (2) the initial 
 starting stimulus to peristalsis is brought about by nervous 
 impulses, the introduced hormone having exerted an 
 action on the abdominal sympathetic ganglia. 
 
 The Relation of the Spleen and Intestines. — Meyer^ of 
 Cologne remarks that intestinal atony not infrequently 
 follows splenectomy. After a time the symptoms dis- 
 appear, the presumed peristaltic action of the spleen 
 having been taken up by the other organs. He tried 
 hormonal in several cases of meteorism and intestinal 
 paresis which followed splenectomy, and obtained striking 
 results. He also has done some interesting experimental 
 work. Six rabbits of one breed were splenectomized, 
 some fasting and some after a full meal. There was a 
 visible swelling of the abdomen of all the animals during 
 the first two days, which otherwise were quite well. On 
 the third day a part of the animals were reopened in a 
 bath of Ringer's solution at body temperature, and 2 c.c. 
 hor7nonal was injected. It was followed by an intense 
 peristalsis. Other animals were examined with the X-rays 
 after the administration of a bismuth meal. Here hor- 
 monal injections showed after ten seconds " a real uproar
 
 The Peristaltic Hormone of Zuelzer 147 
 
 in the visible bov/els." Finally Meyer studied the free 
 spleens of four rabbits after a hormonal injection. The 
 organ was filled with large quantities of blood, and its 
 fiat form visibly swells, while almost at the same moment 
 the peristalsis begins. 
 
 Concerning the Depressor Action of Hormonal. — Not all 
 investigators admit the basis of Zuelzer's work and that 
 of those who have confirmed his position. There must 
 always be dissenters. The Russian investigator, Popiel- 
 ski,^ whose pessimism regarding hormones has already 
 been referred to (p. 61), attributes the action of hormonal 
 to the vaso-dilator substance (" vaso-dilatin "), which he 
 believes to be present in all internal organs, and which 
 primarily reduces tension, and shows a secondary effect 
 on peristalsis. Popielski's position is, in a degree, shared 
 by Dittler and Mohr,^ who lay stress upon the hypotensive 
 action of this hormone. They report experiments upon 
 seventeen animals (thirteen cats, one dog, three rabbits), 
 in which peristaltic stimulation was found in only four of 
 the cats, and was stopped by adrenaline injections. These 
 same authors report in a later paper the results of further 
 research, which confirm their previous statements that 
 the peristalsis-producing action is merely the result of the 
 drop in blood-pressure caused by the hormonal. When 
 the injection is made very slowly, it does not induce peris- 
 talsis in animals. They found that injection of chloral 
 had a pronounced effect in inducing peristalsis in rabbits, 
 even in doses of less than 0-05 gramme per kilogramme. 
 This effect never failed, and it is possible that some of the 
 action attributed to hormonal may have been due to the 
 preliminary injection of chloral in the experimental tests 
 of the remedy. This position does not seem to be tenable, 
 for the depressor action referred to by these writers lasts 
 for a very short time during and immediately following
 
 148 Practical Hormone Therapy 
 
 the injection, whereas the therapeutic effect is not set 
 up until five or six hours later. Then, too, the persisting 
 effects of this treatment cannot possibly be explained by 
 a passing drop in blood-pressure. 
 
 Combining the Peristaltic and Infundibular Hormones. — 
 In a personal communication to the author Zuelzer writes : 
 " I have personally proved on men that the effects of 
 hormonal are not due to the drop in the blood- pressure. 
 I secured a prompt effect in a case of reflex paralytic 
 ileus with a close of horrnonal to which a very small 
 quantity of jntuitrin was added. This amount is, of 
 course, so small that alone it has no effect on the bowels; 
 but not only did the injection cause no fall of blood- 
 pressure, but an actual increase of 10 to 15 millimetres." 
 Here, it seems, is an excellent suggestion, no reference 
 to which can be found in the literature.* It is suggested 
 that to 15 or 20 c.c. of hormonal J to I c.c. of pituitrin 
 be added, and the whole given intravenously with 10 to 
 20 c.c. of warm saline solution. 
 
 The Treatment of Chronic Constipation. — The peristaltic 
 hormone is not simply an organic cathartic. Its influence 
 upon constipation is quite different from the well-known 
 and varied effects of calomel, saline aperients, or cascara. 
 Nor should it be used as a remedy for constipation gener- 
 ally, for there are some forms (notably spastic constipa- 
 tion, in which there is already an overstimulation of the 
 intestine, and volvulus or organic obstipation in which 
 mechanical factors are present) in which it is manifestly 
 contra-indicated. 
 
 Its application has been largely left to the intractable 
 cases of obstipatio chronica, in which evacuations of the 
 bowels are secured at intervals of several days, or even 
 
 * After the proofs of this were received, the author noticed a reference to 
 an article"' the title of whi'^h indicates that others have been co.us.idp.riug 
 this subject.
 
 The Peristaltic Hormone of Zuelzer 149 
 
 weeks, and then only by recourse to drastic medicinal or 
 mechanical means. In such cases good results have been 
 secured, and since, when the initial dosage has once started 
 the bowel movements, it does not have to be repeated as 
 the ordinary cathartic drugs have, it seems that the 
 fundamentals of its therapeutic usefulness are sound. 
 There are numerous reports in which seriously chronic 
 cases were enabled to find the necessary but missing 
 impetus, and peristaltic action was started and continued 
 for months. As Saar'^ has said, it is as though a stationary 
 pendulum, as a result of one single push, had again 
 resumed its motion. 
 
 Numerous cases responded to a single dose, while others 
 required two or three injections at later periods, the 
 intervals between the doses varying from a few days to 
 several months. It should be noted that the commence- 
 ment of the effects of the intramuscular injection in 
 chronic constipation varies, and may not be manifest for 
 two, three, or even five days. Not all cases respond. 
 Zuelzer reports 71 per cent, of lasting successes and 29 per 
 cent, of failures. 
 
 The Control of Intestinal Paralysis. — The other special 
 series of conditions in which this treatment is effective 
 are those in which there is a stoppage of peristalsis and 
 the immediate control of intestinal paresis is desired. 
 This may be due to operative shock, or may accompany 
 severe intestinal infections (appendicitis) and peritonitis. 
 A number of surgeons have reported spectacular results 
 following single intravenous injections of this hormone 
 preparation, and there can be no doubt that this treat- 
 ment was the principal factor in saving life. 
 
 There is already quite a large bibliography on this sub- 
 ject, the principal papers being those of Zuelzer, 2- 3. s gaar,'' 
 Henle,^ Arnaud,^° Lenormant,^^ Aaron, ^"^ and Hesse. ^^
 
 150 Practical Hormone Therapy 
 
 The By-Effects and Dangers of Hormonal. — Several 
 untoward results have been recorded in the literature as 
 due to the action of hormonal. Among these are a 
 transient rise in temperature (which may reach from 103° 
 to 105° F. for a few hours only), the so-called " hormone 
 fever," a slight headache lasting from a few hours to a 
 day, and occasional nausea. Following intramuscular 
 injections there has been more or less local pain, and, 
 rarely, induration, but these are not uncommonly found 
 with intramuscular injections of any preparation. 
 
 During 1912 several more serious cases were reported,^"* 
 which have thrown doubt upon the harmlessness of this 
 preparation, three or four of them having been fatal. 
 The main detrimental result was collapse following the 
 injection. As a result of this, several articles and 
 editorials appeared, condemning more or less forcibly the 
 whole treatment, while the manufacturers and Zuelzer 
 set themselves to discover if there was not something that 
 could be remedied. 
 
 Neohormonal. — Extensive investigation revealed the 
 presence of a hypotensive albumose, which since then 
 has been removed, and all preparations are now tested 
 both chemically and experimentally. In a personal 
 communication to the author regarding the action of this 
 preparation Zuelzer writes: "We intend to call this 
 neohormonal. ... I have no longer observed any rise of 
 temperature following intravenous injections of even 
 40 c.c, but after intramuscular injections a slight rise 
 is sometimes still observed. I believe that this is caused 
 by the absorption of mechanically damaged muscle 
 tissue." 
 
 Hesse^^ tells of encountering collapse after using 
 hormonal in 1912, but in a paper relating his experiences 
 with the purified preparation^^ he refers to " seven cases
 
 The Peristaltic Hormone of Zuelzer 151 
 
 of severe intestinal paresis treated for three or four days 
 with all the other usual measures without results. Hor- 
 monal was used as a last resort, and its effects were re- 
 markable. In no case did it fail. ... A case of collapse 
 has not been seen. . . . The new hormonal has given 
 excellent results, and manifests nothing short of an 
 extraordinary life-saving influence." 
 
 The Usual Methods of Administration. — With a care- 
 fully applied technique this more recent preparation 
 causes the same beneficial therapeutic result with a 
 minimal hypotensive action. One must observe, how- 
 ever, certain precautions in the administration of hor- 
 monal, and the following method of administration is 
 advised : Intravenously : Advised for hospital use only and 
 for acute paretic conditions. Dose, 20 c.c; for children 
 proportionately less.* The liquid is first warmed by 
 immersing the bottle in water at 110° F., and held as 
 nearly as possible at body temperature during the in- 
 jection, which is made drop by drop into the median vein, 
 allowing fifteen to twenty minutes for the entire 20 c.c. 
 to enter. Intramuscularly : Dose, 20 to 40 c.c. for chronic 
 constipation. The liquid is warmed to body temperature, 
 and the injection slowly made from 3 to 4| inches into the 
 gluteal musculature (not the fatty tissues), one-half of 
 the dose on each side. One or two tablespoonfuls of 
 castor oil should be given as a lubricant to assist in the 
 dislodgment of impacted faecal masses from the large 
 intestine. Aseptic precautions are, of course, carefully 
 observed. 
 
 It has been suggested that injections be given in the 
 early morning, and the patient confined to bed during the 
 day to obviate rise of temperature. The administration 
 of opiates shortly before and after hormonal injections 
 
 * Henle" reports the successful use of 1 c.c. in an infant four months old.
 
 152 Practical Hormone Therapy 
 
 should be avoided, as they oppose the desired physiologic 
 action. 
 
 The Oral Administration of Hormonal. — Until recently 
 the peristaltic hormone has been recommended to be 
 given by intramuscular or intravenous injection. The 
 idea (proved time and again to be erroneous) that prac- 
 tically all organic remedies are destroyed in the stomach 
 has doubtless hindered a wide use of this and other animal 
 remedies. The first reference to the administration of 
 hormonal by mouth is a paper by Achard.^^ In it he 
 states that — " The difficulties attendant on the intra- 
 muscular injection of hormonal in cases of constipation 
 led me to try oral administration. I was further drawn 
 to this method by the argument that the peristaltic 
 hormone exercises its effect directly on the alimentary 
 tract. Hormonal was given to four persons, all of whom 
 suffered from severe constipation. Two of these, men 
 aged twenty and fifty respectively, derived no benefit 
 whatever. The results in the other two patients, how- 
 ever, were most remarkable. These were both women. 
 The first, aged fifty-four, unmarried, had suffered from 
 constipation nearly all her life. A dose of 20 c.c. was 
 given ; slight discomfort was felt for a day, and four days 
 later a spontaneous evacuation took place. On each of 
 the subsequent days the bowels moved freely, until the 
 motions gradually settled down to one every second 
 day. This continued practically for nine months, and 
 at the time the article was written she was still fairly 
 regular, only the one initial dose having been given. 
 The second female patient, aged thirty-six, married, gave 
 similar results, which lasted for about two months, after 
 which the effect gradually wore off." 
 
 In concluding his interesting paper, Achard writes: 
 "If it can be established that hormonal can exert its
 
 The Peristaltic Hormone of Zuelzer 153 
 
 favourable action upon the peristalsis on being introduced 
 directly into the stomach, and if this action persists at 
 least fairly well, even if it is not as intense or as pro- 
 longed as after intramuscular or intravenous injection, 
 our means of overcoming constipation with all its harmful 
 consequences, and with all its immense power to produce 
 injury to the organism, will have been strengthened 
 materially. The important point to my mind is that if 
 hormonal can be established as an efficient treatment for 
 selected cases of constipation, we have in this preparation 
 a physiological remedy the use of which is a priori far 
 preferable to that of any laxative or cathartic drug." 
 
 BIBLIOGEAPHY 
 
 ^ Ott (I.): The peristaltic action of tlie intestine; action of 
 certain agents upon it; new function of tlie spleen, Med. 
 Bull. (Pliiladelpliia), 1897, xix, 376. 
 
 2 Zuelzer (G.), Dohrn (M.), and Marxer (A.): Specifisclio 
 
 Anregung der Darmperistaltik durcli intra venose Injektion 
 des Peristaltikhormons, Berl. M. Wchnschr., 1908, xlv, ii, 
 2065. 
 
 3 Id.: Ueber Heilungen der clironischen Obstipation durch das 
 
 Peristaltikhormon, 3Ied. Klin. (Wien), 1910, vi, 422; 
 
 see also: Die Hormontherapie. Das Peristaltikliormon, 
 
 Ther. d. Gegen. (Berlin), 1911, lii, 197. 
 * Meter (A.): Beitrag zur Kenntnis der Milzfunktion, Centr 
 
 f. d. Grenz. d. Chir. u. Med. (Jena), 1914, xviii, 41. 
 5 Popielski (L.): Die Wirkung der Organextrakte und der 
 
 Tbeorie der Hormone, Munch, med. Wchnschr., 1912, lix, 534. 
 " Dittler (R.) and Mohr (R.): Untorsuchungen ueber die 
 
 Wirkung des Hormonals, Ztschr. f. Id. Med. (Berlin), 1912, 
 
 Ixxv, 275. 
 ' Saar ( — .): Ueber das Peristaltikhormon Zuelzer, Med. Klin. 
 
 (Wien), 1910, vi, 425. 
 ^ Zuelzer (Gr.): Ueber KoUapswirkung des Hormonals, Deut. 
 
 med. Wchnschr. (Leipzig), 1912, xxxviii, 1233. 
 ^ Henle (A.): Beksempfung dor Darmparese durch Hormonal, 
 
 Zentr. f. Chir. (Leipzig), 1911, xxxviii, 73. 
 ^"^ Arnaud (L.): L'hormone peristal tique, Lyon Chir., 1911, vi, 
 
 523.
 
 154 
 
 Practical Hormone Therapy 
 
 Lenormant (C): Un traitement nouveau des paralysies aigues 
 de rintestin: Fhormone peristaltique, Pr. Med. (Paris), 1911, 
 xix, 755. 
 
 Aaron (C. D.): The hormones, with special reference to peri- 
 staltic hormone, J. Am. Med. Assn. (Chicago), 1912, Ixviii, 
 407. 
 
 Hesse (F. A.): Ueber Nebenwirkung des Hormonals, Deut. 
 med. Wchnschr. (Leipzig), 1912, xxxviii, 643. 
 
 See bibliography in Merck (E.): " Annual Report," 1912, xxvi, 
 323. 
 
 Hesse (F. A.): Klinisches ueber Hormonal, Ther. Monatsh. 
 (Berlin), 1913, xxvii, 698. 
 
 AciiARD (H. J.): The action of the peristaltic hormone after 
 oral administration, Amer. Med. (New York), 1913, xix, 111.
 
 CHAPTER XI 
 
 THE VALUE OF LIVER EXTRACTS 
 
 The Numerous Functions of the Liver — The Hormone Control 
 of Hepatic Action — The Active Principle of Cod-Liver Oil — 
 The Fundamental Value of Hepatic Extracts — The Treat- 
 ment of Digestive Disorders — Stimulating Liver Inactivity — 
 Hepatic Cirrhosis — The Influence upon Haemorrhage — A 
 Reported Action upon Phlebitis — Possible Usefulness in 
 Icterus — A Consideration of Hepatic Diabetes — Augmenting 
 Elimination in Gout — In Anaemia and Tuberculosis — Com- 
 bining Biliary and Hepatic Extracts — Dosage and Adminis- 
 tration. 
 
 There can be no question that the administration of 
 suitable extracts of the liver renders very real service in 
 the treatment of several affections. While the scientific 
 application of this idea has been in use for fifteen or 
 twenty years, there are evidences that this therapeutic 
 procedure is extremely old. It is recorded that Dios- 
 corides treated hepatic dropsy by administering a prep- 
 aration of the liver of hedgehogs which had been dried 
 in the sun, and Galen extols the use of wolf's liver as a 
 means of treating icterus. 
 
 The Numerous Functions of the Liver.— Many physi- 
 cians still consider the main function of the liver to be 
 that of bile production. On second thoughts, they re- 
 member its capacity to manufacture and store glycogen, 
 as well as its influence upon the genesis of urea. It is 
 granted that these several and widely divergent functions 
 are of extreme importance, but the less well - known 
 
 155
 
 156 Practical Hormone Therapy 
 
 detoxicative action of the liver and its antibacterial 
 powers are also worthy of consideration. 
 
 Our knowledge of the hepatic functions is broadening, 
 and it is maintained that, in addition to numerous fer- 
 ments (proteolases, nucleases, adinases, oxidases, etc.), 
 and the well-kno^vn bile salts (sodium glycocholate and 
 sodium taurocholate) and pigments (bilirubin, biliverdin, 
 and urobilin), the hepatic cells also produce other chemical 
 substances of the nature of hormones. 
 
 Apart from its better-known work, then, the liver has 
 several other functions. The role that the administra- 
 tion of liver substance or extract plays depends upon its 
 power to injfluence these "lesser functions," which have 
 been conveniently classified under the following four 
 heads : 
 
 1. The regulation of nitrogenous metabolism, and espe- 
 cially the production of urea. 
 
 2. The regulation of the normal sugar content of the 
 blood and the preparation and storing up of glycogen. 
 
 3. A reported noticeable influence upon the coagula- 
 bility of the blood. 
 
 4. The destruction of toxins and the regulation of 
 toxaemia both by inhibition of production and by destruc- 
 tion of completed substances resulting from intestinal 
 fermentation and putrefaction. 
 
 The Hormone Control of Hepatic Action. — With our 
 present knowledge of the effects of the hormone secretin 
 (see Chapter V.) and the factors concerned in the produc- 
 tion of various digestive ferments, it is quite reasonable 
 to suppose that similar factors influence the work of the 
 liver. 
 
 Luciani^ refers to the fact that all nerves to the liver 
 can be divided without causing arrest of the biliary secre- 
 tion ; also that all branches of these nerves can be excited
 
 The Vahie of Liver Extracts 157 
 
 successfully without influencing the flow of bile either by 
 accelerating it or by stimulating a suspended flow. 
 Evidently, then, the physiology of the secretory function 
 of the liver is quite similar to that of the pancreas and 
 other glandular organs, and in spite of some objections 
 that have been raised by physiologists to the " secretin 
 theory," there seems to be reasonable ground for the 
 assumption that hormones materially influence the func- 
 tion of the liver. 
 
 The study of the functions of the liver has been carried 
 on for many years, and as yet we are still very much in 
 the dark as to how this remarkable organ performs its 
 equally remarkable work. The supposition that the 
 liver itself is a source of hormones has been mentioned by 
 several writers, and the fact that its detoxicating func- 
 tion is conceded to be greater than that of any other 
 organ seems to give weight to this suggestion. 
 
 The Active Principles of Cod-Liver Oil. — In this connec- 
 tion a word or two regarding a well-known and universally 
 used liver preparation may be in place. In his con- 
 sideration of "The Therapeutic Promise of the Internal 
 Secretions," Williams^ says: " There can be no doubt of 
 the superiority of cod-liver oil in fortifying the tissues 
 against the bacillus of tuberculosis, neither can there be 
 any doubt that cod-liver oil is different from all other 
 oils in this respect. Now, it is evident that its superiority 
 is due to the fact that in addition to the oil it contains 
 the internal secretion of the liver of the fish. It is not, 
 of course, to be supposed that this internal secretion 
 enters at once into the human liquor sanguinis. The way 
 in which it acts must, in the present state of our know- 
 ledge, be a matter of mere conjecture. Inasmuch, how- 
 ever, as we know that certain of the internal secretory 
 glands exercise certain antagonisms to certain others, so
 
 158 Practical Hormone Therapy 
 
 that an excessive secretion in one will provoke an in- 
 creased activity in one or more of the others, it is very 
 probable that this biliary secretion of the cod, when 
 introduced into the human economy, acts as a stimulant 
 to one of the normal internal secretory glands, and that 
 the secretion of the one so stimulated is inimical to the 
 development of the tubercle bacillus. Some of these 
 internal secretions are subtle entities, and it is a signifi- 
 cant fact that the darker and more crude the cod-liver 
 oil, the more efficacious is it. The refining process de- 
 prives it of many of its virtues, whereas the dried extract 
 of the cod's liver is almost as active as the crude oil." 
 
 Quite recently Iscovesco^ has published some experi- 
 mental work which shows the soundness of this position. 
 He is convinced that the special properties of cod-liver 
 oil are due to the lecithides which it contains, and that 
 while the fat is useful, it is no more so than vegetable 
 fats. Some of the figures from his experiments are in- 
 teresting. He treated a large series of animals for four 
 months. To some he gave cod-liver oil [a), to others cod- 
 liver oil from which the lecithides had been removed (6), 
 a further series received olive oil (c), and others olive oil 
 to which was added 0-5 'pro mille of the lecithides extracted 
 from cod-liver oil {d). There were, of course, a number 
 of control animals (e). Here are the a-verage weight 
 increases recorded: {a) 55 per cent., (6) 27 per cent., 
 (c) 33 per cent., {d) 56 per cent., and (e) 29 per cent., 
 showing a considerable increase in the classes receiving 
 the active liver product. 
 
 This seems to indicate that the administration of cod- 
 liver oil might as well be dispensed with — a procedure 
 which would doubtless bring joy to not a few disgusted 
 sufferers — and in its place a more palatable fat be given, 
 with pills or capsules of the extracted lecithides.
 
 The Valne of Liver Extracts 159 
 
 The Fundamental Value of Hepatic Extracts evidently 
 depends — in a degree, at least — ^on the internal secretions 
 present in these extracts, the administration of which 
 supplements those of the disordered organ by introducing 
 into the body the ready-prepared products of the normal 
 liver, thus bringing to the hepatic cell units materials 
 which stimulate their regeneration as well as their 
 action. 
 
 Hepatic opotherapy, the value of which was first em- 
 phasized in 1896 by Gilbert and Carnot'* of Paris, is 
 based upon the fact that certain of the physiologic func- 
 tions of the liver are transmitted in suitably prepared 
 extracts of this organ, and that by administering prep- 
 arations of this character one can demonstrate in vivo, 
 as well as in vitro, several of the well-known physiologic 
 powers of the liver. Their work has placed the applica- 
 tion of liver preparations upon a scientific basis. 
 
 The therapeutic activity of liver extracts is not con- 
 sidered by all to be due to a certain specific substance or 
 hormone. It is known that there are a number of fer- 
 ments and heat-stable substances of a hormone nature in 
 extract of liver, and it is likely that its curative value is 
 due to a combination of all the active substances contained 
 in the properly prepared extract. 
 
 Lorand^ believes — and his opinions are corroborated 
 by Gilbert, H, Strauss, and others — that the liver is a 
 gland with an internal secretion that is strongly antagon- 
 istic to intestinal poisons, destroying toxic products 
 brought to it from the intestine by the portal vein. This 
 antitoxic power claimed for the liver is dependent, not 
 upon the blood that may be present in the organ, but 
 upon the liver tissue itself, and the activity of this organ 
 in destroying toxins must be due to some chemical sub- 
 stance at present unknown. A part, at least, of this
 
 160 Practical Hormone Therapy 
 
 power remains in vacuum-dried extracts, and is probably 
 the source of the benefits which follow its therapeutic 
 administration. 
 
 The Treatment of Digestive Disorders. — Naturally, then, 
 the use of preparations of liver tissue has been tried in the 
 treatment of digestive affections, and especially in con- 
 stipation, for hepatic extract has a definite influence upon 
 the functions of the liver itseK, both as regards its pre- 
 sumed internal secretion as well as bile production. 
 
 For a number of years our French confreres have em- 
 ployed hepatic opotherapy with undoubted success. 
 They have not contented themselves with the adminis- 
 tration of several forms of bile and bile salts, but ad- 
 minister liver extract in various forms, principally in the 
 form of cachets or tablets. 
 
 Stimulating Liver Inactivity. — The principal indication 
 for this method of treatment is the presence of hepatic 
 insufficiency. Unfortunately, there are numerous forms 
 of this disorder, not a few of which are of a severe organic 
 nature. Therefore we must not expect that any method 
 of treatment consisting of the administration of any drug 
 or drugs is going to regenerate a destroyed organ. We 
 can, however, augment the diminished action of the 
 partially destroyed organ by increasing the usefulness of 
 the sound remainder, and thus render valuable service 
 to the patient. Palliative treatment is better than no 
 treatment. 
 
 In the strictly functional disorders of the liver sur- 
 prisingly good results can be obtained, for hepatic opo- 
 therapy affords the overburdened organ an opportunity 
 for self -regeneration. In hepatic insufficiencies associated 
 frequently with a decrease of the solids in the urine, and 
 especially in the amount of urea and other nitrogenous 
 compounds, hepatic extract has served to good advantage.
 
 The Value of Liver Extracts 161 
 
 Hepatic Cirrhosis. — ^This capacity of animal extracts to 
 stimulate the function of the corresponding organ and — • 
 in a degree, at least — to favour regeneration has led to 
 the use of hepatic extract in the treatment of cirrhosis 
 of the liver. Experiences in the treatment of atrophic 
 cirrhosis have been much more encouraging than in the 
 hypertrophic form. 
 
 Spillmann and Demange*^ of Nancy have tested the 
 applicability of this method, and have attempted to 
 define its limitations. They have drawn the following 
 conclusions from an extended experience: (1) Medication 
 by means of liver extracts constitutes a rational and 
 specific treatment for hepatic insufficiencies; (2) hepatic 
 opotherapy has a decided action on nutrition, as well as 
 an influence upon the urinary excretion; (3) the results 
 following its use have been especially favourable in 
 atrophic cirrhosis of the liver, passive congestion, and 
 even cancer of the liver. 
 
 The following paragraph is quoted from their com- 
 munication to the congress at Lille: "It is especially in 
 atrophic cirrhosis of the liver that the effects of this form 
 of opotherapy have proved favourable. In the first four 
 cases we secured surprising results. In the first observa- 
 tion the general condition was so bad that we expected a 
 fatal outcome. All methods of treatment had been em- 
 ployed without results. One month after commencing 
 hepatic medication the patient was able to get up and 
 follow the usual hospital regime." 
 
 The results following this method of treating atrophic 
 cirrhosis are of a definite and tangible character. The 
 amount of urine is increased from 100 to 300 per cent., 
 and the urea index is markedly augmented. In addition 
 to this, ascites is diminished, and in some cases entirely 
 removed. Punctate haemorrhage — a common complica- 
 
 11
 
 162 Practical Hormone Therapy 
 
 tion — becomes less frequent, and finally disappears. In 
 the terminal stages of cirrhosis, with cachexia and the 
 inevitably rapid decline which usually terminates fatally, 
 this form of medication is of no avail. It is idle, there- 
 fore, to attempt its use, or at least to expect results 
 therefrom (for it is quite innocuous). 
 
 The Influence upon Haemorrhage. — One of the first de- 
 ductions made regarding the use of liver extracts was 
 concerning their possible antihaemorrhagic influence. 
 More than fifteen years ago, in an attempt to isolate an 
 active principle from the liver, Mairet^ prepared several 
 substances which had an influence on the coagulation of 
 the blood. Since petechias, haemorrhage, and extravasa- 
 tion are not uncommonly found with disorders of the 
 liver, it was inferred that these phenomena might be due 
 to the loss of a certain element which was concerned in 
 the coagulation of blood, and therefore in the prevention 
 of haemorrhage. The reasonableness of this theory was 
 soon confirmed, and hepatic extracts are now used in the 
 prevention and treatment of the haemorrhages due to 
 liver disorders as well as in distiu^bances of the blood- 
 coagulating equilibrium, such as haemophilia and pur- 
 pura. 
 
 Gilbert and Carnot have used liver preparations in the 
 treatment of haemoptysis, especially in tuberculosis, with 
 very encouraging results. Gilbert^ was the first to em- 
 phasize the haemostatic action of the liver extract in 
 epistaxis and uterine haemorrhages. Several \vriters have 
 noticed, while using hepatic extract in the treatment of 
 cirrhosis of the liver, that the oozing from haemorrhoids, 
 and also haematinic disorder, have abated. 
 
 Carnot,^ in a paper on the therapy of the haemorrhagic 
 syndromes (read before the thirteenth Congres Frangais 
 de Medecine, 1912), reiterates his faith in hepatic opo-
 
 The Value of Liver Extracts 163 
 
 therapy. His experience covers a large series of intract- 
 able haemorrhages successfully treated in this manner 
 after failure with other haemostatic measures. In the 
 treatment of the haemorrhagic diathesis he called atten- 
 tion to the necessity for the use of organic extracts corre- 
 sponding to the organic insufficiencies which may be 
 present. If there is evident hepatic insufficiency, use 
 liver extracts. In cases with evidence of renal disorder, 
 with symptoms of uraemia, Carnot suggests renal extracts 
 or the serum of the renal vein. In haemophilia, however, 
 he admits that hepatic opotherapy does not often give 
 good results. 
 
 A Reported Action upon Phlebitis. — Another appHcation 
 of hepatic medication, of which the mode of action is 
 somewhat obscure, has been mentioned by Keim.^^ He 
 has tried the rectal administration of emulsions of fresh 
 liver substance, both in the prophylactic and adjunct 
 curative treatment of puerperal phlebitis. He suggests 
 that in all cases the action of the intestines and liver must 
 be supervised with special care during pregnancy, and 
 the uterus should be completely emptied after delivery. 
 Keim recommends the following somewhat empirical 
 treatment, which, however, has given him gratifying 
 results: 100 grammes of fresh calf's liver is thoroughly 
 emulsified with 250 c.c. of water, and 10 grammes of 
 peptone is added. This mixture is given as an enema. 
 He regards this almost as a specific treatment, and has 
 never had phlebitis develop in the cases in which the 
 method has been applied, and records the prompt relief 
 of symptoms in cases in which phlebitis had already 
 developed. He states that Sobre-Casas has also reported 
 equally favourable experiences with this form of opo- 
 therapy in puerperal phlebitis. 
 
 Possible Usefulness in Icterus. — Combe^^ of Lausanne
 
 164 Practical Hormone Therapy 
 
 has used hepatic extract in the treatment of jaundice, 
 and doubtless in some cases it may be helpful. In com- 
 bination with bile it is likely to be considerably more 
 effective (see Chapter XII.). 
 
 A Consideration of Hepatic Diabetes. — In diabetes, espe- 
 cially that form in which the pancreatic disturbance is a 
 minor factor, and there are evidences of disturbed hepatic 
 function — diahete par anhepatie, as the French term it — 
 liver preparations have proved useful. 
 
 Personally, the author has come to the conclusion that 
 the best method of arriving at any differential diagnosis 
 is, in addition to the clinical diagnostic procedm-es, to 
 administer suitable pancreatic preparations as a part of 
 the regular treatment, and if no favourable result is ob- 
 tained after one month (55 or 60 per cent, usually re- 
 spond), to presume that the pancreatic causative element 
 is absent or of minor consequence, and then to try the 
 liver preparations. 
 
 On the other hand, it has been suggested that hepatic 
 extract is deserving of a trial in all forms of diabetes, 
 with the expectation that after a few days or a week the 
 increase or decrease of the glycosuria will determine 
 whether the treatment should be continued or not. 
 
 Now, the form of diabetes in which hepatic extracts are 
 useful is associated with defective hepatic function, as a 
 result of which this organ cannot retain the sugar in- 
 gested. The glycosuria in these cases is not very great, 
 and seems to have a characteristic rhythm, appearing 
 after the evening meal, then after all meals, and con- 
 tinuing with two maximum points — the one after lunch 
 and the other after dinner. Occasionally the urinary 
 sugar disappears entirely during the fasting period. At 
 the same time, the amount of urea is particularly low — 
 one-half the normal amount, or even less — while the
 
 The Value of Liver Extracts 165 
 
 major sjmaptoms of diabetes (thirst, polyuria, etc.) are 
 not so marked. The tendency to infection and gangrene 
 seems to be quite noticeable, indicating that the liver is 
 failing also in its antibacterial powers. 
 
 Castaigne,^^ in a recent lecture, differentiates the several 
 forms of diabetes, and urges the examination of indi- 
 vidual specimens of urine passed at intervals of two 
 hours. Glycosuria post cibum is quite likely due to dis- 
 turbed hepatic conditions, especially if little or no sugar 
 is found in the specimens passed remote from meals. 
 The diagnosis is confirmed when the glycosuria is found 
 to diminish or disappear after the administration of 
 alkalies, hepatic extract, etc. 
 
 Such cases of diabetes do not usually culminate in 
 coma. Acetone is not often found, and the usual signs 
 of diabetes are not so patent. On the other hand, these 
 cases are very liable to develop pulmonary tuberculosis, 
 and Castaigne reports six out of sixteen cases of hepatic 
 diabetes. 
 
 Labbe and Bouchage^^ consider glycosuria quite a 
 common finding in the course of certain liver affections, 
 and divide hepatic diabetes into five classes: (1) The 
 glycosurias that occur during the course of hepatic 
 lesions; (2) the hepatic congestions in overfed people; 
 (3) the post-infectious or toxic hepatic disorders; (4) the 
 diabete sans denutrition, with enlarged liver of the over- 
 fed; (5) the hepato-pancreatic cirrhosis, with severe 
 diabetes. They give a number of typical case reports 
 to illustrate each of these conditions, and outline the 
 treatment, which consists for the most part in mineral 
 waters, hepatic opotherapy, and the lacto-vegetarian 
 regime. 
 
 Gilbert and Carnot^^ have published numerous observa- 
 tions which demonstrate the value of hepatic prepara-
 
 166 Practical Hormone Therapy 
 
 tions in those forms of diabetes which are associated with 
 disorders of the liver. The dose is 30 to 60 grains (2 to 
 4 grammes), and it may be given three or four times a day. 
 
 Augmenting Elimination in Gout. — The capacity of 
 liver extract to augment the detoxicating powers of the 
 body has suggested a possible field of usefulness in gout 
 and allied conditions. Some investigators believe that 
 the ferments of the liver (preserved in carefully dried 
 extracts) exert an influence on the metabolism of the 
 nucleo-albumins, purins, and uric acid. Gilbert has 
 noticed favourable results of this character, and advises 
 the daily use of 30 to 60 grains (2 to 4 grammes) of desic- 
 cated liver extract in divided doses during the intervals 
 between attacks. This adjunct, at present rarely used 
 in England or America, seems to be none the less valuable, 
 the more especially where the gout is accompanied by 
 manifest hepatic indolence. 
 
 In Ansemia and Tuberculosis. — Attention has been 
 called to the fact that the use of liver extract often is 
 followed by a considerable increase in the red-cell count, 
 and the suggestion has been made that this may be due 
 either to a control of toxaemia or to an actual stimulating 
 influence upon the hsemopoietic organs. The former 
 theory seems the most reasonable, for it is well known 
 that toxaemia, both alimentary and infective, is com- 
 monly found with anaemias, and that the toxic sub- 
 stances frequently manifest a haemolytic influence. At 
 all events, the use of this form of medication is of known 
 value in toxaemias, and may often be associated with the 
 orthodox treatment of anaemia with advantage. 
 
 Numerous other hepatic derangements, which are less 
 serious and not associated with noticeable changes in the 
 hepatic cell structure, especially the functional disturb- 
 ances of digestion and nutrition, and particularly the
 
 The Value of Liver Extracts 167 
 
 toxaemias and evidences of a waning of the normal de- 
 toxicating powers of the liver, often respond to this 
 method of treatment. Several writers have emphasized 
 the good results which follow the application of this idea 
 in the treatment of certain infections, and particularly 
 in tuberculosis. 
 
 Lereboullet places special emphasis on the important 
 fact that the endocrinous organs suffer in a greater or 
 lesser degree in tuberculosis, and that the alterations in 
 function, and sometimes in structure, of these organs 
 have a decided effect on the progress of this disease. 
 " The logical conclusion, then, would be to resort to 
 organotherapy to substitute or stimulate the function of 
 these various organs." Here is Lereboullet 's^^ opinion 
 of the use of liver extracts in tuberculosis: "Most inter- 
 esting is hepatic opotherapy, which, as a symptomatic 
 medication in haemoptysis, has given good results, and 
 which has recently been praised by Triboulet in the tuber- 
 culosis of alcoholics with liver disease. Personally, I have 
 several times seen favourable results in tuberculous alco- 
 holics, especially where enlargement of the liver was 
 present, and whether haemoptysis was present or not." 
 Liver medication is essentially an adjunct in tuberculosis, 
 and its use should be limited to those in which the symp- 
 toms indicate that it may be useful. 
 
 The author has seen very encouraging results follow the 
 use of a combination of extracts of liver, spleen, and 
 pancreas, ^*^ the principal evidence of their value being 
 the modification of nutrition and the augmentation of 
 weight which followed several weeks of this adjunct 
 treatment. 
 
 Parmentier^'^ believes that hepatic extract exerts a 
 favourable influence on the tuberculous. It increases 
 weight, controls night sweats, and benefits haemoptysis.
 
 168 Practical Hormone Therapy 
 
 Gerard and Lemoine^^ have brought out a petroleum- 
 ether extract of bile, called 2^^^'^ioxine, which they 
 recommend in tuberculosis. Its action is not due to the 
 active substances of liver extract, and is referred to in 
 Chapter XII. 
 
 Combining Biliary and Hepatic Extracts. — According to 
 Gilbert and Carnot, hepatic extract has a comparatively 
 insignificant effect upon the bilogenic function of the liver. 
 It cannot be used effectively in disorders of the biliary 
 secretion. It will be found, however, that the activity 
 of hepatic extract in this direction is considerably en- 
 hanced by combining with it a dried and purified extract 
 of bile, and it will also be noticed that the action of bile 
 preparations are increased by combining them with liver 
 extracts. The two are complementary, and where both 
 the general hepatic function and its bilogenic capacity 
 are diminished, a bilo-hepatic extract will prove very 
 useful. The author has used a combination similar to 
 that just mentioned, with the addition of a secretin- 
 bearing extract of the duodenum. It is a splendid com- 
 bination for the treatment of chronic constipation and 
 disorders of the liver. 
 
 Dosage and Administration. — In the application of 
 hepatic medication it is necessary to use rather generous 
 dosage, and little or no harm can result from it, as hepatic 
 extracts are very slightly toxic (the toxic limit has been 
 set at 60 grammes of liver substance per kilo of body 
 weight), and cause no unfavourable reactions. The 
 average dose of vacuum-dried liver extract (which corre- 
 sponds to about 15 per cent, by weight of the fresh organ) 
 is 15 to 20 grains (1 gramme), and 15 grains (1 gramme) 
 can be given every two hours, and increased to as much 
 as 60 grains (4 grammes), three or even four times a day. 
 Liver extracts are obtainable in numerous forms for
 
 The Value of Liver Extracts 169 
 
 administration by mouth — in dried or liquid form — or 
 hypodermically. 
 
 The hypodermic and intravenous routes are not ad- 
 visable, as toxic accidents have occasionally resulted, due 
 to the introduction at one time of too great a quantity 
 of the extract. This is obviated by giving the extract 
 by mouth or rectum. Either mode of administration is 
 effective, as the digestive juices have no appreciable in- 
 fluence upon these preparations, certain statements to 
 the contrary notwithstanding. 
 
 As with other organic preparations, there seems to be 
 no reason for discontinuing other treatment — i.e., hepatic 
 opotherapy is complementary to the indicated procedures. 
 Hepatic organotherapy is a useful addition to everyday 
 therapeutics, even though we will only admit that no 
 other influence can be specifically attributed to the 
 administration of the hepatic extract than the stimulation 
 of the normal hepatic functions. 
 
 BIBLIOGRAPHY 
 
 1 LuciANi,* p. 142. 
 
 2 Williams (L.): The therapeutic promise of the internal secre- 
 
 tions, Pract. (London), 1911, Ixxxviii, 605. 
 
 3 IscovESCO (H.): Sur les lecithides contenus dans I'huile de foie 
 
 de morue, G. r. Soc. Biol. (Paris), 1914, Ixxvi, 34. 
 * Gilbert (A.) and Carnot (P.): Note preliminaire sur I'opo- 
 
 th^rapie h^patique, C. r. Soc. Biol. (Paris), 1896, xlviii, 934. 
 5 LoRAND (A.): " Old Age Deferred " (Philadelphia), 1911, 120. 
 ^ Spillmann (P.) AND Demange (J.): L'opoth6rapie h^patiquo 
 
 dans les affections du foie, Pr. med. (Paris), 1899, vii, 82. 
 ' Mairet (L.) and Vires (M.): Action physiologique de I'extrait 
 
 de foie sur rhomme sain. Arch. d. Physiol. (Paris), 1897, 5, 
 
 ix, 783. 
 8 Gilbert (A.) and Carnot (P.): De I'opoth^rapie h6patique 
 
 dans les hemorragies, C. r. Soc. Biol. (Paris), 1897, xlix, 445. 
 ^ Carnot (P.): L'h6mostase par opoth6rapie h6patique, Paris 
 
 Medical, 1911-12, p. 484. 
 ^** Keim (G.): Les phl6bites puerperales, leur prophylaxie et 
 
 traitement ni6dicalo, Eev. pr. d'Obs. et Gyn. (Paris), 1913, 
 
 xxi, 289.
 
 170 Practical Hormone Therapy 
 
 ^^ Combe (A.): Contribution a I'etude de la pharmacologie de 
 
 Forganotlierapie, Bev. mid. d. I. Suisse rom. (Geneva), 1896, 
 
 xvi, 396. 
 ^2 Castaigne (J.): Ict6re chronique par retention d'origine 
 
 syphilitique, Pr. med. (Paris), 1913, xxi, 1012. 
 ^3 LABBfi (M.) AND BouCHAGE (A.): Glycosuria in tlie course of 
 
 affections of the liver: Hepatic diabetes, Lancet (London), 
 
 1914, i, 13. 
 ^* Gilbert (A.) and Carnot (P.): De Faction des extraits h6pa- 
 
 tiques sur les glycosnries alimentaires, C. r. Soc. Biol. (Paris), 
 
 1896, xlviii, 1112; see also id.: De I'opoth^rapie Mpatique 
 
 dans le diabete sucr6, Sem. med. (Paris), 1897, xvii, 189. 
 IS Lereboullet (P.): Les opotherapies li6patiques, biliaires et 
 
 pancreatiques, leur emploi tli6rapeutique, J. med. frnnQ. 
 
 (Paris), 1911, v, 481. 
 ^^ Harrovp^er (H. E.): The adjunct treatment of tuberculosis 
 
 with certain organic extracts, Br. J. Tuber. (London), 1913, 
 
 vii, 170. 
 ^' Parmentier (H.): Traitement de la tuberculose par les ex- 
 traits h6patiques totaux, BiM. gen. d. Ther. (Paris), 1911, 
 
 clxi, 218. 
 1^ Gerard (E.) and Lemoine (G.): Sur la composition de I'ex- 
 
 trait 6there (lipoide) de la bile, Bull, et Mim. Soc. Med. 
 
 d'Hop. d. Paris, 1909, xxviii, 935. 
 
 Lemoine (G.): D6fense de I'organisme centre les infections et 
 la tuberculose en particulier, par leslipoides biliaires, Nord 
 med. (Lille), 1910, xvii, 129; and also id.: Statistique des 
 malades tuberculeux traites par la paratoxine a la consulta- 
 tion speciale du bureau de bienfaisance de Lille, Nord med. 
 (Lille), 1909, xvi, 241, 253. 
 
 Regnault (J.): Opoth^rapie h6patique, Bev. d. ther. Mkl.- 
 cliir. (Paris), 1904, Ixxi, 695. 
 
 MuLOT (0. L.): The use of desiccated liver extract in diabetes 
 and chronic gastro-intestinal autointoxication, Long Is. 
 Med. J. (Brooklyn), 1910, iv, 496. 
 
 Capitan (F.): L'opoth^rapie h6patique, Med. moderne (Paris), 
 1904, XV, 350.
 
 CHAPTER XII 
 THE THERAPEUTICS OF BILE PREPARATIONS 
 
 Early References to Bile as a Medicine — The Broader Functions 
 of Bile — Bile as a CJiolagogue — The Indications for Bile 
 Administration — Constipation — The Prevention of Hepatic 
 Colic — The Pathogenesis of Gall-Stones — Increasing the 
 Digestion of Fat — The Treatment of Muco- Membranous 
 Colitis — Bile Extracts in Tuberculosis — Dosage and Ad- 
 ministration. 
 
 While the bile, as everyone knows, is produced by the 
 liver, its action is quite different from that of liver ex- 
 tracts, and its administration must not be confounded 
 with hepatic opotherapy. Strictly speaking, bile does not 
 come within the scope of a volume of this character; so 
 far as we know it does not contain a hormone, and the 
 administration of bile derivatives is not hormone therapy, 
 but it seems advisable, nevertheless, to follow a discussion 
 of the administration of hepatic extracts with a brief 
 outline of the possibilities of extracts made from bile. 
 
 Early References to Bile as a Medicine. — ^The use of bile 
 in medicine dates back thousands of years. Nearly five 
 hundred years before Christ, Hippocrates prescribed oxgall 
 and honey in the form of suppositories for congestion of 
 the bowels. It is recorded that Dioscorides, in B.C. 75, 
 treated a number of digestive disorders with the bile of 
 hedgehogs, and from those remote days to the present, 
 occasional references have been made to the esteem in 
 which gall was held as a therapeutic agent. 
 
 It will not be necessary here to go into the physiology 
 
 171
 
 172 Practical Hormone Therapy 
 
 or chemical composition of bile secretion. One fact is to 
 be emphasized: certain of the biliary constituents, after 
 serving their purpose in the intestinal canal, are reabsorbed 
 into the blood, thus returning to the liver and bringing 
 about its bile-producing function. This fact is generally 
 appreciated, and for this reason bile is regarded as the best 
 of the cholagogues and numerous preparations of bile 
 are now in general use. Notwithstanding its value, the 
 mineral and vegetable hepatic stimulants are still much 
 more extensively used. 
 
 The Broader Functions of Bile. — It happens that the 
 possibilities of what has been called " biliary opotherapy " 
 are considerably broader than its cholagogue action, and 
 a number of new facts have been recently discovered 
 regarding the role of bile action in the intestine. 
 
 Roger, ^ who is an authority on this subject, gives a 
 concise resume of this subject, and summarizes his con- 
 clusions under the following seven propositions : 
 
 1. The bile does not contain digestive ferments, but 
 exercises a strengthening influence on other enzymes, 
 augmenting the action of certain ferments, such as pan- 
 creatic amylase and intestinal lactase. 
 
 2. It has the property of abstracting from the intes- 
 tinal walls those ferments which have been elaborated 
 therein, notably invertase, and therefore plays an im- 
 portant part in the digestion of certain forms of sugar. 
 
 3. It is concerned in the digestion and absorption of 
 fats. 
 
 4. It exerts a special action on albumins and peptones, 
 which it precipitates from the acid solution in order to 
 redissolve them immediately. 
 
 5. Bile has no bactericidal properties, but it hinders 
 intestinal putrefaction in three ways: (1) By favouring 
 the development of certain micro-organisms, such as the 
 
 I 
 
 t
 
 The Therapeutics of Bile Preparations 173 
 
 colon bacillus, to the detriment of the anaerobes, which 
 are the principal elements in the causation of putrefaction ; 
 (2) by diminishing the secretion of ferments by bacterial 
 flora; (3) by exerting a hindering action upon the influence 
 of the bacterial ferments on fermentable matter. 
 
 6. It diminishes the toxic action of the product of the 
 intestinal flora. 
 
 7. It prevents the coagulation of mucus in the intestine 
 by the so-called " mucinase " (which asserts itself under the 
 disordered conditions due to lack of bile) ; the deficiency or 
 absence of the biliary secretion explains the genesis of 
 certain forms of muco-membranous enteritis. 
 
 Bile as a Cholagogue. — We are told by the French 
 clinician, Huchard, that "bile is the physiologic chola- 
 gogue, just as urea is the physiologic diuretic," and by 
 far the most important therapeutic service that the 
 administration of bile or its preparations can render is its 
 bile-inducing action. 
 
 Bile gives very good results in those cases where the 
 biliary secretion has been totally or incompletely arrested, 
 as in icterus and hepatic colic, as well as in the other 
 more common disorders where the biliary secretion is 
 insufficient. 
 
 Its use prompts a more normal condition in the intestine, 
 and favourably controls certain forms of constipation, 
 bringing about its salutary action by several methods 
 which have already been enumerated. Some experiments 
 by Dauguet^ give weight to the importance of bile as a 
 cholagogue. He found that if 100 c.c. of bile (containing 
 r53 grammes of the biliary salts) is introduced into the 
 stomach, a secretion of bile is brought about with a total 
 of 4-53 grammes of bile salt, whereas before the experi- 
 ment this amounted only to r86 grammes. 
 
 Clinically the results are just as good. The report of
 
 174 
 
 Practical Horrnone Therapy 
 
 Del ore and Cotte^ upon the results of the administration 
 of choleine (an extract of ox-gall) to an individual with a 
 biliary fistula is of special interest, as it shows how great 
 is the quantitative influence of this form of medication. 
 Before the test the amount of bile collected from the tube 
 varied from 103 to 200 c.c. The exhibition of 06 gramme 
 (approximately 10 grains) of the extract raised the ex- 
 cretion of bile to 550 c.c, and 1-2 gramme (20 grains) 
 still further increased it to 750 c.c. 
 
 The Indications for Bile Administration. — The principal 
 disorders in which the administration of bile is indicated 
 are hepatic and biliary insufficiency with constipation, 
 fermentation in the bowel, auto-intoxication, hepatic 
 colic, biliary lithiasis, and other forms of occlusion of 
 the ductus choledochus (including the inflammatory 
 conditions), and muco-membranous enterocolitis. We 
 will briefly consider each of these separately. 
 
 Constipation. — More than 50 per cent, (some authorities 
 say as high as 90 per cent.) of all cases of constipation are 
 due to disorders of the liver. The liver becomes " torpid " 
 from overwork and long abuse, and needs the right kind 
 of stimulation. Bile is the remedy par excellence, because 
 it is the best cholagogue, and also because it is actually 
 the missing element. It must not be thought, however, 
 that one can do more than begin to replace the reduced 
 quantity of bile in the intestine, for the normal average 
 flow of bile is 1,200 to 1,300 c.c. in twenty-four hours, 
 15 per cent, of which (or 180 to 200 grammes) consists of 
 solid elements; and of course even half that amount of 
 inspissated bile would be a most inconvenient dose.* 
 
 The results of this form of treatment are less strenuous 
 
 * Although Dauguet has shown that a dog of average size can take 
 300 grammes of ox-gall (representing about 45 grammes of solid elements) 
 with no toxic phenomena and only a rather severe diarrhcea.
 
 The Therapeutics of Bile Preparations 175 
 
 than the usual cathartics, and it has the advantage of 
 being a rational restorative procedure rather than a 
 vigorous whipping, as with calomel. As a matter of 
 fact, 10 grains of bile extract are usually cathartic, and 
 3 to 5 grains (or more) continued for some weeks form a 
 most satisfactory treatment of chronic constipation, the 
 foetid odour of the stools being rapidly controlled, their 
 consistency and regularity being brought to normal, and 
 with these changes there is naturally a regulation of the 
 toxic manifestations, the colour of the skin, and the 
 health in general. 
 
 It is unnecessary to repeat the observations of Roger 
 and others on the value of bile as an intestinal antiseptic. 
 While not antiseptic itself, bile is one of the best intestinal 
 antiseptics, because it facilitates the re-establishment of 
 the normal conditions in the intestines. 
 
 The Prevention of Hepatic Colic. — Tradition has set 
 apart ox-gall as a marvellous remedy for colic of hepatic 
 origin, and during the past twenty- five years this empirical 
 confidence has been justified by our knowledge of how 
 and in what degree the bile acts. 
 
 Manifestly one cannot expect any preparation of bile 
 to control the pain or inconvenience of hepatic colic. 
 The acute manifestations must be controlled in the usual 
 manner by heat and opiates; but nevertheless bile is a 
 most reasonable curative remedy, because it tends to ob- 
 viate the stagnation and thereby to facilitate the removal 
 of concretions obstructing the bile channels. 
 
 So far as we know there is no remedy that will dissolve 
 gall-stones in situ, and bile is no exception to the rule, 
 nor will it facilitate the passage of a stone too large for the 
 duct. Its augmentation of the flow of bile may favour 
 the removal of the obstruction provided it is not solidly 
 fixed, in which event the only recourse is to surgery.
 
 176 Practical Hormone Therapy 
 
 The Pathogenesis of Gail-Stones. — The importance of 
 normal bile production is even greater than has just been 
 indicated, for Chauffard^* and his assistants have demon- 
 strated that when there is a reduced supply of bile salts, 
 the cholesterin (which it will be remembered is the chief 
 consistent of gall-stones) is not held properly in solution, 
 and hence is retained in the blood. This excess facilitates 
 precipitation at points favourable to sedimentation, 
 especially in the gall-bladder and ducts. The principal 
 disorder is a form of hepatic insufficiency, and an attempt 
 should be made to restore the normal activity or to sup- 
 plement it by administering bile and liver preparations, 
 in addition to the usual hygienic and dietetic measures. 
 
 Increasing the Digestion of Fat. — Bile is an important 
 factor in the digestion of fats, and without going into the 
 physiology of this occurrence we may say that the ad- 
 ministration of bile regulates, in a considerable degree, 
 fmrther absorption. Carnot^ has shown that extracts 
 of bile favour an increase in weight, since by their in- 
 fluence the assimilation of fat may be increased as much 
 as 75 per cent. Robin states that fully 95 per cent, of 
 ingested fats are metabolized, but if the proportion of 
 bile decreases, one-half of the fat is not assimilated. 
 
 The therapeutic indication of cream-coloured stools is 
 almost invariably bile. 
 
 The Treatment of Muco-Membranous Colitis. — To the 
 French is due the credit for having enlightened us upon 
 the pathogenesis of muco-membranous enterocolitis, and 
 thereby upon an effective treatment for it. The researches 
 of Roger^ on the coagulation of mucus in the intestines, 
 and the regulative action that the bile exerts upon this 
 
 * Chauffard has just published a new book (see Appendix) whicli considers 
 the whole subject of biliary lithiasis. Chapters I. and X. especially concern 
 the pathogenesis aud treatment of this condition.
 
 The Therapeutics of Bile Preparations 177 
 
 phenomenon, have demonstrated a close relationship 
 between intestinal affections, especially mucous enteritis 
 and colitis, and the normal supply of bile. 
 
 It seems that the intestinal walls normally secrete a 
 ferment named by Roger "mucinase," the function of 
 which is to coagulate mucin. This ferment is rendered 
 inactive by certain alcohol-soluble, heat stable substances 
 in the bile, and Roger inferred that, since this disease 
 was so often associated with biliary insufficiency, and 
 experimentally produced by diverting the bile-flow from 
 the duodenum, the membrane formation was due to in- 
 sufficiency of bile. Later Riva isolated mucinase in the 
 faeces of patients suffering from this disease. From these 
 studies we have come to recognize the value of bile as 
 a remedy for this intractable and painful disease. 
 
 Nepper"^ and others have also investigated the subject 
 very carefully, and supplemented their physiologic investi- 
 gations with a large number of clinical tests. He puts 
 forward as an axiom that muco-membranous colitis is the 
 result of deficient bile production (oUgocholie), and can- 
 not exist without it, and also that the membrane is due 
 (1) to the increase in the ferment mucinase, and (2) to a 
 relative and simultaneous diminution in biliary secretion, 
 especially as regards its anticoagulating power, which 
 permits the mucinase secreted by the epithelial walls of 
 the intestine to assert its coagulating powers. 
 
 This explains the following statement in Roger's book 
 on digestion^: "For those who pass membranes, pre- 
 scribe an extract of ox-gall, and you will frequently see a 
 subsidence of the pain and a complete disappearance of 
 the membranous casts." 
 
 This disease may be treated locally or by oral adminis- 
 tration of bile. Nepper administers solutions of bile by 
 means of high rectal injections, allowing the solution to 
 
 12
 
 178 Practical Hormone Therapy 
 
 remain in contact with the membra,ne-covered intestinal 
 walls for about two hours, carrying out a procedure exactly 
 similar to the orthodox high rectal injection. He also 
 supplements this by a course of pills containing bile 
 extract, which should be preferably keratin coated. The 
 dose by mouth varies from 5 to 20 grains, and may be given 
 at intervals of two or three hours. It seems advisable to 
 continue the administration of bile in slightly smaller 
 doses for some months after the colitis is controlled. 
 
 Bile Extracts in Tuberculosis. — Lemoine and Gerard^ seem 
 to have established the value of a petroleum-ether extract 
 of bile (jparatoxine) in the treatment of tuberculosis. It must 
 be admitted, however, without in the least degree deprecia- 
 ting the results obtained, that the extract is virtually a 
 solution of cholesterin, and its virtues are due to the power 
 of this lipoid to " fix " certain toxic substances. m 
 
 It does not seem, then, that the subject rightly comes 
 under the title of this chapter, but it will be briefly 
 referred to again in the chapter devoted to the lipoids. 
 
 Dosage and Administration. — The average dose of 
 extract of bile is 8 to 25 grains (0-5 to 1-5 grammes) from 
 two to five times a day, or of the repurified and vacuum- 
 dried preparation 5 to 10 grains (0*3 to 0*6 gramme). 
 The French preparations are usually put up in keratin- I 
 
 coated pills or ovoids, each containing 0-2 gramme 
 (3 grains) of the extract. 
 
 In constipation small doses over a long period are 
 advised, and extracts of liver and duodenum may be 
 combined with bile to considerable advantage (see p. 168). 
 In hepatic colic it should be given in frequently repeated 
 doses (3 grains every hour during attacks), and should be 
 kept up during the intervals in 6-grain doses four or five 
 times a day. The dosage in colitis has already been 
 suggested.
 
 The Therapeutics of Bile Preparations 179 
 
 BIBLIOGEAPHY 
 
 ^ Roger (H.): Quelqiies considerations sur le role de la bile, 
 Pr. med. (Paris), 1913, xxi, 137. 
 
 2 Dauguet (A.): "Etude sur la Physiologie de la Bile: Conse- 
 
 quences Therapeutiques. Opotla6rapie Biliaire." These de 
 Paris, 1907. 
 
 3 Deloke (X.) AND COTTE (G.): Reclierclies sur 1' excretion de la 
 
 bile a I'etat normal et apres cliol6cystectomie, Bev. d. Chir. 
 
 (Paris), 1911, liv, 33. 
 * Chauffard (A.): Pathogenie de la litbiase biliaire; role do 
 
 rhypercbolesterin6mie, Pr. med. (Paris), 1913, xxi, 929. 
 5 Carnot:* p. 233. 
 ® Roger (H.): La coagulation de la mucine, C. r. Soc. Biol 
 
 (Paris), 1905, lix, 423. 
 ' Nepper (H.): " Pathogenese et Traitement de la Colite Muco 
 
 membraneuse." These de Paris, 1906. 
 8 Roger (G. H.): " Alimentation et Digestion " (Paris), 1907 
 
 pp. 475-476. 
 ^ GliRARD (E.) AND Lemoine (G.): Sur la composition de I'ex 
 
 trait ethere (lipoide) de la bile, Biill. et 31 em. 8oe. Med. 
 
 d'Hop. de Paris, 1909, xxviii, 935. 
 
 Inoute (Z.) and Sato (T. J.): Ueber die therapeutische An 
 
 wendung der Galle, Arch. f. Verdauungskr. (Berlin), 1911 
 
 xvii, 185. 
 Croftan (A. C): The bile acids as a remedy, N. Y. Med. J. 
 
 1906, Ixxxiii, 810. 
 Alquier (L.): L'opoth6rapie biliaire et pancr^atique dans les 
 
 dyspepsies, Gaz. d. Hop, (Paris), 1913, Ixxxvi, 841. 
 Hallion (L.) and Nepper (H.): Influence excito-motrice do la 
 
 bile sur I'intestin, G. r. Soc. Biol. (Paris), 1907, Ixi, 182, 254. 
 Roger (H.): Influence de la bile sur la production des poisons 
 
 dans I'intestin, G. r. Soc. Biol. (Paris), 1909, Ixiii, 666. 
 Lereboullet (P.): Les opotherapies hepatiques, biliaires et 
 
 pancr6atiques ; leur emploi th^rapeutique, J. Med. frang. 
 
 (Paris), 1911, v, 481. 
 Nigat (M.): Action therapeutiquo de la bile dans les affections 
 
 hepatiques et gastro-intestinales, J. d. Med. d. Paris, 1906, 
 
 sviii, 214.
 
 CHAPTER XIII 
 
 THE THYROID GLAND AND THE TREATMENT OF 
 ITS INSUFFICIENCIES 
 
 The Keystone of the Eiidocrinous System — The Thyroid Hor- 
 mones — The Polyvalence of the Thyroid Secretion — The In- 
 fluence of the Thyroid on Nutrition — The Relation of the 
 Thyroid to the other Ductless Glands — The Iodine in the 
 Thyroid and Extracts thereof — The Rise of Thyroid Therapy 
 — The Artificial Replacement of the Thyroid Secretion in 
 Myxcedema, Goitre, etc. — The Frequency of Functional 
 Hypothyroidism — Levi and de Rothschild's Deductions — The 
 Basis of Empirical Thyroid Therapty — The Treatment of 
 Obesity — Imnmnity, Resistaiice, and Detoxication — Thyroid 
 Therapy in Rheumatism — The Value of Thyroid Extract in 
 Dermatology — The Use of Thyroid Extract in Gyncscology — 
 The Action upon the Vascular System — Nervous Disorders 
 and their Treatm,ent with Thyroid Extract — Nutrition and 
 Developmental Disorders in Children- — The Newer Concep- 
 tions of Graves's Disease — Pluriglatidular Combinations — 
 The Contra-indications to Thyroid Therapy — The Indis- 
 criminate Use of Thyroid Preparations — Dosage of Thyroid 
 Preparations. 
 
 The literature on the thyroid gland and its internal 
 secretion, as well as on the therapy which this knowledge 
 has made possible, is immense. Many hundreds of papers 
 have appeared since the inauguration of this most impor- 
 tant study. Not a few books are devoted solely to this 
 subject, and if all the information at present on record 
 could be gathered here, it would add many hundreds of 
 pages to this book. 
 
 Thyroid therapy is the best known application of 
 hormone-bearing products m therapeutics, and its value 
 
 180
 
 Thyroid Therapy 181 
 
 in certain conditions makes it possible to class it with 
 that limited number of remedies known as " specifics." 
 
 Here it is only possible briefly to summarize the gist 
 of our knowledge, and perhaps to emphasize the fact that 
 thyroid therapy has a considerably broader field than is 
 generally known, and that its value is by no means 
 limited to the control of those glandular insufficiencies 
 which are obvious, and which might properly be called 
 "major thyroid insufficiencies." 
 
 The Keystone of the Endocrinous System. — The thyroid 
 has been called " the keystone of the endocrmous system," 
 and the use of preparations of it is virtually the founda- 
 tion-stone of modern organotherapy. It is really amazing 
 how our knowledge of its usefulness has developed in 
 little more than two short decades. 
 
 The views concerning the function of the thyroid have 
 been frequently changed, and have varied from the 
 presumption that it was a comparatively useless fatty 
 covering of the neck, to the more scientific suggestion 
 that it acted as a regulator of the hsemopoietic and cir- 
 culatory mechanism. Galen knew of its existence, and 
 even described it as a ductless gland, but offered no 
 suggestions regarding its action. The early views of the 
 function of the thyroid are summarized in a very interest- 
 ing manner in Swale Vincent's book.^ 
 
 The Thyroid Hormones. — This remarkable gland pro- 
 duces and discharges into the blood and lymph a complex 
 secretion, which contains the active principle or hormone. 
 This substance influences certain tissues directly, and by 
 its profound action upon metabolism indirectly affects 
 many functions of various organs. For a long time the 
 mode of these activities was not well known, and within 
 the present decade the thyroid secretion is referred to as 
 acting " probably through the nervous system." There
 
 182 Practical Hormone Therapy 
 
 can be no doubt that it acts on the nervous system, but 
 it seems conclusively proved that it acts through humoral 
 channels, and physiologists generally credit the thyroid 
 action to its hormone-content. 
 
 Schafer, m his address, ^ refers to the important position 
 of the thyroid in the following terms: " Another instance 
 of an internally secreting gland which is essential to life — 
 or, at least, to its maintenance in a normal condition — 
 is the thyroid. The association of imperfect development 
 or disease of the thyroid with disorders of nutrition and 
 inactivity of the nervous system is well ascertamed. 
 The form of idiocy laiown as ' cretinism,' and the affec- 
 tion termed ' myxoedema,' are both associated with 
 deficiency of its secretion. Somewhat similar conditions 
 to these are produced by the surgical removal of the gland. 
 The symptoms are alleviated or cured by the adminis- 
 tration of its juice. On the other hand, enlargement of 
 the thyroid, accompanied by increase of its secretion, 
 produces symptoms of nervous excitation, and similar 
 symptoms are caused by excessive administration of the 
 glandular substance by the mouth. From these observa- 
 tions it is inferred that the juice contains hormones which 
 help to regulate the nutrition of the body and serve to 
 stimulate the nervous system, to the performance of the 
 higher functions of which they appear to be essential. 
 To quote M. Gley, to whose researches we owe much of 
 our knowledge regarding the functions of this organ: 
 ' La gene.se et Vexercice des plus hautes facultes de Vhomme 
 sont conditionnes par Vaction purement chimique d''u7i 
 produit de secretion. Que les psychologues meditent ces 
 fails r " 
 
 The Polyvalency of the Thyroid Secretion. — The chief 
 means of studying the action of this gland has consisted 
 in the clinical consideration of the several disorders of
 
 Thyroid Therapy 183 
 
 the thyroid. The variability of these symptoms has led 
 Murray,^ amongst others, to the belief that the thjrroid 
 secretion is polyvalent, and contains different hormones 
 which are capable of activating different organs. This 
 rather suggests that one of these hormones may have a 
 special influence upon the sweat glands and hak follicles, 
 while another may mfluence the heart, still another the 
 bronchial mucous membrane, and so on. Attention is 
 called to the fact that in some cases of Graves's disease 
 not only may there possibly be an increase in the amomit 
 of thyroid secretion, but in some cases also a considerable 
 difference in the proportion of the hormone-content of 
 the secretion. Sudden temporary increases m various 
 of these hormones would account, for example, for the 
 so-called " goitre heart." This theory is sufficiently 
 invitmg to build upon it the idea that the various forms 
 of hj'perthyroidism are due to variations in the charac- 
 teristics of the increased thyroid secretion that is ab- 
 sorbed. Fiu'ther proof of the polyvalent character of the 
 thyroid secretion will be found in the consideration of the 
 influence of thyroid extract upon the heart and blood- 
 pressure. This may also account for the very extended 
 list of indications for thjrroid therapy, and especially 
 for the large class of widely varying conditions which are 
 presumed to be due to functional hypothyroidism. 
 
 Siegmund"* is convinced of the soundness of this theory, 
 and relates experiences to show that from the standpoint 
 of the therapeutic activity of thyroid preparations (as 
 compared with the varying symptoms of thyroid excess) 
 in certain cases Baumann's iodoihyrin failed, while ordinary 
 thyroid extract was very effective, and vice versa. He 
 concludes that there are numerous substances produced 
 by the thyroid gland, the absence or diminution of which 
 may explain the simultaneous occurrence of thyroid
 
 184 Practical Hormone Therapy 
 
 weakness and thyroid hypersecretion, and their conse- 
 quences. Each of these substances probably has a 
 definite function and a special relation with a definite 
 tissue or organ, including the other endocrinous glands. 
 
 The Influence of the Thyroid on Nutrition. — ^While 
 a number of the ductless glands are intimately concerned 
 m the regulation and maintenance of nutrition, none of 
 them play such a decided part as the thyroid. It may 
 be said that the thyroid presides over the nutrition of the 
 body, although, of course, its influence is augmented from 
 many other quarters. It is difficult to set down within 
 these brief limits an adequate discussion of the importance 
 of this subject, for it is peculiarly complex. 
 
 The extraordmaril}'' stunted condition of cretins, the 
 prevalence of disordered fat metabolism in patients 
 suffering from comparatively slight thyroid insufficiencies, 
 the relation of thyi^oid disease to bone growth, and, finally, 
 its intimate connection with the establishment of the 
 sexual activities and the accompanying mental and 
 physical growth, are all incontestable evidences of the 
 essential influence of the thyroid on metabolism and 
 nutrition. 
 
 The major share of this control of growth and the 
 bodily interchanges generally is undoubtedly purely 
 thyroid m origm, and while obvious connections may be 
 traced between other mternal secretory organs and various 
 phases of nutrition, it will be astonishing how closely 
 the thyroid is concerned in the work of these other 
 glands. 
 
 The Relation of the Thyroid to the other Ductless 
 Glands. — -The importance of the mterrelation between 
 the thyroid and its endocrinous fellows has already been 
 considered (Chapter III.), and it is well known that the 
 evidences of these relations are more thoroughly worked 
 
 %
 
 Thyroid Therapy 185 
 
 out than is the case with any of the other endocrinous 
 glands. As we have seen, the thjnroid is in known and 
 proved relations with the adrenals, pancreas, hypophysis, 
 and gonads, and very probably quite intimately con- 
 nected with the thymus, parathyroids, and intestine. 
 A still more indirect relation may be traced between the 
 thyroid and the remaining members of the endocrinous 
 family. A knowledge of these relations is of paramount 
 importance in the consideration of all metabolic dis- 
 turbances, as well as in disorders of any of the above- 
 mentioned organs; in fact, the thyroid should be taken 
 into consideration in the study of practically every phase 
 of internal medicine. There is nothing speculative in the 
 greater part of the information which we now have at 
 our command, though much of this definite know- 
 ledge was admittedly quite speculative a very few years 
 ago.* 
 
 Briefly, then, it may be well to recapitulate the prin- 
 cipal relations between the thyroid and the other impor- 
 tant ductless glands, since upon this knowledge depends 
 the effective and successful basis of thyroid therapy. 
 Evidence has been collated by Hoskins^ to show the inter- 
 relations of the endosecretory organs. The thyroid by 
 its internal secretion stimulates the adrenals. Its re- 
 lation to the hypophysis may be called that of a mutual 
 friend, and it has been presumed, as a result of a number 
 of experiments, that the hypophysis under certain 
 circumstances functionates vicariously for the thyroid. 
 This, however does not preclude the idea that the thyroid 
 normally exercises an inhibitory action upon the hypo- 
 physis, as indicated by the pituitary hypertrophy which, 
 
 * Tliis should be of considerable encouragement to ns in our consideration of 
 the less well-known endocrinous organs, for undoubtedly knowledge concern- 
 ing them is destined before very long to be jnit upon a much more detinite 
 basis.
 
 186 Practical Hormone Therapy 
 
 so constantly seen, is associated with experimental or 
 clinical athyroidia. 
 
 The influence of the thyroid upon the testes and 
 ovaries is of such a nature that it is now stated definitely 
 that the thyroid controls the activities of these glands, 
 and furnishes at least the major part of the stimulating 
 effect that is necessary for the normal continuance of 
 their functions. 
 
 Hertoghe^^ has shown that the thyroid secretion is 
 indispensable to the establishment of the activities of 
 the gonads. He was also the first to point out the 
 antagonistic action which the thjrroid exerts upon the 
 ovarian secretions. Attention may also be called to 
 the fact that the thyroid evidently exerts an action upon 
 the menses, for myxoedematous females frequently suffer 
 from profuse menstrual haemorrhage which is not easily 
 controlled, while thyroid medication moderates it in a 
 remarkable manner. On the other hand, women with 
 Graves's disease frequently have a diminished monthly 
 flow which even may amount to complete amenorrhoea. 
 
 The thjnroid also influences the mammary secretion. 
 Hertoghe reports that the administration of thyroid 
 extract to lactatmg animals augments, in a considerable 
 degree, the amount of milk produced. 
 
 Reference has already been made to von Noorden's 
 ideas regarding the antagonistic interaction of the thyroid 
 and pancreas (Chapters III. and VII.). 
 
 The evidence regarding the relation of the thymus to 
 the thyroid is somewhat conflicting. The experimental 
 work indicates that there is a connection between these 
 organs, but whether it is a synergism or an antagonism 
 is not quite clear, as under certain experimental con- 
 ditions both these stimuli may be brought into play. 
 
 It is, of coiu'se, understood that these relations just
 
 Thyroid Therapy 187 
 
 mentioned are subject to numerous stimuli from other 
 sources, and while quite definite statements are now 
 generally made, it is very easy, in both experimental 
 work and clinical observation, to bring forward presumable 
 evidence to show how much we are still in the dark about 
 what we consider to be the best-laiown facts regarding 
 the correlation of the thyroid with the other ductless 
 glands. 
 
 The Iodine in the Thyroid and Extracts thereof. — The 
 thyroid gland is very rich m iodine, containing as it does 
 nearly ten times more of this element per gramme of 
 gland substance than any other organ or tissue. This 
 iodine is considered to be the active element in the 
 thyroid secretion, since it has been shown that the thera- 
 peutic activity of thyroid preparations varies directly 
 with their iodine content; in fact, the importance of the 
 presence of iodine in thyroid extract has established the 
 iodine percentage as the recognized standard of efficiency 
 of such extracts. The essential role of the iodine is 
 emphasized by Osborne,^ who remarks at the close of a 
 valuable paper that, " though much of the thyroid sub- 
 stance on the market is not active, a little coincidentally 
 admmistered iodine as an iodide will render it active." 
 This, however, should not permit of the use of any but 
 the most active products obtainable. 
 
 It now seems to be evident that many of the failures 
 of thyroid therapy, and of the varying results that were 
 so commonly found some years ago, were due to the un- 
 certain iodine content of the preparations. Fortunately 
 we have passed this stage, and practically all trade 
 preparations are now standardized to contam 0-2 per 
 cent, of actual iodine. 
 
 It must not be imagined that the iodine is the active 
 principle, for in spite of the important part that this
 
 fi 
 
 i 
 
 188 Practical Hormone Therapy ?f 
 
 element plays in the presumed molecular. make-up of the 
 thyroid hormone, it cannot be used as a substitute.* The 
 combination is as yet too complex for the biological 
 chemist; but it is predicted that before long a graphic 
 formula will have been worked out, just as has the formula 
 of adrenalin, and iodine will be found to be an important 
 part of it. In all probability a synthetic product re- 
 sembling thyroid extract eventually will be produced, 
 just as suprarenin is now made in the laboratory with no 
 recourse whatever to animal mother-substances. 
 
 The Rise of Thyroid Therapy. — As soon as Schiff and 
 Horsley (1884-86) showed that the thyroid was essential 
 to the well-being of the body, the study of its influence in 
 health and disease was taken up with avidity. The 
 innumerable experiments on animals and clinical re- 
 searches in medicme, which were thus initiated, opened * 
 up a field of physiology that had been hitherto unseen; 
 and as a better knowledge of the activities of the thyroid 
 was gained, it was but a step to apply the fundamental 
 rule of organotherapy, and to attempt to use thyroids, 
 raw or extracted, in the treatment of the deficiencies of 
 this organ. The results, as all know, were startling; and 
 upon these experiences, in a far greater degree than upon 
 the experience of Brown-Sequard with testicular extract, 
 the scientific and rational foundation of hormone therapy 
 has been laid. 
 
 The credit for having first applied thyroid preparations 
 in clinical practice must be awarded to G. R. Murray'^ 
 
 * Swale Vincent, in his book (p. 352), is not quite so emphatic. He writes ; 
 " As to the chemical nature of the internal secretion, nothing definite is 
 known. The significance of iodine is problematic, though the beneficial 
 effects of thyroid substance administered as a drug seem to depend very 
 largely upon its iodine content. It is impossible altogether to escape from 
 the suspicion that treatment with thyroid preparations may after all only be 
 a mode of treatment with organically combined iodine in an easily assimilable 
 form." The present author, like many others, does not quite agree with this.
 
 Thyroid Therapy 189 
 
 of England. Gley,^ in France, and Vassale,^ in Italy, 
 were then at work with the initial attempts to control 
 the disorders produced by thyroidectomy in dogs J" Tn 
 1890-91 these investigators independently published the 
 beginnings of the voluminous literature on thyroid 
 medication. The comparatively crude preparations then 
 used have passed through a process of evolution, until 
 to-day the profession is served with numerous active 
 and standardized products,* and has a very much more 
 thorough idea of their therapeutic indications and 
 clinical possibilities. But the maze of thyroid action 
 and interaction is so complex, and the range of the 
 limitations of thyroid therapy so great, that there are 
 yet many points to be learned. Only a short time ago 
 (1914) the author learned, in a personal communication 
 from Beebe, that he had isolated a new and hitherto 
 unknown " X-substance " from the thyroid, which has 
 a marked hypotensive action, without the therapeutic 
 effect usually expected from thyroid preparations. 
 Further reference to this will be made later. 
 
 The Artificial Replacement of the Thyroid Secretion 
 in Myxoedema, Goitre, etc. — This is not the place to dis- 
 cuss the relation of the thyroid to simple goitre, myxoe- 
 dema, endemic or sporadic cretinism, or cachexia strumi- 
 priva. This is well done in several books and " systems " 
 of medicine; but it is necessary briefly to mention the 
 salient facts involved, in order that the chief link in the 
 chain of thyroid therapy may not be omitted. 
 
 It is now an unquestioned fact — and unquestioned facts 
 in medicine, especially in therapeutics, are very few and 
 far between — that hypothyroidia and athyroidia are 
 amenable to treatment with thjrroid extracts. The 
 
 * In an annotation accompanying the MSS. of this chapter Professor Murray 
 remarks: "It is curious that ray original thyroid extract is stiUtQ-day Xh& 
 official B.P. Liq. thyroidei."
 
 190 Practical Hormone Therapy 
 
 literature is as extended as it is convincing, and thyroid 
 extract is conceded to be numbered among the very few 
 " specifics." It is the cure* for myxoedema and athy- 
 roidia. 
 
 The Frequency of Functional Hypothyroidism. — In 
 goitre the thyroid may be inactive, underactive, or over- 
 active. Individuals with an inactive thyroid are virtually 
 suffermg from myxoedema, and exhibit a series of symp- 
 toms diametrically opposed to those of patients with an 
 overactive thyroid. When the thyroid is underactive, 
 the results of its deficient supply of hormones may or 
 may not be manifested. A marked hjrpothyroidism is 
 akin to, and may be called, " myxoedema." More often, 
 however, this faultiness is not so evident, and in such 
 cases we have the minor form of thyroid incompetence, 
 which Hertoghe has called " myxcedeme fruste.'''' He 
 was the first to lend emphasis to the so-called " benign 
 thyroid insufficiencies." In 1899 Hertoghe ^° introduced 
 the term " hypothyro'idie benigne chronique,'''' and the 
 study of this subject rapidly became popular in Europe, 
 and especially m France was investigated by numerous 
 authors, mcluding Leopold Levi, de Rothschild, Delacour, 
 Apert, Tremolieres, and others, who warmly defended 
 this position. The subject is fully considered in the re- 
 port of Verriest,^^'' who was selected to analyze Hertoghe's 
 work on the lesser forms of myxoedema, and report upon 
 it to the Belgian Academy of Medicine. A knowledge 
 of this minor and frequently overlooked thyroid inade- 
 quacy is of considerable therapeutic service, as we may 
 shortly see. 
 
 * By " cure " is meant " amedicine effective in treating disease " (Borland). 
 Of course, the thyroid treatment does not grow a new gland in the con- 
 gcnitally athyroidic, nor does it regenerate a hopelessly atropliied gland ; but 
 it does relieve and remove the symptoms, and in a degree the stigmata, of 
 this condition, keeping them in control as long as the remedy is judiciously 
 administered.
 
 Thyroid Therapy 191 
 
 If the major thyroid insufficiencies be termed " phases 
 of organic hypothyroidism " (for in them aU there is an 
 obvious change m the thyroid structure), then it is right 
 to assume that there must be a corresponding functional 
 disturbance in which the secretory activities of the gland 
 are modified with no evident change in the structure. 
 This disorder has also been called " chronic benign thyroid 
 insufficiency," or Hertoghe's syndrome. This is un- 
 doubtedly a clinical entity, and it may be connected with 
 a large variety of endocrinous syndromes, as well as with 
 many conditions not yet definitely connected with dis- 
 orders of the mternal secretory mechanism. Many 
 obscure conditions are undoubtedly associated with, and 
 in many cases probably due to, minor thyroid insuffi- 
 ciency — a condition for which the author suggests the 
 term " functional hypothyroidism." 
 
 Levi and de Rothschild's Deductions. — Shice Hertoghe 
 originated the study of this subject, Leopold Levi and 
 Baron H. de Rothschild, of Paris, have been among its 
 foremost students, and an hour or two with their latest 
 book* will convince the most confirmed sceptic that 
 what Leonard Williams has said of thyroid therapy is 
 very true : " The broad Imes of thyroid therapy are simple 
 enough, but the byways are fascinatingly complex." 
 
 A few points culled from the introduction to this book 
 
 * " La Petite Insuffisance Thyroidienne." It has been said that the writers 
 of this book are " thyroid mad," and that every case they mention is related 
 in some way to a disorder of the thyroid. This may be quite true, but it 
 should be remembered that MM. Levi and de Rothschild are studying the 
 intricacies of known and supposed thyroid disorders, and purposely look at the 
 subject from this particular view-point. They may not be invariably right 
 in their deductions, nor may the clinical tests of their suggestions be always 
 successful ; but it is quite certain that the physician who acquaints himself 
 ■with the observations of these gentlemen, taking as mucli of the })roverbial 
 "grain of salt" as may seem to be necessary, will find his appreciation of 
 hormone action and thyroid therapy broadened in a degree which the author 
 is convinced will be of much practical help.
 
 192 Practical Hormone Therapy 
 
 will explain how and why these authors draw their con- 
 clusions: "Considerable importance attaches to minor 
 thyroid insuiSiciency, for, unlike myxoedema, it is very 
 frequent. It should be also especially interesting to the 
 physician because of its usually rapid response to treat- 
 ment. Clinical experience is the basis of these deductions, 
 just as it was the original basis of the present knowledge 
 of the stigmata of hypothyroidism. 
 
 "In 1905 we first tried thyroid therapy in conditions 
 other than myxoedema. The first subject suffered from 
 chronic rheumatism and psoriasis. After commencing 
 this medication, the appetite was increased to a point 
 where it seemed that the patient might have a tape- 
 worm; and the patient also was remarkably relieved of 
 extreme sensitiveness to cold. This directed attention 
 to the influence of the thyroid upon the appetite and 
 bodily warmth. Later a favourable action upon con- 
 stipation was noticed, and the similarity was remarked 
 between these symptoms and those of myxoedema, the 
 difference being merely one of degree. 
 
 ' ' We then encountered a case of severe constitutional 
 neurasthenia in a gu'l showing numerous signs of hypo- 
 thyroidism — e.g., short stature, anorexia, sensitiveness 
 to cold, loss of hair and teeth, cracking noises in the joints, 
 a tendency to colds, a bad state of the gums, haemor- 
 rhoids, etc. Were these phenomena and the neurasthenia 
 coincidental with, or actually due to, the hypothyroidism ? 
 The treatment was effective, and after taking sixty-one 
 cachets (each containing 0-1 gramme — 1| grains — of 
 thyroid powder) the patient considered herself cured. 
 Two months later there was a relapse, which, however, 
 was again controlled in the same way. This therapeutic 
 experience indicates a relation between hypothyroidism 
 and certain forms of neurasthenia.
 
 Thyroid Therapy 193 
 
 " In the same manner we have studied transitory 
 oedemas, periodic herpetic anginas, nervousness (especially 
 in children), neuroarthritic disturbances, migraine, asthma, 
 certain dermatoses, etc. When thyroid therapy controls 
 these diverse symptoms, one must admit that hypo- 
 thyroidism, in a certain degi-ee, was concerned in their 
 production. Hence the treatment itself acquires a diag- 
 nostic value." 
 
 The Basis of Empirical Thyroid Therapy. — These in- 
 vestigators wisely warn against a common source of error, 
 which must be avoided if our deductions are to be of 
 value. For example, hypothyroidism is an extremely 
 common condition; adenoids, incontinence of urine, and 
 rickets are far from rare. Have we, then, the right, 
 when in some subject we meet evidence of hypothyi'oidism 
 and adenoids, to conclude that there is a thyroid origin 
 of the adenoids ? Another example, chronic rheu- 
 matism, is often of thyroid origin. Now, it may coincide 
 with myxoedema without bemg influenced by the thyroid 
 treatment. The application of this treatment offers no 
 irrefutable proof one way or the other. Clmical medicine 
 merely permits us to suppose a thyroid origin for this 
 phenomena or that, it cannot prove it absolutely. Even 
 in myxoedema the symptoms may not all necessarily be 
 due to the deficient thyi'oid secretion, for other local 
 troubles may, and often do, intervene to produce certain 
 of the symptoms. Hence clinical experiences do not 
 permit definite conclusions, but simply lead to the utiliza- 
 tion of a method of treatment. 
 
 This, then, is the raison d'etre of the emphical use of 
 thyroid extract — an immensely valuable procedure which 
 is " quite unscientific," but none the less resultful. This 
 is by no means an isolated experience, for there are a largo 
 number of established therapeutic^measures in general 
 
 13
 
 194 Practical Hormone Therapy 
 
 use for which, on the closest analysis, one cannot assign 
 a fundamentallj^ scientific excuse. 
 
 The mode of action of the thyroid hormone is not 
 known, at least in detail. It is not likely that its in- 
 fluence is confined to the thyroid itself: its stimulating 
 powers may reach the whole endocrmous system. Hence 
 there is a likelihood that thyroid medication not only 
 re-establishes the thyroid equilibrium, but also tends to 
 restore the mternal secretory balance. This may account 
 for the remarkable action of thyroid medication in some 
 conditions, as well as for the activating effect of minute 
 doses of thyroid extract upon other glandular substances 
 given simultaneously (see Chapter XXX.). 
 
 The Treatment of Obesity. — One of the empirical 
 applications of thyroid therapy that is most frequently 
 made is m the treatment of obesity. There is no doubt 
 that many of the individuals with this disorder, especially 
 women, are in a state of hypoendocrinism, and that the 
 judicious use of thyroid may stimulate the metabolism 
 and enhance oxidation, thus reducing a part of the 
 superfluous fat. Just how this is accomplished is difficult 
 to say, but the treatment has come into quite general 
 use, in spite of some drawbacks which must be briefly 
 referred to. The use of organotherapy in " home 
 medicine " is not advisable. Always it is best to have 
 patients who are undergoing treatment, whether with 
 thyroid, ovary, adrenal, or pituitary preparations, under 
 close professional observation. Thyroid extract is too 
 often used in a senseless and indiscriminate manner, and 
 in no condition does this obtain to such a degree as in 
 obesity. As a result, not a little harm has been brought 
 about, and conditions which are much more serious than 
 obesity have resulted. 
 
 The dosage cannot definitely be stated, for too many 
 
 f
 
 Thyroid Therapy 195 
 
 concomitant circumstances enter into the question. It 
 is certain, however, that heretofore the doses of thyroid 
 extract, especially in the treatment of obesity, have been 
 far too large. 
 
 Immunity, Resistance, and Detoxication. — There can 
 be little doubt that one of the most essential of the 
 activities of the thyroid gland is concerned in the resist- 
 ance of the organism to disease, and that the thyroid 
 hormone is intimately connected with these factors which 
 produce immunity. This appears to have been first 
 suggested by Sajous^^ in 1903, and has smce been con- 
 firmed by numerous clinicians and experimentalists. 
 Sajous's origmal observations are interesting: "(1) The 
 thyroid secretion is an active factor in the immunizing 
 processes. (2) It takes part mdirectly in this process by 
 increasing the functional activity of the adrenals as well 
 as general oxidation and metabolism. (3) The resulting 
 increase of functional activity of the organs producing 
 protective substances (alexins) correspondingly augments 
 the quantity of these alexins in the blood. 
 
 Langmead^2 ^as considered the evidence which seems to 
 point to a relationship between the thyroid gland and 
 alimentary toxaemia. He believes that facts are accu- 
 mulating to show that among the many functions of the 
 thyroid one of the most important is a protective action 
 against toxins which may enter the circulation. A series 
 of cases is described by Langmead, in which dilatation of 
 the colon produced symptoms similar to those of gastric 
 tetany, and he calls attention to the reports of Sir Arbuth- 
 not Lane and others, of the fact that the Lane operation 
 — ileo-sigmoidostomy — was followed by a visible reduc- 
 tion in the size of the goitre. 
 
 Slosse^3 of Brussels has suggested that the disturbances 
 in protein metabolism, which are commonly associated
 
 196 Practical Hormone Therapy 
 
 with chronic joint diseases, especially in those cases in 
 which the function is not of a gouty nature, and in which 
 the metabolism of nuclems does not appear to be in- 
 fluenced, are probably related to thjToid inefficiency. 
 According to his suggestion, we are to believe that the 
 thyroid produces a deaminizing hormone, which specifi- 
 cally influences the course of protein metabolism. He 
 remarked that when thyroid preparations were first 
 given to sufferers from chronic arthritis of the type above 
 mentioned, there was always an increase in the ammonium 
 salts in the urine. 
 
 Thyroid Therapy in Rheumatism. — This detoxicating 
 influence, with the hypothetical deaminizing hormone to 
 which Slosse refers, may be the explanation for the fre- 
 quent good results which follow the use of thyroid extract 
 in the treatment of chronic rheumatic disorders. Numer- 
 ous writers have called attention to the beneficial results 
 in joint disturbances which are often associated with 
 thyroid medication, and presumably are a result of it. 
 Pathological evidence of thyroid disorder in chronic 
 articular affections and in rheumatism has been brought 
 forward by Aubertin and Pascarno,^^ who relate the 
 autopsy findings in a number of cases in which well- 
 marked thyroid lesions were prominent. 
 
 The New York Medical Journal in an editorial article 
 discusses in the following terms the relation of the thyroid 
 gland to chronic rheumatism ^^ : " There is a form of 
 rheumatism, not infrequently met with, wliich is dis- 
 tinctly due to hypothyroidism and associated with the 
 characteristic symptoms of this condition; it consists of 
 severe pain in the occipital region or between the shoulder 
 blades, which rest m bed tends to aggravate rather than 
 mprove. Such cases never yield to salicylates and other 
 agents used commonly in the various forms of rheumatism;
 
 Thyroid Therapy 197 
 
 but the patients gradually recover under the persistent 
 use of desiccated thyroid gland. Care must be taken, 
 however, to avoid large doses. The so-called ' average 
 dose ' of the United States pharmacopoeia is positively 
 dangerous here: in no case should the initial dose of 
 desiccated gland exceed 1 grain." 
 
 Undoubtedly much of the good which follows the 
 empirical use of thyroid extract is due to the enhance- 
 ment of detoxication, and the stimulation of resistance 
 which it indirectly brings about. Sajous,^^ in consider- 
 ing the antitoxic fimctions of the thyroid, aptly remarks 
 that the recognition of the connection of the thyioid — 
 always including the parathyroids — with the defensive 
 mechanism of the body, enables us also to get better 
 results in the treatment of goitre by emphasizing the 
 importance of endogenous intoxication m the causation 
 of the disease. A patient may not do well, as is often the 
 case, under iodine or thyroid gland — or both combined, 
 the best plan— even when given early, avoiding strictly 
 all cases showmg signs of Graves's disease; but this will 
 soon change if, besides giving these agents, attention is 
 paid to any condition whatsoever — intestinal, hepatic, 
 gastric, renal, etc. — capable of provoking auto-intoxica- 
 tion. 
 
 Another phase of this interesting subject was men- 
 tioned by Noble ^^ of Washington, who refers to the fact 
 that "many striking results follow its administration in 
 failure of metabolism. Small doses of thyroid extract 
 have cleared up, in what appeared to be a marvellous 
 manner, the effect of metabolic poisons. The most strildng 
 results were seen in a patient with alcoholic msanity. 
 It was a very pronounced case in which the patient was 
 becoming demented. The patient was put upon 2 grains 
 of thyroid extract, and in four days the symptoms of
 
 198 Practical Hormone Therapy 
 
 dementia entirely disappeared. The drug was stopped, 
 and the dementia reappeared. It was again given, with 
 reappearance of normal intellection." 
 
 The Value of Thyroid Extract in Dermatology. — 
 Realizing that many dermatoses are the result of toxaemia, 
 it was not unreasonable to attempt the control of certain 
 sldn disorders by associating with the usual local treat- 
 ment the empirical use of thyroid extract, and a number 
 of very encouraging results have been recorded. Levi 
 and de Rothschild^'^ have reported a number of cases of 
 the more intractable forms of skm diseases, includmg 
 psoriasis, scleroderma, and eczema, that responded to 
 this treatment. Among numerous dermatological in- 
 dications for thyroid therapy, Morris^^ records a case of 
 keloid, in which thyroid appeared to have been useful. 
 He also states that multiple warts have been found rapidly 
 to disappear under thyroid medication. 
 
 The influence of the thyroid upon the nutrition of the 
 skui and its appendages is well laiown, and disturbances 
 in the nutrition of the scalp, nails, and epidermis have 
 been benefited by the revolution in metabolism brought 
 about by a more or less protracted course of small doses 
 of thyroid extract. 
 
 The manner in which the sclerotic conditions of sclero- 
 derma and chronic rheumatism have been influenced 
 suggested a possible special action of the thyroid in the 
 control of the conditions of this nature, and as an out- 
 growth of the application of this idea, Gilbert ^^ calls 
 attention to the fact that Leopold Levi has in this manner 
 successfully treated five out of seven cases of Dupuytren's 
 contraction. Folio whig thyroid medication, the in- 
 durated tissue became softened, and the function of the 
 hand was regained. It is suggested in an editorial con- 
 sideration of this subject^*^ that " these results point to
 
 Thyroid Therapy 190 
 
 a thyroid origin of the contraction of the pahnar fascia. 
 This view is borne out by the incidence in these cases of 
 other symptoms of thyroid deficiency — subacute ' rlieu- 
 matism,' pains, headache, alopecia, oedema, which were 
 also improved by the treatment. ... M. Gilbert's treat- 
 ment [really M. Levi's] seems worth a trial." 
 
 The Use of Thyroid Extract in Gynseeology.— From an 
 experimental standpoint the influence of the thyroid upon 
 the reproductive organs is decided, but complex. In 
 animals Blair Belpi has shown that thyroidectomy pro- 
 duces an mtense degree of uterine atrophy, while the 
 ovaries do not retrogress. On the contrary, there appears 
 to be an increase in their activity, especially in the 
 follicles. 
 
 The intimate relation of the thyroid and the female 
 reproductive organs has already been referred to, and is 
 one of the endocrinous relations that is most commonly 
 noticed in everyday clinical observation. The menstrual 
 disorders of hyperthyroidism and myxoedema, the in- 
 fluence of certain changes in the reproductive activity, 
 notably pregnancy, upon the thyroid, and other clinical 
 findings, mdicate that we may expect a considerable 
 amount of help from the application of thyroid therapy 
 in gjmsecology. 
 
 The stimulating action of the thyroid on the ovaries 
 has been used to good advantage m the treatment of 
 ovarian insufficiency with its various manifestations — 
 e.g., infantilism, amenorrhoea, scanty menstruation, and 
 even sterility. It is not possible exactly to explain the 
 broad influence of thyroid medication upon this class of 
 diseases: it is far too complex. We can only accept 
 the indubitable clinical results which have frequently been 
 obtained as a stimulus to continue the use of this method 
 of treatment, m the hope that this empirical application
 
 200 Practical Hormone Therapy 
 
 of thyroid therapy may eventually be scientifically ex- 
 plained. Of course, it is no explanation to say that the 
 thyroid, through one of its hormones, stimulates the 
 ovary;* nor can we get much satisfaction out of the 
 statement that thyroid medication seems to re-establish 
 the hormone balance, and thus favourably to mfluence 
 disorders which really have little or no direct connection 
 with the thyroid itself. The fact remains, however, that 
 in gynaecologic practice thyroid extract has been found 
 to be a most valuable remedy. 
 
 A number of writers have recorded good results follow- 
 ing the use of thyroid extract in the toxaemias of preg- 
 nancy, notably eclampsia and hyperemesis gravidarum; 
 and Thompson, 22 in his consideration of the infl.uence of 
 the thyroid on pregnancy and lactation, shows that lack 
 of thyroid secretion influences sexual activity adversely, 
 and that sexual activity, whether physiological or patho- 
 logical, causes overactivity of the thyroid. This form 
 of hyperthyroidism is considered by Thompson to con- 
 stitute an index to the toxaemia of pregnancy, to counter- 
 act which the thyroids raise their antitoxic protective 
 power. Abundant clinical evidence supports the theory 
 that the physiological overactivity of the thyroid dm:ing 
 pregnancy is a valuable safeguard against the toxaemias 
 incidental to that state. 
 
 Thyroid extract is beginning to be used quite often in 
 dysmenorrhoea, for many times the cause of certam dis- 
 turbances in ovarian action, etc., must be sought in the 
 other endocrinous organs, especially the thyroid. Pro- 
 vided no organic condition, such as stenosis of the cervix, 
 is present, and when the ovaries seem to be sound, 
 Dalche23 uses small doses of powdered thyroid (0 025 to 
 
 * As a matter of fact, evidence has been recorded earlier in this chapter 
 which indicates that under certain circumstances the thyroid exerts an 
 entirely opposite effect .
 
 Thyroid Therapy 201 
 
 005, or even 01 gramme, daily), and continues this treat- 
 ment for a month or more. This exhibition of thyroid 
 extract frequently seems to restore the normal balance, 
 and a short course of treatment results in the regulation 
 of the incidence and quantity of the flow, as well as in a 
 considerable reduction of the abdominal pain. After the 
 first month he gives the extract during the ten days pre- 
 ceding the date of menstruation. Occasionally ovarian 
 (luteal) extract may be alternated with the thyroid. 
 
 Dalche remarks that if by careful treatment and 
 proper hygiene the painful periods are controlled two or 
 three months m succession, the tendency to dysmenor- 
 rhcBa seems to be broken up, and menstruation proceeds 
 normally thereafter. 
 
 The Action upon the Vascular System. — Thyroid 
 extract, like extracts of the adrenal medulla and posterior 
 pituitary body, exerts quite an important influence upon 
 blood-pressure, although it cannot be said to compare 
 with these either in rapidity or extent. Usually it has a 
 slight depressor action, although overdoses of thyroid 
 extract materially increase the pulse-rate, and the 
 pressure may be raised principally by the direct action 
 on the heart, rather than upon the vessels, as with the other 
 preparations mentioned. 
 
 In a personal communication the author learned from 
 Beebe that he has recently isolated a substance from the 
 thyroid gland which has a valuable reducing action on 
 blood-pressure. This substance has not yet been named, 
 but has been used clinically by Beebe m a number of 
 cases of hypertension with good results, although nothing 
 definite regarding the characteristics and mode of action 
 of this depressor thyroid hormone have yet been pub- 
 lished. He mentioned a case in which the blood-pressure 
 was persistently near 200 millimetres Hg., and by small
 
 202 Practical Hormone Therapy 
 
 daily doses of this " X-substance '''' it has been reduced 
 to 150 milHmetres, and is kept there by occasional in- 
 jections of this preparation. At present it does not 
 appear that this substance has any of the other character- 
 istics of thyroid extract, but is evidently one of a number 
 of the active principles of the thyroid gland which are 
 known to be present, but extremely difficult to isolate. 
 
 The reduction of excessive blood-pressure by means 
 of animal preparations is not at all an easy matter, such 
 as is, for example, the increase of blood-pressure — e.g., 
 with pituilrin — and Beebe's discovery bids fair to add 
 another extremely important hormone preparation to 
 the present list. 
 
 Nervous Disorders and their Treatment with Thyroid 
 Extract. — The frequent occurrence of disturbances of the 
 nervous equilibrium in patients sufiering from thyroid 
 disorders has stimulated much speculation as to the rela- 
 tion of certain nervous and mental disorders to thyroid 
 disease, as well as to the possibilities of thyroid therapy 
 in the treatment of these conditions. We have already 
 seen that thyroid extract has an influence for good upon 
 the mental backwardness of certain individuals, whether 
 suffering from an obvious hypothyroidism or with the 
 minor and usually overlooked deficiency. It seems that 
 considerable benefit may accrue from a course of thyroid 
 therapy in certain forms of insanity in adolescence and 
 the climateric. In some mysterious manner a stimulus 
 is given which often leads to considerable amelioration 
 and even ultimate recovery. In many hospitals for the 
 insane thyroid extract is an important remedy, although 
 in organic diseases it must needs be of very limited value. 
 These facts, however, should lead us the more thoroughly 
 to consider the manifestations of thyroid activity in 
 patients suffering from mental and nervous disorders,
 
 Thyroid Therapy 203 
 
 and wherever the least connection can be made between 
 thyroid disorder and the disturbance in question, careful 
 and judicious attempts should be made to influence the 
 conditions by means of thyroid therapy. 
 
 Nutrition and Developmental Disorders in Children. — 
 Since many of the disorders of growth are, as we have 
 seen, due to defective thyroid activity, we must expect 
 to find m the literature frequent references to the value 
 of thyroid preparations in developmental disturbances, 
 and this is decidedly the case , for there are a large number 
 of references to numerous phases of its usefulness in this 
 branch of medicine.* 
 
 In defective mental and physical development thyroid 
 extract has been used with surprisingly good results both 
 alone and associated with other synergistic drugs or 
 animal extracts. In rickets, and occasionally in osteo- 
 malacia, it has been used with varymg results, and there 
 are numerous references to its value in the treatment of 
 Mongolism, cryptorchism, infantilism, and other dis- 
 turbances of growth and development, which may not 
 necessarily be due to an obvious thyroid deficiency or 
 myxoedema. 
 
 Another common disorder of children — nocturnal in- 
 continence — in some indefinable way is very often favour- 
 ably affected by this treatment. Leonard Williams^^ and 
 Hertoghe were the first to make this important applica- 
 tion of thyroid therapy, and report some very interesting 
 cases in which the results can only be attributed to this 
 medication since otheL- methods had been tried and proved 
 
 * The bibliographic references in this chapter are very superficial and far 
 from complete. So many books and monographs are devoted to this phase 
 of organotherapy, most of which have extensive bibliographies, that it seems 
 unnecessary to take the time or space to do more than connect the essential 
 statements which are the basis of this chapter with the original literature on 
 the various subjects.
 
 204 Practical Hormone Therapy 
 
 futile. The dose suggested is ^ grain (003 gramme) 
 twice daily for a child from two to six years, and 1 grain 
 (0065 gramme) twice daily for a child from ten to thirteen. 
 In younger children | grain is suggested. Ordinarily the 
 condition should be relieved in a week's treatment, but 
 if it proves refractory, it may be alternated with a short 
 course of calomel in ^\j-grsbm (0-0065 gramme) doses. 
 This work has been frequently confirmed in the literature 
 of the last two or three years, although as yet there seems 
 to be no definite explanation of the mode of action of the 
 extract in this particular disorder. 
 
 The Newer Conceptions of Graves's Disease. — For a 
 number of years exophthalmic goitre has been considered 
 to be a disease of hyperthyroidism, and doubtless in some 
 degree it is; but this conception is changing, and at 
 present it is believed that Graves's disease can no longer 
 be regarded as a simple hyperthyroidism On the con- 
 trary, evidence is accumulatmg to establish the view that 
 the function of the thyroid gland in this disease has been 
 perverted, and hence, instead of classing it as hyper- 
 thyroidism, it should rather be called " dysthyroidism," 
 provided this term is used to indicate a change in the 
 proportion of the various constituents of the secretion. 
 Klose^'^ has shown that injections of extracts of thyroids 
 taken from cases with Graves's disease cause symptoms 
 very different from those which are produced by the 
 preparations of normal gland. 
 
 It is a little beyond the intentions of the present author 
 to attempt to consider a subject of such complexity in 
 other than a very perfunctory manner, and reference is 
 made to it only to call attention to the importance that 
 the hormones play in the causation and control of 
 this disease. It is well to know how to attempt to 
 control conditions of hyperf unction of the endocrinous
 
 Thyroid Therapy 205 
 
 organs.* There are certain drugs which are said to have a 
 neutralizing effect upon the thyroid secretion. Principal 
 among these are hydrobromate of quhiine, the salicylates, 
 and aspirin. The so-called " neutral hydrobromate of 
 quinine " seems to be best tolerated. 
 
 On general principles the X ray has been used, since 
 its influence very materially retards the activity of the 
 ductless glands exposed to it. The thymus gland having 
 been frequently found enlarged or persistent during 
 exophthalmic goitre has been considered to produce a 
 substance which is antagonistic to the thyroid secretion, 
 and is still used in the treatment of Graves's disease (see 
 Chapter XV.). 
 
 Extracts of the thyroid gland itself have been used in 
 both stages of this disease: in the condition of hyper- 
 thyroidism to diminish the need for the compensatory 
 increase in the size and activity of the gland, and in the 
 stage of hypothyroidism to supplement, in a degree, the 
 diminished secretion. Leonard Williams,^^ referring to 
 this subject, writes: " If I were to be asked if I had any 
 confidence in any drug treatment of Graves's disease, 
 I would reply in the affirmative. I believe in calcium 
 chloride and in thyroid extract ; the former in large doses, 
 the latter in small doses. The calcium seems to give the 
 thyroid something to do, and diverts its exuberant activi- 
 ties from undesirable channels into those which are 
 harmless. The thyroid seems to readjust the broken 
 equilibrium, but to do this it must be given in very small 
 doses." He also adds: "If I can assert anything in 
 connection with the thyroid with any degree of dog- 
 matism, it is that Graves's disease is not due to a simple 
 excess of thyroid secretion. That the thyroid is pro- 
 
 ♦ A further consideration of the subject of "The Control of Hyperen- 
 docrinism" will be found in Chapter XXXI.
 
 206 Practical Hormone Therapy 
 
 foundly disturbed in this condition is obvious enough, 
 but in almost every case there are symptoms of thyroid 
 insufficiency." 
 
 Several preparations for the treatment of Graves's 
 disease have been made from thyroidectomized animals. 
 Preparations of the blood of such animals have been used 
 since 1884 with varying results. Principal among the 
 more recent of these preparations are antithyroidin 
 (Moebius), hemato-ethyroidine, and thyroidectin, 
 
 Beebe has evolved a valuable method of treating hyper- 
 thyroidism by means of an antiserum produced by in- 
 oculating a th3rfoid preparation into rabbits and sheep. 
 Further information regarding the details of this treat- 
 ment may be found in his book.* Its value has been 
 demonstrated in more than three thousand cases, and a 
 number of very good results have been obtained. 
 
 The administration of all preparations, irrespective 
 of their source and connection with other measures, is 
 rarely followed by uniform results. Sometimes the in- 
 fluence upon the conditions is good; as often it is in- 
 different. It seems, however, that while surgery has 
 undoubtedly been beneficial in the treatment of Graves's 
 disease, the eventual successful treatment will depend 
 upon hormone influences, and be available through prep- 
 arations or combinations of animal origin, regarding 
 which we are just beginning to classify om loiowledge. 
 
 Thyroid Preparations and their Administration. — 
 Naturally there are a large number of preparations of 
 thyroid gland upon the market, and it is quite impossible 
 to refer to all of them. Preparations are now official in 
 the majority of pharmacopoeias, and information re- 
 gardmg these may be found in any standard work of 
 pharmacology and therapeutics. ^^ 
 
 * ' ' The Diseases of the Ductless Glands." (See list of bookg ia Appendix. )
 
 Thyroid Therapy 207 
 
 The standardized dried and powdered preparations, pre- 
 ferably in tablet form, are most convenient, and, in spite 
 of numerous excellent proprietary preparations, constitute 
 the major part of the thjo^oid extract at present used. 
 
 Among the proprietary preparations worthy of mention 
 are iodothyrin, a preparation brought out by Baumann 
 (who was the first to discover the importance of the 
 iodine content of thyroid extract). It has been spoken 
 of very favourably, but its therapeutic action is hardly 
 that which has been attributed to it, and often, for some 
 unexplained reason, it is less active and not so well 
 tolerated as the ordinary desiccated powder. Thyro- 
 protein is one of the best preparations, and is prepared 
 according to the method of Beebe,^^ which is briefly as 
 follows: "The glands are separated from all extraneous 
 tissue, ground up, and extracted with normal saline solu- 
 tion, which has been made slightly alkaline. It is then 
 filtered, heated, and the thyroid nucleoprotein is pre- 
 cipitated with acetic acid. The supernatant liquid is 
 then separated by decanting and half-saturated with 
 ammonium sulphate, to throw down the thyroglobulin, 
 which, according to Beebe, corresponds approximately 
 to the colloid, or fully formed normal thyroid secretion. 
 These two precipitates — the nucleoproteid and the globu- 
 lin — may be dried and prepared in tablet form, or re- 
 dissolved and used for hypodermic administration. 
 Thyroprotein is a mixture of these two substances 
 standardized to represent 0-33 per cent, of iodine per 
 gramme of fresh gland. The dosage of this preparation 
 differs from that of the usual extract. Tablets of different 
 strengths are prepared. A " 1 per cent, tablet " indicates 
 that there is 1 per cent, of the active material in the 
 tablet — i.e., -^ grain in a 2-grain tablet, or „V grain 
 in a 5-grain tablet. This is a standard dose, and is used
 
 208 Practical Hormone Tliera^py 
 
 with exactly the same indications and precautions as 
 ordinary thyroid extract; and it has the advantage that 
 it contains the physiologically active portion of the 
 thyroid without the toxic and deleterious substances 
 which are present in the dried extract. 
 
 Another preparation of this character is called thyra- 
 loxine, which is the usual dry thyroid extract deprived 
 of its lipoids, peptones, and bases by extraction and auto- 
 lysis. It is said to be one of the most active, and at the 
 same time harmless, preparations, and that its adminis- 
 tration may be " pushed " without the symptoms of 
 hyperthyroidism which would follow similar doses of the 
 ordinary extract. 
 
 Since thyroid therapy has become a comparatively 
 common procedure, there have, unfortunately, crept into 
 the market preparations which are variable and at times 
 inert. It is difficult to detect such preparations by 
 their appearance, and the only way to be sure of getting 
 a good preparation is to see that the name on the bottle 
 is a good one. As we have learned, Osborne hints that 
 a little iodine will render the negative preparations active. 
 It would seem, however, better to secure as perfect a 
 preparation as possible. 
 
 Pluriglandular Combinations. — Clinical experience with 
 minute doses of thyroid extract, given in conjunction with 
 extracts from other glands, leads to the supposition that 
 it materially enhances their action. This connection does 
 not necessarily have to be a synergistic one, for Bandler ^^ 
 of New York reports that ovarian extract may be ad- 
 vantageously combined with thyroid, especially when used 
 to promote metabolism and encourage oxidation. He 
 incidentally noted that the annoying symptoms occa- 
 sionally produced by thyroid medication are often greatly 
 diminished by the addition of ovarian extract.
 
 Thyroid Therapy 209 
 
 It has been suggested that thyroid extract stimulates 
 the resistance of the system to certain drugs which may 
 be given concomitantly with it. It is at least true that 
 the influence of pluriglandular extracts, of which the 
 small doses of thyroid extract constitute a part (see 
 Chapter XXX.), increases the general reactive powers of 
 the system in a manner which renders them more sus- 
 ceptible and responsive to therapeutic procedures, both 
 medicinally and otherwise. The empirical use of thjn^oid 
 and other hormone combinations, while essentially 
 " medication in the dark," has undoubtedly justified itself 
 m the hands of many physicians, and further reference to 
 this subject will be found in the chapter devoted to the 
 application of pluriglandular extracts. 
 
 Heinrich Stern^° writes mterestingly on the numerous 
 untoward effects that may result from the administration 
 of thyroid, and suggests how to obviate them. He has 
 also suggested a combination of thyroid extract, f grain; 
 epinephrine, gL grain; and sodium cacodylate, -^^ gram, 
 as especially suitable for the treatment of alopecia, as he 
 supposes defective growth of the hair to be a symptom 
 of hypothyroidism. Strangely enough this same com- 
 bination has been also used by him m the treatment 
 of interstitial gingivitis. He believes that the adrenal 
 content of this preparation serves as an antidote against 
 certain of the thyroid toxins. 
 
 The Contra - Indications to Thyroid Therapy. — There 
 seems to be a general consensus of opmion that pul- 
 monary tuberculosis is a definite contra-indication to the 
 administration of thyi'oid extract. All are not agreed on 
 this point, however, and while the use of thjrroid extract 
 in tuberculous cretins is manifestly not contra-mdicated, 
 it may be used with extreme care in patients known to 
 be suffering from tuberculosis. 
 
 14
 
 210 Practical Hormone Theraj^y 
 
 Obviously the symptom complex of hyperthyroidism 
 is a partial contra-iiidication to thyroid therapy, and 
 tachycardia, extreme irritability, and nervousness should 
 be a warning to exercise extreme care if it seems neces- 
 sary to resort thereto. It has been said, however para- 
 doxical it may seem, that thyroid extract may be used 
 with advantage m some cases of Graves's disease. Natur- 
 ally the commencement of the treatment is made with 
 extremely small doses. 
 
 C41ycosuria and diabetes mellitus constitute another 
 mdication for special care in the administration of thja^oid 
 extract, and m some cases a direct contra-indication 
 against its use. It will be remembered that the thyroid 
 antagonizes the pancreas, and while the influence of 
 thyroid extract upon the sugar elimination in diabetes is 
 not nearly so marked and persistent as that of adrenal 
 preparations, there is no doubt that thyroid extracts may 
 be detrimental in this disease. Garnier and Schulmann^^ 
 have shown that this action may be very marked. An 
 experimental adrenal glycosuria, m which the amount of 
 sugar m the urine amounted to 2' 96 grammes, was in- 
 creased to 5- 13 grammes when a double dose of thjToid 
 extract was injected simultaneously with the adrenaline. 
 
 The Indiscriminate Use of Thyroid Preparations. — By 
 far the most important contra-indication to thyroid 
 therapy is its mdiscriminate admmistration m numerous 
 serious or msignificant conditions without careful medical 
 supervision. More particularly does this apply to the 
 treatment of obesity, which, while favourably mfluenced 
 by judicious thyroid therapy, is as often a means of com- 
 plicating matters because of the much more extended 
 influence of the thyroid extract than upon fat metabolism 
 alone. Thyroid' extract is far from being a home remedy, 
 and to gain the best results, its administration requires
 
 Thyroid Therapy 211 
 
 even more skill and attention than many physicians at 
 present give to it. 
 
 Dosage of Thyroid Preparations. — Thyroid prepara- 
 tions are not harmless, and improper dosage can cause 
 considerable inconvenience, and even organic disease. 
 There has been a tendency to use larger doses than 
 necessary, but in the last five years very frequent refer- 
 ences have been made to the necessity of using small doses. 
 
 Since practically all thyroid products of reputable 
 manufacturers are standardized to contain a minimum 
 of 02 per cent, of iodine, the dosage usually can be easily 
 gauged. Of the standard preparations the maximum 
 initial dosage should be \ grain (003 gramme), and, 
 depending upon the circumstances, this dose may with 
 advantage be reduced to as little as -^jj grain (0-00 3 
 gramme), or increased to 1 grain (0-065 gi-amme), or 
 \\ grains (0- 1 gramme) given from two to four times a day. 
 
 Apparently insignificant initial doses of thyroid extract 
 are often sufficient to produce the desired favourable 
 effects, and it is much better to give small doses for a 
 longer period than a few large ones. 
 
 Leopold Levi^'^ has suggested a standard treatment 
 consisting of 10 centigrammes (1| grains) of desiccated 
 thyroid daily, and advises the administration of this dose 
 for ten days, followed by five days without the drug. 
 Occasionally he gives twice this dose every other day. 
 In cases of decided hypothyroidism or myxoedema the 
 dose must be made to fit the conditions, as with every 
 other organotherapeutic preparation. 
 
 Leonard Williams,^*' in this connection, emphasizes 
 the need for small doses. He says: " Doses of 15 grains 
 a day or even 5 grains a day, apart from any mischief 
 that they may work, will defeat their own purpose, for 
 this peculiar principle is quite established in my mind
 
 212 Practical Hormone Therapy 
 
 that you can produce the symptoms of thyroid in- 
 sufficiency by overdoses of thyroid extract." 
 
 Overdosage of thyroid extract is shown by a slight 
 rise in the temperature, and an increase in the pulse-rate, 
 and later by dizziness, headache, nausea, occasional 
 tremors in the fingers, and a general feelmg of restlessness. 
 Such signs indicate a complete stoppage of the treatment 
 for some days. It has been suggested that the coincident 
 administration of arsenic reduces the possibilities of in- 
 convenience from thyroidism. 
 
 In myxoedema and cretinism the dosage necessarily 
 varies. Enough of the substance must be given to control 
 the cretm manifestations and to replace the missing secre- 
 tion. In some cases 5 grains of the extract daily suffices, 
 in others as much as 15 or 20 grains needs to be given. 
 The original case first treated in England by Murray is 
 still alive and continuing her thyroid medication. Recently 
 he referred to this case, and writes^^- " Xhe condition of 
 health is bemg maintained by a dose of 10 minims of 
 liquid thyroid extract each weekday, or 6A ounces in the 
 course of a year. Less than a gallon of thyroid extract 
 in all has therefore maintamed her in health for twenty- 
 two years. No variation of the dose has been found 
 necessary. In some cases the best results can only be 
 obtained by adjusting the dose from time to time accord- 
 ing to physiological requirements, in a manner which 
 some patients learn to do accurately for themselves." 
 
 BIBLIOGRAPHY 
 
 1 Vincent:* pp. 283-286. 
 
 2 ScHAFER (E. A.): Life: its nature, origin, and maintenance, 
 
 Lancet (London), 1912, ii, 675. 
 
 3 Murray (G. R.): The therapeutic value of hormones, Proc. 
 
 Boij. SoG. Med. (Sec. Ther.), 1914, vii, 23.
 
 Thyroid Therapy 213 
 
 * SiEGMUND (A.): Grundsatze und Grenzen der Behandlung mit 
 
 Thyreoidin und andern Organstoffen, Wien. med. Wchnsclir., 
 
 1912, Ixii, 1614. 
 ^ HosKiNS (E. G.): The interrelation of the organs of internal 
 
 secretion, Am. J. Med. Sci. (Philadelphia), 1911, cxlii, 374. 
 ^^ Hertoghe (E.): Del'hypothyroidie benigne chronique ou myx- 
 
 cedeme fruste, Bull. Acad. toy. d. med. Belg. (Brussels), 1899, 
 
 xiii, 231 ; see also id., Le myxcedeme franc et le myxcedeme 
 
 fruste de I'enfance, Nouv. Icon. d. I, Saltp. (Paris), 1900, xiii, 
 
 411. 
 ^ Osborne (0. T.): Some common types of hyposecretion of the 
 
 thyroid, J. Am. Med. Assn. (Chicago), 1912, lix, 1618. 
 ' Murray (G. R.): Note on the treatment of myx oedema by 
 
 hypodermic injections of an extract of the thyroid gland of 
 
 a sheep, Br. Med. J. (London), 1891, ii, 796. 
 ^^ Hertig (A.): Die therapeutische Verwendung des Schild- 
 
 driisen-Extractes, Wien. med. Bl., 1891, xiv, 672. 
 ^ Gley (E.): Surles fonctions du corps thyroide, C. r. Soc. Biol. 
 
 (Paris), 1891, xlviii, 841; see also Arch. d. Physiol. (Paris), 
 
 1892, xxix, 311. 
 ^ Vassale (G.): Intorno agli effetti dell' iniezione intravenosa di 
 
 succo di tiroide nei cani operati di estirpazione della tiroide, 
 
 Biv. sper. d. freniat. (Reg. Emilia), 1890, xvi, 439. 
 ^° Hertoghe (E.): No uveli es recherches surles arrets de croissance 
 
 et I'infantilisme, Bull. Acad. roy. d. med. Belg. (Brussels), 
 
 1897, xi, 750. 
 103 Verriest (M.) : Rapport de la commission que a 6t6 oharg^e 
 
 d' examiner la communication par M. le Dr. Hertoghe d'Anvers, 
 
 intitule : De I'liypo-thyroidie benigne chronique ou mj'xoedeme 
 fruste, 1899, xiii, 196. 
 ^^ Sajous:* vol. i, p. 148; see also id.. The antitoxic functions 
 
 of the thyroid in the pathogenesis and treatment of goitre. 
 
 Mo. Cyc. and Med. Bull. (Philadelphia), 1914, vii, 4. 
 ^2 Langmead (F.): Alimentary toxaemia in relation to the thyroid 
 
 gland. Lancet (London), 1913, i, 1312. 
 ^3 Slosse (A.) : Etudes sur le m^tabolisme normal et pathologique: 
 
 Une nouvelle fonction thyroidienne. Bull. Acad. roy. d. 
 
 Med. d. Belg. (Brussels), 1913, xxvii, 697. 
 1* AuBERTiN (C.) AND Pascarno (A.): Lcsions thyroidiennes dans 
 
 le rheumatisme chronique, Br. med. (Paris), 1913, xxi, 785. 
 15 Editorial: The thyroid gland and chronic rheumatism, N. Y. 
 
 Med. J., 1913, xcviii, 826. 
 1^ Noble (C. P.): Discussion in symposium on organotherapy. 
 
 Am. J. Obs. (New York), 1912, Ixvi, 645. 
 "^ Levi (L.) and de Rothschild (H.):* "La Petite InsufiQsance 
 
 Thyroidienne" (Paris), 1913, pp. 179-191. 
 1^ Morris (M.): The internal secretions in relation to derma- 
 tology; Br. Med. J., 1913, i, 1037.
 
 214 Practical Hormone Therapy 
 
 ^^ Gilbert (A.): La retraction de I'aponevrose palmaire et le 
 traitement thyroidien, Bull, de VAcad. d. Med. (Paris), 1913, 
 Ixix, 23. 
 
 20 Editorial: The thyroid treatment of Dupuytren's contraction, 
 
 Br. Med. J. (London), 1913, i, 1041. 
 
 21 Blair Bell (W.): The relation of the internal secretions to the 
 
 female characteristics, Proc. Boy. Soc. Med. (Sec. Obs.) 
 (London), 1913, vi, 47. 
 
 22 Thompson (W. M.): The influence of the thyroid gland on 
 
 pregnancy and lactation, Surg. Gyn. and Ohs. (Chicago), 
 1913, xvii, 226. 
 
 23 Dalche (P.): Les dy8m6norrh6es dites essentielles et leur 
 
 traitement, Progr. Med. (Paris), 1913, xxix, 329; see also 
 id., Bev. mens. d. Gyn. et d'Obs. (Paris), 1913, viii, 641. 
 2'* Williams (L.): Adenoids, nocturnal enuresis, and the thyroid 
 gland, Lancet (London), 1909, i, 1245; see also id., Br. J. 
 Child. Bis. (London), 1909, vi, 241. 
 
 25 Klose (H.) AND Lampe (A. E.) : Zur experimentellen Erzeugung 
 
 des Morbus Basedowii, Centr. f. Chir. (Leipzig), 1912, xxxix, 
 641. 
 
 26 Williams (L.): Discussion on the therapeutic action of hor- 
 
 mones, Proc. Boy. Soc. Med. (Sec. Ther.), (London), 1914, 
 vii, 32. 
 " Sajous (C. E. de M.): The thyroid preparations in practice, 
 3Io. Cyc. and Med. Bull. (Philadelphia), 1909, ii, 83. 
 
 28 Eeebe (S. p.): Glandular therapy. In Hare's " Modern Treat- 
 
 ment " (Philadelphia), i, 554. 
 
 29 Bandler (S.W.): The therapeutic differential diagnosis of con- 
 
 stitutional dysmenorrhoea, ArcJi. Diag. (Xevv York), 1913, 
 vi, 5. 
 3'' Stern (H.): Untoward effects of thyroid medication and how 
 to forego them, Amer. Med. (New York), 1910, v, 11. 
 
 31 Garnier (M.) AND ScHULMANN (E.): Actiou de I'extrait 
 
 thyroidien sur la glycosurie adr6nalinique, G. r. Soc. Biol. 
 (Paris), 1914, Ixxvi, 287. 
 
 32 Murray (G. E,.): Some aspects of internal secretion in disease, 
 
 Br. Med. J. (London), 1913, ii, 157, 212.
 
 CHAPTER XIV 
 
 THE CURATIVE PROPERTIES OF PARATHYROID 
 EXTRACTS 
 
 The Parathyroid Hormone — The Detoxicating Powers of the 
 Parathyroids — The Relation between the Thyroid and the 
 Parathyroids — The Influence of the Parathyroids on Calcium 
 Metabolism — Calcium in Cellular Hyperexcitability — Para- 
 thyroid Therapeutics — The Treatment of Paralysis Agitans 
 — Puerperal Eclampsia — A Parathyroid Element in Epilepsy 
 — Tetany — Other Uses of Parathyroidine — Combining Para- 
 thyroid with Other Glandular Extracts — Dosage and Ad- 
 ministration. 
 
 From the standpoint of anatomy, the parathyroid 
 glands are, perhaps, the most insignificant of all the 
 organs of internal secretion, yet it is no exaggeration to 
 say that their hormone influence is comparatively greater 
 than that of any other of the endocrinous organs. Their 
 influence in physiology and the possibilities of their 
 therapeutic value have only recently been considered; 
 and this is not to be wondered at when we recall the 
 ignorance of the whole subject of glandular therapeutics, 
 say, twenty years ago. As a matter of fact, this set of 
 organs was entirely overlooked until Sandstrom^ of 
 Upsala discovered them in 1880. Even this important 
 discovery was incomplete, for he had only found the pair 
 now termed the " external parathjrroids," and it remained 
 for Kohn^ to locate and describe the so-called " internal 
 parathyroids " fifteen years later. These glandules are 
 occasionally called the "epithelial bodies," the name 
 
 215
 
 216 Practical Hormone Therapy 
 
 being a translation of the German term used to designate 
 the parathyroids. 
 
 Of the numerous experiments in which two, three, or 
 the whole of these glands were removed, and the resulting 
 disturbances, of the physiologic relation between the 
 parathyroids and other glands, and whether their removal 
 is followed by a compensatory hypertrophy elsewhere, we 
 can only briefly wTite. It forms the basis of a most ex- 
 tensive hterature, and since it does not strictly concern 
 therapeutics, it must be passed over, although, of course, 
 all the facts thus established are concerned in the ground- 
 work of our present knowledge of the therapeutic value 
 of parathjrroid extracts. We are still in the early stages 
 of this special laiowledge, and there is doubtless much 
 more to be learned which will prove of eminently prac- 
 tical usefulness. It seems quite clear that, in spite of 
 their apparent insignificance, the parathyroids must be 
 considered absolutely essential to life, and that their 
 principal service to the organism lies in their power to 
 destroy certain toxic wastes which seem to have a special 
 predilection for the nervous tissue. It has been experi- 
 mentally shown that these substances produce, by their 
 action as well as by the removal of their benign influence, 
 a series of nervous manifestations, the principal of which 
 is the symptom complex termed " tetany." 
 
 The Parathyroid Hormone. — It is generally agreed that 
 the principal source of the activities of the parathjrroids 
 is a hormone which is distributed by the blood to the 
 appropriate tissues, although it is not impossible that 
 these glandules may produce antitoxic substances which 
 neutralize, attenuate, or destroy products which, if 
 allowed to remain, would be harmful. 
 
 In discussing the chemical activators in his presidential 
 address before the British Association in 1912, Sir E. A.
 
 Curative Properties of Parathyroid Extracts 217 
 
 Schafer^ said: " The case of the parathyroid glandules is 
 still more remarkable. They are four minute bodies, 
 each no larger than a pin's head, embedded in the thyroid. 
 Small as they are, their internal secretion possesses hor- 
 mones which exert a powerful influence upon the nervous 
 system. If they are completely removed, a complex of 
 symptoms, technically known as 'tetany,' is liable to 
 occur, which is always serious, and may be fatal. Like 
 the hormones of the thyroid itself, therefore, those of the 
 parathyroids produce effects on the nervous system, to 
 which they are carried by the blood, although the effects 
 are of a different kind." 
 
 Not only is the parathyroid hormone essential to 
 normal metabolism, but it is available as a therapeutic 
 agent, and, as will shortly be shown, its detoxicative 
 powers make it indeed a most valuable weapon. 
 
 The Detoxicating Powers of the Parathyroids. — It may 
 be that the parathyroid hormone activates certain tissues 
 — as, for instance, the thyroids — to produce antitoxic 
 bodies; or, on the other hand, it may have a direct de- 
 structive action upon these poisonous substances. How- 
 ever this detoxicating action may be accomplished, it is 
 of considerable interest, for upon it is based practically 
 every phase of parathyroid therapy. 
 
 The importance of this factor is emphasized by the 
 recent work of Koch"* in the laboratories of the University 
 of Michigan. He discovered certain toxic bases in the 
 urine of parathjnroidectomized dogs. In every case 
 methylguanidin was found, and, where the amount was 
 smaller than usual, other bases, such as cholin, neurin, 
 etc., were present. 
 
 As a result of his findings, Koch suggests that " the 
 parathyroid internal secretion appears to be concerned 
 also with anabolic processes related to the synthesis of
 
 218 Practical Hormone Tlieraj>y 
 
 nuclear contents." Whether or not such a hypothesis 
 can be further substantiated remains to be seen. In any 
 event, the final isolation of recognized toxic chemical 
 products of traceable origin has paved the way to definite 
 conceptions and specific lines of inquiry, where hitherto 
 the explanations have been vague and the outlook un- 
 promising.^ 
 
 The Relation between the Thyroid and the Parathyroids. 
 — It must be borne in mind that the parathyroids are not 
 connected with the thyroid, certain statements to the 
 contrary notwithstanding. Their similarity in name and 
 their anatomic proximity are liable to be misleading. The 
 parathyroids are quite distinct bodies, differing from their 
 neighbour in origin, structure, and action. It has also 
 been shown that there is a difference in their chemical 
 composition, as, unlike the thyroid and the thymus, they 
 contain no iodine. 
 
 However, there certainly is some connection, just as 
 the other endocrinous organs are related, although there 
 are diffences of opinion on this subject. Gley^ has made 
 some very decided statements to the effect that these 
 organs are physiologically intimate, and states that total 
 thjToidectomy is followed by a compensatory hyper- 
 trophy of the external parathyroids. This position is 
 supported by numerous writers, while Walbaum '^ believes 
 that these glands are antagonists; but Gley has since 
 shown that tetany can be made to disappear by injecting 
 thyroid extract. This position is rendered rather com- 
 plicated, since Gley's deductions are contradicted by 
 Blum, Pfeiffer, and others. 
 
 Jeandelize suggests that, while the thyroid promotes 
 metabolism, the parathyroids co-operate with it only in 
 that they render innocuous the toxic by-products of 
 metabolic activity.
 
 Curative Properties oj Parathyroid Extracts 219 
 
 Moussu^ has consistently declared that the parathyroid 
 function is distinct and different from that of the thyroid, 
 the chief effects of the latter being of a trophic character, 
 while the former are of an antitoxic nature. There is a 
 considerable difference between the cachexia strumipriva 
 which follows thyroidectomy and the condition following 
 parathjnroidectomy. This difference extends to the re- 
 action of the body to parathyroid extracts. Moussu 
 found that the symptoms of th5T.'oidectomy are not con- 
 trolled with parathyroid extract, but that sufficiently 
 large doses of this extract cause the tetany which follows 
 parathyroidectomy completely to disappear. This he 
 considers to be further evidence of the independence of 
 these two organs. 
 
 Rudinger^ seems to have given the most reasonable 
 explanation of the interrelation of the thyi'oid and para- 
 thyroids. He concludes that — (1) Thyroidectomy is 
 followed by parathyroid hypertrophy; but (2) the mani- 
 festations of hyperthjrroidism (exophthalmic goitre) are di- 
 minished by parathyroid treatment, while hypothyroidism 
 (myxoedema) is made worse; (3) tetany follows thyroidec- 
 tomy, but the effects are less marked than those following 
 parathyroidectomy later; and, finally, (4) parathyroidec- 
 tomy is followed by a degree of thyroid hypertrophy. 
 The difference of opinion between experimenters is seem- 
 ingly due to the fact that there may be accessory para- 
 thyroids in the thymus and elsewhere, and the operations 
 have not always accomplished just what was intended. 
 BiedP° writes: " I have found in numerous cases that the 
 removal of the thyroid, together with the internal para- 
 thyroids, is nearly always followed by hypertrophy of the 
 external parathyroids. The hypertrophy is more or less 
 clearly marked according to the length of time after 
 operation. The reason for this seems obvious, and may
 
 220 Practical Hormone Therapy 
 
 be an explanation of the statements preceding. With 
 thjrroidectomy, the hypertrophy of the external pair of 
 glands is Nature's effort to replace the removed internal 
 pair." 
 
 Evidently, then, the intimacy of these glands is estab- 
 lished, although it is equally clear that they are only 
 associated and not actually connected in any way. 
 
 The Influence of the Parathyroids on Calcium Metab- 
 olism. — There seems to be an intimate connection be- 
 tween the whole of the endocrinous system and the 
 metabolism of calcium salts. Elsewhere several facts 
 have been recorded to substantiate this, and here a few 
 words must be said as to the influence of the parathyroids 
 upon this special phase of metabolism. 
 
 MacCallum^^ and his associates have made a special 
 study of this subject, and conclude that the hyper- 
 excitability which is the principal symptom of para- 
 thyroid tetany is produced by the withdrawal of calcium 
 from the cells.* 
 
 This is a partial explanation of the frequency of acidosis 
 in parathyroidectomized animals. Since there is not 
 enough calcium to neutralize the carbamic and other 
 acids, the accumulation results in uraemia, convulsions, etc. 
 
 Calcium in Cellular Hyperexcitability. — Convincing evi- 
 dence of the value of calcium medication is furnished by 
 
 * Ringer and Loeb have sliown the importance of certain of the metallic 
 ions in the maintenance of cellular activity. These elemental substances are 
 an essential and integral part of the cell protoplasm, and a predominance of 
 one or another of these electrolytes materially influences the activity and 
 reactivity of the cells. For example, nerve and muscle cells are stimulated 
 in direct ratio to their sodium content, while calcium exerts a diametrically 
 opposite effect. In other words, the increase of the calcium content of the 
 cell is accompanied by depression, while the diminution of calcium causes an 
 excitability which may reach serious and pathological proportions if the 
 amount of calcium electrolytes is reduced below a certain minimum. 
 
 Williaras^^ considers the relation of the ductless glands to calcium metab- 
 olism in a very lucid address on arterio-sclerosis which is well worth reading 
 in full.
 
 Curative Properties of Parathyroid Extracts 221 
 
 MacCallum and Voegtlin^^, Frouin, and others, who show 
 that injections of solutions of calcium salts into para- 
 thyroidectomized animals very promptly control the 
 manifestations of tetany. Edmunds^'* and others have 
 found that the administration of large doses of calcium 
 prevents the tetanic results of thyro- parathyroidectomy. 
 From this a valuable suggestion may be drawn as to the 
 importance of studying the urinary acidity, the other 
 evidences of acidosis (acetone, etc.), and the calcium con- 
 tent of the blood, in all cases where there is a cellular 
 hyperexcitability, whether supposedly parathyroid in 
 origin or not. The present author's research work with 
 the urinary acid index ^'^ has convinced him of the ex- 
 treme importance of acidsemia in everyday practice, and 
 In the clinical investigation of those suffering from Par- 
 kinson's disease, chorea, epilepsy, or other allied diseases, 
 it will be sm'prising how often the urinary acidity is from 
 200 to 500 per cent, above the normaJ. 
 
 Another point is deserving of mention here. Calcium 
 therapy can often be coupled with the use of animal 
 extracts, and particularly parathyroid extract. This 
 combination is not empirical, and each element is com- 
 plementary to the other. The calcium helps to replace 
 that which has been lost by the cells, which loss, we have 
 seen, is often accompanied by cellular hyperexcitability; 
 while the parathyroid extract, in addition to any direct 
 influence that it may have, favours the re-establishment 
 of the lost calcium balance by the regeneration of the 
 normal parathyroid activity where this is possible. 
 
 Parathyroid Therapeutics.— All the available hterature 
 dealing with the use of parathyroid extract indicates that 
 its value is dependent upon a marked antagonistic action 
 which it seems to exert on certain metabolic toxins. The 
 action of these extracts coincides with the physiologic
 
 222 Practical Hormone Thera'py 
 
 activities of the glands, and has been successfully applied 
 in the treatment of such diseases as tetany, paralysis 
 agitans, hyperthyroidism, eclampsia, epilepsy, chorea, 
 etc. 
 
 The Treatment of Paralysis Agitans.— Berkeley^^ of 
 New York has worked with those extracts for eight or 
 nine years, and his principal study has been their appUca- 
 tion in the treatment of Parkinson's disease. In his 
 latest paper^"^ he states that this form of medication " has 
 wrought a revolution." This writer has brought forward 
 several plausible considerations which indicate that there 
 is a relation between paralysis agitans and parathyroid 
 pathology, and, best of all, he backs them up with numer- 
 ous reports of evidently successful results. 
 
 In as progressive disease as this, it is clear that treat- 
 ment must be persistent in order to be successful. If 
 benefit is found, it manifests itseK just as does the disease 
 itself — slowly and gradually. If small doses — -^ grain 
 of purified parathyroid extract once or twice a day — are 
 given over a period of months, there are good chances of 
 success. The cases reported by Berkeley are convincing, 
 and his experience with a large number of patients, " now 
 well up in the hundreds," shows that benefit has accrued 
 in over 80 per cent. After some weeks, sometimes months, 
 one notices a gradually lessened muscular rigidity and 
 bettered muscular control, diminished pain and tremor, 
 and the abolition of drooling. Often the distressing in- 
 somnia is controlled. This \vriter is most insistent that 
 real parathyroid extracts must be used, and states that 
 "apparently bits of lymph nodes, thymus, accessory, 
 thyroid, and even fat have done duty in many laborious 
 experiments." It seems quite possible that the failures 
 — for, of course, the inevitable failures and depreciations 
 of this method have appeared in the literature — are due
 
 Curative Properties of Parathyroid Extracts 223 
 
 to carelessly prepared and consequently inactive extracts. 
 Berkeley explains his methods of locating the glands, and 
 states his preference for those taken from the ox. 
 
 These interesting statements do not all come from a 
 single source, and Berkeley's treatment is becoming more 
 generally used. Alquier^^ has made several communica- 
 tions in which he tells of the good effects of this method 
 of treatment. It seems that, contemporaneously with 
 Berkeley, Lundborg^^ was studying this subject in Sweden. 
 He came to the conclusion that paralysis agitans and the 
 other motor neuroses — Thomsen's disease and myoclonia 
 — are due to hypoparathyroidism. 
 
 It seems as though the parathyroid treatment of Par- 
 kinson's disease has a sound physiologic basis, and is 
 rational and deserving of the study of and clinical applica- 
 tion by the profession generally. 
 
 Puerperal Eclampsia. — Several investigators have ap- 
 plied the fundamentals of parathyroid therapy in the 
 treatment of other severe toxic states. Vassale^^ of Turin 
 lays stress upon the value of this medication in puerperal 
 eclampsia. In certain cases this treatment has controlled 
 the convulsions, and Vassale inclines to the idea that 
 there may be a parathyroid origin of eclampsia. His 
 results have warranted a belief that large doses of para- 
 thyroid extract are useful in eclampsia in the same ratio 
 as thyroid extract is useful in myxoedema. This is a 
 sanguine view, but not to be dismissed on that account. 
 In his researches Vassale makes formal distinctions be- 
 tween the antitoxic functions of the parathyroids and 
 those of the thyroid. He calls attention to the fact that 
 parathyroid insufhciency may be congenital, and may 
 also follow pathologic processes in these glandules. It 
 seems that this insufficiency is quite compatible with 
 ordinary existence, but, should there come an incident —
 
 224 Practical Hormone Therapy 
 
 as, for example, obesity, accouchement, chronic eczema, 
 etc. — the convulsive phenomena somewhat similar to 
 tetany promptly appear. There is no doubt that very 
 slight straws are sufficient " to break the camel's back," 
 and others have shown that seemingly slight pathologic 
 changes in the parathyroids are not infrequently found in 
 patients dying with tetany, paralysis agitans, eclampsia, 
 etc. 
 
 A Possible Parathyroid Element in Epilepsy.— Vassale 
 suggests that the other convulsive conditions not infre- 
 quently met with in general practice may all be asso- 
 ciated with parathyroid insufficiency, and gives weight 
 to his contention by reporting two cases of epilepsy which 
 were controlled by this form of medication. This was 
 apparently first suggested by MacCallum^^ of New York, 
 who in 1903 intimated that there might be a connection 
 between parathyroid disorder and epilepsy. Naame gives 
 his conception of epilepsy as a disorder due to organic 
 hypoparathyroidism. Perhaps this might be better 
 termed a " parathyroid dystrophy," since this writer's idea 
 is that in epilepsy the parathyroids do not accomphsh 
 their antitoxic function, and that certain metabolic 
 poisons, \Ahich electively influence the nervous system, 
 are allowed to accumulate until a violent reaction to their 
 presence is brought about — the seizure which is pathogno- 
 monic of epilepsy. His theory is very interesting, and he 
 reports having put it into practice in numerous cases over 
 a period of some years with most encouraging results. A 
 resume of his paper^^ is worthy of a place here : 
 
 There can be no doubt that the manifestations of 
 epilepsy are of a toxic nature. The atonic and tonic 
 convulsions of the crises, the rise in temperature often 
 noted at these times, the frequent and severe headaches, 
 and the profound prostration, all point to this. Naame
 
 Curative Properties of Parathyroid Extracts 225 
 
 suggests that the parathyroids, because of an intermittent 
 disabihty {''claudication intermittent'"), are unable to 
 detoxicate the system. Bearing in mind the secretory 
 antagonisms of the gonads and parathyroids, we see a 
 possible reason for the frequency of epilepsy at puberty. 
 There is indubitable evidence that there is a relation 
 between epileptic crises and the genital functions. Fits 
 are intensified at the menstrual periods, and, on the other 
 hand, are considerably diminished during pregnancy. 
 The prescription that Naame suggests is as follows : 
 
 Parathyroid extract ... ... ,. 0"03 gramme 
 
 Thyroidine ... ... ... ... 0-003 
 
 Sacch.-lact. ad. ... ... ... ... 0*10 ,, 
 
 M. ft. One cachet. Administer during the seizure, or, preferably, the 
 premonitory symptoms, two or four daily. 
 
 " Under the influence of this treatment," continues this 
 writer, " I state it definitely, in the cases which I have 
 watched in patients whose age is over twenty, the crises 
 are rapidly suppressed and reduced to a simple vertigo. 
 They become rare and benign, without incontinence of 
 urine or tongue-biting, and neither headache nor prostra- 
 tion follows. Further, the humour of the epileptic 
 changes. He enjoys life, his memory is better, and his 
 intelligence clearer." 
 
 Does this apply to all forms of epilepsy ? It is not 
 likely. Naame proceeds: "After having eliminated 
 traumatic epilepsy and that which is a sequel of menin- 
 gitis, I will say that the epileptic who observes the rules 
 of hygiene and submits himself methodically to the treat- 
 ment given above, should not have fits — that is to say, 
 he can be functionally cured. As far as an anatomical 
 cure is concerned, it is conditional. If the parathyroid 
 lesions are definite and of long standing, the reparative 
 process may not be fully accomplished, and a degree of 
 
 15
 
 226 Practical Hormone Therapy 
 
 parathyroid insufficiency will remain. But if the epilepsy 
 is recent, and not severe, the glands may respond to the 
 treatment, and perhaps return to a quasi-normal anatomic 
 condition, especially if the treatment is patiently con- 
 tinued." 
 
 Tetany, whether post- operative or epidemic, is now 
 considered to be the result of parathyroid insufficiency, 
 and the results of the parathyroid treatment of the tetany 
 of parathyroidectomized animals have been usually deci- 
 sive. Several reports laud this method, but, fortunately, 
 the disease is so rare that opportunity to test the treat- 
 ment is not often obtained. It seems that parathyroid 
 extract should always be added to the sedation, hydro- 
 therapy, and rest, which constitute the usual treatment 
 recommended for this disorder. 
 
 Other Uses of Parathyroidine. — A number of other re- 
 ports of the efficiency of the parathjrroid treatment are to 
 be found. The majority of these are of Italian origin, 
 doubtless due to the fact that practically the only Euro- 
 pean preparation is the paratiroidina of Vassale. Chi- 
 dichimo^^ records his experiences with this preparation. 
 Simonini reports having secured favourable results in the 
 treatment of five cases of chorea, and praises this method. 
 More recently Meriggio^^ has contributed a lengthy out- 
 line of his experiences with parathyroidine (Vassale). 
 He used it in eclampsia, chorea, uraemia, and toxic states 
 which were accompanied by convulsive seizures. Many 
 of his experiences with it were encouraging. Salvioli and 
 Carraro^ also discuss the action and clinical possibilities 
 of this treatment. 
 
 Combining Parathyroid with other Glandular Extracts. — 
 Attempts have been made to reinforce parathyroid extract 
 with other endocrinous substances, on the admittedly 
 sound theory that there are distinct synergisms and
 
 Curative Properties of Parathyroid Extracts 227 
 
 antagonisms among the hormones. Naame has recom- 
 mended the addition of small doses of thyroidine in 
 epilepsy [q.v.), while Berkeley impresses the fact that 
 thyroid extracts are distinctly contra-indicated in Parkin- 
 son's disease, and hints that failures in the application of 
 his parathyroid treatment may not only be due to inactive 
 preparations, but that thyroid extract may aggravate the 
 conditions. This same author found that the pancreatic, 
 duodenal, and adrenal hormones do not synergize with 
 the parathyroid — at least, in the treatment of paralysis 
 agitans — but that pineal extract, so far, seems to have 
 produced "relatively happy results." 
 
 Bearing in mind the presumed physiologic action of the 
 parathyroid hormone — that of detoxication — it would seem 
 that extracts of the liver might be usefully combined. 
 Morel,^® whose work on the physiology of the parathyroids 
 is of a very high character, and whose book^^ is a most 
 interesting resume of the knowledge on this subject, 
 recently outlined certain functional relations between the 
 liver and parathyroids, and in this paper ^^ summarizes 
 these points as follows : As a result of experiment, a close 
 relationship between the parathjrroids and the liver is 
 manifested: (1) Anatomically: After the parathyroidec- 
 tomy the most constant and precocious manifestations 
 are locahzed in the liver. (2) Clinically: The incidents 
 following parathyroidectomy recall those following physio- 
 logic exclusion of the liver. (3) From the biochemical 
 viewpoint parathyroidectomy in the dog causes acidosis, 
 excessive elimination of urinary nitrogen, and di acetic 
 acid, as well as diminished power to utilize dextrose, and 
 carbamic intoxication. (4) From the therapeutic view- 
 point it is shown that hepatic opotherapy — {a) increases 
 (almost doubles) the life of the animal deprived of the 
 parathyi'oids ; (6) diminishes convulsions, anorexia, vomit-
 
 228 Practical Hormone Therapy 
 
 ing, and asthenia, and benefits the general condition; and 
 (c) brings about an abundant diuresis. 
 
 Scliiotz,29 in a study of the relation of the internal 
 secretions to cataract, seems convinced that the para- 
 thjToids may be connected with this disorder. He says : 
 "It has already been established beyond question that 
 parathyroid insufficiency may lead to cataract." This 
 may or may not be the case. At least, it does not seem 
 to be a settled fact so far as the literature is concerned, 
 but it shows possibihties which have not by any means 
 become generally appreciated. And if parathyroid in- 
 sufficiency is a factor in the causation of cataract, may 
 not the use of parathjToid extracts be of possible service 
 in its treatment ? There is yet much to be done in this 
 special field of research. 
 
 Dosage and Administration. — The dosage of parathyroid 
 extract varies very considerably, for, unfortunately, prep- 
 arations are very often inactive. Berkeley's experiences, 
 already referred to, indicate the difficulty of securing an 
 effective preparation. Undoubtedly a share of the in- 
 different results reported must be laid to indifferent prep- 
 arations, but this should not deter the prospective user, 
 for the method is midoubtedly good. Carnot^^ has 
 evidently found that the collection of parathyroids from 
 the abattoirs is no sinecure, and adds; " II est inevitable 
 quHl y ait erreur ou fraude dans leur recolte." 
 
 The dried extract represents approximately one-sixth 
 by weight of the fresh gland. The glands are best 
 secured from the ox, although Hallion^^ beheves the 
 external parathyroids of the horse to be most suitable. 
 In England or America this is not convenient, but, of 
 course, in France and Belgium circumstances are dif- 
 ferent, since horse-meat is an " article de degustation de 
 tous les jours."
 
 Curative Properties of Parathyroid Extracts 229 
 
 The average dose of an active preparation, such as that 
 recommended by Berkeley (made by Perry of New York) 
 is ^ to Jy grain (0-003 to 0-001 gramme) once or twice 
 daily over a long period. In acute cases (eclampsia), 
 2V grain may be given every four hours for four or five 
 doses. Hypodermic preparations are occasionally used, 
 the usual dose being J^ grain. 
 
 Vassale's preparation is in liquid form, each c.c. of 
 which corresponds to 0-01 gramme of fresh substance. 
 The usual dose is 1 to 2 teaspoonfuls (4 to 8 c.c), or a 
 httle less than 1 grain of the fresh gland. 
 
 BIBLIOGRAPHY 
 
 1 Sandstrom (I.): Om en ny Kortel hos Menniskan, Upsala 
 
 Ldkarefor. Farh., 1880, xv, 441. 
 
 2 KoHN (A.): Studien ueber die Schilddriise, Arch. f. miJcroslc. 
 
 Anat. (Bonn), 1895, xliv, 366. 
 
 3 ScHAFER (E. A.): " Life: its Nature, Origin, and Maintenance " 
 
 (London), 1912, p. 30; or Lancet (London), 1912, ii, 675. 
 
 * Koch (W. F.): Toxic bases in urine of parathyroidectomized 
 dogs, J, Biol. Ghem. (Baltimore), 1913, xv, 43. 
 
 s Editorial: Chemical consequences of removal of para- 
 thyroids, J. Am. Med. Assn. (Chicago), 1913, Ixi, 1049. 
 
 ^ Glet (E.): Sur la fonction des glandules parathyroides, C. r. 
 Soc. Biol. (Paris), 1897, xlix, 46. 
 
 ' Walbaum (O.): Untersuchungen ueber die Epithelkorperchen 
 beim Kaninchem, Mitt. a. d. grenz. Med. u. Chir. (Jena), 
 1903, xii, 298. 
 
 ^ Moussu (G.): De la medication parathyroidienne, G. r. Soc. 
 Biol. (Paris), 1899, li, 242. 
 
 ^ RuDiNGER (K.): Physiologie und Pathologie der Epithelkorper- 
 chen, Erg. d. inn. Med. u. Kind. (Leipzig), 1909, ii. 
 1° Biedl:* p. 52. 
 ^1 MacCallum (W. G.): The function of the parathyroid glands, 
 
 J. Am. Med. Assn. (Chicago), 1912, lix, 319. 
 ^2 Williams (L.): On arterio- sclerosis. Lancet (London), 1914, 
 
 i, 815. 
 ^3 MacCallum (W. G.) and Voegtlin (C): On the relation of 
 tetany to the parathyroid glands and to calcium metabolism, 
 J. Exp. Med. (New York), 1909, xi, 118.
 
 230 Practical Hormone Therapy 
 
 ^* Edmunds (W.): Further observations on the thyroid gland, 
 J. Path, and Bact. (Cambridge), 1912, xvi, 481. 
 
 ^^ Harrower (H. E.): A study of the urinary acidity and its 
 relations, Med. Record (New York), 1909, Ixxv, 966; see 
 also id., Acidemia: systemic hypoalkalinity, Med. Brief (St. 
 Louis), 1910, xxxviii, 458. 
 
 1^ Berkeley (W. N.): A brief report of experiences with para- 
 thyroid gland in paralysis agitans, N . Y. Med. J., 1907, 
 Ixxxvi, 974. 
 
 ^^ Id.: The parathyroid treatment of paralysis agitans. Int. 
 Clinics (Philadelphia), 1912, xxii, 4, 1. 
 
 ^^ Alquier (L.): Les parathyroides et la maladie de Parkinson, 
 Bev. d. Neurol. (Paris), 1909, xvii, 934. 
 
 19 LuNDBORG (H.): 1st Myoklonie eine klonische Entitat ? Neur. 
 Centralbl. (Leipzig), 1904, xxiii, 162; see also Deut. Ztsehr. f. 
 NervenJi. (Leipzig), 1904, xxvii, 217. 
 
 2° Vassale (G.): Le traitement de I'^clampsie gravidique par la 
 parathyroidine. Arch. Ital. d. Biol. (Turin), 1905, xliii, 
 177. 
 
 21 MacCallum (W. Gr.): On the physiology and pathology of the 
 
 parathyroid glands, etc., 3Ied. News (Philadelphia), 1903, 
 Ixxxiii, 820. 
 
 22 Naame (— ): "Etudes d'Endocrinologie " (Paris), 1913, 
 
 pp. 46-53. 
 
 23 Chidichimo (F.): La paratiroidina Vassale, Ginecol. (Florence), 
 
 1905, ii, 495. 
 2* Meriggio (Gr.): La paratiroidina Vassale nella corea, nell' 
 
 eclampsia puerperale, e nell' uremia convulsiva da nefrite 
 
 scarlatinosa, Bioch. e terap. sper. (Milan), 1912-13, iv, 
 
 127. 
 25 Salvioli (J. H.) AND Carraro (A.): Ueber die Wirkung der 
 
 Parathyreoidextrakte, Verh. d. deut. path. Gessel. (Jena), 
 
 1912, XV, 264. 
 
 2^ Morel (L.): L'insuffisance parathyroidienne et son traitement, 
 
 Paris Med., 1913, 361. 
 2' Morel:* 
 
 28 Morel (L.): Les relations fonctionelles entre le foie et les 
 
 parathyroides, G. r. Sac. d. Biol. (Paris), 1913, Ixxiv, 28. ' 
 
 29 ScHioTZ (C): Staer og de indre Vaedsker (Cataract and the 
 
 internal secretions), Norsk Mag. f. Lagevid. (Christiania), 
 
 1913, Ixxiv, 9, 1161. 
 
 30 Carnot:* p. 384. 
 
 31 Hallion:* p. 32. 
 
 Munaron (L.): Esperimenti di cura fatti con la paratiroidina, 
 
 PoUcl. (Rome), 1905, xii (P), 974. 
 Walsh (J. J.): Parathyroids in physiology and therapeutics, 
 
 N. Y. Med. J., 1906, Ixxxiv, 1109.
 
 Curative Properties of Parathyroid Extracts 231 
 
 Beebe (S. p.): The parathyroid gland, with demonstrations 
 
 of the effects of hypodermic injections of parathyroid 
 
 nucleoproteid after parathyi'oidectomy, Proc. Soc. Exp. Biol. 
 
 and Med. (New York), 1906, iv, 64. 
 Castaigne (J.), GouRAUD (F. X.), AND Parisot (J.): L'opo- 
 
 th6rapio thymique et parathyroidienne, J. med. frang. 
 
 (Paris), 1912, vi, 129. 
 Greenwald (I.): The supposed relation between paralysis 
 
 agitans and insufficiency of the parathyroid glands, Am. J. 
 
 Med. Sci., 1914, cxlvii, 225.
 
 CHAPTER XV 
 THE THYMUS 
 
 The Function of the Thymus — Is there a Thymus Hormone ? — 
 The Relation of the Thymus to other Endosecretory Glands — 
 The Thymus, Calcium Metabolism and Growth — Thymus 
 Extract in Malnutrition and Delayed Development — The 
 Thymus Treatment of Simple Goitre — Tfie Influence upon 
 Exophthalmic Goitre — The Possibilities of Thymus in 
 Chlorosis — A New Method of Treating Rheumatoid Ar- 
 thritis — Contra-IvdicatioTis. 
 
 The development of the thymus gland in the foetus 
 and early childhood, and its subsequent retrogression and 
 eventual disappearance* in adult life, indicate that the 
 part played by this organ is concerned in the formation 
 of the body. Occasionally the thymus may be divided, 
 and small areas of thymus tissue may be found separated 
 from the principal gland. These " aberrant " glands, 
 however, are not common, 
 
 Pende^ of Palermo believes that he has discovered a 
 hitherto unknown internal secretory gland which he is 
 able to find with ease in new-born puppies. This gland 
 is, of course, small, and lies above the thymus close to 
 
 * Tho majority of physiologists assert that the thymus normally disappears 
 at or soon after puberty. Not all, however, agree with this. Morel^ states 
 tliat in man the thymus is a constant and permanent organ, but that it lias 
 a rapid evolution. It weighs about .5 grammes at birth, 2 grammes at aV)out 
 three years, and at about tlie fourth year commences its normal involution, 
 which is not completed until the twentieth or twent3T-fiftliyear. The tliymus 
 does not disai)pear ; there remains, at least, a fatty vestige (the retrosternal 
 body of Waldeyer). More often there is persistence of glandular elements, 
 whicli in certain pathological circumstances are the seat of a remarkable 
 degree of regeneration. 
 
 232
 
 The Thymus 233 
 
 the thyroparath5n:oid combination, but is easily differen- 
 tiated from these organs, the thymus, and from chromaffin 
 tissue. He supposes this gland to have some endocrinous 
 function, and it may be that future research may develop 
 its importance in physiology, pathology, and thera- 
 peutics. 
 
 The Functions of the Thymus. — Experimental proof of 
 convincing accuracy shows that the thymus is, in its 
 period of activity at least, an essential organ, and while 
 not all cases of thymectomy are fatal, every case thus 
 operated on manifests well-defined symptoms, some of 
 which can be modified by thymus organotherapy. 
 Lampe^ of Halle gives a very interesting representation 
 of this subject, from both the anatomical and the physio- 
 logical viewpoints. The experiments of various investi- 
 gators are reported, and the results are summarized as 
 follows : The thymus gland is an organ of vital importance, 
 as extirpation at the height of its development results 
 finally in death. Probably its most important function 
 consists in the inhibition of acids, and the consequent 
 removal of injurious substances from the blood. This 
 supposed function gives an explanation of the disturbances 
 occurring in the calcium metabolism after extirpation of 
 the organ, as well as for the changes in bone and in the 
 central nervous system. The thymus gland, during its 
 stages of importance, occupies a dominating position 
 over the lymphatic apparatus. Between the thymus 
 on the one hand, and the various organs of internal 
 secretion on the other, complex relations exist. This is 
 especially true of the spleen, for this organ is, so to speak, 
 " prepared " by the thymus to take up some of the latter 
 organ's still unexplained functions after its involution. 
 
 Is there a Thymus Hormone ? — It seems quite reason- 
 able to suppose that the influence of the thymus is due to
 
 234 Practical Hormone Therapy 
 
 a hormone, for it is undoubtedly brought about through 
 the blood. Thymus grafts will take the place of the 
 ablated organ, and dried extracts of the gland exert an 
 undeniable therapeutic effect in spite of Starling's^ state- 
 ment that " the effect of extracts made from the thymus 
 do not differ from those of extracts made from any other 
 cellular organ." 
 
 Biedl,^ in referring to the blood coagulating powers of 
 thymus extracts, calls attention to the fact that thymus 
 extract remains active after boiling, and this shows that 
 its active principle is not in itself a ferment, but that it 
 is a substance which causes the formation of a ferment 
 having the property of coagulating blood. It will be 
 remembered that the majority of the hormones are also 
 heat-stable bodies. 
 
 The Relation of the Thymus to other Endosecretory 
 Glands. — During the period of activity, the thymus is an 
 integral part of the endocrinous system, and has been 
 shown to be an important factor in the maintenance of 
 the hormone balance. Its relation to the other ductless 
 glands is beginning to be better understood,^* "^ although 
 for a long time it was considered to be a part of the system 
 of lymphatic glands which are scattered throughout the 
 body. That it is connected with the lymphatic system 
 is undoubted, and numerous facts have been brought 
 forward to show this. Poensgen^ has recently outlined 
 the evidence of reciprocal relations between the thymus, 
 the thyroid, and the lymph glands, and Magnani^ has 
 shown that the work of the thymus is related to that of 
 the spleen. 
 
 The connection between the thymus and the gonads 
 is, perhaps, the best understood at present. It has been 
 noticed with comparative frequency that the reproductive 
 glands do not develop properly until the thymus has
 
 The Thymus 235 
 
 atrophied, and there is a relation between these organs 
 in normal growth as well as in pathologic physiology. 
 Whether the gradual reduction and final absence of the 
 thymus internal secretion permits the development of 
 the gonads, or whether sexual growth with the intro- 
 duction of the hormones of the generative glands causes 
 the thymus retrogression, is a mooted point. Noel 
 Paton^° intimates that both factors are concerned, for 
 ovariotomy causes thymus hypertrophy, even after the 
 normal atrophy has occurred; and thymectomy in male 
 guinea pigs is followed by rapid development of the 
 gonads. 
 
 There may be still other interrelations between the 
 thymus and other members of the endocrinous system, 
 although the proof is not yet very clear. Adler^^ has 
 intimated that there must be a relation between the 
 thymus and the chromaffin system. 
 
 The Thymus, Calcium Metabolism, and Growth. — The 
 belief is becoming quite general that the thymus is con- 
 cerned in the retention of calcium salts by the body, and, 
 particularly, that it has an influence upon the ossification 
 of bones. In proof of this is offered the experiments of 
 Basch^2 and others, who found that thymectomized 
 animals suffer from marked softening of the bones. 
 
 Klose and Vogt^^ report the results of removing the 
 thymus from fifty-four dogs. In the first two or three 
 months there was an increase in weight as compared with 
 the control animals. The psychic condition was modified, 
 and they grew very fat ; but soon the weight began to fall, 
 and the so-called " cachexia thymipriva " gradually 
 supervened, and with it a form of idiocy known as 
 " idiotia thymica." Spontaneous fractures, osteomalacia, 
 and rachitis were frequently seen, and the evident 
 common cause was a great want of calcium in the thymec-
 
 236 Practical Hormone Therapy 
 
 tomized organism. The cause of the deficiency of calcium 
 and the idiocy is presumed to be an acidosis.* Klose 
 holds the view that the thymus also is the chief organ for 
 the synthesis of nuclein. 
 
 Sommer and Florcken^^ showed that thymectomy in 
 dogs caused the body to become unwieldy and improperly 
 developed. They also found that a thymus graft 
 obviated the developmental changes in such animals. 
 
 According to Ott,^^ " the removal of the thymus permits 
 the lower building stones of the organism — perhaps a great 
 excess of the incombustible phosphoric acid — to circulate 
 in the blood. The acid dissolves the calcium salts, or 
 holds them in solution. Artificially produced fractures 
 do not unite with callus, but only with connective 
 tissue." 
 
 Sajous^^ states that the function of the thymus is to 
 supply the excess of phosphorus in organic combination 
 required during the growth of the body, particularly while 
 the development of the osseous and nervous systems 
 demands such reserve. This has been sustained by the 
 recognized facts that certain diseases of childhood and 
 adolescence, especially marasmus, rachitis, and trophic 
 disorders of the brain and nervous system are due in 
 part to derangement of the thymus. 
 
 Thymus Extract in Malnutrition and Delayed Develop- 
 ment. — With such important nutritional factors under its 
 control, the thymus would naturally be expected to be 
 disturbed in pathological states of nutrition and develop- 
 
 * From the literature which has been collated in this book, it will appear 
 that calcium metabolism is intimately related to the work of the internal 
 secretory organs. The evidence is somewhat confusing, since so many of 
 the individual endocrinous glands are concerned in this particular phase of 
 metabolism ; for, in addition to the thymus, the adrenals, parathyroids, 
 spleen, and ovaries have been definitely connected with this. In Chapter XIV. 
 will be found further information regarding the importance of calcium meta- 
 bolism, as well as certain therapeutic deductions that can be made from these 
 rather complicated facts. (See especially p. 220.)
 
 The Thymus 237 
 
 ment, and such is unquestionably the case. The impor- 
 tance of the thymus hormone upon metabolism is the 
 basis of its administration in several nutritional disorders 
 of children. It may also exert a beneficial effect in 
 delayed development. Kerley and Beebe^'^ report a 
 remarkably interesting case which is an illustration of the 
 action of thymus medication in developmental disorders. 
 A boy of sixteen had the apparent development of a 
 ten or eleven year-old child, but was mentally bright. 
 Nine months' treatment with rest, diet, arsenic, etc., 
 made no material difference; but 15 grains (1 gramme) 
 of thymus extract each day soon caused an increasing 
 height and evidences of sexual development, and within 
 one year this was normal; and the increase in height in 
 eighteen months amounted to 4 inches. 
 
 Stoppato^^ secured good results from this treatment in 
 children suffering from rickets ; and MendeP^ insists that 
 the persistent thymus treatment of rickets is encouraging. 
 He even secured good results in cases where the improve- 
 ment so necessary in general hygiene could not be 
 properly maintained. 
 
 Castaigne, Gouraud, and Parisot^^ bring evidence to 
 support the belief in the value of the thymus treatment 
 of the dystrophies of children. They state that it raises 
 the strength and resistance, and stimulates, in a consider- 
 able degree, the physical development in rickets, athrepsia, 
 marasmus, malnutrition, etc. This influence is said to 
 be due to important modifications which are brought 
 about in the metabolism, especially of calcium and 
 phosphorus. 
 
 The Thymus Treatment of Simple Goitre. — It was in 
 1895 that thymus was first used by Owen in the treatment 
 of exophthalmic goitre [q.v.). It is reported to be of 
 considerable service in the treatment of simple goitre.
 
 238 Practical Hormone Therapy 
 
 An advantage which this form of medication has over the 
 usual th3rroid treatment is that improvement can be 
 secured without running the risk of thyroidism, palpita- 
 tion, loss of weight, etc. It is by no means in general 
 use, although many cases are on record in which the 
 administration of thymus has produced improvement 
 when the previous thyroid treatment had failed or pro- 
 duced unfavourable results. 
 
 Shortly after Owen's original communication, Mikulicz^^ 
 reported the results of treating eleven cases of simple 
 goitre by means of thymus extract. At the 1895 Congress 
 of German Surgeons he gave statistics of his work, and 
 the records showed that 30 to 75 grammes of calf's 
 thymus were used daily, and of the eleven cases thus 
 treated, ten v/ere successful. Since then, in Germany, 
 the thjrmus treatment of goitre has been called " Miku- 
 licz's method." From that time many have tried thymus 
 therapy, and numerous successes and failm'es have been 
 reported. 
 
 The Influence upon Exophthalmic Goitre. — In exoph- 
 thalmic goitre, thymus therapy has proved very efficient 
 in the hands of Owen^^ and others. It was by accident 
 that Owen first used thymus extract.* He ordered a 
 preparation of thyroid for a case of exophthalmic goitre, 
 and the butcher in error sent up thymus. The effects 
 were remarkably good, and as a result of this fortunate 
 mistake, Owen was stimulated to make a fm-ther in- 
 vestigation, and later was able to report four more 
 cases which were considerably benefited by thymus treat- 
 ment. 
 
 A few years later Kinnicutt^^ collected sixty- two cases 
 of exophthalmic goitre treated by this method. In 
 
 * It appears that this was tliu first recorded clinical application of thj-mus 
 therapy.
 
 The Thymus 239 
 
 thirty-six cases improvement of varying degree occurred, 
 in twenty-five there was no improvement, and in one 
 there was an aggravation of the symptoms. After nearly 
 twenty years S. Solis-Cohen^'* states that he prefers 
 thymus extract to all other organotherapeutic prepara- 
 tions in the treatment of exophthalmic goitre. Of course, 
 he does not confine the treatment to this medication 
 alone, although, save for a local iodine ointment, his 
 recommendations are confined to diet, hygiene, and 
 hydrotherapy. Solis-Cohen uses 1^ to 45 grains (0'5 to 
 3 grammes) per day in divided doses, and continues this 
 for months. It is especially useful in advanced cases, 
 when all other remedies have failed to bring about 
 improvement, and its beneficial influence seems to act 
 more particularly upon the nervous system of the disease 
 without affecting the exophthalmos. 
 
 ]\IM. Dor of Lyons^'^ are enthusiastic about the value 
 of thymus extracts. One of them writes that " nothing 
 ameliorates exophthalmic goitre like thymus "; while 
 numerous other authors might be cited to give emphasis 
 to the reputed value of persistent thymus medication in 
 diseases of the thyroid gland. 
 
 Hirsch^^ advocates this method of treatment, and 
 reports that thymin (tablets made from the thymus of 
 the calf) causes an improvement in the restlessness and 
 sleeplessness, a regression of the struma, reduction of the 
 exophthalmos, as well as a lessening of the cardiac dis- 
 turbances. She states that improvement was noticed in 
 two cases in which operation had been without effect. 
 Hirsch recommends thymin as a soporific, and gives it in 
 doses of one or two ^-gramme (7| grains) tablets in certain 
 cases of diabetes insipidus, neurasthenia, arterio-sclerosis, 
 and dyspepsia. No untoward action has been noticed, 
 and in animal experimentation, two daily doses of thymin
 
 240 Practical Hormone Therapy 
 
 of 0'5 gramme each, produced an increase of nitrogen 
 metabolism. 
 
 The Possibilities of Thymus in Chlorosis. — A record of 
 the work of Blondel, who pointed to good results with 
 thymus treatment in the chlorosis which occurs during 
 the period of puberty, deserves to be mentioned. He 
 regards chlorosis as an intoxication by certain products 
 of metabolism which normally should be neutralized by 
 the ovarian secretion. During the earlier stages of 
 development, before the ovaries are functional, or when 
 their function is still slight, these products may give rise 
 to chlorosis unless prevented by the activity of the thymus 
 gland. Starting on this hypothesis, BlondeP^ gave chlorotic 
 girls, for months at a time, 10 grammes (150 grains) of 
 the fresh gland daily, and records that improvement 
 followed. Since then the dried substance has been used 
 with moderately good results. 
 
 A New Method of treating Rheumatoid Arthritis. — As 
 a result of the clinical and laboratory work of Nathan 
 of New York,-^ it seems clear that thymus extract may 
 be useful in certain cases of chronic rheumatic arthritis. 
 He advises that all previous measures should be dis- 
 carded before beginning this treatment; and suggests 
 that there is absolutely no necessity for restricting the 
 diet. Rest, a nutritive diet, and thymus medication will 
 nearly always relieve the more active symptoms in the 
 milder cases; but in severe and intractable cases treat- 
 ment should be continued for months. The cases re- 
 ported seem most encouraging, many hopeless bedridden 
 patients being markedly benefited. Nathan thinks that 
 "it is certain that when the thymus is taken conscien- 
 tiously for a long time, and the patient otherwise judiciously 
 handled, marked improvement, if not perfect cure, can 
 always be expected."
 
 The Thymus 241 
 
 Delany^^ has had equally good results. He admits 
 that this is empirical medication, and says that " desic- 
 cated thymus gland . . . has proved a great boon, at least 
 in relieving pain and in checking the progress of the 
 disease." He continues: " The medical profession is not 
 quick to accept such innovations, yet when we feel that 
 relief is obtained, we prefer to have it, even though it is 
 not directly in line with our usual trend of thought. 
 We begin with one 5-grain tablet four times daily, and 
 give an additional tablet every sixth day, until the 
 general symptoms are relieved; then the drug is con- 
 tinued at that dosage, which is usually about 35 grains 
 per day. There is no appreciable systemic reaction to 
 the drug, and it seems to be tolerated alike by young 
 and old." 
 
 Nathan states that the attainment of success with the 
 thymus treatment takes considerable time, and requires 
 both persistence and good judgment, as well as careful 
 attention to detail. 
 
 Contra-Indications. — Thymus extract is not especially 
 toxic. In some cases as much as 3 or 4 grammes (45 to 
 60 grains) may be taken daily without inconvenience. 
 It is, however, rich in nucleins, and some have stated 
 that it is not advisable to give it to patients with the uric- 
 acid diathesis, as it is likely to aggravate the gouty 
 symptoms. 
 
 BIBLIOGRAPHY 
 
 ^ Pende (N.): SuU' esistanza di una nuova glandola a secrezione 
 interna, Bif. med. (Naples), 1913, xxix, 589. 
 
 2 Morel (L.): Les fonctions du thymus, Mouvem. med. (Paris), 
 
 1913, i, 184. 
 
 3 LAMPi! (A. E.): The function of the thymus gland, Am. J. Ohs. 
 
 (New York), 1913, Ixvii, 808. 
 * Starling:* p. 1334. 
 6 Biedl:* p. 121. 
 
 16
 
 242 Practical Hormone Therapy 
 
 * Basch (K.): Ueber die Thymusdriisf^, Dent. med. Wchnschr. 
 
 (Leipzig), 1913, xxxis, 1456. 
 ' YoKOYAMA (Y.): Ueber die Wirkung des Thymus im Organis- 
 
 mus. Arch. f. path. Anat. (Berlin), 1913, ccxiv, 83. 
 ^ PoENSGEN (F.): Beitrag zur Frage der Wecbselbeziehungen 
 
 zwisclien Thymus, Schilddriise und lymphatischem System, 
 
 Med. Klin. (Berlin), 1913, ix, 1504. 
 ^ Magnini (M.): Le funzioni del timo ed i rapporti fra timo e 
 
 milza. Arch, di Fisiol. (Florence), 1912-13, xi, 333. 
 1° NofeL Baton (D.): The relation of the thymus to the sexual 
 
 organs, J. Physiol. (London), 1905, xxxii, 28. 
 ^^ Adler (L.): Thymus und Adrenalsystem, Arch. f. path. Anat. 
 
 (Berlin), 1913, ccxiv, 91. 
 ^2 Basch (K.): Beitrage zur Physiologie und Pathologie der 
 
 Thymus. Die Beziehung der Thymus zur Schilddriise, 
 
 Ztschr.f. exp. Path. u. Ther. (Berlin), 1912-13, xlii, 180. 
 " Klose (H.) and Vogt (H.): " Klinik und Biologie der Thymus- 
 
 driise " (Tiibingen), 1910. 
 " SOMMER (A.) AND Florcken (H.): Ueber die Funktion der 
 
 Thymus, Sitzungsber. d. phys. med. Gessel. z. Wurzb., 1908, 45. 
 15 Ott:* " Internal Secretions," p. 109. 
 i« Sajous:* vol. i, pp. 178-185, 
 
 ^' Kerley (C. G.) and Beebe (S. P.): A case of delayed develop- 
 ment in a boy treated with thymus gland. Am. J. Med. Sci. 
 
 (Philadelphia), 1912, cxliv, 219. 
 ^8 Stoppato (N.): Contributo alio studio dell' organoterapia in 
 
 pediatria, Policl. (Kome), 1897, iv (M), 172. 
 ^^ Mendel (F.): Thymusdriise und Rachitis, Miinch. med. 
 
 Wchnschr., 1902, xlix, 134. 
 
 20 Castaigne (J.), GouRAUD (F. X.), AND Parisot (J.): L'opo- 
 
 therapie thymique et parathyroidienne, J. med. fran^. 
 (Paris), 1912, vi, 129. 
 
 21 Mikulicz (J.): Ueber Thymusfiitterung bei Kropf und Base- 
 
 dow's cher Krankheit, Berl. Jcl. Wchnschr., 1895, xxxii, 343. 
 
 22 Owen (D.): Thymus feeding in exophthalmic goitre, 5r. 3Ied. 
 
 J. (London), 1895, i, 361; see also id., 1896, ii, 1017. 
 
 23 KiNNicuTT (F. P.): The therapeutics of the internal secretions. 
 
 Am. J. Med. Sci. (Philadelphia), 1897, cxiv, 1. 
 2* SoLis-COHEN (S.): The non-surgical treatment of exophthalmic 
 
 goitre. Am. J. Med. Sci. (Philadelphia), 1912, cxliv, 13. 
 25 Dor (H.) and Dor (L.): Du traitement de la maladie de 
 
 Basedow par le thymus, Lyon med., 1907, cviii, 19. 
 2* HiRSCH (R.): Thymin und seine Wirkung in der Behandlung 
 
 des Morbus Basedowii; und Thymin als Schlafmittel, Deut. 
 
 med. Wchnschr. (Leipzig), 1913, xxxix, ii, 2141, 
 2' Blondel (F.): Essai d'une th6orie nouvelle de la chlorose; 
 
 Emploi th6rapeutique du thymus dans cette affection, 
 
 Bull. gen. d. ther. (Paris), 1897, ii, 233,
 
 The Thymus 243 
 
 28 Nathan (P. W.): A new and apparently successful method of 
 
 treating metabolic osteo- arthritis, J. Am. Med. Assn. 
 (Chicago), 1911, Ivi, 1779. 
 
 29 Delaney (C): The treatment of arthritis deformans, Med. 
 
 Council (Philadelphia), 1913, xviii, 327. 
 
 Groter (F.): Thymxis gland treatment of certain diseases: 
 goitre, arterio-sclerosis, cystic tumour of breast, pulmonary 
 tuberculosis, cancer; A report of experimental work, N. Y. 
 Med. J., 1910, xci, 373. 
 
 Vincent (S.) : On the physiological effects of extracts of thymus, 
 ProG. Physiol. Soc. (London), 1903, xxx, p. xvii. 
 
 Albanese (G.): Influenza dell' estratto timico sulla cloronar- 
 cosi, Gf^ior. int. d. sc. Med. (Naples), 1906, xxviii, 931. 
 
 Heimann (F.): Thymus, Ovarien und Blutbild, Miinch. med. 
 Wchnschr., 1913, Ix, 2829.
 
 CHAPTER XVI 
 RENAL OPOTHERAPY 
 
 The Basis of Renal Medication — The Evidence against an In- 
 ternal Secretory Function — The Therapeutic Value of Kidney 
 Extracts — Disadvantages of Fresh Preparations — The Reduc- 
 tion of Albuminuria — Renal Insufficiency and Urcemia — 
 Treatment with Serum from the Renal Vein — Kidney Sub- 
 stance an Adjunct Remedy. 
 
 The evidence concerning the supposed internal secre- 
 tory capacity of the kidneys is most conflicting. Many 
 authorities insist that the kidneys, like numerous other 
 secretory organs, evidently have a supplementary func- 
 tion in addition to their powers of excreting the various 
 effete materials which they are known to pass from the 
 body in the urine, and that the importance of their 
 better-known function has quite overshadowed the pre- 
 sumably lesser, but nevertheless important work. 
 
 The Basis of Renal Medication.— Whether this function 
 of the kidney is a result of an internal secretion or is due 
 to other factors is not decided. As far back as 1869 
 Brown-Sequard held that the kidneys produced an in- 
 ternal secretion, and in 1892, with d'Arsonval,^ he re- 
 ported a series of experiments, which showed that the 
 administration of renal extract postponed uraemic mani- 
 festations, and prolonged the lives of nephrectomized 
 animals. Since that time numerous communications, 
 especially from French writers, have substantiated this 
 position. 
 
 Lepine^ noted that the injection of the filtrate of a 
 
 244
 
 Renal Opotherapy 245 
 
 watery extract of kidney produced a reaction with a rise 
 of temperature and dyspnoea; while renal extracts 
 evidently have an action different from that hypotensive 
 property, supposed by Popielski to be inherent in all 
 animal extracts. Their action is hypertensive, as Oliver 
 and Schafer^ showed, for a cold, watery extract of fresh 
 kidney, when injected intravenously in rabbits, soon 
 produced a more or less marked increase in the tension. 
 
 Teissier,'^ applying the results of experimental physi- 
 ology in therapeutics, found that the administration of 
 a glycerin extract of kidney substance caused a diminu- 
 tion, and sometimes complete disappearance of certain 
 serious symptoms, such as the dyspnoea, headache, and 
 vomiting of severe kidney affections. 
 
 The Evidence against an Internal Secretory Function. — 
 On the other hand, BiedP states that " one thing is 
 clear, however, and that is that these experiments supply 
 no proof of a physiological internal secretion on the part 
 of the kidneys." 
 
 Sajous is also opposed to the idea that the kidneys 
 have an internal secretory function, and believes that the 
 action of renal extracts is possibly due to the active 
 principle of the adrenals. In an editorial article^ entitled 
 "Do the Kidneys produce an Internal Secretion V the 
 following evidence is brought forward: "In the hght of 
 recent data, however, these phenomena can as readily 
 be attributed to physiological substances which normally 
 form part of the renal tissues and fluids as to any sup- 
 posititious internal secretion. As is well known, hyper- 
 nephromata of the kidney are developed from adrenal 
 rests in the renal substance, while the adrenal active 
 principle is now known to be found in the blood through- 
 out the entire organism, including, therefore, that of the 
 kidneys. That an extract of the latter should contain
 
 246 Practical Hormone Therapy 
 
 the adrenal principle is therefore self-evident. This fact 
 being borne in mind, all the phenomena attributed to 
 the so-called ' renal internal secretion ' are found to 
 coincide precisely with those awakened by the adrenal 
 product. The elevated blood- pressure witnessed is a 
 familiar effect of the latter. The rise of temperature 
 was not only noted as a concomitant effect by Reichert, 
 Lepine, and Morel, but Fuchs and Roth found recently 
 that adrenaline increased markedly the intake of oxygen 
 and the output of carbon dioxide. As to the dyspnoea 
 and the ensuing arrest of respiration, obviously due to 
 toxic spasm of the respiratory muscles, it has also been 
 found to be a characteristic effect of adrenal extracts by 
 OUver and Schafer, and more recently by Langlois and 
 Garrelon, Even Brown-Sequard's observation, that renal 
 extracts postponed the development of uraemia in 
 nephrectomized animals and prolonged life, falls in presence 
 of the fact, shown long ago by Langlois and developed by 
 others since, that adrenal extracts are endowed with 
 antitoxic activity — an essential feature in combating 
 uraemia, itself due to retained poisons. Finally, Lewan- 
 dowsky has shown that the effects ascribed to a supposed 
 renal secretion could be obtained with venous blood 
 derived from any other structure of the body. On the 
 whole, the evidence is decidedly against the existence of 
 a renal internal secretion, and it is hoped that the true 
 status of other organs credited with such will soon be 
 established. Then will it be possible to realize how truly 
 important to the organism at large are the bona fide 
 internal secretions." 
 
 The Therapeutic Value of Kidney Extracts. — While 
 admitting the reasonableness of the above contention, 
 there can be no denying the facts on record concerning 
 the use of kidney preparations in the treatment of certain
 
 Renal Opotherapy 247 
 
 conditions, and whether the therapeutic activity of such 
 extracts is due to a hormone or not, the evidence is 
 certainly in favour of the method, as will shortly be seen. 
 The results published concerning the use of renal sub- 
 stance in therapeutics are already sufficiently extended, 
 not only to authorize the employment of renal opotherapy 
 in albuminuria, but also to establish its usefulness as an 
 efficacious adjunct in a number of other disorders of the 
 kidney. 
 
 The literature on the action of kidney extract in chronic 
 nephritis is still very limited. Many divergent views are 
 held by most authors, some claiming a complete cure 
 following its use, while others disclaim any benefit what- 
 ever, and even warn against its use. 
 
 It is the opinion of several French v/riters that the 
 favourable results of kidney extract may be looked for in 
 uncomplicated cases of nephritis. When cardiac com- 
 plications have arisen, this treatment is not so Ukely to 
 be effectual. Subcutaneous injections are not without 
 danger, probably owing to the fact that the extract is 
 easily decomposed. Unquestionably a number of the 
 unfavourable results reported are due to this cause. It 
 is certain that a properly prepared extract, when 
 given by mouth, presents no danger whatever. 
 
 Renaut^ of Lyons has added much to our knowledge 
 of this subject, and, inspired by the same fundamental 
 facts outlined by Brown-Sequard and others, uses and 
 recommends the use of macerations of the fresh pulp of 
 kidneys. He concludes that it constitutes one of the 
 most active and effective means of treating conditions 
 associated with renal insufficiency. He stated that it 
 was better than any means then (1903) known, for it opens 
 up the kidney incapacitated by the oedema of uraemia. 
 It causes a rapid diuresis, and, when given over a suffi-
 
 248 Practical Hormone Thera'py 
 
 ciently long period, brings the amount of urine to the 
 normal without harm to the glomerular structure. 
 Renaut continues: " This method has the advantage over 
 others in that it reduces in a decided manner the albumin 
 passed by the defective kidneys, at the same time fre- 
 quently restoring their full activity. It can, therefore, 
 be used to favour the restoration of the epithelia, which, 
 in numerous cases, is histologically possible. No other 
 form of treatment applied in nephritis has been known 
 to do this." It also possesses another advantage — 
 namely, its antitoxic action. Dubois^ states that the 
 antitoxin is derived from the products of the glandular 
 epithelial cells of the convoluted tubules, and that this 
 substance is not destroyed by its passage through the 
 intestinal tract. When introduced into the organism by 
 the mouth, it effects a true disintoxication. However, it 
 has a somewhat cumulative action, and after twelve to 
 fourteen days may cause pruritus and urticaria, with 
 some slight gastro-intestinal disturbances. With that 
 exception no ill-effects have ever been observed. The 
 favourable results are regular, constant, and progressive, 
 and the arterial hypertension, with a tendency to passive 
 terminal dilatation of the heart, so frequently observed 
 in interstitial nephritis, seems to be prevented. 
 
 Disadvantages of Fresh Preparations. — Several writers, 
 notably Castaigne,^ find that fresh kidney substance is 
 not well borne when given j)er os, and therefore it has been 
 given per rectum. When given by the rectal route, one- 
 half to one fresh kidney is chopped fine, and water is 
 added. This should be divided into three enemata of 
 200 c.c. each, and should be given through a high rectal 
 tube after previous cleansing e:iemata, 
 
 Gilbert^^ does not recommend the fresh preparations, 
 for he has found, in a series of experiments, that they
 
 Renal Opotherapy 249 
 
 usually contain toxic substances in addition to those 
 which are of therapeutic value. These toxins in certain 
 cases may be neutralized and eliminated, and the value 
 of this medication may be very evident ; while, again, the 
 capacity to destroy the harmful substances may not be 
 present, and thus an already serious toxaemia may be 
 added to. Again, disease may be present in the kidneys 
 which are to be used, and this consideration militates 
 against Renaut's method. 
 
 To obviate the inconvenience of this rather unpleasant 
 method of administration, active vacuum-dried extracts 
 are now used in the form of powder, cachets, or tablets, 
 although it is still insisted by a few writers that fresh 
 preparations are more desirable. Such preparations are 
 in comparatively frequent use, and in many cases of kidney 
 disease render really effective service. 
 
 The Reduction of Albuminuria. — Besides the detoxi- 
 cating influence already mentioned, and that which is 
 frequently manifest in uraemia and other evidences of 
 renal insufficiency, renal medication has other thera- 
 peutic virtues. Perhaps the most remarkable influence 
 of this form of treatment is the reduction, sometimes in 
 a very large degree, of albuminuria. It seems to indicate 
 that extracts of kidney substance have the power to 
 influence the passage of albumin through the kidneys. 
 In the attempts which have been made to explain this 
 action, several possibilities have been considered. Some 
 think that these preparations play an antagonistic and 
 neutralizing part, as poisonous substances undoubtedly 
 are factors in the production of the disorders in question. 
 In the opinion of Hallion^^ the general fundamental in- 
 fluence of opotherapy is in evidence here — viz., extracts 
 of an organ act especially by stimulating the activity and 
 regeneration of the corresponding cells which are disturbed.
 
 250 Practical Hormone Therapy 
 
 Renal Insufficiency and Uraemia. — Under the influence 
 of this medication one frequently notes the diminution 
 or complete control of certain ursemic symptoms. One 
 of the most troublesome of these, insomnia, is favourably 
 influenced. Often cedema is reduced very rapidly, and 
 at the same time the amount of urine is increased, and its 
 low solid content is raised. 
 
 Capitan^^ reported a striking cure in a case of ursemia. 
 The numerous and severe complications make the results 
 obtained the more remarkable. An old man with a 
 double aortic and mitral lesion, oedema of the lungs and 
 limbs, ascites, dysuria, Cheyne Stokes breathing with very 
 severe dyspnoeic crises, and continuous delirium was 
 given an injection of 3 c.c. of a hypodermic kidney extract 
 {nephrine). At this time he was passing 300 c.c. of urine 
 in twenty-four hours, and was supposed to be moribund. 
 Several hours later an improvement was seen, and the 
 total amount of urine the day after treatment was 
 850 c.c. No other medication was given. The injections 
 were made daily, and two hours after the second dose 
 800 c.c. of urine were passed, the sjanptoms were sub- 
 siding, and the total urine on the third day amounted to 
 1,500 c.c. Injections were continued for a week, and all 
 the symptoms, though, of course, not the heart lesions 
 (which, however, eventually became well compensated), 
 disappeared, and the patient was able to return to his 
 business. 
 
 Roque and Lemoine^^ have had similar experiences. 
 They find that a week or ten days of this treatment is 
 usually sufficient. Within forty-eight hours of the first 
 injection the acute phenomena of renal insufficiency begin 
 to subside, with a marked increase in the urinary quantity 
 and total solids. 
 
 Pulmonary congestion and the bronchitic disturbances
 
 Renal Opotherapy 251 
 
 so commonly associated with certain forms of albuminuria 
 are reported to have been ameliorated in consequence, 
 doubtless, of an influence upon the circulatory disturbances, 
 which at the same time are benefited. This is evidenced 
 especially by the favourable changes in both pulse and 
 tension. In addition to this, under the influence of renal 
 opotherapy, digestive disorders, associated with renal 
 insufficiency, mend encouragingly. 
 
 Vialard has used renal opotherapy in the treatment of 
 what the French term ^^ impermeabilite renale,^^ and has 
 made two important communications to the Paris Societe 
 de Therapeutique. In the second^'* he offers the following 
 conclusions : 
 
 1 . In cases of chronic nephritis a course of opotherapy, 
 repeated several times, has caused a complete cure; but 
 such cases are exceptional. 
 
 2. In the majority of cases of nephritis, renal opotherapy 
 stops or lessens the crises of acute renal insufficiency, 
 causing temporary disappearance of albuminuria, and of 
 the signs of Bright's disease. It is to uraemia what 
 digitalis is to asystole. 
 
 3. But in every case it acts only after causing abundant 
 diuresis. This diuretic effect is almost always observed 
 when the kidneys are not completely destroyed, and are 
 able to react. If opotherapy is not a regenerator of the 
 renal cellule, it is at least a powerful stimulant and a 
 good diuretic. 
 
 Treatment with Serum from the Renal Vein. — Teissier 
 and several other authors have given injections of serum 
 obtained from the renal vein. The first application in 
 man was made in 1897 by Turbure of Bucarest. In 
 1898 Teissier injected a serum in a young man suffering 
 from very severe scarlatinal nephritis, and he was cured. 
 Hypodermic injections into the abdominal wall of 20 c.c.
 
 252 Practical Hormone Thera'py 
 
 of the serum are given daily. This method has given 
 very good results, but is rarely used on account of the 
 difficulty in obtaining the serum. 
 
 Kidney Substance an Adjunct Remedy. — It goes without 
 saying that renal opotherapy, in spite of the value which 
 has been attributed to it, must be considered only as an 
 adjunct method of treatment, save in exceptional in- 
 stances. That the advantages are not due to the orthodox 
 methods of treatment is clearly proved by considerable 
 gains which have followed its addition to other procedures 
 which have been in use for weeks or months. It is also 
 well to remember that disturbances of the kind under 
 discussion are serious, progressive, and quite often fatal, 
 and that to expect too much of any method of treatment 
 is unreasonable. However, one cannot overlook the 
 advantages which have been recorded, and since the 
 addition of this form of medication to the regime of 
 nephritis is not accompanied by serious or inconvenient 
 consequences, it seems on that account deserving of 
 more extended application. 
 
 It is also well to mention that renal opotherapy is 
 frequently combined with other animal extracts, and 
 especially with preparations of liver, since, for obvious 
 reasons, hepatic insufficiency is a predominating factor 
 in many cases of renal disease. 
 
 BIBLIOGRAPHY 
 
 Brown-Sequard (C. E.) and d'Arsonvax (A.): Des injections 
 souscutanees d'extraits liquides de nombre d'organes comme 
 methode th6rapeutique, G. r. Acad. d. Sci. (Paris), 1892, 
 cxiv, 1399. 
 
 LUPINE (R.): Cf. N. Y. Med. J., 1913, xcviii, 333. 
 
 Oliver (G-.) and Schaper (E. A.): On the physiological action 
 of extracts of pituitary body and certain other glandular 
 organs, J. Physiol. (London), 1895, xviii, 277.
 
 Benal Opotherapy 253 
 
 * Teissier (J,): Traitement de rinsuffisance r6nale; EfEets de 
 
 I'opoth^rapie, r6noth6rapie et serotli6rapie r6nale, Bull. med. 
 (Paris), 1904, xviii, 617. 
 ^ Biedl:* p. 444. 
 
 * Editorial: Do the kidueys produce an internal secretion ? 
 
 -Z^. r. Med. J., 1913, xcviii, 333. 
 ' Renaut (J.): Pouvoir s6cr6toire et signification glandulaire 
 des epitheliums des tubes contournes du rein, et valeur 
 therapeutique des leurs produits solubles dans I'eau, Bull. d. 
 VAcad. d. Med. (Paris), 1904, 1, 599 ; see also id.. Bull. gen. 
 d. Ther. (Paris), 1904, cxlvii, 147. 
 
 * Dubois (R.): Antitoxiue renale et albuminurie, C. r. Soc. Biol. 
 
 (Paris), 1903, Iv, 289. 
 ® Castaigne (J.) AND Parisot (J.): Les m^ications opoth6ra- 
 piques applicables au traitement des affections renales, Bev. 
 d. Ther. (Paris), 1910, xxvi, 741. 
 
 10 Gilbert (A.): Cf. Carnot:* p. 276. 
 
 11 HALLI0N:*p. 33. 
 
 12 Capitan (L.): Un cas d'ur6mie grave gu6rie par I'extrait de 
 
 rein en injections souscutan^es, C. r. Soc. Biol. (Paris), 1904, 
 Ivi, 26. 
 
 13 RoQUE (G.) AND Lemoine (G.): Reveil de 1' activity 6pith61iale 
 
 au cours d'une nephrite chronique p.ar la chlorurie exp6ri- 
 mentale, Lyon med., 1904, cii, 1093. 
 1* ViALARD (F.): Imperm6abilit6 r6nale et opoth6rapie, Pr. med. 
 (Paris), 1908, xvi, 812, 
 
 Meyer (E.): Faits r61atifs a la s6cr6tion interne des reins. 
 
 Arch. d. Physiol. (Paris), 1894, xxvi, 179. 
 Lewandowsky (M.): Zur Frage der inneren Sekretion von 
 
 Nebenniere und Niere, Ztschr. f. hi. Med. (Berlin), 1899, 
 
 xxxvii, 535. 
 Silvestri (L.): L'opoterapia renale e la teoria del nefrolisme, 
 
 Policl. (Rome), 1902, ix (P), 1665. 
 Ingegnatti (G.) : Contributo alia opoterapia renale col 
 
 metode del Renaut, Qior. int. d. sc. med. (Naples), 1905, 
 
 xxvii, 555. 
 SiMENONi (V.): Le iniezioni di estratto renale in terapia, 
 
 Oaz. int. d. med. (Naples), 1905, viii, 28; see also id., 1906, 
 
 ix, 322. 
 Arquembourg (L.): Apropos de I'opoth^rapie x^nale. Echo 
 
 med. du Nord (Lille), 1905, ix, 325.
 
 CHAPTER XVII 
 ARE THE TONSILS ENDOCRINOUS ORGANS ? 
 
 The Anatomy of the Tonsils — Ott's Experiments — A Powerful 
 Diuretic Principle — Influence on the Circulation. 
 
 The function of the tonsils is not definitely known, and 
 they are usually considered as a pair of more or less super- 
 fluous lymph nodes, whose value to the organism is con- 
 siderably overbalanced by the facility with which they 
 become infected and cause trouble. 
 
 The Anatomy of the Tonsils is well known, and frequent 
 opportunity is had to study them both in situ and after 
 excision. It is supposed by many that since the tonsils 
 are composed mainly of lymphoid tissue, they serve to 
 supply phagocytes to the mouth and pharynx wherewith 
 to combat the bacteria entering the mouth. If this is so, 
 it is easy to understand why they are so readily overcome 
 and rendered useless ; and one might be tempted to wonder 
 why these organs, in the passage of generations, have 
 not been modified by circumstances, and hyper- 
 trophied sufficiently to serve their presumed purpose 
 usefully. 
 
 Many surgeons and general practitioners still appear to 
 consider that the principal service of these bodies, like 
 that of the ovary in times now happily past, is by their 
 presence, so that their removal may furnish a convenient 
 and remunerative addition to the day's work. 
 
 254
 
 Are the Tonsils Endocrinovs Organs f 255 
 
 Ott's Experiments. — The possibility that the tonsils are 
 internal secretory organs has only recently been con- 
 sidered, and it is to Ott^ of Philadelphia that credit is due 
 for considering this question. 
 
 Experiments were made with powdered dried tonsils 
 of the calf and watery extracts of the same. The effect 
 of these extracts was marked on the circulation and urinary 
 secretion, while they caused a slight increase in the con- 
 tractility of involuntary muscle, as noted in experiments 
 with the intestines, bladder, and uterus. 
 
 A Powerful Diuretic Principle. — The most remarkable 
 effect of injections of tonsil extract was on diuresis. An 
 infusion of 0-13 gramme was injected in divided doses into 
 cats, and an increase was recorded in the urinary secretion 
 of over thirty times the original amount. As with extracts 
 of the infundibulum, parathjrroids, and pineal body, tonsil 
 extract temporarily increases the volume of the kidney, 
 and acts directly upon the cells of the renal tubules for 
 some time after the vaso-dilatation has subsided, showing 
 that the sum total of its action is not limited to the action 
 attributed by Popielski to the theoretical "vasodilatin," 
 which he states is to be found in extracts of all the various 
 glands. 
 
 Ott^ states that tonsil extract " seems to be a stronger 
 diuretic agent than either infundibulum, parathyroid, or 
 the pineal gland. In fact, it is the most powerful of all 
 the internal secretions." 
 
 Influence on the Circulation. — Small or large doses cause 
 a brief fall of blood-pressure and a decrease of the number 
 of heart-beats. A reaction follows, during which the 
 tension and pulse are increased. Large doses cause sudden 
 arrest of the heart, and the authors infer that tonsil 
 extracts act upon the heart muscle itself. 
 
 It is evident that the tonsil must be considered as more
 
 256 Practical Hormone Therapy 
 
 than a lymphoid node, and that the above experiments 
 prove that it contains certain substances closely resem- 
 bling, if not actually, internal secretions. 
 
 Whether the hypothetical tonsil-hormone is of impor- 
 tance in the normal economy, and whether the removal of 
 the tonsils may be the cause of the remote harm, one 
 cannot yet say. It is quite possible that future investi- 
 gations may throw light on this, and it is not improbable 
 that our increased laiowledge on the subject may give us 
 a new organotherapeutic preparation. 
 
 At present, however, tonsil extracts are used only in 
 the laboratories of a very limited number of enthusiastic 
 delvers into the mysteries of the endocrinous organs. 
 
 BIBLIOGRAPHY 
 
 1 Ott (I.) AND Scott (J. C): Action of the tonsil, Alienist and 
 
 Neurologist (St. Louis), 1913, xxxiv, 2, 
 
 2 Id. : Note on the action of tonsillar extract, Proe. 8oe. Exp. Biol, 
 
 and Med. (New York), 1912-13, x, 47.
 
 CHAPTER XVIII 
 
 THE CHROMAFFIN SYSTEM— ADRENAL THERAPY 
 
 The Components of the Chromaffin System — The Adrenals and 
 their Active Principles — The Physiological Action of the 
 Chromaffin Hormone — The Action of the Adrenal Cortex — 
 The Relation of the Adrenals to the Gonads — The Action on 
 Nutrition and Sugar Combustion — The Adrenals and Mus- 
 cular Work — The General Indications of Adrenal Thera2nj — 
 Hypoadrenia or Hypoepinephrinia — Hypoadrenia in the 
 Acute Infections — The Adrenal Treatment of Typhoid — 
 Adrenal Therapy in Asiatic Cholera — The Vomiting of Preg- 
 nancy — Cyclic Vomiting in Children — Chronic Hypoadrenia 
 in Children — The Stimulation of Bone Growth and Nutri- 
 tion — Adrenal Medication in Ptdmonary Disorders — The 
 Combination of Adrenal and other End,ocrinou^ Preparations 
 — The Influence of Adrenaline on Urticaria — The Adrenal 
 Principle as an Angiotonic Remedy — The Treatment of Snake 
 Bite — The Method of Causing Local Vaso-Constriction — The 
 Control of Local Hoemorrhage — Adrenalin as a Rational Treat- 
 ment of Asthma — Adrenal Extracts in the Salvarsan Treat- 
 ment — The Relation of the Mind to Adrenal Activity — 
 Chemistry and Nomenclature — Contra-Indications to Adrenal 
 Therapy. 
 
 The Components of the Chromaffin System consist of a 
 number of rather widely scattered cell aggregates, chief 
 among which are the adrenal bodies or suprarenal capsules 
 of Eustachius (discovered by this great anatomist between 
 1550 and 1560), These organs are classed as " the chro- 
 maffin system," because they contain certain substances 
 which stain a characteristic yellowish-brown coloiu" by 
 chromium salts. This staining capacity was first noticed 
 by Henle (1865), and in 1890 Stilhng apphed the term 
 " chromophil," which is still vised by some writers. The 
 
 257 17
 
 258 P7'acfical Hormone Therapy 
 
 term '" chromaffin " was introduced by Kohn in 1898. 
 The units composing this series of organs have also been 
 given the name " paraganghon." 
 
 As far as is known at present, all chromaffin tissue is 
 considered to be very similar to the chromium-staining 
 tissue of the adrenals, and many insist that the chromaffin 
 organs other than the adrenals themselves are virtually 
 accessory adrenal glands ; at least, it has been shown that 
 the extracts of these organs have practically the same 
 action as extracts of the adrenal medulla. 
 
 The chromaffin system, then, includes the intercarotid 
 body, or carotid gland of Luschka, Zuckerkandl's aortic 
 paraganglion in the foetus, the accessory adrenals or 
 interrenal bodies, and the medullary substance of both 
 the adrenal glands. The anterior lobe of the pituitary 
 body also contains many cells which give the same 
 characteristic staining reaction. 
 
 There is a close relationship between the chromaffin 
 system and the sjmipathetic nervous system, and several 
 writers have connected them, and it is for this reason that 
 this chapter has been included in the section dealing with 
 the " Nervous System." 
 
 The coccygeal body has for some time been considered 
 a part of the chromaffin system, although it does not 
 manifest all the characteristic staining reactions. Biedl 
 denies that it belongs to the sympathetic system. 
 
 The Adrenals and their Active Principle. — Concerning 
 the action of the internal secretion of the adrenals we have 
 accumulated a great deal of information in the past fifteen 
 years^ — much more than can be condensed into this 
 chapter. It must still be admitted, however, that we 
 cannot yet satisfactorily explain the whole of the activities 
 of these pecuUar bodies, which, it is now known, are con- 
 stantly yielding to the blood a chemical agent, or hormone,
 
 The Chromaffin System, — Adrenal Therapy 259 
 
 which stimulates the contractions of the heart and 
 arteries, and assists in the promotion of every action de- 
 pendent upon the sympathetic nervous system (Langley), 
 
 The best recent reviews of this subject are to be found 
 in Lucien and Parisot's book, chapter xi. of Swale 
 Vincent's book, and Biedl's second German edition.* 
 Naturally the majority of the pages of these books are 
 concerned with general considerations, for which we have 
 httle space here, while the therapeutic phase of the subject 
 is incidental. An attempt will be made to concentrate 
 here the gist of our present knowledge of the administra- 
 tion of adrenal preparations in general and special practice. 
 
 Three points brought out in the introduction to Vin- 
 cent's^ monograph may well be reiterated here; and it 
 seems advisable to quote his statements in extenso : 
 " There are two important discoveries which stand out 
 among all others as epoch-making. The first is the 
 observation by Addison in 1849, that certain cases of 
 disease characterized by pigmentation of the skin, languor, 
 and other symptoms, are associated with destructive 
 lesions — usually tuberculous — of the adrenal bodies. The 
 second is the discovery in 1894 by Oliver and Schafer of 
 the blood-pressure-raising activity of extracts of the 
 medullary portion of the gland. We are, however, by no 
 means clear, as will be seen in the sequel, what is the pre- 
 cise relationship between the facts revealed in these two 
 discoveries. A third very important step in our progress 
 ought to be referred to in this place. This is the isolation 
 in crystalline form of the active principle of the medulla 
 of the gland {i.e., of the chromaphil tissues) by Takamine 
 and Aldrich independently." 
 
 The Physiological Action of the Chromaffin Hormone. — 
 The activity of this active principle of the adrenal medulla 
 
 * See the " List of Books " in Chapter XXXVII. of the Appendix.
 
 260 Practical Hormone Therapy 
 
 [adrenalin) is very great, extremely minute doses sufficing 
 to cause marked physiological responses. The principal 
 influence is upon the musculature of the vascular system, 
 a fact which is responsible for the two factors which have 
 made the discovery of this substance so eminently useful — 
 i.e., (1) constriction of the arterioles and capillaries due to 
 the excitation of the peripheral nerve endings and quite 
 apart from other nerve influences, since the constricting 
 action continues in spite of section of the medulla or 
 paralysis of the vasomotor centre; and (2) direct stimula- 
 tion of the heart muscle. As a result of this the two main 
 therapeutic indications are made evident: (1) The control 
 of local haemorrhage, and (2) the raising of blood-pressure. 
 This will be referred to more fully farther on. 
 
 The Action of the Adrenal Cortex. — The adrenals, like 
 the pituitary and ovaries, are supposed to have a double 
 function, and histologically they are found to be composed 
 of two distinct forms of cells — the cortex and medulla. In 
 certain fish these two parts are completely separated, and 
 comparative anatomy has shown us that developmentally 
 the adrenal bodies represent two distinct sets of organs 
 which in the higher vertebrates are fused. It is the 
 medullary portion which is used in the preparation of the 
 angiotonic substances used in therapeutics, and their 
 activity corresponds to that of the adrenal or chromaffin 
 hormone. The cortical cells evidently also have an 
 internal secretory function, and, according to Bernard, ^ 
 their presumed hormone has the power to neutralize the 
 poisonous substances produced during muscular activity. 
 It is concluded that the myotonic action of the adrenals 
 is due to the activity of the cortex, while the angiotonic 
 action is caused by the medulla. 
 
 The presence of a myotonic internal secretion in the 
 adrenal cortex may account for the tonic and anti-
 
 The Chromaffiii System — Adrenal Therajpy 261 
 
 asthenic action of extracts made from the whole gland. 
 This may also be a good explanation of the vogue of the 
 several excellent powdered total extracts (tablets or 
 cachets) which are commonly used in France. The 
 general tonic results, other than those due to adrenaline, 
 are frequently used in the hypoadrenia of children and the 
 acute infectious diseases, as outlined later. 
 
 The Relation of the Adrenals to the Gonads.— There is a 
 more or less intimate connection between the adrenals and 
 the ovaries. A remarkable fact emphasizing this is 
 brought forward by Bulloch and Sequeira,^ who have 
 showTL from the study of pathological phenomena that 
 the adrenal cortex is largely responsible for the develop- 
 ment of the secondary sex characteristics. 
 
 As we have seen, the adrenal cortex and medulla have 
 a different development and different functions ; according 
 to Glynn'* the former is especially connected with growth 
 and sex characters, the latter with blood-pressure. The 
 enlargement of the adrenal cortex during breeding, during 
 pregnancy, and after castration, and the small size in 
 deficient sexual development, are additional exidence of 
 the association of the cortex with sex characters.^ Glynn 
 continues: "Adrenal hypernephromata are associated 
 with sex abnormalities almost invariably in children, 
 usually in adult females after the menopause, or in adult 
 males. Hyperplasia and hypernephromata of the adrenal 
 cortex in females are usually associated with a diminution 
 of certain female, and a development of male, sex char- 
 acters. The converse rarely occurs. The functional 
 association of the adrenal with the pituitary and other 
 ductless glands, and the appearance of certain sex abnor- 
 mahties in acromegaly and pineal tumours, indicate that 
 a true solution of the connection between the adrenal 
 cortex and sex will only be found when the inter-relation-
 
 262 Practical Hormone Therapy 
 
 ships of the various ductless glands are better under- 
 stood." 
 
 The adrenal medulla is also intimately connected with 
 the ovaries. Keller^ suggests that the ovaries have an 
 inhibitory action on the adrenal internal secretion. After 
 castration he found that the glycosuric action of the 
 chromaffin hormone was markedly increased. The ab- 
 sence of the ovaries causes an increased functional 
 activity of the chromaffin system with the well-known 
 climacteric sjmiptoms — increased blood-pressure, flashes 
 of heat, dizziness, headache, etc. — which are identical with 
 the manifestations of hyperadrenia. Varaldo^ demon- 
 strates this relationship in another way. He injected 
 epinephrin into a series of rabbits. During pregnancy 
 epinephrin-poisoning was increased, but was diminished by 
 castration. Repeated injections caused an obvious de- 
 crease in the size of the ovaries with degenerative changes 
 in which the glandular structures were replaced by con- 
 nective tissue. 
 
 In Chapter XXlV. further evidence is given to show that 
 there is a relation between the adrenals and the ova,ries, 
 and that therapeutic advantage may be gained from the 
 application of the knowledge. 
 
 The Action on Nutrition and Sugar Combustion.— The 
 chromaffin hormone appears to exert an important action 
 upon the phenomena of nutrition, but it is difficult to 
 augment our knowledge of the limits of its activities 
 because of the toxic effects produced, chief among which 
 is glycosuria. 
 
 In 1901 Blum^ made the notable discovery that glyco- 
 suria is produced in certain animals following the hypo- 
 dermic injection of adrenaline. This has since been 
 considerably amplified by Zuelzer^ and his co-workers. 
 This fact must be remembered when one is tempted to use
 
 The Chromaffin System — Adrenal Therapy 263 
 
 adrenal preparations in diabetes mellitus, for patients 
 suffering with pancreatic diabetes, being already in a 
 state of hyperadrenia because of the lack of the pancreatic 
 hormone, are extremely sensitive to all adrenal prepara- 
 tions. The relation of the hormone balance to glycosuria 
 is more thoroughly considered in Chapter III., and also in 
 the chapter on the pancreas (Chapter VII.). 
 
 The Adrenals and the Muscular Work. — Langlois was 
 the first to show that the adrenals are an important factor 
 in the destruction of muscle poisons; and Dieulafoy noted 
 the connection between asthenia and certain pathological 
 adrenal states. The fact that one of the prominent 
 symptoms of Addison's disease is severe muscular asthenia, 
 has led many to believe that muscular efficiency is de- 
 pendent upon the adrenal secretion. Other experimental 
 proof has been brought forward to establish the associa- 
 tion of these factors. Experimentally it has been shown 
 that partial or complete ablation of the suprarenal 
 capsules reduces the muscular power, and injections of 
 extracts of these glands have a stimulating effect. 
 
 " Cannon and Nice^° have attempted to unravel the 
 relations of the adrenals to the muscular functions. There 
 can be no question, from the evidence now available, that 
 there is a marked improvement in muscular contraction 
 after adrenal secretion is evoked or after epinephrin* is 
 injected. A large part of this increased efficiency is 
 unquestionably due to the improved circulation . . . and 
 fatigued muscles may thus be prepared by the secretion of 
 the adrenal glands for better response to the demands of 
 powerful nervous discharges. "^^ 
 
 The General Indications of Adrenal Therapy. — The value 
 of preparations of these glands is well known, and they are 
 in general use to-day. Many thousands of articles and 
 
 * Note Uic paiayiapli, "Chemistry and Noinenclature," on p. 282.
 
 264 Practical Hormone Therapy 
 
 clinical reports concerning their uses are scattered through- 
 out the world's medical literature. These are, for the 
 most part, devoted to their styptic or pressor value. 
 Adrenal preparations have a wider range of usefulness 
 than is ordinarily supposed. 
 
 The conditions in which this form of medication is of 
 value may be divided into two classes: (1) Adrenal in- 
 sufficiency or hypoadrenia, in which there is a definite 
 pathologic lack of the chromaffin hormone, the chief 
 among which are Addison's disease, adrenal tumours 
 with consequent disturbed secretory function, certain 
 acute infectious diseases, during which a hj^poadrenia 
 develops [e.g., diphtheria, cholera, scarlet fever, typhoid 
 fever), and certain nutritional disorders, especially 
 osteomalacia, rickets, etc. (2) Those conditions in which 
 the vaso-constrictive, myotonic or diuretic properties of 
 adrenahne are available — its empiric apphcation as a 
 remedy.* 
 
 Addison's disease was naturally first among the dis- 
 orders in which this form of treatment was tried, and 
 while the results have been by no means uniform, numerous 
 cases are recorded by such men as Oliver, Langlois, Osier, 
 Robin, and others, in which the general condition was 
 improved, pigmentation was diminished, and nutrition 
 was benefited. In most cases the results were temporary, 
 though Beclere^2 obtained a complete and permanent cure 
 
 * This is strictly the case, although the author is frank to state that the 
 classitication as " empiric " of the application of the vaso- contractor action of 
 adrenaline has been criticized. As a matter of fact, the word "empiric" 
 comes from the Greek e/x7retpi/c6s, experimental, and is used to classify those 
 methods of treatment that are based on experience. With this definition in 
 in mind, the author's position will be clear. There is no particular lack of 
 the adrenal hormone in, say, conjunctivitis ; but the application of what wc 
 have learned from experience, as regards the local vaso-constrictor action of 
 this substance, indicates that it would likety be useful in reducing the local 
 congestion in the conjunctiva ; and clinical results have established the 
 indubitable value of this empiric application.
 
 The Chromaffiyi System — Adrenal Therapy 265 
 
 in one case. He credits the treatment with causing a 
 compensatory hypertrophy of the unaffected areas of 
 adrenal tissue. The dosage in Addison's disease is 
 necessarily greater than ordinarily would be the case. 
 Two or three grains of desiccated adrenal substance should 
 be given three times a day. 
 
 Hypoadrenia or Hypoepinephrinia. — The disorders of the 
 adrenals accompanied by anatomic changes are fortun- 
 ately not very common, while functional hypoadrenia 
 (sometimes termed " hypoepinephrinia "), varying very 
 greatly in degree and the consequent manifestations, is 
 of frequent occurrence. In general, the evidences of the 
 presence of such conditions are lack of vascular tone, 
 hypotension, myasthenia, and instabihty of the sym- 
 pathetic nervous system. This class of disorders is still 
 frequently overlooked; and, because of the intimate re- 
 lations of the endocrinous organs, almost invariably 
 associated with, and comphcated by, disturbances in 
 other internal secretory organs. 
 
 Many of the theories, for which he was roundly criti- 
 cized, advanced by Sajous in his monumental work,^^ 
 are now established facts, and as such form the basis of a 
 therapeutic procedure of proved utility. The prominence 
 which this writer has given to the activities of the adrenal 
 system* is none too great, for undoubtedly the part that 
 the adrenals play in the essentially vital processes is as im- 
 portant as it is complex. Attention is again called to 
 the reference made to Crile's^^ theory (see p. 38) and 
 remarks regarding the "kinetic system," and by com- 
 paring the statements in this chapter with those in 
 Chapter III., it will be evident that the " adrenal system " 
 
 * Fully 700 of the 1,800 pages of Sajous's "Internal Secretions and 
 Principles of Medicine " are devoted to the part of the endocrinous system 
 ■which lie terms the "adrenal system." This, it should be remembered, con- 
 sists of the thyroid apparatus, anterior pituitary, and the adrenals themselves.
 
 266 Practical Hormone Thera'py 
 
 of Sajous and the " kinetic system " of Crile are very 
 nearly, if not quite, identical. 
 
 According to Bernard,^ the syndrome hypoepinephrie 
 is characterized by the presence of muscular asthenia 
 and diminished arterial tension. The former, which is 
 the chief manifestation, may be so intense as to simulate 
 a veritable paralysis. The arterial hypotension may 
 express itself in a number of ways ; there may be tachy- 
 cardia, arrhjiihmia, a tendency to collapse and syncope, 
 and peripheral vasomotor disturbances. There is also 
 an impairment of the digestive functions. The nervous 
 manifestations include mydriasis, headache, delirium, 
 convulsive or apoplectiform states, coma, and sudden 
 death. Sergent^^ has distinguished three different types 
 of adrenal insufficiency — the chronic, the subacute, 
 and the acute. The last of these, which has not been 
 recognized until recently, may be revealed under the 
 guise of an acute poisoning, a peritonitis, or a meningitis. 
 Many of the manifestations of acute infections or toxic 
 conditions are to be attributed to adrenal insufficiency. 
 These manifestations are apt to occur particularly in 
 diphtheria, scarlet fever, typhoid fever, erysipelas, and 
 chloroform-poisoning. 
 
 Hypoadrenia in the Acute Infections. — Numerous other 
 authors have drawn attention to the fact that there is a 
 connection between several of the more severe acute 
 infectious diseases and acute toxic hypoadrenia. The 
 adrenal insufficiency thus brought about may complicate 
 matters very seriously, and it has been proved by 
 numerous autopsies that the adrenals are not infre- 
 quently the seat of haemorrhages. The serious toxaemias 
 of such fevers are often the cause of an adrenal disturb- 
 ance producing a decrease in the normal supply of the 
 all-essential internal secretion, which results in a con-
 
 The Chromaffin System — Adrenal Thera'py 267 
 
 siderable reduction in blood-pressure, myasthenia, and 
 a tendency to collapse. Netter has done much to impress 
 the importance of this, and records many cases in which 
 benefit followed adrenal therapy. Several French writers 
 recommend a dosage of ^ to 1 milligramme of adrenaUne, 
 according to the conditions present. Where circum- 
 stances warrant its use, the application of adrenal therapy 
 quickly results in an increase of strength and reactive 
 powers, and, of course, the tension is raised and the 
 heart strengthened. 
 
 The Adrenal Treatment of Typhoid. — In a paper on 
 the relation of hypoadrenia to typhoid fever, read before 
 the French Academic de Medecine, Sergent connects 
 certain conditions which may supervene in typhoid fever 
 with the syndrome of adrenal insufficiency. This is 
 in harmony with this investigator's previous efforts to 
 prove that adrenal insufficiency may be observed in all 
 infectious diseases as well as in all severe intoxications. 
 Sergent's theory is of great practical importance, as it 
 involves the use of adrenal medication in such cases. 
 Adrenal insufficiency may be suspected in an infectious 
 disease when agitation, excitement, and fever give place 
 abruptly to prostration, lower temperature, and arterial 
 hypotension, with the white adrenal line* and a tendency 
 to collapse. The not infrequent complete prostration and 
 small pulse found in typhoid are signs of adrenal in- 
 sufficiency. These symptoms attain their maximum in 
 certain severe typhoid cases, even simulating peri- 
 tonitis or internal haemorrhage, and disappear rapidly 
 under adrenal therapy. Certain complications of con- 
 
 * This is a derraographic sign conaisting of a white line upon the skin of 
 the abdomen, which follows light ijencilliug with the finger, and which remains 
 much longer than usual, sometimes two or three minutes. This ligne 
 blanche surrenalc is considered by Sergent to be a characteristic sign of 
 hypoadrenia.
 
 268 Practical Hormone Therapy 
 
 valescence, such as prostration, angemia, psychasthenia, 
 etc., are also due to deficient adrenal activity from subacute 
 inflammation of the adrenals. From the data which he 
 has so carefully gathered, Sergent concludes that the 
 systematic employment of adrenal preparations is justi- 
 fied in all cases of typhoid, and that the extracts of the 
 entire gland are indicated for the severe comphcations 
 due to acute hypoadrenia. Except in those hypertoxic 
 or hsemorrhagic cases which defy all treatment, this 
 method, associated with the ordinary treatment of 
 typhoid, gives considerably better results. 
 
 One of the outstanding features of dengue fever is the 
 profound asthenia, and only recently it has been shown 
 that this symptom (as well as the lumbar pain, cramps, 
 vomiting, etc.) is amenable to adrenal medication. This 
 fact, accidentally discovered, has led to an investigation 
 of the relation of adrenal insufficiency to dengue fever, 
 and it seems clear that this is a constant and essential 
 factor in this, to most physicians, rather rare disorder. 
 Khoury^^ relates having seen rapid improvement follow 
 the administration by mouth of 30 minims (2 c.c.) of 
 adrenaline solution (1 in 1,000), and urges its use in 
 every case. 
 
 Sajous^'^ describes a form of adrenal insufficiency occur- 
 ring late in the course of a febrile disease, which he con- 
 siders a result of exhaustion of the adrenals due to their 
 effort to protect the organism. He designates this con- 
 dition "terminal hypoadrenia," and suggests adminis- 
 tering dried adrenal gland in 3-grain (02 gramme) cap- 
 sules three times a day, the dose being gradually increased 
 to 5 grains (0-3 gramme). In more dangerous cases 
 adrenalin may be injected intravenously in saHne solu- 
 tion, or the solution (1 in 1,000) may be given subcu- 
 taneously in 10-minim doses.
 
 The Chromaffin System — Adrenal Therapy 269 
 
 Adrenal Therapy in Asiatic Cholera. — It seems that the 
 most useful drug in the treatment of cholera is adrenaline. 
 This does not mean that the use of vaccines, sera, or 
 other drugs is supplanted, but rather supplemented. 
 Sajous in 1903 first pointed to a connection between 
 adrenal insufficiency and Asiatic cholera, and since then 
 several interesting clinical reports have appeared. 
 
 Naame^^ of Tunis has reported the favourable results 
 of this treatment during an epidemic of cholera. He 
 finds that doses of 1 to 2 milligTammes of adrenaline 
 (not the total extract, for it is suggested that the cortical 
 part of the gland has a detrimental action in this par- 
 ticular condition) given hypodermically, or preferably 
 intravenously with normal sahne solution, stop the rice- 
 water stools, stimulate the heart, raise the pressure, and 
 in many cases cure the disease. Naame writes: "I am 
 firmly convinced that the cholera syndrome is an acute 
 hypoadrenia due to poisoning of the adrenals by toxins 
 of the cholera spirillum. . . . The attack consists of 
 two phases — the first bacillary, or intestinal, compara- 
 tively harmless; the second toxic, or adrenal, frequently 
 fatal. The grea.t tolerance to adrenaline manifested by 
 cholera patients shows that the organism is appropriating 
 an active principle of which it has been deprived by 
 the disease." ^^ 
 
 A number of other reports from India and elsewhere 
 confirm this position, and it seems estabhshed that 
 adrenal preparations are always indicated as a part of 
 the treatment of Asiatic cholera, plague, and similar 
 seriously toxic infections. 
 
 The Vomiting of Pregnancy. — Sergent and Lian^^ 
 think that the adrenals are a means of defence in the 
 control of the toxaemias of pregnancy arising from the 
 chorionic villi. They noted that where this toxaemia is
 
 270 Practical Hormone Therapy 
 
 unusually marked, the adrenals ma^/ become rapidly 
 exhausted through overwork. They therefore treated 
 refractory vomiting with adrenal extracts, and record 
 several cases in which prompt results were secured from 
 cachets containing 5 grains (OS gramme) of extract 
 given two or three times a day. 
 
 Silvestri,2° as well as other Italian investigators, is quite 
 partial to this method of treatment. He administers 
 adrenaline internally. He noticed that severe vomiting 
 often occurs in cases of Addison's disease, as also in 
 animals from which the adrenals had been removed. In 
 the case of a woman in whom the vomiting had resisted 
 all forms of treatment, adrenaline caused a complete 
 cessation in two days. Zanfrognini and Rebaudi also 
 report successful treatment. The latter describes the 
 case of a young woman in the third month of her second 
 pregnancy who was so exhausted that abortion had been 
 decided upon. Adrenahne was, however, first tried, 
 10 drops of a 1 in 1,000 solution being given twice daily. 
 The effect of the treatment was so rapid that in about a 
 fortnight the dose was reduced to half. In another ten 
 days the vomiting was entirely controlled, and remained 
 so until term. 
 
 Silvestri,^^ in a more recent reference to his use of this 
 method in pregnant women, does not agree with those 
 writers who emphasize the harmlessness of this treatment 
 in the dosage advised. Two recent experiences tend to 
 contradict this assumption. Two women in the second 
 month of pregnancy were given a mild course of adrena- 
 line and calcium salts, on account of an incipient apical 
 process and defective nutrition. Each aborted in less 
 than a month. He has given this treatment to other 
 women in later months of pregnancy, and never before 
 witnessed any tendency to abortion; and one of the
 
 The Chromaffin System. — Adrenal Thera/py 271 
 
 present patients had taken it without disturbance 
 during the last three months of a preceding pregnancy. 
 
 Cyclic Vomiting in Children. — This condition, occa- 
 sionally called " acetonsemic vomiting," because of the 
 frequency with which it is associated with acetonuria, 
 is considered by Terrien and others to be due to a transient 
 hypoadrenia. This being the case, the value of adrenal 
 therapy will be obvious. Terrien reports three cases in 
 detail in which rapid cessation or relief of the symptoms 
 followed injections of adrenaline. This writer enumerates 
 the signs of hypoadrenia very similarly to those already 
 mentioned. They vary from simple lassitude to com- 
 plete depression and somnolence ; lumbo-abdominal pains, 
 digestive disturbances varying from a comparatively un- 
 important hypotension to syncope and sudden death. 
 These same symptoms are found in cyclic vomiting of 
 children as well as in hyperemesis gravidarum and certain 
 cases of typhoid fever. They have frequently yielded 
 to the adrenal treatment, and this seems to be proof of the 
 relation of hypoadrenia to the causation of these serious 
 conditions. 
 
 Chronic Hypoadrenia in Children. — The disorders with 
 which adrenal insufficiency has been associated in the 
 preceding pages are for the most part acute or subacute 
 conditions. Occasionally, however, a chronic hypo- 
 adrenia may be found. 
 
 D'CElsnitz22 called attention to this at the recent Inter- 
 national Congress of Medicine (London, 1913). He 
 points out that there may occur in childhood, either 
 spontaneously or as a sequel to some acute disease, 
 slightly marked but persistent disturbances, which at 
 length react seriously on the general state and growth of 
 the child, and which are due to partial insufficiency of the 
 adrenal function. In very young children thus affected
 
 272 Practical Hormone Therapy 
 
 development in weight and height is at a standstill, the 
 muscles are flabby, walking is delayed, and the child is 
 apathetic and at times somnolent. Adrenal therapy 
 usually brings about more or less rapid cessation of these 
 manifestations. In boys before puberty there is noted 
 a condition of apathy, fatigue, and physical and mental 
 indolence. The child grows thin, and the blood-pressure 
 is low. Administration of adrenal preparations under 
 these conditions renders the boy more alert, and leads 
 him to work better and suffer less fatigue; the blood- 
 pressure rises, and the body-weight and stature augment 
 in a few months. Manifestations such as those described 
 may. of course, be due to other conditions, but the benefit 
 accruing from adrenal therapy in many cases would 
 seem to indicate a specific deficiency on the part of the 
 corresponding organs. 
 
 Usually the hypoadrenia is associated with deficient 
 internal secretory activity on the part of certain of the 
 other ductless glands. This hypoendocrinism is more 
 fully dealt with in the consideration of the use of pluri- 
 glandular extracts (Chapter XXX.). 
 
 The Stimulation of Bone Growth and Nutrition. — The 
 adrenals are evidently concerned in the growth and 
 maintenance of the osseous system. Carnot and Slavu^^ 
 seem to have demonstrated this most conclusively. In 
 order to ascertain the action of adrenahne in osseous 
 repair, they detached from the tibia a small ring of bone 
 and replaced it in position. Certain of the animals 
 experimented on were treated daily with injections of 
 adrenal extract in doses of 006 gramme; others served 
 as controls, and received no injections. It was found 
 that osseous repair was further advanced on the eighteenth 
 day in the treated animals than it was in the controls on 
 the twenty-third day.
 
 The Chromaffin System — Adrenal Therapy 273 
 
 In this connection it is interesting to note that Carnot^^ 
 has reported good results from this adjunct method of 
 treating fractures, and its value is increased where the 
 fractures are slow in uniting. 
 
 Numerous observations have confirmed the value of 
 adrenal extracts in osteomalacia, although it is evident 
 from a few contradictory reports that its value is not 
 constant. In spite of much clinical and experimental 
 research, it is still difficult to say to what factors the 
 beneficial effects of adrenal therapy are due. It may 
 result from a direct influence upon the calcium metabolism ; 
 or, again, it may be brought about by the action of the 
 adrenal hormones on the other endocrinous glands, stimu- 
 lating some or antagonizing others. Probably Blair Bell 
 is the nearest to the solution of this question in his ideas 
 regarding the control of calcium metabolism by the 
 ovaries, and the favourable action of adrenal prepara- 
 tions is due in part to their reflex (humoral) action upon 
 these glands. 
 
 Blair Bell^ states that: " The administration of supra- 
 renin has been successfully employed for osteomalacia. 
 This may be not only because suprarenin is antagonistic 
 to the ovarian secretion, but also because in this disease 
 there may be suprarenal insufficiency, a supposition 
 which is supported by the fact that in one case in which 
 I produced experimentally suprarenal insufficiency in a 
 rabbit, the bones of the fore-legs became bowed. Further, 
 in most of the animals operated on there was an enormous 
 increase in the urinary excretion of calcium. It appears, 
 therefore, that the secretions of the suprarenals are of 
 great importance during pregnancy in assisting the 
 absorption and retention of lime." A valuable resume 
 on this subject is found in the communication of Bon- 
 namour and Badolle.^^ 
 
 18
 
 274 Practical Hormone Therapy 
 
 Adrenal Medication in Pulmonary Disorders. — Sergent^^ 
 is partial to adrenal therapy in certain cases of tuber- 
 culosis. In many sufferers ^^from this disease will be 
 found a hypoadrenia which manifests itself by symp- 
 toms of asthenia out of proportion to the pulmonary 
 lesion. Occasionally there may be a pigmentation of 
 the skin or mucous surfaces. Then, too, there are cases 
 of phthisis in which a tendency to collapse is prominent, 
 or in which the heart itself is evidently especially weak; 
 and, finally, the favourable influence of the adrenals 
 upon calcification renders such medication of still 
 broader service. 
 
 Hence the administration of dry adrenal extracts or 
 adrenalin often may be followed by encouraging progress 
 in the control of a tubercle infection. Sergent especially 
 recommends an extract of the whole gland — cortex and 
 medulla — in the asthenic cases. 
 
 Adrenaline has been used with very good results in 
 pleurisy. Wedensky^'^ mentions a series of twenty cases 
 in which intrapleiu-al injections of a 1 in 1,000 solution 
 of epinephrine hydrochloride constantly yielded such 
 favourable results that he has discarded all other methods 
 of treating this condition, except by surgical intervention 
 where indicated. The amount injected was at first 
 03 c.c. (5 minims), and on the four or five succeeding 
 days 0-2 c.c. (3-33 minims), in saline solution. As a 
 result, the temperature begins to descend on the third 
 day, and the effusion is rapidly absorbed, so that by the 
 tenth day the presence of fluid was difficult to demon- 
 strate. In dry and in purulent pleurisy this treatment 
 was employed with benefit. Distinct improvement in 
 the general condition was among the additional favourable 
 effects noted. 
 
 The same procedure was tried by Volkova in six
 
 The Chromaffin System— Adrenal Therapy 275 
 
 cases of pleurisy with effusion, all in children ranging 
 from two to ten years of age. The dose used was at first 
 0-15 c.c. (2-5 minims) of the solution; this was later in- 
 creased to 0*3 c.c. (5 minims), and in one case even to 
 0*5 c.c. (8 minims). Rapid absorption of the effusion 
 followed, even in cases where previous exploratory punc- 
 ture had shown little or no tendency to initiate absorp- 
 tion. 
 
 The Combination of Adrenal and Other Endocrinous 
 Preparations. — Adrenal extracts are almost invariably 
 given alone, but there are a few references in the literature 
 to its administration in combination with pituitary 
 preparations. 
 
 Houssay^s says that the combination of adrenalin and 
 hypophysin unites the extensive adrenaline action upon 
 the heart and bloodvessels with the protracted effect of 
 hypophysin upon these organs. When these two sub- 
 stances are properly mixed, the depressive action of the 
 pituitary extract is lessened. Four to five drops of a 
 1 in 1,000 solution of adrenalin, with 1 c.c. of the " active 
 constituents of hypophysis," or of a 20 per cent, dilution 
 of some of the other constituents of the posterior lobe, 
 may be given intravenously in cases of shock or collapse. 
 Houssay beheves that, as adrenalin is rather toxic and 
 hypophysin is comparatively harmless, it is possible to 
 reduce the dose of adrenalin by this combination, and 
 yet increase its beneficial action. The combination may 
 be used successfully in fulminating intoxications asso- 
 ciated with hypotension, in tachycardia, and in myo- 
 carditis toxica, either subcutaneously or by mouth. The 
 combination produces a greater and more persistent local 
 ischsemia than adrenalin alone. The adrenalin neutrahzes 
 the powerful enterokinetic action of hypophysin, while 
 the active constituent of the posterior lobe of the hypo-
 
 276 Practical Hormone Therapy 
 
 physis counteracts the mydriatic effect of the adrenal 
 extract. 
 
 Weiss^^ recommends, in the treatment of asthma, a 
 preparation of adrenal and pituitary extracts known as 
 asthmolysin, and believes that in many cases asthma is 
 of humoral origin, and due to disturbance in the balance 
 of the internal secretions. Other combinations have been 
 suggested, and several of them are mentioned in Chap- 
 ter XXX. 
 
 The Influence of Adrenaline on Urticaria. — In six cases 
 of urticaria which Swann^° has treated by the subcu- 
 taneous administration of adrenaline, the injections were 
 followed by a rapid disappearance of the erythema and 
 wheals. In each case a dose corresponding to about 
 8 minims (1 in 1,000 solution) for an adult was given 
 hypodermically, and the dose was repeated in ten minutes. 
 Two doses sufficed in every instance to cause the com- 
 plete fading of the rash. An improvement was usually 
 seen about eight minutes after the initial dose, and was 
 most marked between ten and twenty minutes, during 
 which time, especially in the severe cases, the rapidity 
 with which the eruption subsided was very striking. 
 After twenty minutes there usually remained some 
 erythematous blotches, or small pale wheals, which con- 
 tinued to fade until the skin looked entirely normal. All 
 itching ceased in from five to twenty minutes after the 
 first dose. 
 
 The Adrenal Principle as an Angiotonic Remedy. — We 
 now must consider briefly the influence of certain prepara- 
 tions of the adrenal medulla in the treatment of circula- 
 tory conditions. Adrenal extracts produce an extra- 
 ordinary hypertensive action due to the vaso-constrictive 
 influence of the chromaffin hormone upon the periph- 
 eral vessels as well as upon the heart itself. This action
 
 The Chromaffin System — Adrenal Therapy 277 
 
 upon blood-pressure was, as we have already noted, first 
 discovered by Oliver and Schafer in 1894. This con- 
 stitutes the principal therapeutic property of these prep- 
 arations, and is the basis of almost nine-tenths of its 
 application as a local haemostatic — a matter which will 
 be referred to again. 
 
 For several years adrenaline has been used with excel- 
 lent results in the treatment of shock and collapse, but 
 it is now almost entirely superseded by pituitary prep- 
 arations, which have an equally salutary effect, and the 
 additional advantage that the influence is not so ephemeral 
 but persists for hours, where the action of the adrenal 
 preparations lasts only for minutes. 
 
 Bernouilh,^^ referring to this, states that: "It is pos- 
 sible that pituitary preparations, the stimulating action 
 of which is less dangerous and more lasting, will in the 
 future replace adrenal preparations, to which will always 
 remain the chief place in local anaesthesia and haemo- 
 stasis." 
 
 A number of writers have recommended adrenal ex- 
 tracts as a means of treating functional and organic 
 diseases of the heart. Floersheim^^ calls it an ideal heart 
 stimulant, and says that " no other drug can compare 
 with it for rapidity of action, strength, efficiency, and 
 safety combined." He reports a favourable influence 
 upon arrhythmia, dilatation and the strength of the 
 heart, but found no effect in those cases of organic cardiac 
 disease in which the pulse was strong and regular. 
 
 In the opinion of the present author, every case in 
 which adrenal preparations are used internally should 
 have both pulse and blood-pressure recorded. Where 
 this remedy is given for two or more days, charts should 
 be carefully kept, so that the physician may be aware of 
 the changing status of these manifestations.
 
 278 Practical Hormone Therapy 
 
 The manufacturers of adrenalin have culled the litera- 
 ture and collated many valuable clinical reports^^ refer- 
 ring to the successful use of this preparation in over 
 ninety different conditions, which fill a most interesting 
 104-page brochure. These experiences show the broad 
 scope and unquestioned value of this remedy, especially 
 in what has previously been called " the empiric use " of 
 this substance. 
 
 The Treatment of Snake-Bite. — It has been shown that 
 adrenaline has the property of retarding absorption from 
 the tissues into the circulation. This, combined with its 
 profound influence upon the circulation, has led to its 
 use in the treatment of snake-bite. A number of reports 
 may be found which show that it has been of great value 
 in such cases. It would almost appear that there is an 
 associated antitoxic action, as the following case reported 
 by Lankford^^ seems to indicate: "A young man was 
 brought from the country bitten by a large rattler snake, 
 and was in a condition of profound prostration, with 
 rapid and feeble heart action, pulse somewhat irregular, 
 temperature 96° F., vomiting frequently, restless and 
 delirious. I used adrenalin freely, and in a very short 
 time was rewarded by a reaction. The pulse came down 
 and grew stronger, blood-pressure rose, temperature came 
 up to the normal and a little above, the vomiting ceased, 
 and altogether the general condition was such within 
 two hours that I could see that the first results of the 
 poison were under control. This was quite remarkable 
 to me in face of an extremely dangerous condition. Of 
 course, there was the typical swelling and severe inflam- 
 mation, but besides overcoming shock, the adrenalin 
 seemed at once to arrest the poisonous action of the 
 venom upon the organism at large."
 
 The Chromaffin Sy-^^fem. — Adrenal Therapy 279 
 
 The Method of causing Local Vaso-Constriction.— Scores 
 of disorders in which local vaso-constriction is useful fre- 
 quently respond to adrenal preparations when applied 
 locally or given internally. As a local vaso-constrictor 
 these have supplanted all other preparations and pro- 
 cedures. In nose and throat therapeutics and surgery 
 it is daily used alone, or associated with cocaine, eucaine, 
 novocaine, or other local anaesthetics. Such combina- 
 tions are especially useful since less of the alkaloid is 
 required on account of the anaesthesia produced by the 
 local constriction of the vessels, while general absorption 
 of the alkaloid is to a certain extent hindered. In local 
 inflammations of the various mucous membranes it is of 
 much value, and the local hyperaemia associated with 
 such conditions as acute and chronic coryza, rhinitis, ton- 
 sillitis, pharyngitis, laryngitis, and hay fever respond to 
 its action very readily. 
 
 The Control of Local Hssmorrhage. — In gastric and 
 duodenal ulcer, when haemorrhage had occiu-red, there 
 are numerous reports of the good results of this treat- 
 ment. Some writers have mentioned a reaction follow- 
 ing the treatment, which it is desirable to avoid. It has 
 also been used in typhoid fever to prevent further loss 
 of blood, but it should be borne in mind that adrenaline 
 is a two-edged sword. 
 
 Haemorrhoids, especially those in which there is a con- 
 tinual slight haemorrhage, may be treated by means of 
 suppositories containing adrenal extracts. It is well to 
 remember that a condition of turgescence has often been 
 found to follow the temporary local anaemia caused by 
 the adrenahne. 
 
 In genito-urinary practice adrenaline has been success- 
 fully used as a decongestive agent generally, and in 
 urethritis, renal and ureteral haemorrhage, cystitis and
 
 280 Practical Hormone Therapy 
 
 cystic haemorrhages, prostatic congestion (as a local 
 application and in suppositories), and the reduction of 
 paraphimosis. 
 
 In dentistry the various adrenal preparations are 
 currently used alone or with local anaesthetics. Anal- 
 gesia is facilitated, and the congestion of the inflamed 
 areas diminished. 
 
 In the treatment of morphine addiction the circula- 
 tory disorders and collapse may be temporarily con- 
 trolled by this method, and Reichert is encouraged by his 
 successes with it. 
 
 Adrenalin as a Rational Treatment of Asthma. — The 
 vaso-constricting action of the adrenal principle has made 
 it a useful means of controlling the paroxysms of bron- 
 chial asthma. The mechanism of its action is now well 
 understood, although this should strictly be considered 
 an empiric method of treatment. A number of papers 
 relate very good results following the administration of 
 adrenalin by any of the usual methods — locally as a 
 spray, by mouth, subcutaneously, or intravenously. A 
 most interesting report was recently made by Meulen- 
 gracht,^^ who considers adrenalin to be the most satis- 
 factory means of treating asthma. He gives hypodermic 
 injections of | c.c. (corresponding to 0-0005 gramme 
 adrenaline chloride), and finds this method much more 
 satisfactory than the local spray. It has no cumulative 
 action, nor does the system become accustomed to the 
 drug. A case is reported to whom Meulengracht gave 
 no less than 1,500 such injections in nine months. 
 
 Adrenal Extracts in the Salvarsan Treatment. — It has 
 been suggested by Milian'"^*' that the occasional accidents 
 following the Ehrlich treatment of syphilis are in part 
 due to a disturbance of the adrenal function. The 
 symptoms of salvarfian--^omomng — vomiting, profuse
 
 The Chromaffin System — Adrenal Therapy 281 
 
 diarrhoea, cyanosis, anuria, etc. — are very similar to those 
 of the cholerif orm type of acute adrenal insufficiency, and 
 this writer is convinced from practical chnical experience 
 that adrenahne injections may be used as a preventive 
 of this condition. He also reports a case in which its 
 curative effect was manifest in a moribund patient. The 
 suggested dose is 1 to I". 5 milligrammes of suprarenin, 
 injected into the muscles of the buttock. Ravaut con- 
 firms this, and tells of having observed the disappearance 
 of the symptoms of nitrite-poisoning {les crises nitritdides) 
 following injections of the adrenal principle. This new 
 chapter in salvarsan therapy is of considerable im- 
 portance, and further investigative work should be 
 done.^'^ 
 
 The Relation of the Mind to Adrenal Activity.—The 
 broader influence of the chromaffin hormone in normal 
 physiology, and possibly in therapeutic practice, will be 
 better appreciated when the results of the most recent 
 work on this subject are mentioned. It is fortunate that 
 we are able to estimate very minute quantities of adrena- 
 line; and instead of having to depend upon extirpation 
 experiments, certain physiological phenomena may bo 
 brought about, and the resulting changes in the adrena- 
 hne-content of the blood accurately noted. Cannon^^ of 
 Harvard has recently published some suggestive con- 
 clusions regarding an emergency function of the adrenal 
 medulla. Fear, rage, or pain, causes an increased libera- 
 tion of the internal secretion of these glands, and by its 
 stimulation* bring about changes that are directly ser- 
 
 ♦ The results of this stimulation are thus explained by Cannon: "The 
 cessation of activities of tlie alimentary canal (thus freeing energy for other 
 parts), the shifting of the blood from the less insistent abdominal viscera to 
 the organs immediately essential to life itself, such as the lungs, the heart, 
 the central nervous system, and, at critical moments, the skeletal nmscles as 
 well the increased cardiac vigour, the quick abolition of muscular fatigue, 
 and the mobilizing of energy-giving sugar in the circulation."
 
 282 Practical Hormone Tlierapy 
 
 viceable in making the organism more efficient in the 
 struggle which may be in prospect. 
 
 Occasionally this stimulation may be too great, and 
 the resulting condition of adrenal depletion may be 
 serious. In this connection it may be interesting to 
 recall that in Asiatic cholera the most distressing symp- 
 tom is the terrible pain in the abdomen. Attention has 
 been directed to the theory that cholera is always asso- 
 ciated with acute adrenal insufficiency; and, with Can- 
 non's conclusions in mind, it is not unreasonable to sup- 
 pose that the pain itself is an important factor in causing 
 the hypoadrenia. If this is so, the great indication is 
 to obviate the pain as much as possible, at the same time 
 attempting to replace the lost adrenal principle, and, of 
 course, to control the infection. 
 
 Chemistry and Nomenclature. — The chromaffin hor- 
 mone is one of the most active of all the internal secre- 
 tions. It has been isolated in the form of a definite 
 crystalline compound, having the formula C9H13O3N 
 (Aldrich), and a very similar body has been prepared 
 synthetically. There is a vast literature on this subject. 
 Scores of preparations are upon the market, each with 
 its different name, a fact which is at once inconvenient 
 and unscientific. The Council of Pharmacy and Chemistry 
 of the American Medical Association has suggested the 
 word "epinephrin " * as being the most suitable, and the 
 Journal of the American Medical Association now uses it 
 exclusively, and reports work done with adrenalin, 
 hemisine, or swprarenin, etc., with the " standard " word 
 "epinephrin," which hardly seems fair to the reader or 
 the manufacturer. 
 
 * This ^vord " epinephrin " was given by Abel to what he supposed to be 
 tlie active principle of the adrenal gland, but wliich was found later to be a 
 niono-benzoyl derivative of the active principle. Later Abel retained this 
 name, and it has been emi)loyed as a synonym for adrenalin and other similar, 
 but different, preparations.
 
 The Chromaffin System, — Adrenal Therapy 283 
 
 Contra-Indications to Adrenal Therapy. — One of the 
 principal contra-indications of the administration of all 
 adrenal preparations is diabetes mellitus, and it will be 
 quickly apparent that these products cause a consider- 
 able increase in the elimination of sugar. We have 
 already seen how this is brought about, 
 
 Lucien and Parisot^^ mention a case of diabetes in 
 which the amount of sugar was largely increased, not 
 merely for a few hours, but for several days, following 
 an injection of y^ milligramme of adrenaline for the 
 performance of a dental operation. This indicates that 
 the action of the adrenaline is not confined to the in- 
 fluence of the actual remedy, but that it is a strong 
 stimulant of the adrenal secretion.* These authorities 
 also warn against the possibilities of untoward reactions 
 in cachectic individuals and those who are very debili- 
 tated. Naturally, hypertension is an important contra- 
 indication, and with it, of course, must be included 
 vascular disease, atheroma, aneurism, etc. 
 
 The instillation of a weak adrenalin solution into the 
 conjunctival sac may cause, in patients with hyper- 
 adrenia, serious palpitation, dyspnoea, and general weak- 
 ness. This is sufficient indication for extreme care in 
 the employment of this potent remedy and in cases of 
 known adrenal overactivity (diabetes, hypertension, etc.) 
 it should be used only in great necessity. One should also 
 institute adrenal therapy with very small doses, in order 
 to test the susceptibilities of each patient to its action, 
 and to obviate unfortunate results which in not a few 
 recorded cases have had a fatal outcome. 
 
 * In spite of this it may be read in a pamphlet circulated by a prominent 
 manufacturer that "suprarenal substance has been highly recommended by 
 authorities in . . . diabetes" — surely only in the installation test already 
 mentioned in this chapter. Dr. Sajous comments on this as follows : " Care 
 is necessary here. Adrenal gland is sometimes useful in the asthenic form."
 
 284 
 
 Practical Hormone Therapy 
 
 The activity of adrenal preparations may be a detri- 
 ment, and, unfortunately, untoward results are not un- 
 common. Donaldson'*^ considers this side of the subject, 
 and wisely recommends care in the selection of cases as 
 well as in the administration of the remedy. 
 
 Although we have seen that there are certain common 
 indications for adrenal and pituitary (posterior) medica- 
 tion, especially in shock, haemorrhage, etc., adrenahne 
 cannot be used as an oxytocic, for as a matter of fact 
 such an application would be hkely to be attended by 
 unfortunate results, since adrenaline has a relaxing 
 action upon the uterus. 
 
 Adrenalin is distinctly contra-indicated in haemoptysis, 
 and, according to Sergent,^^ when adrenal preparations 
 have been given to tuberculous patients, they should be 
 immediately stopped if pulmonary haemorrhage occurs. 
 
 BIBLIOGEAPHY 
 
 Vincent:* p. 89. 
 
 B:fiRNAED (L.): Relations entre les syndromes surr^naiix et les 
 
 troubles des fonctions siirr^nales, Pr. med. (Paris), 1913, 
 
 xxi, 81. 
 Bulloch (W.) and Sequeika (J. H.): On the relation of the 
 
 suprarenal capsules to the sexual organs, Trans. Path. Soe. 
 
 (London), 1905, Ivi, 189. 
 Glynn (E. E.): Some observations on the influence of certain 
 
 ductless glands upon the sex characters, Liverpool Med. Chir. 
 
 J., 1912, xxxii, 149. 
 See Editorial: The adrenal cortex in relation to sexual 
 
 characteristics, J. J,m. Med. Assn. (Chicago), 1912, Iviii, 1017. 
 Keller (R.): Ueber Funktionspriifungen der Ovarialtatigkeit, 
 
 Munch, med. Wchnschr., 1913, Ix, ii, 2162. 
 Varaldo (F. R.): Experimentelle Untersuchungen ueber Eier- 
 
 stocks veranderungen infolge wiederholter Adrenalin insprit- 
 
 zungen, Zentr.f. Gyn. (Leipzig), 1913, xxx\'ii, 1350. 
 Blum (F.): Ueber Nebeunierendiabetes, Deut. Arch. f. kl. Med. 
 
 (Leipzig), 1901, cxlvii, 71. 
 Zuelzer (G.): Zur Frage des Nebennierendiabetes, Berl. kl. 
 
 Wchnschr., 1901, xxxviii, 209; see also id., Untersuchungen 
 
 ueber den experimentellen Diabetes, Centr. f. inn. Med. 
 
 (Leipzig), 1907, xxviii, 528.
 
 The Chi'omafjin System — Adrenal Therapy 285 
 
 10 Cannon (W. B.) and Nice (L. B.): The effect of adrenal secre- 
 
 tion on muscular fatigue, Am. J. Physiol. (Boston), 1913, 
 xxxii, 44. 
 
 11 Editorial: The adrenals and muscular eflBciency, J. Am. Med. 
 
 Assn., 1913, Ixi, 123. 
 
 12 See Merck's Annual Report, 1908, xxii, 17. 
 
 13 Sajous:* vol. i. 
 
 1* Crile (G. W.): The kinetic system, Clev. Med. J., 1913, xxvi, 
 
 693. 
 15 Sergent (E.): Maladies des capsules surr6nales: syndromes 
 
 surr^naux; maladies 1' Addison at insuffisance suir^nalo: 
 
 opoth6rapie surr6nale. Bull. gen. d. Ther. (Paris), 1912, 
 
 clxxii, 881. 
 1® Khoury (A.): L'insufflsance surrenale dans la fievre dengue. 
 
 Bull, et mem. Soc. mid. d. Hop. (Paris), 1913, xxxvi, 498. 
 1' Sajous (C. E. de M.): Hypoadrenia as a cause of death in 
 
 infections and its treatment, Mo. Cyc. and Med. Bull. 
 
 (Philadelphia), 1911, iv, 725. 
 1^ Naame: Organotherapie ou serotherapie, J. d. Pract. (Paris), 
 
 1912, xxvi, 87; see also id., " ;6tudes d'Endocrinologie " 
 
 (Paris), 1913, p. 13. 
 19 Sergent (E.) and Lian (C): Du role de I'insuflQsance surrenale 
 
 dans les vomissements gravidiques incoercibles, Pr. med. 
 
 (Paris), 1912, xx, 1033. 
 2° SiLVESTRi (L.): L'adr6naline contre les vomissements de la 
 
 grossesse, Sem. med. (Paris), 1909, xxix, 536. 
 -1 Id.: Puo r adrenalina provocare 1' aborto, Gaz. d. Osp. e. d. 
 
 Clin. (Milan), 1913, xxxiv, 1351. 
 
 22 D'CElsnitz: L'insuffisance surrenale chronique fruste chez 
 
 Fenfant, Pr. mid. (Paris), 1913, xxi, 755. 
 
 23 Carnot (P.) AND Slavu (G. I.): Influence de I'adr^naline sur 
 
 la reparation osseuse et revolution du col, C. r. Soc. Biol. 
 
 (Paris), 1910, Ixviii, 832. 
 2* Blair Bell (W.) : The internal secretions and female character- 
 istics, Proc. Boy. Soc. Med. (Sec, Obs.), (London), 1913, vi, 
 
 74; see also Bossi (L. M.): The influence of the suprarenal 
 
 glands on the bony skeleton in relation to osteomalacia and 
 
 rickets, Br. Med. J. (London), 1908, ii, 797. 
 25 BONNAMOUR (S.) AND Badolle (A.): Lc Syndrome osteo- 
 
 malacique, ses diff6rents causes, Bev. d. mid. (Paris), 1913, 
 
 xxxiii, 889. 
 28 Sergent (E.): L'opotherapie surrenale dans la tuberculose, 
 
 Pr. mid. Beige (Bruxelles), 1913, Ixv, 579. 
 2' Wedensky (M.): Traitement des pleuresies par les injections 
 
 intrapleurales d'adrenaline, Sem. mid. (Paris), 1913, xxxiii, 
 
 441. 
 2^ HoussAY (B. A.): Ueber die Kombination von Adrenalin und 
 
 Hypophysin und dereu klinische Verwendbarkeit, Wien. kl. 
 
 Wchnsckr., 1913, xxvi, 489.
 
 286 Practical Hormone Therapy 
 
 28 Weiss (0.): Neuer Weg zur Asthmabehaudlung, Deut. med. 
 
 Wchnschr. (Leipzig), 1912, xxxviii, 1789. 
 ^° SwANN (A. W.): Urticaria treated with epinephrin. Am. J. 
 
 Med. Sci. (Philadelphia), 1913, cxlv, 373. 
 
 31 Bernouilli (E.): Wirkung uiid therapeutische Verwendung 
 
 der Nebennierenpreparate, Corr. f. Schw. Aertze (Basle), 
 1912, xlii, 1149. 
 
 32 Floersheim (S.): The use of the suprareual capsule in diseases 
 
 of the heart, N. Y. Med. J., 1901, Ixxiii, 761, 847. 
 
 33 "Adrenalin": see under "Manufacturers' Literature" in 
 
 " List of Books " (Appendix). 
 3* Lankford (J. S.): Adrenal preparations in snake-bite, N. ¥. 
 
 Med. J., 1913, xcvii, 1379. 
 3* Meulengracht (E.): Adrenalin Behandliug ved Asthma 
 
 bronchiale, Ugeskr.f. Lceger. (Copenhagen), 1913, Ixxv, 1847. 
 3^ MiLiAN : L'importance de I'insuffisance surrenale dans la genese 
 
 et le traitement des accidents consecutifs au neo-salvarsan, 
 
 Pr. med. (Paris), 1914, xxii, 129. 
 3' Editorial: The physiological antagonism of adrenalin and 
 
 salvarsan, Br. Med. J. (London), 1914, i, 212. 
 
 38 Cannon (W. B.): The emergency function of the adrenal 
 
 medulla in pain and the major emotions, Am. J. Physiol. 
 (Boston), 1914, xxxiii, 356; see also Cannon (W. B.) and 
 De la Paz (D.): The stimulation of adrenal secretion by 
 emotional excitement, J. Am. Med. Assn. (Chicago), 1911, 
 Ivi, 742. 
 
 39 Lucien and Parisot:* p. 361. 
 
 *" Donaldson (M.): Some observations on the [harmful] effects 
 of adrenalin, Br. Med. J. (London), 1914, i, 476. 
 
 Menger (R.): The rational treatment of snake-bites with 
 
 adrenal in chloride, Tex. Med. J. (Au.stin), 1902, xviii, 445. 
 Sajous (C. E. de M.): Physiological action and uses of adrenal 
 
 extractives. Mo. Cyc. and Med. Ball. (Philadelphia), 1910, 
 
 iii, 67. 
 Floersheim (S.): Adrenalin therapy, Amer. Med. (New York), 
 
 1908, iii, 450. 
 Roger (H.): Les substances hypotensives des capsules sur- 
 
 renales, C. r. Soc. Biol. (Paris), 1910, Ixix, 160; see also ibid., 
 
 p. 185. 
 Belfield (W. T.): a case of retrograde puberty, impotence, 
 
 and diabetes insipidus relieved by suprarenal cortex, J. Am. 
 
 Med. Assn. (Chicago), 1910, Iv, 215. 
 Sergent (E.): L'opotherapie surrenale, J. med. frant;. (Paris), 
 
 1911, V, 47. 
 Marie (A.): Glandes surrenales et toxi-infections. Troisieme 
 
 note, C. r. Soc. Biol. (Paris), 1913, Ixxiv, 221. 
 SiLVESTRi (T.): Opoterapia surrenomidollare ed epilessia, 
 
 Poiicl. (Rome), 1913, xx (M), 917.
 
 CHAPTER XIX 
 
 THE HYPOPHYSIS OR PITUITARY BODY 
 
 Histologic Structure and Physiologic Action — Schafcr's Outline 
 of the Functions and Relations of the Pituitary — The Physio- 
 logical Actio7i of Pituitary Extract — The Manifestations 
 and Treatment of Pituitary Disease — The Active Principles 
 of the Pituitary — Pituitary Therapeutics — The Effect on 
 Shock and Collapse — Pituitary Extract in Labour — The 
 Contra- Indications in Obstetrics — In Gyncecological Practice 
 — The Influence on Amenorrhosa — A71 Enterokinetic or Peri- 
 staltic Excitant- — The Value in Post-Operative Intestinal 
 Disturbances — The Action on Diuresis — Diabetes Insipidus 
 and the Pituitary — The Control of Polyuria voith Pituitrin 
 — The Galactagogue Action — Pituitary Extract in threatened 
 Mammary Abscess — The Tonic Effect of Pituitary Powder 
 — A Hypotensive Pituitary Extract — Miscellaneous Thera- 
 peutic Possibilities — The Differences between Pituitary Pre- 
 parations — Methods of Administration — Dosage — Contra- 
 indications. 
 
 The internal secretory organs have given investigators 
 many a surprise, and not least remarkable is the informa- 
 tion that has been obtained by studying the hypophysis 
 or pituitary body. 
 
 While the existence of this organ has been known for 
 ages — it is asserted by some writers that in the days of 
 priest-medicine this gland was considered to be the 
 envelope of the soul — the present-day knowledge of the 
 physiology of the pituitary, and more especially its 
 therapeutic possibilities, is of quite recent discovery. 
 
 Not so long ago the pituitary was called by the French 
 Vorgane enigmatique, but now that the riddle is being 
 solved, it is almost as hard to believe the truth concerning 
 
 287
 
 288 Practical Hormone Therapy 
 
 the importance of this organ and the action of its extracts 
 as it is to reahze how ignorant we have been. 
 
 Histologic Structure and Physiologic Action. — Embry- 
 ology has taught us that the pituitary body develops from 
 two dissimilar cell aggregates, the one part from the roof 
 of the mouth (Rathke's pouch), and the other from the 
 nem*al canal or ventricle. The epithelial part is now known 
 as the " anterior lobe," while the smaller neural portion 
 is called the " posterior lobe," or the " infundibulum." 
 
 Physiology has explained that the function of the 
 different portions of the pituitary are quite diverse, and 
 histology shows that their structure is also different, the 
 anterior or glandular portion having a yellow or reddish- 
 grey colour, and showing microscopically well-formed 
 columns of cells; while the smaller posterior lobe is of a 
 whitish colour, and under the microscope shows much 
 connective tissue, fibres, neurogUa, and eosinophile cells. 
 Between the lobes, and connecting them, is a third 
 portion, the so-called " pars nervosa " or " pars inter- 
 media," which consists almost wholly of cellular tissue, 
 which has been compared to neuroglia fibres, and contain- 
 ing many basophile cells. 
 
 Some still insist that the pituitary is virtually an 
 aberrant thyroid (Gauthier^), but this is most unlikely, 
 although it is not impossible that there may be some 
 developmental relation between the anterior lobe, which 
 will shortly be mentioned. 
 
 The whole study of the subject has been rendered 
 difficult by the inaccessibility of this gland, and the 
 danger hitherto associated with experimental operations 
 upon it ; but with increasingly efficient surgical procedures 
 and better cUnical information our present useful know- 
 ledge has been gained. 
 
 The chnical study of patients suffering from pituitary
 
 The Hypophysis or Pituitary Body 289 
 
 disease has been quite thoroughly outUned, fii'st by the 
 French, and later by American, Enghsh, and other writers. 
 Pierre Marie, and later Renon and DeUlle of Paris 
 deserve much credit for pioneer work done on this inter- 
 esting study, and Delille's book^ must have been a series 
 of surprises when it was first published. Gushing of 
 Harvard has made himself famous by his thorough study 
 of this subject, and his magnificently illustrated mono- 
 graph^ gives a concise outhne from which one can easily 
 compare the history, clinical and physical findings, and 
 outcome of numerous cases of pituitary disorder. 
 
 Schafer's Outline of the Functions and Relations of the 
 Pituitary. — One of the most concise summaries of our 
 present knowledge of the pituitary hormones is that given 
 by Schafer,^ and as it could not well be stated more 
 succinctly, it is given here : 
 
 " Some functions of the organ might be conceived to 
 be carried out through the agency of the nerves, but it is 
 much more probable that the gland produces its action 
 by means of chemical agents or hormones, which pass 
 either directly or indirectly into the blood, and through 
 this fluid influence other and distant organs. No hor- 
 mone has hitherto been separated from the pars anterior, 
 but there is reason to believe that its influence on growth 
 is not produced through nerves. ... It is difficult to 
 explain the fact of hyperplasia of the pars anterior in pro- 
 ducing the hypertrophy which occurs in acromegalics 
 otherwise than by assuming that the enlarged gland is 
 giving a greater amount than normal of a hormone which 
 stimulates the growth of the skeleton, and probably of 
 connective tissue generally. 
 
 " The hormone obtained from the posterior lobe 
 resembles in some of its eft'ects the hormone obtained 
 from the medulla of the suprarenals, but it is both chemi- 
 
 19
 
 290 Practical Hormane Therajjy 
 
 cally and physiologically a different body. It is at present 
 uncertain whether there is only one hormone in the 
 sahne extract of the posterior lobe.* It is probable, 
 however, that the effects upon secretion are brought about 
 by a different agent or agents from that which causes 
 contraction of involuntary muscle. 
 
 " Some relationship appears to exist between the 
 thyroid and the pituitary. This is indicated by pituitary 
 enlargement and the formation within it of colloid-con- 
 taining vesicles following removal or atrophy of the 
 th3rroid. Other tissues may also be influenced, as is 
 evidenced by the symptoms produced on removal or 
 destruction of either gland, amongst these being defects 
 of the nervous system. There also seems to be a correla- 
 tion between the pituitary and sexual organs, since where 
 supposed pituitary deficiency exists, sexual infantilism 
 is established, secondary sexual characters may remain 
 undeveloped, or in males may exhibit a feminine type." 
 A further consideration of this subject is found in Dunan's^ 
 paper. The various physiologic effects of these hor- 
 mones are available in therapeutics, since the active 
 principles are found in suitably prepared extracts of the 
 posterior lobe of the hypophysis. 
 
 The Manifestations and Treatment of Pituitary Disease. 
 — Pituitary disease is divided into two distinct groups — 
 those cases in which there is an increased function of the 
 pituitary (hyperpituitarism), and those showing dimin- 
 ished or lost function (hypopituitarism). Clinical findings 
 in these various cases enable us to gather a very good 
 idea of the importance of the pituitary hormones, and to 
 draw many conclusions concerning pituitary therapeutics. 
 The intricacies of the study of pituitary disease are 
 too complex to be considered here. Gushing has fully 
 
 * See Flihnei's later conclusions on p. 293.
 
 The Hypophysis or Pituitary Body 291 
 
 discussed the various aspects of this subject in his book. 
 It remains for us to refer to the use of pituitary extracts 
 in the treatment of these conditions. Pituitary medica- 
 tion does not cure hypopituitarism, probably for the 
 same reason that Addison's disease is not usually amen- 
 able to adrenal therapy, and thyroid therapy will not 
 entirely replace an absent or atrophied gland. There 
 can be no doubt, however, about the value of substitution 
 therapy with pituitary extract. Many cases are on 
 record which show that the continuous use of whole-gland 
 preparations reduces the adiposity so commonly found in 
 these cases, stimulates the skin action as well as the 
 growth of hair, reduces the asthenia, and stimulates the 
 sexual organs, especially in individuals with infantilism 
 and Frohlich's syndrome {dystrophia adiposo-genitalis). 
 Occasionally a seemingly permanent result is mentioned, 
 and there is no relapse after discontinuing the medication. 
 On the other hand, too often there is a recurrence of the 
 symptoms if the necessary dosage is not kept up. The 
 dosage is somewhat indefinite, and must be adjusted to 
 the exigencies of each case. Gushing*^ suggests a good 
 method of estimating the proper dosage in these cases: 
 " In hypopituitarism the rational dosage of glandular 
 extract to be administered by mouth can possibly be 
 determined by giving the individual daily an amount of 
 glucose or laevulose sufficient to produce a temporary 
 mellituria in a normal individual of equal body weight; 
 meanwhile an increasing amount of the extract is ad- 
 ministered daily until, under the conditions of increased 
 carbohydrate tolerance which the patient exhibits, hyper- 
 glycaemia occurs, with a trace of sugar in the urine." 
 
 In acromegaly the usual condition of hyperpituitarism 
 may eventually become what is termed " dyspituitarism," 
 and in such cases moderately good results have followed
 
 292 Practical Hormone Therapy 
 
 pituitary medication, while pluriglandular therapy has 
 also been recommended. 
 
 It happens that the occasions for applying substitution 
 pituitary therapy are rare, since definite pituitary disease 
 is not common; but the study of the physiological action 
 of the various extracts of the hypophysis will open up a 
 vast field of empirical pituitary therapy which will be seen 
 to be much more frequently available. 
 
 The Physiological Action of Pituitary Extract. — It was 
 in 1895 that Schafer and Ohver'^ studied the influence of 
 numerous glandular extracts, and made the first important 
 announcement regarding the physiological action of 
 extracts of the pituitary gland. They found that watery 
 or saline extracts, even when boiled, raised the blood- 
 pressure and constricted the peripheral bloodvessels. 
 Three years later HowelF observed that the property of 
 increasing blood-pressure was confined to the extracts of 
 the posterior lobe alone, and that when the blood- 
 pressure was raised, the pulse was slow. In 1901 Magnus 
 and Schafer^ found that this extract was markedly 
 dim-etic, and in 1906 Herring and Schafer^^ observed that, 
 although infundibular extract constricts the arteries in 
 general, it dilates those of the kidneys. King and 
 Stoland^^ have also reported on this phase of the action 
 of pituitary extracts. Wiggers^^ showed that the extract 
 slows the heart and increases the amplitude of its con- 
 tractions. This Avriter also noticed that it inhibits the 
 flow of pancreatic juice, and is slightly mydriatic. In 
 addition to this, it was later discovered that pituitary 
 extract causes contraction of involuntary muscles gener- 
 ally, raising blood-pressure, and has a particularly 
 noticeable effect on uterine,* vesical, and intestinal 
 
 * A substance with a somewhat similar action iii>on involuntary muscle is 
 obtained from extracts of intestine, and, unlike pituitary preparations, it 
 reduces blood -pressure. This subject is referred to more fully in Chapter VI.
 
 The Hypophysis or Pituitary Body 293 
 
 muscles. Ott and Scott^^ have shown that it promotes 
 the flow of milk, and this observation has since been con- 
 firmed by Schafer and MacKenzie.^"* 
 
 The Active Principles of the Pituitary. — The pituitary 
 is one of the few glands from which a definite chemical 
 has been obtained. It is available as the salt of sulphuric 
 acid — hypophysin sulphate — and standardized 1 in 1,000 
 solutions are now put up. Hertzberg^^ tried it in a series 
 of thirty-two parturient women, and found that it com- 
 bined all the advantages of the usual extracts with few, 
 if any, of the imdesirable effects. About one month 
 later Fiihner's^® report appeared, and he evidently refers 
 to the same active principle. Fiihner was able to isolate 
 no less than eight different substances from the extract 
 of the infundibular portion of the hypophysis. Only four 
 of these manifested the well-known action upon the 
 uterine musculature. The preparation called hypophysin 
 consists of a sterile mixture of these four substances, and 
 thus it has become possible to give, with precise dose and 
 with a definite object in view, the active principles of 
 the pituitary body. Furthermore, this writer's experi- 
 ments on cats, rabbits, rats, and guinea-pigs have 
 demonstrated that this preparation has a specific action 
 upon the uterus, and that the action upon respi- 
 ration and blood-pressure occurs only with relatively 
 higher doses than are required to produce the uterine 
 effect. 
 
 Pituitary Therapeutics. — From the information collated 
 above, it will be evident that pituitary extracts have an 
 exceptional range of therapeutic possibilities, and in the 
 eighteen years that have passed since Schafer and Oliver's 
 original discovery, and especially during the last four 
 years, many hundreds of cases are reported which suggest 
 startling possibihties. Without attempting the almost
 
 294 Practical Hormone Thera'py 
 
 impossible task of going thoroughly into this literature, 
 a summary can be given which embodies the principal 
 facts brought out by various investigators. 
 
 One is tempted to discount statements which attribute 
 to pituitary extract such widely differing possibilities, 
 and were it not for the fact that the deductions are based 
 upon thousands of cases and experiments almost without 
 number, one might be permitted to think that the state- 
 ments are too good to be true. 
 
 Fortunately, there are a number of very good pituitary 
 preparations on the market, and some of the more pro- 
 gressive manufacturers are now standardizing their prep- 
 arations by physiological tests. Hence personal con- 
 viction of their therapeutic value is very quickly and 
 easily obtained in clinical practice. Biedl and several 
 others have a predilection for an extract of the whole 
 gland, and he recommends it in cases where it is desirable 
 to increase blood-pressure, reduce the pulse, stimulate 
 diuresis, improve the appetite and capacity for sleep, 
 and, generally speaking, to combat asthenia and stimulate 
 nutrition. Hallion also, like many French writers, is in 
 favour of preparations made from the whole gland. 
 However, by far the greatest experience has been gained 
 with the use of extract of the posterior lobe, or infundi- 
 bulum, and at least 200 papers on the value of piiui- 
 trin, hyjjophysin, infundibuhn, and other similar prepa- 
 rations, are to be found in the literature of the last four 
 years. 
 
 The Effect on Shock and Collapse. — The principal worth 
 of preparations of the posterior lobe lies in their remark- 
 able contractile influence upon unstriped muscle. This is 
 especially evident in the control of the vascular muscu- 
 lature that is exercised by them in shock. Pituitary
 
 The Hypophysis or Pituitary Body 295 
 
 extract* is the remedy par excellence in shock, since this 
 condition is essentially a state of vasomotor paralysis, 
 and consequent reduced blood-pressure. Its power of 
 contracting involuntary muscle makes pituitary extract 
 invaluable, for the accumulation of the blood in the large 
 veins (splanchnics) is prevented in this condition. Blair 
 Bell of Liverpool" was the first to make a thorough 
 laboratory and clinical study of this subject; and while 
 there are references to the experimental use of pituitary 
 preparations before 1909 (it will be remembered that the 
 tonic effect on the bloodvessels was described by Schafer 
 and Oliver as far back as 1895), Blair Bell deserves great 
 credit for having given us the first information regarding 
 their clinical possibilities. His conclusions regarding the 
 applicability of infundibulin in surgical shock (as well 
 as in intestinal paresis and uterine atony) are generally 
 accepted; in fact, no operating-room is now considered 
 properly equipped unless a pituitary preparation is at 
 hand to meet the emergency. Adrenal preparations have 
 been quite superseded, at least in this particular condition, 
 for pituitary extract causes a rise in blood-pressure fully as 
 rapid as that produced by adrenalin, and has the addi- 
 tional advantages of much greater safety and more pro- 
 longed action; for while the influence of adrenal prepara- 
 tions is very transitory and is asserted by some to be 
 followed by undesirable after-effects, that of pituitary is 
 prolonged for hours, and in proper doses is without the 
 least danger. Bernouilli^^ expresses the opinion that 
 "it is possible that pituitary preparations, the stimulant 
 
 * In this chapter, as is usual elsewhere in the vohiminous literature on 
 pituitary extracts, the extracts referred to are all made from the posterior 
 lobe. As a matter of fact, preparations from the anterior lobe alone are not 
 generally obtainable and are rarely used, for their influence is quite unlike 
 that of infundibular preparations.
 
 296 Practical Hormone Therapy 
 
 action of which is less dangerous and more lasting, will 
 [in shock and collapse] replace in future adrenalin, to 
 which will always remain the chief place as a local anaes- 
 thetic and haemostatic." 
 
 HilP^ of Pittsburgh reports that, thanks to pituitrin, 
 shock has become unknown in his service, for he uses it as 
 a prophylactic, giving all laparotomy patients an injec- 
 tion prior to their entering the operating-room, and 
 again every hour for three hours on the return to 
 bed. 
 
 Another interesting point which has been mentioned 
 is that infundibulin acts, as is the case with certain 
 drugs, in raising blood-pressure better when the animal 
 or subject is in a condition of shock than under the normal 
 conditions. Dale^^ remarks in this connection that 
 "there is an increasing body of evidence which indicates 
 that the pituitary principle acts on plain muscle more 
 by increasing its sensitiveness to normal stimuli than by 
 acting as a direct stimulant {cf. v. Franld-Hochwart and 
 Frohlich). In the normal person it causes no rise of 
 blood-pressure; in the experimental animal with high 
 blood-pressure it may even cause a fall. Yet when the 
 pressure is artificially lowered, as by cutting off the vaso- 
 motor centre, the tonic effect of pituitary extract on the 
 arteries is great and prolonged." 
 
 Pituitary Extract in Labour. — Most remarkable of all 
 is the physiologic stimulation of the uterus that is made 
 possible by injecting pituitary extract. The credit for 
 this important discovery belongs to Dale^i of the Well- 
 come Research Laboratories, although he did not then 
 recognize its potential value or suggest its clinical 
 use. 
 
 It is probably the ideal oxytocic and uterine haemostat. 
 Blair Bell,^'^ working independently, foresaw the obstetric
 
 The Hypophysis or Pituitary Body 297 
 
 possibilities of pituitary extract, and recorded cases 
 illustrating its value in this respect as a result of his 
 experimental work carried out in conjunction with 
 Hick. 21a In 1909 he wrote: " I am inclined to think that 
 in the future we shall rely on infundibular extract to 
 produce contractions of the uterus in many serious 
 obstetric comphcations, although in my opinion it ought 
 but rarely to be given before delivery." However, it 
 was about a year later that Hofbauer's^^ paper started 
 a veritable avalanche of reports on the obstetric value 
 of pituitary extract. The prompt results obtained in 
 difficult and delayed labour place this substance far 
 above the old methods of uterine stimulation. Intra- 
 muscular injections are often active in five minutes or 
 less, and the effects following its proper administration 
 are apparently not harmful to either mother or child.* 
 Blair Bell intimates that pituitary extract exercises a 
 selective action which is more apparent upon the preg- 
 nant uterus, and states that " not only are the contrac- 
 tions in the human uterus made more powerful, but they 
 are more prolonged than are those produced by any other 
 preparation. There is little doubt that this preparation 
 acts on the atonic uterus as well as, if not better than, 
 on the contracting organ." 
 
 A very good resume of the value of pituitary extract 
 in obstetrical practice is contained in a paper by Watson,^^ 
 who sums up his experience as follows : 
 
 1. Pituitary extracts have a powerful effect in in- 
 ducing and in strengthening uterine contractions. 
 
 2. The type of contractions induced is similar to that 
 
 * There are isolated cases on record where tlie child died after delivery, 
 the pulse being very slow during the short period of its life. These almost 
 invariably can be traced to ignorance in the administration of this remedy 
 (see Sjiaeth's articles). ^3 Then, too, pituitary extract does not always act so 
 rapidly or witli average dosage, and very rarely seems to have no favourable 
 influence upon the uterus at all.^*
 
 298 Practical Hormone Therapy 
 
 which occurs normally, although at first there may be a 
 tendency to prolongation of the pains. 
 
 3. Such prolonged contractions result in slowing of the 
 foetal heart, but the child is seldom in danger. 
 
 4. When given in the late part of the first and in the 
 second stage of full-time labour, the polarity of the uterine 
 contractions is not interfered with ; but in early abortions 
 and early in the first stage, a simultaneous spasm of the 
 OS may occur. 
 
 5. Its chief field of usefulness is in the first and second 
 stages of labour when there is delay due to feebleness 
 of the pains, alone or when combined with other com- 
 plications, such as malpositions of the head, malpresenta- 
 tions, multiple pregnancy, slight narrowing of the pelvis, 
 etc. 
 
 6. In the induction of abortion, in the treatment of 
 abortion already in progress, and in incomplete abortion, 
 its action is so uncertain that it is not to be recommended' 
 except in cases where the os is widely dilated. 
 
 7. In the induction of premature labour its effects are 
 uncertain, but if sufficient dosage is given, they may be 
 good. 
 
 8. In the induction of labour at full term and after, 
 better results are obtained than in premature cases. 
 
 9. It gives good results in many cases of post-partum 
 haemorrhage, but is not superior to the various prepara- 
 tions of ergot. It has the power of sensitizing the uterus, 
 so as to allow these preparations to act more powerfully, 
 the combination being most effective. 
 
 10. It is a useful adjunct in the treatment of placenta 
 prsevia, used in conjunction with rupture of the mem- 
 branes, the use of hydrostatic dilators, or turning. 
 
 It is obviously impossible to refer even briefly to all 
 the papers on this subject. It is fair to state that the
 
 The Hypophysis or Pituitary Body 299 
 
 majority of writers on the use of pituitary preparations 
 in labour are decidedly in favour of it, and many write 
 in an enthusiastic vein. One paper, by Vogt^^ of 
 Dresden, describes experiences with pihiitrin in over 100 
 cases. The results were both uniform and encouraging. 
 It was used in all stages of labour, the majority receiving 
 it during the second stage. Vogt writes: " It failed only 
 once. In all other instances its action was very pro- 
 nounced; and although we encounter a great many cases 
 of narrow pelvis in Dresden (from 40 to 50 per cent.), it 
 was not necessary to have recourse to forceps delivery 
 in a single instance in which pituitrin was employed. . . . 
 According to our experience, it is the most ideal oxytocic 
 we possess to-day." 
 
 It is extremely important to know just how, and 
 especially when, to administer this remedy. It is best 
 given by intramuscular injection, and the dose is usually 
 1 c.c, sometimes less, of a solution corresponding to 
 20 grammes of fresh gland, or a 20 per cent, solution. 
 It should preferably be given in the late stages of labour, 
 after the pains have weakened a little, or when it seems 
 necessary to hasten matters. The best results follow its 
 use when the head is on the perineum, and the pains are 
 weak or come on at long intervals. Given during ex- 
 pulsion, this remedy often obviates the need of forceps. 
 Second doses are occasionally necessary, but do not cause 
 a full effect unless an hour, or preferably more, has elapsed 
 since the first dose was given. 
 
 In prolonged labour pituitary extract shortens the 
 period of waiting in a remarkable manner. This is 
 nicely emphasized by some figures given by Bondy^'^ of 
 the results in eight out of ten cases treated with pituitrin. 
 In the first column are figures showing the duration of 
 labour previous to the injection, and in the second
 
 300 
 
 Practical Hormone Therapy 
 
 column the period before delivery. The figures are 
 astonishing : 
 
 34 hours 
 
 45 
 
 minutes. 
 
 44 ,, 
 
 30 
 
 
 48 ., 
 
 15 
 
 
 23 ,, 
 
 5 
 
 
 36 ,, 
 
 35 
 
 
 27 „ 
 
 60 
 
 
 44 ,, 
 
 10 
 
 
 32 „ 
 
 29 
 
 
 Average 36 hours 
 
 28 minutes. 
 
 Contra-Indications in Obstetrics. — Pituitary prepara- 
 tions should not be used if the pelvis is very narrow or 
 the head very high. If given in the early stages of 
 labour, or when there is rigidity of the cervix, dangerous 
 stricture has been caused. It is manifestly contra- 
 indicated in conditions where there is a risk of uterine 
 rupture, and in cases with cardiac, pulmonary, or renal 
 disease, it should be used with extreme caution. Gussew,^^ 
 however, does not consider such conditions are contra- 
 indications to its use, but states: "On the contrary, 
 oedema completely vanished in eight to eighteen hours, 
 the quantity of albumin in the urine was considerably 
 reduced, and in some cases entirely disappeared." 
 
 Some writers have found its activity reduced or absent 
 where fever is present, and others point out that the 
 administration of chloroform and other narcotics (mor- 
 phine, etc.) hinders its action. 
 
 It should never be used early in labour or as an aborti- 
 facient, as in abortion or premature labour the prolonged 
 contractions which are caused may seriously interfere 
 with later operative interference, if found necessary. If 
 used early in the course of labour, or in large doses, the 
 foetal pulse-rate may be considerably reduced (to 80, 60, 
 or even 40 beats per minute). Asphyxia and, very rarely, 
 death of the child have been caused.
 
 The Hypophysis or Pituitary Body 301 
 
 In Gynaecological Practice it is evident that while 
 pituitary extract may often be of much service, its 
 therapeutic usefulness is not to be compared to that which 
 is available in obstetrics, as briefly outlined in the pre- 
 ceding pages. 
 
 It is undoubtedly a valuable haemostatic, the contrac- 
 tions of the uterus making it of service especially in 
 postpartum haemorrhage. There are numerous records 
 of the styptic action of pituitary extract in menorrhagia 
 and haemorrhage following gynaecological operations, 
 abortion, and even cancer of the uterus. Bab,^^ among 
 numerous other wTiters, speaks most favourably of this 
 method of treating various forms of uterine haemorrhage. 
 He writes: " Out of thirty cases which we have treated, 
 in ten the haemorrhage was arrested on the second day, 
 and only in seven was it necessary to continue the treat- 
 ment for from four to eight days. It must be admitted 
 that pituitrin is a valuable gynaecological styptic. Most 
 remarkable are the cases in which haemorrhage was 
 arrested after lasting from two to seven weeks ; in several 
 of these cases a single subcutaneous injection cured the 
 metrorrhagia." 
 
 The Influence in AmenorrhoBa. — Paradoxical as it may 
 seem, pituitary extract has been successfully used in 
 establishing or increasing the menstrual flow. 
 
 It is now recognized that certain of the ductless glands 
 often vicariously carry on one another's functions, and the 
 pituitary body is known to undergo hypoplasia when the 
 catamenia are arrested by pregnancy. Fromme,^° there- 
 fore, tried injections of 'pituglandol in the treatment of 
 amenorrhoea, after eliminating all cases where incipient 
 phthisis was suspected. One c.c. was injected each day 
 until the desired effect was obtained, or until it was clear 
 that the treatment was doing no good. In five out of
 
 302 Practical Hormone Therapy 
 
 twelve test cases the menses came on promptly; in two 
 they appeared, but the merit of this treatment was less 
 evident; and, lastly, in five Fromme admits that the 
 periods did not reappear, nor was there any evidence that 
 the treatment had any effect, although some of the 
 patients felt, or fancied that they felt, something like 
 the molimina. Thirty c.c. given daily for several weeks 
 seemed harmless even when no menstrual flow appeared. 
 This writer beheves that pituitary extract is likely to 
 answer in cases where young women become corpulent 
 as the amenorrhoea develops, the fatty change being 
 related in some way to disturbances in the ductless 
 glands. 
 
 Leonard Williams^^ relates an interesting case of 
 amenorrhoea which, after " a perfect orgie of treatment — 
 medicinal, surgical, and suggestional — into the details of 
 which it would be painful to enter," was controlled with 
 whole pituitary extract in doses of 10 grains (07 gramme) 
 three times a day. In this case the amenorrhcea recurred 
 after discontinuing this medication, and the flow re- 
 appeared after recommencing it. 
 
 An Enterokinetic or Peristaltic Excitant. — A similar 
 action of the pituitary extract to that upon the uterus, 
 bladder, and bloodvessels, is obtainable upon the in- 
 testinal musculature, and various pituitary extracts 
 have been used with good results in intestinal atony and 
 paresis, especially in post-operative cases. Blair Bell 
 and Hick^^^ first discovered this action, and used it in 
 clinical practice. 
 
 Houssay and Beruti^^ of Buenos Aires maintain that 
 fluid pituitary preparations constitute the most efficient 
 agent now available for bringing about intestinal con- 
 tractions. This enterokinetic influence has been fre- 
 quently mentioned, but rarely used until these writers
 
 Tlie Hypophysis or Pituitary Body 303 
 
 suggested that this particular virtue had not been 
 generally recognized because insufficient doses had been 
 used. The dose for the purpose should be larger than 
 that used as an oxytocic. Two c.c. of a 20 per cent, 
 solution is the proper dose for adults, and will induce 
 defsecation in 88 per cent, of all cases. Within two or 
 three minutes after the subcutaneous injection, the patient 
 becomes conscious of intestinal movements, and almost 
 always within six to sixty minutes evacuation follows. 
 Slight pain is often experienced ; pallor is also a customary 
 symptom, and the pulse-rate increases. The bowel move- 
 ment ma}^ recur on the day of the injection, and fre- 
 quently remains satisfactory on the succeeding day or 
 two. In faecal impaction the drug may be given in con- 
 junction with mechanical treatment and enemata. In 
 addition to its use as a prophylactic and curative agent 
 in post- operative intestinal paresis, pituitary extract per- 
 mits of the use of morphine in cases where its employ- 
 ment would otherwise be unjustifiable, counteracting the 
 paralyzing effect of morphine on the intestine, and pre- 
 venting meteorism. In peritonitis the favourable effect 
 of the extract on the intestinal and general circulations 
 and its diuretic action are also of value. A tonic effect 
 on the bowel can be secured by continued use. Small 
 hypodermic doses are stated to stimulate gastric motility 
 and increase the flow of gastric juice. Administration by 
 mouth, even in large doses, does not afford results com- 
 parable with those already mentioned, and does not 
 appear to be indicated at any time. In a previous com- 
 munication Houssay^^ (and Ibanez) called attention to 
 the presumed superiority of pituitary preparations over 
 hormoTKil. 
 
 The Value in Post-Operative Intestinal Disturbances. — 
 Another extremely useful application of pituitary extract
 
 304 Practical Hormone Therapy 
 
 is of special interest to surgeons. It may be used to 
 relieve annoying post-operative symptoms, such as 
 meteorism and distension. The rapid and irregular 
 pulse which not infrequently accompanies these symp- 
 toms is also favourably modified. 
 
 Bidwell^'* tried the enterokinetic effect of a solution of 
 pituitary extract in twenty-one laparotomy cases. In 
 three the bowels acted without an enema, and in all but 
 two of the others a simple enema sufficed to bring about 
 a satisfactory action without any aperient by the mouth. 
 All passed flatus freely a few hours after the injection, 
 and were free from abdominal pain or distension. The 
 pulse was much lower than usual, and even after 
 some of the severest operations did not exceed 80 per 
 minute. Bidwell recommends that -1 c.c. should be 
 injected intra - muscularly six hours after operation, 
 and be followed by two or more such doses at six-hour 
 intervals. 
 
 Blair Bell,^'^ in his first clinical paper, already referred 
 to, relates a case which shows the extent of its value in 
 intestinal atony and paresis. His patient suffered from 
 intestinal obstruction; an operation — ileo-sigmoidostomy 
 — was performed, and calomel in ^-grain doses was 
 given every two hours without effect. A glycerin enema 
 had no better action. A second operation — right lumbar 
 colotomy — was performed, and more calomel and other 
 drugs, including eserine, were given, without result. 
 Acute obstruction had now existed for five days, vomiting 
 was continuous, and the patient was in great pain from 
 flatulence and distension. An injection of pituitary 
 extract was made into the muscles of the forearm. Within 
 a few minutes the severe distension was reduced, much 
 flatus was passed by the colotomy wound, and immediate 
 relief was obtained.
 
 The Hypophysis or Pituitary Body 305 
 
 The Action on Diuresis. — To all the foregoing must be 
 added still two other important physiologic actions. 
 Pituitary extracts have been observed to exert a decided 
 diuretic effect, which seems to be due to a selective 
 influence of one of the contained hormones upon the cells 
 of the renal tubules. Small doses of the extract given by 
 mouth or hypodermically produced a prolonged and 
 decided diuresis, and this, combined with the effects 
 upon the heart and cardio- vascular system, seems to in- 
 dicate that pituitary extract in some cases has a better 
 influence than the diuretic group of drugs. This action 
 has been supposed to be due to a special diiu-etic hor- 
 mone from the pars intermedia, and it is not yet certain 
 that this is not the case ; but it seems more probable that 
 all the effects that it causes are due to the active 
 principles of the posterior lobe. 
 
 Frequently an increase in micturition results from the 
 administration of pituitary extracts in obstetrics, and 
 many writers mention this incidentally. In shock, too, 
 the diuretic effect is noticeable, and may be the cause of 
 a part of the good effects so generally obtained. 
 
 In nephritis with hypotension, such as frequently 
 follows scarlatina and diphtheria, the action upon the 
 kidneys is good, and the general hypertensive and tonic 
 influence is of additional advantage. In the occasional 
 ischurias of the puerperal period pituitary extract quickly 
 causes a marked diuresis. Hofstatter^^ finds that injec- 
 tions of pituitrin permanently relieve the majority of the 
 anurias or dysurias following labour or operations. 
 
 Uraemia also has been favourably influenced, and the 
 diuretic principle present in extracts of the pituitary 
 deserves consideration in all cases of arrested kidney 
 action. Intravenous injection may be resorted to, and 
 in such cases a pint or more of warm saline solution, to 
 
 20
 
 306 Practical Hormone Therapy 
 
 which 1 c.c. of pituitary extract is added, is a suitable 
 injection. 
 
 In vesical paralysis and atony the influence upon urina- 
 tion is twofold. In addition to the direct diuretic action, 
 the tonic action upon the musculature of the bladder 
 makes pituitary extract of considerable utility. French 
 physicians frequently prescribe the dried extract of 
 pituitary in 10 or 20 miUigramme {1| to 3 grain) doses 
 three to five times a day in cases with insufficient urina- 
 tion and kidney disorder. 
 
 Diabetes Insipidus and the Pituitary. — Experimentally, 
 a relation between polyuria and pituitary disease has been 
 shown to exist. Frank^*^ states that it can be proved 
 clinically, as well as experimentally, that the pars inter- 
 media produces a diuretic hormone, and that diabetes 
 insipidus is due to hyperfunction of this part of the gland. 
 Simmonds^' also reports clinical and autopsy findings 
 which lead him to conclude that the uropoietic activity, 
 which is pathognomonic of diabetes insipidus, is caused 
 by a hormone produced in the pars intermedia. 
 
 Gushing^* has made many experiments with the elucida- 
 tion of this point in view. He summarizes his experi- 
 mental data by saying that — 
 
 1. The infundibular region contains, in addition to the 
 substance capable of glycogenolysis, a hormone capable 
 of eliciting diuresis. 
 
 2. Under certain operative conditions that entail pos- 
 terior lobe manipulations there often occurs a diuretic 
 response, and occasionally an extreme diuresis is apt to 
 follow other operative procedures requiring an equally 
 long anaesthetization. 
 
 3. Posterior lobe implants may cause a temporary 
 polyuria, which subsides on the removal of the implanted 
 tissue.
 
 The Hypophysis or Pituitary Body 307 
 
 4. Certain operative procedures, such as separation of the 
 infundibular stalk and occasionally a simple posterior lobe 
 excision, may call forth a somewhat prolonged polyuria. 
 
 In connection with his clinical observations Gushing 
 suggests not only that the emotional polyurias are in all 
 likelihood the expression of a neurogenic discharge of 
 hypophyseal secretion, but also that the clinical polyurias 
 of longer duration are in many instances merely the 
 symptomatic expression of an internal secretory dis- 
 turbance, brought about by injury or disease involving 
 the hypophyseal neighbourhood. Hence, whether or not 
 there actually proves to be a form of polyuria of primary 
 renal origin, our present conceptions of diabetes insipidus 
 need to be recast, with special reference to the factor of 
 the secretory activity of the pituitary body, and par- 
 ticularly of its posterior lobe. 
 
 It is possible that this interesting relation between 
 polyuria and hyperfunction of the pituitary may lead to 
 the use of hormones that are antagonistic to the pituitary 
 hormone with good results. 
 
 The Control of Polyuria with Pituitrin. — Francesco^^ of 
 Venice gives a valuable review of the relation of polyuria 
 to pituitary disorders. His experience adds weight to the 
 previous statements regarding the relation of diabetes 
 insipidus to pituitary disease, and at the same time shows 
 the extreme complexity of hormone action.* as he reports 
 in detail, and with charts, two cases of diabetes insipidus 
 which were controlled by injections of pituitrin. The 
 average quantity of urine in both cases varied from 
 6,000 to 8,000 c.c, and when in control from 1,000 to 
 2,000 c.c. daily. The curve of one case is especially 
 interesting, as from it it appears that interruption of the 
 
 * Elsewhere we have noted that pituitary preparations have a decided 
 diuretic effect, and may be used in ischuria as a means of increasing the 
 urinary output. Here the same treatment reduces it.
 
 308 Practical Hormone Therapy 
 
 pituitary treatment for a few days allowed the urinary 
 quantity to rise very materially, while a later substitution 
 of ovarian for pituitary extract caused an equally great 
 rise. A recent editorial'*^ consideration of this subject 
 gives a number of additional references, and includes a 
 statement to the effect that Farini also reports that he 
 was able to reduce the polyuria of diabetes insipidus as 
 long as active pituitary treatment was kept up. 
 
 The Galactagogue Action. — Last, and by no means 
 least, of the specific activities of pituitary extract is its 
 galactagogue action. We have seen that Ott and Scott^^ 
 were the first to call attention to this, and their experi- 
 ments have since been confirmed by numerous other 
 investigators. Several other gland extracts exert a 
 similar action, notably that of corjjus luteum, epiphysis, 
 and mammas. Pituitary extract, however, contains the 
 most effective galactagogue hormone, and, suitably com- 
 bined, has been suggested as a rational and valuable 
 postpartum remedy, both for its galactagogue action as 
 well as for its tonic and antihsemorrhagic influence upon 
 the involuting uterus. 
 
 Schafer^^ states that the effect upon lactation of the 
 injection of pituitary extract is one of the most striking 
 experiments in physiology. The milk pours from the 
 gland in a continuous stream, the flow gradually diminish- 
 ing and ceasing after ten to fifteen minutes. However, 
 this does not appear to influence milk production, but 
 merely to be an emptying of the gland. It seems as if 
 the alveoh and ducts were contracted and squeezed out 
 the milk, yet no muscle fibres have been found in the 
 alveolar walls. It is difficult to reconcile the large amount 
 of milk and the length of its flow with this idea.* 
 
 * Not all agree as to the therapeutic apiilication of this undoubted galacta- 
 gogue action. Heaney*^ ^yntes : "In conclusion it may be stated with some 
 assurance that the results of experimentation with pituitrin upon lactating
 
 The Hypophysis or Pituitary Body 309 
 
 Gavin^^ finds that the administration of extracts of 
 pituitary body and corpus luteum to dairy cows, by the 
 mouth or by subcutaneous or intravenous injection, 
 causes practically no alteration in the total quantity per 
 diem or in the quality of the milk; while, on the other 
 hand, Schafer records having given pituitary and corpus 
 luteum extracts to a young married woman nursing her 
 second baby, and states that there is ample evidence of 
 the positive effect of these extracts, especially as regards 
 the pituitary extract. 
 
 Sutherland Simpson of Cornell, in a personal communi- 
 cation, suggests that Gavin's dosage was too small, and 
 writes of a series of experiments upon goats. In his 
 letter is the following interesting statement: "What we 
 found was this — when milked about fifteen minutes after 
 injection, the yield was about doubled, but there was a 
 corresponding diminution at the next milking, so that 
 there was little if any increase in the total twenty-four- 
 hour quantity. The milk withdrawn after the injection, 
 however, was found to be very rich in fat ; on one occasion 
 it contained as much as 18 per cent, of fat, about four and 
 one-half times the normal quantity. The fat at the second 
 milking did not fall below the normal, but was usually 
 still a little above. The other constituents of the milk 
 did not appear to be affected." 
 
 Pituitary Extract in threatened Mammary Abscess. — 
 The galactagogue action which has just been considered 
 may be used to good advantage where there is stasis of 
 the fluids in the breast and a threatened abscess formation, 
 since the stimulating or expressing action is useful when 
 
 animals and humans do not support the assumption of its galactagogic effect. 
 The stimulus which it appears in some cases to give to the milk flow should 
 probably be explained by the effect in contracting the smooth muscle fibres 
 of the breast, and this very fact makes it probable that its continued admini- 
 stration would discourage rather than stimulate the secretion of milk "
 
 310 Practical Hormone Therapy 
 
 the ducts are blocked with pus. White^** considers 
 pituitary extract very useful in aborting threatened 
 abscess of the breast, and found that, in addition to 
 facilitating absorption of the gathering, this medication, 
 which was supplemented with lactagol (a proprietary 
 extract of cotton-seed), facihtated an abundant secretion 
 of milk. He reports the case of a woman with a threat- 
 ened mammary abscess who was enabled to nurse triplets 
 for seven months, as a result of this combined medication. 
 
 The Tonic Effect of Pituitary Powder. — The general 
 physiologic effects of pituitary extract can be used in the 
 treatment of numerous conditions. Small and persistent 
 doses of the total extract, especially when combined with 
 suitable amounts of other synergistic hormone-bearing 
 extracts, exercise a tonic effect that is quite advantageous, 
 and seems to be more particularly evident in the neuro- 
 muscular system. As a means of combating asthenia it 
 seems equal to, if not better than, the usual vegetable and 
 mineral tonics; and this is amplified by the fact that it 
 favours the appetite^ increases nutrition, and facilitates 
 sleep, as is emphasized especially by Delille.^ In the 
 neurasthenias which are accompanied by hypotension, and 
 n myocardial asthenias, pituitary extract often gives 
 satisfaction; the pulse is slowed while the pressure is 
 raised. 
 
 Musser^'5 records his experience with the oral adminis- 
 tration of a total dry extract of pituitary in eighteen cases. 
 Its most constant influence was upon the blood-pressure; 
 in seventeen of the cases it rose, the highest rise being 
 28 millimetres. Several of the cases were subjectively 
 benefited by this pressor effect. The other results were 
 variable and somewhat less definite. Six patients noted 
 a diuretic effect, but there was no particular change in 
 the urinary constituents. A diarrhoea developed in seven
 
 The Hypophysis or Pituitary Body 311 
 
 cases; and four, previously costive, had regular move- 
 ments whilst taking the extract. 
 
 Jaschke'*® concludes that pituitary extract is an excellent 
 general tonic after operations. He used it in forty-four 
 cases, and states that it is possible to increase the action of 
 the cardio- vascular mechanism, and in the majority of 
 cases to stimulate the action of the bladder. Combined 
 with sahne injections, he found it particularly useful in 
 those cases in which chloroform has been employed as the 
 anaesthetic. 
 
 A Hypotensive Pituitary Extract. — It has been known 
 for some time that under certain conditions the hyper- 
 tensive action of injections of pituitary extract could be 
 changed to a hypotensive reaction, and Schafer, Howell, 
 and others, have shown that the alcoholic extract of 
 pituitary maceration separated certain depressor sub- 
 stances, while the pressor substances remain in the 
 albuminous residuum. 
 
 Claude and Baudouin^"^ have outlined a method of 
 isolating this extract, and in a later communication^^ 
 Claude considers the diversity of action of various hypo- 
 physeal products which depends upon the method of 
 preparing them. These investigators have shown that by 
 suitable procedures, chief among which is the removal of 
 the lipoids from the glandular maceration (of the posterior 
 lobe), they could secure a substance, with considerable 
 depressor activity, which has more than experimental 
 value, for they relate its application in several cases of 
 haemoptysis in which the good results are illustrated by 
 graphic curves. 
 
 If the possibilities just outlined are more generally 
 conceded, it seems that another extremely valuable agent 
 will be available, for chief among the disadvantages of 
 pituitary medication is the fact that its pressor influence
 
 312 Practical Hormone Therapy 
 
 is too often inconvenient. Many cases which would be 
 the better for certain of the tonic and reconstructive 
 effects of total pituitary extract, have too high a blood- 
 pressure to allow of its effective administration. It is 
 entirely probable that other pituitary preparations, with 
 different properties than those at present on the market, 
 will eventually be available in clinical practice. 
 
 Miscellaneous Therapeutic Possibilities. — In addition to 
 the already long hst of conditions in which the adminis- 
 tration of pituitary extract is useful, there are several 
 disorders in which this preparation has been occasionally 
 prescribed. 
 
 Wallace and Child'*^ present a preliminary report on the 
 use of pituitary extract in rheumatoid arthritis, giving the 
 histories of ten cases, five of which were hospital cases 
 in children, and five in adults in private practice. All the 
 patients showed improvement in the general condition, 
 in the pains, in the swellings and motions of the joints 
 affected, and in the effect on the bowels. The blood- 
 pressure was elevated throughout the treatment, and had 
 a tendency to remain so. There was a slight irregular rise 
 in temperature during the first week or ten days. In one 
 of the children the prognosis under the treatment was 
 changed from fatal to favourable. The adult patients 
 were slightly nauseated and suffered from head symptoms, 
 such as giddiness, lightness, and headache. 
 
 Klotz^° reports good results from the pituitary treat- 
 ment of rickets in children, and strongly recommends its 
 use in this disease. In osteomalacia also good results 
 have been recorded, and it has also been recommended 
 in hyperthyroidism, although no remarkable results have 
 come to the author's notice. Pituitrin has also been used 
 topically for its astringent effect, and it is claimed that 
 this influence is of equal, or perhaps greater, value than
 
 The Hypophysis or Pituitary Body 313 
 
 that of adrenalin in hay fever and asthma. For this 
 purpose the 1 in 1,000 solution is diluted with two to five 
 times its volume of warm salt solution. 
 
 The Differences between Pituitary Preparations. — There 
 are two forms in which pituitary extracts are obtainable — 
 dry, in powder or tablets, and liquid, usually in ampoules. 
 The powdered preparations in France are generally total 
 extracts of the whole gland, and are given chiefly for the 
 tonic and stimulating effects as well as when prolonged 
 glandular feeding is indicated, as in hypopituitarism. 
 The liquid extracts, however, are invariably made from 
 the posterior lobe, and are used most often for their 
 pressor and musculo-tonic action. 
 
 The majority of the clinical reports obtainable relate 
 to the liquid preparations, and these vary somewhat in 
 action. Parisot and Mathieu^^ have made a series of 
 comparative tests of certain proprietary extracts. These 
 include Fiihner's preparation [hyjjophysin), pituitrin, 
 pituglandol, and a personally prepared extract from the 
 fresh gland. From the physiologic standpoint, hypo- 
 physin possesses the essential properties of the extract of 
 the macerated posterior lobe; it manifests particularly a 
 hypertensive and cardio-tonic action. Pituitrin is especi- 
 ally cardio-tonic in action, and in a less degree hyper- 
 tensive. From the toxicologic standpoint, hypophysin 
 seems to be the least toxic and pituglandol the most 
 toxic. 
 
 In a second communication Parisot and Mathieu^^ 
 have reported the comparisons between the actions of 
 these preparations upon smooth muscle. The extracts 
 which show the greatest hypertensive action are those 
 which have the most marked exciting action upon mus- 
 cular organs such as the uterus. According to these 
 authorities, Fiihner's preparation is the most active.
 
 314 Practical Hormone Therapy 
 
 Methods of Administration. — Pituitary extract is not so 
 rapidly diffusible as adrenaline, and therefore is not so 
 quickly absorbed by the gastric mucosa. As it may be 
 destroyed by the pancreatic juice when given per os, it 
 should be taken an hour or more before meals. When the 
 general tonic influence or prolonged diuretic or galacta- 
 gogue effect is desired, oral administration is usually quite 
 satisfactory, but in obstetrical and emergency practice, 
 where it is desired to combat uterine atonia, shock, or 
 other cardiovascular conditions, the intramuscular method 
 is most generally useful. Attention has been called to 
 the fact that pituitary preparations should not be given 
 hypodermically, as necrosis is possible, due to the local 
 vaso-constricting effects of the injection. Occasionally it 
 seems advisable to administer pituitary extract intra- 
 venously, in which case the contents of an ampoule 
 should be well diluted with artificial physiologic 
 serum. 
 
 Dosage. — There is considerable variation in the strength 
 of various proprietary preparations, so accurate state- 
 ments regarding definite dosage cannot easily be made. 
 Usually these preparations are put up in ampoules or 
 tablets of known strength, and the dosage is easily con- 
 trolled. Effective watery extracts contain approximately 
 from 20 to 30 grammes of fresh gland substance per litre, 
 and the dose ranges from | to 1 c.c. (8 to 16 minims), while 
 as much as 2 to 3 c.c. may be given in any one case. Ott^^ 
 reports having given as much as 1 ounce of pituitrin at a 
 dose, and later intimates that " infundibulin is not very 
 poisonous; it can be used oftener than three times a day 
 if the conditions necessitate it." As far as the less fre- 
 quently used dried extracts are concerned, each part of 
 the powdered substance or tablets represents from 4 to 5 
 parts of fresh gland, and the dose varies from | to IJ
 
 The Hypophysis or Pituitary Body 315 
 
 grains (0-015 to 0- 1 gramme). Small doses in tablet form, 
 frequently repeated, have a general tonic effect. 
 
 Contra-Indications. — Manifestly the main contra-indica- 
 tion is hypertension, because of the general hypertensive 
 action of the pituitary hormone. Mairet advises against 
 its use in epilepsy, and reports inconvenience resulting 
 from its use in epileptics. In those diseases in which 
 hyperpituitarism is a factor, pituitary extracts necessarily 
 would be contra-indicated. 
 
 In obstetrics there are certain extremely important 
 points, especially regarding the time of the injection, 
 which must not be overlooked. They have already been 
 mentioned on p. 300. 
 
 Aarons^ believes that pituitary extract is liable to 
 cause arterial degeneration if used for long, and empha- 
 sizes the fact that it is essentially an emergency remedy. 
 This is not generally conceded, however, Thaon^^ advises 
 against the use of pituitary extracts in cases of kidney 
 disease, for he has produced (with quite large doses, it 
 should be remarked) haematuria and glomerulitis. The 
 usual dosage would not seem to be contra-indicated 
 because of this experimental work, and many favourable 
 results have been noticed in cases in which there was an 
 unquestioned destruction of a part of the kidney tissue. 
 
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 ^ Gauthier:* p. 158, 
 
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 3 Gushing:* 
 
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 316 Practical Hormone Therapy 
 
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 in surgical shock, Bost. Med. and Surg. J., 1913, clxviii, 72. 
 
 2" Dale (H. H.): Discussion on the therapeutic value of hor- 
 mones, Proc. Boy. Soc. Med. (Sec. Ther.), (London), 1914, 
 vii, 34. 
 
 21 Ibid.: On some physiological extracts of ergot, J. Physiol. 
 (London), 1906, xxxiv, 163.
 
 TJie Hypophysis or Pituitary Body 317 
 
 Blair Bell (W.) and Hick (P.): Observations on the 
 
 physiology of the female genital organs, Br. Med. J., 1909, 
 
 i, 517, 592. 
 HoFBAUER (J.): Hypophysenextrakt als Welicnmittel, Zentr. 
 
 f. Gyn. (Leipzig), 1911, xsxv, 137. 
 Spaeth (F.): Hat das Pituitrin einen nachteiligen Einfluss anf 
 
 das Kind ? Zentr. f. Gyn. (Leipzig), 1913, xxxvii, 165. 
 Delmas (P.): Une serie d'insucces de la medication hypo 
 
 physaire, Bev. prat, d'ohs. et gyn. (Paris), 1913, xxi, 269. 
 Watson (B. P.): Pituitary extract in obstetrical practice 
 
 Can. Med. Assn. J. (Toronto), 1913, iii, 739. 
 VoGT (E.): Geburtshilfiiche Erfahrungen mit Pituitrin, Munch 
 
 med. Wchnschr., 1911, Iviii, 2734. 
 BoNDT (0.): Pituitrin in der geburtshilflichen Praxis, Berl. M 
 
 Wchnschr., 1911, xlviii, 1461. 
 GussEW (W.): Das Pituitrin in der Geburtshilfe, Zentr. f. Gyn 
 
 (Leipzig), 1912, xxxvi, 1755. 
 Bab (H.): Pituitrin als gynakologisches Styptikum, Miinch 
 
 med. Wchnschr., 1911, Iviii, 1554. 
 Fromme (F.): Zur Behandlung der Amenorrhoe, Zentr. f. Gyn 
 
 (Leipzig), 1912, xxxvi, 1366. 
 Williams (L.): Discussion on the therapeutic value of hor 
 
 mones, Proc. Boy. Soe. Med. (Sec. Tlier.), (London), 1914 
 
 vii, 32. 
 HoussAY (B. A.) AND Beruti (J.): Sur I'emploi de la medica 
 
 tion hypophysaire comme agent ent6rocin6tique, Pr. med 
 
 (Paris), 1913, xxi, 613. 
 HoussAT (B. A.) AND Ibanez (M.): Applications therapeu 
 
 tiques de Faction exerc6e sur les fibres musculaires lisses par 
 
 le principe actif de I'hypophyse, Pr. med. (Paris), 1912 
 
 XX, 393. 
 Bidvs^ell (L.): Investigation into the effect of pituitary extract 
 
 on the bowels after abdominal operation, Clin. J. (London), 
 
 1911, xxxviii, 351. 
 Hofstatter (R.): Pituitrin als Blasentonikum, Wien. M. 
 
 Wchnschr., 1911, xxiv, 1702; see also id., Ueber Misserfolge 
 
 und Schadigungen durch die Hypophysen-medikation, 
 
 Monats.f. Geb. u. Gyn. (Berlin), 1913, xxxviii (Erghft.), 142. 
 Frank (E.): Ueber Bezieghungen der Hypophyse zum Diabetes 
 
 insipidus, Berl. M. Wchnschr., 1912, xlix, i, 393. 
 SiMMONDS (M.): Hypophysis und Diabetes insipidus, Munch. 
 
 med. Wchnschr., 1913, Ix, 127. 
 Gushing (H.): Concerning diabetes insipidus and the polyurias 
 
 of hypophyseal origin. Post. Med. and Surg. J., 1913, clxviii, 
 
 901. 
 Francesco (F.): Diabete insipido ed opoterapia ipofisaria, 
 
 Gaz. d. Osp. e. d. Clin. (Milan), 1913, xxxiv, 1127. {QqoA 
 
 bibliography.)
 
 318 Practical Hormone Therapy 
 
 Editorial: Diabetes insipidus and iniautilism, Lancet (Lon- 
 don), 1914, i, 552. 
 ScHlFER (E. A.): The physiology of milk secretion, Med. Pr. 
 
 and Circ. (Loudon), 1913, i, 306. 
 Heaney (N. S.): a contribution to the study of pituitrin, 
 
 Surg. Gyn. and Obs. (Chicago), 1913, xvii, 103. 
 Gavin (W.): On the effects of adminstration of extracts of 
 
 pituitary body and corpus luteum to milch cows, Quar. J. 
 
 Exp. Physiol. (London), 1913, vi, 13. 
 White (J. A. H.): Cotton-seed extract and pituitary extract 
 
 during lactation, Pract. (London), 1913, xci, 422. 
 MussER (J. H.): The effects of continuous administration of 
 
 hypophysis extract, Am. J. Med. Set. (Philadelphia), 1913, 
 
 cxlvi, 208. 
 Jaschke (R. T.): Pituitrin als postoperatives Tonikum mit 
 
 besonderer Berucksichtigung der Blasenfunktion, Munch. 
 
 med. Wchnschr., 1912, Ix, 1661. 
 Claude (H.) and Baudouin (A.): Sur les effets de certains 
 
 extraits hypophysaires, C. r. Acad. Sci. (Paris), 1911, cliii, 
 
 1513. 
 Claude (H.) and Porak (R.): Sur Taction hypotensive de 
 
 certains extraits hypophysaires, Pr. mid. (Paris), 1914, xxii, 
 
 25. 
 Wallace (C.) and Child (F. S.): Extract of the pituitary in 
 
 the treatment of rheumatic arthritis, Med. Eecord (New 
 
 York), 1913, Ixxxiv, 608. 
 5° Klotz (R.): Zur Aetiologie der Rachitis, auf Grund ihrer 
 
 therapeutischen Beeinfiussung durch Hypophysenmedika- 
 
 tion, Milnch. med. Wchnschr., 1912, lix, 1145. 
 ^ Parisot (J.) and Mathieu (P.): Les substances extraites du 
 
 lobe post6rieur de I'hypophyse, fitude comparative de leurs 
 
 effets, C. r. Soc. Biol. (Paris), 1914, Ixxvi, 222. 
 62 Id., p. 225. 
 53 Ott (I.): Which preparation of the pituitary is the best to use 
 
 in tetany ? Mo. Cyclop, and Med. Bull. (Philadelphia), 1910, 
 
 iii, 99. 
 ^* Aarons (S. J.): On the use of pituitary extract in obstetrics 
 
 and gynecology. Lancet (London), 1910, ii, 1828. 
 55 Thaon (P.): Action des extraits d'hypophyse sur le rein, 
 
 Remarques sur I'opoth^rapie hypophysaire, G. r. Soc. Biol. 
 
 (Paris), 1910, Ixix, 288. 
 
 HoussAT (B. A.): Ueber die Kombination von Adrenalin und 
 Hypophysin und deren klinische Verwendbarkeit, Wien. kl. 
 Wchnschr., 1913, xxvi, 489. 
 
 Miller (J. L.): Lewis (D. D.), and Matthews (S. A.): The 
 effects of extracts of the different parts of the hypophysis, 
 Proc. Am. Physiol. Soc. (Boston), 1911, xxvii, p. xvii.
 
 The Hypophysis or PituiUiry Body 319 
 
 RoMER (C): Die Beziehungen zwischen der Funktion der 
 
 Hypophysis cerebri imd dein Diabetes insipidus, Deut. med. 
 
 Wchnschr. (Leipzig), 1914, xli, 108. 
 Jewett (D. B.): Hypophyseal disease as related to diabetes 
 
 insipidus, Med. Record (New York), 1914, Ixxxv, 242. 
 Parisot (J.): Action de I'extrait d'hypophyse dans quelques 
 
 maladies, Bev. med. d. VEst (Nancy), 1907, xxxix, 303. 
 Williams (L.): Pituitary extract and some of its effects, Clin. J. 
 
 (London), 1910, xxxvi, 92. 
 HoussAY (B. A.): Contribucion al estudio de la accion de los 
 
 extractos hipofisiarios; ensayo sobre la glandula cardiovas- 
 cular del lobulo posterior, Escuela de med. (Mexico), 1911, 
 
 xxiv, 225, 243, 267, 295. 
 Crookshank (F. G.): a note on the value of pituitary gland 
 
 substance in some cases of asthma. Lancet (London), 1914, i, 
 
 747. 
 DoERN (W. G.): Two interesting results from the use oi 
 
 pituitary extract, Buffalo Med. J., 1912, Ixviii, 78. 
 Lagane (L.): La medication hypophysaire, J. med. d. Brux., 
 
 1912, xviii, 326. 
 Pater (H.): L'opoth^rapie hypophysaire. Bull. gen. d. ther. 
 
 (Paris), 1911, clxii, 241. 
 TiLLES (R. S.): Hypophyseal extract in obstetrics and gyne- 
 cology (Review), Interstate Med. Jour. (St. Louis), 1913, xx, 
 
 451. 
 Kreiss (P.): Die Bekampfung der postpartalen Blutungen 
 
 durch intravenose Hypophysin-injektion, Zentr. f. Gyn. 
 
 (Leipzig), 1914, xxxviii, 119. 
 Oppenheimer (H.): Pituitrin in der Geburtshilfe, Arch. f. Gyn. 
 
 (Berlin), 1914, cii, 500. 
 Linderman (H. E.): Pituitary extract in obstetrics. Am. J . 
 
 Ohs. (New York), 1914, Ixix, 232. 
 Gottfried (S.): Hypophysen-extrakt als Wehenmittel, Zentr. 
 
 f. Gyn. (Leipzig), 1911, xxxv, 542. 
 Jaeger (F.): Hypophysenextrakt als Wehenmittel, Munch. 
 
 med. Wchnschr., 1912, lix, 297. 
 VON DEN Velden (R.): Die Nierenwirkung von Hypophysen- 
 
 extrakten beim Menschen., Berl. kl. Wchnschr., 1913, 1, ii, 
 
 2083. 
 Jayle (F.): L'opotherapie hypophysaire en gynecologie; ses 
 
 resultata immediats. Pr. med. (Paris), 1914, xxii, 245.
 
 CHAPTER XX 
 
 THE EPIPHYSIS OR PINEAL BODY 
 
 The Pineal Body as an Endocrinous Organ — The Physiological 
 Action of the Pineal Gland and Extracts thereof — The 
 Relation of the Pituitary and Pineal Glands — The Influence 
 of the Pineal u])on Development — The Ex2'>eriments of Dana 
 and Berkeley — Clinical Conclusions regarding Pineal Medi- 
 cation — Dosage and Administration. 
 
 The firmly estabKshed facts concerning the internal 
 secretory activities of the hypophysis not unnaturally 
 have led to the study of the epiphysis with the idea that 
 it might also have a similar action. For some years 
 these two organs have been studied together {vide de Cyon,^ 
 Poppi,^ etc.). 
 
 The Pineal Body as an Endocrinous Organ. — As yet 
 preparations of the pineal gland have not been applied 
 jn general practice. This does not indicate, however, 
 that the pineal gland has no influence as an internal 
 secretory organ, or that extracts of this organ have no 
 therapeutic action. From the data which are gradually 
 accumulating in current medical literature, it is evident 
 that the pineal gland is a definite secretory organ, that it 
 produces a hormone, and that its physiological action is 
 transmitted to suitably prepared extracts of this organ. 
 Leading neurologists and other investigators have been 
 clinically testing pineal extracts for some years, with 
 results which seem to be very promising. Hence a few 
 collated statements regarding the function of this organ 
 
 320
 
 The Epiphysis or Pineal Body 321 
 
 and its present and prospective application are quite in 
 order. 
 
 As has been the case with practically all the endocrinous 
 glands, it has been pathology which has served to guide 
 us to the study of physiology. The study of the patho- 
 logical anatomy of children suffering with certain mental 
 manifestations has occasionally indicated the presence of 
 disorders of this pineal gland. 
 
 Not every physiologist is agreed that this organ de- 
 serves to be classed with the ductless glands. Patten, in 
 his recent work, considers this organ as a remnant of a 
 primitive eye, and in Starling's " Physiology " he says^: 
 ''The pineal gland has, so far as we know, no functions 
 in metabolism. It is interesting as a vestigeal remnant 
 of a primitive dorsal eye." 
 
 Morphologically this may be correct — it is not capable 
 of proof — but so far as the relation to metabolism is con- 
 cerned, it is evidently a mistake, for modern literature on 
 the subject indicates that changes in the structure of the 
 pineal body often may be associated with disturbances of 
 the metabohsm of fat, and evidence seems to be accumu- 
 lating that obesity may be connected with pineal hypo- 
 function. It has also been stated that children with con- 
 genital changes in this organ (hyperf unction) frequently 
 manifest abnormal tallness, an increase in the hair in 
 different parts of the body, together with an in- 
 creased mental development and premature sexual 
 maturity. 
 
 An interesting case, which seems to show the influence 
 of the pineal body upon the mentality, is that of a child 
 in whom a teratomatous hypertrophy of the pineal was 
 diagnosed. So rapid was the mental development, that 
 at five years he reasoned as would a young man, with a 
 predilection for ethics and philosophy ! 
 
 21
 
 322 Practical Hormone Therapy 
 
 De Cyon'' of St. Petersburg has studied this gland for 
 a number of years, and in 1905 suggested that the action 
 of pineal extracts was probably totally due to the salts 
 which were found therein. At that time he beheved that 
 the function of the gland was purely mechanical, regu- 
 lating the entry of the cerebro-spinal fluid into the third 
 ventricle and its exit therefrom; in other words, it auto- 
 matically controlled the himen of the aqueduct of Sylvius. 
 Lately, however, his conclusions have been somewhat 
 modified, and while mechanical regulation may possibly 
 be caused by this body, investigations in America by Ott 
 and Scott,^ Dana and Berkeley,® Eyster and Jordan,'^ 
 Bailey and Jelliffe,^ and others, give us light on a more 
 useful phase of the subject. 
 
 The Physiological Action of the Pineal Gland and Ex- 
 tracts thereof. — An interesting study of the functions of 
 the pineal body is published by Kidd,^ who reviews in 
 detail all that has been pubMshed during recent years 
 concerning this gland. He admits that its functions are 
 little known, although at least it is evident that it is no 
 longer looked upon as a rudimentary or disappearing 
 organ, but in all probability it furnishes an internal 
 secretion analogous to those of the other ductless glands. 
 In birds and young mammals this secretion appears to 
 have an inhibitory action on the development of the 
 sexual organs, removal of the gland having produced 
 sexual precocity. Extracts of the pineal body, when ad- 
 ministered, act as a diuretic and galactagogue. Cases of 
 tumour of the gland show symptoms of nutritional change, 
 the most typical of these being precocity of the genital 
 apparatus and marked adiposity. The author concludes 
 that the pineal body has two distinct functions, the first 
 being a restraining influence on sexual development, which 
 ceases at puberty, and the second an unknown influence
 
 TTie E'pifhysis or Pineal Bcdy 323 
 
 on the general metabolism of the body, which continues 
 through hfe. 
 
 The pineal gland does not seem to be absolutely essen- 
 tial to the organism. Exner and Boese^° report that they 
 succeeded in extirpating or destroying the epiphysis in 
 rabbits, and in the 20 per cent, of animals that survived 
 this rather difficult operation, no effects were noticed 
 after the first twenty-four hours. This gland, however, 
 influences certain functions of the body, principally the 
 mental activity and the development of the sexual charac- 
 teristics. 
 
 Ott and Scott confirm the experiences of Eyster, who 
 states that the extracts of the pineal gland have a marked 
 transitory diuretic action by the causation of a consider- 
 able increase in the volume of the kidney. Also small 
 proportions of glucose have been found in the urine fol- 
 lowing pineal injections. These same physiologists notice 
 that the effect of pineal extract upon the uterine muscle 
 was negative, but in the pregnant uterus it increased the 
 contractile power. They also found that it caused vaso- 
 dilatation in the male genital. All of which goes to prove 
 that there is evidently a connection between the internal 
 secretion of the pineal gland and the hormone balance, 
 which has already been referred to in Chapter III. 
 
 The Relation of the Pituitary and Pineal Glands. — There 
 is a similarity between the effects of disease of the pitui- 
 tary and the pineal, as well as between certain of the 
 physiological activities resulting from injections of ex- 
 tracts of these glands. 
 
 Marburg^^ believes that there is an antagonism between 
 the hormone of the epiphysis and the hypophysis, and his 
 opinion is shared by Biach and HuUes.^^ This antagon- 
 ism is probably the cause of the phenomena frequently 
 seen following the castration of male animals. The
 
 324 Practical Hormone Therapy 
 
 pineal body atrophies, while the pituitary is hyper- 
 trophied. 
 
 The Influence of the Pineal upon Development. — Berke- 
 ley^^ suggests that the pineal gland appears to have a 
 definite and important function — namely, it promotes the 
 development of the human nervous system. How it acts 
 so as to produce this remarkable result can be only matter 
 for surmise at present, but presumably the gland supplies 
 a minute amount of an intracellular ferment accelerating 
 the growth of the grey matter of the brain. 
 
 He continues: "In metabolic experiments upon young 
 animals we were able only to hasten their somatic develop- 
 ment, but when giving it to defective children we found 
 that in most cases where there was no grave organic 
 defect of the brain, the mentality showed a steady and 
 gratifying improvement lasting over the whole period of 
 administration. It has occurred to me also that pineal 
 gland will not only hurry the slow mind of the defective 
 child, but that it will also arrest or retard many cases of 
 premature senile decay of the mental faculties, thus 
 making it a physiological stimulant or food for the failing 
 powers of old people who yet have no grave organic 
 disease. I have had encouraging success so far, and I 
 hope to report shortly a long series of cases of this kind 
 showing the successes and limitations of the treatment." 
 The Experiments of Dana and Berkeley. — This promised 
 paper appeared some months later, and it outlines the 
 experiments of Dana and Berkeley.®* These were: 
 (1) The nucleoproteids and entire pineal extracts were 
 obtained and injected into the veins to test the effect 
 upon the blood-pressure; (2) they were also injected into 
 
 * This is the most comprehensive paper in the English language, and refers 
 to most of the literature on the pineal gland, its anatomy, comparative anatomy, 
 physiology, and pathology. It is esjiecially valuable since it contains the 
 data secured from the treatment of twenty-one cases with pineal extracts.
 
 The Efi'physis or Pineal Body 325 
 
 young animals — rabbits, guinea-pigs — for a long time to 
 determine the effect upon nutrition; (3) the whole gland 
 was given to young animals; (4) the whole gland was 
 given to defective and retarded children. Since the be- 
 ginning of the summer of 1911 the investigation has been 
 confined almost to feeding experiments. The authors 
 gave the gland to guinea-pigs and rabbits, and to certain 
 selected children, if possible under eight or nine years of 
 age, and to children who seemed to be cases of simple 
 retardation without notable anatomic defect and mthout 
 epilepsy. Children in the retarded grades of the public 
 schools were used for this purpose, as well as the private 
 cases at the New Jersey Training School for the Feeble- 
 minded at Vineland. The gland was fed to twenty- one 
 children, watching these and comparing them with 
 twenty-one controls. The work was carried on for nearly 
 eight months. 
 
 Clinical Conclusions regarding Pineal Medication. — 
 These authors state their provisional conclusions as 
 follows: During the early period of life it has influence 
 over nutrition, including the development of the genital 
 organs, the deposit of subcutaneous fat, general growth, 
 and mental progress. Extracts of the pineal gland of 
 buUocks given to babies caused an increase in metabolic 
 activity, as evinced by increases in the nitrogen ehminated 
 by the urine. 
 
 As to the results upon the mental development of the 
 twenty-one children treated thus, they found that as a 
 group they gained 2-23 points. Of the fourteen who 
 gained, the average mental gain is 3- 35 points. The 
 control group gained 1'35 points. The gain in standing 
 height for the subjects averaged 18-52 millimetres, while 
 the gain in weight averaged 2-16 kilogrammes. For the 
 controls, the height gain was 24 milUmetres, and the
 
 326 Practical Hormone Therapy 
 
 weight 2-89 kilogrammes. There was therefore a slight 
 loss of weight in the treated cases. 
 
 Some of the clinical reports of the gain in mental 
 capacity, however, are quite decided, and there seems to 
 be reason to suppose that we are likely to be able to add 
 a new agent to the hmited number which seem to have 
 any effect on mental abnormalities. In a recent editorial ^"^ 
 consideration of this work there is a call for further 
 work in institutions, since no great difficulty should be 
 encountered, and no ill-effects are likely to offset the 
 possible advantages. 
 
 Dosage and Administration. — ^Watery extracts of dried 
 pineal substance are used in experimental work. For 
 clinical practice there seems to be no definite information 
 regarding dosage, save a statement in Dana and Berkeley's 
 paper which follows: "After various unsatisfactory 
 methods of dosage, a physiological dose was adopted, 
 the attempt being made to estimate the actual work that 
 one gland could do instead of its mere weight. Twelve 
 bullocks' pineals, perfectly fresh, are rubbed up with a 
 suitable amount of milk-sugar till extinguished. The 
 mass thus obtained, after thorough drying, is distributed 
 into one hundred capsules. . . . Each capsule is calcu- 
 lated to correspond to 150 pounds of live bullock." 
 
 BIBLIOGRAPHY 
 
 ^ DE Cyon (E.): Les fonctions de I'liypophysc et dc la glaado 
 pineale, C. r. Acad. Sci. (Paris), 1907, cxliv, 868. 
 
 2 Poppi.* 
 
 3 Starling,* p. 1334. 
 
 * DE Cyon (E.): [A contribution to the study of the physiology 
 of the pineal gland^Russian], Arch. biol. 8ci. (St. Peters- 
 burg), 1905, xi (suppl.), 297. 
 
 5 Ott (I.) AND Scott (J. C): The action of the corpus luteum 
 and the pineal body, Mo. Cyc. and Med. Ball. (Philadelphia), 
 Id 12, V, 2U7.
 
 The Epiphysis or Pineal Body 327 
 
 * Dana (C. L.) and Berkeley (W. N.): The functions of t.he 
 
 pineal gland, Med. Record (New York), 1913, Ixxxiii, 835; 
 
 see also Pr. mid. (Paris), 1913, xxi, 769. 
 ' Eyster (J. A. E.) AND Jordan (H. E.): Effect of intravenous 
 
 injection of extracts of the pineal body, Am. J. Physiol. 
 
 (Boston), 1910-11, xxvii, p. xxiii. 
 
 8 Bailey (P.) and Jelliffe (S. E.): Tumours of the pineal body, 
 
 Arch. Int. Med. (Chicago), 1911, viii, 851. 
 
 9 Kidd (L. J.): The pineal body: a review, P,ev. Near, and Psych. 
 
 (Edinburgh), 1913, xi, 1. 
 ^° ExNER (A.) and Boese (J.): Ueber experimentelle Extirpa- 
 
 pation der Glandula pinealis. Dent. Ztschr. f. Chir. (Leipzig), 
 
 1910, cvii, 182. 
 *^ Marburg (0.): Zur Kenntnis der normalen und pathologischen 
 
 Histologie der Zirbeldriise. Die Adipositas cerebralis, 
 
 Arbeit a. d. neur. Inst. Univ. Wien., 1909, vol. xvii. 
 ^2 Biach (P.) AND HuLLES (E.): Ueber die Beziehungen der 
 
 Zirbeldriise zum Genitale, Wien. M. Wchnschr., 1912, xxv, 
 
 373. 
 13 Berkeley (W. N.): How far have we got with the clinical use 
 
 of the internal secretions ? Old Dom. J. of Med. and Surg. 
 
 (Richmond), 1913, xvi, 213. 
 ^* Editorial: The function of the pineal gland, Lancet (London), 
 
 1914, i, 401.
 
 CHAPTER XXI 
 
 THE THERAPEUTIC PRODUCTS OF BRAIN AND 
 NERVE SUBSTANCE 
 
 Preparations of Nerve Substance — The Therapeutic Influence 
 of Nerve Extracts — The Antitoxic Action of Cerebral Ex- 
 tracts — Brain Extract in the Treatment of Certain In- 
 sanities. 
 
 The jDrinciple which underhes the application of ex- 
 tracts of nervous tissue in therapeutics is the fundamental 
 principle of organotherapy. If ingested products made 
 from healthy tissue possess a characteristic action due 
 to their chemical constituents, as well as a supplementary 
 and stimulating action, which results from the influence 
 of extracts of organs upon other similar organs, there 
 should be some basis for the use of extracts of brain and 
 nerve substance as remedial agents. 
 
 This subject has been studied by a number of in- 
 vestigators,^ and for a time seemed to enjoy considerable 
 popularity ; but for some reason or other it seems to have 
 been discarded, though recently a number of clinicians 
 have begun to avail themselves of this method of treat- 
 ment with what they claim to be a warrant of success. 
 
 As a means of functionally stimulating the brain and 
 nervous mechanism, there can be no doubt that suitably 
 prepared preparations of this character have some degree 
 of usefulness, for from a chemical standpoint nerve sub- 
 stance contains elements the therapeutic value of which 
 is generally conceded. Chief among these are lecithin 
 
 328
 
 Products of Brain and Nerve Substance 329 
 
 and cholesterin, besides certain other lipoids which have 
 a stimulating action upon the work and nutrition of the 
 nervous system as a whole. 
 
 The Preparations of Nerve Substance. — Various authors 
 have recommended different preparations. Some use 
 glycerinated extracts, and administer them by intra- 
 muscular injection; others use extracts dissolved in oil 
 and given in the same manner, and a record will be foimd 
 of a presumably useful preparation which consists of an 
 emulsion of certain substances derived from nerve sub- 
 stance suspended in oil. In addition to the above there 
 are certain preparations which are given by mouth. 
 These include a simple emulsion of brain and nerve sub- 
 stance preserved with glycerine, and desiccated powders 
 prepared from the various parts or the whole of the con- 
 stituents of the nervous system. Satisfactory dried ex- 
 tracts are not easily made, because of the difficulty of 
 making suitable preparations from a substance so rich in 
 fats as brain is well known to be. Treatment with 
 various solvents, such as acetone, ether, or chloroform, 
 removes, of course, certain of the lipoids, and deprives 
 the product of a good share of the cholesterin and perhaps 
 of the whole of the lecithin, probably the most important 
 therapeutically active agents in brain substance.* 
 
 The Therapeutic Influence of Nerve Extracts. — Prepara- 
 tions of this character have been used in the treatment 
 of defects of nutrition, especially where there is involve- 
 ment of the nervous system. It has been claimed fre- 
 quently that extracts of brain, spinal cord, and nerve 
 tissue generally exert a favourable influence upon the 
 
 * Serono aud Palozzi^ have analyzed brain and nerve substance (cejilialine), 
 and find that for the most part it consists of lipoids. There are four principal 
 substances of this nature : (1) lecithin, 3'9 to 4 "4 per cent. ; (2) cholesterin, 
 1*4 to 1"6 per cent. ; (3) cerebrin, 1'4 per cent. ; and honiocerebrin, 0'3 to 0*5 
 per cent.
 
 330 Practical Hormone Therajyy 
 
 functional capacity of the nervous system, and by the 
 tonic stimulation of the nutritional activities of this part 
 of the body may cause favourable changes in its func- 
 tional capacity. The principal conditions in which this 
 treatment has been applied are the functional nervous 
 disorders, such as neurasthenia, hj^steria, and certain 
 mental diseases. Where such functional disturbance is 
 accompanied by definite lesions, the results are less likely 
 to be satisfactory; but there seems no doubt from the 
 records that, in spite of organic changes that may have 
 taken place, the reduction of the functional disabihty of 
 the remaining histologically sound tissue may be of con- 
 siderable advantage. RosenthaF believes that — " In 
 cases with lesions, even serious lesions, nervous opo- 
 therapy acts favourably upon the functional troubles 
 which accompany even medullary sclerosis, and may be 
 employed as a palliative." This same writer concludes 
 his communication to the Paris Societe de Therapeutique^ 
 with the following statement: "Limited in its precise 
 province, born of an exact conception, responding to a 
 determined indication^ combined with other symptomatic 
 medication, nervous opotherapy- by the injection of prod- 
 ucts rich in zymases will justly become a customary 
 factor in practical medicine." This has, however, yet to 
 be accomplished, for at present the extent of the applica- 
 tion of this method of treatment is extremely limited. 
 
 The Antitoxic Action of Cerebral Extracts. — The 
 " fixing " action of brain substance upon certain poisons 
 was brought into prominent consideration by Wasser- 
 mann and Takaki^ in 1898. It was shown that prepara- 
 tions of this character would neutralize the tetanus toxin, 
 and this treatment has been used experimentally to pro- 
 duce an artificial immunity against tetanus. The ad- 
 vent of the antitoxins has relegated the application of
 
 Products of Brain and Nerve Substance 331 
 
 brain extracts in tetanus to the background, but it may 
 be of value to remember this antitoxic action. An 
 extract of brain substance is prepared bj'' Page® in the 
 following manner: The brains are dried in vacuo, then 
 extracted with ether, and the ether distilled off. The 
 remaining emulsion is dissolved in oil, 1 gramme to each 
 10 c.c. This product is of a lipoid nature, but is neither 
 lecithin nor cholesterin. Page considers it to be the sole 
 therapeutically active principle of brain substance. 
 
 Ten injections, each consisting of 2 c.c. of the solution, 
 are made, one every other day. After an equal period 
 of rest the treatment may be continued. The principal 
 results are thus summarized by Page : 
 
 ( 1 ) The blood-pressure is raised slightly, and falls again 
 after several hours. (2) The strength, as measured by the 
 dynamometer, is increased. Asthenia rapidly is reduced, 
 and with it the headache. (3) The appetite is increased, 
 and later the weight. The increase may be as much 
 as 2 kilogrammes weekly. (4) Following these injections, 
 there is an increase of phosphates in the urine, a diminu- 
 tion of the conjugate sulphates, and of indican, if present. 
 (5) Occasionally the increased function is accompanied by 
 a mild and passing insomnia. This treatment is recom- 
 mended in functional nervous and mental diseases 
 generally. 
 
 Further evidence of the detoxicating action of this 
 class of substances has been brought forward by Voegtlin 
 and TowlesJ who found that an aqueous extract of 
 autolyzed spinal cord substance from which the coagu- 
 lable proteids were removed contained a substance which 
 exerted a favourable action upon experimental poly- 
 neuritis. This extract is said to contain an antineuritic 
 substance, which evidently removed the nervous sjaiip- 
 toms, but does not re-establish a normal metabolism.
 
 332 Practical Hormone Therapy 
 
 Brain Extract in the Treatment of Certain Insanities. — 
 
 The original application of extracts of brain in mental 
 disorders seems to have been by Babes. ^ A few years 
 later Ryan^ and Robertson^ reported fairly satisfactory 
 results in chronic mania and in melanchoha. No ex- 
 tensive work seems to have been done, however, although 
 quite recently Maule Smith^° states that an extract of 
 brain (of foetal calves) has given him good results in 
 various forms of insanity. He used it in both chronic 
 and acute cases, and among those which were improved 
 by this treatment were cases of dementia, delusional 
 insanity, dementia prsecox, melancholia, and epileptic 
 insanity. The results were, of course, by no means uni- 
 form, but the percentage of improvement was good, and 
 no harm resulted from this medication in any case. 
 
 Smith prepares the extract by boiUng finely divided 
 brain substance in a mixtm'e of alcohol and ether, and 
 straining through muslin. When cold, the deposit is 
 poured into boiling normal saline solution, to which 
 glycerine has been added; 30 c.c. of the deposit with 
 1 litre of saline solution makes an opalescent emulsion. 
 The extract should be made with fresh brains, and the 
 younger the animal from which they are taken, the more 
 active the preparation. The emulsion contains choles- 
 terin and a substance which reduces Fehling's solution. 
 It is beheved to be more active than the dried prepara- 
 tions and cerebrin. 
 
 Smith does not attempt to explain the therapeutic 
 action of this remedy, but states that it has a powerful 
 influence in various diseased mental states, and doubt- 
 less is active in that it induces the re-establishment of a 
 more normal condition of the brain tissue, which is known 
 to be altered in various diseases. 
 
 The importance of this subject is the greater because
 
 Prodvcis of Brain and Nerve Substance 333 
 
 our present methods of treating the insanities are none 
 too energetic, and in many institutions lean toward the 
 side of passive care rather than to active attempts to 
 cure. 
 
 BIBLIOGRAPHY 
 
 ^ Babes (V.): Ueber die Behandlung der genuineu Epilepsie und 
 der Neurastheuie mittels subcutaner Injection von normaler 
 Nervensiibstanz, Deut. mecl. Wchnschr. (Leipzig), 1892, xviii, 
 683 ; see also id. : Ueber Injectionen niit normaler Nerven- 
 substanz, Wien. hi. Bund., 1898, xii, 203. 
 
 2 Serono (C.) and Palozzi (A.): Sur les lipoides contenus dans 
 
 la substance nerveuse, Arch. Ital. d. Biol. (Pisa), 1913, Ix, 
 136. 
 
 3 Rosenthal (G.): L'opotli6rapie nerveuse, c6rebrale et m6dul- 
 
 laire, Bev. med. (Paris), 1910, xx, 580. 
 
 * Id.: L'opoth6rapie nerveuse, Bev. pr. d. Biol. Appl. (Paris), 
 
 1912, x, 34. 
 5 Wassermann (A.) AND Takaki (T.): Ueber eine neue Art von 
 
 kiinstliclier Immunitat, Berl. hi. Wchnschr., 1898, xxxv, 4. 
 ^ Page (M.): Une antitoxine c6rebrale: sa preparation, son 
 
 action et son mode d'emploi, Pr. med. (Paris), 1909, xvii, 516, 
 ■^ VoEGTLiN (C.) AND TowLES (C): Treatment ot experimental 
 
 beriberi with extracts of spinal cord, J. Pharmacol, and Exp, 
 
 Ther. (Baltimore), 1913, v, 67. 
 
 * Ryan (R. P.): Hypodermic injections of brain extract in mental 
 
 diseases, Br. Med. J. (London), 1894, i, 240. 
 ^ Robertson (A.): A discussion on the treatment of mental 
 and nervous diseases by animal extracts, Br. Med. J. 
 (London), 1896, ii, 800. 
 10 Maule Smith (W.): On the use of brain extract in the treat- 
 ment of various forms of insanity, Br. Med. J. (London), 
 1912, ii, 1451. 
 
 GuiRAUD (M.): " Essai de Traitement de I'lnsuffisance C6r6- 
 brale par les Injections de Sue de Cerveau," These de 
 Toulouse, 1907.
 
 CHAPTER XXII 
 
 THE TESTES— ORCHITIC EXTRACTS 
 
 The Renaissance of Organotherapy — The Physiological Action 
 of the Testicular Hormone — The Influence on Growth and 
 Development — Brown- Sequard's Personal Experiences — 
 The Mode of Action of Orchitic Extracts — Von Poehl's 
 Spermin — The Dynamogenic Action of Testicular Extract — 
 The Antitoxic Action in Asthenias and Dermatoses — The 
 Present Status of Orchitic Therapy. 
 
 As far as we know, the use of testicular substance was 
 the first of the numerous attempts to use the organs of 
 animals as remedial agents, and the records will show 
 that its use dates back to many hundred years before 
 Christ. 
 
 The Renaissance of Organotherapy. — The remarkable 
 and epoch-making studies of Brown-Sequard, published 
 in July, 1889,^ have placed the use of orchitic extracts 
 upon a much more rational basis, and the results of this 
 work virtually may be considered to be the renaissance 
 of organotherapy. 
 
 While to-day this method of treatment is by no means 
 so far advanced as the use of thyroid or adrenal prepara- 
 tions, and many physicians look still askance upon those 
 who manifest an interest in it, preferring to stand by 
 other means of treatment, there can be no doubt that 
 the internal secretion of the testes is a vital factor in the 
 cell metabolism, and that equally with preparations of 
 the ovaries and corpora lutea it deserves application in 
 therapeutics. As a matter of fact, it has been stated 
 
 334
 
 The Testes— Orchitic Extracts 3^5 
 
 that didymin is capable of producing results such as may 
 be expected from ovarian medication. ^ 
 
 Unfortunately, a great deal of the literature on this 
 subject is of questionable accuracy, and some of the 
 books seem to have been published with ulterior motives. 
 Suffice it to say, however, that orchitic therapy is useful, 
 and hence worthy of consideration. 
 
 The Physiological Action of the Testicular Hormone.^ 
 Like several of the endocrinous glands, the testes have a 
 dual role in their physiological action, just as their struc- 
 ture falls into two distinct histological definitions, the one 
 part of the gland being the so-called " seminal gland," 
 with spermatogenesis as its function, and the other an 
 interstitial gland having the internal secretory powers 
 which are now so well known. Most of the scientific* 
 knowledge that is available on this subject has come from 
 experiments on animals and pathologic reports. 
 
 The influence of castration upon animals is obvious, 
 and from the deductions of hundreds of experiments, 
 which have been amplified by not a few pathologic 
 findings in man, it is clear that the internal secretion of 
 the testes is the principal factor in the establishment of 
 the secondary sexual characteristics. The nutrition is 
 affected in such a way that, when this hormone is absent, 
 the normal vigour and aggressiveness is lost, physical 
 changes in the appearance are obvious, oxidation is 
 diminished, and there is a tendency to obesity and 
 flabbiness. This lack of virility favours the onset of 
 
 * Let it be understood that the author admits frankly that, with a very 
 few exceptions, the use of hormone preparations is empiric, and hence not 
 strictly to be classed as scientific. It is only for this reason that organo- 
 therapy as a whole has not yet the repute that it deserves ; but it is well to 
 remember that empiric methods may be just as rational as those which are 
 absolutely scientific, for in practical medicine one is not so much concerned 
 as to how the results are obtained, as that they are obtained, and that they 
 are as good and rapid as possible.
 
 336 Practical Horwone Therapy 
 
 premature senility, with undue wealaiess, changes in the 
 form of the body, facies, etc. 
 
 The Influence on Growth and Development. — Experi- 
 mentally, at least, the removal of the male gonads results 
 in very striking changes in both growth and development, 
 and there is considerable clinical evidence which seems 
 to show that in cases of infantilism, cryptorchism, and 
 occasionally following the removal of the testes, the 
 administration of the corresponding animal extract 
 favours a restoration of the disordered nutrition. In 
 animals, at least, very decided and remarkable changes 
 have been brought about m this manner, although the 
 evidence of the changes brought about m the animals 
 is still denied in some quarters, Gilford having stated, as 
 recently as the Seventeenth International Congress of 
 Medicine (1913), that "all attempts to influence growth 
 and development by extracts from the sex glands have 
 failed." This does not seem to be quite in harmony with 
 the facts, for it has been, and will continue to be, done. 
 It must be remembered, of course, that the administra- 
 tion of preparations of this character cannot begin to 
 take the place of the organs removed, and, if possible, a 
 graft might be attempted which, if successful, will be 
 much more effective in bringing about the desired change 
 than the administration of extracts hypodermically or by 
 mouth. 
 
 Brown-Sequard's Personal Experiences. — Numerous 
 clinical tests have been made to establish the physical 
 action of orchitic substance or extract. It has been shown 
 to have a remarkable revivifying influence, and one can- 
 not do better than relate the gist of Brown-Sequard's 
 original communication : 
 
 " I am seventy-two years of age. My health is, on the 
 whole, good. Having ceased to take much exercise for 
 
 1
 
 The Testes— Orchitic Extracts 337 
 
 over thirty years, my natural vigour has gradually 
 dimmished, and during the last ten years I have become 
 very weak. 
 
 " On May 15 1 removed the testicles of a vigorous dog. 
 After having chopped up the whole organ, and also the 
 greater portion of the vas deferens, I rubbed up the 
 mixture with a small quantity of water. On filtration, 
 the mixture yielded 4-|- c.c. of liquid. I injected into my 
 leg nearly 1 c.c. of this liquid, and repeated the injection 
 on the two following days, as well as on May 24, 29, 
 and 30. 
 
 " Before the first injection I was unable to keep on my 
 feet more than half an hour, and even when I remained 
 seated throughout my work m the laboratory three or 
 four hours of experimenting exhausted me. On the day 
 following the first injection, and still more so during the 
 following days, a radical improvement took place. Con- 
 siderable work at the laboratory hardly produced any 
 fatigue, and to the astonishment of my two prmcipal 
 assistants I was able to do experimental work for several 
 hours in succession in a standing position. My limbs, which 
 I tested with a dynamometer durmg the week preceding 
 my experiments, and also during the week after the first 
 injection, showed a very considerable gain in strength. 
 
 " There can be no doubt that the power of the spinal 
 cord upon the bladder has considerably increased. A 
 radical change also occmTed in the reflex action of defseca- 
 tion. The need of laxatives was much reduced, and the 
 expulsion of faeces could take place without mechanical 
 assistance. There was, in fact, a distinct return to the 
 normal condition which existed many years ago. Bram- 
 work has also become more easy than it had been for a 
 very long time, and I have regained on this ground all 
 that I had lost." 
 
 2i
 
 338 Practical Hormone Therapy 
 
 The Mode of Action of Orchitic Extracts. — The conclu- 
 sions of Brown-Sequard and d'Arsonval,^ which were 
 made following reports from 1,200 physicians who had 
 clinically applied this method during the first four years 
 of its use (1889-1893), are essentially those of the present 
 time, with the prmcipal exception that the channel of 
 action is now known to be different, the action being 
 through humoral rather than nervous paths. They 
 reached the following conclusions: (1) Though orchitic 
 fluid does not possess any direct curative influence upon 
 the diverse morbid conditions of the system, it may, when 
 injected under the skin, cure or considerably improve 
 diseases, either organic or not, of the most varied char- 
 acter, or at least cause their effects to disappear. (2) These 
 actions of the orchitic liquid are due to two kinds of 
 influences : by means of one of them the nervous system, 
 gainmg in strength, is enabled to improve the dynamic 
 or organic condition of the diseased parts, and by the 
 other, which depends upon the introduction mto the 
 blood of new materials, this liquid contributes to the cure 
 of morbid conditions by the formation of new cells or 
 other new anatomical elements. 
 
 There is no doubt of the stimulatmg effect of this treat- 
 ment upon the nervous system, but this nervous action 
 is evidently rndkect — that is to say, the orchitic substance 
 does not directly stimulate the nerves. The value of this 
 treatment depends upon the fundamental basis of hor- 
 mone therapy, which has already been discussed. Not 
 only does Hallion's axiom hold good, but there is a 
 stimulation of the whole hormone-producing system, 
 especially those parts of it which are concerned in the 
 production of energy — the Idnetic system — and hence to 
 administer preparations of this character is in the majority 
 of cases to enhance the hormone content of the blood,
 
 The Testes — Orchitic Extracts 339 
 
 and to strengthen the value and frequency of the chemical 
 messages which play such an important part in the main- 
 tenance of the vital processes. 
 
 Von Poehl's Spermin. — About twenty-five years ago, 
 von Poehl'* of St. Petersburg, stimulated doubtless by 
 the reports from' Paris, suggested that certain organs 
 produced remedial agents with which the organism 
 regenerated itself and overcame disease. He isolated a 
 substance called " spermin " from a number of organs, 
 chiefly from the testicles, and considers it as one of the 
 normal protective agents of the body, which, when given 
 internally, may be also an active remedy. Its adminis- 
 tration is merely an imitation of Nature. Spermm is 
 prepared from the testicles of bulls and stallions, which 
 are macerated with water and extracted. The albu- 
 minous substances are removed, and the spermin chemi- 
 cally isolated, usually as a salt of phosphoric acid. 
 
 This substance has been recommended in a large 
 number of conditions, chief among which is what von 
 Poehl has called " auto-intoxication from decreased 
 intra-organic detoxication." Its value has been stated 
 to be due to its capacity to oxidize the organic acids 
 which originate in the course of a disturbed metabolism, 
 and thus to facilitate the restoration of the normal alka- 
 linity of the blood. This stimulant action upon metab- 
 olism is the explanation of its usefulness in certam func- 
 tional nervous disorders, particularly neurasthenia, which 
 is, after all, virtually a form of auto-intoxication. 
 
 Most of the literature on this subject is in Russian, and 
 hence not available to very many. The translation of 
 von Poehl's book* gives his explanation of the rationale 
 of this method of treatment, as well as quite an extensive 
 bibliography. 
 
 * See under "Manufacturers' Literature" in the List oi' Books in 
 Appendix.
 
 340 Practical Hormone Therapy 
 
 The Dynamogenic Action of Testicular Extract.— Clini- 
 cally, as well as in laboratory experiments, there has 
 been brought together a number of facts which demon- 
 strate that extracts of the testicles contain a principle 
 which acts chiefly upon the energy-producing factors. 
 It will be remembered that the original application of 
 this method of treatment resulted in increased power, 
 both mental and physical. Several experiments have 
 been carried out by Zoth^ and others with Mosso's ergo- 
 graph, which conclusively prove that this principle can, 
 and does, influence in a very evident manner the mus- 
 cular energy. How this is brought about is not quite 
 clear, but it is usually supposed to be due to an increase 
 m oxidation, and the consequent removal of inter- 
 mediary products of metabolism, which clog the machine. 
 According to Carnot,^ it produces an excitation of the 
 entire organism by increasing the oxidizing power of the 
 blood, and causing a more complete combustion of the 
 cellular products. 
 
 The Antitoxic Action in Asthenias and Dermatoses. — 
 BouiiC " has shown that the principal worth of this method 
 in therapeutics is dependent upon an antitoxic action. 
 He calls attention to the frequent benefit following the 
 exhibition of testicular extract in certain toxic derma- 
 toses, and even psoriasis, and considers that these clinical 
 experiences lend weight to his contention of this anti- 
 toxic action. A number of other investigators have used 
 preparations of this nature m dermatology, and Scharff^ 
 is convinced of its value. Bouffe believes that testicular 
 extract may also influence the phosphorus metabolism, 
 thus accounting for part of its good eifects. This he has 
 called the " toni-sedative " mfluence, because the effects 
 often combined sedation of certain functions with stimu- 
 lation of others. He has found the administration of
 
 The Testes — Orchitic Extracts 341 
 
 testicular extracts to be particularly useful in asthenic 
 states, and especially in those individuals who also mani- 
 fest an instability of the nervous system. 
 
 The Present Status of Orchitic Therapy. — It is difficult 
 to set down the present opinion of this method of treat- 
 ment. It is not in general use, nor is it of particularly 
 good repute, but nevertheless there can be no question as 
 to its value. The consensus of opinion has been modified 
 by the somewhat highly painted pictures, many of which 
 seemed to be stimulated by more than scientific motives. 
 
 The action of testicular extracts is not so limited as we 
 are accustomed to expect. A course of treatment with 
 testicular extract frequently accomplishes such a number 
 of changes of such remote organs, and influences such 
 widely disconnected ones, that to report actual results 
 might even be sufficient to discount the position of this 
 method. The extent of these results is undoubtedly due 
 to the stimulating action of the testicular hormone upon 
 the endocrinous system as a whole, and as a means of 
 revitalizing an mdividual with deficient oxidation, poor 
 nutrition, nervous inactivity, and general weakness, the 
 system is of undoubted value. There are few single 
 remedies which can compare with active and properly 
 prepared testicular extracts. 
 
 One particular advantage of this method of treatment, 
 to say the least, is that it facilitates the production of a 
 new supply of substances vital to the economy. The 
 alkaloidal tonics are not superior to organotherapy — at 
 least, in the treatment of chronic conditions — and the, 
 action of the alkaloids may be compared to the stimulus 
 of the whip to a tired horse, while the organotherapeutic 
 measures are more like the comparison of a good meal to 
 a hungry one. 
 
 There are a number of proprietary testicular extracts
 
 342 Practical Hormone Therapy 
 
 on the market, some in liquid and others in cachet or 
 tablet form. The best known are didymin (English), 
 testikidin (German), sequarine (Swiss), spermiri (Russian), 
 orchipina (Italian), and orchitine (French). 
 
 BIBLIOGEAPHY 
 
 1 Brown-Sequaed (C. E.): Experience demontrant la puissance 
 
 dynamogenique cliez rhomme d'un liquide extrait de testic- 
 
 ules d'animaux, Arch. d. Physiol. (Paris), 1889, xxvi, 651; 
 
 see also ibid., 739. 
 - EwAN Waller (H.): Tlie relationship of the thyroid gland to 
 
 other internal secretions of sexual origin, Pract. (London), 
 
 1912, Ixxxix, 286. 
 ^ Brown-S^quard (C. E.) and D'Arsonval (A.): Effets physio- 
 
 logiques et th^rapeutiques d'un liquide extrait de la giande 
 
 sexuelle male, C. r. Acad. d. Sci. (Paris), 1893, cxvi, 856. 
 * VON PoEHL (A.): Zur Erklarung der Wirkung des Sperinins als 
 
 physiologisches Tonicum auf die Autointoxicationen, Berl. 
 
 kl. Wchnschr., 1893, xxx, 873. 
 ^ ZoTH (0.): Zwei ergographische Versuchsreihen ueber die 
 
 Wirkung orchitischen Extractes, Arch. f. d. ges. Physiol. 
 
 (Bonn), 1896, Ixii, 335. 
 ® Carnot,* p. 291. 
 ^ BouFFE (F.): I)e Topoth^rapie testicvdaire consid6ree au point 
 
 de vue de son action antitoxique et toni-s6dative, J. d. med. 
 
 d. Paris, 1903, xv, 141. 
 ^ ScHARFF (P.): Testikulin in der Praxis der Dermatologie und 
 
 Urologie, Med. Kl. (Berlin), 1913, ix, 1461. 
 
 USPENSKI (D. M.): Testikulare Organotherapie, Deut. aerzte 
 
 Ztg. (Berlin), 1909, pp. 1, 28, 54, 80, 101, 123, 145, 173, 196. 
 Noi; (J.): La spermine, Arch. gen. d. med. (Paris), 1903, ii, 1757. 
 ScAiALLERO (M.): L' orchipina, preparato di testicolo fresco in 
 
 veicolo oleso, Bif. med. (Naples), 1905, xxi, 113. 
 MiLiAN (G.): Les utilit^s du testicule, Bev. d. hop. d. France et 
 
 etrang. (Paris), 1905, vii, 1. 
 ScHMANCH (G.): Orcliitic and ovarian therapy, Interstate 3Ied. 
 
 J. (St. Louis), 1910, xvii, 92. 
 Levi (L.): Psoriasis et rhumatisme chronique. Transformation 
 
 parl'opotherapie thyroidienne et testiculaii-e, C r. Sac Biol. 
 
 (Paris), 1913, Ixxiv/l 156.
 
 CHAPTER XXIII 
 THE ACTION OF PROSTATIC EXTRACTS 
 
 The. Control of Prostatic Hypertrophy — Prostatic Neurasthenia — 
 The Effects upon Bladder Contractility — Administration and 
 Dosage. 
 
 The prostate, like many other glands, has been pre- 
 sumed to have an internal as well as an external secretion. 
 It seems that the evidence to-day is in favour of this 
 theory, although there are many conflicting reports in 
 the literature on this subject. It has been suggested that 
 the prostate influences spermatogenesis, and in conse- 
 quence extracts of it have been used in the treatment of 
 impotence, but with indifferent results. 
 
 The Control of Prostatic Hypertrophy. — There are several 
 published clinical reports of cases of hypertrophy of the 
 prostate in which good results have followed the adminis- 
 tration of extract of prostate. Reinert^ found that both 
 the subjective and objective symptoms were improved, 
 and his experiences have been confirmed by Bazy,^ 
 Oraison,^ Englisch,'* and others. Oppenheimer^ suggests 
 that this method may be applied in non-specific prostator- 
 rhoea; he found that the discharge was rapidly controlled 
 following several days' treatment with extract of prostate. 
 
 These results, however, do not seem to have been 
 sufficiently stimulating to the profession, for of late years 
 there have been very few favourable reports, and outside 
 of France very few attempts are made to apply prostatic 
 organotherapy in genito- urinary practice. 
 
 343
 
 344 Practical Hormone Therapy 
 
 Prostatic Neurasthenia.— The frequency of neurasthenic 
 manifestations in individuals suffering with prostatic 
 disorders has led several investigators to suppose that the 
 prostate supplies some essential element which is con- 
 cerned in the establishment of the normal control of the 
 nervous system. This seems to be emphasized by 
 Rovsing's statement^, that individuals frequently become 
 sufferers from melancholia following prostatectomy. 
 Beard'^ also believes that removal of the prostate is a 
 frequent cause of neurasthenia, and that prostatic extract 
 will replace a part of the missing hormone (?), and cause, 
 or at least favour the causation of, a satisfactory control 
 of the neurasthenic manifestations. Other writers agree 
 with this idea, and it seems that the principal indication 
 for prostatic organotherapy is in the treatment of the 
 neuroses that occasionally follow prostatectomy and 
 prostatic hypertrophy. 
 
 The Effects upon Bladder Contractility. — Dubois and 
 Boulet^ assert that freshly prepared watery extract of 
 adult dog's prostate stimulates the movements of the 
 bladder in vivo, and that this action is produced just as 
 well in animals with the spinal cord destroyed as in those 
 in which the nervous system is intact; it is, then, inde- 
 pendent of the arterial pressure. This may be a part of 
 the explanation of the results obtained in the treatment 
 of prostatic hypertrophy, and especially those cases in 
 which there was retention of urine. 
 
 Battez and Boulet^ reported before the Societe de 
 Biologic (Paris) that they had had a fortunate opportunity 
 to corroborate their experiments with extract of canine 
 prostate gland as causing, on intravenous injection, lively 
 contractions of the bladder. Half an hour after his execu- 
 tion they were able to secure a perfectly healthy gland 
 from a criminal, aged twenty years, and to make an
 
 The Action of Prostatic Extracts 345 
 
 extract therefrom. They found that this human extract 
 had the same effect on the bladder as the canine prepara- 
 tion, and also possessed a marked hypotensive action on 
 arterial pressure. 
 
 Administration and Dosage. — The prostate glands of 
 bulls or boars are used in the preparation of the extracts. 
 The gland substance is dried in vacuo, and each part of the 
 finished powder represents six parts of the fresh substance. 
 
 Extracts of prostate are quite toxic, and it has been 
 shown that 2| grains (0'16 gramme) of powdered prostate 
 corresponding to 15 grains (1 gramme) of fresh substance 
 are sufficient to kill a dog weighing 17 or 18 pounds. 
 This toxicity is variable, and depends principally 
 upon the age of the animal from which the gland is 
 obtained. 
 
 In France prostatic extracts are occasionally pre- 
 scribed, and the usual dose is 0-10 gramme (1| grains) to 
 0-20 gramme (3 grains), two or three times a day. 
 
 BIBLIOGRAPHY 
 
 ^ Reinert (E.): Verkleinerung der hypertrophirten Prostata 
 
 nach Darreichung frischer Thierprostata, Deut. med. 
 
 Wchnschr. (Leipzig), 1895, xxi, 79, 
 ~ See Merck's Ann. Report, 1908, xxii, 15. 
 3 Id. 
 * Englisch (J.): Ueber die neueren Behandlungsmethoden der 
 
 Prostatahypertrophie, Wien. med. Pr., 1896, xxxvii, 112. 
 5 Oppenheimer (H.): Die innerliche Behandlung der Prostator- 
 
 rhoea ex Prostatitide chronica rait Prostatasubstanz, Derm. 
 
 Zentr. (Berlin), 1899, ii, 104. 
 " RovsiNG (Th.): Kastration ved Prostatahypertrofi, Hosp. Tid. 
 
 (Copenhagen), 1895, iii, 1101. 
 ' See Byla and Delaunay:* p. 334. 
 ^ Dubois (C.) and Boulet (L.): Action des extraits de prostate 
 
 sur les circulations c6r6bra]e et r^nale, G. r. Soc. Biol. (Paris), 
 
 1913, Ixxiv, 811; see also ibid., 1912, Ixxii, 701.
 
 346 
 
 Practical Hormone Therapy 
 
 Battez (G.) and Boulet (L.): Action de Textrait de prostate 
 liumaine sur la vessie et sur la pression arterielle, 0. r. 8oC' 
 Biol. (Paris), 1913, Ixxiv, 8. 
 
 Hallion (L.), Morel (L.), and Papin (E.): Action vaso- 
 
 dilatrice penienne de I'extrait prostatique, C. r. 8oc. Biol. 
 
 (Paris), 1913, Ixxiv, 401. 
 Jappelli (G.) and Matozzi Scafa (G.): Sugli effeti dell' 
 
 iniezioni intravenose di estratto prostatico de cane, Gior. int. 
 
 d. sc. med. (Naples), 1905, xxvii, 1066. 
 GoTZL (A.): Versuche ueber die Wirkung von Prostatapress- 
 
 saften, Ztschr. f. Urol. (Berlin), 1910, iv, 743.
 
 CHAPTER XXIV 
 
 THE OVARIES AND CORPORA LUTEA 
 
 The Discovery of the Ovarian Secretion — Two Ovarian Hor- 
 mones — The Luteal Internal Secretion- — A Pathological 
 Ovarian Hormone — The Influence of the Ovaries upon Me- 
 tabolism — The Regulation of Calcium Eliniiination — The 
 Relation between Ovaries and Thyroid — The Influence of 
 the Ovaries upon the Other Endocrinous Organs — Luteal 
 versus Ovarian Preparations — Ovarian Therapy at the 
 Climacteric — The '" Run-Down Conditions " — Amenorrhcea, 
 Anoemia, and Chlorosis — The Vomiting of Pregnancy — 
 Hysteria and Insanity — Miscellaneous Suggested Applica- 
 tions of Ovarian Medication — Hyperoophorism — Contra- 
 indications — Dosage and Administration. 
 
 The ovaries are concerned in the temporary function 
 of the perpetuation of the species, and in the human 
 species are active from puberty to the menopause. 
 During this period they perform a much more complex 
 function than ovulation, for they produce a substance or 
 series of substances concerned in the establishment and 
 correlation of certain of the essential feminine attributes. 
 Their influence extends to the regulation of the intricacies 
 of metabolism and oxidation, and a critical analysis of all 
 the several and rather widely separated ovarian functions 
 demonstrates their fundamental importance, not merely 
 as a pair of ovum-producing organs, but as a remarkable 
 factor in bending the metabolism and regulating the whole 
 reproductive mechanism, as well as the internal secretory 
 system in the preparation for, establishment of, and con- 
 summation of, the reproduction of the species. 
 
 347
 
 348 Practical Hormone Therapy 
 
 The Discovery of the Ovarian Secretion. — It appears 
 that Claude Bernard was the first to suggest the possi- 
 bihty of the dual role of the ovaries, while Brown- Sequard/ 
 shortly after his notable announcement regarding orchitic 
 extracts, referred to in the previous chapter, expressed 
 his ideas concerning the similarity between the testicular 
 and ovarian juices, and the possibility that the use of 
 ovarian preparations might produce in women results 
 corresponding with those produced by testicular extracts 
 in himself and numerous other men. He was convinced, 
 however, that ovarian extracts are not so powerful as 
 extracts of the male glands. 
 
 While the internal secretion of the ovary has not yet 
 been isolated, its influence is very evident. An intimate 
 study of this subject cannot conveniently be gone into 
 here.* It is well known that the removal of the ovaries 
 causes such objective changes as atrophy of the breasts, 
 uterus, and external genitaha, as well as favouring a 
 tendency to obesity, while the subjective symptoms are of a 
 nervous and nutritional character. It is a matter of general 
 knowledge that ovarian disease is frequently the cause of 
 similar disturbances. Many experiments "vvith ovarian 
 grafts in women, as well as in animals, have served to 
 emphasize the vast importance to the economy of the 
 ovarian internal secretion. 
 
 Two Ovarian Hormones. — From all the information at 
 hand, it is clear that more than one hormone is produced 
 by the ovary. An " ovarian hormone " is produced by 
 the interstitial stroma of the gland, and is indirectly con- 
 
 * There is a large and, at time.i, somewhat contradictory literature on the 
 functions of the ovary. The subject can only briefly be mentioned here, in 
 order to give an outline basis for the statements regarding tJurapentics whicli 
 follow. In addition to tlie chapters in the reference books (see list in 
 appendix) the papers by Frank, 2 Blair Bell,^ and Morley,* cover the subject 
 very thoroughly, and the last-mentioned paper is amplified by an extensive 
 bibliography of 46.5 references.
 
 The Ovaries and Corpora Lutea 349 
 
 cerned in the regulation of menstruation and nutrition 
 generally. Further, according to Blair Bell,^ the activity 
 of the uterus is maintained, and regular contractions are 
 promoted, probably by the secretion of the interstitial 
 cells. 
 
 On the other hand, the corpus luteum produces a hor- 
 mone which seems to be an antagonist to the ovarian 
 hormone, in that it " inhibits ovulation between the 
 oestrus periods and ovulation during pregnancy. Ott and 
 Scott ^ have found the corpus luteum to be a galacta- 
 gogue." Some are of the opinion that this position is 
 wrong, since ovulation has been known to occur during 
 pregnancy. 
 
 The Luteal Internal Secretion. — The first reference in 
 the literature to the activities and importance of the 
 luteal cells was made by Prenant^ in 1898. Fraenkel,'^ 
 shortly after, made an exhaustive report of his studies 
 of the function of these bodies. He believes that the 
 luteal hormone also specifically controls the uterine nutri- 
 tion during the reproductive life. He has shown also 
 that the corpus luteum is strictly an internal secretory 
 gland, and that it brings about the alterations necessary 
 for the embedding of the ovum, and is therefore essential 
 in the foetal development in the early part of pregnancy. 
 Fraenkel also believes that the corpus luteum is respon- 
 sible for the cyclic engorgement of the uterus which pre- 
 cedes menstruation. 
 
 The corpus luteum sensitizes the uterine mucosa, ren- 
 dering it responsive to mechanical stimuli, with the re- 
 sulting formation of the maternal placenta (Frank).- It 
 also inhibits ovulation. This is evidently brought about 
 by a humoral or hormone action, and is essential in the 
 early stages of pregnancy. It might be inferred from 
 this that in certain cases luteal disorder is responsible
 
 350 Practical Hormone Therapy 
 
 for sterility, and lutein might be used to facilitate the 
 attachment of the ovum. Ellice McDonald^ reports 
 chnical experiences which seem to confirm this idea. 
 He tells of an interesting case of " a woman over forty- 
 five, with commencing menopause, who has been under 
 treatment for three years, with the result that the menses 
 are still regular, and after she had been under treatment 
 for eight months she conceived and miscarried. Her last 
 child was born eighteen years before this. She still con- 
 tinues the medication in the hope that she has discovered 
 the fountain of youth." 
 
 The luteal hormone is also an important factor in the 
 growth of the mamma. Frank^ concludes that — ^" Growth 
 of the mammary gland is due to ovarian influence (matura- 
 tion of folhcles, activity of corpus luteum). The same 
 factors which produce the persistence of the corpus luteum 
 probably cause the breast hyperplasia of pregnancy." 
 Heape,^ and later Ancel and Bouin,^° have shown that 
 the normal production of this hormone causes mammary 
 hypertrophy irrespective of any other usually concomi- 
 tant factors. They found that in the rabbit ovulation 
 (and consequent formation of a corpus luteum) results 
 only after copulation. With this there is a development 
 of the mammary glands, even though no impregnation 
 follows, the vas of the buck having been tied. They also 
 found that they could artificially rupture the folhcle with 
 the same result. O'Donoghue^^ has confirmed this, and 
 his work is referred to, and the relation of the luteal hor- 
 mone to mammary growth is further considered, in 
 Chapter XXV. 
 
 The latest communication of Bouin and AnceP^ indi- 
 cates that the luteal hormone is not the only factor in 
 the development of the breasts, but that it renders the 
 mammary cells more sensible to the influence of another
 
 The Ovaries and Corpora Lutea 351 
 
 substance, probably a hormone, and is evidently an 
 essential in this preliminary preparatory work. 
 
 A Pathological Ovarian Hormone. — Seitz^^ beheves that, 
 under certain conditions, a depraved hormone is produced 
 in the ovaries, and that it is the principal exciting cause 
 of uterine fibromata. It may be akin to the " ovarian 
 hormone " which presides over uterine growth and 
 development during puberty, and particularly during 
 pregnancy. This product of ovarian katabolism is prob- 
 ably one of the so-called " parhormones " (Gley). If this 
 supposed relation is real, by its excitation of myomatous 
 growths it is clear that this hormone is no longer physio- 
 logic, but the product of a diseased ovary. This accounts 
 for the favourable action of the X rays upon fibroids — the 
 excess of depraved ovarian hormone-stimuli is removed.* 
 
 The Influence of the Ovaries upon Metabolism.— The 
 prominent part that the gonads play in the regulation of 
 groAvth and development is as important as it is easy to 
 demonstrate. The ovaries undoubtedly are a factor in 
 the regulation of the hormone balance, as well as of the 
 metabolism. The facts already referred to have shown 
 that the nutrition of the reproductive system is evidently 
 controlled by these hormones, and a number of experi- 
 ments have been carried out to show to what extent the 
 ovary and preparations of it modify oxidation and the 
 general ceUular activities. 
 
 Charrin and Guillemonat^^ showed that ovarian ex- 
 tracts were capable of improving the retarded nutrition 
 which occasionally supervenes in pregnancy — a fact which 
 may justify the assumption that such reductions in 
 metabolism are possibly dependent upon diminished 
 
 * Reference to Cliapter XXV. will show that the niainniary hormone is 
 directly antagonistic to this pathological hormone, and hence is frequently 
 used in tlie attempt to control myomatous growths and the concomitant 
 uterine hicmorrhages.
 
 352 Practical Hormone Therapy 
 
 ovarian activity. Aii interesting series of figures secured 
 by Ricliter^ from studies of the metabolism in a cas- 
 trated bitch showed that the metabohc activities, which 
 had been considerably reduced by the operation, were 
 remarkably augmented by the administration of a 
 preparation of ovary. 
 
 This seems justification for the results reported by 
 Sicard^*^ and others, to the effect that obesity frequently 
 is due to hypo-oophorism, and that it often may be treated 
 advantageously in this manner. It has been since found 
 that there is a close relation between the ovary and the 
 pituitary body, deficient ovarian activity resulting in a 
 dyspituitarism. In these cases this combination of in- 
 ternal secretory disorders further favours deficient fat 
 oxidation. This fact is also occasionally of diagnostic as 
 well as of therapeutic assistance in the investigation and 
 treatment of obscm^e disorders in obese girls and young 
 women. 
 
 In the asthenic. conditions associated with a reduction 
 in the urinary sohds the author has frequently noticed 
 that the ovarian treatment of amenorrhoea, climacteric 
 disturbances, etc., caused, besides the more specific effect 
 desired, a considerable increase in the total solids — a fact 
 which emphasizes the evident increased metaboUsm which 
 this medication occasionally brings about. 
 
 Chnical experiments have shown that ovarian therapy 
 increases oxygen consmnption, and, according to Offer- 
 geld,^^ the internal secretion of the ovary in some manner 
 presides over the metabolism of the inorganic salts, thus 
 regulating and maintaining the chemical composition of 
 the blood. 
 
 The Regulation of Calcium Elimination. — The experi- 
 mental deductions of Blair Bell regarding the calcium 
 excretion following oophorectomy are worth considera-
 
 The Ovaries and Corpora Lutea 353 
 
 tion. He found that this operation diminished the 
 urinary calcium one-haK, and beheves that "the ovaries 
 take an active part in promoting the excretion of calcium, 
 especially in connection with menstruation."^ This writer 
 quotes the experiences of Curatulo and TaruUi,^^ and of 
 Neumann and Vass,^^ who found a reduction in the ex- 
 cretion of calcium and phosphorus after administering 
 ovarian substance. Chnical proof of this position is 
 found in the favourable results in osteomalacia following 
 oophorectomy, indicating that a condition of calcium 
 retention is brought about in this manner. 
 
 The Relation between Ovaries and Thyroid. — Chnical 
 observation will usually show the observer numerous indi- 
 cations that hypo-oophorism may manifest similar charac- 
 teristics to hyperthjrroidism, and the most plausible inter- 
 pretation of these facts is that there must be an intimate 
 relation between the thjroid and ovarian hormones. 
 
 One has but to recall the frequent enlargement of the thy- 
 roid during pregnancy, when ovarian function is dormant, 
 and the remarkable preponderance of Graves's disease in 
 women, to realize the relationship of these two organs. 
 
 Further proof of the close connection between the 
 gonads and the thyroid may be adduced from the fre- 
 quent lack of sexual desire, and even impotence in the 
 male, and the disturbances of the menses in the female, 
 as well as from several reports of favourable results fol- 
 lowing ovarian therapy in Graves's disease. One of the 
 earhest communications on this subject is that of Seelig- 
 mann,^^ who reports three cases of hyperthjrroidism, of 
 which one was quite cured, and the other two were 
 definitely improved. Leopold Levi and de Rothschild ^^ 
 have mentioned good results following the use of luteal 
 substance in hyperthyroidism which was associated with 
 hypo-oophorism. 
 
 23
 
 354 Practical Hormone Therapy 
 
 This does not prove that these two glands are antago- 
 nistic to one another ; rather must one conclude that they 
 supplement one another. There is considerable clinical 
 evidence to show that the addition of small doses of 
 thyroid extract to ovarian medication frequently produces 
 a more satisfactory result, as will be seen later. 
 
 The Influence of the Ovaries upon the Other Endocrinous 
 Organs. — A very important communication was made 
 by Blair Bell in his introduction to a discussion on the 
 internal secretions before the Royal Society of Medicine. ^^ 
 This writer pointed out that the activities of the ovaries 
 are correlated, and added: "My experiments," he says, 
 " seem to point to a correlated action in so far as the 
 ovary is principally concerned, and an action in regard 
 to the thyroid and pituitary body, which is partly inde- 
 pendent, partly correlated. The importance of these 
 assumptions, if true, is obvious; . . . the way seems 
 clearer to the solution of the problem which has so long 
 troubled us — I mean the question of a substitution pro- 
 duct in cases of ovarian insufficiency. It seems certain 
 that we shall find that ovarian extract alone is of little 
 value in the majority of cases — in spite of a few favour- 
 able reports — because, after ovarian atrophy or removal, 
 the other endocrinous glands are affected, as we have 
 found experimentally, in a way which is different from 
 that which occurs in a case of the removal of one of the 
 other glands ; so that the substitution of ovarian extract 
 alone is not sufficient to combat all the metabohc dis- 
 turbances, or to prevent the changes in the uterus. If, 
 however, we make use of our knowledge of the cor- 
 related changes in other glands, I believe before long we 
 shall find a combined extract that will give us some 
 measure of success." 
 
 Harrower,22 {^i the same discussion, referred to Blair
 
 The Ovaries aiid Corpora Lutea 355 
 
 Bell's intimation that the use of certain combinations of 
 animal extracts is likely to prove of better therapeutic 
 service than ovarian or luteal extracts alone, and " sug- 
 gested that the results, or lack of results, not uncom- 
 monly following ovarian therapy, such as those just men- 
 tioned by Leonard Wilhams, perhaps might have been 
 obviated had a suitable combination been substituted 
 for the single extract. Several French observers, notably 
 Renon and Delille, have recorded their belief in the ad- 
 vantages of this procedure. This opens up a most com- 
 plicated, but nevertheless promising, field for therapeutic 
 apphcation, and suggests that possibly in the future pluri- 
 glandular therapy may be much more frequently resorted 
 to, with increasingly encouraging results." 
 
 Luteal versus Ovarian Preparations. — For a good many 
 years desiccated ovary has been used, with widely vary- 
 ing results. Doubtless much good that has been at- 
 tributed to it by various writers has really been due to 
 minor concomitant factors which did not receive the full 
 credit due to them. Nowadays, the consensus of opinion 
 is against the total extract, and many reports regarding 
 its uselessness are to be found. 
 
 Extracts of the corpus luteum have generally taken the 
 place of the total ovarian extract, for it has been shown 
 that it is much more therapeutically active, and that the 
 results are better with much smaller doses than were 
 necessary with ovarian extract. Drevet^^ considers that 
 the corpus luteum contains the active therapeutic prin- 
 ciple of the ovary, and he has used it with good results. 
 Kelly24 jjg^g found good results follow the use of 20-grain 
 doses of lutein extract three times a day, given con- 
 tinuously in certain cases, and for ten-day periods in 
 others. He believes that the total ovarian extract has 
 little or no value.
 
 356 Practical Hormone Therapy 
 
 Ovarian Therapy at the Climacteric. — When the repro- 
 ductive hfe is completed, and the genital organs begin to 
 atrophy, the loss of the hormone stimuli to which the 
 body has accustomed itself in the thirty or more years 
 of reproductive life very frequently causes considerable 
 disturbance. This is gradually readjusted in the course 
 of time, but the nervous and mental derangement is often 
 a serious matter. It has seemed reasonable to replace in 
 a degree the lost hormones, and to attempt by ovarian 
 therapy to lessen the severity of these reactions. Among 
 the earliest attempts to apply ovarian substance in the 
 treatment of the disturbances of the menopause is that of 
 Mond.^'' The results were very good, and since then 
 scores of papers have been pubUshed extolling this 
 rational method of treating climacteric disorders. The 
 sympathetic neuroses, such as palpitation, flushing, in- 
 somnia, amnesia, etc., are often promptly relieved, in 
 some cases for a moderate period, and in others perma- 
 nently. 
 
 Geissler^^ reports good results following ovarian therapy 
 in cases of angina pectoris occurring at the menopause. 
 In certain skin diseases which occur during this period 
 Saafeld^^ noted the disappearance of such skin disorders 
 as eczema and prurigo when ovarian therapy was insti- 
 tuted at the menopause. In metabohc disorders, such 
 as gout, rheumatism, and psoriasis, Seeligmann^^ re- 
 ported the advantageous use of ovarian preparations, 
 especially in cases which recurred during the menopause. 
 Huchard has used this method in arterio-sclerosis follow- 
 ing the menopause, and recommends it. 
 
 Merck^^ beheves that " we are justified in stating that 
 this remedy is a specific for all troubles occurring at the 
 climacterium, whether this be produced artificially or 
 occur naturally."
 
 The Ovaries and Corpora Lutea 357 
 
 The results of this form of medication are, however, 
 not uniformly successful, especially in cases of surgical 
 menopause. One of the fundamentals of hormone therapy 
 — Hallion's law — emphasizes that the administration of 
 animal extracts markedly stimulates the functions of the 
 organs corresponding to that from which the preparation 
 was made. The actual content of the useful therapeutic 
 agent in desiccated corpora lutea is small, and even large 
 doses cannot begin to replace the continuous supply of 
 the ovarian hormones which has so suddenly been re- 
 moved by operation. It may be slightly useful, although 
 Ellice McDonald^ believes that its value is practically 
 limited to cases in which the uterus and ovaries, or uterus 
 alone, are retained. He finds it particularly valuable in 
 the treatment of scanty menstruation and the premature 
 menopause. This value is, of course, due to the stimula- 
 tive action upon the pelvic organs and the augmentation 
 of their output of chemical messengers. McDonald very 
 correctly states that " the internal secretion of the ovarj^ 
 is but one factor in the process of the menstrual life. , . • 
 Let no one expect to control these physical changes and 
 nervous alterations of the surgical menopause by the 
 supply of an artificial internal secretion unless at the same 
 time a new uterus to menstruate can be supplied." 
 
 FraenkeF has used lutein with uniformly good results 
 in the disturbances of the menopause, and recommends 
 0-3 gramme of the extract of the corpus luteum of the 
 cow three times a day. 
 
 The " Run-Down " Conditions. — In the so-called " run- 
 down " conditions and neura-sthenia, especially in women 
 with ovarian insufficiency, ovarian preparations may be 
 of encouraging usefulness. In many cases of this char- 
 acter their activity is enhanced by the addition of a very 
 small dose ( Vo to ^V grain) of thyroid extract, and in cases
 
 358 Practical Hormone Therapy 
 
 with hypotension a small dose of pituitary extract may 
 well be added. It seems that in addition to the local 
 influence of each respective extract, the whole favours the 
 regeneration of the functional activity of the adrenal 
 system, for in many of these cases asthenia, hypotension, 
 and reduced metabolic activity are commonly present 
 (see Chapter XXX.). 
 
 Burnam,^° from personal observations in liis own prac- 
 tice, as well as in that of Howard A. Kelly of Baltimore, 
 reports encouraging results from the application of luteal 
 therapy in this class of cases, and wTites: " Certainly our 
 most striking results have been obtained with a class of 
 patients usually described as neurasthenics. Most of 
 them are over thirty- five years of age. . . . These 
 patients are excessively nervous, very easily fatigued by 
 either mental or physical work, usually more so at the 
 menstrual periods than at other times. Many improve 
 slowly on rest-cures. Immediately, however, on trying 
 to resume the duties of a normal life, they go back. The 
 general physical, as well as the local pelvic, examinations 
 are entirely negative. ... It must be clearly under- 
 stood that this group of symptoms may arise from other 
 causes than insufficient ovarian function. It is, however, 
 astonishing how quickly and completely many such 
 patients will respond to lutean therapy. It has been my 
 custom to give about nine tablets* a day in the ten days 
 before menstruation, to reduce this to six after the flow 
 begins, and in the period from the end of the flow until 
 the next time to give three tablets a day. Often this 
 therapy, carried out for a month, will give relief for many 
 months. The result is, as it were, a re-establishment of 
 a broken compensation between the internal secretory 
 glands." 
 
 * Each tablet corresponds to 20 grains of fn.sli corpus luteum of the sow.
 
 The Ovaries and Corpora Lntea 359 
 
 Amenorrhoea, Anaemia, and Chlorosis. — In irregular 
 menstrual conditions, varying from complete amenorrhoea 
 to profuse dysmenorrhoea, Jayle^^ urges ovarian opo- 
 therapy. Where anaemia is secondary to general inac- 
 tivity of the reproductive system, the good results due 
 to this treatment are reflected upon the blood-findings, 
 which are considerably augmented. Bandler'^^ states that 
 in certain forms of dysmenorrhoea, which he ascribes to 
 a mild form of hyperthyroidism, ovarian extract is of 
 great value. 
 
 Many cases of amenorrhoea are reported by various 
 authors in which a complete cure v/as accomplished by a 
 longer or shorter course of ovarian or luteal therapy. In 
 some cases it would seem that the introduction from 
 without of a substance containing the ovarian hormones 
 was just the stimulus that the inactive ovaries needed, 
 and with a few weeks of treatment the menses are satis- 
 factorily established. Not all, however, are enthusiastic 
 about its value. 
 
 Bandler found ovarian extract to be the best remedy 
 for amenorrhoea, relative and absokite. He believes that 
 combinations of iron, arsenic, and ovarian extract are 
 particularly useful in such cases, and he considers the 
 indication for iron equally an indication for ovarian 
 therapy. For some years Merck has made a combina- 
 tion of their ovarian preparation (ovaraden) with an iron 
 salt of nucleinic acid {ovaraden-triferrin), which has been 
 highly recommended in the common complex of ovarian 
 insufficiency and anaemia or chlorosis. An article by 
 Offergeld^^ outlines his favourable experiences with this 
 preparation, and numerous other reports might be cited 
 if space permitted. 
 
 Several writers have used ovarian preparations in 
 chlorotic girls in whom there was a palpable reduction in
 
 360 Practical Hormone Therapy 
 
 the ovarian activity, with amenorrhoea and general 
 asthenia and suboxidation. Spilhnann and iStienne^"* 
 long ago considered chlorosis to be an intoxication of 
 menstrual or ovarian origin, and their success with 
 ovarian therapj?^ was considered by them to be due to 
 the neutralization of the poisonous substances by the 
 ovarian substance itself. This does not appear to be the 
 correct explanation, for it seems well established that the 
 regulation of a disordered hormone balance and the re- 
 generation of a function as important as that of the 
 ovaries cannot but favourably influence haematogenesis 
 and nutrition generally. 
 
 The Vomiting of Pregnancy. — Several references in the 
 literature praise luteal extract as a means of controlling 
 the disturbances due to toxaemia in pregnancy, Lebreton^^ 
 having used a preparation of ovary with moderately good 
 results as far back as 1899. Stella urges the use of 
 ovarian extracts in hyperemesis gravidarum, and C. H. 
 Mayo^^ states that " vomiting of pregnancy is perhaps 
 best treated by the administration of corpus luteum," 
 although opinion on this subject is not unanimous. 
 
 According to Hallion,^^ ovarian extracts have an elec- 
 tive action upon thyroid activity, and in that part of the 
 chapter on the thyroid (Chapter XIII.) which refers to the 
 treatment of the vomiting of pregnancy, several interest- 
 ing experiences of Naame with combined ovarian and 
 thjrroid extracts are recorded. 
 
 Hysteria and Insanity. — A number of reports are on 
 record which indicate the therapeutic value of the ovarian 
 hormones in certain mental disturbances of women. 
 Magalhaes^^ succeeded in curing a patient who had been 
 suffering from hysterical crises, which occurred from two to 
 eight times a day. The recent literature on the relation 
 of ovarian disease and insanity is summarized hy Dunbar
 
 The Ovaries and Corpora Lutea 361 
 
 Hooper,^^ who reports a somewhat remarkable case in 
 point from his own practice. The patient, when he first 
 saw her, was twenty-one years old. She was anaemic and 
 constipated, and had suffered from melancholia for three 
 years, during which time she had menstruated twice only, 
 very scantily, and with great pain. After more than 
 twelve months of treatment, which included curetting, 
 she was placed in an institution, where she spent a year. 
 She was then found to be suft'ering from religious mania, 
 with amenorrhoea, was occasionally vicious, and at such 
 times refused food. It was decided to remove an ovary, 
 and to substitute for it a more normal organ taken from 
 a sane person. A hysterectomy upon another patient 
 provided the required material, which, after removal, was 
 placed in Ringer's solution at blood-heat. Four and a 
 half hours later the abdomen of the insane woman was 
 opened. Both ovaries were very small, hard, pale, and 
 cirrhotic. The more abnormal of the two was removed, 
 the broad ligament on that side split, and the new ovary, 
 cut into three shces, was embedded in the nest thus pro- 
 vided. Recovery was uneventful, and twenty-four days 
 after the operation a normal, painless, profuse menstrua- 
 tion took place. The mental condition improved rapidly, 
 and in six months the patient was dismissed to her home. 
 She was then menstruating regularly, had put on 6 pounds 
 in weight, and was exceptionally bright and happy. She 
 declared her intention of doing her utmost to repay her 
 parents for the trouble and expense of her treatment ; in 
 a word, her insanity had entirely vanished. 
 
 Miscellaneous Suggested Applications of Ovarian Medica- 
 tion. — -There seems to be no doubt that this form of 
 medication has been rather overdone. The application 
 of the fundamental idea of ovarian opotherapy has been 
 made in several other conditions associated with ovarian
 
 862 Practical Hormone Therapy 
 
 insufficiency. Dalche has tried it in rheumatic condi- 
 tions, others in such serious nervous manifestations as 
 epilepsy and melanchoha, with results which are said to 
 have been encouraging. Of course, the primary indica- 
 tion in all these cases was to supplement a deficient 
 ovarian function which would naturally have a favour- 
 able influence upon concomitant conditions. Reference 
 to the aphrodisiac action which not infrequently'' results 
 from this form of treatment also deserves mention. At 
 present luteal therapy is wisely confined more particu- 
 larly to the several forms of hypo-oophorism and their 
 associated disturbances. 
 
 Hyperobphorism, — Manifestly the treatment of this 
 condition can have little to do with ovarian therapeutics, 
 but it is of sufficient interest to deserve a paragraph here, 
 if only to direct attention to those parts of this book in 
 which the treatment is considered more fully. 
 
 Excessive ovarian secretion is likely to be manifested 
 by profuse menstruation. It has been demonstrated that 
 the hormones secreted by the ovaries are carried by the 
 blood to the endometrium, where irritation is set up, and 
 such changes as congestion, cell proliferation, oedema, 
 and at times even tissue necrosis, are caused. Sanes^° 
 puts forward a hypothesis which is of interest. He 
 writes: "It is possible that the degree of intensity of 
 this hormone decides the intensity of the menstrual 
 process — that is, the more active the liormone, and the 
 more susceptible the endometrium, the more extensive 
 and the more destructive are the uterine changes. If, 
 then, the hormones are insufficient to call forth in the 
 uterine stroma the necessary amount of crystalloid 
 material for induction of the oedema, might not the 
 superficial layer remain insufficiently oedematous to allow 
 the blood to break through it ? On the other hand, if
 
 The Ovaries and Cor for a Lntea 363 
 
 the hormones are excessive or the mucosa too sensitive 
 to them, might they not induce destructive changes in 
 the cells, calling out fibrin formation or coagulation 
 necrosis ? . . . May it not be, therefore, that the normal 
 menstruation, with the slight superficial shedding of 
 epithelium and the exfoliation of endometrial shreds or 
 membranes, is the result of the same normal process, the 
 difference being due to the variable degree of intensive- 
 ness of the stimulant action of the hormones ?" This is 
 evidently what happens in amenorrhoea, for, as we have 
 already seen, hypo-oophorism often may be the principal 
 cause, while in hyperoophorism the effect of the excess of 
 hormone is even worse than the lack of it. 
 
 In addition to the excessive menstrual flow in hyper- 
 oophorism, there is often an increased sexual excitability, 
 and with this may be various other associated symptoms 
 and a disordered metabolism, with an unusually large 
 increase in the elimination of lime-salts. Several cases 
 of osteomalacia have been found in hyperoophorism, and 
 ovariotomy has been practised with good results. 
 
 The antagonism of the adrenals to the ovary and corpus 
 luteum has been put to good account by Bossi"^^ of Genoa, 
 who suggested the use of adrenal preparations instead of 
 sexvial mutilation. Blair Bell^^ suggests the use of 
 pituitary extracts in this connection, and states that 
 " apparently many cures have been effected by this 
 treatment, and also by the injection of pituitary extract. 
 . . . Substitution of other extracts is a great advance on 
 removal of the ovaries in osteomalacia, and the success 
 thus attained indicates the line of attack that will probably 
 be followed in the future in those diseases of the endo- 
 crinous organs in which there is an excessive secretion — 
 that is to say, metabolically antagonistic extracts will take 
 the place of removal of portions of the diseased organs."
 
 364 Practical Hormone Therapy 
 
 Contra-Indieations. — Swale Vincent states that ovarian 
 extracts should not be given during pregnancy,'*^ but it 
 seems that luteal preparations are frequently used, espe- 
 cially in the treatment of the vomiting of pregnancy {q.v.). 
 Obviously, also, they are contra-indicated in conditions 
 associated with ovarian hyperactivity — i.e., where mam- 
 mary preparations are indicated. Menorrhagia may be 
 aggravated by ovarian therapy, and, according to Band- 
 ler,^2 the main contra-indication is profuse bleeding. 
 
 Dosage and Administration. — Numerous preparations 
 are available, not all of which, however, are uniformly 
 active. Some writers prefer the hypodermic method of 
 administration, but the majority give the various prep- 
 arations in cachet or tablet form. The dose of ovarian 
 extract is 5 to 8 grains (OS -0-5 gramme) two to fom' 
 times a day, depending entirely upon the conditions and 
 reaction of the individual to it. 
 
 Merck makes two preparations of ovary. In the one, 
 1 part representing 2 parts of fresh gland, the dose is 
 15 to 30 grains (1 to 2 grammes) three times a day, and 
 in the other, ovaraden 1 part representing 8 parts of fresh 
 gland, the dose is 3 to 6 grains (02 to 0*4 gramme). 
 
 Most of the older preparations of dried ovary have been 
 superseded by the luteal extracts. These are often pre- 
 pared from the corpus luteum of the cow, since this organ 
 represents more than one-half of the ovary. Ellice 
 McDonald, in a personal communication, remarks that he 
 knows of cases that have been benefited by cow's ovary 
 (lutein), and not by that from pigs, but has never seen a 
 case benefited by the pig preparation who did not also 
 respond to that made from cows. The products should 
 be as fresh as possible. The dosage is variable, and 
 depends wholly upon the individual needs of the patient 
 and the response to its action. Usually the initial dose
 
 The Ovaries and Corpora Lutea 365 
 
 is 2 to 5 grains (01 to 025 gramme), increasing to 20 or 
 30 grains (1-25 to 2 grammes), three times a day. Occa- 
 sionally lutein tablets may cause slight gastric discomfort, 
 and if the dose is large and the treatment prolonged, it 
 may cause a reduction in the blood-pressure. 
 
 It is advisable to continue this form of medication for 
 a considerable time. It should be begun immediately 
 after menstruation, in order to affect the succeeding 
 period — i.e., the influence of the hormone, to be most 
 effective, must be felt during the pre-cestrus stage. 
 
 BIBLIOGEAPHY 
 
 ^ Brown-Sequard (C. E.): Remarques sur les effets produits 
 sur la femme par les injections souscutanees d'un liquide 
 retire d'ovaires d'animaux, Arcli. d. Physiol. (Paris), 1890, 
 xxvii, 456. 
 
 2 Frank (R. T.): The functions of tlic ovary, Surg. Gyn. and Obs. 
 
 (Chicago), 1911, xiii, 36. 
 
 3 Blair Bell (W.): The genital functions of the ductless glands 
 
 in the female, Lancet (London), 1913, i, 809. 
 * MORLEY (W. H.): The internal secretion of the ovary, Phys- 
 
 and Surg. (Ann Arbor), 1910, xxxii, 49. 
 5 Ott:* pp. 436-437. 
 ^ Pr^nant (A.): Sur Faction physiologique et th6rapeutique 
 
 possible du corps jaune, Bev. mid. d. FEst (Nancy), 1898, 
 
 XXX, 385. 
 ■^ Fraenkel (L.): Die Funktion des Corpus luteum, Arch. f. 
 
 Gyn. (Berlin), 1903, Ixviii, 438; see also Neue Experimentes 
 
 zur Funktion des Corpus luteum, ibid., 1910, xci, 705. 
 ^ McDonald (E.): Lutein extract in the treatment of decreased 
 
 menstruation and premature menopause, J. Am. Med. Assn. 
 
 (Chicago), 1910, Iv, 205. 
 ^ Heape (W.): Ovulation and degeneration of the ova in the 
 
 rabbit, Proc. Boy. Soc. (B), (London), 1905, Ixxvi, 260. 
 1^° Angel (P.) and Bouin (P.): Sur les fonctions du corps jaune 
 
 gestatif, J. d. Physiol, et Path. gen. (Paris), 1911, xiii, 31. 
 ^1 O'DONOGHUE (C. PL): The corpus luteum in the non-pregnant 
 
 Dasyurus, Anat. Anz. (Jena), 1912, xli, 353. 
 ^2 Bouin (P.) and Ancel (P.): Sur lo role du corps jaune dans 
 
 le determinisme 6xp6rimentale de la s6cr6tion mammaire, 
 
 C r. Soc. Biol, (Paris), 1914, Ixxvi, 150.
 
 366 Practical Hormone Therapy 
 
 13 Seitz (L.) : Ovarialhorrnone als Wachstumsursacheu derMyome, 
 
 Munch, med. Wchnschr., 1911, Iviii, 1281. 
 1* Charrin (A.) AND GuiLLEMONAT (M.): Influence des extraits 
 
 d'ovaires sur les modifications le da nutrition dans la gro- 
 
 sesse, C. r. Soc. Biol, (Paris), 1900, lii, 585. 
 1^ KiCHTER (P. P.): Die Organotherapie und ihre praktische 
 
 Bedeutung, Dent. med. Wchnschr. (Leipzig), 1899, xxv, i, 53. 
 1® SiCARD (J. A.) AND Berkovitsch: Adipose douleureuse de 
 
 Dercum par insuf&sance ovarienne; ses relations avec 
 
 I'obesite d'origine genitale. Bull, et mem. Soc. med. d. Hop. 
 
 (Paris), 1908, xxv, 955. 
 1' CuRATULO (G^. E.) AND Tarulli (L.): Sulla secrezione interna 
 
 delle ovarie, Ann. d. Ostet. (Milan), 1896, xviii, 737. 
 1* Neumann (S.) and Vass (B.): Ueber den Einfluss der Ovarium 
 
 praparate auf den Stoffwechsel, Monats. f. d. Geb. u. Gyn. 
 
 (Berlin), 1902, xv, 433. 
 1^ Seeligmann (L.): Der Behandlung mit Ovarialsubstanz, Allg. 
 
 med. Gentrztg. (Berlin), 1898, Ixvii, 25. 
 -•^ Levi (L.) and de Rothschild (H.): " Nouvelles ifitudes sur la 
 
 Physiopatbologie du Corps Thyroide et des Autres Glandes 
 
 Endocrines " (Paris), 1911, p. 475. 
 -1 Blair Bell (W.): The relation of the internal secretions to 
 
 the female characteristics and functions in health and 
 
 disease, Proc. Boy. Soc. Med. (Sec. Obs.), (London), 1913, 
 
 vi, 47. 
 -2 Harrower (H. R.): Ibid., p. 97. 
 -3 Drevet (L.): " Effets Therapeutiques du Corps Jaune de 
 
 rOvaire" (Paris), 1907. 
 -* Kelly (H. A.): "Medical Gynecology" (Philadelphia), 1908, 
 
 p. 606. 
 -° MoND (R.): Die Behandlung der veranlasster Amenorrhoea 
 
 mit Eierstockconserven (Ovariin), Miinch. med. Wchnschr., 
 
 1896, xliii, 314. 
 2® Geissler (K.): L'opoth6rapie ovarienne centre I'angine de la 
 
 menopause, Sem. med. (Paris), 1900, xx, 86. 
 2' Saapeld (E.): Beitrag zur Oophorinbehandlung, Berl. kl. 
 
 Wchnschr., 1988, xxxv, 283. 
 29 Merck (E.): " Annual Report for 1908," xxii, 78. 
 3" Burn AM (C. F.): Corpus luteum extract in gynecologic prac- 
 tice, J. Am. Med. Assn. (Chicago), 1912, lix, 698. 
 2^ Jayle (F.): Opotherapie ovarienne, Pr. med. (Paris), 1896, iv, 
 
 437; see also id.: Bev. d. Gyn. et d. Chir. abd. (Paris), 1903, 
 
 vii, 437. 
 3- Bandler (S. W.): The therapeutic differential diagnosis of 
 
 constitutional dysinenorrhoea, Arch. Diag. (New York), 1913, 
 
 vi, 5. 
 33 Offergeld (H.): Kliuische Versuche mit Ovarialsubstanz, 
 
 Veut. med. Wchnschr. (Leijjzig), 1911, xxxvii, i, 1172.
 
 The Ovaries and Corpora Lutea 367 
 
 "* Spillmann (P.) AND Etienne (G.): Sur le traiteinent de la 
 chlorose par I'ovareine, Sem. med. (Paris), 1896, xvi, 337. 
 
 35 Lebketon (J. A.): " Opotherapie Ovarienne: Role du Corps 
 Jaune " (Paris), 1899. 
 
 2^ jIayo (C. H.): Discussion of Buruam's paper,30 j^ j^^_ Med. 
 Assn. (Chicago), 1912, lix, 702. 
 
 " Haelion:* p. 30. 
 
 2^ Magalhaes (F.): [Corpus luteuni extract in tlie treatment of 
 ovarian distui-bauces — Portuguese], Brazil Med. (Rio), 1907, 
 xxi, 491. 
 
 ^^ Dunbar Hooper (H. W.): Homoplastic transplantation of one 
 ovary into a woman suffering from amenorrhoea with in- 
 sanity. Austral. Med. J. (Melbourne), 1913, ii, 1297. 
 
 *° Sanes (K. I.): Is membranous dysmenorrhoea caused by endo- 
 metritis i J. Am. Med. Assn. (Chicago), 1913, Ixi, 1437. 
 
 *^ Bossi (L. M.): The influence of the suprarenal glands on the 
 bony skeleton in relation to osteomalacia and rickets, Br. 
 Med. J. (London), 1908, ii, 797. 
 
 *2 Vincent:* p. 87. 
 
 Prenant (A.): De la valeur morphologique du corps jaune; 
 
 son action physiologique ot th6rapeutique possible, Eev. gen. 
 
 d. Sci. (Paris), 1898, 646. 
 UsPENSKi (D. M.): Die Ovarialorganotherapie, Deut. Aertzte 
 
 Ztg. (Berlin), 1906, pp. 145, 176, 244. 
 Maits (C. B.): The therapeutic value of extract of human 
 
 corpus luteum, Univ. Pa. Med. Bull. (Philadelphia), 1910-11, 
 
 xxiii, 269. 
 Jaeger (A. S.): The value of extract of corpora lutea, Ther. 
 
 Gaz. (Detroit), 1912, xxviii, 461. 
 Hill (C. A.): The use of corpora lutea in gynecology: a report 
 
 of twelve cases of artificial menopause, Surg. Gyn. and Obs. 
 
 (Chicago), 1910, xi, 587. 
 Roos (L. L.): Report of three cases showing the therapeutic 
 
 value of ovarian extract. Postgrad. (New York), 1906, xxi, 
 
 340. 
 Ferroni (E.): Sugli effette dell' iniezioni sperimeutale di 
 
 estratti di corpo luteo, Ann. d. Ostet (Milan), 1907, i, 405. 
 Lambert (M.): Sur Faction des extraits du corps jaune de 
 
 I'ovaire, C. r. Soc. Biol. (Paris), 1907, Ixxii, 18. 
 Dannreuther (W. T.): Corpus luteum organotherapy in 
 
 clinical practice, J. Am. Med. Assn. (Chicago), 1914, Ixii, 356. 
 KiuTSi: Ueber die innere Sekretion des Corpus luteum, Monats. 
 
 f. Geb. u. Gyn. (Berlin), 1912, xxxvi, 399. 
 BucuRA (C. J.): Zur Theorie der inneren Sekretion des Eier- 
 
 stocks, Zentr.f. Gyn. (Leipzig), 1913, xxxvii, 1839. 
 Miller (J. W.): Corpus luteum. Menstruation und Graviditat, 
 
 Arch.f. Gyn. (Berlin), 1914, ci, 586.
 
 CHAPTER XXV 
 
 THE THERAPEUTIC VALUE OF MAMMARY 
 EXTRACTS 
 
 The Hormones which activate the Mammce — The Role of Hor- 
 mones in Mammary Evolution and Function — The Establish- 
 ment of Mammary Therapeutics — An Antagonist to Ovarian 
 Overactivity — The Control of Uterine Congestion and Hcemor- 
 rhage — The Treatment of Uterine Fibroids — An Oxytocic 
 Action — A Reported N euro-Sedative Action — A Useful Post- 
 partum Remedy — Dosage and, Administration. 
 
 Sufficient clinical evidence is available to show that 
 the mammary gland, in addition to its galactogenic 
 function, is an integral part of the endocrinous system. 
 Its activities are influenced to a considerable degree by 
 hormones from other internal secretory organs (notably 
 the pituitary, ovaries, and th3rroid), and it also produces 
 a hormone, which is concerned in the control of the female 
 reproductive system. 
 
 Luncz^ states that the mammary gland is of the same 
 physiologic character as certain other glands, in that it 
 has a dual function — the production of an external secre- 
 tion, and also of an internal secretion ; and he has shown 
 that it is possible to secure from it a therapeutically active 
 substance which may be used as a means of bringing 
 about those f mictions which, under ordinary circumstances, 
 it would have caused in the animal from which it was 
 taken. 
 
 The Hormones which activate the Mammse. — Shortly 
 after the announcement of the discovery of secretin and 
 
 368
 
 The Therapeutic Value of Mammary Extracts 369 
 
 its important influence upon digestive physiology, another 
 hormone was demonstrated and classified under this title. 
 It was found by Lane-Claypon and Starling^ that the 
 foetus in utero is the seat of the production of a certain 
 hormone-like substance, the function of which seems to 
 be the stimulation of the mammary glands, first to enlarge, 
 and later to perform their normal function of lactation. 
 These investigators have demonstrated that this hormone 
 can be secured even from the dried embryo, and have 
 prepared it in a similar manner to that of the preparation 
 of secretin from the duodenum. They report that by its 
 influence they have been able to induce lactation even in 
 virgin rabbits. Foa repeated these experiments, using 
 bovine foetal extracts upon animals of a different species, 
 with the same results as the English investigators. 
 
 Previously to this Ribbert,^in 1898, had shown that the 
 development of the mammary gland was not controlled 
 by the nervous system. He transplanted a portion of the 
 mamma from a virgin rabbit into a pregnant one, and the 
 transplanted gland developed and secreted milk. Most 
 physiologists are agreed that glandular development and 
 function occur as a result of a chemical stimulus due to 
 a hormone carried into the blood, although Luciani"* does 
 not yet appear to be convinced of this. It seems that, 
 from the experiences already mentioned above, that 
 hormones which develop and activate the mammary gland 
 are not specific for the species from which they are taken, 
 but their action, as noted by numerous authors, is quite 
 similar to that of the secretins. 
 
 These hormones are not the only factors involved in the 
 growth of the mammary gland. Bouin and AnceP have 
 furnished evidence that the corpus luteum — the tissue 
 produced when a follicle of the ovary is ruptured and an 
 ovum discharged — may also be concerned in the develop- 
 
 24
 
 370 Practical Hormone Therapy 
 
 ment of the mammary gland, and lead to its hypertrophy 
 quite independently of the presence of actual products 
 of conception in the uterus. The rupture of ripe follicles 
 can often be induced by purely mechanical or artificial 
 means. The French investigators have shown that such 
 rupture " is ordinarily followed by the formation of 
 corpora lutea, and also by a growth of the mammary 
 glands. . , . These facts serve to lend new emphasis to 
 the dependence of such physiologic responses as mammary 
 development on other than purely nervous relations. 
 They add to the coming significance of hormone activities 
 in the interdependence of various parts of the organism. "e 
 
 This has been confirmed in quite a different manner by 
 a series of experiments on animals, in which it was found 
 that complete ovariotomy resulted in a practical dis- 
 appearance of the mammae, and on the successful graft 
 of a piece of ovary in the same animals the lost glands 
 reappeared, showing conclusively the close relation 
 between the ovaries and breasts, and also that the in- 
 fluence depends upon certain chemical messengers, or 
 hormones, and not upon nerve-supply. 
 
 The close relation of the breasts and the uterus, as 
 manifested in so common an occurrence as the enlarge- 
 ment of the breasts at puberty, the frequency of pain in 
 the breast during menstruation, the relation of the 
 mammary nerve-supply with that of the clitoris, etc., 
 all go to show that the mammary glands are intimately 
 related to the whole of the pelvic reproductive organs. 
 
 A hormone with a similar action has been found in the 
 placenta, which von Basch'^ proved had no connection 
 with the nerve-supply of the breasts. He showed that 
 its administration in other animals, as well as its influence 
 upon transplanted portions of mammary gland, was un- 
 questioned, the cells hypertrophying and producing milk.
 
 The Therapeutic Value of Mammary Extracts 371 
 
 Ott has called attention to the fact that the mammary 
 glands of new-born infants are often noticed to be function- 
 ating, and suggests that the activating cause is the same 
 as in the mother — the so-called " mamma hormone." 
 
 The Role of Hormones in Mammary Evolution and 
 Function. — A knowledge of the physiology of the relation 
 of the mammary activities to the various stages of activity 
 of the reproductive organs is of considerable importance, 
 if it is desired to consider mammary opotherapy from a 
 scientific standpoint rather than from the empiric stand- 
 point of our grandfathers. 
 
 The most lucid statement upon this subject is to be 
 found in Schil's thesis.^ This writer, however, is not so 
 interested in the hormones produced by the mammae as 
 in those which influence the various phases of its develop- 
 ment. This may seem a little beside the subject, but it 
 has, nevertheless, a close and essential bearing upon it. 
 
 Schil recognizes six stages in the evolution of the 
 mammae: (1) The stage of development, divided into an 
 organogenetic phase and a phase in which there is 
 secretory activity (the lactation of the new-born already 
 referred to). This secretory phase is dependent upon a 
 hormone passing from mother to foetus through the 
 placenta. This same hormone activates mammary secre- 
 tion in the mother. (2) The 'prepubertal stage, which 
 lasts until puberty (or the first rut in animals), during 
 which the glands are functionally inactive. (3) The stage 
 of puberty, characterized by a considerable increase in the 
 glandular parenchyma. This growth is dependent upon 
 the exciting influence (by means of a hormone) of the 
 mature Graafian follicles in animals, in which non- 
 spontaneous ovulation is produced artificially,* and in 
 
 * O'Donoghue^ and others have artificially ruptured the ripe follicles in 
 animals, and thereby caused a noticeable increase in mammary growth and
 
 372 Practical Hormone Therapy 
 
 the case of spontaneous ovulation to the follicles and the 
 corpora lutea, which develop from these follicles after 
 dehiscence. (4) The gravid stage, which is divided into 
 two phases: [a) Growth, especially evident during the 
 early part of gestation, as a result of which the glands 
 attain their complete development; and (6) a so-called 
 *' phase glandulaire gravidique,^' which follows the com- 
 pletion of growth and is characterized by secretory 
 activity, the product of which is known as the " colo- 
 strum," Each of these two phases is a result of hormone 
 action, the first due to a kinetogenic hormone from the 
 corpus luteum to pregnancy, and the second to a critico- 
 genic hormone, which seems to come from a secretory 
 portion of the placenta during the second part of gesta- 
 tion, or from a myometrial gland. (5) A post-partum 
 stage, continuing during lactation until the glands are 
 again in repose, and divided into two phases: (a) Post- 
 partum glandular activity, in which the milk is produced ; 
 and (b) the phase of postpartum retrogression, in which 
 galactogenesia ceases, and the parenchyma is shghtly 
 diminished. Of these two phases only the first is of 
 interest, since the second is caused by an absence of 
 stimuli. The milk, released during pregnancy by an 
 endogenous stimulus, is maintained by an exogenous 
 stimulus — the act of suction. (6) A senile stage, asso- 
 ciated with involution, and corresponding to the period 
 of cessation of genital activity. 
 
 An interesting and convincing proof of the galac- 
 tagogue action of this hormone is found in the record of 
 the observations of Basch^° upon the Blazek pyopagous 
 
 activity. The results of these experiments warrant the following conclusion : 
 "The totality of the above evidence appears to justify the conclusion that 
 the corpus luteum is a ductless gland producing a secretion, which is the 
 inciting cause of the growth of the mammary gland. "
 
 The Therapeutic Value of Mammary Extracts 373 
 
 twins. One of these became pregnant, and was success- 
 fully confined, and after delivery, milk secretion also took 
 place in the non-puerperal sister. 
 
 The Establishment of Mammary Therapeutics. — On 
 general principles extracts of the mamma, equally with 
 those of the corpus luteum and ovary, should contain 
 certain activating substances which could be used with 
 advantage in those cases where this stimulation seems to 
 be needed. This is fully confirmed by the results of the 
 administration of preparations of this character. 
 
 As far back as 1896 Robert Bell^^ of Glasgow proved 
 the physiologic influence of extracts of cows* udders, and 
 indicated their therapeutic value. This seems to be the 
 initiation of the present-day use of this preparation, 
 although dried cow's udder has been known to have a 
 galactagogue action for many years, several pharma- 
 copoeias including reference to preparations of dried 
 teats of sheep and cows for the same purpose. Danhardt 
 believes that the breasts also contain a ferment capable 
 of changing albumin into casein, and a Copenhagen 
 physician records his successful use of dried sheep's 
 udder in the treatment of women who were unable to 
 nurse well. His reports state that both the amount and 
 quality of milk were noticeably augmented. 
 
 An Antagonist to Ovarian Overactivity. — It seems from 
 the experiences of HaUion and Battuaud,-^ and others, 
 that the mammary hormone is concerned in the hormone 
 balance, as it is antagonistic to the ovarian hormone. 
 Changes in the proportion of these hormones result in 
 disturbances of function, just as changes in the relation 
 of the adrenal and pancreatic hormones result in glyco- 
 suria and other manifestations of disturbed sugar com- 
 bustion. This suggestion is confirmed by the fact that 
 the exhibition of mammary extracts is recommended in
 
 374 Practical Hormone Therapy 
 
 conditions where it is fair to presume that there is ovarian 
 overactivity and uterine underactivity. 
 
 Forgue and Massabuan^^ have reported that there may 
 be an evident hypertrophy of the luteal cells of the 
 ovary at the menopause, and, as a result, the haemorrhages 
 so common at this time are caused by the increased 
 hormone production by the corpus luteum. This is quite 
 in harmony with the ideas just set down, and is further 
 evidence of the soundness of the position of mammary 
 therapy in such cases. 
 
 The Control of Uterine Congestion and Haemorrhage. — 
 The antagonistic action of the mammary and ovarian 
 hormones is probably the most effective antihormone 
 action which is available in therapeutics. Functional 
 overactivity of the pelvic organs is very nicely controlled 
 in this manner. Pochon^^ states that the administration 
 of the mamma hormone* has a tendency to cause uterine 
 depletion, while it is well known that the administration 
 of ovarian extracts tends to increase the uterine blood 
 content. 
 
 According to Battuaud,^^ in menorrhagia of yoimg girls 
 this form of medication has proved very valuable, just as 
 it has in the metrorrhagia of the climacteric. Ovarian 
 congestion due to salpingo-oophoritis and other causes is 
 reduced, although, of course, the influence is purely 
 decongestive, and not directly antagonistic to the in- 
 fective process. In haemorrhage due to uterine sclerosis 
 and fibroids, as well as in those indefinite uterine oozings 
 of the menopause which are not associated with malignant 
 growths, this method offers a valuable and physiologic 
 means of control. Batuaud has found it useless in the 
 haemorrhage resulting from retention of placental frag- 
 
 * Pochon means the hormone from tlie breasts— the mammary hormone. 
 The "mamma hormone " comes from tlie products of gestation, and, as wc 
 have seen, activates the mamnue.
 
 The Therapeutic Value of Mammary Extracts 375 
 
 ments, and from mucous or fibrous polypi. A number 
 of writers have called attention to the possibility of 
 diminishing an excessive menstrual flow, and curtailing 
 its undue length by the use of mammary extract. It is 
 also useful in lengthening the abnormally short interval 
 betAveen the catamenia, bringing back the normal rhythm 
 of menstruation as to frequency, amount, and duration. 
 Luncz^ especially credits this method of treatment with 
 remarkable efficacy, and emphasizes its absolute harm- 
 lessness. 
 
 A study of other references to the subject cannot but 
 impress one with the antihsemorrhagic and sedative effects 
 of mammary opotherapy in cases of functional over- 
 action of the pelvic organs ; but it should be emphasized 
 that preparations of this character are not styptics, as 
 a study of their physiologic action will quickly show. 
 
 The Treatment of Uterine Fibroids. — While the physio- 
 logic antagonism between the mammae and pelvic organs 
 has been realized for some decades, although the " how " 
 of its action was not settled till the " hormone theory " 
 was brought forward and substantiated, it was Bell's 
 experience in the treatment of uterine fibromata, in 1896, 
 that gave the impetus to the wide study of this subject 
 that has since occupied so many investigators. Bell's 
 first attempts were with thyroid extracts, but he later 
 substituted mammary extracts with very encouraging 
 success. Since then he reports good results from the 
 use of mammary substance in the treatment of uterine 
 fibroids, and mentions a number of cases in which the 
 tumour disappeared or was decidedly diminished in size. 
 He showed that irregular haemorrhage, as well as the pain, 
 was much diminished, and in some cases disappeared 
 altogether. Shober^^ reports similar results, and recom- 
 mends mammary extract in fibroids, menorrhagia, and
 
 376 Practical Hormone Therapy 
 
 metrorrhagia, and states that the addition of a small 
 amount of thyroid extract to the dose of mammary 
 extract assures even better results. Feodoroff^'' also 
 found that uterine myomata associated with metritis 
 were favourably influenced by this form of treatment, 
 and that the usual haemorrhages were considerably re- 
 duced. He also noticed that associated mastodynia was 
 relieved. These experiences were confirmed by Pry or and 
 Krause. More recently Feodoroff^^ has published another 
 statistical report of the results secured from the use of 
 mammary extract in the treatment of uterine fibro- 
 myomata. He noted a reduction in the size of the tumour 
 in 53 per cent, of all cases treated in this manner. Haemor- 
 rhage and profuse menses were absolutely controlled in 
 83 per cent. The pain usually noted in the development 
 of the tumour was abolished in 40 per cent., and in only 
 14 per cent, was there total failui'e. This author noticed 
 that there seemed to be a secondary influence upon the 
 intestinal function as the bowels were frequently regulated, 
 and there seemed to be a special advantage where 
 meteorism was present. 
 
 Mekerttschiantz^^ records fifty personally treated cases, 
 and is most enthusiastic in his praise of this method, 
 which he considers " the touchstone for all cases of 
 uterine fibroids " before deciding upon operative measures. 
 He also applies the same treatment in all forms of uterine 
 congestion. 
 
 Luncz^ prescribes 5 to 10 grains of the dried extract two 
 or three times a day, and suggests its administration 
 before the principal meals. Gastric disturbances are not 
 unlikely, and when they manifest themselves treatment 
 should be immediately stopped. The treatment of 
 fibroids must be continued without interruption for 
 months, and no harm comes from it. Very frequently
 
 The Therapeutic Value of Mammary Extracts 377 
 
 the control of uterine haemorrhage is so marked that an 
 operation which seemed imperative can be dispensed 
 with. If, however, operation is necessary, the course is 
 more favourable under the influence of mammary opo- 
 therapy, and where there are definite contra-indications, 
 the operation is the only safe treatment. 
 
 An Oxytocic Action. — The active influence which 
 mammary extracts exert on the uterus and adnexa con- 
 tra-indicate its administration during pregnancy, and 
 reference has been made to an oxytocic action which 
 followed its use. 
 
 Schiffmann and VystaveP^ report that injections of 
 7nmnmin had an undeniable abortifacient effect. Four 
 pregnant animals treated with this mammary extract, all 
 aborted. They state that in growing animals injection 
 of the extract of mammary glands from other and the 
 same animals has an inhibitory effect on the development 
 of the reproductive glands and the genitals. 
 
 A Reported Neuro-Sedative Action.— Several Russian 
 writers, especially Sellheim,^! insist upon the sedative 
 action of mamrnin upon the nervous system. This is, of 
 course, more noticeable in females, and this writer reports 
 success in certain cases of neurasthenia, hysteria, epilepsy, 
 etc., which were associated with gynsecologic affections. 
 This seems more likely to be due to the benefits of the 
 control of the pelvic condition, which reflexly influences 
 the nervous state. 
 
 A Useful Post-partum Remedy.— It is possible that 
 all these ideas may be applied to advantage in the 
 adjunct treatment following parturition. The tonic 
 influence upon the galactagogue function is much more 
 reasonable than the use of such drugs as atropine and 
 pilocarpine, which are supposed to influence glandular 
 secretion principally through nerve endings, and which
 
 378 Practical Hormone Therapy 
 
 have little influence upon milk production. The author 
 Suggests a formula consisting of mammary substance, 
 extract of placenta, and extract of cotton-seed, which, in 
 addition to the galactagogue influence, has a valuable 
 decongestive influence upon the uterus, hastening in- 
 volution and the return of this organ to the normal. 
 The addition of cotton-seed extract is a result of the 
 experiences of many farmers in giving cotton-seed cakes 
 to their cows. The seeds contain a valuable galactagogue 
 active principle, and the study of a number of Bulletins 
 published by the United States Department of Agricul- 
 ture should be convincing proof of the relation of cotton- 
 seed feeding to increased milk production. 
 
 It has been suggested that the addition oi I to ^ grain 
 of pituitary extract would be of advantage, as the in- 
 fluence of the pituitary hormone upon milk production 
 is stated by Schafer to be one of the most striking ex- 
 periments in physiology. It should be remembered also 
 that the pituitary hormone influences favourably the 
 general nutrition and muscular tonicity; but in those 
 cases where there is hypertension, it is contra-indicated for 
 obvious reasons. 
 
 The administration of such a preparation for a few days 
 prior to, and a week or two following, delivery tends to 
 shorten the lying-in period, and increases the important 
 function of lactation, which in these days seems to have 
 taken quite a secondary place in infant feeding, to the 
 detriment of many mothers as well as children. It is well 
 to remember that mothers who do not nurse their children 
 are very frequently subject to utero-ovarian disturbances. 
 
 The majority of the authors whose work has already 
 been cited have mentioned a variability of action which 
 must be referred to. There can be no doubt of the action 
 of mammary preparations in suitable cases, and especially
 
 The Therapeutic Value of Mammary Extracts 379 
 
 in uterine hsemorrhages ; but this influence is unfortunately 
 not constant. In many cases the results are rapid and 
 most encouraging ; again the response is moderately good 
 and evident only after some time, while occasionally the 
 effects are quite negative. The author is convinced that 
 this is an important corollary of hormone therapy, and 
 is due to the fact that hormone excess or insufficiency is 
 by no means easily demonstrated, and the degree of the 
 excess or loss can never be demonstrated. This should 
 not be a deterrent to the use of this method; and, re- 
 verting to the subject under discussion — the mammary 
 preparations — they are valuable and have proved their 
 worth hundreds of times, and are altogether the most 
 physiologic agents for the control of utero-ovarian super- 
 function. 
 
 Dosage and Administration, — By means of the vacuum- 
 drier one can prepare an active extract of mammary 
 glands, each grain of which represents from 6*5 to 
 7 grains of the fresh substance. Luncz^ recommends 
 0-5 gramme (8 grains) twice a day just before the principal 
 meals. Battuaud also advises this dosage, and suggests 
 that in the attempt to control haemorrhage between the 
 periods the dose should be continued daily and doubled 
 at the time of haemorrhage. 
 
 BIBLIOGRAPHY 
 
 LuNCZ* : See also ibid.: " L'OpotMrapie Mauimaire dans les 
 H6morragies et dans lo Fibrome do I'Ut^rus," These de Paris, 
 1911. 
 
 Lane-Claypon (J. E.) AND Starling (E. 11.): An experimental 
 inquiry into the factors which determine the growth and 
 activity of the mammary glands, Proc. Boy. Soc. (B), 
 (London), 1906, Ixxvii, 505. 
 
 RiBBERT (A.): Ueber Transplantation von Ovarium, Hoden 
 uud Mamma, Arch. f. Entwiclclungsmech, 1898, vii, 4.
 
 380 Practical Hormone Therapy 
 
 * LuciANi:* p. 517. 
 
 * BouiN (P.) AND Ancel (P.): Sui' les fonctions du corps jaune 
 
 gestatif, J. d. Physiol, et d. Path. Gen. (Paris), 1911, 
 
 xiii, 31. 
 ^ Editorial: Corpus luteum and mammary gland, J. Am. Med. 
 
 Assn. (Chicago), 1913, Ixi, 689. 
 ' Basch (K.): Die Brustdriisensekretion des Kindes als Masstab 
 
 der Stilltaliigkeit der Mutter, Miinch. med. Wchnschr., 1911, 
 
 Iviii, 2266. 
 ^ ScHiL (L.): " Recherclies sur la Glande Mammaire," These de 
 
 Nancy, 1912. 
 ^ O'DoNOGHUE (C. H.): The relation between the corpus luteum 
 
 and the growth of the mammary gland, J. Physiol. (London), 
 
 1911-12, xliii, xvi. 
 ^•^ Basch (K.): Ueber experimentelle Milchauslosung und ueber 
 
 das Verhalten der Milchabsonderung bei den zusammenge- 
 
 wachsenen Schwestern Blazek, Deut. med. Wchnschr. 
 
 (Leipzig), 1910, xxxvi, i, 897. 
 ^^ Bell (R.): The treatment of carcinoma of the uterus, certain 
 
 forms of ovarian disease, and fibroids of the uterus by 
 
 means of thyroid, parotid, and mammary gland extracts, 
 
 Med. Times and Hasp. Gaz. (London), 1897, xxv, 398. 
 ^'- Battuaud (J.): L'opoth6rapie mammaire en gyn6cologie, 
 
 Bev. d. mal. d. la nutr. (Paris), 1909, vii, 260. 
 13 FoRGUE (E.) AND Massabuan (Gt.): Les m6trorragies de la 
 
 menopause, Pr. med. (Paris), 1912, xx, 793. 
 1* PocHON (G.): Observations sur I'opoth^rapie mammaire et 
 
 ovarienne: Antagonisme des deux secretions, J. d. mid. d. 
 
 Paris, 1909, xxi, 195. 
 1® Shober (J. B.): The physiologic and theraj)eutic action of 
 
 extract of the mammary gland, 3Ied. News (New York) 
 
 1898, Ixxiii, 264 ; see also id. : Mammary gland therapy in 
 
 gynaecology, Phila. Med. J., 1899, iv, 921. 
 ^"^ Feodoroff (J. J.): [Action of Mamminum-Poehl on the 
 
 musculature of the uterus and its fibroid bodies — Russian], 
 
 J. med. Ichim. i. organoter. (St. Petersburg), 1901, vii, 655. 
 1^ Id. : [Influence of mamrain on uterine fibroids — Russian], 
 
 ibid., 1906, xii. 111. 
 1^ Metkertschiantz (A. J.) : Mammin-Poehl als ueue Behand- 
 
 lungsmethode bei Fibromyomen und chronischen Entzen- 
 
 dungen der Gabiirmutter, Monats. f. Geb. u. Gyn. (Berlin), 
 
 1910, xxi, 26. 
 20 ScHiFFMANN (J.) AND Vystavel (A.): Vcrsuche zur Frage 
 
 einer inneren Sekretion der Mamma, Wien. Id. Wchnschr., 
 
 1913, xxvi, 261. 
 21- Selliieim (F.): [Mamminum-Poehl in certain nervous disorders 
 
 in the female — Russian], J. med. Ichim. i. organoter. (St. 
 
 Petersburg), 1908, xiv, 645.
 
 The Therapeutic Value of Mammary Extracts 381 
 
 Abler (L.): Versuche mit " Mamminum-Poehl " betreffend 
 
 die Funktion der Brustdriiso als innerlich sezornierendcs 
 
 Organ, MuncJi. mecl. Wchnschr., 1912, lix, 13. 
 Grouse (H. W.): Mammary substance in uterine fibroids, Am. 
 
 J. Obs. and Dis. Women "(New York), 1902, xlvi, 309. 
 GoLDMANN (H.): Zur Tlierapie der Uterusblutnungen, Deut. 
 
 Aerzte Ztg. (Berlin), 1908, ii, 12. 
 Kleinwaechter (L.) : Die Organotherapie in der Gyna- 
 
 kologie, ZtscJir. f. Geb. u. Gyn. (Stuttgart), 1897, xxxvii, 367. 
 Shober (J. B.): The use of mammary glands in the treatment 
 
 of fibroids of the uterus and of parotid gland for ovarian 
 
 disease. Am. J. Obs. (New York), 1898, xxxviii, 352. 
 COHN (F.): Die innersekretorischen Beziehungen zwischen 
 
 Mamma und Ovarium, Monats. f. Geb. u. Gyn. (Berlin), 1913, 
 
 xxxvii, 93. 
 Kastle (J. H.): The internal secretion of the mammae as a 
 
 factor in the onset of labour, J. Infect. Dis. (Chicago), 1912, 
 
 X, 244.
 
 CHAPTER XXVI 
 
 THE PLACENTAL HORMONE 
 
 Tlte Action of the Placental Secretion — A Galactagogue Hormone 
 — The Role of the Placenta in Eclampsia — The Myometrial 
 Gland — The Decidua as an Endocrinous Organ — The Thera- 
 peutic Possibilities of Placental Substance — The Influence 
 on Lactation — Uterine Subinvolution — Alopecia and Pla- 
 cental Medication — Administration and Dosage. 
 
 Several of the temporary structures which come into 
 existence during pregnancy serve a double purpose. 
 Principal among them is the placenta, which, in addition 
 to its relation to the foetal circulation and nutrition, 
 evidently has an internal secretion. It is none too clear 
 whether the placenta and the " myometrial gland," which 
 is shown by Bouin and Ancel to have a distinct internal 
 secretory function, are separate organs, or, like the corpus 
 luteum and ovary, are different parts of the same struc- 
 ture. Reference to some of the literature on the subject 
 may clear up this point. 
 
 The Action of the Placental Secretion. — It is beheved 
 that the placenta is more than a vascular organ, for a 
 histological examination demonstrates the presence of 
 structures which are closely analogous to glands. Letulle 
 and Larrier^ in 1901 described certain secreting areas in 
 the placenta, and brought forward scientific proof that 
 the placenta is an internal secretory organ. Halban^ 
 suggests that the chorionic epithelium of the placenta 
 and ovary exert a similar action upon the body, and that 
 
 382
 
 The Placental Hormone 383 
 
 during the ovarian quiescence of pregnancy the placenta 
 to a certain extent undertakes its work. 
 
 Schickele^ has found that the placenta contains two 
 active substances, the one having the power to hasten 
 the coagulabihty of the blood, while the other causes 
 prolonged lowering of the blood-pressure. This is in con- 
 firmation of Dixon and Taylor's^ experiments, which 
 showed that placental extract causes a rapid rise of blood- 
 pressure, which was immediately followed by a prolonged 
 fall. It is interesting to note that these investigators also 
 observed that it exerts in a mild degree an influence upon 
 uterine contractility. Felhier^ of Vienna has done con- 
 siderable research work on the action of extracts of 
 placenta upon the other female genital organs, and has 
 shown that such extracts have a stimulating influence on 
 the growth of the mamma, uterus, and other parts of the 
 genital tract, but he did not find that the secretion of 
 milk was influenced by it. It seems, however, that there 
 is incontestable evidence to support this, as will shortly 
 be seen. 
 
 A Galactagogue Hormone. — Several authorities con- 
 sider that the principal action of the placenta hormone 
 is the stimulation of the milk-producing activities of the 
 mammae. Ott and Scott ^ experimentally used an ex- 
 tract of air-dried human placenta, and found that its 
 administration caused increased secretion of milk in a 
 lactating goat. Lederer and Prizbram'^ caused a similar 
 increase of the milk in goats, while Basch^ injected ex- 
 tracts of the placenta into adult animals which at one 
 time had lactated and produced milk. He also injected 
 these extracts into infants in whom the milk secretion 
 had ceased, but this medication renewed it. He concludes 
 that the so-called " witch's milk " is due to the passage 
 into the foetus of a hormone circulating in the blood cf
 
 384 Practical Hormone Thera/py 
 
 the mother. Schafer,^ however, intimates that the 
 placental as well as the foetal ("mamma ") hormones pro- 
 duce an inhibitory action on milk secretion. 
 
 The Role of the Placenta in Eclampsia.— Biedl^° beheves 
 that "the internal secretion of the placenta plays an 
 important part in the modern theory of eclampsia." 
 
 It is not definitely known whether the placental hor- 
 mone is toxic or whether another endotoxin is produced 
 in the abnormal course of events which is the basis of the 
 toxaemias of pregnancy, and especially of eclampsia. 
 Liepmann,^^ at least, shows that, whereas extracts of 
 normal human placenta in large doses are not toxic when 
 injected into rabbits, extracts made from the placenta 
 from patients who suffered from eclampsia proved to be 
 extremely toxic. Many consider that the thyroid nor- 
 mally antagonizes the placental hormone or toxin, and 
 several have suggested that eclampsia is a result of 
 thyroid insufficiency. Schickele has also found that 
 placental extract had a neutrahzing action on the de- 
 pressor influence of thyroid extract when given simul- 
 taneously. 
 
 The Myometrial Gland. — Ancel and Bouin^^ discovered 
 in the uterine wall of a pregnant rabbit what they have 
 termed the " myometrial gland." They believe that the 
 corpus luteum produces a hormone (see Chapter XXIV.), 
 which stimulates the growth of the mammary gland, but 
 that this action is not evident in the later stages of preg- 
 nancy. The hormone of the myometrial gland — in the 
 rabbit, at least — is supposed to be responsible for the 
 activation of the mammary secretion. Some have ex- 
 pressed the opinion that there may be a close structural 
 relation between this gland and the placenta itself. 
 
 The Decidua as an Endocrinous Organ. — The decidua, 
 too, has recently been shown to have an action which
 
 The Placental Hormone 385 
 
 seems to be attributable only to a theoretical hormone 
 that is elaborated within it, but it is not on record that 
 it has been used in therapeutics. 
 
 Gentih^ gives a detailed description of experiments 
 with aqueous extracts of the decidua of cows, dogs, and 
 human beings. These extracts proved very toxic when 
 injected in small doses into the circulation of rabbits. 
 Extracts of rabbit and guinea-pig decidua are not so 
 toxic for their own species, though larger doses cause 
 death. The toxic phenomena are very similar to those 
 caused by the injection of extracts of internal secretory 
 glands, but, contrary to the action of these extracts, the 
 decidua extract is more toxic for different species. 
 Animals dying from the injection of decidual extract 
 show similar manifestations to those animals d5ang 
 from fatal doses of extracts of other organs having in- 
 ternal secretion. There is thrombosis of the pulmonary 
 veins, showing the presence of some substance that 
 favours coagulation of the blood within the body, and it 
 seems that this substance can be neutrahzed by blood- 
 serum from the same species of animal from which the 
 decidua was taken. In cows particularly, greater toxicity 
 was noted in the early stages of pregnancy. 
 
 Aside from its toxic effects, decidua extract always 
 causes a marked fall in blood-pressure. It lessens the 
 force of the systohc wave, and produces disturbance in 
 the cardiac and respiratory rhythm. It is evident from 
 these results that the conjecture that the decidua has an 
 internal secretion is no longer merely a logical supposi- 
 tion, but has been experimentally demonstrated to be a 
 fact.14 
 
 The Therapeutic Possibilities of Placental Substance.— 
 It is asserted that in certain parts of China the liuman 
 placenta is considered to be a valuable remedy for the 
 
 26
 
 386 Practical Hormone Therapy 
 
 angemias that frequently follow the puerperium. Boucha- 
 coiirt^^ recalls the fact that many animals are in the 
 habit of eating their placenta immediately after dehvery, 
 and mentions that this instinctive act is not confined to 
 animals, but that among certain races in Brazil, the 
 Sudan, and remote districts of Asiatic Russia, this 
 rather disgusting habit has persisted . He believes that this 
 \\va,y have a favourable influence upon lactation, and brings 
 a series of clinical experiences to confirm his theory. 
 
 The Influence on Lactation. — The galactagogue influ- 
 ence of placental preparations may be of service in prac- 
 tical therapeutics, and for a number of years these ex- 
 tracts have been used for this purpose. Bouchacourt 
 reports a case of a young married woman, aged twenty- 
 two, in Vv'hom. by administering 2 grammes daily of dried 
 ewe's placenta, he was able to produce a considerable 
 increase in the size of the breasts, with the establishment 
 of a definite colostral flow. A number of other cases 
 were reported, some purely experimental, and others in 
 which a deficient or absent flow of milk in the nursing 
 woman was satisfactorily established. In one case he 
 was able to re-establish lactation in a woman eight 
 months after delivery. 
 
 Not all cases will respond to this treatment, although 
 Carnot^'^ refers to the observations of several other 
 writers, all of whom record favourable experiences with 
 placental preparations as a means of influencing the pro- 
 duction* of milk. 
 
 Miklas^"^ of Munich has given the most complete and 
 recent consideration of the present possibilities and actual 
 therapeutic value of the placental hormone. He relates 
 
 * The action of placental extracts is quite different from that of the 
 posterior lobe of the pituitary. Tlie former seems to influence the production 
 of colostrum or milk, while the latter (see Chapter XIX.) acts more as a 
 means of emptying the breasts.
 
 The Placental Horwcme 387 
 
 clinical experiences with a number of cases, and concludes 
 that the therapeutic application of placental extract as 
 a galactagogue is still in the experimental stage (in Ger- 
 many). He is convinced of its value when given by 
 mouth to nursing women, although its action is relatively 
 slight; but he is not so sure of the results in primary 
 hypogalactia. All his work was done with preparations 
 given by mouth, since subcutaneous injections are alto- 
 gether too painful to be considered. 
 
 The administration of preparations of dried placenta is 
 quite harmless, and the reports indicate that there are 
 considerable possibilities in this form of treatment. 
 
 Uterine Subinvolution. — Okintschits, in a series of ex- 
 periments, noticed tliat the administration of extract of 
 placenta prevented the atrophy of the uterine walls which 
 so uniformly follows extirpation of both ovaries. This 
 gave an idea to Iscovesco,^^ who shortly afterwards tried 
 placental extract in an attempt to modify subinvolution 
 of the uterus. He records several observations in which 
 the administration of this remedy exerted a favourable 
 influence upon uterine involution, and especially in certain 
 cases of clironic hyperplastic metritis which followed 
 accouchement. 
 
 Alopecia and Placental Medication. — A most unusual 
 experience has been recorded by Maurice Petit, ^^ which 
 is so extraordinary that it seems worth recording as a 
 thought stimulator, if for no other reason. Petit hap- 
 pened at one time to have two cases of alopecia in women 
 which were spontaneously cured during pregnancy. Here 
 is the gist of his communication: One case, a woman of 
 thirty, had had four children, and during each pregnancy 
 the scalp became normal, only to have the bald areas 
 return a few weeks after each delivery. The second case 
 was that of a young woman of twenty-four, with five
 
 388 Practical Hormone Therapy 
 
 areas of alopecia which would not respond to any treat 
 ment. During her first pregnancy the alopecia of years 
 disappeared, only to return two months after delivery. 
 Petit therefore prescribed a cachet of placental extract 
 twice daily for twelve days, with a period of rest for 
 eight days, followed by twelve more days of treatment 
 and eight of rest for several weeks. After two months 
 the cure was complete. 
 
 These results doubtless will not last, and lack confirma- 
 tion, but in spite of this, must be considered evidence 
 that — occasionally, at least — alopecia is a disorder of the 
 endocrinous system, that the placenta has an internal 
 secretory action, which, as in these cases, can be trans- 
 mitted to pharmaceutical preparations, and used with 
 obvious therapeutic results. 
 
 Administration and Dosage. — Quite often the thera- 
 peutic value of placental extracts may be enhanced by 
 the addition of mammary extract, and the author has 
 suggested a combination in the previous chapter which 
 in many cases may be useful as a galactagogue and post- 
 partum uterine tonic (see p. 378). 
 
 The placental extracts of commerce are usually made 
 from the fresh placentae of ewes, although occasionally 
 that of the cow is used. It is deprived of its blood, washed, 
 chopped, and dried in vacuo, as in the preparation of 
 other animal extracts. The dry powder is quite innocuous 
 when given internally, and represents approximately 
 15 per cent, by weight of the fresh substances. The dose 
 varies from 3 to 10 grains. (02 to 07 gramme) two to 
 four times a day. Hypodermic injections of aqueous 
 extracts have been discontinued, owing to the excessive 
 local reaction which so often results. Gaifami^^ has 
 shown that this method is accompanied by fever and 
 considerable pain.
 
 The Placental Hormone 389 
 
 BIBLIOGRAPHY 
 
 ^ Letulle (M.) and Larrier (L. N.): Fonction s6cr6toire du 
 
 placenta, Bev. d. Gyn. et d. Chir. abd. (Paris), 1901, v, 195. 
 - Halban (J.): Schwangerscliaftsreaktioneii der fotalen Organe 
 
 und ihre puerperale Involution, Ztschr. f. ^ Geb. u. Gyn. 
 
 (Stuttgart), 1903, liii, 191. 
 ^ Schicb:j;le (G.): Zur Lehre von der inneren Sekretion der 
 
 Placenta, Biochem. Ztschr. (Berlin), 1912, xxxviii, 214. 
 * Dixon (W. E.) and Taylor (F. E.): An epidiascopic demon- 
 stration of the physiological action of the placenta, Proc. 
 
 Boy. Soc. lied. (Sec. Obs.), (London), 1907-08, i, 11. 
 ^ Fellner (0. O.): Experimentelle Untersuchungen ueber die 
 
 Wirkung von Gewebsextrakten aus der Placenta und den 
 
 weiblichen Sexualorganen auf das Genitale, Arch. f. Gyn. 
 
 (Berlin), 1913, c, 641. 
 ® Ott (I.) and Scott (J. C): Action of different agents upon the 
 
 secretion of milk, Ther. Gaz. (Detroit), 1912, xxviii, 310. 
 ' Lederer (R.) and Prizbram (E.): Experimenteller Beitrag zur 
 
 Frage ueber die Beziehung zwischen Placenta und Brust- 
 
 driisenfunktion. Arch. f. d. ges. Physiol. (Bonn), 1910, 
 
 cxxxiv, 531. 
 ^ Basch (K.): Die Brustdriisensekretion des Kindes als Masstab 
 
 der Stillfahigkeit der Mutter, Munch, med. Wchnschr., 1911, 
 
 Iviii, 2266. 
 ® ScHAFER (E. H.): The physiology of milk secretion, Med. Pr. 
 
 and Circ. (London), 1913, i, 307. 
 10 Biedl:* p. 411. 
 " LiEPMANN (W.): Zur Technik und Kritik der Placentarfor- 
 
 schung, Zentr.f. Gyn. (Leipzig), 1909, xxxiii, 138, 379. 
 12 BouiN (P.) and Angel (P.): Sur revolution du glande mam- 
 
 maire pendant la gestation. Determinisme de la phase 
 
 glandulaire gravidique, C. r. Soc. Biol. (Paris), 1912, Ixxii 
 
 129. 
 1' Gentili (A.): La decidua considerata come glandola endo- 
 
 crina, Ann. d. Ostet. e Ginecol. (Milan), 1913, xxxv, ii, 257. 
 1* Abstract in J. Am. Med. Assn. (Chicago), 1913, Ixi, 2086. 
 1^ BouCHACOURT (L.): Nouvclles recherches sur I'opoth^rapio 
 
 placentaire, C. r. Soc. d. Biol. (Paris), 1902, liv, 133. 
 i« Carnot:* p. 346. 
 1' MiKLAS (F.): Zur Frage der Placentarhormon und der Ver- 
 
 wenduug von Placentarsubstanzen als Laktagoga, Monats. 
 
 f. Geb. u. Gyn. (Berlin), 1913, xxxviii, 60. 
 
 18 IscovESCO (H.): Pr. med. (Paris), 1898, vi, 223. 
 
 19 Petit (M.): Bons effets de I'opoth^rapio placentaire sur la 
 
 pelade, Bev. pr. d. biol. appl. (Paris), 1913, xi, 220.
 
 390 
 
 Practical Hormone Therapy 
 
 20 Gaifami (P.): Sulla tossicita degli ostratti acquosi placentare, 
 Pathologiea (Rome), 1913, v, 415. 
 
 Oktali (C): L'opotherapie placentare. Gas. d. Osp. (Milan), 
 
 1904, XXV, 590.^ 
 Chaleix-Vivie: 7\.ijroi)os de I'opotlierapie placentaire, J. d. 
 
 Med. de Bordeaux, 1903, xxxiii, 237; ibid., Bev. mens. d. 
 
 gyn. (Bordeaux), 1903, v, 296. 
 GuGGiSBERS (H.): Ueber die Wirkung der inneren Sekrete auf 
 
 die Tatigkeit des Uterus, ZUclir. f. Geh. u. Gyn. (Stuttgart), 
 
 1914, Ixxv, 231.
 
 CHAPTER XXVII 
 PULMONARY OPOTHERAPY 
 
 The Action of Lung Extracts — Brunet's Studies — Value in 
 Chronic Pulmonary Infections — The Limitations of this 
 Method of Treatment — ThromhoJdnase . 
 
 Foe, a number of years certain French writers have 
 insisted that preparations of lung tissue have a thera- 
 peutic vakie in a certain class of cases. From time to time 
 papers and case reports have been published which appear 
 to justify this position, and yet, if one excepts the French 
 literature, there is hardly a reference, favourable or un- 
 favourable, to this method of treatment. 
 
 The Action of Lung Extracts. — ^The introduction of 
 preparations of lung substance into therapeutics is 
 attributed to Brunet, ^ a medical officer in the French Navy, 
 who, in a series of experiments on rabbits, found that 
 subcutaneous injections of lung extract possess a tonic 
 action. The pharmacological trials on experimental 
 tuberculosis led to the suggestion that lung extract may 
 serve as a useful auxiliary remedy in the treatment of 
 phthisis. For this reason Brunet decided to use the 
 preparation in man. In a large scries of cases of chronic 
 bronchitis and emphysema, chronic and acute tubercu- 
 losis, advanced pulmonary and laryngeal phthisis, etc., it 
 is reported that this method of treatment led to an 
 appreciable improvement in the condition of the patients. 
 
 Brunet's Studies. — -This investigator has devoted much 
 
 391
 
 392 
 
 Practical Hormone Therapy 
 
 study to this subject, and his first communication was his 
 thesis^ (Bordeaux, 1896), which was favourably received, 
 and for which he received the gold medal presented by 
 the Faculty. His serial article on the present position of 
 pulmonary opotherapy is a valuable piece of literature; 
 in it he has gathered together all the references to this 
 method in the literature. It occupies more than one 
 hundred pages, and contains a full bibliography.^ 
 
 Brunet regards pulmonary opotherapy as justified in 
 all chronic diseases of the lungs and the diaphragm, such as 
 chronic bronchitis and pnemnonia, asthma, emphysema, 
 fibrinous and purulent pleurisy, abscess of the lung, 
 chronic tuberculosis. The value of this remedy seems to 
 be greater in the chronic purulent infections of the 
 respiratory tract. This writer prepares an extract of 
 lung tissue according to Brown-Sequard's formula, and 
 injects it subcutaneously in doses of 3 to 5 c.c. (45 to 75 
 minims). He occasionally gives 10 c.c. (160 minims) of 
 the juice with a little water in the morning on an empty 
 stomach. 
 
 Value in Chronic Pulmonary Infections. — Arnozan^ con- 
 firmed the good results of this method in the treatment of 
 the more chronic forms of these diseases of the lungs and 
 bronchi, but did not find it so useful in pulmonary 
 tuberculosis. Cassaet observed only a transient improve- 
 ment and a favourable action on the general condition in 
 phthisis. Grande^ gave a phthisical patient a dose of 
 4 to 5 grammes (60 to 75 grains) of the dried organ daily 
 for five months, with the result that the fever disappeared, 
 the sweats and expectoration ceased, and the weight 
 increased. This author also performed experiments on 
 animals which led to the conclusion that this application 
 of organotherapy is of definite use, and is worthy of 
 extended investigation.
 
 Pulmonary Opotherapy 393 
 
 Dried lung substance is prepared by Merck for thera- 
 peutic purposes from the lung parenchyma of young 
 healthy sheep. The average dose is 5 grammes (75 grains) 
 daily, usually divided into three equal doses. 
 
 The Limitations of this Method. — Carnot^ does not con- 
 sider that this method is of especial promise, and with the 
 thorough establishment of vaccine therapy for the control 
 of infections, and particularly of bronchial and non- 
 tuberculous infections, and the present position of tuber- 
 culin and other indirect forms of hormone therapy as 
 adjuvant measures, it seems that pulmonary opotherapy 
 is not destined to come into general usage. The 
 passage of years at least has not shown any great 
 enthusiasm in this direction, although the work done 
 is sufficiently interesting to be worthy of a brief reference 
 here. 
 
 Thrombokinase. — A preparation for the control of 
 haemorrhage is secured from lung tissue, and may be 
 mentioned. This is the "thrombokinase " suggested by 
 Batelli,^ and later by Strong.'^ Of course, this is not a 
 hormone preparation. The method of preparation is as 
 follows : 
 
 " Sheep's lungs are taken direct into sterile towels, and 
 the larger bronchi are removed to avoid as many bacteria 
 as possible. The lungs are then ground in a meat grinder, 
 and soaked in twice their volume of sterile water for an 
 hour; 1-5 c.c. glacial acetic acid for every litre of extract 
 is then added, drop by drop, with constant stirring. A 
 white flocculent precipitate results, which is immediately 
 collected by centrifuging. The free acetic acid is removed 
 by washing thoroughly with salt solution. The centrifuge 
 tubes are then filled with alcohol, and the mixture is again 
 centrif uged thoroughly, when the alcohol may be decanted, 
 and the nearly dry precipitate may be spread on crystal-
 
 394 Practical Hormone Therapy 
 
 lizing dishes, and rapidly evaporated at a low temperature 
 in vacuo. ^'''^ 
 
 The chief indication for the use of thrombokinase is 
 haemorrhage, local application, especially in nose and 
 throat practice, having given very good service. It has 
 also been useful in sporadic and hereditary haemophilia, 
 and the limited number of reports show that it is valu- 
 able in cases where adrenaline fails to render sufficiently 
 permanent help. 
 
 BIBLIOGRAPHY 
 
 ^ Brunei (F.): !Etat actuel de I'opotlierapie piihiionaire, Arch. 
 
 d. mid. navale (Paris), 1906, Ixxxv, 372. 
 - Id. : " Le Sue Puhnonaire ; Effets Physiologiques et Thera- 
 
 peutiques," Bordeaux, 1896. 
 '■^ Arnozan (H.): Contribution a I'etude de Fopotherapie pul- 
 
 mouaire, Province med. (Bordeaux), 1907, xlvii, 587. 
 ^ Grande (E.): II pohnone in opoterapia, Bif. med. (Naples), 
 
 1897, xiii, 397. 
 2 Carnot:* p. 517. 
 '■' Batelli (F.): L'oxydation de I'acide succinique conime niesure 
 
 du pouvoir oxydant dans la respiration principale des 
 
 animaux, C. r. Soc. Biol. (Paris), 1910, Ixviii, 554. 
 ^ Strong (L. W.): The preparation and use of thrombokinase, 
 
 N. Y. Med. J., 1912, xcv, 591. 
 
 Arnozan (H.): Des indications et des effets tberapeutiques du 
 sue pulmonaire, Bev. int. d. ther. et pharmacol. (Paris), 1898, 
 vi, 161. 
 
 Jacobson (J.): Ueber Pneuinin und Pulnioiorni, Bed. Id. 
 WcJinschr., 1900, xxxvii, ii, 360. 
 
 SiLBERSTEiN (L.): Ueber Pneumin und Pulmot'orui, Bed. Id. 
 Wchnschr., 1901, xxxviii, i, 23. 
 
 Sardou (G.): Sur rinsuffisance defensive des premieres voies 
 respiratoires et son traitement opotherapique. Arch. gen. d. 
 med. (Paris), 1904, cxciii, 679. 
 
 CASSAiiT (P.): De I'utilite du sue pulmonaire dans les suppura- 
 tions peripulraonaires, Gaz. d. sc. med. d. Bordeaux, 1901, 
 xxii, 603.
 
 CHAPTER XXVIII 
 THE CAROTID GLAND 
 
 The carotid gland, discovered by Luschka in 1862, has 
 been considered respectively a nervous structure, a 
 vascular organ, and now a portion of the adrenal system ; 
 therefore it should be included in the general discussion of 
 the chromafRn system found in Chapter XVIII. 
 
 Not all investigators are convinced even that the carotid 
 gland is an internal secretory organ, although the fact that 
 it has been classed by Kohn^ with the adrenal system has 
 led some to believe that it produces an internal secretion 
 similar to that of the adrenal bodies. 
 
 Frugoni-' has made numerous experiments with a view 
 to determining whether this organ has a true internal 
 secretion, and in a comparatively recent communication 
 he sums up his conclusions for and against. He is of 
 opinion that an internal secretion is not only possible, 
 but probable ; but so far this is a mere hypothesis, for he 
 admits that the results of his experiments are incon- 
 clusive. 
 
 It is very evident that the action of this small body is 
 not to be compared with that of, for example, the equally 
 small parathyroids or even the pineal body, and hence 
 no attempt has been made to overcome the difficulties in 
 regard to the manufacture of an organotherapeutic 
 preparation, because no advantage is at present known to 
 
 395
 
 396 
 
 Practical Hormone Therapy 
 
 accrue from its exhibition to warrant the laborious and 
 expensive task which the preparation of such an extract 
 would undoubtedly be. 
 
 \ 
 
 BIBLIOGRAPHY 
 
 KoHN (A): Ueber den Bau und die Entwickelung der sog. 
 Carotisdruse, Arch. f. mikrosJcop. Anat. (Bonn), 1900, Ivi, 81. 
 
 Frugoni (C): La glande carotidienne de Luschka possede-t- 
 elle une secretion interne propre ? Sem. Med. (Paris), 1912, 
 xxxii, 481; see also id. : ^Studes sur la glande carotidienne 
 de Luschka, Arch. Ital. de Biol. (Turin), 1913, lix, 208.
 
 CHAPTER XXIX 
 LYMPHATIC GLAND EXTRACTS 
 
 The Lymph Nodes and the Bodily Defences — The Relation of 
 the Lymph Glands to other Ductless Glands — The Action of 
 the Lymph-Gland Extracts — The Indications of Lymphatic 
 Therapy — A71 Organotherapeutic Treatment of Adenoids 
 and Enlarged Tonsils — Possible Value in Hodgkin's Disease 
 — Mesenteric Gland Extracts in Scleroderma — The " Lym- 
 phoid Compound" — The Preparation of Lymphatic Gland 
 Extracts. 
 
 The Lymph Nodes and the Bodily Defences. — It has been 
 asserted now for some time that the Ijanph nodes are 
 virtually internal secretory organs, and that a part of 
 their capacity to defend the body against bacterial inva- 
 sion is due to an internal secretion which they produce. 
 This may or may not be true ; at present it does not seem 
 to be very thoroughly demonstrated experimentally. 
 Clinical experience, however, has indicated that a certain 
 limited therapeutic value is found in preparations of 
 lymphatic gland substance. 
 
 There is no doubt that these organs are an important 
 part of the system of defences of the body, but this does 
 not indicate that their activity is necessarily of a hormone 
 nature. Because of their known phagocytic and hsemo- 
 poietic action, it has been presumed that they might con- 
 tain active principles which would be useful in stimulat- 
 ing phagocytosis and modifying anaemia, and therefore 
 extracts have been made and used in therapeutics to some 
 extent. Either the results of their administration have 
 
 397
 
 398 Practical Hormone Therapy 
 
 been mediocre, or there are other means wherewith to 
 accomplish the same ends more effectively, for references 
 to lymphatic gland therapy are still few and far between. 
 
 The Relation of the Lymph Glands to Other Ductless 
 Glands. — A syndrome called " status thymolymphati- 
 cus "* is worthy of mention as showing a likely relation 
 between the thymus and lymphatic glands. Its principal 
 manifestations are a persistent or enlarged thymus, which 
 is accompanied by general lymphoid hyperplasia. The 
 patient is usually obese, occasionally rachitic, and verj^ 
 often dies suddenly, with no obvious sign of the cause 
 of death at autopsy. This symptom-complex — it can 
 hardly be called a disease — seems to suggest an endo- 
 crinous relationship, which may in time lead to further 
 more useful knowledge. 
 
 The Action of Lymph-Gland Extracts. — Experimentally 
 Bartel and Neumann^ have shown that tubercle bacilli lose 
 their virulence after remaining in contact with emulsions 
 or extracts of lymph glands. This is in harmony with his 
 demonstration that splenic extracts exert a similar 
 influence (see Chapter IX.). Bartel has attempted to 
 apply this antibacterial action in the treatment of experi- 
 mental tuberculosis, and reports that some encouraging 
 results have been obtained. It is not likely that these 
 findings may be applied in clinical practice, and it should 
 be added that the best results are obtained with freshly 
 prepared extracts — a fact which militates against a very 
 extensive application of this method of treatment. 
 
 The Indications of Lymphatic Therapy. — In addition to 
 their use in the treatment of experimental tuberculosis, 
 preparations of lymphatic gland extract have been recom- 
 mended in streptococcal angina and in adenitis generally. 
 
 * For an interesting and recent communication on this subject see the 
 articles of Bierring' and others or any recent standard Avork on medicine.
 
 Lym/pliatic Gland Extracts 399 
 
 It is not deniable that there may be a certain modicum 
 of value in this treatment, but in the present author's 
 opinion general tonic treatment by any of the approved 
 methods — even by the suitable application of hormone 
 therapy — and the special treatment of the glands by X 
 ray, local medication, and particularly by the use of suit- 
 able bacterial vaccines, is much more likely to be effectual. 
 
 It is stated that the administration of lymphatic gland 
 extract causes a favourable leucocytosis, and Perez^ 
 reports having secured good results from this treatment 
 of tuberculosis, and suggests that it is available not only 
 as a curative treatment, but also in prophylactic or 
 immunizing treatment. 
 
 An Organo therapeutic Treatment of Adenoids and 
 Enlarged Tonsils. — Ashby^ has assumed that the hyper- 
 trophy of the tonsils and growth of adenoids is a defensive 
 act of the body, and that this increase in the lymphoid 
 tissue is an attempt on the part of Nature to supply to the 
 organism some secretion which it requires at the par- 
 ticular age when this hypertrophy is most common. It 
 occurred to him that lymphatic gland extract might 
 supply the needed element, and obviate, to some extent 
 at least, the physiologic need for the hypertrophy. He 
 therefore gave to a series of thirty children 5 grains of 
 lymphatic gland extract three times a day for some time. 
 No bad effects were observed ; on the contrary, nearly all 
 improved in a very satisfactory way, the snoring and 
 noises in breathing disappeared, and the tonsils have 
 diminished in size. 
 
 This preliminary report is of more than passing interest, 
 and it may be that the treatment of benign lymphatic 
 enlargements, and especially adenoids and hypertrophied 
 tonsils, will be materially modified by the introduction of 
 this form of organotherapy.
 
 400 Practical Hormone Therapy 
 
 Possible Value in Hodgkin's Disease.— The destruction 
 of large tracts of the lymphatic system, as in Hodgkin's 
 disease, gives rise to a syndrome in which emaciation and 
 debihty are prominent. Whether these symptoms are due 
 to a particular systemic loss, or to the production of 
 deleterious substances, is not yet definitely known ; but it 
 has been thought that perhaps lymphatic extracts might 
 be useful as a part of the treatment of this disease. 
 Practically no results are yet on record, and this remains 
 one of the many points regarding glandular therapeutics 
 which are still to be elucidated. 
 
 Markwald^ reports the favourable action of lymph- gland 
 extract in the treatment of a case of Hodgkin's disease. 
 The patient showed an idiosyncrasy to arsenic, and the 
 lymphatic preparation was tried. He states that the size 
 of the enlarged glands was considerably reduced. 
 
 Mesenteric Gland Extracts in Scleroderma. — In 1905 
 Schwerdt^ attempted the use of extracts of the mesenteric 
 glands of sheep as a remedy for scleroderma. He presumes 
 that this disease is the result of an intestinal toxin which 
 is absorbed, and which should be normally neutrahzed by 
 hypothetical internal secretions of these glands. If these 
 mesenteric lymph nodes become diseased and unable 
 thoroughly to neutralize these toxins, then the sclero- 
 derma occurs. Upon this hypothesis Schwerdt suggested 
 the use of extracts of these glands, and his favourable 
 results indicate that possibly this might be a new addition 
 to organotherapy. His second communication'^ on the 
 subject has been followed lately by two other communica- 
 tions from Kolle,^ who reports having used 7|- grains 
 daily, of a preparation made by Merck, called cceliacin, 
 the dose being later increased to 10 grains. This treat- 
 ment, continued over a period of six weeks, seemed to be 
 the cause of a striking improvement in appearance as well
 
 Lymphatic Gland Extracts 401 
 
 as an increase in general health and weight. In his second 
 paper he lends emphasis to his previous suggestion, and 
 although no definite opinions can yet be formed as to the 
 merits of this method of treatment, the results obtained 
 to date indicate that this is a method deserving of con- 
 sideration in the treatment of similar cases. 
 
 The " Lymphoid Compound." — An empirical, but none 
 the less useful, form of organotherapj?^ is embodied in a 
 preparation of lymphatic glands, nervous substance from 
 brain and spinal cord, and testicular substance, called 
 Lymphoid Compound. It is difficult to decide which of 
 the ingredients is the most active, and doubtless the 
 specific virtue of the individual elements in the compound 
 varies with the particular needs of the patient to whom 
 it is administered. The neiu'o-sedative action of the 
 nervous constituent, the defence-stimula^nt action of the 
 lymphatic constituent, and the well-known tonic and 
 oxidizing action of the orchitic constituent are all useful, 
 and together they make up a combination which has been 
 used with considerable success in conditions in which the 
 nervous and general tone is deficient. Obviously the value 
 of such a preparation is greatest in functional disturbances, 
 but cases of organic disorder — e.g., tabes, etc. — have come 
 to the author's notice in which a restoration of functions 
 supposed to be organically lost was evident. This is 
 probably due not to regeneration of destroyed nerve 
 columns, but rather to the increased responsiveness 
 induced in the remaining sound tracts. 
 
 {Strangely enough there is practically no " Hterature " 
 upon this subject, probably because the combination is 
 used principally in England and America, and not in 
 France or Germany. However, this should not mihtate 
 against the application of this idea in practice, for the 
 administration of a combination of this character is rarely 
 
 26
 
 402 Practical Hormone Therapi/ 
 
 attended A\ith a reaction of any kind, and offers hope in 
 cases which are usually considered to be hopeless. 
 
 The clinical indications for the administration of 
 Lymphoid Compound are rather extensive. Generally 
 speaking, it is used in chronic defects of the nervous 
 mechanism in which toxic and nutritional factors are 
 prominent, and as a result functional capacity is reduced. 
 Undoubtedly this form of treatment is active through its 
 influence upon the endocrinous system as a whole, and 
 the benefits which may accrue are due not solely to the 
 remedy itself, but to the hormones and similar substances 
 w^liich its administration seems to call forth. 
 
 The Preparation of Lymphatic Gland Extracts. — Par- 
 ticular care should be exercised in the preparation of 
 remedies of this character. It would seem that consider- 
 able difficulty is likely to be met with in the attempt to 
 produce suitable products because of the difficulty in 
 obtaining healthy glands. Since the mesenteric and 
 bronchial lymph nodes are often the seat of tuberculosis, 
 particular care must be taken to examine each node 
 separately, not omitting to scrutinize the inside of the 
 gland stroma. It is advisable that in the processes of 
 manufacture all such preparations should be tested upon 
 guinea-pigs, in order to obviate the inclusion of tubercu- 
 lous material. The preparation already referred to — 
 cceliacin — corresponds to equal parts by weight of the 
 gland substance, the quarter which has been removed 
 having been replaced by sugar of milk. The average dose 
 is 5 grains, given two or three times a day, and it is said 
 to be borne without difficulty, but caution is advised in 
 its administration in cases of Graves's disease, as Schwerdt 
 mentions having seen unpleasant results follow its use 
 in one case of this disease. 
 
 I
 
 Lymphatic Gland Extracts 403 
 
 BIBLIOGRAPHY 
 
 ^ BiERRiNG (W. L.), Goodrich (J. A.), et ah: Status thymo- 
 lymphaticus, Am. J. Child. Dis. (Chicago), 1913, vi, 641. 
 
 2 Bartel (J.) AND Neumann (W.): Experimentalenunter- 
 
 suchungen ueber den Einfliiss vou organisclieu Substanzen 
 auf den Gang der Tuberkuloseinfektion, beim Meerschwein- 
 chen, Wien. M. Wchnschr., 1907, xx, 1321; see also Bartel 
 (J.): Der normale und abnormale Bau des lympliatisclien 
 Systems und seine Beziehungen zur Tuberkulose, ibid., 1143. 
 
 3 Perez (G. ) : SuU' importanza lunzionale delle glaudole linfaticbe 
 
 e su talune proprieta degli estratti di glaudole tubercolare, 
 Policl. (Rome), 1912, xix (S), 481. 
 
 * AsHBT (H. T.): The cause of enlarged tonsils and adenoids in 
 
 children, and their treatment with lymphatic gland extract, 
 
 Br. Med. J. (London), 1913, i, 1159. 
 ^ Markwald (B.): Eiu Fall von Hodgkin'scher Krankheit mit 
 
 eigenthiimlichen Verlaiif, Ztsclir. f. lyrald. Aerzie (Berlin). 
 
 1897, vi, 12. 
 ® SCHWERDT (C): Ein Fall von zirkumskripter Sklerodermie 
 
 behandelt mit Mesenterialdriise, Munch, med. Wchnschr., 
 
 1905, lii, 509. 
 ' Id.: Weitere Falle vou Sklerodermie behandelt mit Mesenter- 
 
 ialdriisen, Miinch. med. Wchnschr., 1907, liv, 1230. 
 
 * KoLLE (W.): Kasuistisches und Therajjeutisches zur Sklero- 
 
 dermie, Miinch. med. Wchnschr., 1912, lix, i, 864. 
 
 ViDAL (E.): Essai de therapeutique ceUulaire; opoth6rapie 
 gangHonnaire, Pr. mid. (Paris), 1905, xxi, 907. 
 
 MooRHEAD (T. G.): The action of lymphatic extracts, Br. Med. 
 J. (suppl.), 1906, ii, 12. 
 
 Pennington (J. R.): Lymph therapy; further observations on 
 the use of the animal cell of lymph compound with expei'i- 
 mental tests and reports of cases, Med. Standard (Chicago), 
 1908, xxxi, 660.
 
 CHAPTER XXX 
 THE USE OF PLURIGLANDULAR EXTRACTS 
 
 Unnoticed Endocrinous Disorders — A Guiding Principle in 
 Therapeutics — " Kinetic Therapy " — The " Run- Down Con- 
 ditions " — The Application of Pluriglandular Therapy — 
 The Relation of Hypoendocriyiism to Neurasthenia — Tropical 
 Neurasthenia, or " Punjab Head " — Pluriglandular Therapy 
 in Other Nervous Disorders — The " Jerry-built " Constitu- 
 tion and Hypoendocrinism — The Ductless Glafids in Mental 
 Disorders — Opotherapy in Hyposphyxic Conditions — Pros- 
 pects in the Pluriglandular Treatment of Cancer — The 
 Administration of Antagonist Hormones. 
 
 " All the protective substances which are involved in 
 the cure of disease are to be regarded as produced by the 
 internal secretions." This, in a few words, is the basis of 
 a new system of therapeutics which hinges upon the action 
 and interaction of the internal secretions. Although the 
 words of Sir Alnu'oth E. Wright, quoted above, are in a 
 sense hypothetical, for we are not yet able to give con- 
 clusive scientific proof to this effect, the empirical apphca- 
 tion of this principle has shown that it is evident that the 
 ideas of the great Claude Bernard have a much wider 
 range of applicabihty than even he dreamed. We are in 
 the beginning of an era of glandular therapy, which looks 
 extremely promising. 
 
 Unnoticed Endocrinous Disorders, —it has already been 
 suggested that the influence of the ductless glands in 
 cases with no evident disturbance of any particular one of 
 these organs is worth extended investigation, especially 
 in those individuals with a generally deteriorated func- 
 
 404
 
 The Use of Pluriglandular Extracts 405 
 
 tional capacity. With the thought in mind that general 
 disturbances of the internal secretions are very frequently 
 found in these disorders, it seems reasonable to attempt 
 to benefit such cases by the administration of suitably 
 prepared and combined animal extracts, and, while years 
 must elapse before any decided statements can be made, 
 the clinical evidence at hand indicates that good results 
 often follow such treatment. 
 
 It appears that the endeavour to influence metabolism in 
 this way is rational, and that hormone therapy deserves 
 to be more frequently associated with those other thera- 
 peutic measures which ordinarily would be adopted. It 
 also seems entirely probable that the physical and drug 
 treatment of such conditions will be much more effective 
 if the capacity of the cells to react to such treatment is 
 increased by the simultaneous use of suitable animal 
 extracts. 
 
 A Guiding Principle in Therapeutics. — The profound 
 influence that the internal secretions exert upon metabo- 
 Usm explains, on the one hand, why success often follows 
 a change of environment, and, on the other, why there 
 are so many failures in the treatment of certain symptoms- 
 complex. The restoration of the disturbed cell- activities 
 should be one of the guiding principles in all therapeutics, 
 and special assistance is available from suitable pluri- 
 glandular combinations. This accounts for the success 
 which so often attends this form of treatment in " run- 
 down conditions," and partially explains the remarkable 
 changes in all the bodily activities which accompany 
 the sanatorium and spa cures. Snowman^ makes some 
 very sensible remarks on this subject. He writes: "It 
 must be confessed that the general practitioner is only 
 vaguely concerned with the problems of metabolism in 
 his routine work, and that textbooks of therapeutics
 
 406 Practical Hormone Therapy 
 
 hardly proceed in this direction much beyond a general 
 recommendation in most diseases of ' good food, fresh air, 
 and sunhght.' It is often pointed out that recovery from 
 disease is encouraged by such improved conditions. A 
 tardy convalescence is hastened by residence at the sea- 
 side, obstinate anemia begins to improve in the sur- 
 roundings of a country life, and chronic indigestion will 
 often refuse to yield until the patient has a ' thorough 
 change.' The true reason that success attends these 
 measures is that they exercise an effect on the metabolism, 
 and tend to restore it to the normal, and then the oppor- 
 tunity is afforded, either to Nature or to Art, to bring 
 about a complete recovery. This endeavoiu" to influence 
 metabolism should therefore accompany the therapeutic 
 measures which may be adopted in any case, and there 
 can be no doubt that if attention to this physiological 
 need became a routine principle in treatment, drugs would 
 achieve more than they do at present." 
 
 The frequency with which disturbance in one of the 
 endocrinous organs is followed by, or associated with, 
 changes in both structure and function of others — the 
 evidence of upset of the " hormone balance " — has led 
 several investigators to experiment A^ith various com- 
 binations of glandular extracts. Carnot,^ in this con- 
 nection, remarks that more recently pluriglandular in- 
 sufficiencies have become better known, and, in order to 
 profit by certain glandular synergisms, mixed extracts 
 have been used with encouraging results. Commenting 
 editorially on this same subject, the Lancet^ makes the 
 following statement: " If this correlation of effects really 
 exists, it is theoretically possible that for therapeutic 
 purposes the use of a combination of gland preparations 
 might prove superior to that of one alone." As a matter 
 of fact, combined extracts are often much more active
 
 The Use of Pluriglandular Extracts 407 
 
 and render much more effective service than the same 
 substances given singly. The experimental employment 
 of such a combination has been carried out a number of 
 times. 
 
 Woodwark^ of St. Bartholomew's Hospital, London, 
 relates his experiences with a combination of thjToid, 
 thymus, pituitary, and adrenal. He used tablets con- 
 taining 1 grain each of the four extracts in myxoedema, 
 Mongolian idiocy, rickets, and obesity. Improvement 
 was general, save that of the five cases of obesity only two 
 improved, and one of the remaining three suffered from 
 palpitation, evidently due to the medicine.* Elsewhere 
 in this chapter will be found references to the work of 
 others in this line. 
 
 " Kinetic Therapy." — If the postulates laid down by 
 Crile in his " kinetic theory "^ (see p. 38) are sound, and 
 the " kinetic system " that he describes is a definitely 
 correlated mechanism — and the author is firmly con- 
 vinced of the fundamental soundness of this position — ■ 
 what can be more reasonable than a " kinetic therapy " 
 based upon the tonic and regenerating powers of combined 
 organic extracts ? With regard to pluriglandular action, 
 Ott^ says : " Just as glands with an external secretion 
 concur in taking up the work not accomplished by the 
 others, and unite in the perfection of the products to be 
 brought forth, in a similar way the glands with an internal 
 secretion concur in the metabolites to be produced, a sort 
 of physiological balance is maintained between the 
 activities of the different glands in the wilderness of 
 metabolism." 
 
 * The autlior believes tliat much of the good recorded in Woodvvarlc's paper 
 would have doubtless followed thyroid or pituitary - thyroid medication 
 alone, especially in the cases with evident hypothyroidism. It is likely that 
 the dosage of thyroid and adrenal may have been too large, and that the 
 combination suggested is suitable only in cases where thyroid medication is 
 indicated.
 
 408 
 
 Practical Hormone Therapy 
 
 We can catch a glimpse from such statements as these 
 of the power for good that a suitable combination of 
 glandular extracts can be. in cases where half-speed 
 function is common, and the decreased output of energy 
 is not confined to the muscles, brain, nerves, or digestive 
 glands, but also to the all-important hormone-producing 
 organs. 
 
 It is quite reasonable that this form of medication 
 should be extended to the treatment of many disorders 
 in which the disturbance in the internal secretory organs 
 may be seemingly neghgible, but in which, however, there 
 is a general decrease in the bodily activities, where it is 
 right to suppose that the asthenic condition is not con- 
 fined to the muscles, nerves, or elimination, but influences 
 all the hormone-producing organs to the detriment of the 
 whole system. 
 
 Amongst these must be classed many of those nervous 
 diseases which are the bane of the general practitioner's 
 existence, such as the "run-down conditions," neuras- 
 thenia, melancholia, and certain other insanities. It may 
 be of advantage to collate a number of comparatively 
 recent quotations from medical hterature, which seem 
 to give emphasis to the importance of the internal secre- 
 tions in the causation and cure of these functional 
 disorders. 
 
 The "Run-Down Conditions," etc. — Granting that the 
 " guiding principle in therapeutics " stated previously is 
 correct, it is clear that there are additional means whereby 
 the deficient metabohsm can be increased. The " change 
 of air " is in itself a valuable tonic, but it is not always a 
 convenient measure, and even if available, its influence 
 can be enhanced by pluriglandular therapy. 
 
 In the so-called "run-down conditions," which include 
 a large number of disorders of which no very definite
 
 The Use of Pluriglandular Extracts 409 
 
 diagnosis can be made, as, for example, asthenia, neuras- 
 thenia, post-febrile conditions, convalescence, presenility, 
 etc., there is of necessity a more or less obvious hypo- 
 endocrinism, which of itself is a serious matter. One 
 cannot expect the internal secretory organs of the indi- 
 vidual manifesting suboxidation, defective digestion, 
 malassimilation, and the obvious evidences of being 
 "run-down," to be working normally and supplying to 
 the body the essential hormones which regulate practically 
 the whole of its metabolic activities (see Chapter III.). 
 
 This hypoendocrinism is not only a symptom, it is also 
 a serious factor in the further reduction of the forces of 
 the body, for, as we have already seen, the protective 
 substances involved in the cure of disease are presumed 
 to be produced by the internal secretory organs. 
 
 This is a factor to be taken into consideration in all 
 asthenic states. The encouraging results which follow 
 the application of hormone therapy will amply repay one 
 for the study and application necessary accurately to 
 discern and treat these insidious but nevertheless im- 
 portant deficiencies. 
 
 The multiplicity of hormones and their potent influence 
 on function prepare us for the conclusion that " many 
 functional disorders are hormonically induced." It is 
 obvious that the plasma normally contains many different 
 hormones, and that if health is to be preserved, the supply 
 of the hormones must be regulated with great nicety. 
 " There is thus abundant opportunity for the plasma to 
 become faulty in respect of its hormonic constituents; 
 it may, e.g., contain too little, too much, or a perversion 
 of any one hormone, and these individual defects may be 
 combined in endless ways, producing an endless yariety of 
 plasmic imperfections, each of which has its own peculiar 
 effect upon metabolism. There can, indeed, be no doubt
 
 410 Practical Hormone Therapu 
 
 that disordered hormonic function is responsible for 
 numerous functional disorders. . . . Whenever disease 
 is due to a hormonic or enzymic defect, the treatment 
 obviously consists in correcting that defect."^ 
 
 The Application of Pluriglandular Therapy. — The most 
 important point to know, in applying these essentials in 
 therapeutics, is what constitutes the most prominent 
 element in the complex of hypoendocrinism. It is not 
 always possible definitely to state which of the ductless 
 glands is faiUng in its normal duties, nor can one measure 
 the extent of the inactivity. Only by careful investiga- 
 tion of the minutiae of the diagnosis can one gain an idea 
 of the disturbance and its extent. At times it seems 
 almost advisable to presmne what cannot definitely be 
 proved, and surely there are sufficient evidences of the 
 hypoendocrinism, even though one cannot locate the 
 principal secretory deficiencies. 
 
 There can be no doubt that the pituitary, adrenals, 
 gonads, and thyroid are the principal endocrinous organs 
 concerned in maintaining the vitahty or tone of the body. 
 Their influence upon muscular and vessel tone, on oxida- 
 tion, and on the vital functions generally, are decidedly 
 plus. Will the application of a mixture of extracts of 
 these glands be useful, and if so, how are they to be 
 combined ? 
 
 There is more than enough evidence to show that the 
 empiricism which initiated pluriglandular therapy is well 
 founded, as the evidence gathered here will show. The 
 author is quite confident that this is a most effectual 
 method of treatment. 
 
 In 1907 Renon and Delille^ described a " polyglandular 
 syndrome," which is a prominent symptom-complex 
 brought about by insufficient activity of several of the 
 endocrinous organs. This corresponds to the term
 
 The Use of Pluriglandular Extracts 411 
 
 "hypoendocrinism " used throughout this book. As far as 
 possible they carefully differentiated the various deficien- 
 cies, and where certain signs suggested disorders of two 
 or more organs, they gave corresponding pluriglandular 
 extracts. 
 
 Sajous, in an editorial in the New York Medical Journal^* 
 commenting on this field of study, says: "Cases of this 
 class, which are steadily accumulating, show clearly that 
 a vast field lies before us, sown with difficulties for the 
 time being, but of immense promise for the future. . . . 
 Its far-reaching meaning can hardly be overestimated, 
 not only owing to the additional evidence it contributes 
 in favour of the intimate relationship between various 
 ductless glands and the vital process — i.e., of oxidation 
 and metabolism throughout the whole gamut of pathology 
 — but also as an indication of the power of organic 
 preparations when, in their therapeutical application, 
 empiricism is replaced by rationalism." 
 
 The Relation of Hypoendocrinism to Neurasthenia. — 
 The complicated conditions which are usually so indefinite 
 as to have remained for years unnamed, the most im- 
 portant of which is termed "neurasthenia," because of 
 the prominence of the nervous asthenia, must in a greater 
 or lesser degree either be dependent upon, or at least 
 associated with, disturbances in the hormone balance. 
 We know that suboxidation, cell torpor, or deficient 
 metabolism, is perhaps the most prominent factor in this 
 class of cases, and if the nervous system, the muscular 
 system, the digestion and metabohsm in general, are 
 working at low pressure, it is reasonable to suppose that 
 the work of the internal secretory organs is equally 
 deficient. 
 
 Lorand, in the Introduction to his book, " Old Age 
 Deferred," states that nemrasthenia is a disease which is
 
 412 Practical Hormone Therapy 
 
 often based upon changes in the ductless glands, especially 
 the thyroid, the sexual glands, and the pituitary body. 
 The poor state of nutrition so often found in these persons 
 is another manifestation of the endocrinous disorder, for, 
 as Lorand reiterates, " in typical cases of this class there 
 is a diminution of metabolism — i.e., of the assimilation 
 and conversion of food into energy. We shall have to 
 think of the possibility of alterations in those organs which 
 govern the process of metabolism . . . — the organs of 
 internal secretion." 
 
 The frequency with which such conditions as amenor- 
 rhoea and impotence are found is conclusive proof that 
 the gonads and their secretions are prominently concerned 
 in the class of disorders which rightly or wrongly is called 
 "neurasthenia." This also gives an idea of at least a 
 part of the glandular extracts which are to be combined 
 and used in its treatment. 
 
 Regarding the treatment of neurasthenia minor, Camp- 
 bell Smith^" emphasizes the need for steady and persistent 
 treatment, and states that " for a priori reasons one would 
 think that a similarly extended course of combined 
 organic extracts would be very advantageous, and some 
 recent reports of such a treatment of neurasthenia major 
 and some forms of insanity tend to confirm this behef." 
 
 Starkey^^ has experimented with a combination of 
 extract of thyroid, parathyroids, pituitary, ovaries, and 
 testicles, and reports many encoiu-aging results, giving 
 his experience in the treatment of no less than 480 cases. 
 The results obtained by him are briefly mentioned in the 
 conclusion of his paper, which is as follows: "In con- 
 clusion, I think we may safely say that the polyglandular 
 substance described herein has a marked stimulating 
 effect, and that in acute asthenic conditions with low 
 blood-pressure and suboxidation it activates the vital
 
 The Use of Pluriglandular Extracts 413 
 
 process, and thus tides the patient over the most critical 
 stages of the disease, while increasing the efficiency of his 
 autoprotective resom*ces. This is fiilly sustained by 
 Sajous's views. 
 
 " The same polyglandular solution seems also to be 
 almost a specific for neurasthenia. It has a marked 
 stimulating effect on mental, nervous, and muscular 
 activity, as well as on general metaboHsm and oxidation in 
 general. It augments powerfully the contractile power 
 of the cardiovascular system, and is therefore contra- 
 indicated in cases of high blood-pressure. Finally, it 
 increases the action of other drugs, arsenic, mercury, 
 iodides, and sahcylates in particular, and their curative 
 efficiency." 
 
 It is particularly interesting to note that the adminis- 
 tration of this pluriglandular substance by Starkey in a 
 series of fifty persons in apparently normal health showed 
 that the nitrogenous elimination was increased; they 
 gained an average of 8 pounds in weight, following a short 
 series of injections, they felt better, and their appetite, 
 as well as their muscular and mental efficiency, was con- 
 siderably increased. Sexual vigour was also augmented. 
 
 Practically as well as theoretically this medication 
 has proved its importance, and it is predicted that the 
 coming treatment of those conditions where function is 
 diminished, due either to acute toxaemia as in fevers, or 
 to the chronic toxaemias due to deficient metabohsm, 
 wiU be an attempt to supply some of the hormones that 
 have been lost, and thus to restore the hormone equi- 
 librium. Personal experience has convinced the author 
 that the administration by mouth of a combination of 
 glandular extracts* enhances the work of the whole 
 
 * For some years the author has been experimenting with various amounts 
 and combinations of organic extracts. He lias used a phiriglandular prepara- 
 tion ([uite like Starkey's, but made from glands more easily obtained, and in
 
 414 Practical Hormone Therapy 
 
 system. The laboratory tests associated with such 
 treatment have also demonstrated the increased capacity 
 of the body to ehminate wastes, relieving the cells of not 
 a little unnecessary toxaemia. 
 
 Tropical Neurasthenia or " Punjab Head." — It may be 
 well to call attention to a common symptom-complex 
 which is very closely allied to some of the conditions that 
 have just been shown to be either due to or associated 
 with hypoendocrinism. The majority of Europeans who 
 live in the tropics eventually suffer from a combination of 
 manifestations known as "Punjab head" or "Bengal 
 head." This is, strictly speaking, a "run-down" con- 
 dition, and the individual shows it by a change in his 
 humour, a disinclination to accept responsibihty, insomnia, 
 and decreased power to concentrate. Often there are no 
 evident organic disturbances, and the whole is set down 
 as an attack of "liver." 
 
 Later, however, according to Sir R. Havelock Charles, ^^ 
 there develops a congeries of mental and sensory dis- 
 turbances, generally accompanied by signs of defective 
 metabolism. Moreover, such a condition of what is 
 reaUy a form of nerve exhaustion lowers the vitaUty and 
 natural immunity or power of resistance to disease, and 
 so renders the subject more susceptible to infection. 
 This writer considers that the conditions of continuous 
 residence in hot countries influence the nervous system 
 of Europeans, both directly and also indirectly, by pro- 
 ducing anaemia, imperfect metabolism, and affections of 
 the alimentary and other systems. He finds an explana- 
 tion of this in the old saying of Cuvier: "The nervous 
 
 a more convenient form, as it may be given hy mouth in capsules. This 
 consists of a mixture of luteal and testicular extracts with the addition of 
 small doses (xo to ^V ^^'■) of thyroid and infundibular extracts. It has lately 
 been put up in tablet form under the name Iwrmotone, which was recently 
 called a " luilraillciisc,"^^ but which is none the less cll'ective.
 
 The Use of Pluriglandular Extracts 415 
 
 system is at bottom of the whole animal, and the other 
 systems are only to serve it."^^ 
 
 Cuvier evidently was wrong, for we now know that the 
 sympathetic nervous system, and with it metabolism, 
 oxidation, and resistance to infection, is definitely con- 
 trolled by the hormones produced by the endocrinous 
 organs. It seems most reasonable that the enervating 
 climatic conditions of tropical countries have a specific 
 and unquestioned influence upon the endocrinous organs, 
 and tend to produce a hypoendocrinism which, in the 
 author's opinion, is the fundamental cause of the neuras- 
 thenias of tropical origin. 
 
 Real value is given to this position bj^ clinical evidence 
 following pluriglandular therapy, and while the author 
 has had no personal clinical experience in tropical coun- 
 tries, correspondents have mentioned the tonic influence 
 of this method of treatment. It at least seems deserving 
 of a much more extended trial, and doubtless will assume 
 a more prominent position as the subject becomes better 
 known. 
 
 Pluriglandular Therapy in Other Nervous Disorders. — 
 Many facts which have been elicited in the study of the 
 internal secretory organs indicate that numerous nervous 
 disorders are the result of disturbances of the hormone 
 balance. This has led a number of investigators to try 
 various forms of organotherapy in their treatment, and 
 without a doubt a valuable measure has been discovered 
 in the administration of suitable combinations of extracts. 
 
 Delille and Vincent' ' relate encouraging results in the 
 treatment of bulbo spinal myasthenia. They found that 
 a combination of the total extracts of the hypophysis and 
 ovary effected a complete cure. This meant that the 
 paretic manifestations of long standing disappeared, and 
 the patient was able to walk. They found, however, that
 
 416 Practical Hormone Therapy 
 
 the cure was not permanent, as the withdrawal of either 
 one of the extracts led to a recurrence of all the symptoms ; 
 but as long as the plmdglandular medication was con- 
 tinued, the patient was seemingly quite weU. This ex- 
 perience indicates the essential role of these internal 
 secretions, and reminds one of the decided and specific 
 influence of thyroid extract in myxoedema, etc. 
 
 Starkey^^ records good results from his pluriglandular 
 treatment (see p. 42) in tabes. He writes: "Due to 
 recent developments in organotherapy, we now have a 
 gleam of hope, and I am satisfied that when this subject 
 is better understood, many real cures of this disease will 
 be recorded." He believes that this method "seems to 
 fit very closely to the scheme of Nature in the use of these 
 glands, the internal secretions of which have a profound 
 effect on metabohsm, increasing cellular activity and 
 nerve tone." 
 
 He reports a number of successful cases from his 
 records, the outhne of one of which is sufficiently extra- 
 ordinary to include here: " Case V. (exhibited before the 
 Philadelphia County Medical Society, December 11, 1912). 
 The patient, a lady, forty years of age, had been afflicted 
 with tabes for twenty-seven years. Diagnosis had been 
 made and confirmed by a number of eminent physicians 
 from time to time. All this time she had complained of 
 stabbing pains in the region of the stomach radiating down 
 the legs. She had also girdle pains, Argyll-Robertson 
 pupils, staggering gait, and inability to make quick short 
 turns. The knee-jerk was not lost. She had been treated 
 with potassium iodide, mercury, and morphine, or other 
 hypnotics. She had also received salvarsan on two 
 occasions. 
 
 "The family history was negative. Previous history: 
 Had ordinary diseases of childhood, including measles.
 
 The Use of Pluriglandular Extracts 417 
 
 No specific history. At age of thirteen commenced to 
 have pain and spasms of legs, which were relieved by rest. 
 This condition increased in spite of treatment, and at 
 nineteen she began to have stabbing pains in stomach, 
 eyes, and back. Double vision, lasting for several months, 
 was present between twenty and twenty- one. These 
 paroxysms of pain came at such frequent intervals as to 
 be almost constantly present, and practically made her 
 an invalid, confining her to her rooms. 
 
 " She first came to me on July 12, 1912, was examined, 
 and received her first treatment the following day, and 
 for four months has received injections twice weekly of 
 my pluriglandular extract. At the present time she is 
 entirely free from pain, and has been so almost from the 
 first treatment. During the entire four months of obser- 
 vation she has had but one attack of pain, and that was 
 mild in character, and due to over-exertion. She has 
 received no other treatment, and has had neither seda- 
 tives nor mercury. At present I consider her cured 
 and able to return to her family. She is now abso- 
 lutely free from pain, has no ataxia in her gait, can 
 walk a chalk fine and turn corners sharply, stand with 
 her eyes closed, and walk an average of three or four 
 miles a day. She has also gained 12 pounds in weight. 
 Her vision, which was nearly gone in the left eye, is now 
 normal." 
 
 The " Jerry-built Constitution *' and Hypoendoerinism.— 
 The class of individuals who are far from normal and yet 
 cannot consistently be called " defectives " has been 
 considered by many to be congenitally deficient in the 
 endocrinous activities. These individuals are sufferers 
 from hypoendoerinism, and consequently "the vital stream 
 flows sluggishly," and physically as well as mentally they 
 are always below par. Most of these cases are congenital, 
 
 27
 
 418 Practical Hormone Titer ayy 
 
 and have been given an excellent name — they are indi- 
 viduals with " jerry-built constitutions." 
 
 Jamin^'' of Heidelberg calls attention to the fact that 
 frequently symptoms of chlorosis were noticed in young 
 persons without the associated and characteristic altera- 
 tions in the blood. He is convinced that it is probable 
 that this disease, to which the name " juvenile asthenia '* 
 has been given, is due to endocrinous disorders, and is 
 virtually an evidence of arrested development. He laid 
 no particular emphasis upon which internal secretion was 
 principally at fault, but without doubt here is another 
 condition in which the use of organotherapeutic com- 
 binations eventually will prove useful. Boncour refers 
 to a constitutional psychomotor asthenia in children, 
 in which the patient suffers from a combination of motor 
 debility, with marked muscular weakness and mental 
 inertia and disability. He found that pluriglandular 
 extracts had a marked influence upon the mental and 
 physical development, 
 
 Dupuy^^ has made an extended study of the treatment 
 of backward and defective children, and has used what 
 he terms ^^ polyopotherapie endocrinienne associee,^^ and 
 reports very encouraging results, which he summarizes 
 as follows: (1) A rapid increase in stature, which had been 
 slow to show itself with thyroid treatment, and a reduc- 
 tion in the rapid growth in those which seemed to be 
 suffering from gigantism. (2) A less marked reduction 
 in emaciation than with thyroid treatment alone, and a 
 more decided tendency to regain the initial weight than 
 when thyroid alone had been allowed. (3) An extra- 
 ordinarily rajjid modification of the urinary elimination, 
 clearly indicating that metabolism is re-established on a 
 more nearly normal basis and that assimilation has become 
 regular. (5) A beneficial effect on the disorders due to
 
 The Use of Plwriglandular Extracts 419 
 
 morbid phenomena, as well as on those lesions of a sympa- 
 thetic character which are found in the backward (and 
 which thyroid treatment often does not influence), 
 including troubles in vision, incontinence, visceral ptoses, 
 umbilical hernia, etc. (6) A general physical meta- 
 morphosis and a re-establishment of the sexual functions 
 (menstruation, ovulation, etc.). (7) A psychic and sen- 
 sory metamorphosis and a reduction of asthenia and 
 excitabihty, as well as a noticeable progress in the intel- 
 lectual capacity, thus allowing these unfortunates to take 
 their proper place in society. 
 
 Quite often it is possible to augment the growth and the 
 physical as well as mental activities of such individuals 
 by suitable combinations of animal extracts. 
 
 The Ductless Glands in Mental Disorders. — It is not a 
 very far cry from the jerry-built constitution to functional 
 mental disorders, and again from the functional to the 
 organic forms of insanity. Many papers of exceptional 
 interest have suggested a relation between faulty internal 
 secretory activity and various mental syndromes. ^'^ "' Judg- 
 ing from the view-point of the general practitioner, at 
 least, psychiatry — to which might be added its sister 
 branch, neurology — does not afford as great a degree of 
 satisfaction, in so far as therapeutic results are concerned, 
 as do other specialities. An academic explanation of the 
 morbid process supposed to be present in a given case is 
 usually vouchsafed, but the results are in most cases dis- 
 appointing. Modern researches, however, seem to be 
 fm-nishing a clue to the cause of this unfortunate state of 
 affairs. Defective anabolism through deficient oxidation 
 and, conversely, imperfect catabolism of toxic wastes, 
 have been known to explain many morbid phenomena of 
 the cerebrospinal system, but the underlying cause of 
 these departures from normal metabolism remained
 
 4:20 Practical Hormone Therapy 
 
 obscure until the marked influence of the ductless glands 
 upon these processes opened a new field of study." ^° 
 
 Sainton^^ is convinced that a large share of the etiology 
 of mental disorders may be traced to pluriglandular 
 insufficiency, and has shown that the proper application 
 of combined opotherapy is often very helpful. He writes : 
 " If the old adage, Naturam morhorum ostendunt cura- 
 tiones, is true, one must admit that it is in a large degree 
 due to the influence of the internal secretions in the 
 pathology of mental alienation." 
 
 Dercum and Ellis, ^^ holding the view that dementia 
 prsecox is associated with auto-intoxication, studied the 
 pathology of the glands of internal secretion in eight cases 
 of this disease. All the patients died of tuberculosis, a 
 most interesting point in the pathology of dementia 
 praecox. A striking finding was the underweight of the 
 thyroid in seven of the cases. The adrenals also presented 
 noted variations from the normal in weight and in size; 
 the small amount of fat in their cortical cells was constant, 
 probably indicating the diminished functional activity. 
 These authors consider that " it is a remarkable fact that 
 the almost universal cause of death in dementia prsecox 
 is tuberculosis, and if the feebleness to resistance to the 
 tubercle bacillus is due to a fault of the adrenal system 
 (pituitary, thyroid, and adrenals) we have reason to infer 
 that it is one of the factors in the make-up of dementia 
 praecox. The conclusion is not justified that an abnor- 
 mality of the adrenal system is the cause of the mental 
 symptoms, but our findings are at least in keeping with 
 the inference that anomalies of the ductless glands exist 
 in dementia prsecox." 
 
 Bornstein,23 from the results of his experiments during 
 the past ten years, concludes that there exists a disturbed 
 function of the sexual glands in dementia praecox, and
 
 The Use of Pluriglandular Extracts 421 
 
 that the decreased function brings about a pathological 
 mental exaggeration at puberty, and accordingly we have a 
 disturbed metabolism which expresses itself in a psychic 
 derangement. This coincides with the work of Abder- 
 halden and Fauser, who found that the serum in dementia 
 prsecox decomposes sexual gland substances, and at the 
 same time there is a disturbed function of the internal 
 secretion of the ovaries and testicles. 
 
 Opotherapy in Hyposphyxic Conditions. — Martinet^-* 
 describes an interesting circulatory syndrome — reduced 
 tension with a diminution in the output of arterial blood, 
 and a consequent venous stasis and general circulatory 
 sluggishness — which he has called "hyposphyxia." This 
 condition he finds to be invariably accompanied by hypo- 
 endocrinism, which may be advantageously treated by 
 giving suitable pluriglandular extracts in conjunction with 
 the physical and other means calculated to strengthen the 
 circulatory function. Martinet finds that in these cases 
 there is a digestive disorder which reacts upon the circu- 
 latory disturbance, and forms a vicious circle. He there- 
 fore treats it with secretin preparations, and at the same 
 time augments the endocrinous dyscrasia by pituitary or 
 adrenal extracts combined, as circumstances indicate, 
 with thjrroid and ovarian extracts. Excellent results 
 were secured by this treatment of the hyposphyxia follow- 
 ing acute infectious diseases, malnutrition, neurasthenia, 
 and in the pretuberculous state. Improvement was even 
 noted in congenital conditions in which this circulatory 
 syndrome was prominent. 
 
 Prospects in the Pluriglandular Treatment of Cancer. — 
 In Chapter III. the influence of certain of the interna 
 secretions has been shown to be related to experimental 
 cancer — certain transmissible tumours " took " better in 
 castrated mice than in other animals. The relation of the
 
 422 Practical Hormone Therapy 
 
 X ray to the activity of the endocrinous organs, and the 
 possibiHties of a connection between the artificially 
 induced hypoendocrinism and cancer, are briefly men- 
 tioned in Chapter XXXI. 
 
 Cancer is essentially a disease of nutrition — i.e., errors 
 in nutrition, whether local or general, are the factors 
 which permit of the implantation of cancer cells and the 
 growth of the tumour. The ductless glands preside over 
 nutrition. Hence it is not unreasonable to suppose that 
 there may be some relation between disturbances of the 
 hormone balance and cancer, and, too, that there may 
 be some prospects of therapeutic value in the treatment 
 of this disease by organotherapy. 
 
 As yet very little is known, but it seems that another 
 door has just been opened a crack, and shortly we may 
 expect to hear of some of the interesting things that lie 
 just beyond that door. 
 
 At present there are three communications which show 
 that this subject is receiving chnical consideration. 
 Reference to these is made, not to " establish a new 
 method of treatment," but to indicate the fruitfulness of 
 this field of research, and perhaps to stimulate further 
 consideration in this direction. Shirlaw^^ suggests the 
 administration of a pluriglandular extract containing the 
 extracts of the thyroid, adrenal, and hypophysis in their 
 approximate normal proportions. The preparation in 
 commerce, ''Tabloid Three Glands,'''' contains 6 grains 
 thyroid, f grain adrenal, and yV grain pituitary in each 
 tablet. Shirlaw relates a case of pharyngeal carcinoma 
 treated with this combination for two months, in which 
 there was an obvious gain in weight and strength and an 
 improvement in deglutition. 
 
 Bazzochi^^ has used a rather different pluriglandular 
 combination for pyloric cancer. He prepared a fluid
 
 The Use of Pluriglandular Extracts 423 
 
 extract of foetal organs — thyroid, thymus, and spleen — 
 which he injected on four successive days with immediate 
 benefit. One year later the gain in weight amounted to 
 18-| pounds (8*5 kilogrammes), the health was good, and 
 no trace of the tumour or suspicious symptoms remained. 
 In this case the pathological examination of excised 
 supraclavicular glands had shown the presence of typical 
 epithelial nests. ^^ 
 
 Previous to the above Billard^^ suggested the use of a 
 combination of extracts of spleen, liver, and pancreas as 
 an adjunct remedy in cancer. Its administration is not 
 intended as an attempt to cure the disease, but was used 
 by Billard to reduce the toxaemia and cachexia, and to 
 increase the nutrition and general well-being. His 
 reports were quite encouraging. 
 
 These suggestions, while somewhat divergent, are of 
 peculiar interest, and, since practically no harm can come 
 from the judicious application of pluriglandular therapy 
 in cancer, may lead to other equally remarkable results. 
 
 The Administration of Antagonist Hormones. — It has 
 been suggested that the administration of antagonizing 
 hormone-bearing extracts is unscientific, and that the 
 antagonism nullifies any possible therapeutic action. 
 This may be true. It is certain that simultaneous ad- 
 ministration of adrenal and pancreatic extracts shows the 
 antagonism, since adrenaline glycosuria is controlled or 
 not produced when the pancreatic extract is given at the 
 same time. 
 
 It must be remembered, however, that the therapeutic 
 action of hormones does not seem to be due so much to 
 the replacing of the particular hormone in the economy 
 (for the dosage must indeed be very small compared with 
 the amount of the " chemical messengers " normally pro- 
 duced), as to its specific action upon the corresponding
 
 424 Practical Hormone Therapy 
 
 hormone-producing cells — e.g., a minute dose of thyroid 
 serves a much broader purpose than could be ascribed to 
 it alone ; it tends to cause the production of more of the 
 thyroid internal secretion, and hence has a much wider 
 influence. This is according to the axiom laid down by 
 Hallion (see p. 24), and it can readily be appreciated that 
 the action of small doses of antagonizing extracts serves 
 to stimulate the corresponding organs, and thus to increase 
 the hormone content of the blood — to strengthen the 
 various " chemical messages " which are of such vital 
 importance. 
 
 Another point worthy of emphasis concerns the capacity 
 of the individual ductless gland to respond to such stimuli. 
 It seems estabhshed that the degree of stimulation 
 exerted by the administration of a hormone-bearing sub- 
 stance is in direct ratio to the need for such stimulation — 
 i.e., an extract is more efficient when the corresponding 
 active principle is deficient in the body than when present 
 in normal amounts. Hence in a combination of several 
 extracts the principal action is the one which is deficient — 
 that is to say, the more it is needed the more useful it is. 
 
 The " shot-gun " idea in hormone therapy is by no 
 means so unscientific as some might think. In fact, it is 
 quite possible that some of the failures following the use 
 of a single animal extract may be obviated by combining 
 it with one or more other synergistic extracts. This is 
 particularly true of ovarian preparations (see Chap- 
 ter XXIV., especially pp. 354-5). 
 
 " The internal secretory glands already unfold before 
 the astonished view of the seeing eye a land of promise 
 beside which the vast territories conquered by Lister and 
 Pasteur are destined to pale into honourable insignificance. 
 The ductless glands and their hormones come to us as 
 peaceful conquerors who brook no denial. They lighten
 
 The Use of Phiriglandular Extracts 425 
 
 our darknesses and show us miracles. In studying them 
 and endeavouring to unravel their intricate and esoteric 
 mysteries one seems ever and anon to be on the trail of the 
 Great Secret, and in danger of losing one's mental 
 perspective. "2^ 
 
 BIBLIOGRAPHY 
 
 1 
 
 Snowman ( J. ) : A guiding principle in therapeutics, Med. Pr. and 
 
 Circ. (Loudon), 1913,^cxlvii, 12. 
 - Carnot:* p. 43. 
 ^ Editorial: The therapeutic action of the internal secretions, 
 
 Lancet (London), 1913, i, 1750. 
 * Woodwark (A. S.): A line of treatment in mental and physical 
 
 deficiency based upon the therapeutic action of the internal 
 
 secretions, St. Bart. Hosp. Bep. (London), 1913, xlviii, 39. 
 
 5 Crile (G. W.): The kinetic system, Gler. Med. J., 1913, xii, 
 
 665. 
 
 6 Ott:* " Internal Secretions," p. 108. 
 
 ' Campbell (H.): The role of the blood-plasma in disease (II), 
 
 Lancet (London), 1907, i, 377. 
 ® Renon (L.) and Delille (A.): De I'utilitd d'associer les m6dica- 
 
 tions opotherapiques, Pr. med. (Paris), 1907, xv, 391. 
 ^ Editorial: Polyglandular therapy, N. Y. Med. J., 1912, xcv, 
 
 1277. 
 ^•^ Smith (P. C. C): Neurasthenia minor, Pract. (London), 1911, 
 
 Ixxxviii, 107. 
 *^ Starke Y (F. R.): The combined use of thyro-parathyroid, 
 
 jjituitary, ovarian, and testicular extracts, N. Y. Med. J., 
 
 1912, xcv, 1257. 
 ^- Williams (L.): Discussion on the therapeutic value of hor- 
 mones, Proc. Boy. Soc. Med. (Sec. Thcr.), (London), 1914, 
 
 vii, 33. 
 ^^ Havelock-Charles (R.): Neurasthenia and its bearing on the 
 
 decay of northern peoples in India, J. Trop. Med. arid Tlyg. 
 
 (London), 1913, xvi, 382. 
 ^* Editorial: Neurasthenia in tropical climates. Lancet (London), 
 
 1914, i, 124. 
 1^ Delille (A.) and Vincent (C): Myasthenic bulbo-spinale, 
 
 Pr. med. (Paris), 1907, xv, 102. 
 1** Starkey (F. a.): Glandular extracts in the treatment of tabes 
 
 dorsalis, Prescriber (Edinburgh), 1913, vii, 103. 
 1' Jamin (P.): Ueber juvenile astlienie, Verh. Dent. Kong. inn. 
 
 Med. (Wiesbaden), 1913, xxx, 344.
 
 426 Practical Hormone Therapy 
 
 1* DuPUT (R.): Le traitement des enfants " arri6r6s " par 
 ropoth6rapie endocrinienne associee, J. d. med. d. Paris, 1912, 
 
 xxiv, 87; see, Arri^ration infantile et polyopoth^vapie endo- 
 crinienne, C. r. Acad. d. 8ci. (Paris), 1912, cliv, 229. 
 ^^ HoCHWART (L. V. F.): The relations of internal secretion to 
 
 mental conditions, Am. J. 3Ied. Sei. (Philadelphia), 1913, 
 cxlvi, 186. 
 2° Editorial: Mental diseases and their relation to the internal 
 
 secretions, N. Y. Med. Jour., 1913, xcviii, 381. 
 2^ Sainton (P.): Les troubles psychiques dans les alterations des 
 
 glandes a secretion interne, Encephale (Paris), 1906, iii, 
 
 242, 377. 
 -- Dercum (F. X.) and Ellis (A. G.): The examination of the 
 
 ductless glands in dementia praecox, J. Nerv. and Ment. Dis. 
 
 (Boston), 1913, xl, 73. 
 23 BoRNSTEiN (A.): Ueber den Stoffwechsel der Geisteskranken, 
 
 Iliinch. med. WcJmschr., 1913, Ix, 1994. 
 -* Martinet (A.): Traitement des hyposphyxies, Pr. med. (Paris), 
 
 1913, xxi, 635. 
 2s Shirlaw (J, T.): The nature and origin of cancer, Brit. Med. J, 
 
 (London), 1911, ii, 1625; see also L'pool Med.-Chir. J., 
 
 1913, xxxiii, 398. 
 2^ Bazzochi (A.): Sulla istoterapia del tumori maligni dell' uomo, 
 
 Tumori (Rome), 1913, iii, 320. 
 2^ Editorial: The study of new growths. Lancet (London), 1914, 
 
 i, 478. 
 2^ Billard (M.): Essai d'opoth^rapie anticancereuse, Centre med. 
 
 etpharm. (Gannat), 1909, xiv, 319. 
 29 Williams (L.): Introduction to the Special Hormone Number 
 
 of the Prescriber (Edinburgh), 1913, vii, 89. 
 
 R]enon (L.): Les syndromes polyglandulaires et I'opotherapie 
 associee, Eev. gen. d. clin. et d. ther. (Paris), 1908, xxii, 
 465. 
 
 Rknon (L.) and Delille (A.): Sur les effets des extraits 
 d'hypophyse, de thyroide, de suiT^nale, d'ovaire employes en 
 injections intrap6riton6ales (simples et corabin6es) chez le 
 lapin, 0. r. Soc. Biol. (Paris), 1908, Ix, 1037. 
 
 Editorial: The effects of the ductless glands upon develop- 
 ment, N. T. Med. J., 1913, xcvii, 781. 
 
 Claude (H.) and Gougerot (H.): Sur I'insuffisance simultan^e 
 de plusieurs glandes a secretion interne (insuflflsance j)luri- 
 glandulaire), G. r. Soc. Biol. (Paris), 1907. li, 785. 
 
 Id. : Les syndromes d'insuffisance pluriglandulaire, Leur place 
 en nosographie. Rev. d. med. (Paris), 1908, xxviii, 861, 950. 
 
 Id. : Insuffisance pluriglandulaire endocrinienne (premiere 
 memoire), J. d. physiol. et d. path. gen. (Paris), 1908, x, 469; 
 (deuxiemo memoire), ibid., 505.
 
 The Use of Pluriglandular Extracts 427 
 
 Lavastine (L.): Des troubles psychiques par perturbation des 
 
 glandes a secretion interne, Bev. neurol. (Paris), 1908, xvi, 
 
 836. 
 Claude (H.): L'opotherapie uni ou pluriglandulaire comme 
 
 adjuvant du traitement bromure dans I'epilepsie, Clinique 
 
 (Paris), 1912, vii, 257. 
 Naam^! (M.): " ifitudes d'Endocrinologie " (Paris), 1913, p. 46. 
 McNaught (H. Y.): Ductless gland extracts in relation to ear 
 
 affections, Col. State J. Med. (San Francisco), 1913, xi, 470.
 
 CHAPTER XXXI 
 
 THE CONTROL OF HYPERENDOCRINISM 
 
 The Use of Antagonist Hormones — Surgical Procedures — The 
 Value of the X Bay — Rontgenotherapy in Exophthalmic 
 Goitre — The Treatment of the Thymus in Graves's Disease — 
 The Combined Treatment of Hyperpituitarism — The Reduc- 
 tion of Blood-Pressure by X-Ray Exposures. 
 
 HYPERENDOCRINISM, as Contrasted with its opposite 
 hypoendocrinism, is fortunately a much more infrequent 
 condition, and clinically is not even a recognized entity. 
 There are, however, a number of conditions due to the 
 overactivity of certain endocrinous glands which already 
 liave been mentioned in the previous pages as occasion 
 demanded. Some general principles may be gathered 
 together in a short chapter upon the control of endo- 
 crinous overactivity. 
 
 The Use of Antagonist Hormones. — If a condition of 
 hyperendocrinism is functional in character — that is to 
 say, if there is no evident change in the structure of the 
 affected organ — recourse may be had to the administration 
 of hormone-bearing preparations that are known to have 
 an opposing action to the secretion which, by its excess, 
 is the cause of the trouble. This, we have seen, is occa- 
 sionally possible in certain forms of Graves's disease by 
 the administration of thymus extract ; and adrenal extract 
 was considered by Gibson^ to be a remedy par excellence 
 in this condition. In hyperovaria good results have 
 been ascribed to the use of pituitary or mammary extracts, 
 
 428
 
 The Control of Hyperendocrinism 429 
 
 and, more rarely, in hyperadrenia by recourse to pancreas 
 preparations. In osteomalacia due to excessive ovarian 
 activity, rather than mutilate the patient, Blair BelF 
 urges that pituitary and adrenal preparations should first 
 be given a thorough trial. 
 
 Unfortunately, however, hyperendocrinous conditions 
 are rarely functional, and the control of an organic change 
 by the administration of antagonist hormones is not very 
 satisfactory, although it is a sufficiently reasonable pro- 
 cedure to warrant its trial whenever feasible. 
 
 Surgical Procedures. — The surgical removal of offending 
 organs, in part or wholly, has been practised for a number 
 of years. Theoretically the results have been fairly good, 
 although by no means as uniform as might be expected. 
 Surgical interference, too, often goes farther than is best 
 for the patient ; for while overactive glands are a decided 
 inconvenience, the absence of important organs is often 
 of equal detriment to the maintenance of a physiological 
 harmony. Ovariotomy is a most serious step, and total 
 excision of these organs should only be resorted to in 
 extreme cases and where absolutely necessary. 
 
 A combination of surgery and hormone therapy is 
 occasionally useful, and it is quite common to remove 
 a part of an enlarged thyroid, or to operate upon the skull 
 to decompress the brain in pituitary disease, and supple- 
 ment such treatment with organotherapy. 
 
 The Value of the X Ray. — Workers with the Rontgen 
 ray have too often found out the remarkable antagonistic 
 action that this ])hysical ])Ower has upon endocrinous 
 tissue. It may even be that the senile changes in the 
 skin — that unhealthy, dried-up appearance which used 
 to be so commonly seen in Rontgenographers — as well as 
 the tendency to cancerous degeneration, is the result of 
 an artificial hypoendocrinism due to the action of the
 
 430 Practical Hormone Therapy 
 
 rays. It is certain that exposures to the X ray produce 
 sterihty, both in the male and female, and therapeutic 
 use frequently has been made of this fact in the treatment 
 of hyperovaria. 
 
 This method may be also used to reduce, rather than to 
 suppress, glandular overactivity; and by careful dosage 
 the results of the excessive secretion lessened without 
 causing atrophy and the equally bad effect of entire 
 absence of the hormones. Zimmern and Cottenot^ have 
 suggested that when a gland is in a state of functional 
 overactivity, it is more sensible to the influence of the 
 X ray, and that in such cases radiotherapy is particularly 
 effective. 
 
 Rontgenotherapy in Exophthalmic Goitre. — There is 
 considerable literature on the treatment of Graves's 
 disease by means of X-ray exposures, and the reports are 
 somewhat conflicting. It can be said that in general this 
 treatment reduces the thyroid activity, but does not 
 always do it sufficiently well or permanently. Murray"* 
 believes that " the application of suitable doses of X ray 
 to the enlarged thyroid gland has in some cases proved 
 to be of great value. The gland gradually diminishes in 
 size, and the other symptoms subside. Atrophic changes 
 in the secretory epithelium, and both interstitial and 
 extracapsular fibrosis, appear to be induced by the action 
 of the rays. . . . These changes are slow in development, 
 so that the full effect of the treatment is not obtained 
 until some months have elapsed. In favourable cases 
 fifteen to twenty doses of the rays have been sufficient 
 to bring about great improvement or practical recovery, 
 but in others only slight improvement has followed a 
 similar course of treatment. It is worth while to per- 
 severe with X-ray treatment for as long as a year if slow 
 but satisfactory progress is being made. We have, more-
 
 The Control of Hyperendocrinism 431 
 
 over, still much to learn of this valuable method of treat- 
 ment." 
 
 The Treatment of the Thymus in Graves's Disease. — 
 Persistence or hypertrophy of the thymus is quite a 
 common finding in exophthalmic goitre, and since 
 Capelle's^ first reference to this subject, the literature 
 carries the conviction that the thymus is concerned in 
 this disease, and that hypertrophy of this organ is not 
 simply a coincidence. Thymectomy is advised where the 
 gland is demonstrable, but Lenormant*^ advises recourse 
 to the X-ray treatment as a preliminary. Its elective 
 influence upon the ductless glands may be of service, and 
 reports are on record of the value of this treatment. If, 
 however, little or no benefit is obvious, recourse to surgical 
 removal of the gland is indicated, the field of operation 
 frequently being extended to the thyroid. 
 
 The favourable influence of the Rontgen treatment of 
 thymus hypertrophy is further emphasized by the report 
 by Luzzati'^ of the successful treatment of two cases of 
 thymic asthma in children. He considers that recovery 
 may usually be induced by a prolonged course of treat- 
 ment, and that the X rays may be used as a prophy- 
 lactic in cases with the signs of latent thymic en- 
 largement. 
 
 The Combined Treatment of Hyperpituitarism.— In 
 hyperpituitarism, too, the X rays have been used, and 
 occasionally have rendered good service. This has 
 occurred sufficiently often to be convincing evidence that 
 the rays have an action upon this gland similar to that 
 which they exercise upon the ovaries or testes in spite 
 of the intervening bone; but we are not destined to find 
 so easily as this the means whereby such a condition 
 may be controlled. Surgical measures are now often 
 used, and are especially helpful in relieving the local
 
 432 Practical Hormone Therapy 
 
 symjitoms due to the pressure, and at times also by the 
 removal of a portion of the gland. 
 
 Gushing^ advises combining surgery and Rontgeno- 
 therapy, and has this to say of the value of such proce- 
 dures: " In some of our more recent cases the results [of 
 the X rays as a means of controlling the advance of a 
 strumous hyperplasia] have been so encouraging as to 
 justify a word in regard to this therapeutic adjunct to 
 the operative measures. Certain observations show that 
 in certain forms of hypophyseal tumour prolonged 
 Rontgenization has a notable effect in ameliorating the 
 neighbourhood symptoms. A widening of the constricted 
 fields of vision serves as a reliable index of any diminution 
 in the size of the struma. These results are explicable 
 on the gromid of the elective sensitivity of certain cells 
 to the action of the Rontgen rays; and it would appear 
 that neoplastic cells of epithelial type are particularly 
 prone to undergo atrophy without inflammatory reaction 
 under prolonged exposiures. Hence, in view of the fact 
 that the surgical measures at our disposal are merely 
 palliative and directed toward neighbourhood symptoms 
 alone, and in the case of an advancing struma are in no 
 sense curative, it is possible that radiotherapy should 
 often be employed as a supplementary measure. In 
 several cases after almost complete blindness, vision has 
 been restored under the combination of partial surgical 
 removal of the struma and subsequent repeated ex- 
 posures." 
 
 The Reduction of Blood-Pressure by X-Ray Exposures. 
 — Presuming that hypertension is in many cases a result 
 of hyperadrenia, Zimmern and Cottenot^ have attempted 
 to reduce excessive blood-pressure by exposing the 
 adrenals to the X ray. The technique of their method 
 is outlined in their paper and in a previous one,'-^ which 
 
 I
 
 The Control of Hyper endocrinisrn 433 
 
 was read before the Societe de Biologie of Paris. They 
 are convinced that material reductions (from 10 to 70 
 millimetres Hg.) of the tension are in this way made 
 possible, and that this new application of radiotherapy 
 is an effective and rational method. 
 
 BIBLIOGRAPHY 
 
 ^ Gibson (G. A.): Tlie relations of the circulation, Br. Med. J. 
 (London), 1912, ii, 163. 
 
 2 Blair Bell (W.): The genital functions of the ductless glands 
 
 in the female, Lancet (London), 1913, i, 809, 937. 
 
 3 ZiMMERN (A.) AND CoTTENOT (P. H.): Traitemeut par les 
 
 rayons X des glandes a secretion interne en etat d'hyperac- 
 
 tivit6, Pr. med. (Paris), 1914, xxii, 133. 
 * Murray (G. R.): Some aspects of internal secretion in disease, 
 
 Br. Med. J. (London), 1913, ii, 163. 
 ^ Capelle (A.) : Ueber die Beziehungen der Thymus zum 
 
 Morbus Basedow, Beitr. z. Tel. Chir. (Tiibingen), 1908, Iviii, 
 
 353. 
 ^ Lenormant (C): La thymectomie dans la goitre exophthal- 
 
 mique, Pr. med. (Paris), 1914, xxii, 126. 
 ' LuzzATi (T.): Contributo al trattamento radioterapico dell' 
 
 ipertrofia del timo (asma timico), Eevista Osped. (Rome), 
 
 1913, iii, 689. 
 ^ Gushing:* p. 321. 
 ^ ZiMMERN (A.) AND CoTTENOT (P. H.): Modifications de la 
 
 pression arterielle chez I'homme par 1' exposition aux rayons 
 
 X de la region surrenale, C. r. Soc. Biol. (Paris), 1912, Ixxii, 
 
 676; see also Sergent (E.) and Cottenot (P. H.): L'irra- 
 
 diation des glandes surr6nales dans da th6rapeutique de 
 
 r hypertension, Pr. med. (Paris), 1914, xxii. 177. 
 
 29
 
 CHAPTER XXXII 
 
 MISCELLANEOUS EXTRACTS OF MINOR VALUE 
 
 SpecAilative Worh with Animal Extracts — The Use of Extracts 
 of Epithelium — An Extract of Heart Muscle — Bone Sub- 
 stance in Demineralized States — Ophthalmic Organotherapy 
 
 For the sake of completeness it may be weU to mention 
 certain other forms of organotherapy which are occa- 
 sionally used, but the value of which is still quite proble- 
 matir. 
 
 Speculative Work with Animal Extracts. — Doubtless the 
 fundamental principle of organotherapy has caused a 
 good deal of speculative clinical work to be done, and 
 results which may have followed this work have naturally 
 been credited to the treatment which was uppermost in 
 the mind of the attending physician, while it is entirely 
 probable that in many cases purely concomitant circum- 
 stances were responsible for any benefit that accrued. 
 This is still the position of the sceptic in regard to nine- 
 tenths of all forms of organotherapy. 
 
 Now that the science of the chemical correlation of the 
 various parts of the body by means of hormones has been w 
 generally recognized, and the extremely complex condi- 
 tion of the body fluids is beginning to be appreciated, not £ 
 a few prospectors in this vast field have presumed that 
 not only the endocrinous organs per se are concerned in 
 maintaining this balance, but, as Blair Bell has said, " it 
 is probable that every cell of the body is a ductless gland, 
 and has some influence on the life and functions of the 
 
 434
 
 Miscellaneous Extracts of Minor Valve 435 
 
 rest. But at present such a conception exists only as a 
 dream in the minds of philosophical biochemists." Not 
 a few physicians, especially m France, have attempted to 
 materialize this dream. That they have done so in many 
 instances is beyond question, as, it is hoped, previous 
 chapters in this book have made clear, but it would seem 
 that considerably more has to be learned and much sup- 
 plementary work done before general use will be made of 
 the several organotherapeutic preparations which will 
 now briefly be referred to. 
 
 The Use of Extracts of Epithelium.— In France an occa- 
 sional reference is found in books devoted to organic 
 medication, as well as in the literature, to what has been 
 called " cutaneous opotherapy." It is well known that 
 keratin is prepared from epidermal substance, and, of 
 course, is in regular use as a means of preventing the 
 disintegration and absorption of drugs in the stomach 
 which are given by mouth, and are intended to be princi- 
 pally active m the intestine. Zypldn has attributed 
 therapeutic properties to this substance, and suggests 
 that it prevents interstitial fibrosis following chronic 
 inflammations of different organs. 
 
 Certain conditions in which there is a considerable 
 involvement of the skin have been supposed to be bene- 
 fited by treatment with extract of skin, and it has been 
 applied following extensive burns and certain dermatoses, 
 chief among which is the exfoliating form of dermatitis. 
 
 Carnot has suggested that preparations of skin might 
 be used in burns, but, generally speaking, the therapeutic 
 indications (the keratin coating of pills is hardly to be 
 considered as a therapeutic agent) of cutaneous extracts 
 are scarcely worth considering. 
 
 An Extract of Heart Muscle. — In myocardial disorders, 
 where there is particular insufficiency of the heart muscle,
 
 436 Practical Hormone Therapy 
 
 extracts of the heart itself have been recommended. 
 These are said to have a restorative and tonic action. 
 
 Bone Substance in Demineralized States. — Preparations 
 of bone are recommended in certain quarters as a means 
 of recalcifying the system. They must, of course, not be 
 confounded with bone marrow, which is a totally different 
 thing. 
 
 Robin has put quite a scientific aspect upon the use of 
 preparations of bone as a means of treating the deficiencies 
 of calcium and mineral salts which are often associated 
 with tuberculosis. The basis of this method is the fact 
 that calcium salts of an organic nature are more easily 
 assimilated and fixed by the tissues than the calcium salts 
 in general use. In a communication by Brunet, in the 
 Annates de Therapeutique Scientifiqiie, we read : " The only 
 calcium preparations easily assimilated are those which 
 are given in the food, and this explains why they are 
 found in this organic form, because phosphates, car- 
 bonates, chlorides, and iron salts are absorbed by vege- 
 table or animal tissues, and become a component part of 
 their constitution. Thus, in the treatment of deminer- 
 alized conditions, one should employ organic recalcifying 
 bodies, and there is no other than powdered bone. The 
 osseous tissue is the body's storehouse of calcium salts, 
 and this store of calcium varies with the physiologic needs. 
 In order to supply its lack of calcium, the body draws 
 upon the reserve of salts in the bone, and in the assimila- 
 tion of these salts nothing is lost, and the absorption by 
 the tissues is complete, but, of course, this is a detriment 
 to the bones — a fact which has been noticed frequently 
 in disorders of calcium metabolism." 
 
 It is quite possible that the calcium and other salts 
 which constitute the mineral part of bone are funda- 
 mentally different from those obtained by chemical 
 
 1
 
 Miscellaneous Extracts of Minor Value 437 
 
 means. Much regarding this work has yet to be done. 
 Suffice it to say that suitably prepared powders of bone 
 are recommended as a means of supplying the specific 
 lack in what is called the " demineralized states," and a 
 number of prominent men, chief among whom is Pro- 
 fessor Robin of Paris, have expressed their faith in this 
 method of treatment. 
 
 Ophthalmic Organotherapy. — Last, and probably least, 
 of the minor organotherapeutic agents are certain products 
 of the eye itself. The ciliary body has been used in certain 
 ophthalmic affections (principally irido-cyclitis), and even 
 extracts of the crystalline lens of the eyes of young cattle 
 have been used in Germany in the attempt to influence 
 the onset of threatening cataract. It is stated that a 
 course of such treatment has benefited vision, and caused 
 an amelioration of the condition in the lens.
 
 CHAPTER XXXIII 
 
 THE PREPARATION OF ANIMAL EXTRACTS FOR 
 THERAPEUTIC PURPOSES 
 
 The Selection of the Fresh Glands — The Treatment of Excised 
 Glands — The Preparation of the Extract — The Physical 
 Form of Animal Extracts — The Present Methods of Stan- 
 dardization — The Estimation of Dose Units. 
 
 In the preparation of active, efficient organothera- 
 peutic extracts several important points must be ob- 
 served. There are not a few second-rate preparations 
 on the market, and their use has not strengthened the 
 position of " hormone therapy." The crude, old-fashioned 
 methods of our ancestors no longer hold good. Scientific 
 methods must be followed in order to obtain the highest 
 degree of activity, as well as a definite standard thereof. 
 Nomenclature, too, is in a most chaotic state. 
 
 The Selection of the Fresh Glands.— It need scarcely be 
 said that everji,hing depends upon the selection of the 
 crude material, and experience has shown many points 
 which make for more effective preparations, and there- 
 fore more satisfactory results. 
 
 The selection of the species of animal from which to 
 secure the organ, the physical condition of these animals, 
 their age, and even the state of certain physiological 
 functions at the time of killing, are all evidently im- 
 portant factors. The species depends upon what organ 
 is required; and it has become customary (though by no 
 means an invariable rule) to take thyroids from sheep, 
 
 43S
 
 Animal Extracts for Therapeutic Purposes 439 
 
 adrenals from sheep or calves, pancreas from cattle or 
 pigs, ovaries from pigs or goats, testes from boars or 
 guinea-pigs, etc. The physical condition of the animals 
 must necessarily be good, and the optimum age naturally 
 depends upon the glands desired. The gonads, for 
 example, are secured from adults, the thymus from the 
 young, and in some cases, as with bone marrow, the crude 
 product is obtained preferably from the foetus. In 
 general, old animals in which development has ceased 
 are not suitable, and the best preparations are made from 
 the glands of animals in the height of development. 
 
 The relation of certain physiological states, such as 
 the height of digestion or sexual excitement, the reac- 
 tion to certain infections (as in the case of the spleen in 
 tuberculosis — see p. 139), and pregnancy, must be also 
 considered. Naturally it is desirable to secure an organ 
 at a time when it is in a state of maximum activity or 
 contains the largest possible amount of its active prin- 
 ciples. Unfortunately, in practice this is not always an 
 easy matter, especially when the manufacture is on a 
 large scale. 
 
 The Treatment of Excised Glands.— After having se- 
 lected the gland, it is cut out and very carefully freed 
 from surrounding fat and tissue. Some have urged 
 aseptic precaution in the recovery of the glands, sug- 
 gesting sterile instruments, receptacles, etc. This seems 
 hardly necessary, although, of course, cleanhness, not 
 necessarily surgical, is essential. 
 
 In certain cases only parts of the organs are used. 
 In the preparation of the most satisfactory ovarian 
 products the corpus luteum is selected; in pituitary 
 preparations the infundibulum is used; in the prepara- 
 tion of the adrenal principle the medulla is more suitable 
 than the cortex or the whole gland, while the internal
 
 440 Practical Hormone Therapy 
 
 secretion of the pancreas (the Langerhansian hormone) 
 is naturally more abundant in that part of the pan- 
 creas where there are most islets — namely, the tail of the 
 pancreas. 
 
 It is essential that foreign tissue be rejected, and this 
 is especially true with extracts of such small glands as 
 the parathyroids. This is a common stumbling-block 
 to success in the manufacture of active products. 
 
 The Preparation of the Extract. — This is often a com- 
 plex procedure, and is susceptible of many variations. 
 The subject is too broad to receive more than passing 
 mention, especially when its consideration is large enough 
 to fill a book.* 
 
 The largest number and volume of preparations used 
 in opotherapy consist of "total extracts" — i.e., desic- 
 cated gland powder. Carnot considers it preferable, at 
 least at present, not to attack the molecular structure 
 of these organs by violent chemical procedures, but to 
 utilize them as nearly as possible in their hving condi- 
 tion. 
 
 The most satisfactory means of drying the pulp of 
 animal substances is i)h vacuo. The rapidity with which 
 this can be accomplished and the fact that the use of "^ 
 heat may be obviated make this the method par excel- 
 lence. Choay, as a result of a most careful series of 
 experiments in association with Gilbert and Carnot, and 
 also many years of practical experience, states that "the 
 method of choice is that which brings about an ex- 
 tremely rapid desiccation not only in vacuo, but without 
 heat." 
 
 Choay's table — a part of which is included here — gives 
 a very good idea of the average amount of water ex- 
 tracted in this manner, and that the averages are well 
 
 * See Clioay* in " List of Books" (Appendix).
 
 Animal Extracts for Therapeutic Purposes 441 
 
 balanced is evident from the fact that the figures for 
 pituitary, ovary, and thyroid are based upon the desic- 
 cation of 3,621 of the first, 8,863 of the second, and 9,012 
 of the last-named glands. 
 
 Organ. 
 
 Animal generally 
 
 Percentage of Dry 
 
 Used. 
 
 Extract. 
 
 Adrenal 
 
 Sheep 
 
 20 
 
 Duodenum 
 
 Pig 
 
 1.5 
 
 Hypophysis 
 
 Cattle 
 
 22 
 
 Kidney 
 
 Pig 
 
 20 
 
 Liver 
 
 Pig 
 
 30 
 
 Lung 
 
 Calf 
 
 20 
 
 Mammpe 
 
 Cow 
 
 20 
 
 Nerve 
 
 Pig 
 
 33 
 
 Ovary 
 
 Sow 
 
 16 
 
 , 
 
 Cow 
 
 13 
 
 Pancreas 
 
 Pig 
 
 30 
 
 Parathyroid 
 
 Horse 
 
 22 
 
 Placenta 
 
 Ewe 
 
 14 
 
 Prostate 
 
 Horse 
 
 20 
 
 Spleen 
 
 Pig 
 
 23 
 
 Stomach 
 
 Pig 
 
 20 
 
 Testes 
 
 Bull 
 
 12 
 
 Thymus 
 
 Calf 
 
 17 
 
 Thyroid 
 
 Sheep 
 
 25 
 
 >> 
 
 Cattle 
 
 28 
 
 The Physical Form of Animal Extracts. — It has already 
 been intimated that a very chaotic condition obtains in 
 the present - day nomenclature of organotherapeutic 
 products, and the exigencies of trade seem to militate 
 against a satisfactory solution of the difficulty. 
 
 There are certain basic fonns in which these prepara- 
 tions are put up: 
 
 1. The gland substance itself, fresh or preserved in 
 syrup or confections. This form has all but gone out of 
 general usage, as it is uncertain and inconvenient. 
 
 2. Dried and powdered glands — a common and con- 
 venient form, since they may be put up in suitable units 
 as powders, tablets, cachets, and capsules. The suffix
 
 442 Practical Hormone Therapy 
 
 ine has been suggested as a means of identifying this class 
 (adrenahne, hepatine, etc.), but in the present state of 
 affairs the suggestion is quite impossible of consistent 
 application. 
 
 3. Gland substance powdered by trituration with an 
 inert body (usually milk-sugar) " till extinguished " — 
 i.e., until an impalpable combination is made. This 
 mixture is then divided into certain doses, which have a 
 definite relation to the weight or number of the fresh 
 glands. This is the usual method of the pioneer manu- 
 facture of organotherapeutic preparation. 
 
 4. The vacuum-dried gland, which has been treated 
 by dissolving out, digesting, or otherwise removing certain 
 substances which are nauseating, antagonistic to the 
 normal physiological action of the product, or generally 
 superfluous and unnecessary. In Germany the suffix 
 aden has been used to indicate these repurified products 
 (renaden, thyraden, etc.). 
 
 5. Extracts made by means of the usual solvents, 
 chief among which are water, saline solution, and glycerine. 
 These are used principally for hypodermic, and occa- 
 sionally for intravenous, administration. 
 
 6. Basic substances prepared by complex chemical 
 procedures and in th« best state of purity. Frequently 
 these are obtainable as salts of acid radicles {e.g., adrenahne 
 hydrochloride, hypophysin sulphate, etc.). They are put 
 up in standard dilutions, and may be given by any of the 
 usual methods. 
 
 The Present Methods of Standardization. — The better- 
 known hormone preparations — adrenal, pituitary, thy- 
 roid — ^are generally physiologically and chemically stan- 
 dardized, although the accuracy with which one can 
 standardize, say, adrenaline is not attainable in many 
 other animal extracts. Products containing the active
 
 Ani7nal Extracts for Therapeutic Purposes 443 
 
 principle of the adrenal glands, being in definite chemical 
 form, are always standardized by their blood-pressure 
 figure, and are the simplest of the ductless glands for 
 standardization. 
 
 The activity of preparations made from the posterior 
 lobe of the pituitary body is also estimated by animal 
 experiment, as these preparations are valued by their 
 blood-pressure-raising properties and by their power of con- 
 tracting the isolated uterus. The estimation of the action 
 upon blood-pressure is the method commonly adopted, 
 but it is obvious that the action upon uterine contrac- 
 tihty is the more useful, as the principal therapeutic use 
 to which these preparations are put is on account of 
 their power of contracting involuntary muscle. 
 
 The iodine coefficient is the present standard in the 
 preparation of thyroid extracts; but it is by no means 
 certain that the chemical standards are sufficient, and 
 that the therapeutic effectiveness of two different ex- 
 tracts of thyroid, each conforming to the recognized 
 standard, will be the same ; for, after all, the activity of 
 this preparation cannot be solely due to its iodine 
 content. Beebe's method of securing the most active 
 thyroid preparations has already been outlined in 
 Chapter XIII. 
 
 The gist of numerous reports of experiments to deter- 
 mine the activity of several organotherapeutic prepara- 
 tions will be found in a valuable little book called " Physi- 
 ological Criteria for Medicinal Substances." 
 
 Physiological tests on animals are now generally used 
 by the more progressive manufacturers, and this seems 
 to be a very wise and beneficial advance, although in this 
 manner one can ascertain only in a very limited way 
 the uniformity of the preparations. Still greater pro- 
 gress is anticipated in the near future, and much experi-
 
 444 Practical Hormone Therapy 
 
 mental Avork is being done to bring the preparation of 
 animal extracts to the highest possible plane. 
 
 The Estimation of Dose Units. — Practically all the 
 preparations on the market are put up in definite doses. 
 The ampoules contain a certain amount (usually 1 c.c. 
 of a solution containing a definite amount of the active A' 
 principle), while the tablets, capsules, and cachets are all f^ 
 supposed to represent certain uniform quantities of the M^ 
 various extracts. These amounts vary very little, and |S 
 usually represent an average dose; hence the manufac- 
 turers, in a measure, are standardizing dosage. Their 
 arbitrary quantities are invariably based upon chnical 
 work, and thus facilitate the general application of this 
 method of treatment, and obviate possible trouble in the 
 early experiences of the physician with its apphcation. 
 It must be emphasized, however, that while the average 
 dose of parathyroid or adrenal extract is invariably in 
 miUigrammes or fractions of a grain, and of spleen 
 or liver extracts in grains or even grammes, the 
 manufacturer's dose unit must be considered only 
 as a unit of (convenience, and not as a hard-and-fast 
 standard. 
 
 As a matter of fact, the dosage of animal extracts is 
 just like that of the alkaloids or any other drugs; the 
 desired result should be the criterion, and enough should 
 be given to accomplish this. Where one case will respond 
 to a smaU dose, another may require many times the 
 amount, and this fact proves a stumbing-block to many. 
 They presume that the manufacturer's unit is the criterion, 
 and are satisfied to give " two tablets three times a day 
 after meals," instead of acquainting themselves fully 
 with all the factors concerned — the disease to be treated, 
 the minimum dose, its expected influence, and the 
 evidences of reaction to the remedy — and then regulating
 
 Animal Extracts for Therapeutic Purposes 445 
 
 the dosage to fit the case, and using this treatment 
 scientifically. 
 
 Even the makers of pharmacopoeias have fallen into 
 this common error. The British Pharmacopceia gives 
 the dose of thjrroid extract as " 2 to 10 grains," when the 
 average dose should be | grain or less. Indeed, in the 
 case of a cretin, no definite dose can be laid down, except 
 quantum sufflcit.
 
 CHAPTER XXXIV 
 
 THE LIPOIDS 
 
 What the Lipoids are — An Evident Deioxicating Action — Other 
 Physiologic Activities of Various Lipoids — Iscovcsco's 
 Experiments — Homostimulants — The Adrenal Lipoids — 
 A Lipoid from the Pancreas which stimulates the Liver — The 
 Pituitary Lipoid — The Thyroid Lipoid — The Splenic 
 Lipoid in Tuberculosis — The Lipoids obtained from the 
 Gonads. 
 
 Certain of the cells of the body, and particularly 
 those which constitute the structure of the internal 
 secretory organs, have been shown to contain a series of 
 fat-like substances which may be extracted by means of 
 organic solvents. These fatty bodies have been called 
 "lipoids," and evidently have certain definite functions 
 to perform. In a sense they are related to the hormones, 
 for while there is no proof that they influence remote 
 organs through humoral channels, they do exert, both 
 experimentally and chnically, a decided homostimulant 
 influence upon the organs to which they correspond. 
 
 What the Lipoids are. — From the researches of recent 
 years, notably those of Iscovesco of Paris, we must con- 
 clude that the action of the lipoids in physiology is of 
 such a character that it may be applied in therapeutics. 
 As a matter of fact, it has even been suggested that the 
 lipoids are none other than the active principles of the 
 various animal extracts at present in fairly general use.. 
 
 It must be remembered, however, that the term 
 " lipoid " is a broad one, and that it covers all the sub- 
 
 446
 
 The Lipoids 447 
 
 stances that cannot be saponified as fats, but can be 
 extracted by means of ether, chloroform, alcohol, acetone, 
 etc. This includes the phosphatides, of which lecithin is 
 the best-known example, and cholesterin, a very similar 
 substance, which does not have a phosphorus mole- 
 cule. Stepp has laid emphasis on the fact that the 
 physiologic and therapeutic value of the lecithins is 
 practically limited to those lecithins which are produced 
 by the living organism to forward its own functional 
 activities. 
 
 It is very clear, however, from the work of Iscovesco, 
 that a number of additional Upoid-like substances — they 
 are still called "lipoids" — differ from the better- known 
 products of this nature (cholesterin, lecithin, etc.), and 
 resemble much more closely the other active substances 
 of the ductless glands; hence notice of them is taken in 
 this book, and a brief resume of our present knowledge 
 of their action and value is given here. 
 
 An Evident Detoxicating Action. — Overton and Meyer 
 were among the first to report upon the influence of cer- 
 tain of the lipoids upon poisons and toxins, and their 
 early investigations showed that the lipoids have a soluble 
 action upon narcotics. More recent work has amphfied 
 these observations, and Nerking and Reichert state that 
 the administration of certain lipoids into the blood- 
 stream thus diminishes or entirely eliminates the narcotic 
 effect, and, even more important than this, that the 
 lipoid content of various organs may be extracted or 
 used up by means of the administration of narcotics or 
 an excess of the toxins in the blood. This detoxicating 
 action of the lipoids is of considerable significance in 
 cellular physiology, and the fact that this capacity 
 remains in the lipoids after extraction from the mother- 
 cell- aggregate gives us another means of controlling cer-
 
 448 Practical Hormone Therapy 
 
 tain conditions in which general as well as specific toxaemias 
 are constant.* 
 
 Other Physiologic Activities of Various Lipoids. — The 
 fact that hpoids are found in practically all the various 
 cell collections of the body and in some of its fluids 
 indicates in a measure their importance. It is necessary 
 to emphasize the fact that they have absolutely no con- 
 nection, either physically or chemically, with fats. In 
 1908 Iscovesco showed that the normal thjnroid contained 
 a series of lipoids, one of which had the remarkable 
 property of provoking tachycardia with exophthalmos, 
 and among numerous points since emphasized by this 
 investigator is the fact that there undoubtedly are specific 
 lipoids existing in each organ, some of which are antag- 
 onists and others synergists, and that by suitable means 
 these useful lipoids may be extracted and used as a 
 means of physiologically stimulating the organs in ques- 
 tion. Then, too, antagonistic hpoids which may be 
 present in animal extracts, thereby detracting from the 
 desired physiologic action to be gained from their adminis- 
 tration, may be removed by suitable solvents, and a more 
 convenient preparation thus be obtained. This has been 
 done in the case of thyroid extract, as referred to on 
 p. 208. 
 
 Iscovesco's Experiments. — Most of the experimental 
 work in this direction has been carried out by Iscovesco 
 in the physiological laboratories of the Sorbonne in Paris. 
 Generally speaking, the majority of the experiments con- 
 sisted in injecting minute doses of preparations of this 
 
 * In Chapter XXI. reference is made to the detoxicating action of brain 
 substance, which is one of the richest in lipoids of all the organs. The 
 therapeutic action of lecithin and the cholesterins can only be mentioned in 
 passing, as the limits of the scope of this book preclude a more extended study 
 of the subject. For a concise resume of the whole subject of lecithin, its 
 physiology and uses, the reader is referred to "Merck's Annual Report," 1912, 
 XXXVI., pp. 1-71.
 
 The Lipoids 449 
 
 character into rabbits, and continuing the treatment 
 for varying periods. The various phenomena which 
 appeared were carefully noted, and finally, after suitable 
 periods, the animals were killed, and the different organs 
 systematically examined, particular attention being paid 
 to their respective weights. Control experiments with 
 other animals, frequently of the same Utter and always 
 of the same age, weight, and sex, in identical conditions of 
 life, were made. Details of these hundreds of experiments 
 and the figures connected with them must manifestly be 
 omitted, and only the essential deductions made, 
 especially those which may have a therapeutic applica- 
 tion. 
 
 An attempt was made to duplicate in man a number 
 of the results of experiments made on animals, and as a 
 result of this work a series of lipoid preparations have 
 now become available in commerce.* 
 
 The Adrenal Lipoids. — From the cortex of the adrenal is 
 secured a hpoid which provokes hypertrophy of the 
 cortex of the adrenal glands, but exercises no influence 
 whatever upon arterial pressure. It also excites the 
 kidneys and fiver very slightly, and possesses a peculiar 
 stimulating action upon the hair folficles. Iscovesco 
 refers to the use of this preparation in man in the follow- 
 ing terms: "I have had occasion to try this preparation 
 several times in man. When 2 to 5 c.c. are injected into 
 the adult, the following three phenomena appear: 
 (1) Marked acceleration of heart pulse, the beats in- 
 creasing from 70 to 90 beats, and even more, in the first 
 
 * The '^Lipoides H. 7."(homostimulant and for injection) cover practically 
 the whole range of the ductless glands and other endocrinous organs, and are 
 prepared in Carrion's Laboratoire de Biologic in Paris. The makers perti- 
 nently state that "the lipoides H. I. represent the active and specific sub- 
 stances of each organ, just as the alkaloids represent the specific substance of 
 the plants." These preparations are dissolved in oil, the dose is standardized, 
 and they are obtainable in ampoules. 
 
 29
 
 450 Practical Hormone Therapy 
 
 two or three hours following the injection. This in- 
 crease of the pulse is accompanied by a diminution of 
 the arterial tension. These phenomena are variable, 
 and disappear after a few hours. (2) Very frequently 
 (in 60 per cent, of the cases) abundant perspiration is 
 produced, which sometimes continues for twenty-four 
 hours, and is usually nocturnal. I have thought that 
 this phenomenon may be connected with that which I 
 have previously referred to in regard to the stimulation 
 of the growth of hair in my rabbits. This fact may also 
 be an explanation of the nocturnal sweats of phthisis, 
 which may be explained by a stimulation of the cortical 
 part of the adrenals. (3) In cases where the adrenal 
 cortex lipoid is given in daily doses of from 1 to 2 c.c. 
 there is an increase of energy and a feeling of well-being 
 which is particularly noticeable in the cachectic affec- 
 tions." 
 
 There is also another lipoid which is secured from the 
 adrenal medulla. Its administration slightly stimulates 
 these organs, but in a much less degree than the cortical 
 lipoid. Further, this stimulation is confined particu- 
 larly to the medullary portion of the glands, because in 
 man this lipoid causes an increase of the arterial pressure 
 and a reduction of the pulse. In animal experiments it 
 has been found that injections covering a period of two 
 months produce a decided influence upon the size and 
 weight of the heart. The average weight of the controls 
 was 2- 69 grammes per kilo, while in the treated animals 
 this average was increased to 3- 80 grammes per kilo. 
 Clinically, Iscovesco and others have used this medullary 
 lipoid especially in tuberculosis, with the following results : 
 (1) A decrease in the pulse and an increase of tension, 
 which lasts twenty-four hours or more. (2) A decided 
 feeling of well-being, which is particularly noticeable
 
 The Lipoids 451 
 
 in those cases of pulmonary tuberculosis accompanied by 
 hypotension. (3) A much greater aptitude for work 
 during the period of treatment. 
 
 It is interesting to note that further facts showing a 
 relation between the lipoids and tuberculosis have been 
 brought forward by Grinlew, who found in guinea-pigs 
 that the lipoids in the cells of nearly all organs and tissues 
 of the body undergo marked changes in tuberculosis. The 
 aggregate of the lipoids and the phosphorus they contain 
 is reduced in almost all organs, while the lecithin is 
 decreased in all without exception. The organs which 
 suffer most are the lungs, and next to these the spleen, 
 cord, and liver. 
 
 A Lipoid from the Pancreas which stimulates the Liver. 
 — It is of considerable interest to note that the principal 
 physiologic influence of the pancreas lipoid is upon the 
 liver. Its stimulating action upon the hepatic cells was 
 remarkable. The average weight of liver in the control 
 animals corresponded to 36 grammes per kilo, while after 
 a series of injections of the pancreatic lipoid the average 
 weight of the liver had increased to 47 grammes per kilo. 
 
 No other lipoids of the numerous ones examined in- 
 fluences the liver to such an extent. The increase in the 
 liver seems to be quite normal, the tissue is not fatty, 
 and there are evidences that the hepatic powers are aug- 
 mented in proportion to the size of the organ. Experi- 
 ences with the apphcation of this pancreatic lipoid in 
 man in doses of 1 to 2 centigrammes per diem reveals 
 the following facts: (1) A very sHght increase in blood- 
 pressure. (2) A constant increase of weight. Its in- 
 fluence in diabetes is equally remarkable. The cases 
 which have been considered divide themselves into two 
 classes ; in one the sugar increases considerably as a result 
 of the injections, while in the other the glycosuria rapidly
 
 452 Practical Hormone Therapy 
 
 diminishes and finally disappears. This seems to be a 
 confirmation of the idea that certain diabetics are suffer- 
 ing from an essentially hepatic disturbance, while others 
 are the results of pancreatic changes. 
 
 The Pituitary Lipoid. — The lipoid isolated from the 
 anterior lobe of the pituitary seems to have the follow- 
 ing properties: (1) It notably augments the appetite as 
 well as the muscular activity. (2) It materially stimu- 
 lates the Iddneys, and augments not only the quantity 
 of fluid passed, but also the urea and phosphates. (3) It 
 does not act upon the weight of adults, but stimulates 
 the growth of immature subjects. (4) It excites the 
 adrenals, heart, and kidneys, but has no action on the 
 genital organs, liver, or thjToid. (5) In man in doses 
 varying from 2 to 5 centigrammes a day there is an 
 initial increase in the pulse, later followed by diuresis 
 and an increase in the appetite. In myasthenia a con- 
 siderable increase in the muscular capacity follows its 
 administration; while in myocarditis it has given relief 
 by reducing pressure and rendering the heart beats more 
 regular. 
 
 The Thyroid Lipoid. — Iscovesco has isolated from the 
 thyroid a lipoid which strongly excites the adrenals, 
 ovaries, uterus, and testicles. It also stimulates the 
 heart, but curiously enough more in females than males. 
 Its action was particularly marked upon the thyroid 
 itseK, which was also greater in females than in males. 
 The action of this hpoid upon the growth of immature 
 subjects seems to stimulate it slightly, but in adults it 
 has the opposite effect. 
 
 The Splenic Lipoid in Tuberculosis. — It is beheved that 
 in the normal state there are certain substances that are 
 capable of destroying the toxins of the tubercle and other 
 bacilli. One of these, according to Iscovesco, is a lecithide
 
 The Lipoids 453 
 
 which he obtains from the spleen. This product, which 
 is called splenolecithide V.B.d., is said to have a specially 
 favourable influence in the tuberculous. Its use by 
 Iscovesco in 40 cases gave very good results in general, 
 and this author suggests that this preparation exerts a 
 valuable influence especially upon the active manifesta- 
 tions of tuberculosis, reducing tuberculous glands of the 
 neck within a month, and generally increasing weight 
 and resistance. It is given hypodermically in daily 
 doses, and it is advisable to continue the treatment for 
 two or three months. 
 
 The Lipoids obtained from the Gonads. — Three lipoid 
 preparations have been secured from the gonads — andro- 
 crinol, the specific lipoid of the testicle; gynocrinol, the 
 lipoid from the ovary; and gynoluteol, that from the 
 corpus luteum. These aU possess a stimulating effect 
 upon the gonads, augmenting in a considerable degree 
 the activity of the corresponding organs, as regards both 
 actual growth and functional capacity. The testicular 
 lipoid is used in conditions where the activity of the 
 glands needs stimulation, as, for example, in infantihsm 
 and retarded growth, sexual neurasthenia, and impotence, 
 and as a tonic in senility, especially when accompanied 
 with hypertension and atheroma. It is usually given 
 hypodermically in daily doses. 
 
 The ovarian Hpoid has been used in conditions where 
 the pelvic organs manifested aplasia, in the develop- 
 mental troubles of puberty, including infantilism, sclerosis, 
 and amenorrhoea. It has also been used in dysmenor- 
 rhcea, and is said to constitute a very valuable means of 
 controUing painful menstruation. The luteal lipoid 
 {gynoluteol) is more suited for the treatment of menor- 
 rhagia, and as a means of controlling the ovarian dis- 
 turbances of pregnancy. It may also be used as a post-
 
 454 Practical Hormone Therapy 
 
 partum remedy to favour uterine involution and lacta- 
 tion. It exerts in the artificial menopause a similar 
 effect to that of lutein. 
 
 From the clinical and experimental facts at hand it 
 seems established that the lipoids may even revolutionize 
 the revolution which the introduction of the use of 
 animal extracts into medicine is bringing about, as well 
 as proving a means of enlightening us in a considerable 
 degree regarding certain phases of endocrinous metabo- 
 lism, and much credit must be given to those who have 
 devoted so much time and effort to the investigation of 
 this by no means well-studied subject.
 
 CHAPTER XXXV 
 
 A GLOSSARY OF TERMS 
 
 A NUMBER of terms which are not generally used 
 necessarily insinuate themselves into a book of this char- 
 acter. Many of them are not even found in late medical 
 dictionaries, such, for example, as Borland's seventh 
 edition, published in September, 1913. These have been 
 designated by a star (*). It has also seemed advisable 
 to include the trade names of certain of the organo- 
 therapeutic specialities which happen to have been re- 
 ferred to in the text. These are printed in italics. Of 
 course, the list cannot pretend to be complete. It is 
 unfortunate that the nomenclature of this subject is being 
 complicated by a vast number of coined words, each 
 indicating a particular brand of the same preparation. 
 Especially unfortunate is the indiscriminate use of trade 
 names, such as adreiudin, 'pituitrin, etc., when these 
 particular preparations are neither used nor meant. 
 
 Activator. A substance which changes a ferment from 
 an inactive to an active form. Ex. : HCl activates 
 pepsinogen as secreted by peptic glands to pepsin. 
 
 Adrenalin. The pressor principle of the adrenals, isolated 
 by Takamine. The liydrochloride in 1 in 1,000 solu- 
 tion is used generally (Parke, Davis and Co., Detroit). 
 
 Adrenaline*. A name given to adrenal extracts, and 
 generally adopted in British and French scientific 
 literature, and not indicating any particular make, 
 455
 
 456 Practical Hormone Therapy 
 
 Antihormone*. A chalone or antagonistic hormone ; name 
 given first to the internal secretion of the pancreas, 
 because of its action upon the adrenal or chromaffin 
 hormone. 
 
 Antithyroidine* . Moebius's serum from thyroidectom- 
 ized goats, used in Basedow's disease (German). 
 
 Asthmolysin* . A mixture of adrenal and pituitary ex- 
 tracts, used in asthma. Each 1 c.c. ampule con- 
 tains 0-0008 gramme adrenal and 004 gramme hypo- 
 physis and preservatives (German). 
 
 Aulacoid* (Greek auTo?, self, and dKo<;, a remedy). A 
 generic term suggested by Sir E. A. Schafer to in- 
 clude all the chemical messengers — i.e., hormones and 
 chalones {q.v.). 
 
 /3-iminazolylethyIamine*. A depressor and utero-stimu- 
 lant amine prepared from histidine (and therefore 
 also from intestinal extracts) by the action of putre- 
 factive bacteria. Chemical name for Ergamine {q.v.). 
 See also Depressine. 
 
 Cephaline. One of the chemical constituents of the 
 brain, quite similar to lecithin (and perhaps identical 
 with it). 
 
 Cerehrin*. A proprietary dry extract of brain substance 
 (Burroughs Wellcome and Co., London). 
 
 Cerebrine. A French proprietary analgesic containing 
 coca, caffeine, and guarana. Nothing to do with 
 brain preparations. 
 
 Chalone* (Greek x^^"-^- I relax). A term suggested by 
 Sir E. A. Schafer to indicate the hormones which do 
 not excite — the antagonistic hormones. Ex. : the 
 " Langerhansian hormone." 
 
 Chemical reflex. Another term for " humoral reflex " [q.v.). 
 
 Choleine*. A proprietary form of repurified extract of bile 
 in keratin-coated ovoids (Camus, Moulins, France).
 
 A Glossary of Terms 457 
 
 Chromaffin. Staining with chromic acid or its salts. A 
 term applied to the adi^enal system and its hormone — 
 i.e., the chromaffin hormone. 
 
 Coeliacin*. An extract of the mesenteric glands of sheep 
 (E. Merck, Darmstadt). 
 
 Coenzyme. A substance which manifests a co-operative 
 activity between an enzj^ie and some other non- 
 colloidal substance. Ex. : the influence of bile salts 
 on pancreatic lipase. The process differs from 
 activation, for the combination is dissociable instead 
 of permanent. A coenzyme can be separated from 
 an enzyme by dialysis. 
 
 Coferment. Another term for " coenzyme." 
 
 Colloidogen*. A hypothetical substance which is pre- 
 sumed to be concerned in holding the minerals of the 
 body in a colloid or organic state. 
 
 Colloidogenine^ . An extract of spleen, used by Bayle in 
 tuberculosis, obtainable in syrup or dry powder 
 (Chaix, Paris). 
 
 Crinogenic*, crisogenic*. Stimulating the production of 
 secretions generally. (Should strictly be " critico- 
 genic") 
 
 D-quotient*. A term used in metabohc studies, indica- 
 ting the relation between the urinary sugar and the 
 mnnary nitrogen. 
 
 Depressine*. A crystaUine depressor substance, prepared 
 from intestinal extracts by Launoy and CEchslin 
 (similar to, if not identical with, yS-iminazolylethyla- 
 mine, q.v.). 
 
 Endocrinous* (Greek hhov, within, internal ; Kpcvco, I 
 separate, set apart). Pertaining to the internal 
 secretions. Occasionally written " endocrine." [Both 
 words are philological monstrosities. In Greek a 
 verb can be compounded directly only with a prep-
 
 458 Practical Hormone Therapy 
 
 osition. All other parts of speech {evhov is an 
 adverb) form their derivatives from the correspond- 
 ing nomi of agency, in this case Kpla-i'i, whose ad- 
 jective is KpiTLK6<i, or from a verbal adjective, in this 
 case Kpn6<i (which has been set apart); hence the 
 proper word would be " endocrito." When any part 
 of speech other than a preposition is directly com- 
 pounded with a noun of agency, the termJnation of 
 the latter is changed to la. The noun, therefore, 
 should be evSoKpia-La. However, in deference to 
 general usage, the word " endocrinous " is used 
 throughout this book.] 
 
 Enterokinase. A ferment found in the duodenum, which 
 is the activator of trypsinogen. 
 
 Enterokinesia*. The motor function of the bowels — 
 peristalsis. 
 
 Enterokinetic*. An agent having an action upon the 
 intestinal movements. 
 
 Epinephrin. The term given by Abel to the active 
 pressor principle of the adrenal gland. Used errone- 
 ously by some to indicate all adrenal preparations, 
 irrespective of their origin. 
 
 Ergamine*. A synthetic depressor substance, used as a 
 uterine stimulant in haemorrhage, etc. May also be 
 isolated from intestinal extract (Burroughs Wellcome 
 and Co., London). See also Depressine. 
 
 Eusecretine*. An autolized glycerine extract of scrapings 
 of the gastric mucosa (Byla, Gentilly, France). 
 
 Ferment-precursor. See Proferment. 
 
 Flaveiyie* (Latin flavus, yellow). An extract of the 
 corpora lutea of pigs ; made in France (Byla, 
 Gentilly). 
 
 Gastrin. The gastric or pyloric hormone. Sometimes 
 called " gastric secretin." See Secretin.
 
 A Glossary of Terms 459 
 
 Gonads. The essential sex glands — i.e., testes and 
 ovaries. 
 
 Hemato-ethyi'oidine* . Serum of thyroidectomized ani- 
 mals for use in Basedow's disease (Carrion, Paris). 
 
 Histotherapy (Greek l(TT6<i, tissue). A term rarely used 
 instead of opotherapy {q.v.). 
 
 Holadiii. A pancreas ferment preparation (Fairchild 
 Bros, and Foster, New York). 
 
 Homostimulant*. A term used to indicate the particular 
 action which organic extracts and lipoids exert upon 
 the organs to which they correspond. 
 
 Hormonal. Zuelzer's "peristaltic hormone," prepared 
 from the spleen of cattle (Schering, Berlin). 
 
 Hormone. A chemical messenger, which, formed in one 
 organ, travels in the blood-stream to the other 
 organs of the body, and effects a correlation between 
 the activities of the organ of origin and the organs 
 on which they exert their specific effect. Ex. : 
 secretin (in duodenum) activates the pancreatic cell 
 and changes the inert pancreatic protrypsinogen to 
 trypsinogen, ready for use as soon as it reaches the 
 intestine (and in this case further activated by 
 enterokinase). 
 
 Hornioto7ie*. A tonic combination of hormone-bearing ex- 
 tracts, and used in hypoendocrinism and associated 
 run-down states (G. W. Carnrick Co., New York). 
 
 Humoral reflex. The activity brought about through 
 the blood and the hormone contents of its plasma 
 (as compared with the nerve reflex). 
 
 Hyperendocrinism*. The opposite of hypoendocrinism; 
 not, however, clinically known. (Should be hyper- 
 endocrisia; see note on Endocrinous.) 
 
 Hypoendocrinism*. Deficient internal secretory activity ; 
 usually refers to pluriglandular insufficiencies, as
 
 460 Practical Hormone Therapy 
 
 special words (hypopituitarism, hypothyroidism, etc.) 
 are apphed to individual deficiencies. (Should be 
 hypendocrisia; see note on Endocrinous.) 
 
 Hypo'physin. The chemically pure posterior pituitary 
 hormone, marketed as a sulphate (Meister, Lucius 
 and Briining, Hoechst-a.-M.). 
 
 Hyposphyxia*. A circulatory syndrome in which 
 hypotension, venous stasis, and general circulatory 
 sluggishness are present (Martinet). 
 
 Infundibulin. A term frequently used in the Hterature 
 to indicate a standardized 20 per cent, solution of 
 the active extract of the posterior lobe of the pituitary 
 body. 
 
 Infundi7i*. The registered name for the " vaporole " 
 infundibulin {q.v.) (Burroughs Wellcome and Co., 
 London). 
 
 Kinase. A colloid activator which is of unknown com- 
 position. Ex. : enterokinase, which activates tryp- 
 sinogen to trypsin. 
 
 Kinetic. Related to power or energy. The " kinetic 
 system " (Crile) includes the brain, thyroid, adrenals, 
 and muscles. 
 
 Kinetogenic. Producing motion — i.e., causing growth. 
 
 Lipoid. A product of cell metabolism resembling fat, 
 in that it is extractable with ether, chloroform, etc., 
 and said to be similar in physiological and thera- 
 peutic action to the hormone-bearing organic ex- 
 tracts. 
 
 Lipoides H.I.'* A term used to indicate a series of 
 lipoids isolated by Iscovesco, which are said to be 
 homo stimulants injectahles. They are used for thera- 
 peutic purposes, and have a similar action to that 
 of the corresponding glandular extract (Carrion, 
 Paris).
 
 A Glossary of Terms 461 
 
 Tab. Lutein. Extract of corpora lutea of the pig, each 
 tablet representing 20 grains of fresh substance 
 (Hynson, Westcott and Co., Baltimore). 
 
 Liiteine*. A fatty pigment of a yellow colour, found in 
 the corpus luteum. An extract of the corpora lutea 
 made in Germany at the suggestion of Fraenkel. 
 
 Mammin. A preparation consisting of a sodium chloride 
 extract of the udders of cows, freed from precipitable 
 proteins (von Poehl, St. Petersburg). 
 
 Morphogenesia*. The production of growth. 
 
 Morphogenetics*. Substances producing growth — i.e., 
 having a trophic action. A term used by Gley in 
 his consideration of hormones, 
 
 Motiline*. The enterokinetic principle found in extracts 
 of the intestinal mucosa by Hallion and Enriquez. 
 
 Neohormonal*. The most recent preparation of the 
 peristaltic hormone (Zuelzer) in solution from M^hich 
 all albuminous substances have been removed 
 (Schering, Berhn). 
 
 OEstrus* (estrus). The period of sexual activity in ani- 
 mals; the "heat" or "rut." 
 
 Opotherapy (Greek otto?, a juice). A term introduced bj' 
 Landouzy of Paris in 1895, indicating the use of 
 animal extracts in therapeutics. In general use in 
 France. Various other terms that have been used 
 are "zom other apy," " secretotherapy, " "sequardo- 
 therapy," "animal therapy," and "organotherapy." 
 The last of these is in quite general use in England 
 and America. 
 Ovaradentriferrin. Merck's combination of ovarian sub- 
 stance {ovaraden) with nucleinate of iron in tablet 
 form. 
 Parathyroidine* [Paratiroidina). Vass ale's active ex- 
 tract of the parathyroid glands (Italian).
 
 462 Practical Hormone TJierapi/ 
 
 Paratoxine. A petroleum- ether extract of repiirified bile, 
 containing cholesterin and the lipoids of bile. 
 Especially recommended by Gerard and Lemoine 
 in tuberculosis (France). 
 
 Parhormone*. Products of katabolism endowed with a 
 physiological or hormone-like action (Gley). See 
 Ponogen. 
 
 Peptocrinine*. A term suggested by Gley for a substance 
 similar to secretin, which is extracted from the intes- 
 tinal mucosa by means of a hot peptone solution. 
 
 Phosphatides. A class of lipoids which are esters of ortho- 
 phosphoric acid. Ex. : lecithin. 
 
 Pituglandol. A solution of the active principles of the 
 posterior lobe of the pituitary body (Hoffman, La 
 Roche Chemical Works, Basle). 
 
 Pituitrin, A solution of the active principles of the 
 posterior lobe of the pituitary body (Parke, Davis 
 and Co., Detroit). 
 
 Pluriglandular*. A term used to indicate a form of com- 
 pound glandular therapy — i.e., the simultaneous 
 administration of several extracts. 
 
 Polyglandular. A word of mixed derivation which should 
 not be used. See Pluriglandular. 
 
 Ponogen (Greek -n-ovo^, work). A cellular waste which 
 may serve as a " chemical messenger " to influence 
 some remote organ (Laumonier). See Parhormone. 
 
 Proferment. The substance in the glandular cell-unit 
 which, after activation, becomes a ferment. Ex.: 
 propepsin. 
 
 Progastrin*. The precursor of the so-called "gastric 
 secretin." 
 
 Prosecretin. The precursor of secretin, found in the 
 duodenal walls and changed or activated to secretin 
 by hydrolysis -with action of HCl.
 
 A Glos.'iaTy of Terms 463 
 
 Secretin. The typical hormone from the duodenal mucosa 
 secreted as prosecretin, and later activated by HCl. 
 
 (1) Pancreatic secretin: the secretin which activates 
 the pancreatic cells; not secretin from the pancreas. 
 
 (2) Gastric secretin: the secretin which activates the 
 gastric cells. See Gastrin. 
 
 Secretogen'^. An extract of the pyloric and duodenal 
 mucosa containing the chief alimentary hormone — 
 secretin (G. W. Carnrick Co., New York). 
 
 Sequardotherapy*. A httle-used term for opotherapy 
 iq.v.), based on the name of the " discoverer of animal 
 therapy " — Brown-Sequard. 
 
 Sperminum. A definite chemical body obtained from 
 the testicles, said to be a nerve tonic and cell stimu- 
 lant (von Poehl, St. Petersburg). 
 
 Stagnin. An autolyzed, soluble extract of horse 
 spleen, especially recommended in haemorrhage 
 (German). 
 
 Stimulin. A term sometimes wrongly used in the place 
 of " hormone." Stimulins are, according to Metchni- 
 koff, certain protective bodies in blood-serum, which 
 produce immunity when inoculated by stimulating 
 phagocjrtic action. 
 
 S'uprarenin. An adrenal-medulla preparation (Meister, 
 Lucius and Briining, Hoechst-a.-M.). 
 
 Synthetic L-Suprarenin. The active pressor principle 
 produced by chemical synthesis (Meister, Lucius 
 and Briining, Hoechst-a.-M.). 
 
 Tabloid Three Glands * A pluriglandular extract contain- 
 ing thyroid (6 grains), adrenal (f grain), and pituitary 
 {-^ grain), suggested for use in cancer (Burroughs 
 Wellcome and Co., London). 
 
 Testikulin. A proprietary extract of bull's testes, used 
 as a general tonic and cell-stimulant (German).
 
 464 Practical Hormone Therapy 
 
 Thymin. A proprietary extract of the thymus gland 
 (von Poehl, St. Petersburg). 
 
 Thyratoxine* . A thyroid extract from which the toxic 
 substances (lipoids, etc.) have been removed (Byla, 
 Gentilly, France). 
 
 Thyroidectin. A product of the serum of thyroidectom- 
 ized goats for use in Basedow's disease (Parke, Davis 
 and Co., Detroit). 
 
 Thyroprotein. Beebe's nucleoprotein of the thyroid gland. 
 An active thyroid extract (Parke, Davis and Co., 
 Detroit). 
 
 Trypsogen. An extract of the pancreas, said to contain 
 its internal secretion, in combination with adrenal 
 inhibitory drugs for use in diabetes mellitus (G. W. 
 Carnrick Co., New York). 
 
 Vasodilatin*. A hypothetical substance with a marked 
 depressor action which is presumed by its sponsor, 
 Popielski of St. Petersburg, to be present in extracts 
 of all organs. This substance is also supposed to 
 prevent the coagulation of blood. 
 
 Zymase. A soluble ferment or enzyme. ^ 
 
 Zymogen. Another term for a proferment. The pre- 
 cursor of an enzyme ; that part of the enzyme which 
 is produced in the gland. Ex. : pepsinogen.
 
 CHAPTER XXXVI 
 AN ORGANOTHERAPEUTIC DOSE-TABLE 
 
 Since the dosage and application of organotlierapeutic 
 products varies so greatly, it is difficult definitely to out- 
 line the therapeutic indications and the size of the doses 
 to be given. The indications, as has been seen, are in 
 many cases very numerous, and it does not seem advisable 
 to give in the table M^hich follows more than the 
 most essential conditions in which the various animal 
 extracts are available. The dosage, too, is purely sug- 
 gestive, for it has been frequently stated that " there is 
 no dose save dose enough." 
 
 An attempt has been made to indicate the class into 
 which the application of this form of medication falls. 
 It will be remembered that there are four distinct 
 classes into which hormone therapy is divided : 
 
 1. Substitution Therapy : by the supply of a hormone 
 to balance a definite loss due to disease or absence of an 
 organ. 
 
 2. Supplementary Therapy : by augmenting directly 
 or indirectly the so-called " humoral reflex," a presumed 
 hormone deficiency resulting from an increased phj'sio- 
 logical demand, or from a decreased production of the 
 needed principle. This includes the application of 
 Hallion's laAv. 
 
 3. Specific Therapy : by causing a physiological action 
 which is desired, though not as the result of any change 
 in the hormone production. 
 
 465 30
 
 466 
 
 Practical Hormone Therapy 
 
 4. Empirical Therapy: by applying hormone therapy 
 in an unscientific, but nevertheless useful, manner, the 
 origin of which many times was accidental, and the basis 
 of which is not yet wholly explainable. 
 
 These four classes are numbered below in harmony 
 with the numbers corresponding to each class mentioned 
 above. 
 
 Unless indicated to the contrary, the doses mentioned 
 refer to grains of dried extract given by mouth, and indi- 
 cate the average single dose. It is given three or four 
 times a day. Space prevents the use of both the English 
 and French weights. The star (*) indicates that the 
 dose may also be given hypodermically (in which case the 
 standard solutions of the various substances are referred 
 to); the dagger (f) that it is best administered intra- 
 muscularly; and the section (§) that it may be given 
 intravenously. 
 
 This table is neither arbitrary nor exact, but merely 
 suggestive. 
 
 4 
 
 Product. 
 
 Adrenal . 
 (total) 
 
 [medidla) . 
 
 Bile 
 
 Tlierapeutic ludications. 
 
 Addison's disease^; hypoadrenia^ 
 (tj^phoid, cholera, acute fevers, | 
 etc.); osteomalacia'^; rickets^;' 
 tuberculosis'*; asthenia^; etc. 
 
 Haemorrhage^ ; hypotension^ ; 
 cardiac disease^ ; asthma^ ; 
 poisoning'* (strychnia, snake- 
 bite, salvarsan, etc.). 
 
 Liver insufficiency^ (constipa- 
 tion, intestinal putrefaction, 
 etc.); biliary stasis^ (hepatic 
 colic, gall- stone, icterus, etc.) ; 
 muco-membranous colitis.^ 
 
 Average 
 Dose, 
 
 Grains. 
 
 1-2 
 
 ^ 
 
 1-3 
 min.*§ 
 
 2-.'^
 
 An Organotherapeutic Dose-Table 467 
 
 Product. 
 
 Therapeutic Indications. 
 
 Avarage 
 Dose. 
 
 
 
 Grains. 
 
 Duodenum 
 
 Pancreatic insufficiency^ (intes- 
 
 1-3 
 
 {secretin) 
 
 tinal indigestion, steatorrhoea, 
 etc.); gastro-intestinal insuffi- 
 ciencies^ ; diarrhoea^ (especi- 
 ally in childi-en in summer); 
 diabetes mellitus"*; constipa- 
 tion^; etc. 
 
 
 Hypophysis 
 
 Acromegaly^ ; myocardial asthe- 
 
 i-5 
 
 (total) 
 
 nia"* ; hypotension^ (in typhoid, 
 influenza, pneumonia, etc.); 
 asthenia^ (muscular, post- 
 diphtheritic paralysis, etc.); 
 obstipation"*; etc. 
 
 
 Infundt- 
 
 Obstetrics^; ischuria^; shock or 
 
 5-15 
 
 BULUM 
 
 collapse^ ; intestinal paresis"'^ 
 (meteorism, distension, etc.); 
 diabetes insipidus* ; amenor- 
 rhoea^; mammarj'^ flows (breast 
 abscess and insufficient milk) ; 
 etc. 
 
 min.t§ 
 
 Intestine . . 
 
 Dyspepsias^ ; constipation^ ; 
 muco - membranous colitis"* ; 
 enteritis^; etc. 
 
 1-3 
 
 Kidney 
 
 Renal insufficiency^; nephritis^ 
 uraemia^; ischuria^; albumin 
 uria^; etc. 
 
 3-5 
 
 Liver 
 
 Hepatic insufficiency^ ; cirrho- 
 sis^; hc-emorrhagic diathesis'* 
 
 10-25, 
 
 
 (epistaxis, haemoptysis, etc.); 
 
 15-30 
 
 
 intoxications^ ; dermatoses^ ; 
 
 min.* 
 
 
 'diabetes"*; etc. 
 
 
 Lung 
 
 Thoracic suppurations"* (pleurisy, 
 bronchitis, pulmonary ab- 
 scess, etc.); tuberculosis^; etc. 
 
 2-5 
 
 Lymphatic 
 
 Adenoids'^ ; hypertrophy of ton- 
 
 3-5, 
 
 
 sils^ ; lymphatism^ ; Hodg 
 
 3-5 
 
 
 kin's disease^; anaemia'*; etc. 
 
 min.f
 
 468 
 
 Practical Hormone Therapy 
 
 Product. 
 
 Therapeutic Indications. 
 
 Average 
 Dose. 
 
 
 
 Grains. 
 
 Mamm^ 
 
 Menorrhagia^ ; metrorrhagia^ ; 
 fibroids'*; agalactia^; hyper- 
 ovaria^; etc. 
 
 
 Nervous 
 
 Functional nervous disorders-; 
 
 3-5 
 
 {inc. hraiii 
 
 mental disorders^; neurasthe- 
 
 
 and cord) 
 
 nia^; certain organic nervous 
 and psychic conditions^; etc. 
 
 
 Ovary 
 
 Menstrual disorders^ (amenor- 
 
 3-5 
 
 {cor. lut.) 
 
 rhoea.. dysmenorrhoea, etc.); 
 infantilism with genital under- 
 development^ ; climacteric dis- 
 orders^; mahiutrition^ ; neur- 
 asthenia^; etc. 
 
 
 Pancreas . . 
 
 Intestmal indigestions^ ; dia- 
 betes meUitus^ ; tuberculosis^ ; 
 infections"*; etc. 
 
 2-5 
 
 Parathy- 
 
 Paralysis agitans^ ; tetany" ; 
 
 1 _ 1 * 
 
 5 "2 
 
 roid 
 
 athrepsia"* ; epilepsy^ ; chorea^ ; 
 exophthalmic goitre^; etc. 
 
 
 PmEAL 
 
 Mental under-development^ ; de- 
 fective metabolism^; etc. 
 
 3-10 
 
 Pituitary 
 
 See Hypophysis and Infmidibu- 
 Imn. 
 
 
 Placenta . . 
 
 Agalactia^ ; uterine subinvolu- 
 tion^; etc. 
 
 3-5 
 
 Pluri- 
 
 Hypoendocrmism^ ; run-down 
 
 1-5, 
 
 glandu- 
 
 conditions^ ; amenorrhoea^ ; 
 
 2-10 
 
 lar 
 
 neurasthenia'* ; malnutrition^ ; 
 sexual neuroses'*; insomnia^; 
 cancer^; etc. 
 
 min.f 
 
 Prostate . . 
 
 Prostatic hypertrophy^ ; prosta- 
 torrhoea'*; prostatic neuras- 
 thenia^; etc. 
 
 1-3 
 
 Spleen 
 
 ' Tuberculosis'* ; malnutrition'* ; 
 
 2-8, 
 
 
 anaemia'^; paludism^; spleno- 
 
 15min. 
 
 
 megaly^; typhoid'*; etc. (see 
 
 
 
 ! also Zuelzer's hormone). 

 
 An Organ otherapeufic Dose-Table 469 
 
 Product. 
 
 Therapeiitic Indications. 
 
 Average 
 Dose. 
 
 Stomach 
 
 Gastric insufficiency^ ; dyspep- 
 sia^; achylia; etc. 
 
 Grains. 
 
 2-5 
 
 Testes 
 
 Orchitic defects^ (cryptorchism, 
 
 1-3, 
 
 
 infantilism, retarded growth. 
 
 7-15 
 
 
 etc . ) ; impotence^ ; senility ^ ; 
 
 min.* 
 
 
 asthenia^ ; neurasthenia'* ; 
 
 
 
 functional neuroses'*; adyna- 
 
 
 
 mia ; dermatoses^; etc. 
 
 
 Thymus 
 
 Exophthalmic goitre^; rheumatic 
 arthritis'* ; rachitis^ ; early mal- 
 nutrition^; etc. 
 
 5-15 
 
 Thyroid 
 
 Hypothyroidism^ (myxoedema, 
 
 2-10, 
 
 
 cretinism, infantilism, etc.); 
 
 tV-I 
 
 
 goitre^; minor hypothyroid- 
 
 
 
 ism^ ; chronic rheumatism"* ; 
 
 
 
 dermatoses* (ichthyosis, scle- 
 
 
 
 roderma, psoriasis, eczema, 
 
 
 
 etc. ) ; obesity* ; migraine"* ; 
 
 
 
 menstrual disorders^ ; in- 
 
 
 
 sanity*; neurasthenia*; etc. 
 
 
 Zuelzer's 
 
 Intestinal paresis^ ; obstipatio 
 
 
 PERISTAL- 
 
 chronica^ ; post - operative 
 
 10-20 
 
 TIC HOR- 
 
 paresis^; etc. 
 
 c.c.t§ 
 
 MONE 
 

 
 CHAPTER XXXVII 
 
 A LIST OF BOOKS ON THE INTERNAL 
 SECRETIONS, ETC.* 
 
 The list which foUows comprises those books on various 
 phases of hormone activity and therapeutics which are in 
 the author's library, and which, with the cmrent medical 
 literature, have served as the basis for this work. The 
 Ust, of course, does not comprise every book on this and 
 allied subjects, although by far the largest majority are 
 listed here. The arrangement of the list is made with the 
 idea of giving prominence to the comparative usefulness 
 of each book mentioned, and it seems that every really 
 interested reader should have the first-named books in 
 order that more definite information may be secured 
 regarding the physiology and pathology of the ductless 
 glands. 
 
 In order to save needless repetition, the references in 
 the bibliographies to any among the following list of 
 books have been made without giving the title of the book, 
 and with simply a star (*) after the author's name, thus : 
 " Biedl :* p. 52." 
 
 "INNERE SEKRETION: ihre Physiologischen 
 Grundlagen und ihre Bedeutung ruR DIE Patho- 
 LOGIE." t Von Professor Dr. Artur Biedl, Wien. 
 Zweite neubearbeitete Auflage. 1913. Erster Teil. 
 Pp. 534. Urban and Schwarzenberg, Berlin und Wien. 
 M. 26. Zweite Teil. Pp. 692. M. 28. f 
 
 * The books indicated thus (f ) were added to the author's library after Jfe 
 the body of this book was in type. -^ 
 
 470 
 
 ■»
 
 List of Boohs on the Internal Secretions , etc, 471 
 
 "THE INTERNAL SECRETORY ORGANS: their 
 Physiology and Pathology." By Professor Dr. Artur 
 Biedl, Vienna. With an Introductory Preface by Leonard 
 Williams, M.D., M.R.C.P. Translated by Linda Forster. 
 1912. Pp. 586. John Bale, Sons and Danielsson, Ltd., 
 London. 21s. net. 
 
 "THE INTERNAL SECRETIONS AND THE 
 PRINCIPLES OF MEDICINE." By Charles E. de M. 
 Sajous, M.D., LL.D. Sometime Professor in the Medico- 
 Chirurgical College, Philadelphia; Knight of the Legion 
 d'Honneur, etc. Fom^th edition, 1911. Pp. 1873. 2 
 vols. F. A. Davis Co., Philadelphia. Stanley Phillips, 
 London. £2 10s. net. 
 
 " INTERNAL SECRETION AND THE DUCTLESS 
 GLANDS." By Swale Vincent, M.D., D.Sc, Professor 
 of Physiology in the University of Manitoba. With a 
 Preface by Sir E. A. Schafer, F.R.S., etc. 1912. 
 Pp. 464. Edward Arnold, London. 12s. 6d. net. 
 
 "THE DISEASES OF THE DUCTLESS GLANDS: 
 FOR Practitioners of Medicine and Surgery." f By 
 S. P. Beebe, Ph.D., M.D. Professor of Experimental 
 Therapeutics in Cornell University Medical College, New 
 York. 1914. Pp. 400. Lea and Febiger, Philadelphia. 
 
 "MEDICAMENTS ANIMAUX: Opothkrapie." Par 
 le Dr. Paul Carnot, Professeur Agrege de Therapeutique 
 a la Faculte de Medecine de Paris. 1911. Pp. 602. 
 BailHere et Fils, Paris. Fr. 12. 
 
 "HORMONE THERAPY: 1913." By Henry R. 
 narrower, M.D., and Thos. Stephenson, F.C.S., F.R.S.E. 
 1913. Prescriber Offices, Edinburgh. 3s. 6d. Or Paul 
 Hoeber, New York, $1.00. 
 
 " LEHRBUCH DER ORGANOTHERAPIE : mit 
 Berucksichtigung ihrer anatomischen und physio- 
 logischen GRUNDLAGEN."t Hcrausgcgeben von Dr. 
 Wagner v. Jauregg (Wien) und Dr. Gustav Bayer (Inns- 
 bruck). 1914. Pp. 516. Georg Thieme, Leipzig. M. 
 14.00. 
 
 " THE NERVOUS AND CHEMICAL REGULATORS 
 OF METABOLISM." By D. Noel Baton, M.D., B.Sc, 
 Pi^ofessor of Physiology in the University of Glasgow. 
 1913. Pp. 217. Macmillan, London and New York. 
 6s.. or $1.50.
 
 472 Practical Hormone Therapy 
 
 "LIFE: ITS Nature, Origest, and Maintenance." 
 By Sir E. A. Schafer, LL.D., D.Sc, M.D., F.R.S., Pro- 
 fessor of Physiology in Edinburgh. 1912. Pp. 36. 
 Longmans, Green, London and New York. Is. net. 
 
 "INTERNAL SECRETIONS FROM A PHYSIO- 
 LOGICAL AND THERAPEUTICAL STANDPOINT." 
 
 By Isaac Ott, A.M., M.D., Professor of Physiology in the 
 Medico - Chirurgical College of Philadelphia. 1911. 
 Pp. 133. E. D. Vogel, Easton, Pa. 
 
 "ORGANOTHERAPY: or, Treatment by Means 
 OF Preparations of Various Organs." By H. Batty 
 Shaw, M.D. Lond., F.R.C.P., Lectvn^er in Therapeutics, 
 University College Hospital Medical School. 1905. 
 Pp. 256. Illustrated. Cassell, London. 6s. 
 
 " SULLA ORGANOTERAPIA." Conferenzia Tentua 
 11 27 Novembre, 1910. Dinanzi Alia Camera Medica di 
 Trento. Per Professor Augusto Murri. 1911. Pp. 70. 
 Zanichelli, Bologna. L. 2.50. 
 
 " DELL' OPOTERAPIA." Per Dr. Giuseppe Zingale. 
 Estratto del Giornale Medicina Nuova. Roma. 1911. 
 Pp. 92. L. 2. 
 
 "PRINCIPLES OF HUMAN PHYSIOLOGY." By 
 Ernest H. Starling, M.D. Lond., F.R.C.P., F.R.S., etc. 
 1912. Pp. 1436. J. and A. Churchill, London. 21s. net. 
 
 "A TEXTBOOK OF PHYSIOLOGY: for Students 
 AND Practitioners." By Isaac Ott, A.M., M.D., Pro- 
 fessor of Physiology in the Medico-Chirurgical College of 
 Philadelphia, etc. Third and revised edition. 1913. 
 Pp. 911. F. A. Davis Co., Philadelphia. $3.50. 
 
 "HUMAN PHYSIOLOGY." By Professor Luigi 
 Luciani, Director of the Physiological Institute of the 
 Royal University of Rome. Translated by Frances A. 
 Welby. In four volumes. Vol. II., " Internal Secretion; 
 Digestion; Excretion; the Skin." 1913. Pp.558. Mac- 
 millan, London and New York. 18s., or $5.00. 
 
 " LA PRATIQUE DE L'OPOTHERAPIE : Principes, 
 Indications, Posologie." Par le Dr. L. HaUion, 
 Directeur Adjoint du Laboratoire de Physiologic Patho- 
 logique des Hautes ]Etudes a Paris. 1911. Pp. 148. 
 Masson et Cie., Paris. Fr. 2.00.
 
 List of Books on the Internal Secretions, etc. 473 
 
 " LES PRODUITS BIOLOGIQUES MfiDICINAUX." 
 Par P. Byla et R. Delaunay. 1912. Pp. 466. F. 
 Gittler, Paris. Fr. 10.00. 
 
 "DBS EXTRAITS OPOTHl^RAPIQUES : modes de 
 Preparation, Rendements, Posologie." Par E. Choay, 
 Docteur en Pharmacie de rUniversite de Paris, etc. 1911. 
 Pp. 180. Vigot Freres, Paris. Fr. 5.00. 
 
 " L'OPOTHERAPIE THYROIDIENNE (Thyroide, 
 Parathyroides, Hypophyse)." Par le Dr. Gabriel 
 Gauthier (de Charolles). Deuxieme edition. 1913. 
 Pp. 476. J. B. Bailliere et Fils, Paris. Fr. 12.00. 
 
 " GLANDES SURR:ENALES ET ORGANES CHRO- 
 MAFFINES." Par les Drs. M. Lucien et J. Parisot, 
 Professeurs Agreges a la Faculte de Nancy. 1913. 
 Pp. 452. F. Gittler, Paris. Fr. 12.00. 
 
 "LA M:fiDICATION SURRENALE." Par les Drs. 
 Oppenheim et Loeper, Professeurs Agreges a la Faculte 
 de Medecine de Paris. 1904. J. B. Bailliere et Fils, 
 Paris. Fr. 1.50. 
 
 " THE PITUITARY BODY AND ITS DISORDERS." 
 By Harvey Gushing, M.D., Professor of Surgery, Harvard 
 University, etc. Pp. 450. J. B. Lippincott Co., Phila- 
 delphia and London. 18s., or $4.00. 
 
 "L' IPOFISI CEREBRALE FARINGEA E LA 
 GLANDOLA PINEALE IN PATOLOGIA." Per Dr. 
 Alfonso Poppi. 1911. Pp. 226. Paolo Neri, Bologna. 
 L. 10.00. 
 
 "L'HYPOPHYSE ET LA MEDICATION HYPO- 
 PHYSAIRE." Parle Dr. Arthur Delille. 1909. Pp.336. 
 G. Steinhei], Paris. Fr. 10.00. 
 
 " GLYCOSURIA AND ALLIED CONDITIONS." By 
 P. J. Cammidge, M.D. Lond. 1913. Pp. 467. Edward 
 Arnold, London. 16s. net. 
 
 "NEW ASPECTS OF DIABETES." By Professor 
 Dr. Carl von Noorden, late Professor in the First Medical 
 Clinic, Vienna. 1912. Pp.160. John Wright and Sons, 
 Bristol, 5s. ; or E. B. Treat and Co., New York, $1.50. 
 
 "STUDIES CONCERNING GLYCOSURIA AND 
 DIABETES." By Frederick M. Allen, M.D. 1913. 
 Pp.1179. Harvard University Press, Boston. $9.00.
 
 474 Practical Hormone Therapy 
 
 "DIABETES: its Pathological Physiology." By 
 J. J. R. Macleod, M.B., Ch.B., D.P.H., Professor of 
 Physiology, Western Reserve University, Cleveland. 1913. 
 Pp. 224. Edward Arnold, London. 
 
 "THEORY AND PRACTICE OF THYROID 
 THERAPY." By Herbert Ewan Waller, M.R.C.S. (Eng.), 
 L.R.C.P. (Lond.),etc. 1911. Pp.154. John Bale, Sons, 
 and Danielsson, London. 5s. net. 
 
 "DISEASES OF THE THYROID GLAND." By 
 George R. Murray, M.A., M.D., F.R.C.P., Professor of 
 Medicine, Victoria University, Manchester. 1909. Pp.112. 
 H. K. Lewis, London. 7s. 6d. 
 
 " NOUVELLES ETUDES SUR LA PHYSIOPATHO- 
 LOGIE DU CORPS THYROIDE." Par les Drs. Leo- 
 pold-Levi et H. de Rothschild, Laureats de F Academic 
 de Medecine de Paris. Second edition. 1911. Pp. 558. 
 0. Doin et Fils, Paris. Fr. 10.00. 
 
 "LA PETITE INSUFFISANCE THYROIDIENNE 
 ET SON TRAITEMENT." Par les Drs. L. Levi et H. 
 de Rothschild. 1913. Pp.309. 0. Doin et Fils, Paris. 
 Fr. 5.00. 
 
 "CONTRIBUTION SUR L'ETUDE DE L'OPO- 
 THERAPIE MA]\C\L4IRE." Par le Dr. M. Luncz de 
 la Faculte de Medecine de Paris. 1911. Pp. 136. Vigot 
 Freres, Paris. Fr. 4.50. 
 
 "LES PARATHYROiDES." Par Dr. Louis Morel. 
 1912. Pp. 334. A. Hermann et Fils, Paris. Fr. 10.00. 
 
 " fiTUDES D'ENDOCRINOLOGIE." Par Dr. Naame 
 deTunisie. 1913. Pp.72. A. Maloine, Paris. Fr. 1.50. 
 
 "LA SfiCR^TION PANCREATIQUE." Par Emile 
 F. Terroine. 1913. Pp. 133. H. Hermann, Paris. 
 Fr. 5.00. 
 
 " CONTRIBUTION A L'fiTUDE DU MECANISME 
 DE LA SfiCRfiTION EXTERNE DU PANCRl^AS." 
 Par Dr. A. Hustin. 1913. Pp. 101. Impr. Vaillant- 
 Carmanne, Liege. 
 
 " KLINIK UND BIOLOGIE DER THY^IUSDRUSE." 
 Von Dr. H. Klose und Dr. H. Vogt. 1910. Pp. 200. 
 Laupp'schen Buchhandlung, Tiibingen. 
 
 "LECONS SUR LA LITHIASE BILIAIRE." Par 
 Dr. A. Chauffard, Professeur du Clinique Medicale a la
 
 List of Books on the Internal Secretions, etc. 475 
 
 Faculte de Medecine de Paris. 1914. Pp. 244. Masson 
 et Cie., Paris. Fr. 9.00. 
 
 "LES SECRETIONS INTERNES: leur Influence 
 SUR LE Sang." Par Dr. M. Perrin, Professeur Agrege 
 a la Faculte de Medecine de Nancy. Preface de M. le 
 Professeur Gilbert. 1910. Pp. 147. J. B. Bailliere et 
 Fils, Paris. Fr. 4.00. 
 
 MANUFACTURERS' LITERATURE. 
 
 MERCK'S "ANNUAL REPORT FOR 1908." Vol. 
 XXII., 1909. Pp. 394 (102 of which are devoted to 
 Organotherapy). E. Merck, Darmstadt. Is. 6d. net. 
 
 "ADRENALIN: its Properties, Physiological 
 Action, and Therapeutic History." 1912. Pp. 104. 
 Parke, Davis and Co., Detroit and London. 
 
 " MANUEL DE L'OPOTHERAPIE." Public par le 
 Laboratoire Chaix. Pp.98. Chaixet Cie., Paris. Fr. 0.50. 
 
 "Etude physiologique et clinique des 
 
 GLANDES A SECRETION INTERNE." Par Dr. 
 
 Albert Fournier. 1912. Pp.120. Fournier Freres, Paris 
 
 " THE TRANSFUSION OF LIFE." By L. H. Goizet, 
 M.D. Translated into Enghsh by E. Montepic. 1912. 
 Pp. 191. Richter and Co., London. 
 
 "LA TRANSFUSION VITALE." Par Dr. L. H. 
 Goizet de la Faculte de Medecine de Paris. 1912. Pp. 319. 
 Richter et Cie., London. 
 
 "RATIONAL ORGANOTHERAPY: with Refer- 
 ence to UROSEanoLOGY." By Professor Dr. A. von Poehl 
 and others. Translated from the Russian. 1906. Pp.239. 
 J. and A. Churchill, London. 7s. 6d. net. 
 
 " ORGANOTHERAPEUTISCHES COMPENDIUM." 
 1912. Pp. 116. Prof. Dr. v. Poehl and Sohne, Berlin, etc. 
 
 " PHYSIOLOGICAL CRITERIA FOR MEDICINAL 
 SUBSTANCES." 1913. Pp. 59. Burroughs Wellcome 
 and Co., London. 
 
 " TRAITEMENT DE LA TUBERCULOSE PAR LA 
 PARATOXINE bask sur l' Action Antotoxique du 
 FoiE." Par Drs. E. Gerard et G. Lemoine, Professeur 
 du Clinique Medicale a la Faculte de Medecine de Lille. 
 1908. Pp.74. Vigot Freres, Paris. Fr. 1.50.
 
 INDEX 
 
 Abortion caused by adrenaline, 270 
 " Acid reflex," the, 55 
 Acidsemia, relation to disease, 221 
 Acidosis following parathyroidec- 
 tomy, 220 
 thymectomy, 236 
 Acromegaly, 291 
 
 Active principle, first endocrine, 6 
 Activity of various secretins, 56 
 Addison's disease, 259 
 
 adrenal therapy in, 264 
 Adenitis, lymphatic extract in, 398 
 Adenoids, lymphatic extract, 399 
 Administration of pituitrin, 299 
 Adrenal action on sugar combustion, 
 262 
 antagonism to ovaries, 363 
 cortex, action of, 260 
 insufficiency, types of, 266 
 line, the, 267 
 lipoids, 449 
 
 medullary extracts, 259 
 principle, action of, 258 
 " Adrenal system," the, 265 
 Adrenal therapy, 263 
 
 contra-indications to, 283 
 in acute toxaemias, 266 
 indications for, 466 
 Adrenals and glycosuria, 31 
 and muscular work, 263 
 antagonism to pancreas, 101 
 relation to gonads, 261 
 to mind, 281 
 
 to sympathetic system, 
 258 
 Adrenalin, 6, 10 
 
 and hypophysin, 275 
 compared with pituitrin, 277, 
 
 313 
 formula of, 282 
 in asthma, 280 
 
 in control of haemorrhage, 260 
 in snake-bite, 278 
 isolation of, 259 
 mydriasis in diabetes, 103 
 Adrenaline, an angiotonic remedy, 
 276 
 antidote to thyroid toxins, 209 
 a uterine relaxant, 284 
 glycosuria, 101 
 in cholera. 268 
 in dengue, 268 
 in heart disease, 277 
 
 476 
 
 Adrenaline in kidney extracts, 246 
 in salvarsan accidents, 280 
 in urticaria, 276 
 nomenclature, 282 
 sensitiveness to, in diabetes, 
 263 
 Albuminuria, control by pituitrin, 
 300 
 renal extract in, 247, 249 
 Alcoholic insanity, thyroid cure of, 
 
 197 
 Alimentary fermentation, control of, 
 67 
 hormones, 82 
 
 toxaemia, relation of thyroid to, 
 195 
 Alopecia, placenta in, 387 
 thyroid and, 199 
 therapy in, 209 
 Amenorrhoea, ovary in, 359 
 pitiLglandol in, 301 
 thyroid in, 199 
 Anaemia, hepatic extract in, 166 
 secondary, ovary in, 359 
 spleen extract in, 133 
 Androcrinol, 453 
 
 Angiotonic action of adrenal me- 
 dulla, 260 
 of pituitary, 295 
 remedy, adrenaline a, 276 
 Antagonist hormones, use of, 423, 
 
 428 
 Anterior pituitary hormone, 12 
 Antiasthenic action of whole adrenal 
 
 extracts, 261 
 Antidiabetic action of pancreas, 94 
 Antihaemorrhagic effect of mam- 
 mary extracts, 375 
 Antineuritic action of cord extract, 
 
 331 
 Antisecretin, 71 
 
 Antiseptic, bile and intestinal, 175 
 Antithyroidin, 206 
 Antitoxic action of brain extracts, 
 330 
 of parathyroid extracts, 221 
 of renal extract, 248 
 of testicular extract, 340 
 functions of thyroid, 179 
 Anuria, pituitrin in, 305 
 Aphrodisiac action of ovarian ex- 
 tract, 362 
 Appendix, hormone action of, 87
 
 Index 
 
 411 
 
 Appetite, pluriglandular extracts 
 and, 413 
 
 thyroid increases, 192 
 Arrhythmia, adrenal therapy in, 
 
 277 
 Arsenic and thyroid medication, 212 
 Arterio -sclerosis, calcium metabol- 
 ism and, 220 
 Arthritis, pituitary in, 312 
 
 thymus therapy in, 240 
 Ascites, hepatic, control of, 161 
 Asiatic cholera, adrenaline in, 268 
 Asthenia, 409 
 
 juvenile, 418 
 
 pituitary in, 294 
 
 testicular extract in, 341 
 Asthma, adrenalin in, 280 
 
 adrenal treatment, 276 
 
 pituitrin in, 313 
 
 thyroid in, 193 
 Aslhitiolysin, 276 
 Ataxia. See " Tabes." 
 Atrophic cirrhosis of liver, 161 
 Autacoids, 10 
 Auto -intoxication, spermin in, 339 
 
 B. bulgaricus and secretin, 68 
 Baldness. See " Alopecia." 
 Basedow's disease. See " Graves's 
 disease " and " Hyperthyroid- 
 ism." 
 Bayle's splenic treatment in tuber- 
 culosis, 135 
 Beebe's antiserum for hyperthy- 
 roidism, 206 
 hypotensive thyroid extract, 209 
 thyroid " X-substance," 189 
 " Bengal head," 414 
 Bernard (CI.) : inauguration of ani- 
 mal therapy, 3 
 Berthold's work, 3 
 Bile, action on bile jiroduction, 172 
 administration, 174 
 indications, 466 
 functions of, 172 
 medication, early references to, 
 
 171 
 relation of spleen to, 127 
 Biliary and hepatic extracts, 168 
 
 lithiasis, 176 
 /i-iminazolylethylamine, 86 
 Bladder, action of prostate extract 
 
 on the, 344 
 Blood findings in diabetes, 115 
 
 influence of spleen extracts on, 
 
 132 
 plasma, role of, 15 
 pressure, effects of adrenalin 
 on, 260 
 kidney extracts on, 245 
 
 Blood-pressure, pancreas action on, 
 108 
 pituitary action on, 292 
 Bone extract, 436 
 
 growth, hormone control of, 12 
 stimulation by adrenaline, 
 272 
 marrow and spleen extract, 130 
 stimulated by spleen ex- 
 tract, 134 
 Books on internal secretions, etc., 
 
 470 
 Brain extract, action of, 329, 331 
 in insanity, 332 
 preparation of, 332 
 Brighfs disease. See " Nephritis." 
 Bronchitis, lung extract, 391 
 Brown-Sequard's experiences, 339 
 Bulbo-spinal myasthenia, 415 
 Burns, epithelium extract in, 435 
 
 Cachexia, pluriglandular therapy in, 
 423 
 secretin in, 74 
 striunipriva, 189 
 thymipriva, 235 
 Calcium and parathyroid therapy, 
 221 
 chloride in hyperthyroidism, 205 
 metabolism and the endocrine 
 organs, 236 
 and the thymus, 235 
 influence of parathyroids 
 on, 220 
 ovarian control of, 352 
 relation to cellular excitability, 
 
 220 
 salts in parathyroid tetany, 221 
 Cammidge's diagram, 36 
 Cancer and internal secretions, 29 
 pluriglandular therapy in, 421 
 secretin in, 74 
 Carbohj'drate metabolism, 22, 101. 
 
 See also " Glycosuria." 
 Carbon dioxide, 11 
 Carbuncles in diabetes, 114 
 Cardiac disease, adrenal therapy in, 
 277 
 pituitary therapy in, 310 
 Carotid gland, 258, 395 
 Castration, effects of, 335 
 Cataract, lens extract in, 437 
 parathyroid origin of, 228 
 Cej)haline, 329 
 Cerebrin, 332 
 Chalones, 10 
 
 Charlatanism and animal therapy, 5 
 Children, backward, treatment of, 
 418 
 chronic hypoadrcnia in, 271
 
 478 
 
 Practical Hormone Therapy 
 
 Children, cyclic vomiting in, 271 
 pleurisy with effusion in, 275 
 thymus therapy of dystrophies 
 
 in, 237 
 thyroid therapy of nutritional 
 disorders in, 203 
 Chlorosis, ovary in, 359 
 spleen in, 133 
 thymus therapy in, 240 
 Cholagogue, bile a physiologic, 173 
 
 secretin, a, 60 
 Choleine, action of, 174 
 Cholera and hypoadrenia, 264 
 Asiatic, adrenaline in, 268 
 Cholesterin, 329, 447 
 Chorea, acidaemia in, 221 
 
 parathyroidine in, 226 
 Chromaffin hormone, 101 
 action of, 259 
 and glycosuria, 31 
 system, components of the, 257 
 Ciliary extract, 437 
 Cirrhosis, hepato-pancreatic, 165 
 
 of the liver, 161 
 Climacteric. See also " Menopause." 
 insanity, thyroid therapy in, 
 
 202 
 ovarian therapy, 356 
 Coagulation, blood, liver influence 
 on, 156 
 thrombokinase in, 394 
 Codeine and trypsogen in diabetes, 
 
 115 
 Cod-liver oil, 2 
 
 active principles, 157 
 lecithides in, 158 
 Uoeliacin, 400, 402 
 Cold, sensitiveness to, 192 
 Colic, bile in hepatic, 173 
 
 hepatic, prevention of, 175 
 Colitis, causation of membranous, 
 173 
 treatment of, 176 
 Collapse, adrenaline in, 277 
 after liormonal, 150 
 pituitary therapy in, 294 
 Colloidogenine in tuberculosis, 136 
 Colloidogens, the function of the, 
 
 136 
 Cpmbined gland extracts, 406 
 Congestion, adrenaline in, 279 
 Connective-tissue growth, activation 
 
 of, 140 
 Constipation, bile in, 174 
 honnojud in, 148 
 pluriglandular treatment and, 
 
 168 
 secretin in, 66 
 Contracture, palmar, thyroid ther- 
 apy in, 198 
 
 Contraindications to adrenal ther- 
 apy. 283 
 to pituitary therapy, 300, 315 
 to thyroid therapy, 209 
 
 Control of hormone production, 23 
 
 Convulsive conditions, parathyroi- 
 dine in, 226 
 
 Cord extract, detoxicating action of, 
 331 
 
 Corpus luteum, action of, 349 
 
 Cortex, adrenal, lipoid from, 449 
 of adrenals, action of, 260 
 
 Coryza, adrenaline in, 279 
 
 Cretinism, 182 
 
 Crile's theory, 38, 265 
 
 Cryptorchism, thyroid in, 203 
 
 Crystalloids, 14 
 
 Cutaneous opotherapy, 435 
 
 Cyclic vomiting in children, 271 
 
 Cystitis, adrenaline in, 279 
 
 Deaminizing hormone in thyroid, 196 
 Decidual internal secretion, 384 
 Defectives, pluriglandular therapy 
 
 in, 417 
 Definitions in glossary, 455 
 Dementia praecox, 420 
 Demineralization control by spleen, 
 136 
 bone extract in, 436 
 Dengue fever, adrenal therapy in, 
 
 268 
 Depressine, 85 
 Depressor action of thyroid, 201 
 
 hormones in pituitary, 311 
 Dermatology, thyroid extract in, 
 
 198 
 Dermatoses, cutaneous extract in, 
 435 
 testicular extract in, 340 
 thyroid in, 193 
 Detoxicating action of brain and 
 cord extracts, 331 
 of parathyroids, 217 
 Detoxication by intestinal extract, 
 87 
 by lipoids, 447 
 the thyroid a factor in, 195 
 Development, control of, by testes, 
 336 
 pineal in, 324 
 Developmental delay, thymus 
 therapy in, 236, 237 
 disturbances of children, thy- 
 roid in, 203 
 Diabetes, adrenalin mydriasis in, 
 103 
 and tuberculosis, relations of, 
 
 114 
 blood in, 115
 
 Index 
 
 479 
 
 Diabetes, gangrene, trypsogen in, 107 
 hepatic, and tuberculosis, 1(55 
 
 origin of, 164 
 Langerhansian insufficiency in, 
 98 
 origin of, 99 
 opsonic index in, 114 
 pancreas antagonism to, 94 
 causation of, 92 
 treatment of, 103 
 secretin in, 74, 106 
 trypsogen treatment of, 107 
 " Diabete maigre," 102 
 Diabetes insipidus, action of pitui- 
 tary in, 306 
 pituitrin in, 307 
 Diabetics, adrenaline, sensitiveness 
 
 to, 263 
 Diagnosis, functional, of pancreas, 
 102 
 of hypoadrenia, 267 
 Diagram of endocrine relations, 42 
 
 of secretin action, 64 
 Diarrhoea, secretin in, 73 
 Didymin, 335, 342 
 Diet and tumour growth, 30 
 Digestion, influence of splenectomy 
 on, 124 
 in stomach, spleen's action on, 
 
 120 
 salivary, in stomach, 49 
 Digestive disorders, liver extract in, 
 160 
 insufficiencies, secretin in, 72 
 Dioscorides and biliary medication, 
 
 171 
 Diphtheria and hypoadrenia, 264 
 Discovery of hormone action, 6 
 Diuresis, action of pituitary on, 305 
 
 of renal extract on, 247 
 Diuretic action of renal extracts, 251 
 of tonsil extract, 255 
 hormone, 12 
 Dosage, estimation of, 444 
 of hormones, 24 
 of mammary extract, 379 
 of ovarian cxti'acts, 365 
 of pituitary substance, 291 
 of placental extract, 388 
 of spleen preparations, 140 
 of thyroid extract, 197, 211, 445 
 Dose table, 465 
 Drug action, enhanced by glandular 
 
 therapy, 413 
 Duodenal hormone, 12 
 
 therapy, indications for, 467 
 Dupuytren's contraction, thyroid 
 
 therapy of, 198 
 Dynamogenic action of testicular 
 extract, 340 
 
 Dysmenorrhoea, ovary in, 359 
 parotid extract in, 53 
 thyroid therapy in, 200 
 
 Dyspituitarism, 291 
 
 Dysthyroidism, 204 
 
 Dystrophies in children, thymus 
 extract in, 237 
 
 Dysuria, pituitrin in, 305 
 
 Earliestmentionof organo-therapy, 2 
 Eclampsia, parathyroidine in, 223 
 
 placenta in, 384 
 
 thyroid in, 200 
 Eczema, ovary in, 356 
 
 thyroid in, 198 
 Emergencies, pituitary in surgical, 
 
 295 
 Emotional polyuria, 307 
 Empirical application of adrenaline, 
 264 
 
 hormone therapy, 23 
 
 therapy, 23, 466 
 
 thyroid therapy, 193 
 Endocrine relations, diagram of, 42 
 Enteric therapy indications for, 84, 
 
 467 
 Enterokinase, 57 
 
 Enterokinesia, action of pituitary 
 on, 302 
 
 hormone control of, 144 
 
 secretin stimulation of, 60 
 Enterokinetic hormone, 85 
 Enzyme therapy, pancreatic, 93 
 Enzymes compared with hormones, 
 13 
 
 spleen'sactivation of gastric, 126 
 Epilepsy, acidsemia in, 221 
 
 parathyroids in, 224 
 Epinephrin, 263, 282 
 
 composition of, 282 
 Epiphysis. See " Pineal." 
 Epistaxis, hepatic extract in, 162 
 " Epithelial bodies," the, 215 
 Epithelium, extracts of, 435 
 Equilibrium, intercellular, 28 
 Ergamine, 86 
 
 Ergot and pituitary combined, 298 
 Erysipelas, hypoadrenia in, 266 
 Erythrocytes increased by spleen 
 
 extract, 133 
 Eustachius's glands, 257 
 Exo-gastrine, 83 
 
 Exophthalmic goitre. See " Hyper- 
 thyroidism." 
 Experimental diabetes, 93 
 External parathyroids, 215 
 
 Falta's diagram, 35 
 
 Fat indigestion, bile in, 176 
 
 metabolism, thyroid control of, 
 184
 
 480 
 
 Practical Hormone Therapy 
 
 Fear, stimulation of adrenals by, 281 
 Fermentation, alimentary, control 
 
 of, 67 
 Ferments, 13 
 Fibroids, mammary therapy in, 375 
 
 X ray in, 351 
 Flatulence, secretin in, 73 
 Foetal hormone, 12 
 
 pancrea,tic internal secretin, 95 
 Fractures, adrenaline in, 273 
 Frohlich's syndrome, 292 
 Fimctional hypothyroidism, 183, 
 191 
 nerv^ous disorders, lymphoid 
 cam-pound in, 401 
 nerve extracts in, 330 
 Fimdamentals of hormone therapy, 
 24 
 
 Galactagogue action of pituitary, 
 308 
 
 mammarj' extract a, 373 
 
 placental extract a, 383 
 Galen and animal therapy, 2 
 Galen's description of thyroid, 181 
 
 use of dried liver, 155 
 Gall-stones, bile in, 175 
 
 causation of, 176 
 Gangrene, diabetes, irypsogtn in, 
 107, 115 
 
 diabetic, frequency of, 114 
 
 pancreas preparations m, 115 
 Gastric activation by spleen, 125 
 
 extracts, 83 
 
 and peristalsis, 145 
 
 haemorrhage, adrenaline in, 279 
 
 secretin, 12, 57 
 Gastrin, 12, 57 
 Geni to -urinary practice, adrenaline 
 
 in, 279 
 Gland extracts, preparation of, 439 
 Glands, tuberculous, spleen extract 
 
 in, 137 
 Glossary of terms, 455 
 Glycosuria, 30 
 
 action of adrenals on, 262 
 
 of typhoid vaccine on, 117 
 
 adrenaline, 101 
 
 and typhoid, relations of, 117 
 
 experimental, 93 
 
 hepatic extract in, 164 
 origin of, 165 
 
 increased by thyroid extract, 210 
 
 post cibum, 165 
 
 rhythmic, 164 
 
 severe, trypsogen control of, 108 
 
 trypsog&n in, 107 
 Goitre, thymus therapy in, 237 
 
 thyroid therapy in, 1S9 
 Gonads, influence of thyroid on, 186 
 
 Gonads, lipoids from, 453 
 relation to adrenals, 261 
 to parotid, 52 
 to pituitary, 290 
 to thymus, 38, 235 
 Gout, hepatic extract in, 166 
 Graft, ovarian, in insanity, 361 
 of pancreas, 94 
 thjonus, 234 
 Graves's disease. See "Hyperthy- 
 roidism." 
 adrenal in, 428 
 newer conceptions of, 204 
 thymus in, 428, 431 
 thyroid activities in, 183 
 '' Great secret," the, 425 
 Growth, action of lipoids on, 449 
 anomalies of, 5 
 
 influence of cod-liver lecithides 
 on, 158 
 of testes on, 336 
 relation of thymus to, 235 
 thyroid control of, 184 
 Gynsecologj', pituitary in, 301 
 
 thyroid therapy in, 199 
 Gynocrind, 453 
 dynoluted, 453 
 
 Haemoglobin, spleen's influence on, 
 
 127, 133 
 Htemopliilia, opotherapy in, 163 
 Haemoptysis, hepatic extracts in, 
 
 161 
 Hasmorrhage, control of, with adren- 
 alin, 260 
 gastric, adrenal therapy in, 279 
 hepatic extracts in, 162 
 pituitary in, 298 
 spleen extract for, 134 
 (local) thrombokinase in, 394 
 uterine, mammary extract in, 
 374 
 jntuitrin in, 301 
 Haemorrhages, punctate, 161 
 Haemorrhoids, adrenal therapy in, 
 
 279 
 Hallion's law, 24 
 Hay -fever, adrenaline in, 279 
 
 pituitrin in, 313 
 Headache, thyroid and, 199 
 Headaches (ovarian), parotid ex- 
 tract in, 53 
 Heartdisease, adrenal therapy in, 277 
 Heart extract in myocardial disease, 
 
 435 
 Heart-lung preparation (Knowlton 
 
 and Starling), 96 
 Hedon's transfusion experiments, 94 
 Hemafo-ethyroidine, 206 
 Htminine, 282 
 
 I 
 
 I
 
 Index 
 
 481 
 
 Hepatic action, hormone control of, 
 156 
 
 and parathyroid extracts, 227 
 
 cirrhosis, treatment of, 161 
 
 colic, prevention of, 175 
 
 congestion and glycosuria, 165 
 
 diabetes, 164 
 
 extracts, value of, 159 
 
 indolence in gout, 166 
 Hepato-pancreatic cirrhosis, 165 
 Herpetic angina, thyroid in, 193 
 Hertoghe's syndrome, 191 
 Hippocrates and animal therapy, 2 
 
 and ox-gall medication, 171 
 Hodgkin's disease, lymphatic ex- 
 tract in, 400 
 Holadin in diabetes, 106 
 Homoeopathy, 2 
 Homostimulant action of extracts, 24 
 
 of lipoids, 448 
 Hormonal, 85, 145 
 
 administration of, 151 
 
 and pituifrin combined, 148 
 
 dangers of, 150 
 Hormone action, 9 
 
 discovery of, 6, 55 
 
 balance, 16 
 
 relation of secretin to, 76 
 thyroid control of, 34 
 upset of, 406 
 
 control of carbohydrate metab- 
 olism, 32 
 of enterokinesia, 144 
 of liver, 156 
 
 chromaffin, action of, 259 
 
 defects, 409 
 
 definition of, 7, 9 
 
 dosage, 24 
 
 mamma, 7 
 
 mammary, 368 
 
 parathyroid, 215 
 
 pathological, from ovary. 351 
 
 peristaltic, 85 
 
 placental, 383 
 
 production, control of, 23 
 
 testicular, 335 
 
 therapy, beginning of, 8 
 
 thymus, 233 
 Hormones, two ovarian, 348 
 
 administration of antagonist, 
 423 
 
 alimentary, 82 
 
 and enzymes, 13 
 
 and muscle action, 41 
 
 classification of, 10 
 
 list of, 11 
 
 of the pituitary, 289, 293 
 
 psychic control of, 44 
 
 replacing, 20 
 
 the thyroid, 181 ^ 
 
 Hormotone, 414 
 " Humoral theory," the, 2 
 Hustin's experiment, 62 
 Hydrochloric acid, 12 
 
 action of secretogen on, 72 
 Hyperadrenia, pancreas in, 429 
 Hyperendocrinism, 428 
 Hyperfunctiou, ovarian, mammary 
 
 extract in, 379 
 Hyperoophorism, control of, 362 
 Hyperovaria, 428 
 Hyperpinealism, results of, 321 
 Hyperpituitarism, 290 
 
 X ray in, 431 
 Hypertension, control by Beebe's 
 thyroid X-substance, 201 
 
 pancreas extract in, 108 
 
 X ray in, 432 
 Hyperthyroidism. See " Graves's 
 disease." 
 
 drugs which control, 205 
 
 ovarian disorders in, 36 
 therapy in, 353 
 
 physiological, 200 
 
 Rontgenotherapy in, 37 
 
 signs of, 192 
 
 thymin in, 239 
 
 thymus therapy in, 238 
 
 treatment of, 189 
 
 X ray in, 205 
 Hypoadrenia, 264, 265 
 
 in children, 271 
 
 in the acute infections, 266 
 
 in tuberculosis, 274 
 
 manifestations of, 266 
 
 signs of, 267 
 Hypochlorhydria, secretogen in, 72 
 Hypoendocrinism, 409 
 
 in children, 272 
 Hypo-oophorism, 352 
 Hypoparathyroidism, 223 
 Hypophysm, 10, 293, 313 
 Hypophysis. See "Pituitary." 
 Hyposphyxia, 421 
 Hypotensive action of hormonal, 
 145, 147 
 
 pituitary extract, 311 
 Hysteria, ovary in, 360 
 
 Icterus, bile in, 173 
 
 Galen's method of heating, 155 
 
 hepatic extract in, 163 
 Idiocy, Mongolian, 407 
 Idiotia thymica, 235 
 Immunity, thyroid in, 195 
 Impotence, 2 
 
 Incontinence, nocturnal, thyroid ex- 
 tract in, 263 
 Indigestion, animal extracts in, 54 
 
 secretin treatment of, 71 
 31
 
 482 
 
 Practical Hormone Therapy 
 
 Infantile diari'hcea, secretin in, 73 
 Infantilism, pituitary therapy in, 291 
 thyroid in, 199 
 thyroid therapy in, 203 
 Infections following pancreatec- 
 tomy, 113 
 hepatic extract in certain, 167 
 in diabetes, 113 
 pancreas control of, 112 
 splenic defence in, 139 
 Infectious diseases and hypoadrcnia, 
 264 
 spleen extract in, 129 
 Infimdibular hormone, 12 
 
 therapy, indications for, 467 
 Insanity, alcoholic, thyroid in, 197 
 brain extract in, 332 
 ductless glands in, 419 
 ovary in, 360 
 
 thyroid therapy in, 202 
 Insomnia, 414 
 Intercellular equilibrium, 28 
 Interstitial nephritis, renal extract 
 
 in, 248 
 Intestinal antiseptic bile, a valuable, 
 175 
 extracts, 84 
 
 indications of, 467 
 paralj'sis, control of, 149 
 paresis, hormonal in, 146 
 pituitary in, 302, 304 
 Intestine, secretin activation of, 60 
 Intestines, relation of spleen to, 146 
 Iodine and thyroid medication, 197 
 coefBcieut, 443 
 in thyroid, 187 
 
 standard of thyroid activity, 187 
 lodothyrin, 12, 183, 207 
 Irido-cyclitis, ciliary extract in, 437 
 Iron and ovarian therapy, 359 
 loss after splenectomy, 128 
 metabolism, spleen and, 127 
 Islands of Langerhans, fimction of, 97 
 
 Jaimdice, hepatic extract in, 161 
 " Jerry-built constitution," 417 
 Juvenile asthenia, 418 
 
 Keloid, thyroid in, 198 
 
 Keratin, 435 
 
 Kidney. See "Renal." 
 
 disease, renal extracts in, 247 
 
 hormone, 12 
 
 internal secretion of, 245 
 Kinetic system, 38 
 
 therapy, 407 
 Knowlton and Starling's experi- 
 ments, 96 
 
 Labour, delayed. 297 
 
 pituitary extract in, 296 
 
 Lactation, pituitary stimulation of, 
 
 308 
 Lacto-vegetarian regime in diabet 
 
 165 
 Langerhansian compression, 99 
 extracts, 103, 306 
 hormone, 91 
 insufficiency, 98 
 origin of diabetes, 99 
 Laryngitis, adrenaline in, 279 
 Lecithin, 447 
 
 Lens extracts in cataract: 437 
 Leucocytoses, lymphatic gland 
 
 causes, 399 
 Leucocy tosis, spleen extract favours, 
 129 
 thymus extract and, 132 
 Lipo'ides, H. I., 449 
 Lipoids, 446 
 
 action of, 448 
 
 from thyroid and pituitary, 452 
 of gonads, 453 
 relation to tuberculosis, 451 
 Liver disorders, pluriglandular ther- 
 apy of, 168 
 extracts, indications for, 467 
 fimctions of, 155 
 inactions, stimulation of, 160 
 internal secretion of, 159 
 relation to parathyroids, 227 
 secretin activation of, 60 
 stimulation by pancreas lipoid, 
 451 
 Locomotor ataxia. See " Tabes." 
 Loewi's adrenalin test, 103 
 Lung extracts, action of, 391 
 indications for, 467 
 Luteal extract in vomiting of preg- 
 nancy, 360 
 hormone, 349 
 lipoid, 453 
 preparations, 355 
 Lutein, advantages of, 355 
 
 influence on sterility, 350 
 LjTnphatic extracts, action of, 398 
 in Hodgkin's disease, 400 
 preparation of, 402 
 glands and leucocytoses, 399 
 relation of thymvis to, 223, 
 398 
 therapy, indications for, 467 
 Lymph nodes, action of, 397 
 Lymphoid compound, 401 
 
 indications for, 402 
 
 Malaria, spleen extract in, 129 
 Malnutrition, combined liver medi- 
 cation in, 167 
 
 secretin in. 74 
 
 spleen extract in, 141
 
 Index 
 
 483 
 
 Malnutrition, thymus therapy in, 23(5 
 Malpresentations, pituitary in, 298 
 " Mamma hormone," 7, 38 
 Mammte, liormone control of, 369 
 Mammary abscess, pituitary in, 309 
 control of ovaries, 373 
 extract a galactagogue, 373 
 growth, lutein action on, 350 
 secretion, influence of thyroid 
 
 on, 186 
 therapy, indications for, 468 
 Mammin, action of, 377 
 Mania, brain extract in, 332 
 Manufacturer's literature, 475 
 Marasmus, relation to thymus, 236 
 Melancholia, brain extract in, 332 
 Membranous colitis, bile in, 176 
 Menopause, ovarian therapy in, 356 
 Menorrhagia, mammary extract in, 
 374 
 pituitrin in, 301 
 spleen extract in, 134 
 Menstrual disorders, thyroid therapy 
 
 in, 201 
 Menstruation and the luteal hor- 
 mone, 349 
 hormone control of, 362 
 Mental development, pineal in, 325 
 disorders, brain extract in, 332 
 ductless glands in, 419 
 thyroid in, 202 
 Mesenteric gland extract in sclero- 
 derma, 400 
 V. Mcring and Minkowski's experi- 
 ments, 93 
 Metabolism, 5 
 
 action of spermin on, 339 
 importance of, 18 
 influence of ovaries on, 351 
 
 of parathyroids on, 216 
 of iron, 127 
 pineal action on, 324 
 thymus action on, 237 
 thyroid control of, 184 
 Meteorism, hormonal in, 146 
 
 pituitary in, 304 
 Metrorrhagia, mammary extract in, 
 374 
 pituitrin in, 301 
 Mickulicz's method in goitre, 238 
 Migraine, thyroid in, 193 
 Milk production, placental extract 
 in. 383 
 secretion, pituitary stimulation 
 of, 308 
 Mind, influence on hormone })ro- 
 duction, 44 
 relation of adi'enals to, 281 
 Mineralization, ovarian control of, 
 352 
 
 Minor endocrine disorders, 21 
 thyroid insuilicicncy, 190 
 " Mobilization " of sugar, 101 
 Mongolian idiocy, 407 
 Mongolism, thyroid therapy in, 203 
 Morphinomania, adrenal therapy in 
 
 280 
 Morphogenesia, 5 
 Motiline, 85 
 
 Mucinase, action of. 173, 177 
 Muco -membranous colitis, causation 
 
 of, 173 
 Mucous, coagulation of, 176 
 colitis, bile in, 176 
 secretin in, (57 
 Murray's use of thyroid substance 
 
 188 
 Muscle action, hormones and, 41 
 Muscular work, action of adrenals 
 
 on, 263 
 Myasthenia, bulbo-spinal, 415 
 Mydriasis, adrenalin, in diabetes, 
 
 103 
 Myocardial asthenia, pituitary in, 310 
 disorders, heart extract in, 435 
 Myoclonia, 223 
 Myometrial gland, 382, 384 
 Myotonic action of adrenal cortex, 
 
 260 
 Myxoedema, 182 
 
 combined glands in, 407 
 thyroid therapy in, 189 
 
 Neohormonal, 150 
 Nephrine, action of, 250 
 Nephritis, chronic, renal therapy in, 
 251 
 
 pituitary in, 305 
 
 renal extract in, 247 
 Nerve extracts, indications for, 329, 
 
 468 
 Nervous equilibrium, 5 
 Neurasthenia, 411 
 
 and hypothyroidism, 192 
 
 lutein in, 358 
 
 minor, 412 
 
 pluriglandular therapy in, 411 
 
 prostatic extract in, 344 
 
 ap&rmin in, 3;{9 
 
 tropical, 414 
 Neuroses of menopause, ovary in, 356 
 Night sweats, hepatic extracts in, 167 
 Nocturnal incontinence, thyroid 
 
 therapy in, 203 
 Nomenclature. See Glossary, 455 
 Nutrition, action of adrenals on, 262 
 of testes on, 335 
 
 control of, 29 
 
 of. by thyroid, 182, 184 
 
 h(>|mtic extract action on. 161
 
 484 
 
 Practical Hormone Therapy 
 
 Nutrition, influence of spleen on, 124 
 nervous, nerve extracts in, 329 
 pituitaiy stimulation of, 294 
 
 Nutritional disorders in children, 
 thyroid in, 203 
 
 Obesity and testicular action, 335 
 combined glands in, 407 
 from hypo-oophorism, 352 
 parotid involvement in, 51 
 thyroid therapy in, 194 
 Obstetric contra-indications to pitu- 
 itary, 300 
 Obstetrics, pituitary in, 297 
 Obstipation. See "Constipation." 
 Qlldema, thyroid and, 199 
 
 hepatic extract in, 161 
 Ophthalmic organotherapy, 437 
 Opsonic index in diabetes, 114 
 
 pancreatin and, 118 
 Orchipina, 342 
 
 Orchitic extracts. See " Testicular 
 extracts." 
 action of, 338 
 Organotherapeutic dose table, 465 
 Organotherapy, earliest reference 
 
 to, 2 
 Osteo-articular tuberculosis, spleen 
 
 extract in, 137 
 Osteomalacia, adrenaline in, 273 
 ovariotomy for, 353 
 pituitary in, 312 
 thymus and, 235 , 
 Ovaraden, 359 
 
 ■triferrin, 359 
 Ovarian activity, mamma control 
 of, 373 
 and thyroid extracts, 208 
 congestion, mammary extract 
 
 in, 374 
 disease, parotid therapy in, 52 
 disorders in hyperthyroidism, 
 
 36 
 hormone, 13, 348 
 insufficiency, thyroid therapy 
 
 in, 199 
 lipoids, 453 
 origin of chlorosis, 360 
 therapy at the climacteric, 356 
 contra-indications to, 364 
 indications for, 468 
 Ovaries, action on metabolism, 351 
 and calcium metabolism, 352 
 control of adrenals by, 262 
 influence on oxidation, 347 
 pathological hormone from, 351 
 regulation of saline elements, 352 
 relation to pituitary, 352 
 
 to thyroid, 353 
 thyroid action on, 200 
 
 Ovariotomy for osteomalacia, 35? 
 Ovaritis, parotid extract in, 53 
 Overdosage of thyroid, symptoms ul, 
 
 212 
 Oxidation, increasing, 340 
 
 relation of ovaries to, 347 
 Oxytocic action, comparison of 
 adrenaline and pituiirin, 
 284 
 of mammary extracts, 377 
 of pituitary, 296 
 
 Pain in Asiatic cholera, 282 
 
 stimulation by adrenals by, 281 
 Paludism, spleen extract in, 129 
 Pancreas, antagonism to adrenals, 
 101 
 antidiabetic action of, 94 
 control of infections, 112 
 
 of sugar metabolism, 31 
 extract in hypertension, 108 
 
 (Zuelzer), 105 
 feeding, 105 
 graft, 94 
 hormone, 92 
 in hyjieradrenia, 429 
 influence on phagocytosis, 109 
 lipoid, 451 
 opposes thyroid, 30 
 relation to diabetes, 100 
 
 to parotid, 52 
 therapy, indications for, 408 
 treatment of diabetes, 103 
 Pancreatic diabetes, 92 
 
 differentiation of, 102 
 (v. Noorden's ideas), 95 
 digestion, salivary activation of, 
 
 50 
 fimction, influence of spleen on, 
 
 126 
 hormones, 12 
 " Pancreatic secretin," 57 
 activation of. 57 
 Pancreatin in tubrrculosis, 118 
 Paralysis agitans, t.: idsomia in, 221 
 treatment of, 222 
 control of intestinal, 149 
 Paraphymosis, adrenaline in, 280 
 Parathyroid extract, dosage of, 228 
 therapy, 221 
 
 indications for, 468 
 Parathyroidectomy, results of, 216 
 Parathyroidine in epilepsy, 225 
 Parathyroids and glycosuria, 32 
 detoxicating action of, 217 
 discovery of, 215 
 influence on calcium metabol- 
 ism, 220 
 relation to thyroid, 218 
 Paraloxine, 168
 
 Index 
 
 485 
 
 P%rhormoiies, 351 
 1 • ;-kiuson'8 disease. Sec " Paralysis 
 'ugitana." 
 Parotid. See "Salivary glands." 
 
 enlargement in obesity, 51 
 
 relation to gonads, 52 
 to pancreas, 52 
 
 therapy in ovarian disease, 52 
 Pelvic disorders, parotid therapy of. 
 52 
 
 narrowing, pituitary in, 298 
 Pepsin production, 59 
 Peristalsis, hormonal action on, 147 
 
 spleen's action on, 128 
 Peristaltic hormone, the, 85, 129, 144 
 Peritonitis, pituitary in, 303 
 Phagocytosis, organotherapy in, 119 
 
 pancreas influence of, 109, 119 
 Pharyngitis, adrenaline in, 279 
 Phlebitis, hepatic substance in, 163 
 Phosphoric acid, control of, by 
 
 thymus, 236 
 Phosphorus metabolism, action of 
 testes on, 340 
 and the thymus, 237 
 Physiological animal therapy, 23, 465 
 Pineal extracts, action of, 322 
 
 excess, results of, 321 
 
 gland, function of, 322 
 
 morphology of, 321 
 
 relation of, to pituitary, 323 
 
 therapy, indications for, 468 
 PituglaTidd, 313 
 
 in amenorrhoea, 301 
 Pituitary, a diuretic, 305 
 
 and diabetes insipidus, 306 
 
 and ergot in haemorrhage, 298 
 
 and glycosuria, 32 
 
 development of, 288 
 
 disease, signs of, 290 
 
 extract, a hypotensive, 311 
 
 extracts, action of, 292 
 
 administration of, 314 
 
 functions and relations of, 289 
 
 galactagogue action, 308 
 
 hormones, 289, 293 
 
 in gynaecology, 301 
 
 in mammary abscess, 309 
 
 in rheumatoid arthritis, 312 
 
 lipoids, 452 
 
 peristaltic action of, 302 
 
 powder as a tonic, 310 
 
 preparations, 313 
 
 relation to gonads, 290 
 to ovaries, 352 
 to pineal, 323 
 of thyroid to, 290 
 
 therapy, contra-indications to, 
 "300 
 indications for, 467 
 
 Pituitary, total extracts, 294 
 PituUrin, 294, 313 
 
 action on albuminuria, 300 
 and hormonal combined, 148 
 an ideal oxytocic, 299 
 compared with adrenalin, 217, 
 
 313 
 in asthma, 313 
 in diabetes insipidus, 307 
 in uterine haemorrhage, 301 
 prophylactic use of, 296 
 technique of administration of, 
 
 299 
 topical uses of, 312 
 Placenta praevia, pituitary in, 298 
 
 role in eclampsia, 384 
 Placental extract as a galactagogue, 
 386 
 in subinvolution, 387 
 extracts, action of, 383 
 hormone, 38 
 
 therapy, indications for, 468 
 Pleurisy, adrenaline in, 274 
 
 lung extract in, 392 
 Pliny and animal therapy, 2, 5 
 Pluriglandular extracts, 226, 354 
 therapy, 46, 208, 275 
 in cancer, 421 
 in constipation, 168 
 in malnutrition, 167 
 in mental diseases, 419 
 in neurasthenia, 413 
 indications for, 468 
 Pneumonia, lung extract in, 392 
 Polyuria, pituitary origin of, 306 
 pituitrin in, 307 
 trypsogeii in, 107 
 Polyvalency of thyroid secretion, 182 
 Popielski's opinion, 61 
 Post-operative intestinal atony, pitu- 
 itary in, 302, 304 
 Postpartum haemorrhage, ergamine 
 in, 87 
 pituitary in, 298 
 remedy, a, 377 
 Pregnancy, luteal extract in vomit- 
 ing of, 360 
 and the thyroid, 199 
 toxaemias of, thyroid in, 200 
 vomiting of, adrenaline in, 269 
 Premature labour, caution, 298 
 Proferments, 14 
 Progastrin, 59 
 
 Prolonged labour, pituitrm in, 299 
 Prosecretin, 58, 59 
 Prostate, internal secretion of, 343 
 Prostatectomy, prostatic therapy 
 
 after, 344 
 Prostatic congestion, adrenaline in, 
 280
 
 486 
 
 Practical Hormone Therapy 
 
 Prostatic extract, toxicity of, 345 
 hypertrophy, control of, 343 
 therapy, indications for, 468 
 Protein metabolism, thyroid control 
 
 of, 195 
 Protrypsinogen, 65 
 Psoriasis, thyroid in, 198 
 
 thyroid therapy in, 192 
 Psychic control of hormone produc- 
 tion, 44 
 defectives and pineal medica- 
 tion, 325 
 Psychomotor asthenia, 418 
 Ptyalin, 49 
 
 Puerperal eclampsia, parathyroid 
 therapy in, 223 
 phlebitis, control of, 163 
 Pulmonary infections (chronic), Imig 
 extract in, 392 
 tuberculosis. See ' ' Tubercu- 
 losis." 
 spleen extract in, 137 
 Punctate haemorrhage, control of, 
 
 161 
 " Punjab head," 414 
 
 Rachitis. See "Rickets." 
 after thymectomy, 235 
 Rage, stimulation of adrenals by, 281 
 Range of hormone action, 22 
 Rectal administration of bile, 177 
 
 of renal extracts, 248 
 Reizstoffe, 7 
 
 Remineralization, Bayle's theory of, 
 136 
 in tuberculosis, 135 
 Removal of pancreas, results of, 93 
 Renal extract, rectal administration 
 of, 248 
 insufficiency, 250 
 medication, basis of, 244 
 therapy, indications for, 467 
 Renaut's method, 247 
 Reproductive organs, thyroid action 
 
 on, 199 
 Rheumatism, ovary in, 362 
 thyroid in, 192 
 
 therapy in, 196 
 Rheumatoid arthritis, pituitary in, 
 312 
 thymus therapy in, 240 
 Rhinitis, adrenaline in, 279 
 Rickets, combined glands in, 407 
 pituitary in, 312 
 thymus therapy in, 237 
 thyroid in, 203 
 Rontgen ray. See "X ray." 
 Rontgenized spleen extract, 138 
 Rontgenotherapy in Graves's dis- 
 ease, 430 
 
 " Run-down conditions," ovary in, 
 357 
 
 pluriglandular therapy, 
 408 
 
 Saliva, activity of, 50 
 
 and pancreatic digestion, 50 
 Salivary digestion, 49 
 
 glands. See also " Parotid." 
 
 relations of, 51 
 hormone, 12 
 Salvarsan accidents, adrenaline in, 
 
 280 
 Scleroderma, mesenteric gland ex- 
 tract in, 400 
 thyroid in, 198 
 Scleroses, thyroid in, 198 
 Sclerosis, medullary, nerve extracts 
 
 in, 330 
 Secretin, 10, 55 
 action of, 15 
 
 diagram of, 64 
 and Bulgarian milk therapy, 68 
 availability fer os, 70 
 discovery of, 7 
 dosage of, 77 
 in constipation, 66 
 in diabetes, 106 
 preparation of, 57, 69 
 pyloric, 12 
 
 therapy, indications for, 467 
 contra-indications to, 78 
 with bile and hepatic extracts, 
 168 
 Secretogen in indigestion, 72 
 Selective action of hormones, 15 
 Sensitiveness to cold, thyroid in, 192 
 Sequarine, 342 
 Shock, adrenaline in, 277 
 Shock, pituitary therapy in, 294 
 " Shot-gun " hormone therapy, 424 
 Skin disease, cutaneous therapy in, 
 
 435 
 Skin diseases, ovary in, 356 
 
 thyroid in, 198 
 Snake bite, adrenaline in, 278 
 Sodium, relation to cellular excita- 
 bility, 220 
 Specific hormone therapy, 23, 465 
 Spermin, 339, 342 
 Spinal cord extract, 331 
 Spleen a defence organ against in- 
 fections, 139 
 and iron metabolism, 127 
 and peristalsis, 128 
 and stomach digestion, 126 
 control of demineralization by, 
 
 136 
 extract in tuberculosis, 119 
 functions of 121
 
 Index 
 
 487 
 
 Spleen, influence of, on nutrition, 124 
 internal secretion of, 123 
 relation to intestine, 14(5 
 
 to the thymus, 233 
 therapy, indications for, 468 
 trypsin, activation by, 126 
 Splenectomy, influence on digestion, 
 124 
 iron loss in, 128 
 Splenic disease, spleen extract in, 
 130 
 lipoid in tuberculosis, 452 
 opotherapy, 129 
 Splenitis (chronic), spleen extract in, 
 
 132 
 Splenolecithide, 453 
 Splenomegaly, treatment of, 131 
 Stability of enzymes, 13 
 
 of hormones, 13 
 Standardization of gland extracts, 
 
 442 
 Starling's discovery of secretin, 7, 57 
 Steatorrhcea, 102 
 
 Sterility, influence of lutein on, 350 
 thyroid in, 199 
 X ray and, 430 
 Stomach disorders, secretin in, 72 
 extracts of, 82 
 
 indications for, 469 
 Suboxidation, 409 
 Substitution therapy, 22, 465 
 Sugar combustion, adrenal action on, 
 262 
 " mobilization " of, 101 
 " Summer complaint," secretin in, 
 
 73 
 Superstition and animal therapy, 3 
 Supplementary therapy, 22, 465 
 Suppositories, adrenaline, 27 
 Suprarcnals. See " Adrenals." 
 Suprarenin, 282 
 
 Sympathetic nervous system rela- 
 tion to adrenals, 258 
 
 Tabes, lymphoid compound, 401 
 
 pluriglandular therapy in, 416 
 Tabloid three glands, 422 
 Takamine's discovery, 6 
 Tartaric acid in obstipation, 60 
 Technique of pituitrin administra- 
 tion, 229 
 Tension. See " Hypertension," 
 
 " Blood-pressure," etc. 
 Testes, influence on growth, 336 
 Testicular extract as a dynamogenic 
 agent, 340 
 hormone, 13 
 
 action of, 335 
 lipoid, 4.53 
 therapy, indications for, 469 
 
 Testikvlin, 342 
 
 Tests of pancreas inactivity, 102 
 
 Tetanus toxin, brain extract and, 
 
 330 
 Tetany, experimental, 215 
 parathyroidine in, 226 
 Thomsen's disease, 223 
 Thrombokinase, 393 
 Thymin, 239 
 
 Thymus and osteomalacia and 
 rickets, 235 
 development of, 232 
 functions of, 233 
 hormone, 12 
 in Graves's disease, 428 
 in hyperthyroidism, 238 
 in rheumatoid arthritis, 240 
 influence on leucocytosis, 132 
 
 of thyroid on, 181 
 relation to gonads, 38 
 
 to growth and calcium 
 metabolism, 235 
 relations of, 234 
 therapy, indications for, 469 
 Thyratoxine, 208 
 
 Thyroid, antitoxic functions of, 197 
 and tumour growth, 29 
 control of hormone balance, 34 
 of toxaemias of pregnancy, 
 200 
 deficiency, signs of, 199 
 extract, dosage of, 445 
 
 in nervous disorders, 202 
 fimctions, views of, 181 
 hormone, 12 
 in dermatology, 198 
 in nervous and mental diseases, 
 
 202 
 influence on blood -pressure, 201 
 iodine in, 187 
 lesions in rheumatism, 196 
 lipoids, 452 
 
 medication, dangers of, 194 
 opposes pancreas, 30 
 overdosage, symptoms of, 212 
 preparations, 206 
 dosage of, 211 
 early use of, 188 
 relation between, and para- 
 thyroids, 218 
 of ovaries to, 353 
 to endocrinous glands, 184 
 to pituitary, 290 
 secretion, poly valency of, 181 
 therapy, 180 
 
 contra-indications to, 209 
 empirical, 193 
 indications for, 409 
 untoward effects of, 209 
 Thyroidectin, 200
 
 488 
 
 Practical Hormone Thera'py 
 
 Thyroprotein, preparation of, 207 
 Tonic action of lymphoid compound, 
 401 
 pituitaiy powder as a, 310 
 Tonsil extracts, 255 
 Tonsils, enlarged, lymphatic extract 
 in, 399 
 value of, 254 
 Total dry adrenal extracts, 261 
 
 extracts of pituitary, 294 
 Toxsemia in fevers, adrenal therapy, 
 
 266 
 Toxic hepatic disorders, 165 
 Toxicity of pituitary extracts, 314 
 Transfusion from pancreatic vein, 95 
 Transitory cedemas, thyroid in, 193 
 Trophic nervous disorders and the 
 
 thymus, 236 
 Tropical neurasthenia, 414 
 Trypanosomes, spleen extract in- 
 fluence on, 130 
 Trypsin, activation of, by spleen, 126 
 
 in tuberculosis, 118 
 Trypsinogen, 65 
 
 Trypsogen and codeine in gangrene, 
 115 
 and opsonic index, 1 14 
 control of severe glycosuria, lOS 
 in diabetes, 107 
 Tryptogene, the spleen a, 125 
 Tuberculin and pancreatin treat- 
 ment, 118 
 Tuberculosis, action of cod-liver oil 
 in, 157 
 adrenal therapy in, 274 
 and diabetes, relations of, 114 
 and hepatic diabetes, 165 
 bile extractives in, 178 
 colloidogenine in, 136 
 endocrinous inactivity in, 167 
 hepatic extract in, 166 
 lymphatic extract in, 398 
 pancreatin in, 118 
 relation of lipoids to, 451 
 remineralization in. 135 
 secretin in, 74 
 spleen extract in, 119, 134 
 splenic lipoid in, 452 
 trypsin in, 118 
 Tumour growth, 30 
 Types of hypoadrenia, 266 
 Typhoid, adrenal therapy of. 267 
 and hypoadrenia, 264 
 relation to diabetes, 117 
 
 Typhoid, spleen extract in, 129 
 
 vaccine, action on glycosuria, 1 1 7 
 
 UrsDmia, parathyroidine in, 226 
 pituitary in, 305 
 renal extract in, 247 
 treatment of, with renal ex- 
 tracts, 250 
 Urea, low index, 164 
 Urinary solids, influence of ovarian 
 
 therapy on, 352 
 Urine, acid index of, 221 
 Urticaria, control by adrenaline, 276 
 Uterine fibroids, mammary extract 
 in, 375 
 haemorrhage, hepatic extract in, 
 162 
 mammary extract in, 374 
 pitiiitrin in, 301 
 involution, placental action on. 
 
 387 
 stimulant in intestine, 86 
 Uterus, action of pituitrin on, 297 
 of hypophysin on, 293 
 
 Vaccine, typhoid, action on glyco- 
 suria, 117 
 Vaso-constriction (local), bv adren- 
 alin, 279 
 -dilation, 85, 147 
 Vesical paralysis, pituitary in, 306 
 Vomiting, cyclic, in children. 271 
 of pregnancy, adrenal therapy 
 in, 269 
 ovary in, 360 
 Von Noorden's diagram, 33 
 
 ideas of pancreas diabetes, 
 95 
 
 Warts, thyroid in, 198 
 
 Weichselbaum's report on Langer- 
 hansian disease, 99 
 
 Weight, bile extracts to increase, 176 
 increasing, by liver combined 
 extracts, 167 
 
 White line, the (adrenal), 267 
 
 " Witch's milk." 383 
 
 X ray and sterility, 430 
 
 in Graves's disease, 205, 430 
 in hyperendocrinism, 429 
 in hyperpituitarism, 4 
 in hypertension, 432 
 
 Zuelzer's hormone, 144 
 
 indications for, 469 
 pancreatic extract, 105 
 
 BAILLlfeRE, TINDALL AND COX, 8, HENRIETTA STREET, COVKNT OARDEK, 
 
 r
 
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 Practical hormone therapy 
 
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 IRVINE, CALIFORNIA 92664