key: cord-0044581-msbfvd4h
authors: Gunn-Moore, Danièlle; Miller, James B
title: The cat with weight loss and a good appetite
date: 2009-05-15
journal: Problem-Based Feline Medicine
DOI: 10.1016/b978-0-7020-2488-7.50022-3
sha: 5756f748eb5e3dae569b6c4568caca120b137b50
doc_id: 44581
cord_uid: msbfvd4h

nan

While weight loss is a common presenting problem in feline medicine, weight loss in association with a good appetite is seen less frequently. This occurs when the cat is unable to gain sufficient nutrition from its diet. This can result from inadequate nutrition (feeding insufficient food or a diet of inadequate nutritional content), or an inability to derive nutrient from the diet. The latter can result from: • Inability to digest or absorb nutrients (malassimilation syndromes), e.g. parasitism, inflammatory bowel disease, pancreatitis/exocrine pancreatic insufficiency, lymphocytic cholangiohepatitis, alimentary lymphosarcoma or lymphangectasia. • Inability to utilize absorbed nutrients -as seen with diabetes mellitus, or endocrinopathies which result in diabetes, e.g. acromegaly or hyperadrenocorticism. • Increased utilization of absorbed nutrients (hypermetabolic states), e.g. hyperthyroidism, pregnancy, lactation, congestive heart failure, excessive physical activity or neoplasia. • Excessive nutrient loss, e.g. diabetes mellitus, protein-losing nephropathy or lymphangectasia.

Weight loss with a good appetite may be seen when the intestinal tract is unable to digest and/or absorb food (malassimilation syndromes, hyperthyroidism), the body tissues are unable to utilize nutrition that has been absorbed (diabetes mellitus), the body loses essential nutrients through the intestines or kidneys (diabetes, protein-losing nephropathy, lymphangectasia), or the demands of the body have been raised beyond the level that the diet can supply (hyperthyroidism, pregnancy, lactation) .

Weight loss with a good appetite indicates a gastrointestinal problem, renal problem or a probleminvolving tissue metabolism (either metabolic demands have increased, or the tissues are unable to utilize nutrients).

The most common cause of weight loss with a good appetite is hyperthyroidism. Other common causes include various malassimilation syndromes including combinations of inflammatory bowel disease, pancreatitis and/or lymphocytic cholangiohepatitis (in combination termed "triaditis"). Intestinal parasitism, diabetes and alimentary lymphosarcoma are seen reasonably commonly, while hyperadrenocorticism, acromegaly, protein-losing nephropathy and lymphangiectasia are seen very rarely.

Disorders which may occasionally present with weight loss with a good appetite, but more typically present with a poor appetite are discussed elsewhere, e.g. congestive heart failure, congenital portosystemic shunts.

• Disease results from autonomous secretion of thyroxine (T4) and triiodothyroxinine (T3). Negative feedback on the pituitary suppresses release of thyroidstimulating hormone (TSH) and normal thyroid tissue atrophies. • Cause is unknown but may involve diet (iodine content, frequent changes, food additives), environmental causes (in cat litter, toxins, pollution, exposure to allergens), genetic mutation, abnormal immune and/or hormonal responses. • 70% of the cats have both thyroid glands affected.

GIT signs may result from polyphagia, malabsorption or intestinal hypermotility.

Polyuria/polydipsia may result from diuretic effects of T4, increased renal blood flow, associated renal insufficiency or compulsive polydipsia.

Cardiac effects result from a high output state, induced, in part, by a demand for increased tissue perfusion to meet the needs of increased tissue metabolism. Cardiovascular changes include left ventricular hypertrophy, left atrial and ventricular dilation, increased myocardial contractility, and decreased peripheral vascular resistance. Other contributors are the direct effect of thyroid hormones on cardiac muscle and the nervous system.

Associated cardiac hypertrophy may cause congestive heart failure with tachycardia, a gallop rhythm, systolic murmurs, dyspnea, apathy, hindlimb weakness due to aortic thromboemboli or collapse.

Associated hypertension may be seen as ocular hemorrhage, or may cause clinical signs associated with cerebrovascular accidents, dementia and/or renal failure.

• Up to 85% of cats with hyperthyroidism may develop systemic hypertension, either initially or even some time after apparently successful treatment.

Hyperthyroidism is the most common endocrinopathy in cats; affecting ~1 in 300 pet cats.

It is seen mainly in older cats (>8 years of age); it is occasionally seen in cats as young as 4 years, and has even been documented in an 8-month-old kitten.

There is no sex or breed predisposition, but Siamese cats appear to be under-represented.

Weight loss usually occurs over several months.

10-20% of cats will present with signs of inappetence with weight loss.

Cats may have a history of restlessness, aggression and a lack of grooming.

Cats may also show tachycardia ± a gallop rhythm, vomiting and/or diarrhea (feces may become bulky) and/or polyuria/polydipsia.

GIT signs may result from polyphagia, malabsorption or intestinal hypermotility.

Polyuria/polydipsia may result from diuretic effects of T4, increased renal blood flow, associated renal insufficiency or compulsive polydipsia.

Associated cardiac hypertrophy may cause congestive heart failure with tachycardia, a gallop rhythm, systolic murmurs, dyspnea, apathy, hindlimb weakness due to aortic thromboemboli or collapse.

Associated hypertension may be seen as ocular hemorrhage, or may cause clinical signs associated with cerebrovascular accidents, dementia and/or renal failure.

• Up to 85% of cats with hyperthyroidism may have signs of systemic hypertension.

Many hyperthyroid cats are presented for their routine vaccination with no owner complaints.

Hyperthyroidism should be suspected when any older cat presents with weight loss, and especially when the weight loss is associated with a good appetite. However, inappetence should not rule out hyperthyroidism.

Physical examination usually reveals a thyroid nodule on either or both sides of the trachea in the ventral cervical region (80-90%).

Tachycardia and/or a gallop rhythm are usually present.

Liver enzymes (ALT and/or SAP) are often raised. Hepatopathy may be secondary to a direct toxic effect of thyroid hormones, hepatic lipidosis, malnutrition or hepatic hypoxia resulting from cardiac failure.

Definitive diagnosis is based on detecting elevated serum concentrations of total T4 (and/or T3).

Some cats with hyperthyroidism have a T4 concentration that is within the normal range. This may be due to:

• Early or mild hyperthyroidism.

• T4 concentrations varying during the day.

• Severe systemic illness causing a reduction in T4 (euthyroid sick syndrome).

If hyperthyroidism is suspected despite a high normal T4 concentration:

• Retest the cat -either immediately, or in a few weeks time. • Check free T4 -by equilibrium dialysis. • T3 suppression test -Collect blood sample, give 7 × 25 mg doses of T3 PO every 8 h, then collect blood 2-4 h after the 7th dose (i.e. on day 3). An increase in T3 concentration confirms successful medication. Suppression of T4 concentration (below 50% of baseline, <20 nmol/l [1.5 ug/dl] does not usually occur in hyperthyroid cats. • Thyrotropin-releasing hormone (TRH) stimulation test -Collect blood, give 0.1 mg/kg TRH IV, then collect second blood sample 4 hours later. Assess both samples for serum T4 concentration. Stimulation to > 50% does not occur in hyperthyroid cats. Side effects of TRH include transient salivation, vomiting, tachypnea and defecation. • Thyroid-stimulating hormone (TSH) response test -The usefulness of this test has been questioned and TSH may be difficult to obtain. • Nuclear isotope scanning detects hyperactive thyroid tissue. Procedure is relatively safe and simple to perform, but requires access to a licensed facility, which is not always available. • Trial course of anti-thyroid therapy (see below) of approximately 30 days is not without risk of toxic side effects.

These include most other causes of weight loss with a good appetite. However, hyperthyroidism typically occurs in older cats and presents with polyuria, polydipsia, vomiting and/or diarrhea, so diabetes, renal disease, malassimilation syndromes (including IBD, pancreatitis/exocrine pancreatic insufficiency, and early intestinal lymphosarcoma), acromegaly and hyperadrenocorticism are perhaps the most important differentials.

Hyperthyroidism can be treated medically, surgically, or with radioiodine (I 131 ).

Prior to deciding which treatment to use the cat should be assessed for concurrent disease, especially renal disease, systemic hypertension and heart disease, all of which occur commonly in association with hyperthyroidism.

• The interplay between systemic blood pressure and renal function is complex. While systemic hypertension is detrimental to kidney function, a sudden fall in blood pressure or a reduction in glomerular filtration rate (e.g. associated with a sudden fall in T4) can exacerbate renal dysfunction by causing a sudden fall in renal blood flow. Changes in T4 need to be made gradually so there are no sudden changes in renal blood pressure. • By maintaining renal blood pressure, hyperthyroidism can mask low-grade renal insufficiency. It is essential to check serum urea and creatinine concentrations and urine specific gravity prior to inducing irreversible reduction of T4 (i.e. by thyroidectomy or I 131 treatment). A short course of medical therapy may reveal the presence of masked renal insufficiency.

Medical therapy tends to be given to stabilize the cat prior to surgical treatment, to check for masked renal disease prior to thyroidectomy or I 131 treatment, or when neither I 131 nor surgery are possible. 

The success depends on the stability of the patient, the expertise of the surgeon (a bilateral thyroidectomy is usually performed), and the expertise of the anesthetist (e.g. do not give atropine).

• Successful response rate is > 95%. Ectopic overactive thyroid tissue is a cause of failure, as it is usually missed at surgery. • Reduce the risks of surgery by making the cat euthyroid prior to surgery (see Medical therapy, above). • Surgical risks include anesthetic risks in older patients (often with concurrent renal ± cardiac disease), iatrogenic damage to parathyroid tissue leading to transient or permanent hypocalcemia, or to the local nerves leading to laryngeal paralysis or Horner's syndrome.

Radioiodine (I 131 ) is taken up by and destroys the overactive thyroid tissue, but spares the normal tissue.

• Successful response rate is > 95%, but it may take a few weeks, or occasionally months, for the normal tissue to recover function.

• Availability of facilities and length of stay in hospital varies from 2 days to 4 weeks depending on country and state, as it often depends on the interpretation of radiation safety laws. • Side effects are few and include transient dysphagia or dysphonia, or permanent hypothyroidism (~2%).

Without treatment, cats with hyperthyroidism will usually die of concurrent renal disease, heart disease, liver disease or systemic hypertension.

With treatment, prognosis varies from very good to guarded, dependent on the presence of heart disease, renal disease and systemic hypertension, whether or not any damage has become permanent prior to treatment of the hyperthyroidism, and which treatment options are available.

Since it is not known what triggers the development of hyperthyroidism, it is currently not possible to prevent its onset.

• Any age, sex or breed of cat.

• Any combination of progressive weight loss, vomiting and/or diarrhea.

Inflammatory bowel disease (IBD) is a group of chronic idiopathic gastrointestinal tract disorders that are characterized by infiltration with inflammatory cells.

The infiltration may consist of lymphocytes, plasma cells, neutrophils, eosinophils and/or macrophages, and the inflammation may involve the stomach, small intestine and/or colon.

The etiology is probably multifactorial and appears to involve host hypersensitivity responses to antigens within the bowel lumen or mucosa. Suspected antigens include food, bacteria, parasites or self-antigens.

• The hypersensitivity may result from a primary, possible genetic, disorder, or arise secondary to mucosal injury incurred by a number of different disorders including bacterial, viral, protozoal or fungal infections, bacterial overgrowth, food hypersensitivity, drug administration, metabolic disease, neoplasia, pancreatitis or cholangiohepatitis. • Regardless of the initial cause of the hypersensitivity, it results in increased mucosal permeability which allows luminal antigens to cross the mucosa, leading to inflammation and further mucosal damage.

IBD can occur in any age, sex or breed of cat. While it is most commonly seen in middle-aged to older cats, a third of cases occur in cats of less than 2 years of age. Some purebred cats may be predisposed.

Weight loss may result from malabsorption and/ or inappetence (which usually occurs late in the disease). Not all cases show significant enteric signs, so some cats present with only weight loss and a variable appetite.

Vomiting is often intermittent and may occur every few days to weeks, often accompanied by anorexia and lethargy. Vomiting is rarely associated with feeding. It may contain froth, bile-stained fluid and food or, occasionally, blood.

Diarrhea can vary in consistency from almost well formed to liquid. Some cats may show evidence of large bowel involvement with mucus and/or blood and increased frequency.

Clinical signs may wax and wane, and tend to vary with the type and severity of inflammation.

Physical examination is often unremarkable, but may reveal a thin cat, palpably thickened intestines, enlarged mesenteric lymph nodes and/or abdominal discomfort.

Concurrent pancreatitis and/or cholangiohepatitis may result in jaundice, a palpably enlarged liver and/or anterior abdominal discomfort.

When lymphangectasia is present, severe hypoproteinemia may lead to subcutaneous edema and/or ascites.

Before a diagnosis of IBD can be made, all other causes of enteropathy must be ruled out. These include bacterial enteritis (Helicobacter spp., Salmonella spp., Campylobacter spp., Clostridium perfringens, E. coli), intestinal parasites (helminths, cestodes, protozoans), fungal enteritis, GI neoplasia (lymphosarcoma, adenocarcinoma) and viral enteritis (feline leukemia virus, feline immunodeficiency virus, feline coronavirus, feline panleukopenia). IBD is diagnosed by documenting histopathological evidence of GI inflammation and excluding all of other causes of it.

Baseline laboratory tests include hematology, serum biochemistry (including total T4 concentration in older cats), FeLV and FIV tests, urinalysis, fecal culture for pathogenic bacteria and a full examination for fecal parasites.

• Performing all of these investigations can be expensive so the investigation should, where possible, be tailored to the patient, and many clinicians start with a dietary trial (see below). • Since the investigations are being performed to rule out other causes of enteropathy they are frequently unremarkable. However, IBD may be associated with a number of non-specific findings: -Hematology may reveal an inflammatory response; neutrophilia, eosinophilia, lymphopenia or monocytosis. Microcytic anemia may result from chronic blood loss associated with severe IBD. -Hyperglobulinemia may result from chronic inflammation. Panhypoproteinemia may be seen with severe protein-losing enteropathies. -Increases in liver enzymes may result from associated hepatic inflammation (see below).

Non-invasive screening tests may provide additional information. These include abdominal radiography, ultrasound examination, assessment of serum folate and cobalamine (B12) levels, examination of fecal smears for the presence of undigested fats or starch, fat absorption tests, breath hydrogen analysis and sugar permeability studies (where available).

• Survey radiographs tend to be unrewarding, but may reveal gas-or fluid-filled loops of intestines. Barium studies may reveal flocculation or persistent adherence of the barium to the mucosa, irregular mucosal surfaces or delayed transit times. • Ultrasound examination may reveal intestinal wall irregularity or echogenicity. It may also be used to examine the mesenteric lymph nodes and other intra-abdominal structures. • Serum folate and cobalamin levels may be reduced because of malabsorption. • Serum feline trypsin-like immunoreactivity (fTLI) and feline pancreatic lipase immunoreactivity (fPLI) may be helpful in the diagnosis of exocrine pancreatic insufficiency (EPI) and pancreatic inflammation, respectively. • Breath hydrogen analysis and sugar permeability studies may be used to try to demonstrate malabsorption and/or small intestinal bacterial overgrowth (SIBO)/antibiotic-responsive diarrhea.

A dietary trial should be performed in all except very ill patients prior to more invasive investigation.

• Feed a single highly digestible source of protein for at least 3-4 weeks and see if the clinical signs resolve.

It is inadvisable to carry out treatment trials with antibiotics or corticosteroids prior to making a definitive diagnosis.

• This delays making the correct diagnosis, and may cause complicating intestinal bacterial overgrowth (antibiotics) or potentiate secondary infections (corticosteroids).

• Mucosal biopsies may be collected by endoscopy. Unfortunately, it is not always possible to make a definitive diagnosis from these biopsies, so in some cases, full-thickness biopsies must be collected via laparotomy or laparoscopy. • IBD often causes no gross mucosal changes, but changes that may be seen include increased granularity and friability, the presence of erythema, ulcerations, and/or mass lesions and poor distensibility. • Multiple biopsies should be taken since the inflammatory infiltrates may not be spread diffusely throughout the gastrointestinal tract.

• When performing laparotomy or laparoscopy it is advisable to collect biopsies of the mesenteric lymph nodes, liver and, if possible, pancreas, as well as from multiple intestinal sites. Part of the liver and/or mesenteric lymph node biopsy, and bile aspirated from the gall bladder can be sent for culture. • Collection of duodenal aspirates for quantitative culture may help to determine the bacterial load of the small intestine. • Gastric biopsies should always be assessed for the presence of Helicobacter spp. • Histopathology reveals inflammatory cells infiltrating the lamina propria, plus variable degrees of epithelial abnormality and glandular distortion.

-Lymphocytic-plasmacytic IBD is the most common form of IBD in the cat. It may occasionally progress to intestinal lymphosarcoma. -Granulomatous enterocolitis is less common, and often presents as GI obstruction. -Eosinophilic IBD is rare. It may be associated with eosinophilia and/or hypereosinophilic syndrome where tissues other than the GI tract are also affected. -Suppurative IBD is usually associated with an infectious etiology. -Other forms also exist and many cats have mixed populations of inflammatory cells. • Unfortunately, when lymphangectasia is present, severe hypoproteinemia may render these patients a poor anesthetic and surgical risk. It may therefore be necessary to make a presumptive diagnosis based on the presence of diarrhea, panhypoproteinemia and lymphopenia in the absence of finding other diseases on hematology, serum biochemistry, fecal evaluation, abdominal ultrasound examination ± mucosal biopsies.

These include most of the other causes of weight loss with a good appetite. However, since cats with IBD usually develop vomiting and/or diarrhea, other causes of enteropathy, cholangiohepatitis, pancreatitis, hyperthyroidism and the other malassimilation syndromes (including alimentary lymphosarcoma) should be considered as important differentials.

The basic aims of treatment are to remove the source of antigenic stimulation and to suppress the inflammatory response within the GI tract.

• Treatment typically involves dietary management, ± metronidazole, ± prednisolone. • Treatment should be tailored to each patient. • Relapses warrant critical reassessment of the case, and often require repeated intensification of treatment and/or the addition of more potent immunosuppressive drugs.

The diet should contain a single highly digestible source of protein, ideally that the cat has not eaten before.

• The diet should preferably contain few food additives, be gluten-free, lactose-free, low residue, not too high in fat, and adequately supplemented with vitamins and minerals, especially B vitamins and potassium. • High-fiber diets may help when the large bowel is affected. • No other foods should be fed concurrently.

• During the initial phase of treatment, when the bowel is recovering, it may be preferable to feed either a home-cooked diet, a "sacrificial protein" which the cat will then not be fed again, or protein hydrolysate which has reduced molecular weight protein and is supposed to be less antigenic. This should be fed for 1-2 months, after which time the cat can then be fed a commercial "hypoallergenic" diet, or further protein sources can be gradually reintroduced. If feeding homemade diets long-term, great care should be taken to ensure they are balanced.

Metronidazole often forms the mainstay of treatment. Its effect against anaerobic bacteria helps to reduce secondary bacterial overgrowth. It is also effective against protozoa (e.g. Giardia spp.), has positive effects on brush border enzymes levels, and is believed to alter the immune function of the GI tract, perhaps by altering neutrophil chemotaxis and inhibiting cell-mediated immunity. Administer 7.5-15 mg/kg PO q 8-12 hours for 2-4 weeks, then taper gradually over 1-2 months. Some authors suggest that it is inadvisable to give very prolonged courses.

• Immunosuppressive doses of corticosteroids are usually required. Administer prednisolone 2-4 mg/kg q 12-24 hours PO, then taper over 1-3 months and maintain on every other day doses, if needed. Use of budesonide (1 mg/cat PO q 24 hours) instead of prednisolone may help to reduce systemic signs of corticosteroid administration. • Other immunosuppressive agents may be considered. While they all have potential side effects and warrant regular monitoring chlorambucil (2-5 mg/m 2 PO up to once every 48 h) is often very well tolerated. Other less favorable options include cyclophosphamide (50 mg/m 2 PO up to four times a week), cyclosporine (0.5-8.5 mg/kg every 12-24 hours, indefinitely) or, in the cases of colonic disease, sulfasalazine (10-20 mg/kg/day PO for 7-10 days).

However, few have been assessed using controlled studies in cats.

• Tylosin may be effective for its antibiotic actions as well as other, as yet undefined, effects (5-20 mg/kg every 6-12 hours PO). • Motility modifiers may give short-term palliative relief in cases of very watery diarrhea (loperamide 0.04-0.2 mg/kg every 8-12 hours PO). • Metoclopramide may be useful for its anti-emetic and prokinetic effects (0.2-0.5 mg/kg PO up to four times a day, being given just prior to feeding, or as a constant IV infusion 1-2 mg/kg over 24 hours). • Cisapride is a good prokinetic, but it is now more difficult to obtain (0.3-1.0 mg/kg every 8-12 hours PO). • Cobalamin and folate may be needed as they are often reduced by malabsorption (cobalamin 125-250 μg/week SC or IM for 6-8 weeks then q 2-4 weeks [50-100 μg/cat/day PO]; folate 0.5-1.0 mg/cat/day PO for 1 month). • Vitamin K1 is often required because fat malabsorption results in poor absorption of fat-soluble vitamins like vitamin K, and this can result in abnormal hemostasis (0.5 mg/kg/day SC for 3-4 days, then once weekly). • Glutamine may be given as an energy source for the GI mucosal cells (250-5000 mg/cat/day PO, indefinitely). • Lactobacillus acidophilus may be given as a probiotic to help restore intestinal flora (50-500 M organisms/cat/day PO until feces return to normal). • Various nutritional supplements may be given for their potential anti-inflammatory properties. These include vitamin E (50-200 IU/cat/day PO), vitamin A (1000-5000 IU/cat/day PO), vitamin C (50-80 mg/kg/day PO), zinc (7.5 mg/cat/day PO), and N-acetyl glucosamine (125-1500 mg/cat/day PO).

The prognosis depends on the nature and severity of the GI infiltration, and the presence of concurrent and/or associated disease, such as pancreatitis or cholangiohepatitis. In general, the prognosis for control is reasonably good, but the condition cannot be cured, and many cats will need treatment for the rest of their life.

Since it is not known what triggers IBD to develop, it is not currently possible to prevent its onset.

• Usually seen in older, obese, neutered male cats, and Burmese cats may be overrepresented. • History of polyuria, polydipsia and polyphagia. • Possible initial weight gain, followed by weight loss.

Diabetes results from a variety of mechanisms that cause an absolute or relative lack of insulin.

Classification of diabetes in cats is best made by cause, rather than whether or not they require exogenous insulin.

Type 1 diabetes, previously called juvenile-onset diabetes, is due to immune-mediated destruction of pancreatic islet beta cells. It appears to be very rare in cats.

Type 2 diabetes results from impaired insulin secretion, and peripheral resistance to the action of insulin. Hyperglycemia results from decreased glucose uptake in tissues and increased hepatic glucose production.

Many cats with diabetes appear to have type 2 diabetes. • This is often associated with accumulation of isletspecific amyloid polypeptide (IAPP), which occurs in aggregates around pancreatic islets. While IAPP is co-secreted and accumulates as amyloid in normal cats as they age, it accumulates more extensively in cats with diabetes. The accumulation of islet amyloid eventually leads to loss of beta cells. • Obesity is a significant risk factor for diabetes because it results in peripheral insulin resistance.

Other specific types of diabetes, previously called type 3 or secondary diabetes, results from diseases which destroy beta cells or cause marked insulin resistance, such as:

• Beta cell destruction due to pancreatitis or neoplasia. Pancreatitis may be more common than previously thought, as >50% of diabetic cats have evidence of past or current pancreatitis at necropsy (see below under pancreatitis/exocrine pancreatic insufficiency). • Insulin resistance resulting from unrelated endocrinopathies, e.g. acromegaly or hyperadrenocortisim (see below under Acromegaly and Hyperadrenocorticism). • Insulin resistance from drug administration, e.g.

corticosteroids, megestrol acetate.

10-80% of cats with diabetes may lose the need for exogenous insulin. This may result from: • Correction of 'glucose toxicity'. Prolonged hyperglycemia causes impaired insulin and increased peripheral insulin resistance, termed glucose toxicity. Exogenous insulin administration and reduction of hyperglycemia can result in resolution of this toxicity and return of sufficient insulin secretion to maintain normoglycemia. Long-acting insulin administered twice daily and a low-carbohydrate, high-protein diet appear to facilitate this. • Reduction of obesity which deceases insulin resistance. • Resolution of pancreatitis. • Treatment of underlying disease, e.g. acromegaly or hyperadrenocortisim. • Removal of diabetogenic drugs, e.g. progestogens (megestrol acetate) or exogenous corticosteroids.

Diabetes is the second most common endocrinopathy in cats following hyperthyroidism. However, while it It can occur in any age, sex or breed of cat, but is seen most frequently in older obese neutered male cats.

In Australia, New Zealand and Great Britain, Burmese cats appear to be predisposed, with ~1 in 50 affected.

The most consistent signs are polyuria, polydipsia and polyphagia. In the early stages these signs may go unnoticed by the owners, possibly because of free choice feeding and outdoor toileting habits.

Possible initial weight gain is followed by weight loss.

Urinary tract infections are common, and cats may present with signs of cystitis and/or renal failure.

The coat may be ill kept and a pot-bellied appearance may result from hepatomegaly.

Hindlimb weakness and a plantigrade stance due to diabetic neuropathy are seen quite frequently, but cataracts occur rarely.

Cats are frequently presented only when they become systemically ill with signs of anorexia, vomiting and/or diarrhea, jaundiced and depression (see page 261, The Cat With Depression, Anorexia or Dehydration).

Cases of diabetes that result from chronic pancreatitis may have a history that includes episodes of depression, anorexia, vomiting, diarrhea and/or abdominal pain. Since diabetes is most likely to occur when most of the pancreatic mass has been destroyed, it may be accompanied by signs of exocrine pancreatic insufficiency, evidenced by large quantities of voluminous fatty feces and a voracious appetite (see below under pancreatitis/exocrine pancreatic insufficiency).

Diagnosis of diabetes mellitus is based on documenting persistent fasting hyperglycemia (> 11 mmol/l [200 mg/dl]) and glucosuria in a cat with appropriate clinical signs (polyuria, polydipsia and polyphagia).

Stress-induced hyperglycemia can result in glucose levels above the renal threshold and hence glucosuria, so a single documentation of these findings is not diagnostic of diabetes.

Allowing the cat to settle down then re-testing it after a few hours may help to determine whether or not the hyperglycemia is stress-induced. Alternately, the owner can be asked to test the cat's urine for the presence of glucose when it is at home.

Assessing serum fructosamine or glycosylated hemoglobin concentrations will give an indication of how high the blood glucose concentration has been during the preceding 2-3 weeks, and 1-2 months, respectively.

Many cats with diabetes have mild to moderate increases in serum concentrations of cholesterol and liver enzymes. However, more severe changes such as bilirubinemia, acidemia, uremia and electrolyte disorders are unlikely to be present in a cat that is maintaining a good appetite, that is, a cat with uncomplicated diabetes.

Ketones may or may not be present in the urine. Their presence further confirms the diagnosis of diabetes. By the time a cat has developed diabetic ketoacidosis it is unlikely to be maintaining a good appetite (see page 355, The Thin, Inappetent Cat).

These include most of the other causes of weight loss with a good appetite. However, since cats with diabetes develop polyuria and polydipsia, hyperthyroidism and renal disease (particularly protein-losing nephropathies) should be considered as important differentials, as should underlying causes of diabetes, such as acromegaly and hyperadrenocorticism.

• While the signs of diabetes in obese cats may resolve with dietary modification alone, most cats need at least temporary medical intervention. • Oral hypoglycemic agents may be successfully used in some cases of uncomplicated diabetes, or once glucose toxicity has resolved following insulin therapy. • Insulin is required for most diabetics, at least initially.

However, this should be done very gradually, restricting calorie intake to no more than 75% of maintenance requirements and monitoring for changes in insulin requirement. Aim for no more than 2% weight loss per week.

Dietary modification -all cats with diabetes benefit from being fed a well-balanced diet on a regular, consistent, feeding schedule.

• Obese cats may benefit from being fed a low-calorie, high-fiber diet to help them lose weight. However, a low-carbohydrate, high-protein diet may be more beneficial to minimize demand for insulin secretion and minimize post-prandial hyperglycemia. • Non-obese cats benefit from being fed a low-carbohydrate, high-protein diet. The choice of diet may be affected by concurrent illness, especially renal disease. • Regular feeding is essential. Cats on once-daily insulin are usually fed just before their morning insulin, then again in the early evening. Cats on twice daily insulin are usually fed just before both insulin injections. Free-choice feeding can be beneficial, but it is important to monitor the amount of food eaten on a daily basis.

Oral hypoglycemic agents act to increase insulin secretion, decrease peripheral insulin resistance, and/or decrease absorption of glucose from the intestinal tract. They may successfully control some non-ketotic, uncomplicated diabetic cats, either temporarily or longer term, particularly when given in conjunction with dietary modification. Insulin: There are a number of different types of insulin, and the choice is often based on personal preference.

• Most cats with uncomplicated diabetes respond well to once-or twice-daily subcutaneous administration of lente, protamine zinc insulin (PZI) or glargine. • The source of the insulin does not appear to be important in cats, as anti-insulin antibodies do not cause many problems. • The duration of action of the different preparations varies between cats (lente -peak 2-10 h, duration of action 6-16 h; PZI -peak effect at 3-12 h, duration of action 6-24 h; glargine peak effect at 16 h, duration of action > 24 h). In general, PZI and glargine are preferred because of their longer duration of action, improved glycemic control and increased remission rates. • Start at ~0.25-0.5 IU insulin/kg/per injection, then adjust as necessary, usually by 0.5-1.0 IU per dose. See page 239, Diabetes mellitus in The Cat With Polyuria or Polydipsia, for detailed criteria for adjusting the insulin dose. • The aim of therapy is to prevent the clinical signs of diabetes and, if possible, maintain blood glucose concentration between 5.5-14 mmol/l (100-250 md/dl). • It takes 2-3 days for glucose homeostasis to adjust after starting or altering insulin doses. Any changes in dose should therefore be based on recurring effects, not a single urine (or blood) glucose determination. Owners can monitor water intake, urine glucose and ketone levels at home. Ideally glucose will be negative or trace, and ketones will be negative. Glucose curves can also be performed at home by obtaining a drop of blood for glucose testing via ear vein pricking.

-It is generally recommended that glucose curves be performed every 1-2 weeks until the diabetes is stable. After this time they need be performed less frequently, and the dosage can be adjusted in response to changed clinical signs, ± serum fructosamine concentrations. -The usefulness of glucose curves can be very limited in easily stressed cats that become hyperglycemic whenever they are hospitalized. Anorexic cats may have a lower blood glucose concentration in the hospital than at home when eating. -A glucose curve is performed by giving the cat its usual breakfast and dose of insulin, then determining blood glucose level every 1-2 h during a 12-24 h period. The level of the blood glucose at its nadir (lowest point) determines whether or not the dose of insulin needs to be changed, while the duration of insulin action determines how frequently it needs to be given.

Water drunk measured at home on at least two consecutive days is better correlated with mean blood glucose than is fructosamine concentration. If water intake is < 20 ml/kg on wet food or < 70 ml/kg on dry food, it indicates good glycemic control.

At all times, but especially after altering the insulin dosage, the owners should be warned to look for signs of hypoglycemia (weakness, lethargy, shaking, ataxia, collapse and coma). If these signs occur, the cat's gums should be rubbed with sugar water, jam or honey, and immediate veterinary attention sort.

• Reasons for apparent insulin resistance include ineffective insulin (out of date, poor storage, incomplete mixing), poor injection technique, out-of-date urine test strips and insulin overdose leading to insulin-induced hyperglycemia. The Somogyi over-swing occurs when hypoglycemia induces counter-regulatory hormones such as epinephrine and glucagon to induce hyperglycemia. True insulin resistance can result from recent weight gain, infection, acromegaly, hyperadrenocorticism, hyperthyroidism, the administration of diabetogenic drugs, renal or hepatic insufficiency, anti-insulin antibodies or presence of certain types of tumor.

The prognosis is very variable. It depends on the owner's commitment, the presence of concurrent and interacting disease and the ease of glycemic control. If diabetes arises secondary to chronic pancreatitis it can be particularly difficult to control.

The risk of developing diabetes can be reduced by not allowing cats to become obese or physically inactive and not giving long courses of diabetogenic drugs. A low-carbohydrate, high-protein diet may also help to reduce the demand on beta cells to produce insulin.

• Usually in kittens or young adult cats.

• Weight loss or failure to gain weight, usually with a good appetite. • Diarrhea and/or vomiting may be present.

Intestinal parasites that can infect cats and, at least occasionally, cause weight loss associated with a good appetite include nematodes (large ascarid roundworms Toxocara cati and Toxascaris leonina), and hookworms (Ancylostoma braziliense, A. tubaeforme and Uncinaria stenocephala), cestodes (tapeworms Dipylidium caninum and Taenia taeninaeformis), and protozoans (coccidians, Isospora felis, I. rivolta, and Cryptosporidium parvum and flagellates Giardia lamblia and Tritrichomonas foetus). In cats, G. lamblia lives in the jejunum and ileum.

Environmentally resistant cysts are shed in feces, contaminate drinking water or food, and are then ingested by other cats.

• Infection and clinical disease are seen most commonly in cats kept in large unhygienic groups. • Giardia spp. do not appear to be host-specific and have a world-wide distribution in tropical and temperate areas.

In cats, T. foetus lives in the colon and sheds flagellated protozoa into the feces. Infection and clinical disease are seen most commonly in young cats kept in large unhygienic groups.

The prevalence of intestinal parasites varies with geographic location, the level of sanitation, whether or not the cat is an indoor or outdoor animal, and whether or not it hunts and eats its prey.

While infection is common, disease is seen most commonly in young cats living in poorly cleaned multianimal environments.

In these situations, episodes of disease may be seen in kittens or cats of similar ages, and may be preceded by a stressful event such as an environment change, addition of new cats, or weaning, etc.

Clinical signs vary but typically include diarrhea and vomiting (especially with T. cati infections), but anorexia is not often present. 

Intestinal parasites should be suspected in any cat, but especially those coming from a poorly cleaned multianimal environment in a geographic region with a high prevalence of intestinal parasites.

Since some parasites can be transmitted lactationally (T. cati), and infections are frequently more severe in young cats, all young cats should be evaluated for intestinal parasites or treated against the common parasites of the region.

Infection rarely causes systemic changes. However, hematology may reveal an eosinophilia and, in severe cases, low serum proteins may be found on serum biochemistry.

With the exception of tapeworm segments, most intestinal parasites are not noticed in the feces.

Fecal floatation techniques are used to diagnose most intestinal parasites (round worms, hook worms and Isospora spp.). However, special techniques may be necessary for some parasites, such as C. parvum (special stains or, possibly, fecal antigen tests), Giardia spp. (direct saline fecal smears or fecal antigen tests), or T. foetus (PCR, 'In Pouch' culture or direct saline fecal smears).

Rather than confirming the presence of an infection with fecal tests, a therapeutic trial with a suitable drug may be considered.

Differential diagnoses include most of the other causes of weight loss with a good appetite. Inadequate nutrition becomes the most likely differential when there are no signs other than weight loss. However, the variable presence of gastrointestinal signs is more suggestive of some of the malassimilation syndromes such as IBD, exocrine pancreatic insufficiency, or early alimentary lymphosarcoma.

Roundworms and hookworms may be treated with pyrantel pamoate (20 mg/kg/day -two doses need to be given 2-3 weeks apart) or fenbendazole (20-50 mg/kg/day usually given for 3-5 days, then repeated 2-3 weeks later) which are both safe and effective in cats.

Tapeworms may be treated with praziquantel (3.5-7.5 mg/kg SC, PO) or epsiprantel (2.75 mg/kg PO). One dose is effective against D. caninum and T. taeninaeformis.

Isospora spp. may be treated with trimethoprim/sulfonamide (15 mg/kg q 12 hours PO for 10-14 days), plus improved sanitation.

C. parvum can be difficult to treat, but tylosin (10-15 mg/kg q 12 hours PO for 28 days, but may need higher doses), paromycin (125-165 mg/kg q 12 hours PO for 5 days), or azithromycin (7-15 mg/kg q 12 hours PO for 5-7 days) may be effective.

Giardia spp. may be treated with fenbendazole (10-30 mg/kg/day PO for 5 days) or metronidazole (10-25 mg/kg q 12-24 hours PO for 5-7 days). Repeated treatment may be needed. The possibility of vaccination is currently being studied.

T. foetus may be treated with ronidazole (10-30 mg/kg q 12 hours PO for 14 days).

If given the correct treatment, the prognosis for full recovery is usually very good.

Severe infections can occasionally result in permanent intestinal damage and chronic clinical signs.

Resistant C. parvum, Giardia spp. and/or T. foetus infections can occasionally result in chronic disease.

Severe infections can usually be prevented by having a good preventative worming policy, giving prompt and effective treatment to any animals found to be infected or carrying these organisms, improving sanitation, and reducing stocking densities.

• Seen in any age, sex or breed of cat, but mostly typically in kittens from poor environments. • Weight loss, often in association with a voracious appetite. • Few other signs until terminal stages of malnutrition.

Disease due to inadequate nutrition is caused by feeding an inadequate or inappropriate diet.

Disease can be seen in any age, sex or breed of cat, but is seen most commonly in kittens from poor environments.

It may also be seen in pregnant or lactating queens, or in cats that have recently changed environments: e.g. changed from having a sedentary life in a warm environment, to having an active life in adverse weather conditions.

Affected cats show a generalized loss of body condition despite a good appetite.

They are usually bright and active until terminal stages of malnutrition.

There are few specific findings, but severe cases may show lethargy, muscle weakness, depression, diarrhea, neurological signs, blindness and/or ascites.

Diagnosis is based on resolution of clinical signs following correction of diet. If necessary, rule out other likely differentials.

These include most other causes of weight loss with a good appetite. However, given the lack of other clinical signs, the most likely differentials include intestinal parasites and some of the malassimilation syndromes including IBD, exocrine pancreatic insufficiency, early alimentary lymphosarcoma.

Changing the diet to a suitable well-balanced diet is usually all the treatment that is necessary. Very severe cases may need supportive care and nursing.

Provided that the malnutrition was not too severe or prolonged, the prognosis for recovery is very good.

Cats should always be fed appropriate amounts of a suitable well-balanced diet that has been designed to be fed to cats.

• Usually older cats.

• Anorexia and weight loss, ± vomiting, ± diarrhea. • Early in disease may have a good appetite.

Alimentary lymphosarcoma can occur isolated to the intestine, or as part of multicentric disease.

It can occur as a focal lesion or diffuse intestinal thickening. It can arise in the stomach, small intestines and/or colon, and involvement of the ileocolic junction is common. • Concurrent involvement of mesenteric lymph nodes, liver and/or spleen is not uncommon.

The cells may be lymphocytic, lymphoblastic, of B or T cell origin or, occasionally, large granular lymphocytes or globular leukocytes.

Lymphoblastic lymphosarcoma are more likely than lymphocytic lymphosarcoma to present as an abdominal mass.

Alimentary lymphosarcoma may arise secondary to chronic lymphocytic-plasmacytic IBD.

Typically seen in older cats of any sex or breed.

Some cats develop fever, ascites or jaundice, and at this stage they rarely maintain a good appetite.

Hematology may reveal non-specific changes including neutrophilia and lymphopenia. Lymphoblasts may occasionally be seen in the circulation.

Serum biochemistry may reveal panhypoproteinemia and/or hyperbilirubinemia.

Survey radiographs may reveal gas-or fluid-filled loops of intestines. Barium studies may reveal flocculation or persistent adherence of the barium to the mucosa, irregular mucosal surfaces, luminal narrowing or intramural thickening.

Ultrasound examination may reveal intestinal wall irregularity, thickening, or altered echogenicity, and/or enlarged mesenteric lymph nodes, liver or spleen.

Diagnosis is made by examination of a GI tract fineneedle aspirate or biopsy, with or without biopsies from mesenteric lymph nodes and/or other abdominal organs.

Differentiating lymphocytic (small cell) alimentary lymphosarcoma from lymphocytic-plasmacytic IBD can be very difficult.

Determining which types of cells are involved can aid in treatment and prognosis (see below).

These include most of the other causes of weight loss with a good appetite. However, since cats with alimentary lymphosarcoma usually develop vomiting and/or diarrhea, other causes of enteropathy, IBD, cholangiohepatitis, pancreatitis, hyperthyroidism and the other malassimilation syndromes should be considered as important differentials.

Localized alimentary lymphosarcoma may respond to surgical resection and adjunct chemotherapy.

• Large masses involving the entire thickness of the bowel wall should not be treated with chemotherapy alone as this may result in gut perforation.

Diffuse lymphosarcoma are best treated with combination chemotherapy.

• Lymphoblastic lymphosarcoma and lymphosarcoma affecting more than just the GI tract are best treated with combinations of cyclophosphamide, vincristine and prednisolone, ± doxorubicin, ± l-asparaginase (see page 676, for protocols and doses). • Lymphocytic lymphosarcoma may respond more favorably to a combination of only prednisolone (10 mg/cat/day PO) and chlorambucil (2-5 mg/m 2 PO up to once every 48 h or 15 mg/m 2 /day for 4 days PO, every 3 weeks).

The prognosis is guarded. The best prognostic indicators are response to therapy and the duration of the first remission.

Response rates to chemotherapy range from 30-70%, with median remissions of 4-23 months.

Being FeLV positive or having lymphoblastic lymphosarcoma are negative indicators, while having lymphocytic lymphosarcoma is a positive indicator.

• Lymphoblastic lymphosarcoma has a complete remission rate of 18%, and median survival time of 2.7 months. • Lymphocytic lymphosarcoma has a complete remission rate 69%, median survival time 22.8 months.

Since it is not known what triggers lymphosarcoma to develop, it is not currently possible to prevent its onset. However, since lymphocytic IBD has been seen to progress to lymphosarcoma, it would appear sensible to try to control lymphocytic IBD as well as possible, to try to prevent its progression.

• Typically seen in middle-aged to older cats.

• History of episodic anorexia, lethargy, vomiting and/or diarrhea. • If also diabetic; polyuria and polydipsia.

Pancreatitis develops when there is activation of digestive enzymes within the pancreas, which results in some degree of auto-digestion. While there are many possible causes of pancreatitis in cats, over 90% are idiopathic.

In cats, the most common forms of pancreatic disease are chronic non-suppurative (lymphocytic/plasmacytic or, occasionally, eosinophilic) pancreatitis and suppurative (neutrophilic) pancreatitis, while acute septicemic pancreatitis and exocrine pancreatic insufficiency (EPI) are seen less frequently.

It is the presence of exocrine pancreatic insufficiency that results in weight loss with a good, often ravenous, appetite. • Primary exocrine pancreatic insufficiency is uncommon in cats. However, exocrine pancreatic insufficiency secondary to chronic, often episodic, pancreatitis is being recognized more frequently. • In exocrine pancreatic insufficiency the lack of pancreatic digestive enzymes leads to maldigestion and malabsorption.

• This association may occur because the pancreatic duct in some cats enters the common bile duct before it opens into the duodenum. In other cats, the pancreatic and bile ducts enter the duodenum separately. • When disease occurs in the small bowel it may ascend the common bile duct and from there affect the pancreas and the rest of the biliary tree, or it may ascend both ducts from their opening in the duodenum. For the same reason, disease of the biliary tree or pancreas may affect the other two regions. • Regardless of which organ is affected first, the other two organs tend to become involved as inflammatory mediators, infectious agents, bile and/or pancreatic secretions pass from one area to another.

Chronic pancreatitis can occur in any sex or breed of cat, and is typically seen in middle-aged or older cats.

Burmese cats in Great Britain may be predisposed to pancreatitis.

They usually include episodes of anorexia or variable appetite, with or without vomiting and/or diarrhea, weight loss and/or possible abdominal pain.

Once exocrine pancreatic insufficiency develops the cat is usually thin, has a greasy coat and produces large quantities of voluminous, fatty, foul-smelling feces or has severe diarrhea.

Cats with chronic pancreatitis may also develop episodic or persistent diabetes mellitus, which is seen as polyuria and polydipsia.

When both exocrine pancreatic insufficiency and diabetes occur concurrently the polyphagia can be profound.

Physical examination is often unremarkable, but may reveal anterior abdominal discomfort, a palpably irregular and enlarged pancreas, or hepatomegaly associated with cholangitis/cholangiohepatitis complex.

Chronic pancreatitis is very difficult to diagnose.

Hematology and serum biochemistry may reveal nonspecific changes.

• Hematology may show neutrophilia, neutropenia (associated with sequestration during acute exacerbation), monocytosis and/or a mild non-regenerative anemia. • Serum biochemistry may show hyperglobulinemia, bilirubinemia and raised liver enzymes (depending on the degree of associated cholangitis/cholangiohepatitis complex), and/or hypercholesterolemia, hypertriglyceridemia and hyperglycemia (often associated with concurrent diabetes). Hypocalcemia may be associated with • Serum amylase and lipase tests are rarely useful in the diagnosis of pancreatitis in cats, although a raised lipase level may be seen occasionally.

A number of older tests are very unreliable and are now rarely used. These include staining fecal smears to demonstrate undigested fat (Sudan III or IV stain) and starch (iodine stain), and fat absorption tests.

Abdominal radiographs are usually unremarkable.

Ultrasound examination may reveal pancreatic enlargement, irregularity or heterogeneity, evidence of peripancreatic fat necrosis, enlargement of mesenteric lymph nodes, and/or evidence of post-hepatic biliary obstruction (enlarged gall bladder, thickened bile or tortuous common bile duct).

Evaluation of serum trypsin-like immunoreactivity (TLI) may be helpful.

• The species-specific assay must be performed on a fasted serum sample. • Serum TLI may be increase with pancreatitis and decrease with exocrine pancreatic insufficiency. • While it consistently diagnoses exocrine pancreatic insufficiency, it often fails to confirm pancreatitis, possibly because chronic inflammation has reduced the overall ability of the pancreas to produce TLI.

Evaluation of serum pancreatic lipase immunoreactivity (PLI) may be helpful.

• The species-specific assay must be performed on a fasted serum sample. • Serum PLI may increase with pancreatitis and appears to be more sensitive than TLI.

A therapeutic trial with replacement pancreatic enzymes may be considered (see under treatment).

• Providing that any associated IBD and/or cholangitis/cholangiohepatitis complex has been addressed, the response to treatment may be dramatic. However, a positive response is not diagnostic of chronic pancreatitis and/or exocrine pancreatic insufficiency.

• Because triaditis is common, it is advisable to collect liver and intestinal biopsies at the same time, and send part of the liver biopsy and a sample of bile for culture.

These include most of the other causes of weight loss with a good appetite. However, since cats with chronic pancreatitis and exocrine pancreatic insufficiency usually develop diarrhea and/or vomiting, other causes of enteropathy, IBD, cholangiohepatitis, alimentary lymphosarcoma, hyperthyroidism and the other malassimilation syndromes should be considered as important differentials.

(For treatment of acute pancreatitis see page 277, The Cat With Depression, Anorexia or Dehydration)

Replace pancreatic enzymes by adding pancreatic enzyme replacement to food (~ half a teaspoonful of powder per meal, or to effect), or add fresh-frozen then defrosted pig pancreas (~20-40 g per meal, or to effect).

In the non-suppurative form of pancreatitis, immunosuppressive doses of corticosteroids may be needed to reduce ongoing inflammation (prednisolone 1-4 mg/kg q 12-24 hours PO, then taper over 1-3 months and maintain on every other day doses if needed). Alternately, chlorambucil could be considered (2-5 mg/m 2 PO up to once every 48 h).

• Feed a highly digestible, "bland enteric diet", which is low in fat. Feed small meals frequently. • Cobalamin is often reduced by lack of pancreatic intrinsic factor and malabsorption and should be supplemented (125-250 μg/week SC or IM for 6-8 weeks or 50-100 μg/cat/day PO). • Vitamin K1 is often required because fat malabsorption results in poor absorption of fat-soluble vitamins like vitamin K, and this can result in abnormal hemostasis (0.5 mg/kg/day SC for 3-4 days, then once weekly). • Vitamin E may be given for its anti-oxidative properties (50-200 IU/cat/day PO).

Surgical intervention may be required if complete biliary obstruction occurs (cholecystotomy or cholecystoduodenostomy), or if a focal pancreatic mass is detected (partial pancrectomy to remove a pancreatic pseudocyst, abscess, fibrotic mass or tumor).

Diabetes that develops secondary to chronic pancreatitis can be very difficult to stabilize. Insulin requirements may vary widely because of the ongoing pancreatic pathology, and treatment is complicated further when corticosteroids also need to be given.

It is essential to diagnose and treat any concurrent disease (e.g. IBD and/or cholangitis/cholangiohepatitis complex).

Prognosis depends on the severity of damage. Many cats live with low-grade smoldering pancreatitis for many years, however, once exocrine pancreatic insufficiency and/or diabetes has developed the prognosis is worse.

In rare cases of congenital exocrine pancreatic insufficiency, the prognosis is good, as long as the cat receives pancreatic supplementation.

Since it is not known what triggers pancreatitis to develop, it is not currently possible to prevent its onset. However, since chronic pancreatitis can progress to exocrine pancreatic insufficiency, it would appear sensible to try to control it as well as possible to try to prevent its progression.

• Typically seen in middle-aged cats, and Persian cats may be over-represented. • Weight loss, inappetence, some cats may be polyphagic, • ± mild generalized lymphadenopathy, • ± vomiting and/or diarrhea. • In some cats, is associated with IBD and/or pancreatitis.

The cholangitis/cholangiohepatitis complex comprises chronic non-suppurative (lymphocytic) cholangitis/cholangiohepatitis, suppurative cholangitis/cholangiohepatitis and biliary cirrhosis.

• The pathogenesis and interaction of the three conditions is poorly understood and it is highly probably that each of these conditions incorporates a number of different diseases. • Cholangitis describes inflammation of the biliary tract, while cholangiohepatitis describes inflammation of the peribiliary hepatocytes as well as the biliary tract.

• The only condition that may be associated with polyphagia is lymphocytic cholangitis/cholangiohepatitis.

It is probably immunemediated, but is possibly associated with progression of the suppurative form. It is often associated with IBD and/or pancreatitis, and when all three occur together it is termed "triaditis".

Cats of any age may be affected, but disease is seen most typically in middle-aged cats. Persian cats may have an increased risk.

Affected cats are typically jaundiced, but bright, and are often polyphagic.

Vomiting and/or diarrhea may be present.

Cats may have a palpably enlarged liver and mild generalized lymphadenopathy.

Cats may show intermittent signs of systemic illness, with fever, anorexia, weight loss, and vomiting. Systemic signs are sometimes associated with secondary infections, typically of the liver and/or pancreas.

The disease may progress to causing chronic biliary cirrhosis with ascites, hepatic encephalopathy, and bleeding tendencies.

Serum biochemistry often reveals mild to moderately (occasionally severely) increased liver enzymes, increased bile acids, hyperbilirubinemia, hyperglobulinemia and hypoalbuminemia.

Hematology may reveal mild anemia, lymphopenia or lymphocytosis, monocytosis and/or thrombocytopenia. Blood clotting times are frequently prolonged.

Ascitic fluid, if present, is typically high in protein.

Radiographs typically reveal hepatomegaly and occasionally choleliths (gallstones), while ultrasound examination may also show blotchy hepatic hyperechogenicity, "sludging" of bile, and evidence of com-mon bile duct obstruction. Associated findings may include enlarged mesenteric lymph nodes, pancreatic irregularity, and/or thickening of the duodenal walls.

A definitive diagnosis is made by histopathological examination of a liver biopsy.

• A fine-needle aspirate is rarely diagnostic, so a percutaneous needle biopsy or surgical wedge biopsy is required. Blood clotting times and/or a PIVKA test (protein induced by vitamin K absence or antagonism) should be assessed first, and a platelet count should be performed. • Typical gross findings include a very firm often rather irregular liver, and a thickened and distended gallbladder and common bile duct, which often contains inspissated bile. Enlarged mesenteric lymph nodes, pancreatic irregularity and/or thickening of the duodenal walls may also be present. • If performing an exploratory laparotomy, it is sensible to check the patency of the biliary outflow, then collect biopsies from the mesenteric lymph nodes, small intestines and pancreas as well as liver. Send bile and part of the liver biopsy for culture. • Histopathology of the liver reveals lymphocytic and/or plasmacytic periportal inflammation, bile ductule hyperplasia, and periportal fibrosis. Very chronic cases may have biliary cirrhosis.

These include most of the other causes of weight loss with a good appetite. However, since cats with lymphocytic cholangitis/cholangiohepatitis complex often develop vomiting and/or diarrhea enteropathies (including IBD), pancreatitis, and the other malassimilation syndromes should be considered as important differentials. In cases that develop ascites, the wet form of feline infectious peritonitis (FIP) should also be considered. This is because both conditions produce a protein-rich ascitic fluid and have similar biochemical and hematological changes. However, the presence of polyphagia usually differentiates the two conditions as cats with FIP are usually anorexic.

Treatment is largely empirical.

• Ampicillin (10-40 mg/kg q 8 hours PO), amoxicillin (11-22 mg/kg q 8-12 hours PO), or cephalexin (10-35 mg/kg q 8-12 hours PO) • Add metronidazole for its effect against anaerobes and its immune-modulating effects (7.5-10 mg/kg every 12 hours PO). Do not use higher doses, as these can be hepatotoxic.

• Immunosuppressive doses of corticosteroids (prednisolone 2-4 mg/kg q 12-24 hours PO), then taper over 1-3 months, and maintain on every other day doses if needed. • Other immunosuppressive agents may be considered, e.g. methotrexate (0.13 mg/cat every 12 hours × 3 doses PO, repeated once weekly) or chlorambucil (2-5 mg/m 2 PO up to once every 48 h).

• Ursodeoxycholic acid aids bile flow and is believed to have hepatoprotective effects (10-15 mg/kg q 24 hours PO). • Vitamin K1 is often required because fat malabsorption results in poor absorption of fat-soluble vitamins like vitamin K and this can result in abnormal hemostasis (0.5 mg/kg q 24 hours SC for 3-4 days, then once every 7-14 days). • Vitamin E may be given for its anti-oxidative properties (50-200 IU/cat/day PO). • S-adenosylmethionine (SAMe) may be given for its hepato-protective and anti-oxidative properties (18 mg/kg/day PO). • Some authors suggest feeding either hypoallergenic or high-fiber diets.

Surgery will be required where complete biliary obstruction occurs (cholecystotomy or cholecystoduodenostomy).

It is important to address any associated or underlying conditions, such as IBD, pancreatitis, extrahepatic bile duct obstruction or cholecystitis.

Prognosis is very variable and often unpredictable. Some cases respond well and only need temporary treatment, others require continued therapy to maintain remission, while others progress relatively rapidly and require euthanasia. Once severe fibrosis, cirrhosis or ascites has developed the prognosis is usually guarded.

Since it is not known what triggers the development of lymphocytic cholangitis/cholangiohepatitis complex, it is currently not possible to prevent its onset.

• Rare condition of older, typically, male cats.

• Slow increase in body size, especially affecting head and feet. • Variable weight change with a good appetite. • Usually diabetic; so polyuric and polydipsic.

In cats, most cases of acromegaly are caused by the development of a growth hormone-secreting tumor within the pituitary gland.

Unlike the situation in the dog, increased levels of circulating progestogens or progesterone do not stimulate growth hormone secretion in the cat.

Acromegaly is seen most typically in older, male, mixed-breed cats.

Affected cats slowly increase in size, with somewhat disproportionate enlargement and thickening of the head and feet. • Growth of the jaw bones may result in obvious interdental spaces and/or prognathism. • A mild increase in respiratory noise may result from increased soft tissue thickness around the airways. • Distortion of the joints can lead to destructive arthritis.

Acromegalic cats develop insulin-resistant diabetes because excess growth hormone causes peripheral insulin resistance. However, early cases may have unstable diabetes rather than being truly resistant.

• Milk thistle, 7 50 mg/kg q24h PO -.

• They therefore develop polyuria, polydipsia and polyphagia. • They may either gain or lose weight.

While all organs undergo growth and hypertrophy, hepatomegaly and renomegaly are the easiest to detect on palpation. Enlargement of the abdominal organs often results in a pot-bellied appearance.

Organ enlargement may lead to organ failure. The clinical signs will therefore reflect the particular organ systems that have been affected; e.g. cardiac hypertrophy and eventual congestive heart failure, liver failure and/or kidney failure.

Concurrent hypertension may result in clinical signs, typically ocular hemorrhages, sudden blindness and/or neurological signs.

Only rarely do neurological signs result from the pituitary tumor compressing and invading the hypothalmus.

• Hyperglycemia and glycosuria will be present, but ketosis is rare. • Affected cats may also show azotemia, hypercholesterolemia, hyperphosphatemia, hyperproteinemia, erythrocytosis and mildly raised liver enzymes.

Comparing the cat to a previous photograph of itself can be helpful in confirming the disproportionate enlargement and thickening of its head.

A definitive diagnosis can be made by measuring growth hormone levels (where available) or insulinlike growth factor-1 (IGF-1) assay, which gives similar results. Unfortunately, the degree of elevation does not always correlate with the clinical signs, and IGF-1 will also be increased in most cats treated long-term with insulin.

The presence of acromegaly can be confirmed by evaluating the growth hormone response to a glucose suppression test.

Other tests can be used to gain supportive evidence.

• Radiography may show organomegaly, increased interdental spaces, hyperostosis of the skull and/or degenerative arthritis.

• Ultrasonography and, where available, computed tomography (CT) or magnetic resonance imaging (MRI) can also be used to detect organomegaly. CT and MRI may be used to determine the location and extent of the tumor within the brain.

Differential diagnoses include most of the other causes of weight loss with a good appetite. However, since all cats with acromegaly develop diabetes with polyuria and polydipsia, other causes of diabetes, hyperadrenocorticism, hyperthyroidism and renal insufficiency are the most important differentials.

Acromegaly can be treated three ways; surgery, external-beam radiotherapy or medically.

• Surgical excision of the growth hormone-secreting tumor is usually a rapid and effective treatment for affected humans. However, the procedure has rarely been performed in cats, and mapping of the tumor is essential prior to considering surgery. • In humans, external-beam radiotherapy is often effective, although clinical improvement may be slow to develop. The few cats that have been treated in this way have shown variable results. Treatment requires repeated anesthetics and suitable facilities are limited. • Although they require frequent administration and usually cause side-effects, somatostatin analogs (e.g. octreotide) and dopamine agonists (e.g. bromocriptine) are sometimes used in the treatment of humans with acromegaly. Unfortunately, limited trials with octreotide in acromegalic cats have not been promising, and dopamine agonists have not yet been evaluated in this species.

Temporary management consists of trying to treat the diabetes and any other concurrent or related diseases (e.g. hypertension, heart failure, renal disease).

• Control of the diabetes can usually be achieved by giving extremely high doses of exogenous insulin (20-130 IU/day), sometimes in various combinations of short-, intermediate-or long-acting insulin. However, because the severity of the insulin resistance can fluctuate, the dose should not exceed 12-15 IU/injection so the risk of iatrogenic hypoglycemia is reduced.

• Very rarely, spontaneous necrosis of the tumor can result in temporary or permanent remission of clinical signs.

The long-term prognosis is poor. However, because the tumors grow very slowly, the short-term prognosis may be good to guarded with survival times of 4-48 or more months reported.

Since acromegaly is usually caused by a slow growing pituitary tumor, its development cannot be prevented.

• A rare condition of middle-aged and older cats. • Poor coat condition and pot-bellied appearance. • Polyuric, polydipsic, polyphagic and often diabetic.

In cats, hyperadrenocorticism, more correctly termed hypercortisolism, can be caused by: 

Hyperadrenocorticism is typically seen in middle-aged to older cats. Females may be over represented.

History is often vague, but usually includes polyuria, polydipsia, polyphagia, weight loss and lethargy, and affected cats may have a history of recurrent infections and/or abscesses.

Since cortisol antagonizes insulin, approximately 80% of cases develop diabetes, which may or may not be insulin resistant, based on the insulin dose administered.

Cats with hyperadrenocorticism typically have poor coat condition, spontaneous alopecia, very fragile thin skin that bruises easily and a pot-bellied appearance. Hepatomegaly is often palpable.

Hyperadrenocorticism should be suspected in any cat with the clinical signs described above, particularly if it has unstable diabetes, and/or a long history of exogenous corticosteroids administration.

Since hyperadrenocorticism is frequently associated with diabetes, serum biochemistry and urinalysis often reveal persistent hyperglycemia, glucosuria ± ketonuria.

Unlike in dogs, a stress leukogram is rarely present, although lymphopenia may be seen.

Increased liver enzymes and hypercholesterolemia may be seen regardless of whether or not the cat has diabetes.

• Few of the tests have well-established specificity and sensitivity in cats. • It is usually necessary to use a combination of tests.

In cats, the most useful screening tests are: • Adrenocorticotropic hormone (ACTH) stimulation test -Collect baseline blood sample, give 0.125 mg of synthetic ACTH IV, collect blood after 1 ± 2 hours. Normal basal serum cortisol concentration is 10-110 nmol/L (0.36-3.6 μg/dl); at 1 h and/or 2 h after ACTH is 210-330 nmol/L (7.6-11.9 μg/dl); > 330 nmol/L (> 11.9 μg/dl) is 

Differential diagnoses include most of the other causes of weight loss with a good appetite. However, since most cats with hyperadrenocorticism develop polyuria, polydipsia and diabetes, other causes of diabetes, acromegaly, hyperthyroidism and renal insufficiency are the most important differentials.

While there are a number of different treatment options, there have been few good studies into their use in cats.

Medical therapies have generally given poor results, and safe dosages have not been established. They may be given pre-surgically to reduce the operative risks. • Trilostane has produced promising results in a very small number of cases and warrants further investigation, particularly given that side effects have not been significant. • Mitotane gave poor results in early trials, and it has been suggested that higher doses and/or longer courses may be needed. • Ketoconazole has given mixed results and considerable toxicity.

• Metyrapone has given mixed results and is difficult to obtain. • L-depronyl has little information available on use in cats, and no proven efficacy.

Radiation therapy with ablation of the pituitary tumor has given mixed results.

Adrenalectomy. Because of the difficulties of medical therapy, surgery has been considered the treatment of choice. However, this is changing with the success of trilostane treatment. Where a single adrenal tumor is present, the removal of the affected adrenal gland is recommended. With PDH or bilateral adrenal tumors, bilateral adrenalectomy is recommended. While surgery can provide successful treatment, the risk of a fatal peri-operative hypoadrenal crisis, renal failure or surgical complications are great.

The procedure should only be performed by an experienced surgeon. Consideration of the diabetic state must be given, and peri-operative and post-operative treatment with glucocorticoids is essential. Glucocorticoids are needed in all cases. Short-term treatment will be needed after unilateral adrenalectomy, because the contralateral gland will be temporarily atrophied. Long-term treatment will be needed after bilateral adrenalectomy, and should also include mineralocorticoids.

Without successful treatment, the prognosis is poor. Where PDH is present, successful bilateral adrenalectomy will reduce the signs of hyperadrenocorticism, but the risk of a hypoadrenal crisis is high and tumor expansion will eventually lead to neurological signs. If adrenal tumors are successfully removed the hyperadrenocorticism should resolve, and the diabetic state may become less insulin resistant or even resolve. Early studies with trilostane appear to show that while it may ameliorate signs of hyperadrenocorticism, it may not alter the need for exogenous insulin in cats that are also diabetic.

Since hyperadrenocorticism is usually caused by pituitary or adrenal tumors, its development cannot be prevented. Iatrogenic hyperadrenocorticism can be prevented by not giving long courses of exogenous corticosteroids.

Classical signs

• Rare disease seen most frequently in young male cats. • Weight loss with a good appetite early in disease. • Often marked subcutaneous edema and ascites. • ± polydipsia and polyuria. • ± vomiting and/or diarrhea.

Glomerulonephropathy can arise from one of two mechanisms: • Primary glomerulonephritis has antibodies targeted directly against the glomerular basement membrane. • Secondary glomerulonephritis has deposition of immune complexes within the glomeruli that have arisen elsewhere in the body.

-This is the most common form in cats.

-It tends to be membranous or membrano-proliferative in nature. -It may be associated with many different conditions (see below), but in most cases the underlying cause cannot be found. • Diseases that may be associated with secondary glomerulonephritis in cats include infection with FeLV, FIV, FIP, Mycoplasma spp., or Ehrlichia spp., chronic pyoderma, chronic gingivitis, dirofilariasis, endocarditis, pancreatitis, pyometra, neoplasia or other immune-mediated diseases.

Deposition of immune complexes within the glomerulus leads to the initiation of inflammation and this results in proteinuria (protein-losing nephropathy).

Rare condition seen most typically in young male cats.

Clinical signs may be non-specific. Typically in the later stages there is anorexia, depression, weight loss, lethargy and poor coat condition. More specific signs include subcutaneous edema, ascites, and polyuria and polydipsia.

It tends to takes one of two clinical forms: • Nephrotic syndrome with ascites and subcutaneous edema, usually affecting the hind legs, ventral body wall and neck. This form may or may not be associated with signs of renal failure (polyuria, polydipsia). • Renal failure with no signs of nephrotic syndrome.

Cats with early nephrotic syndrome may present with weight loss with a good appetite.

Edema affecting the intestines can exacerbate the protein loss and result in malabsorption, diarrhea, vomiting and weight loss.

Systemic hypertension may arise secondary to the renal dysfunction and result in acute blindness, ocular hemorrhages or signs of CNS dysfunction.

Other clinical signs may result from any primary disease conditions.

On abdominal palpation, the kidneys may appear small and/or irregular or, occasionally, enlarged.

Cats with nephrotic syndrome have marked proteinuria, hypoalbuminemia and hypercholesterolemia.

Other findings may include hypertriglyceridemia, hypocalcemia, non-regenerative anemia and neutrophilia.

Increased concentrations of blood urea and creatinine (azotemia) and a low urine specific gravity (<1.035) will indicate whether or not renal insufficiency is present.

• This should be quantified by determining the urine protein to creatinine ratio (UPC ratio). • UPC ratio: < 0.4 = normal, > 0.4-2 suggestive of glomerulonephropathy or tubular disease, > 2 consistent with glomerulonephropathy.

Urinalysis may reveal an inactive sediment, with or without hyaline and/or granular casts.

It is important to try to determine an underlying cause. This may involve screening radiography and ultrasonography, tests for immune-mediated disease, and numerous tests for infectious disease (see above for the list of possible diseases).

Systemic blood pressure should be assessed.

Abdominal radiographs and ultrasound examination rarely reveal obvious renal changes.

Renal biopsy is necessary to confirm the diagnosis and find which type of glomerular disease is present.

• Blood clotting times, platelet number, and systemic blood pressure should be assessed prior to biopsy. • Ultrasound-guided percutaneous biopsy is relatively safe but laparotomy or laparoscopy reduces the risk of post-operative bleeding. Renal hemorrhage is a risk, especially if hypertensive. • Sample must contain >5 glomeruli to make a diagnosis; this usually means multiple needle biopsies or a wedge biopsy are required. • Routine histopathology (fix sample in buffered normal formalin), electromicroscopy (fix sample in paraformaldehyde-glutaraldehyde), ± immunohistochemistry (keep fresh and paraffin embed) are needed to confirm a diagnosis. • On gross inspection kidneys may appear normal, be slightly small, firm and pale, or show irregular pitting and fibrosis. • Light microscopy typically shows diffuse thickening of the glomerular basement membrane, with variable degrees of cellular proliferation in the affected glomeruli. Special stains can help to define the changes, but electromicroscopy and immunohistochemistry are needed to define the exact nature and extent of the disease.

Chronic renal failure, diabetes, acromegaly, hyperadrenocorticism and hyperthyroidism are important differentials in those cats that develop polyuria and polydipsia. However, the presence of ascites in combination with polyphagia is suggestive of lymphocytic cholangitis/cholangiohepatitis complex. Once hypoalbuminemia is detected, then a protein-losing enteropathy or severe liver failure should be considered.

Treatment for nephrotic syndrome is controversial and usually empirical.

Monitor response to treatment by assessing changes in body weight, serum and urinary protein levels.

Where an underlying cause can be found it should be treated.

• High protein diets may help to correct hypoalbuminemia and reduce protein malnutrition. • However, they may exacerbate proteinuria, glomerular hypertension and glomerular damage. • High-protein diets should not be fed if serum urea is elevated. • Some cats benefit from mild protein addition while others benefit from mild protein restriction. Feed the chosen diet for ~ 2 weeks then reassess.

help to reduce proteinuria and any associated systemic hypertension (e.g. benazepril 0.25-0.5 mg/kg/day PO).

If systemic hypertension is significant, the calcium channel antagonist amlodipine (0.625 mg/cat/day PO) should be given.

Use of corticosteroids and immunosuppressive drugs is controversial. They may or may not help to reduce immune complex formation, will worsen any azotemia, and are contraindicated once renal failure is evident.

Very careful use of diuretics can help to reduce fluid retention and improve the patient's well-being (e.g. frusemide 1-2 mg/kg q 8-12 hours PO, reducing to as low dose as possible and monitoring closely for sideeffects).

Thromboembolic disorder is rare in cats, but if present consider giving low doses of aspirin (10-25 mg/kg every 3 days PO).

Very variable and often unpredictable. Some undergo spontaneous complete or partial remissions (~30%), others need temporary or continuous therapy, while others progress relatively rapidly to require euthanasia.

Approximately 50% survive for 2.5-6 years.

Cats with nephrotic syndrome that do not originally have renal insufficiency, may or may not progress to develop renal insufficiency.

Prognosis is poor with worsening clinical signs or progression to renal failure.

Prompt recognition and treatment of underlying disease may prevent the development of secondary glomerulonephritis. However, since it is not usually possible to detect the underlying cause, it is not usually possible to prevent the onset of glomerulonephritis.

The long-term prognosis of feline idiopathic membranous glomerulonephropathy

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Outcome of cats with diarrhea and Tritrichomonas foetus infection

Diarrhea associated with tritrichomonas in cats

Efficacy of ronidazole in vitro and in vivo for treatment of feline Tritrichomonas foetus infection

Prevalence of and risk factors for feline Tritrichomonas foetus and Giardia infection

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Assessment and management of proteinuria in dogs and cats

Glomerulonephritis in the cat

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Over representation of Burmese cats with diabetes mellitus

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Results of chemotherapy for cats with alimentary malignant lymphoma: 21 case (1993-1997)