key: cord-0818166-9zi5culm
authors: Uddin Chowdhury, Md Reaz; Akter, Kazi Shanzida; Moula, Mohammad Moksedul; Kabir, Muhammad Anwarul; Bhuiyan, Sahedul Islam; Sohan, Arif Mohammad
title: COVID-19 presented with syndrome of inappropriate ADH SECRETION(SIADH):a case report from Bangladesh
date: 2020-11-12
journal: Respir Med Case Rep
DOI: 10.1016/j.rmcr.2020.101290
sha: 84edc3034fbbcc602548ccb7d9a756e074a76669
doc_id: 818166
cord_uid: 9zi5culm

BACKGOUND: Novel corona virus(SARS-CoV-2) which emerged from Wuhan, China, has spread to whole worlds very rapidly causing enormous health effect and death. Current publications worldwide showed that COVID-19 is a disease involving multiple system of the body with many unusual presentations. So physicians face the challenges to manage it in the hospital. CASE REPORT: The syndrome of inappropriate secretion of anti diuretic hormone (SIADH) is one of the most common causes of hyponatremia accounts for approximately one-third of all cases.In the diagnosis of SIADH it is important to ascertain the euvolemic state of extra cellular fluid volume, both clinically and laboratory measurement. Several infections associated with SIADH have been reported. Howover, Coronavirus disease 2019(COVID-19) associated with SIADH were only few cases reported.We are presenting a case of 70 year old female admitted with unconsciousness later diagnosed as severe hyponatremia along with COVID-19 complicated with severe pneumonia.

Hyponatremia is most common electrolyte disorder in clinical practice [1] .Wide spectrum of aetiologies associated with hyponatremia is always a challenge in early diagnosis and treating this serious abnormality. Hyponatremia is associated with an increased risk of overall mortality in all patients [1] . SIADH is characterized by euvolemic hyponatremia, low plasma osmolality ,elevated natriuresis , hypouricemia and lack of evidence of other hypouraemic diseases [2] .The most common pathological conditions such as sub-arachnoid haemorrhage, stroke, tumours, drugs and pulmonary disorders including pneumonia [3] .Besides infectious disease ,several inflammatory conditions also influenced SIADH. In these situations, interleukin-6(IL-6), released by monocytes and macrophages, plays a pathogenic role in inducing the non-osmotic release of vasopressin [4] .

Coronavirus disease 2019 (COVID-19) ,which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),transmitted often from human to human by droplet and contact routes [5] .The disease usually manifests as upper or lower respiratory system illness in majority of clinical presentation [6] .We describe a case of 70 year aged woman with SIADH associated COVID-19 with severe pneumonia. Our aim of this work to share how the patient present, steps of diagnosis and to improve patient management during this pandemic period.

A 70 year old woman non-diabetic with past medical history of hypertension on antihypertensive(amlodipine 5mg/telmisartan 80mg) presented to the emergency department on 24 June,2020 with one(1) day history of high grade fever, shortness of breath and unconsciousness for 4 hours. She has no history of diarrhoea ,vomiting, chest pain ,rhinorrhea , headache ,blurring of vision, anosmia, dehydration or any history of bronchial asthma, chronic obstructive pulmonary disease(COPD) ,heart failure or any history of trauma, she didn't take any antipsychotic rather took only a antihypertensive combination. But she complained of severe fatigue for last 5 days. She developed fever for 1 days which was high grade continued, highest recorded temperature was 104® f relieved by taking antipyretic paracetamol orally and per rectal . On the admission day at morning her son told that she developed drowsiness followed by unconscious, then she was taken to emergency department of Medinova specialized hospital , Feni, Bangladesh. On admission she was unconscious with GCS score 5, Temperature was 103® f, Heart rate was 100/min, Respiratory rate 26/min with oxygen saturation 89% on room air immediately put on supplemental oxygen with simple face mask ,Blood pressure was 160/85mm of Hg. Other general examinations were normal, physical examinations revealed bilateral coarse crepitations in both lungs , Cardiac apex in normal position ,1 st and 2 nd heart sound normal without any added sound, Jugular venous pressure(JVP) not raised, no leg edema or any organomegaly, she was put on urethral catheterisation and found normal urine output and also put on nasogastric feeding tube for feeding.

Emergency blood/serum send for laboratory investigations and were found(see Table: 1) serum sodium of 114mEq/L(normal range 135-145 mEq/L),potassium was 3.6mEq/L(3.5-5.5mEq/L),Other laboratory investigation showed Hemoglobin (Hb%) was 11.1gm/dl (normal range 11.0-16.0 gm/dl),Erythrocyte sedimentation rate(ESR) (westergren) was 54mm in 1 st hour ,total white blood cell count(WBC) was 6900/cmm (normal range 4000-11000/cmm), differential count of neutrophils was 74% (normal range 40-75%), lymphocytes was 11%(normal range 20-50%), eosinophils was 0%(normal range 2-9%),platelet count was 177,000/cmm (normal range 150.000-400,000/cmm),random blood sugar was 5.5mmol/L (normal up to 7.8mmol/L),serum creatinine was 1.3mg/dl (normal range 0.5-1.2mg/dl),SGPT was 16 U/L( normal up to 32U/L),C reactive protein(CRP) was 65mg/l(normal range<7mg/l ),serum ferritin was J o u r n a l P r e -p r o o f 317ng/ml(normal 20-250ng/ml in female), troponin I was <0.1ng/ml (normal <0.1ng/ml),serum thyroid stimulating Figure :1 )., Electrocardiogram (ECG) and Computed tomography of brain(CT brain) was un remarkable. Further workup revealed low normal blood urea which was 11.6mg/dl(normal range 10-50mg/dl), low serum uric acid 2.4mg/dl(normal range 2.4-5.7mg/dl in female),urine osmolality of 353mOsm/kg(reference value 60-1400 mOsm/kg), low plasma osmolality which was 219 mOsm/kg(reference value 275-295)(275-295, urinary sodium was 34 mEq/L(around 20 mEq/L), random serum cortisol at 8 AM was 14mcg/dl(normal ranges :10-20mcg/dl),ACTH stimulation test was not done. As COVID-19 cases increased in Feni, Bangladesh , we sent a nasopharyngeal swab for RT-PCR for corona which came positive. After all workup she was diagnosed as having COVID-19 with severe pneumonia with SIADH.

The treatment was started after getting initial investigation with slow hypertonic 3% sodium chloride solution , after 6 hours of infusion there was remarkable improvement in her consciousness. Nasogastric fluid restriction initiated. She was oriented, responded verbally but drowsy. Sodium levels were monitored in the next 96 hours and fluctuated between 120-130 mEq/L. She was on supplemental oxygen 10-12 L/min through a non-rebreather mask and maintained saturation of oxygen above 94% from the day of admission to next 7days. She was started intravenous antibiotic meropenem 1gm 8 hourly for 10days, thromboprophylaxis with enoxaparin40mg subcutaneous 12 hourly for 7days, antiviral oral favipirapir 1600mg loading on day 1,followed by 600mg twice daily for next 9 days according to national guideline of Bangladesh along with intravenous methylprednisolone 250mg daily for 5 days and oral clarithromycin500 twice daily for 14 days. After 15 days she was withdrawn from nasogastric feeding ,started on oral feeding and gradually improving with less oxygen supplymentation .Follow up investigation report(see Table: 2) and Chest X ray posterior anterior view showing(see Figure  : 2) still bilateral infiltration that is radiological improvement lagged behind the clinical improvement. 

Many causes of hyponatremia in SIADH patients have been documented such as tumours, stroke, Central nervous system trauma, porphyria , psychosis, drugs and pulmonary disorders including tuberculosis, obstructive lung disease [2] .Diagnostic criteria for SIADH comprises low plasma sodium concentration(typically<130mmol/l),low plasma osmolarity (<275mOsml/kg),urine osmolarity not minimally low(typically>100 mOsm/kg),urine sodium concentration not minimally low(>30mmol/l),lownormal plasma urea, serum creatinine , uric acid, clinical euvolemia, absence of adrenal, thyroid, pituitary and renal insufficiency, no recent use of diuretic and appropriate clinical context [7] .Our patient was diagnosed as SIADH based on diagnostic criteria though pituitary functions was not done and she have no symptoms suggestive of adrenal and pituitary disease. Our patient was not taking any drug of inducing hyponatremia and the patient was compliant to antihypertensive drugs (amlodipine 5mg/ telmisartan 80mg combination) for 3years without any change or addition of new drug.

The emergence of SARS-CoV-2 around the world and resulting the disease COVID-19 led to high number of cases with severe pneumonia [8] . Hyponatremia is frequently associated with atypical pneumonia. One of the underlying mechanisms is inappropriate ADH secretion [9] .

A case series of COVID-19 with SIADH published recently, described two patients who presented with respiratory symptoms, were diagnosed with COVID-19, and found to have SIADH [10] . Howover, in all mentioned cases fever was a common feature and there was evident of pneumonia (abnormal chest Xray having pulmonary infiltrates) but not present with unconsciousness. In our case patient presented with fever, unconsciousness and respiratory distress. She was found acute hyponatremia excluding other causes of hyponatremia and diagnosed as SIADH with presence of other laboratory findings. So we suggest that SARS-CoV -2 infection is one of the infective causes of SIADH but still high-quality data are urgently needed to get an impression of the potentially manifold faces of COVID-19 and its multidimensional complications.

The mechanism of SIADH in COVID -19 pneumonia is not well established. But presence of SIADH could be a clue for diagnosing COVID-19.Emotional, physical or psychological stresses and pain associated with infections such as COVID-19 may result in development of SIADH .So we suggest additional large scale studies require to correlate the incidence and pathogenesis of SIADH in COVID-19. This will advance our knowledge about the mechanism of SIADH in COVID-19 patients and specific recommendation for treatment may be required for management of hyponatremia in these cases.

Moderate hyponatremia is associated with increased risk of mortality: evidence from a meta-analysis

Clinical laboratory evaluation of the syndrome of inappropriate secretion of antidiuretic hormone

The syndrome of inappropriate antidiuresis

SIADH in systemic JIA resolving after treatment with an IL-6 inhibitor

Epidemiology of COVID-19

Current status of epidemiology. diagnosis, therapeutics, and vaccines for novel coronavirus disease 2019(COVID-19)

Clinical practice guideline on diagnosis and treatment of hyponatremia

A comprehensive literature review on the clinical presentation and management of the pandemic coronavirus disease 2019(COVID-19) Cureus

Hyponatremia and inappropriate ADH syndrome in pneumonia

The authors would like to thank Medinova specialized hospital, Feni, Bangladesh, SARS-CoV-2 managing director Mr Humayun kabir, Chairman of the hospital Mr Abdul Quddus Sumon , medical assistant team ,nursing team and all other stuffs that are fighting against this pandemic disease.

Written informed consent was obtained from the patient for publication of this case report.

The authors have no conflict of interest relevant to this case.