key: cord-0046542-utgk1cp4
authors: de la Flor Merino, José Carlos; Mola Reyes, Laura; Linares Gravalos, Tania; Roel Conde, Ana; Rodeles del Pozo, Miguel
title: An unusual case of severe acute hyponatremia in patient with COVID-19 infection()
date: 2020-06-29
journal: nan
DOI: 10.1016/j.nefroe.2020.06.015
sha: 35e099fca2d1c5687607da4b34378af9121b4472
doc_id: 46542
cord_uid: utgk1cp4

nan

Letter to the Director An unusual case of severe acute hyponatremia in a patient with COVID-19 infection [ Hyponatremia is the most prevalent hydroelectrolytic disorder in clinical practice, and is linked to higher rates of morbidity and mortality. Coexistence of hyponatremia and COVID-19 infection (an emerging respiratory disease caused by the novel SARS-CoV-2 coronavirus) has been reported in recent studies, but without knowledge of the possible underlying pathophysiological mechanisms. 1, 2 We present the case of a patient with severe hyponatremia and COVID-19 infection.

A 59-year-old man had a history of hypertension being managed with a combination of angiotensinconverting enzyme inhibitors and hydrochlorothiazide, which had been suspended four days before admission. He sought care due to signs and symptoms for 10 days consisting of a dry cough, slight difficulty breathing, and fever. Three days earlier, he also developed abdominal pain, nausea, and vomiting, and 24 h earlier he also experienced headache and drowsiness. During examination he showed confusion, bradypsychia, and clinical signs of mild dehydration of the skin and mucosae. Laboratory testing revealed severe hyponatremia (102 mEq/L) in the absence of azotemia as well as C-reactive protein 5.05 mg/dL (0.02-0.05 mg/dL), ferritin 252 ng/mL (30-400 ng/mL), D-dimer 174 ng/mL (0-500 ng/mL), and lymphocytes 1.35 × 10 3 /µL. All other laboratory values are shown in Table 1 . A chest X-ray showed a bilateral alveolarinterstitial pattern. PCR for SARS-CoV-2 yielded a positive result.

Treatment was started with hypertonic saline 3%, correcting the patient's natremia to 125 mEq/L, as well as azithromycin with hydroxychloroquine for the patient's COVID-19 infection. Initially, syndrome of inappropriate antidiuretic hormone secretion (SIADH) was suspected. Despite treatment with restriction of fluid, salt, and urea, on the fifth day, the patient had not yet achieved natremia values >125 mEq/L. The patient was found to have low levels of adrenocorticotropic hormone (ACTH) and cortisol ( Our patient showed signs and symptoms of severe hyponatremia difficult to account for with only his vomiting and/or diuretic treatment, with a striking discrepancy between his clinical and laboratory findings, i.e. dehydration but no azotemia. Hyponatremia is a known form of presentation of HPT, having been reported in various clinical situations, but uncommonly as an initial sign of a pituitary tumor in the context of a respiratory infection due to COVID-19 3 , which probably exacerbated its presentation. Lippi et al. 4 , following an electronic search on MEDLINE (PubMed), Scopus, and Web of Science, using the keywords sodium, potassium, chlorine, and calcium in patients with COVID-19 disease, identified five studies with a total of 1,415 patients. Sodium was significantly lower in patients with severe disease compared to patients with mild disease due to COVID-19 (weighted mean difference: −0.91 mmol/L, 95% CI: −1.33-0.5 mmol/L). However, it is not yet known whether there is a greater risk of hyponatremia or other electrolyte abnormalities in patients with COVID-19, nor is the mechanism that would cause it understood.

Our patient met nearly all the criteria for SIADH, except for the presence of hormonal abnormalities in thyroid, adrenal, and pituitary function. 5 In the differential diagnosis, we ruled out cerebral salt-wasting syndrome (CSWS) given the absence of polyuria and the correction of natremia following volume and sodium replacement, which are fundamental factors in CSWS. By contrast, secondary AI is caused by insufficient hypothalamic-pituitary stimulation, with deficiencies in ACTH and glucocorticoids, but proper mineralocorticoid function and an intact renin-angiotensin-aldosterone axis. 6 This explains why our patient did not show classic AI symptoms, as mineralocorticoid deficiency is only present in primary AI. 7 Our patient's severe hyponatremia presented after he developed gastrointestinal signs and symptoms and respiratory infection. We do not know whether stress-induced glucocorticoid decompensation was triggered by this infectious condition.

Endogenous cortisol exerts a tonic inhibitory effect on ADH secretion. Glucocorticoid deficiency features ADH release that cannot be suppressed despite existing hyposmolality. 8 Glucocorticoids cause a negative feedback loop in both corticotropin release and ADH release. 9 This corrects the hydroelectrolytic abnormality (which would not occur in CSWS) and normalizes ADH levels and renal aquaporin-2 mRNA expression. 10 In conclusion, in patients diagnosed with severe hyponatremia, unusual causes should be considered among the possible diagnoses. In our case, we believe that COVID-19 infection may have played a role in the severity of the patient's hyponatremia.

J o u r n a l P r e -p r o o f 

Clinical Characteristics of Coronavirus Disease 2019 in China. The New England journal of medicine

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Severe hyponatremia as the presenting feature of clinically nonfunctional pituitary adenoma with hypopituitarism

Electrolyte Imbalances in Paients with severe Coronavirus Disease 2019 (COVID-19)

Clinical practice guideline on diagnosis and treatment of hyponatraemia

Hyponatraemia for the clinical endocrinologist

Adrenal insuficiency

Close association of severe hyponatremia with exaggerated release of arginine vasopressin in elderly subjects with secondary adrenal insufficiency

Effect of arginine vasopressin antagonist on water excretion in glucocorticoid and mineralocorticoid -deficient rats

Exaggerated urinary excretion of aquaporin-2 in the pathological state of impaired water excretion dependent upon arginine vasopressin