INTRODUCTION

Coronaviruses use the homotrimeric spike glycoprotein of their envelope to bind to their cell receptors through membrane fusion, thus allowing their entry. Binding to the angiotensin II receptor (ACE2) is a critical initial step for SARS-CoV-2 to enter target cells, meaning that cells expressing ACE2 are susceptible to infection ¹. Endocrine alterations have been described in COVID-19, and pituitary and hypothalamus lesions are frequent. The dissemination route can be hematogenous, through leukocytes as a vehicle to the central nervous system crossing the blood-brain barrier, or neural, mediated by ACE2 receptors in the vascular endothelium ². Direct alterations of the virus by immune-mediated responses mainly at the pituitary gland generate lesions, low availability of vasopressin, secondary polyuria, and hypernatremia ³.

Diabetes insipidus (DI) is a condition characterized by an imbalance of water in the body, leading to intense thirst and polyuria. Central diabetes insipidus (CDI) occurs when there is a deficiency in the secretion of vasopressin (antidiuretic hormone) from the pituitary gland. The hypothalamic-pituitary axis can be affected by various etiologies, including infections like COVID-19, which may hypothetically lead to CDI due to direct viral invasion or immune-mediated damage.

COVID-19 and hypernatremia: Hydroelectrolyte disorders are frequent in intensive care units. It has been found that hypernatremia has a prevalence of approximately 26% ¹. However, reviews in patients with SARS-CoV-2 have a much higher presentation (50%), associated with higher morbidity, days of mechanical ventilation, and length of ICU stay ². In a series of approximately 10,000 patients, most records correspond to hyponatremia. However, patients with hypernatremia, whatever their level, had higher mortality than eunatremic or hyponatremic patients ³.

Possible explanations from the renal and central points of view are discussed below.

CASE REPORT

A 46-year-old woman with a history of arterial hypertension managed with angiotensin II receptor antagonists and hydrochlorothiazide presented with general symptoms and progressive dyspnea, testing positive for COVID-19 by PCR. She required orotracheal intubation and admission to the intensive care unit (ICU). Nine days after the onset of symptoms, she developed hypernatremia and was managed with hypotonic intravenous fluids and free water by orogastric tube. However, four weeks later, she developed refractory hypernatremia to the established management (sodium 190 mEq/L). Therefore, the patient also required continuous slow hemodialysis for its correction.

During her hospitalization, the patient's urine output was documented to be excessively high, supporting the diagnosis of polyuria. Laboratory tests documented hyposthenuria, high serum osmolarity, and low urinary osmolarity corrected with desmopressin administration, indicating central diabetes insipidus. Furthermore, during evolution, abrupt fluctuations in serum sodium levels were presented (higher than 16 mEq/L in 24 hours), associated with neurological deterioration without pathological findings in simple brain tomography. Magnetic resonance imaging (MRI) was requested (figure 1), documenting a neurohypophysis hypointensity concerning diabetes insipidus of central origin, associated with changes due to extrapontine osmotic demyelination.

The patient was on mechanical ventilation throughout her ICU stay and did not experience cardiac arrest. She was weaned off mechanical ventilation as her condition stabilized. After a prolonged ICU stay of five weeks, she was transferred to a general ward. Her sodium levels gradually stabilized with the continued administration of desmopressin. The patient was discharged home on desmopressin therapy.

Figure A Brain magnetic resonance image showing the absence of hyperintensity in T1 (red circle) 

DISCUSSION

We present the case of a female patient in her fifth decade of life who, during a COVID-19 infection, developed hypernatremia refractory to management with hypotonic solutions, even requiring dialytic therapy for its control. During its study, high serum osmolarity and low urinary osmolarity were documented, which responded to desmopressin management, indicating central origin diabetes, explained by 100% recovery of urinary osmolarity. However, fluctuations in serum sodium led to extrapontine osmotic demyelination, the consequences of which have limited the release of mechanical ventilation.

Hypernatremia in COVID-19 patients poses significant clinical challenges, particularly in those requiring intensive care unit (ICU) management. Our case highlights the complexity of managing hypernatremia in the context of COVID-19 infection and underscores the importance of considering various underlying mechanisms.

CONCLUSION

This case report underscores the importance of considering hypernatremia as a potentially serious complication in patients with severe COVID-19 infection. The variety of underlying mechanisms, including renal dysfunction and alterations in the hypothalamic-pituitary axis, highlight the complexity of its management. Rapid identification and treatment of central diabetes insipidus associated with COVID-19 are crucial for improving clinical outcomes and reducing associated morbidity. Further studies are needed to fully understand the risk factors and optimal management strategies for hypernatremia in this clinical context.