Hypothalamic-Pituitary Axis Function and Adrenal Insufficiency in COVID-19 Patients

The outbreak of COVID-19 has affected more than half a billion people worldwide and caused more than 6 million deaths since 2019. The responsible virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affects the lungs, but it has multisystemic effects. It is well known that dysfunction of multiple endocrine organs may occur during or after COVID-19. Impairment of the hypothalamic-pituitary-adrenal (HPA) axis is of utmost importance as it may lead to death if went undiagnosed. SARS-CoV-2 may cause both primary and secondary adrenal insufficiencies (AIs). The clinical manifestations of AI are generally non-specific and might be attributed to the complications caused by the infection itself. The underlying pathogenetic mechanisms were explained by the immunogenic, vascular effects of the infection or the direct effects of the virus. The diagnosis of AI in critically ill patients with COVID-19 is not straightforward. There is lack of consensus on the cut-off values of basal serum cortisol levels and stimulation tests during the disease. Here we review the literature with a special regard on the evaluation of the HPA axis in patients with COVID-19. We conclude that the possibility of AI should always be kept in mind when dealing with patients with COVID-19, and repeated basal cortisol measurements and the ACTH stimulation test results could guide the clinician during the diagnostic process.