Endocrine Abstracts

Objective: The SARS-CoV-2 requires angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane serine protease 2 (TMPRSS2) for gaining entry inside the cells (1). In humans, ACE2 and TMPRSS2 mRNAs are expressed in several endocrine glands, including the hypothalamus, pituitary, and adrenal cortex (2). Thus, it is possible that patients with COVID19 may have hypothalamic-pituitary-adrenal (HPA) axis dysfunction both during acute COVID19 and/or following recovery from COVID19. We studied the temporal course of hypothalamic-pituitary-adrenal (HPA) dysfunction in patients with corona-virus disease (COVID19).

Methods: After excluding patients receiving glucocorticoids or opiates prior to sampling, and pre-existing pituitary or adrenal disease, 302 patients (median age 54 years [interquartile range 42–64], 76% males, 97 had severe/critical illness) were recruited. HPA axis was evaluated by morning cortisol and adrenocorticotrophic hormone (ACTH) at admission (n=231) withing first 48 hours of admission. Adrenal insufficiency (AI) during acute illness was defined using a morning cortisol <83 nmol/l. AI at 12-months follow-up was defined using a peak cortisol <406 nmol/l in the ACTH-stimulation test (APST) (n=90). Those with AI at 12-months were further assessed by the APST 6-monthly for recovery of hypoadrenalism.

Results: The median morning cortisol and ACTH during COVID19 were 295 (IQR 136–461) nmol/l and 3.9 (0.8–6.9) pmol/l, respectively. AI was present in 33 (14%) patients; ACTH was elevated in three, and low or inappropriately normal in the rest 30 patients. At 12-months, AI was seen in 13% (12/90) patients and hypothalamic-pituitary in origin in all; five (42%) of them had not met the diagnostic criteria for AI during COVID19. AI diagnosed at admission persisted at 12-months in seven patients and recovered in seven; the remaining 19 patients were lost to follow-up. The presence of AI at 12-months was independent of severity, and steroid use during COVID19. A morning cortisol <138 nmol/l during COVID19 predicted presence of AI at 12-months. All patients showed recovery of HPA axis in the ensuing 12-months.

Conclusion: Central AI was common during acute COVID19 and at 12-months of follow-up. AI can be late-onset, developing after recovery from COVID19 and was transient in nature.