The Impact of COVID-19 Viral Infection on the Hypothalamic-Pituitary-Adrenal Axis

Abstract

Objective: To study the adrenocortical response to an acute coronavirus disease-2019 (COVID-19) infection.

Methods: Morning plasma cortisol, adrenocorticotropic hormone (ACTH), and dehydroepiandrosterone sulfate levels were measured in 28 consecutive patients with COVID-19 (16 men, 12 women, median age 45.5 years, range 25-69 years) on day 1 to 2 of hospital admission. These tests were repeated twice in 20 patients and thrice in 15 patients on different days. The hormone levels were correlated with severity of the disease.

Results: The median morning cortisol level was 196 (31-587) nmol/L. It was <100 nmol/L in 8 patients (28.6%), <200 nmol/L in 14 patients (50%), and <300 nmol/L in 18 patients (64.3%). The corresponding ACTH values had a median of 18.5 ng/L (range 4-38 ng/L), and the ACTH level was <10 ng/L in 7 patients (26.9%), <20 ng/L in 17 patients (60.7%), and <30 ng/L in 23 patients (82.1%). The repeated testing on different days showed a similar pattern. Overall, if a cutoff level of <300 nmol/L is considered abnormal in the setting of acute disease, 9 patients (32%) had cortisol levels below this limit, regardless of whether the test was done only once (3 patients) or 3 times (6 patients). When the disease was more severe, the patients had lower cortisol and ACTH levels, suggesting a direct link between the COVID-19 infection and impaired glucocorticoid response.

Conclusion: Unexpectedly, the adrenocortical response in patients with COVID-19 infection was impaired, and a significant percentage of the patients had plasma cortisol and ACTH levels consistent with central adrenal insufficiency.

Keywords: ACTH; COVID-19; SARS-CoV-2; cortisol; glucocorticoids; hypothalamic-pituitary-adrenal axis.

Fig. 1

Morning plasma cortisol and ACTH levels on days 1 to 2 after admission of 28 patients admitted with COVID-19 infection. ACTH = adrenocorticotropic hormone; COVID-19 = coronavirus disease-2019.

Fig. 2

Changes in morning plasma cortisol levels during admission for COVID-19 infection. The blue bar represents cortisol-1 done on days 1 to 2 of admission, the orange bar represents cortisol-2 done on days 3 to 5 after admission, and the gray bar represents cortisol-3 done on days 8 to 11 after admission. COVID-19 = coronavirus disease-2019.

Fig. 3

Bar chart showing the percentage of patients with AM cortisol levels consistently <300 nmol/L on one or more days with respect to severity of the disease. It shows a positive correlation between the severity of the disease and probability of having adrenal insufficiency (defined as AM cortisol level <300 nmol/L).