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Disclosures: The authors report no relevant financial disclosures.
March 19, 2021
2 min read

COVID-19 associated with impaired adrenocortical response in hospitalized patients

Disclosures: The authors report no relevant financial disclosures.
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Most patients hospitalized with COVID-19 at a hospital in Saudia Arabia in May 2020 had an impaired hypothalamic-pituitary-adrenal response, with plasma cortisol at central adrenal insufficiency levels, according to study data.

“It was expected that the hypothalamic-pituitary-adrenal response would be brisk in patients with acute COVID-19 infection,” Ali S. Alzahrani, MD, scientist and head of the molecular endocrinology section at King Faisal Specialist Hospital & Research Centre and professor of medicine at Alfaisal University in Riyadh, Saudi Arabia, told Healio. “To our surprise, the study found the opposite situation in most patients in this study.”

More than half of patients with COVID-19 who had cortisol testing done three times met the criteria for an inadequate cortisol response. Data were derived from Alzahrani AS, et al. Endocr Pract. 2021;doi:10.1016/j.eprac.2020.10.014.

Alzahrani and colleagues analyzed data from 28 adults admitted to King Faisal Specialist Hospital & Research Centre with COVID-19 from May 7 to May 20, 2020. Plasma cortisol and adrenocorticotropic hormone (ACTH) levels were measured on the first or second day of admission between 5 a.m. and 8 a.m. Most patients also had levels measured one to three times on different days. Researchers defined adrenal insufficiency as any plasma cortisol level below 300 nmol/L during the acute phase of illness.

Ali S. Alzahrani

Of the study cohort, 16 were completely healthy without any known illnesses prior to COVID-19, whereas the remaining 12 adults had a medical condition that did not interfere with adrenal function. Fifteen adults had a mild COVID-19 infection, 11 were asymptomatic and two had a moderate infection. None were in the ICU.

In initial testing, 64.3% of the study cohort had a cortisol level of less than 300 nmol/L, 50% had a level below 200 nmol/L and 28.6% had a level less than 100 nmol/L. ACTH values were less than 30 ng/L in 82.1% of patients, less than 20 ng/L in 60.7% and less than 10 ng/L in 26.9%.

There were 20 people who had repeated testing done on another day after additional testing. In this subgroup, 45% of patients had a cortisol level of less than 300 nmol/L, 30% had a level of less than 200 nmol/L and 10% had a level of less than 100 nmol/L. A total of seven patients qualified for a diagnosis of possible adrenal insufficiency based on plasma cortisol level remaining below 300 nmol/L in both initial and follow-up testing.

Fifteen people in the study cohort had repeated cortisol testing done for a third time. Cortisol levels were less than 300 nmol/L in 60% of the subgroup, less than 200 nmol/L in 40% and less than 100nmol/L in 20%. Nine patients met the criteria for an inadequate cortisol response, with three having been tested once and six tested three times. Of the nine adults with inadequate cortisol response, six had a mild COVID-19 infection and one had a moderate infection, whereas only two were asymptomatic.

“This is the first study to draw attention to the possibility of undiagnosed adrenal insufficiency in some patients with COVID-19,” Alzahrani said. “If this is confirmed in further studies, it could have significant implications on the management of COVID-19. This is relevant in view of the RECOVERY trial results showing a substantial benefit of dexamethasone therapy in patients with severe COVID-19 infection. Conceptually, some of those benefits might have been due to the treatment of undiagnosed absolute or relative adrenal insufficiency in such patients. This also goes with the longtime held and controversial issue of relative adrenal insufficiency, also called critical illness-associated adrenal insufficiency, believed to occur in critically ill patients admitted to the intensive care units.”

Researchers aim to confirm their findings in a future study in which a more accurate method, such as a short cosyntropin test, is used to assess adrenal function, according to Alzahrani.

For more information:

Ali S. Alzahrani, MD, can be reached at