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Disclosures: The authors report no relevant financial disclosures.
April 02, 2020
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Endocrinologists warn of increased COVID-19 complication risks with glucocorticoid use

Source/Disclosures
Disclosures: The authors report no relevant financial disclosures.
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Paul M. Stewart
Paul M. Stewart

Adults who are prescribed glucocorticoid therapy for common conditions, such as asthma, allergies and arthritis, as well as individuals with adrenal insufficiency, are at high risk for developing serious complications from COVID-19 due to an inability to mount a normal stress response, according to an editorial published in the Journal of Clinical Endocrinology & Metabolism.

In a press release issued by the Endocrine Society Tuesday, the authors stated that injectable, supplemental glucocorticoid therapy in the setting of more severe complications from the novel coronavirus can reverse the risk for potentially fatal adrenal failure and “should be considered in every case.”

“This is an important update for our readership — comprising endocrinologists and diabetologists — as to things to look out for when handling patients with COVID-19,” Paul M. Stewart, MD, FRCP, FMedSci, executive dean and professor of medicine at the University of Leeds, United Kingdom, told Healio. “We are genuinely concerned about the risk for adrenal suppression in patients treated with glucocorticoids. Among at-risk COVID patients, this group may represent as many as 5% of the total exposed patient cohorts. The risk here is that these patients cannot mount a normal stress response to infection. Particularly in an ICU setting, intravenous steroids should be considered to prevent deterioration and potential loss of life.”

‘Ensuring recognition’

In the editorial, Stewart and colleagues wrote that there is “little evidence” to guide clinicians on when to intervene regarding the duration of prior corticosteroid exposure or on the impact of dose: either at a higher dose, where supplemental steroid cover may not be necessary, or a lower dose, where adrenal suppression may not be as prevalent.

In a press release issued by the Endocrine Society Tuesday, the authors stated that injectable, supplemental glucocorticoid therapy in the setting of more severe complications from the novel coronavirus can reverse the risk for potentially fatal adrenal failure and “should be considered in every case.”
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“In the interim, it seems logical, if not essential, that we identify all patients taking corticosteroids, for whatever reason, as high risk,” the researchers wrote. “We know from the published reports to date that these patients will be overrepresented in those at greatest risk of dying from COVID-19 — the elderly and those with comorbidities that include diabetes, hypertension, and chronic inflammatory disease. Moreover, those patients taking supraphysiologic doses of glucocorticoids may have increased susceptibility to COVID-19 as a result of the immunosuppressive effects of steroids, comorbidities of underlying immune disorders for which the steroids were prescribed, or immunomodulatory actions of other therapies prescribed in conjunction with glucocorticoids for the underlying disease.”

The researchers wrote that reversing potential adrenal failure as a cause of mortality with parenteral glucocorticoid therapy is “easy and simple to do” once the issue has been recognized. “The intent here is to ensure that no patient with a history of prior exposure to chronic glucocorticoid therapy (> 3 months) by whatever route should die without consideration for parenteral glucocorticoid therapy,” the researchers wrote. “As a community, we will be key to ensuring recognition, management and implementation of these important measures.”

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Individuals with known primary adrenal insufficiency, also known as Addison’s disease, and secondary adrenal insufficiency occurring in hypopituitarism, should also take extra precautions, according to the researchers. As Healio previously reported, the American Association of Clinical Endocrinologists issued a position statement March 25 stating that people with adrenal insufficiency or uncontrolled Cushing’s syndrome are at greater risk for death from a respiratory-related infection, such as COVID-19, and should observe several key recommendations to avoid complications. In the event of acute illness, those with adrenal insufficiency are instructed to increase their hydrocortisone dose per instructions and call their health care provider for more details. Standard “sick day” rules for increasing oral glucocorticoids or injectables would also apply, according to the AACE statement.

“If patients develop symptoms such as a dry continuous cough and fever, they should double their oral glucocorticoid dose immediately and continue doing so until the fever has subsided,” the researchers stated in the release. “They, too, will require injectable glucocorticoid therapy should their condition worsen.”

COVID-19/endocrine connections

As research on COVID-19 continues, endocrinologists are focusing on the mechanism of entry of the virus into cells — angiotensin-converting enzyme 2, or ACE2, which has been established as the COVID-19 receptor; however, data are conflicting regarding its translational relevance, the researchers wrote in the editorial.

“It has been suggested that angiotensin-converting enzyme inhibitors/angiotensin receptor blockers might increase susceptibility and severity to COVID-19 through upregulation of ACE2 and thereby possibly explain the overrepresentation of hypertensive patients in patients dying from COVID-19,” the researchers wrote. “Upregulation of ACE2 might also explain the poor outcome in smokers versus nonsmokers, but it is important to stress that these are preliminary reports and should not result in changing prescribed medications at this stage.”

Research also suggests that the downstream transmembrane protease serine 2 is required for COVID-19 viral spike protein priming and onward transmission, the researchers wrote. Camostat mesylate, a transmembrane protease serine 2 inhibitor, has been approved in Japan for the treatment of pancreatic inflammation and prevented entry of the virus into lung cells when tested in an in vitro model.

“Endocrine-related targets are at the forefront of discovery science as we collectively tackle this pandemic,” the researchers wrote. – by Regina Schaffer

For more information:

Paul M Stewart, MD, FRCP, FMedSci, can be reached at the University of Leeds, Room 9.14, Worsley Building, Clarendon Way, Leeds, LS2 9NL; UK; email: p.m.Stewart@leeds.ac.uk.

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Disclosures: The authors report no relevant financial disclosures.