Advise & Consult: How Endocrinologists Can Respond to COVID-19

Endocrine-related disorders can put many patients at risk for severe COVID-19 complications. An editorial in The Journal of Clinical Endocrinology & Metabolism provides recommendations for the specialists who treat these patients to ensure optimal care.

The special needs of COVID-19 patients with endocrine-related disorders must be championed lest they be overlooked in the crush of patients needing treatment, according to the lead editors of The Journal of Clinical Endocrinology & Metabolism. Many endocrine patients are at high risk of developing severe symptoms, so the physicians who know them best must step up to ensure that they receive appropriate care.

Editor-in-chief Paul M. Stewart, MD, and deputy editors-in-chief Ursula B. Kaiser, MD, and Raghavendra G. Mirmira, MD, co-authored a special editorial, “Our Response to COVID-19 as Endocrinologists and Diabetologists,” laying out some special concerns and considerations for treating patients with endocrine-related conditions to “highlight a few areas where our discipline-specific contribution can deliver a major impact.”

“These are unusual times, and unusual times call for unusual actions,” says Mirmira, who works at University of Chicago. “A substantial fraction of people with active COVID disease who are in the hospital have an endocrine-related disease, and their endocrine problems will impact their treatment.”

COVID-19 patients who take corticosteroids for a pre-existing condition are at high risk and need to be identified — keeping in mind that the reason a patient has been receiving steroids will influence their COVID-19 treatment.

Adrenal or Inflammatory Conditions?

Patients receiving glucocorticoids for adrenal insufficiency are generally under the direct care of an endocrinologist, who should emphasize to them the need to follow their “sick day rules” — adjustments for when patients begin to feel ill. In the era of COVID-19, the editorial notes that any patients who develop a dry continuous cough and fever “should double their daily oral glucocorticoid dose and continue this regimen until their fever has subsided.” If their symptoms worsen, they should seek urgent medical care — and their providers need to be made aware of their underlying conditions and the potential need for parenteral glucocorticoids.

“The whole reason [glucocorticoids] are given is to dampen down inflammation, so we know that these drugs are immunosuppressive. These patients may not be able to mount a normal stress response, leaving them more susceptible to COVID-19 infection.” – Paul M. Stewart, MD, editor-in-chief, The Journal of Clinical Endocrinology & Metabolism; executive dean and professor of medicine, University of Leeds, Leeds, U.K.

“But the more worrying patients are those taking glucocorticoids whom we don’t see as endocrinologists,” says Stewart, a professor at the University of Leeds in the U.K. As many as 5% of the general population take exogenous steroids to treat a host of conditions, such as asthma, polymyalgia, arthritis, inflammatory bowel disease, and other immune disorders, with the express purpose of suppressing their immune systems. “The whole reason these drugs are given is to dampen down inflammation, so we know that these drugs are immunosuppressive,” Stewart says. “These patients may not be able to mount a normal stress response, leaving them more susceptible to COVID-19 infection.”

Many of these patients may not be receiving their steroids in consultation with an endocrinologist, and perhaps not receiving adequate advice on how their medications may affect their immune response or in-depth guidance about how to react to illnesses. And it is critical that their treatment be individualized, with their dosage and reason for receiving the medication taken into account.

To Give and Not to Give

“A substantial proportion of this population will have adrenal suppression/adrenal insufficiency as a result of their glucocorticoid treatment and may be vulnerable to acute stress requiring ‘stress dose steroids,’” says Kaiser, who is chief of the endocrinology division at Brigham and Women’s Hospital in Boston. “On the other hand, which patients this may apply to may be difficult to ascertain — those on low doses of corticosteroids may not have adrenal suppression/adrenal insufficiency, while those on supraphysiologic doses may already be on sufficient doses that their baseline dose is already equivalent to ‘stress dose’ levels, but these immunosuppressive doses may increase susceptibility to COVID-19. Therefore, we should consider all patients on corticosteroid treatments to be vulnerable.”

“These are unusual times, and unusual times call for unusual actions. A substantial fraction of people with active COVID disease who are in the hospital have an endocrine-related disease, and their endocrine problems will impact their treatment.” – Raghavendra G. Mirmira, MD, deputy editor, The Journal of Clinical Endocrinology & Metabolism; Professor of Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Chicago, Chicago, Ill.

In general, although COVID-19 is an acute inflammatory condition that might be thought to respond to steroid treatment, the experience with related viruses indicates otherwise. In SARS and MERS patients, glucocorticoid therapy was without benefit and even associated with higher rates of ventilator use and mortality, leading the World Health Organization guidance to recommend against prescribing large doses of glucocorticoids to these patients. “Physiological stress doses of hydrocortisone (50–100 mg intravenously t.i.d.), not pharmacological doses of other corticosteroids, should be given,” the editorial recommends.

Neuroendocrine Considerations

Another category of patients of particular concern are those with pituitary or other neuroendocrine diseases. For example, patients with hypopituitarism often have secondary adrenal insufficiency that requires glucocorticoid treatment, so should receive the same treatment as patients with primary adrenal insufficiency. But an additional consideration for these patients is that many of them also have diabetes insipidus, which can greatly complicate the management of their fluid and electrolyte balances in a flu-like illness that can feature fever, shortness of breath, vomiting, and diarrhea.

Diabetes Mellitus

The endocrine patients who are receiving more attention as the pandemic spreads are those with diabetes mellitus, obesity, and related conditions and co-morbidities. These patients are not necessarily more susceptible to COVID-19 infection, but they are at much higher risk for severe complications. A Centers for Disease Control and Prevention report found that 78% of COVID-19 patients admitted to intensive care units and 71% admitted to hospitals had an underlying condition — with diabetes as the leading underlying condition associated with ICU care and hospital admission. The death rate in New Orleans is reportedly several times that of New York City, with Louisiana health officials attributing much of the difference to conditions such as obesity, according to Reuters. Some 97% of those who died in Louisiana had a pre-existing condition, with diabetes and obesity the most prominent.

The danger of developing more severe cases of COVID-19 underlines the importance for these patients of following social distancing, avoiding family members with influenza-like symptoms, and other measures to avoid exposure. Mirmira says that his healthcare system, like many others, is responding to this need by replacing nonurgent office visits with telemedicine where possible and limiting contact through mechanisms like drive-up testing. Patients needing medication might be reminded to use drive-thru pharmacies and noncontact delivery options.

A Role for Endocrinologists

Mirmira noted that a rough estimate at his hospital found that some 30% to 40% of  inpatients with COVID-19 have an endocrine-related disease: “When these people get admitted for COVID-19, their endocrine problems begin to impact their treatment and have the potential for worsening their disease. That is what we were trying to highlight in our editorial.”

“A substantial proportion of this population will have adrenal suppression/adrenal insufficiency as a result of their glucocorticoid treatment and may be vulnerable to acute stress requiring ‘stress dose steroids,’” – Ursula B. Kaiser, MD, deputy editor, The Journal of Clinical Endocrinology & Metabolism; chief, Endocrinology Division, Brigham and Women’s Hospital, Boston, Mass.

Stewart notes that endocrinologists hold visible positions in referral care and major teaching centers, where they can be advocates for their patients and ensure that their needs are included in  their intensive care protocols. He says that the editorial is a rallying cry “to mobilize in whichever hospital they are to make sure the key people in their centers are aware of this guidance.”

Kaiser adds that sorting out the treatment needs of patients who have received glucocorticoid therapy can be a complex and nuanced process, and endocrinologists need to be ready to consult with critical care doctors about the kinds and doses of steroids that might be needed.

-Seaborg is a freelance writer based in Charlottesville, Va. In the April issue, he wrote about how Medicare has benefitted older people with diabetes who use a continuous glucose monitor.