Endocrine Society Research Round-up

People taking glucocorticoids at higher risk for Covid-19

Individuals taking glucocorticoids on a routine basis may be unable to mount a normal stress response and are at high risk if they are infected with the virus causing Covid-19, according to a new editorial published in the Endocrine Society’s Journal of Clinical Endocrinology and Metabolism.

Published data to date shows that these patients are over-represented 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.

Injectable supplemental glucocorticoid therapy in this setting can reverse the risk of potentially fatal adrenal failure and should be considered in every case, the editorial notes.

Individuals with known primary adrenal insufficiency, ie, Addison’s disease, and secondary adrenal insufficiency occurring in hypopituitarism should also take extra precautions. 

For patients treated with glucocorticoids, it will be invaluable to reiterate ‘sick day rules’ for known patients with primary and secondary adrenal insufficiency taking glucocorticoid replacement therapy.

As it relates to Covid-19, any patient with a dry, continuous cough and fever should immediately double their daily oral glucocorticoid dose and continue on this regimen until the fever has subsided, the article states.

Deteriorating patients and those who experience vomiting or diarrhoea should seek urgent medical care and be treated with parenteral glucocorticoids.

Reversing potential adrenal failure as a cause of mortality with parenteral glucocorticoid therapy is straightforward to do once the issue has been recognised, reiterates the editorial. The intent here is to ensure that no patient with a history of prior exposure to chronic glucocorticoid therapy (>three months) by whatever route should die without consideration for parenteral glucocorticoid therapy.

As a community, endocrinologists will be key to ensuring recognition, management, and implementation of these important measures, the document stresses.

In this context, it will be important to communicate the reason underpinning glucocorticoid use. Based on prior experience in patients with acute respiratory distress syndrome and those affected with SARS and MERS, where glucocorticoid therapy was without benefit or associated with higher rates of invasive ventilation and mortality, the World Health Organisation (WHO) guidance is not to prescribe glucocorticoids. Physiological stress doses of hydrocortisone (50-to-100mg intravenously TID), not pharmacological doses of other corticosteroids, should be given.

Secondly, the impact on patients with pituitary or other neuroendocrine disease also needs to be considered, the article says. As for patients with primary adrenal insufficiency, many of these patients have hypopituitarism, including secondary adrenal insufficiency, requiring stress dose glucocorticoid supplementation, as previously noted. Moreover, these patients may also have diabetes insipidus, further compounding fluid and electrolyte disorders and requiring careful monitoring and judicious water and electrolyte replacement to prevent hyponatraemia or hypernatraemia. This is particularly important in the context of increased insensible fluid loss associated with fever and tachypnoea, combined with impaired ability for fluid intake, with altered level of consciousness.

Third, for patients with diabetes mellitus, whereas the risk of contracting a viral illness is no greater than those without diabetes mellitus, severity of disease from viral infections is notably greater, points out the editorial.

Recent published reports from the Wuhan province in China reveal that those with diabetes mellitus and hypertension were over-represented among the most severely ill patients with Covid-19 and those succumbing to the disease. Whether this susceptibility to illness severity is especially greater in the case of Covid-19 or simply a reflection of the greater risk posed by diabetes remains uncertain at this point.

Current guidance from the US Centres for Disease Control and Prevention (CDC) for prevention of Covid-19 for those with diabetes is no different than the general population, but the recognition that diabetes poses a greater risk for severity of illness should prompt healthcare providers to be more vigilant in the assessment of such patients who present with concerning symptoms (ie, shortness of breath, fever), the editorial states.

Thyroid hormone use may raise death risk in older adults

Thyroid hormone replacement therapy in older adults is associated with a higher risk of death compared with no treatment, a new large study has found. The study results were accepted for presentation at ENDO 2020, the American Endocrine Society’s annual meeting, and published in a special supplemental section of the Journal of the Endocrine Society. 

People with hypothyroidism usually require life-long treatment with levothyroxine to supplement the body’s thyroid hormone, thyroxine (T4). Some people have subclinical hypothyroidism, which occurs when the thyroid gland needs more stimulation to produce adequate thyroid hormone levels. These individuals will have modest elevations in thyroid-stimulating hormone (TSH), which stimulates thyroid hormone production.

Subclinical hypothyroidism is a mild or early form of thyroid disease, and these patients also routinely receive thyroid hormone replacement, said the study’s principal investigator Dr Jennifer Mammen, an Assistant Professor at Johns Hopkins University in Baltimore, US. However, Dr Mammen notes that this interpretation of high TSH with normal T4 levels may not be correct in all older adults.

“Many older adults have an elevation in TSH with normal thyroid levels. Our earlier research showed that this can reflect developing hypothyroidism in some, while in others, it is a form of adaptation to age-related changes in health instead of thyroid disease,” Dr Mammen said. “As a result, some of these older people may be receiving inappropriate or excessive thyroid hormone therapy, treatment that may counteract important adaptations needed for healthy ageing.”

The study examined the effects of levothyroxine therapy on survival in adults aged 65 years and older. They used data from 1,054 participants in the Baltimore Longitudinal Study of Aging, a long-running observational study from the US National Institute on Ageing. All participants had at least one TSH and T4 measurement since 2003. Dr Mammen’s research team looked at the risk of dying during one-year intervals from 2003 to 2018 and adjusted their statistical analyses for multiple demographic and health factors that may influence survival.

They found that among older adults, use of thyroid hormone increased risk of death 60 per cent year-over-year (hazard ratio (HR) 1.6). They also limited the analysis to compare individuals with normal TSH levels, reflecting normal thyroid function, to those on thyroid hormone with normal TSH levels, who were therefore treated to target, and found those on treatment had almost double the risk of dying compared with untreated persons (HR 1.9), Dr Mammen reported.

Despite studies showing that hormone treatment of an isolated high TSH may not benefit older people, Dr Mammen said, “we were surprised that we were able to demonstrate harm associated with thyroid hormone supplementation. Our work supports the growing calls to use age-specific TSH reference intervals to determine the threshold for thyroid hormone treatment.”

Dr Mammen also recommended repeating testing after finding an isolated elevation of TSH in older adults, because levels can fluctuate. “We advocate being cautious and conservative when considering thyroid hormone treatment,” she said.

The Endocrine Society cancelled its annual meeting, ENDO 2020, amid concerns about Covid-19. The Society has more than 18,000 members, including scientists, physicians, educators, nurses and students in 122 countries.

For more information go to www.endocrine.org.

Two types of diabetes drugs similarly effective in reducing heart and kidney disease

Two newer types of medications commonly used to treat type 2 diabetes are similar in their ability to reduce major heart complications, including heart attack, stroke and death from cardiovascular disease, according to research accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and published in a special supplemental section of the Journal of the Endocrine Society.

One class of drugs, SGLT2 inhibitors, has a clear benefit over the other class, GLP-1 drugs, in reducing hospitalisation for heart failure, the study found. “This helps doctors more easily choose a medicine to best treat diabetes,” said lead study author Dr Ali Al-Khazaali of Saint Louis University in St Louis, US.

SGLT2 inhibitors include canagliflozin, dapagliflozin and empagliflozin. The study compared these oral drugs with injected GLP-1 receptor agonists. These include albiglutide, dulaglutide, exenatide, liraglutide and semaglutide.

In prior studies, it was found that these two classes of drugs showed cardiac and renal benefits, besides controlling blood sugar levels.

The researchers analysed data from six previous trials of GLP-1 (including a total of 51,762 subjects) and four trials of SLGT2 inhibitors (including 33,457 subjects). Both drug classes were equally effective in reducing combined major adverse cardiac events such as heart attack, stroke and death from cardiovascular disease, compared to people with diabetes who were not taking the drugs.

The rate of hospitalisation for heart failure was 32 per cent less in patients taking SLT2 inhibitors compared to patients not taking the drugs, especially in those with more severe cardiovascular disease risk. In contrast, people taking GLP-1 drugs did not have a reduced rate of hospitalisation for heart failure compared with people who had diabetes but were not taking the drugs. Both classes of drugs demonstrated kidney benefit; neither class was superior.

The most common serious side-effects for SGLT2 inhibitors included yeast infections in women and diabetic ketoacidosis. The major serious side-effect for GLP-1 drugs was stomach upset.

“Doctors need to balance this side-effect against the possible weight-loss benefits of this medicine,” Dr Al-Khazaali said.