Considerations for Treatment of Endocrine Dysfunction in COVID-19

Novel coronavirus disease 2019 (COVID-19) can both cause and be fueled by endocrine dysfunction, and clinicians should take special considerations when treating endocrine disorders within the backdrop of the pandemic, according to a review published in the Journal of the Endocrine Society.

The COVID-19 pandemic has caused unprecedented challenges for healthcare professionals across all fields of medicine, including endocrinologists. Though the outbreak is still in its infancy, key insights can be gained from preliminary research on the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the endocrine system as well as previous experiences with SARS-CoV-1.

Infection with SARS-CoV-2 may affect several components of the endocrine system, including the pituitary, adrenal, and thyroid glands; the pancreas; and systemic electrolyte balance.

SARS-CoV-2 interacts with angiotensin converting enzyme 2 (ACE2), which is expressed on cells of the lungs, heart, and kidneys, as well as on cells in the hypothalamus, pancreas, and gonads. Interaction with ACE2 not only facilitates viral entry into cells, but also results in dysregulation of the renin-angiotensin-aldosterone system (RAAS). This system regulates blood pressure and fluid/electrolyte balance and its disruption can lead to hypokalemia.

In SARS-CoV-1 infections, the virus has also been found to disrupt the hypothalamo-pituitary-adrenal and hypothalamo-pituitary-thyroid axes, leading to transient cases of hypercortisolism and hypothyroidism, and may be associated with the development of hyperglycemia as well. Anecdotal and emerging evidence from the COVID-19 pandemic suggests that patients with COVID-19 may also have a higher incidence of hyperglycemia and related concerns such as diabetic ketoacidosis.

Hyperglycemia is an indicator of poor prognosis in patients with COVID-19, so prompt recognition and management is needed.

However, certain treatments for diabetes may have important implications within the context of COVID-19. In patients with existing endocrine dysfunction, it is important to consider how treatment may exacerbate COVID-19 symptoms or affect antiviral treatment. Patients on dopamine receptor agonist therapy, for example, may be at risk for drug interactions with certain antiviral agents, which may alter treatment strategies.

Though ACE2 is structurally similar to ACE, early results suggest it is not inhibited by ACE inhibitors or angiotensin II receptor blockers, though it may be upregulated by their use.

Current agents used for the treatment of COVID-19 may exacerbate symptoms of endocrine disorders. Certain drugs such as hydroxychloroquine and azithromycin may cause QT prolongation. Calcium levels should be normalized in patients with hypocalcemia before initiating treatment and careful monitoring should be performed.

In addition to its potential effects on treatment strategies, COVID-19 may have important implications for testing in endocrine dysfunction. In SARS-CoV-1-infected patients, free thyroxine, triiodothyronine, and thyrotropin levels are decreased. Though it is not clear if this effect is observed in patients with COVID-19 as well, it suggests that testing for endocrine disorders may be challenged by COVID-19 disease symptoms. Extra caution should be taken in the differential diagnosis of endocrine disorders within the backdrop of the COVID-19 pandemic.

“As SARS-CoV-2 is a novel virus, limited data is available on the effect of the virus on the endocrine system, including the pancreas,” the review authors acknowledged. However, early clinical reports can be used to build on previous work on the pathogenesis of SARS-CoV-1 to begin to paint a picture of the effects COVID-19 on the endocrine system. In addition to molecular and genomic studies of SARS-CoV-2, the reviewers noted, “[c]linicians should be encouraged to report their experience in managing patients with pre-existing endocrine diseases to improve current practices, which are mostly empirical.”

Reference

Somasundaram NP, Ranathunga I, Ratnasamy V, et al. The impact of SARS-Cov-2 virus infection on the endocrine system [published online July 2, 2020]. J Endocr Soc. doi:10.1210/jendso/bvaa082