COMMENTARY

Is Thyroid Disease Worsened by COVID?

Spyridoula Maraka, MD, MS; Soumya P. Thumma, MD

Disclosures

October 08, 2020

Editorial Collaboration

Medscape &

As COVID-19 continues to sweep across the globe, people with thyroid disease are searching for answers.

"Does my thyroid condition put me at higher risk for infection?"
"What about complications?"
"Is it safe to continue taking my thyroid medication?"

These are common questions that endocrinologists face every day.

As of September 2020, there have been 56,236 articles on COVID-19 published in the medical literature, but only a handful address the relationship between thyroiditis and COVID-19. Because the evidence remains extremely limited, we aim to summarize the available data and offer clinical guidance to practicing endocrinologists and other clinicians.

How Is the Thyroid Involved?

We know that SARS-CoV-2 enters target cells by binding to angiotensin-converting enzyme 2 (ACE2). Because of the high relative expression of ACE2 on thyroid cells compared with lung cells, one hypothesis for thyroid involvement is that ACE2 in thyroid tissue might be a receptor for SARS-CoV-2 invasion.

Case reports, case series, and retrospective studies describing the association of COVID-19 and thyroiditis have reported subacute thyroiditis/de Quervain thyroiditis manifesting as subclinical hyperthyroidism or overt hyperthyroidism, often with high circulating concentrations of IL-6. Both typical (painful) and atypical (not painful) clinical presentations have been described.

Thyroid dysfunction in subacute thyroiditis usually follows a triphasic course (ie, thyrotoxicosis first, followed by hypothyroidism, and then, finally, euthyroidism) that lasts about 3 months. Symptomatic thyrotoxicosis occurs in the majority of patients, but clinical hypothyroidism is uncommon. Because viral infections such as mumps, influenza, adenovirus, coxsackie, and Epstein-Barr and cytomegalovirus viruses are known environmental triggers for subacute thyroiditis, from a biological standpoint it is not surprising that one of the manifestations of COVID-19 could be an episode of thyroiditis.

What's Been Observed?

In a recent study, about 20% of hospitalized patients with COVID-19 and no previous thyroid disease were found to have elevated serum free T4 concentrations in association with decreased (but not suppressed) serum TSH concentrations and a negative antibody panel that included TSH receptor, antithyroglobulin, and TPO antibodies.

The administration of heparin, which can displace T4 from binding proteins, could play a role in these observations. However, these findings are more consistent with a diagnosis of mild hyperthyroidism possibly due to thyroid inflammation and related destructive thyroiditis due to systemic immune activation. As such, management of these patients should focus on controlling adrenergic symptoms rather than initiating antithyroid drugs.

Similarly, another study found that a substantial portion (15%) of patients with COVID-19 requiring ICU care had low TSH concentrations. However, the mean serum free T4 concentrations were not significantly different between ICU patients with and without COVID-19. The biochemical abnormalities and clinical presentation were not typical of either subacute thyroiditis or nonthyroidal illness, also known as euthyroid sick syndrome.

Multiple mechanisms may contribute to the development of euthyroid sick syndrome in the critical care setting, including alterations in TSH secretion, peripheral 5'-deiodination of T4 to T3, thyroid hormone binding to plasma proteins, transport of thyroid hormone in peripheral tissues, and thyroid hormone receptor activity. Currently available data do not support a clear benefit of treatment with thyroid hormones in euthyroid sick syndrome; ongoing clinical trials are focusing on new management strategies to explore whether restoration of normal serum thyroid hormone concentrations improves patient prognosis and clinical outcomes.

Further studies are needed to determine whether it is appropriate to increase thyroid function testing in critically ill patients with COVID-19. While awaiting these data, clinical judgement is required; symptoms of hypothyroidism or thyrotoxicosis in patients with COVID-19 should prompt thyroid function testing.

Risks, Complications, and Treatment

There is no evidence to date that patients with existing autoimmune thyroid disease are more susceptible to contracting viral illnesses, including infection with SARS-CoV-2, or that they are at higher risk of developing more severe COVID-19 disease. There is also no evidence to suggest increased risk for COVID-19 in poorly controlled thyroid disease, but patients with uncontrolled thyroid dysfunction (especially hyperthyroidism) may be at higher risk for complications of overt thyrotoxicosis and thyroid storm triggered by infection. Hence, patients should continue their antithyroid medications to decrease this risk.

We must educate patients about the potential complications of severe neutropenia, the signs and symptoms of agranulocytosis that may occur with antithyroid medications, and the need for urgent medical evaluation. Because symptoms of neutropenia (sore throat, mouth ulceration, fever, and flu-like illness) may overlap with symptoms of COVID-19 (fever, new continuous cough, and flu-like illness), clinical differentiation can be challenging. The best suggested approach is to stop the medication and obtain a complete blood panel to evaluate for neutrophil count. Test for COVID-19 if indicated, as lymphopenia and thrombocytopenia are seen in COVID-19 and are less likely to be related to antithyroid drugs.

After symptom resolution, antithyroid drugs can be resumed at a lower dose, or an alternative drug may be considered. If symptoms recur after reinitiation of the drug, alternative treatments for hyperthyroidism, such as radioactive iodine ablation or surgery, should be considered.

There are no suggested changes for the diagnosis and treatment of hypothyroidism during the COVID-19 pandemic. Advise patients to continue the same form and dosage of thyroid hormone replacement therapy. Thyroid function testing with TSH and FT4 levels is indicated if a patient reports significant change in hypothyroidism-related symptoms, such as worsening fatigue or weight changes, in order to adjust medication if needed. For pregnant patients, the dose of levothyroxine should be titrated to achieve the usual trimester-specific TSH targets.

In conclusion, there are no data available to suggest that patients with preexisting thyroid conditions are at higher risk for COVID-19 or its complications. Advise patients to continue their current treatment for their underlying thyroid condition but to be vigilant about reporting new symptoms. In patients severely affected by COVID-19, changes in thyroid function may be transient and related to thyroiditis or euthyroid sick syndrome, but specific thyroid-related damage and sequelae may also occur, requiring further investigation.

Physician and patient resources on COVID-19 and the thyroid are available on the American Thyroid Association website.

Spyridoula Maraka, MD, MS, is an assistant professor of medicine at the University of Arkansas for Medical Sciences (UAMS), program director of the UAMS Endocrinology fellowship program, and staff physician at the Central Arkansas Veterans Healthcare System. She has published more than 50 articles in high-impact journals, has received multiple awards and invitations to present at national and international conferences, and serves on committees of several professional organizations.

Soumya Thumma, MD, is a senior UAMS clinical fellow in endocrinology with clinical practice interest in thyroidology. She has worked on promoting patient education and serves on national committees of two professional organizations.

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