Clinical Thyroidology® for the Public

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Is thyroid hormone treatment in hypothyroidism a risk factor for stroke?

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Hypothyroidism is a common condition and is treated with thyroid hormone. Levothyroxine was the third most commonly prescribed medication in the United States during 2017 and 2018. Typically, thyroid hormone therapy is lifelong once initiated. There are studies that have shown that despite the widespread use, thyroid hormone overtreatment and undertreatment are common but the long term adverse effects of both are unclear. Some studies have shown that high thyroid hormone levels, as seen in hyperthyroidism, increases the risk of heart disease, specific atrial fibrillation, and stroke. However, it is not clear if high thyroid hormones produced by thyroid hormone prescribed for treatment of hypothyroidism is associated with either atrial fibrillation or stroke.

Stroke is a leading cause of death and serious disability in the United States. Although there is a large amount of knowledge about risk factors for stroke, many of these factors cannot be changed (such as age and sex). Therefore, the attention has moved to identify risk factors that can be changed to reduce the risk of stroke.

The aim of the study was to determine if abnormal thyroid hormone levels in patients taking thyroid hormone is associated with increased risks for atrial fibrillation and stroke over time.

Papaleontiou M et al 2021 Thyroid hormone therapy and incident stroke. J Clin Endocrinol Metab. Epub 2021 Jun 17. PMID: 34137866.

This study was done using data from 733,208 adult patients who received thyroid hormone therapy in the United States. These patients were followed between January 2004 and December 2017 at the Veterans Health Administration. Medical records of patients who were found to have at least two serum TSH measurements and at least two free thyroxine levels since the start of treatment until either the development of a stroke or atrial fibrillation or the conclusion of the study were selected for review.

Patients who had thyroid cancer (these patients are intentionally slightly over treated with thyroid hormone), or who were on lithium or amiodarone ( these medicines may alter the results of thyroid function tests) were excluded from the analysis. Participants were grouped into categories according to TSH level : Serum TSH <0.1mIU/L; 0.1-0.5 mIU/L; >0.5-5.5 mIU/L and >5.5 mIU/L and free T4 level <0.7 ng/dl;0.7 to 1.9 ng/dl and >1.9ng/dl. A normal thyroid level was considered as having a serum TSH between 0.5-5.5 mIU/L with a free T4 between 0.7-1.9 ng/dl. The main outcomes measured were the onset of atrial fibrillation and acute stroke after having initiated thyroid hormone therapy.

Overall, 11.08% of patients developed atrial fibrillation, and 6.32% of patients had an acute stroke during time of study. Patients taking thyroid hormone and with a very low TSH ( <0.1) or high free T4 levels had a higher risk for stroke and atrial fibrillation when compared to patients with normal TSH and free T4, after controlling for other risk factors such as smoking status, age, race, hypertension, diabetes mellitus among others. An unexpected finding was that the patients who had a high TSH or low free T4 levels (undertreatment), also were found to have a higher risk of atrial fibrillation when compared to patients who had normal thyroid hormone levels. Another important observation is that the risks for atrial fibrillation and stroke continued to increase over time in patients who were overtreated and undertreated with thyroid hormone.

The conclusion of this study is that among patients treated with thyroid hormone, those who have higher or lower than normal thyroid hormone levels have a higher risk to develop a stroke or atrial fibrillation over time. Those patients with normal thyroid hormone levels did not have an increased risk, emphasizing the need to maintain normal thyroid levels in patients that are being treated with thyroid hormone. Although the findings related to low thyroid hormone levels while on treatment are not consistent with other studies, it highlights the need to design other clinical studies to help clarify this association.

—Jessie Block-Galarza, MD


Hypothyroidism: a condition where the thyroid gland is underactive and doesn’t produce enough thyroid hormone. Treatment requires taking thyroid hormone pills.

Levothyroxine (T4): the major hormone produced by the thyroid gland and available in pill form as Synthroid™, Levoxyl™, Tirosint™ and generic preparations.

TSH: thyroid stimulating hormone — produced by the pituitary gland that regulates thyroid function; also the best screening test to determine if the thyroid is functioning normally.

Atrial Fibrillation: An irregular heart rhythm which can lead to strokes.

November is Hyperthyroidism Awareness Month