BACKGROUND
Hypothyroidism is a common condition in which the thyroid gland does not produce enough thyroid hormone. It is treated with thyroid hormone replacement, called levothyroxine, to replace the hormone the body can no longer produce. Doctors monitor thyroid-stimulating hormone (TSH) levels to determine whether a patient is receiving the appropriate dose of thyroid hormone. A high TSH level generally indicates too low a dose of levothyroxine, whereas a low TSH level suggests the levothyroxine dose may be too high. Because hypothyroidism is usually a lifelong condition, most patients require regular TSH monitoring and periodic adjustments to their medication.

Maintaining TSH within the recommended range is important for several reasons. Appropriate thyroid hormone replacement helps relieve hypothyroid symptoms, including fatigue, weight gain, and constipation. Thyroid hormone also plays a critical role in heart health by affecting heart rate, blood pressure, and the heart’s ability to beat effectively. When that happens, it can cause heart failure. As a result, the body may not receive enough blood and oxygen, leading to symptoms such as shortness of breath, fatigue, and fluid retention. Both too much and too little thyroid hormone, even when mild, can adversely affect heart function.

Studies have shown that many patients taking levothyroxine have TSH levels outside the recommended target range, indicating that both too much and too little levothyroxine remains common in clinical practice. Given the important effects of thyroid hormone on the cardiovascular system, the authors sought to determine whether patients with high or low TSH levels were at increased risk of heart failure.

THE FULL ARTICLE TITLE
Evron J, et al. Association between over- and under-replacement with thyroid hormone and incident heart failure. J Clin Endocrinol Metab 2026;111(6):e1634–e1642.

SUMMARY OF THE STUDY
The authors reviewed the medical records of 641,504 adults in the U.S. Veterans Health Administration who started thyroid hormone treatment between 2004 and 2017. Patients with thyroid cancer and those taking medications known to affect thyroid function (lithium or amiodarone) were excluded, as were patients with a prior diagnosis of heart failure. During follow-up, 12.7% of patients developed heart failure. Patients whose thyroid hormone replacement kept their TSH level within the normal range had the lowest risk. In contrast, patients who were undertreated (high TSH levels) or overtreated (very low TSH levels) had a higher risk of developing heart failure, even after accounting for other important risk factors such as age, sex, and smoking.

The strongest association occurred in patients with elevated TSH levels, suggesting undertreated hypothyroidism. Heart failure risk rose progressively as TSH increased above the normal range. Compared with patients whose TSH remained within the target range, those with TSH levels above 5.5 mIU/L were nearly six times more likely to develop heart failure over the next five years. Very low TSH levels due to overtreatment were also associated with increased heart failure risk, although the increase was smaller than with undertreatment.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study suggests that some patients with hypothyroidism who are overtreated (TSH too low) or undertreated (TSH too high) appear to have an increasing risk of heart failure. This reinforces the need to ensure TSH levels stay in the normal range during treatment of hypothyroidism. Once treatment for hypothyroidism begins, regular blood tests and appropriate dose adjustments are important to keep TSH levels within the target range.

— Philip Segal, MD

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