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Association between over- and under-replacement with thyroid hormone and incident heart failure
Josh Evron1, Brandon Moretti2, Richard Evans3
1Division of Endocrinology and Metabolism, Department of Internal Medicine, University of North Carolina, Chapel Hill, NC 27514, USA.
The Journal of Clinical Endocrinology and Metabolism
|December 17, 2025
Summary
Thyroid hormone under- or over-replacement increases heart failure risk. Adjusting thyroid hormone levels may help prevent heart failure, a significant cardiovascular event.
Area of Science:
- Cardiology
- Endocrinology
- Public Health
Background:
- The association between thyroid hormone replacement therapy dosage and incident heart failure is not well-established.
- Thyroid hormone plays a crucial role in cardiovascular function.
Purpose of the Study:
- To investigate the relationship between thyroid hormone under- and over-replacement and the incidence of heart failure.
- To determine if thyroid hormone treatment intensity is a modifiable risk factor for heart failure.
Main Methods:
- A retrospective cohort study was conducted using data from the Veterans Health Administration.
- Over 640,000 adults initiating thyroid hormone treatment between 2004 and 2017 were analyzed.
- Time-varying thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels were used to assess thyroid hormone replacement adequacy.
Main Results:
- Both thyroid hormone under-replacement (e.g., TSH > 20 mIU/L) and over-replacement (e.g., TSH < 0.1 mIU/L) were associated with increased incident heart failure.
- Under-replacement showed a stronger association with heart failure risk, particularly with prolonged TSH levels above 5.5 mIU/L.
- The risk of heart failure accumulated over time with both under- and over-replacement therapy.
Conclusions:
- Thyroid hormone treatment intensity is a significant and potentially modifiable risk factor for heart failure.
- Optimizing thyroid hormone replacement therapy may be crucial for cardiovascular health.
- Further research should focus on individualized thyroid hormone dosing strategies to minimize heart failure risk.
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