Association between over- and under-replacement with thyroid hormone and incident heart failure
Authors' conclusion
Our findings suggest that thyroid hormone treatment intensity may be a modifiable risk factor for heart failure.
Study context
- Population
- Adults aged ≥18 years who initiated thyroid hormone 2004–2017 at the Veterans Health Administration; Thyroid stimulating hormone (TSH) cohort 638,323 (≥2 outpatient TSH), free thyroxine (FT4) cohort 338,249 (≥2 outpatient FT4); 87.9% men, median age 66 years
- Participants
- 641,504 adults
- Exposure
- Thyroid hormone under- or over-replacement vs euthyroidism
- Outcome
- Incident HF
Methodological detailstime-varying exposure, two separately studied cohorts (TSH and FT4)
- Time-varying exposure
- Two separately studied cohorts (TSH and FT4)
Main finding
As reported in the abstract
Each group vs euthyroidismAdjusted odds ratio (95% CI)
TSH > 20 mIU/L
1.93(1.84–2.02)
FT4 < 0.7 ng/dL
1.08(1.04–1.12)
TSH < 0.1 mIU/L
1.06(1.01–1.12)
FT4 > 1.9 ng/dL
1.23(1.14–1.32)
- Incident HF overall
- 81 286/641 504 (12.7%)
Observational data: associations, not effects.
Further findings
- TSH > 5.5 mIU/L: increase in incident HF over 5 years
- 5.8-fold
- Risk cumulative over time with both over- and under-replacement; strongest with under-replacement
Original publication
Association between over- and under-replacement with thyroid hormone and incident heart failure. J Clin Endocrinol Metab. Published 17 December 2025. doi:10.
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