Low-normal TSH and risk of atrial fibrillation and vertebral or hip fractures in older adults: a population-based cohort study

Background Subclinical hyperthyroidism is a known risk factor for atrial fibrillation and osteoporotic fractures, but whether this risk extends into the low-normal euthyroid range remains debated. We evaluated the long-term association of low-normal TSH levels with incident atrial fibrillation and vertebral or hip fractures in older adults. Methods We conducted a retrospective cohort study using data from Clalit Healthcare Services (CHS), Israel, from January 1, 2002, through June 30, 2025. For each individual, we selected the first two consecutive TSH tests performed after age 50 that were separated by 6 to 24 months and fell within the same predefined category (<0.4, 0.4 to <1.0, or 1.0–2.5 mIU/L). The index date was the date of the second TSH test. Individuals were excluded if they had documented abnormal free T4 or T3 levels; a history of anti-thyroid medication or levothyroxine treatment, radioactive iodine, or thyroid surgery; or a diagnosis of atrial fibrillation, osteoporosis, or vertebral or hip fractures prior to the index date. Follow-up continued until June 30, 2025, disenrollment from CHS, or death. Multivariable Cox proportional hazards models, adjusted for age, sex, body mass index, population group, socioeconomic status, and hypertension, were used to estimate hazard ratios (HRs) for incident outcomes. Competing-risk cumulative incidence was additionally estimated using the Aalen–Johansen method with all-cause death as the competing event. Results The cohort was stratified into three groups: low TSH (<0.4 mIU/L; n=8,494), low-normal TSH (0.4 to <1.0 mIU/L; n=107,791), and reference (1.0–2.5 mIU/L; n=558,003). The mean age at the index date was 63.0 ± 10.9 years, and 49% were female. The median follow-up was 12.9 (IQR 6.4–17.9) years. Compared with the reference group (1.0–2.5 mIU/L), the low-normal TSH group (0.4 to <1.0 mIU/L) had an increased risk of incident atrial fibrillation (adjusted HR 1.05, 95% CI 1.03–1.07) and vertebral or hip fracture (adjusted HR 1.12, 95% CI 1.09–1.15). In the low TSH group (<0.4 mIU/L), the risk was elevated for atrial fibrillation (adjusted HR 1.19; 95% CI 1.11–1.27) and vertebral or hip fracture (adjusted HR 1.19; 95% CI 1.10–1.28). Conclusion In adults aged ≥50 years, repeated concordant low-normal TSH levels were associated with modestly higher risks of atrial fibrillation and hip or vertebral fracture.