Changes in serum TSH across the adult lifespan: 22-year follow-up of the HUNT Study

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Abstract Objective Some evidence suggests that higher serum TSH may be a part of normal aging, but current studies are limited to 13-year follow-up. We examined TSH changes during 22 years of follow-up across the adult lifespan. Design Longitudinal analyses of the population-based HUNT Study in Norway, with TSH measurements from 1995-97, 2006-08 and 2017-19. Methods In the overall population and in individuals without thyroid medication or disease, we estimated i) geometric mean serum TSH by age, integrating cross-sectional and longitudinal measurements using linear mixed models, ii) percentiles of the TSH distribution by age, and iii) within-individual TSH change during follow-up, expressed by geometric mean ratios (GMR) reflecting the fold change in geometric mean TSH. Results We included 136,925 TSH measurements among 84,342 participants, of whom 40,615 had ≥2 measurements and 13,613 had ∼22-year follow-up. Mean TSH was higher at older age in men, but weaker and less consistent in women. The TSH distribution widened at older age in men and women. Among individuals without thyroid medication or disease, mean TSH increased modestly by 0.13 mIU/L (GMR 1.09; 95%CI 1.08,1.11) during 22-year follow-up in men, but not in women (GMR 0.99; 95%CI 0.98,1.00). This increase was stronger at 0.5 mIU/L in men aged ≥70 years at baseline (GMR 1.32; 95%CI 1.18,1.48). Conclusions Mean serum TSH increased with age in older men, but showed only modest or no age-related change in younger men and in women. The wider TSH distribution at older age supports the need for age-specific TSH reference ranges. Significance statement Previous evidence of higher TSH concentrations at older age comes from cross-sectional studies and longitudinal studies with up to 13-year follow-up. We utilized a large population-based study to extend the evidence on within-individual TSH changes to ∼22-year follow-up across the adult lifespan. Mean TSH increased with age in men, modestly at 0.13 mIU/L overall, but stronger at 0.5 mIU/L in men followed from their 70s to their 90s. In women, mean serum TSH appeared stable during follow-up, but more frequent thyroid hormone supplementation may have skewed the TSH distribution away from higher, but still physiological levels. The TSH distribution widened at older age in both men and women, supporting the need for age-specific TSH reference ranges.

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