Reduced central thyroid hormone sensitivity is associated with adverse body composition and lower biological age acceleration in euthyroid adults

Central thyroid hormone sensitivity reflects the responsiveness of the hypothalamic-pituitary-thyroid feedback axis to circulating thyroid hormones. Reduced central sensitivity has been linked to age-related cardiometabolic diseases, but its association with biological age acceleration has not been well characterized. To comprehensively assess central thyroid hormone sensitivity, we developed a dual-hormone thyroid feedback quantile index (dTFQI) that integrates free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH). We investigated its associations with both body composition-related aging phenotypes and biological aging acceleration, assessed using Klemera–Doubal method biological age (KDM-BA) and Phenotypic Age (PhenoAge), in a cohort of 18,993 euthyroid adults. Multivariable linear regression, restricted cubic splines, subgroup analyses, and sensitivity analysis were performed. After full adjustment for covariates, higher dTFQI, indicating reduced central thyroid hormone sensitivity, was associated with higher visceral fat area (β = 1.35, P = 0.035) and body fat percentage (β = 0.50, P < 0.001), as well as lower skeletal muscle index (β = −0.10, P < 0.001) and bone mineral content (β = −0.03, P < 0.001). Higher dTFQI was also associated with lower KDM-BA acceleration (β = −0.42, P < 0.001) and lower PhenoAge acceleration (β = −0.14, P = 0.035). The association with PhenoAge acceleration was modest and did not reach statistical significance within individual subgroups. In this cross-sectional Chinese euthyroid population, reduced central thyroid hormone sensitivity was associated with an adverse body composition profile but lower biological age acceleration. These divergent associations suggest that thyroid feedback-axis variation may relate differently to tissue-level phenotypes and systemic biomarker-based aging metrics. The dTFQI weights require independent external validation, and longitudinal studies are needed to verify the observed associations.