Thyroid Hormone Sensitivity as a Possible Determinant of Metabolic Phenotypes in Young Adults, Not in Older Individuals

Abstract Context Although thyroid hormones regulate metabolism, the relevance of thyroid hormone sensitivity indices in distinguishing metabolic phenotypes across age groups remains unclear. Objective We evaluated the association between thyroid sensitivity indices and metabolic phenotypes, including metabolically healthy and unhealthy individuals with obesity (MHO, MUO) and normal weight (MHNW, MUNW), focusing on age-specific differences. Methods Data from participants aged 18 years and older in the National Health and Nutrition Examination Survey (NHANES) 2007 to 2012 were analyzed. Thyroid sensitivity indices, including the Thyroid Feedback Quantile-based Index (TFQI), Thyrotropin Index (TSHI), and Thyrotroph Thyroxine Resistance Index (TT4RI), were calculated. Multivariable regression and piecewise regression analyses were performed to examine associations between metabolic phenotypes and thyroid sensitivity indices, stratified by age groups (<65 and ≥65 years). Results In the total population, the MUO group exhibited significantly higher values for TSHI (P = .035) compared to the MHNW group, while there were borderline and no significant differences for TT4RI (P = .093) and TFQI (P = .134), respectively. Among younger adults (<65 years), MUO showed the highest values for TSHI (β = 0.122; P = .006), TT4RI (β = 2.006; P = .010), and TFQI (β = 0.058; P = .018), with significant linear and quadratic trends (P < .05). No significant associations were observed in older adults (aged ≥65 years). Conclusion Our findings highlight the importance of thyroid sensitivity indices in understanding metabolic health, particularly among younger adults. Incorporating these indices into clinical assessments may enhance metabolic phenotype stratification and inform targeted management of obesity.