Thyroid hormone sensitivity and insulin resistance in euthyroid adults in Beijing: A cross-sectional study

This study aimed to investigate the relationship between indices of thyroid hormone sensitivity and insulin resistance (IR) in euthyroid adults. In this cross-sectional study of 1393 euthyroid individuals from Beijing, participants were stratified into IR (Homeostatic Model Assessment for Insulin Resistance ≥ 2.5) and non-IR groups. We calculated indices of central thyroid hormone sensitivity: Thyroid Feedback Quantile-based Index, Thyrotroph T4 Resistance Index, and Thyroid-Stimulating Hormone Index and the peripheral free triiodothyronine/free thyroxine ratio. Multivariable logistic regression analyses were performed to determine their associations with IR, adjusting for key metabolic confounders including age, sex, body mass index, blood pressure, glycated hemoglobin, and lipids. A significant inverse association was observed between central thyroid hormone resistance and IR. After full adjustment, participants in the highest quartile of Thyroid Feedback Quantile-based Index, Thyrotroph T4 Resistance Index, and Thyroid-Stimulating Hormone Index had approximately 50% lower odds of IR. In contrast, a higher free triiodothyronine/free thyroxine ratio, indicating enhanced peripheral conversion, was positively associated with increased odds of IR. These relationships followed a threshold effect, being most pronounced in the extreme quartiles. Among euthyroid adults, reduced central sensitivity to thyroid hormones is independently associated with lower odds of IR, while increased peripheral conversion is linked to higher odds. This dissociation underscores the critical role of the hypothalamic-pituitary-thyroid axis set-point and peripheral hormone activation in metabolic health, suggesting these indices could be valuable for stratifying metabolic risk.