Association Between Thyroid Function and Development of Different Obesity Phenotypes in Euthyroid Adults: A Nine-Year Follow-Up

Background: Considering inconsistent and conflicting data on associations of thyroid function, within the reference range, with anthropometric measures and metabolic syndrome, this study aimed to investigate the relationship between thyroid function and different obesity phenotypes over nine years of follow-up. Methods: This study was conducted on 1938 individuals from an ongoing population-based cohort study, the Tehran Thyroid Study. Participants were categorized into four obesity phenotypes based on body mass index and metabolic status. To investigate the associations of thyrotropin and free thyroxine (fT4) with incidence of different obesity phenotypes across the study period, a multivariate approach based on a generalized estimating equation method was used. Results: At baseline, individuals with the metabolically healthy normal weight (MHNW) phenotype had higher serum fT4 levels (1.20.16ng/dL vs. 1.14 +/- 0.14ng/dL, 1.16 +/- 0.14ng/dL, and 1.17 +/- 0.15ng/dL in metabolically healthy obese [MHO], metabolically unhealthy normal weight, and metabolically unhealthy obese individuals, respectively). The results of the generalized estimating equation analysis after multivariate adjustment for age, sex, smoking, physical activity, education level, thyroid peroxidase antibody status, and homeostasis model assessment-insulin resistance showed that each 1ng/dL increment in fT4 levels within the reference range was accompanied with a 1.65-fold [confidence interval (CI) 1.09-2.5] increase of developing the MHNW phenotype during 9.2 years of follow-up. Moreover, each 1.0ng/dL increment in fT4 within the reference range was associated with a 50% decreased risk of developing the MHO phenotype (odds ratio=0.50 [CI 0.32-0.76]). Meanwhile, a significant positive association was found between serum thyrotropin levels and development of the metabolically unhealthy normal weight phenotype (odds ratio=1.22 [CI 1.01-1.48]). Conclusions: Serum fT4 concentrations within the reference range are associated with the development of some obesity phenotypes, including the MHNW and MHO phenotypes, after consideration of potential confounders.