Higher Sensitivity to Thyroid Hormones May Be Linked to Maintaining the Healthy Metabolic Condition in People with Obesity: New Insight from NHANES

INTRODUCTION: Obesity contributes to the pathogenesis of diverse metabolic diseases, yet the mechanism underlying metabolically healthy obesity (MHO) remains elusive. Thyroid hormones and sensitivity to them have a major impact on metabolism. Our study aimed to investigate the association between MHO and thyroid hormone sensitivity. METHODS: Thyroid hormone indices, including the thyroid-stimulating hormone (TSH) index (TSHI), the Thyrotroph Thyroxine Sensitivity Index (TTSI), the Thyroid Feedback Quantile-Based Index (TFQI), and the Parametric Thyroid Feedback Quantile-Based Index (PTFQI), were calculated based on a non-institutionalized US sample in the National Health and Nutrition Examination Survey (NHANES, 2007–2012). Participants were divided into four groups (metabolically healthy non-obesity [MHNO], metabolically unhealthy non-obesity [MUNO], MHO, and metabolically unhealthy obesity [MUO]) according to their body mass index and metabolic profiles. Linear regression, logistic regression, and restricted cubic splines were employed to analyze the association between thyroid hormone indices and metabolic phenotypes. RESULTS: A total of 4,857 participants (49.6% men; mean age, 42.6 years) were included, with 1,539 having obesity and 235 identified as MHO. Participants in the MHO group exhibited lower levels of TSH, TSHI, TTSI, TFQI, and PTFQI compared with the MHNO group (all p < 0.05), while the differences among MHNO, MUNO, and MUO groups were not statistically significant (all p > 0.05). Among participants with obesity, TSH, TSHI, TTSI, TFQI, and PTFQI were positively associated with metabolic abnormality (all p < 0.05). CONCLUSION: Participants with MHO exhibited higher thyroid hormone sensitivity among various obesity phenotypes, even when compared with those with MHNO. A positive association was observed between metabolic abnormality and thyroid hormone sensitivity, while the trend of TSH was observed to be consistent with sensitivity to thyroid hormone indices in discriminating metabolic abnormality. Hence, TSH has the potential to serve as a convenient index for detecting sensitivity to thyroid hormones and further metabolic conditions.