Sex Differences in the Association Between Thyroid Hormone Sensitivity and Cardiovascular-Kidney-Metabolic Syndrome

Abstract Background The relationship between thyroid hormone sensitivity and cardiovascular-kidney-metabolic (CKM) syndrome remains unclear. This study aims to investigate the association between thyroid hormone sensitivity and the early-stage of CKM syndrome, with a specific focus on the moderating effects of sex and age. Methods A total of 8391 euthyroid participants were enrolled in this cross-sectional study. Data on metabolic parameters and thyroid hormone levels were collected. Thyroid hormone sensitivity indices-thyroid feedback quantile index (TFQI), thyroid-stimulating hormone index (TSHI), thyrotrophic thyroxine resistance index (TT4RI), and free T3 to free T4 ratio were calculated. Logistic regression models and restricted cubic spline regression (RCS) were used to analyze the association between thyroid hormone sensitivity and stage 2 of CKM syndrome stratified by sex and age. Results In men, the higher TFQI, TSHI, and TT4RI values were significantly associated with increased risks of stage 2 of CKM syndrome. In women, these associations were weaker but still present, particularly for TSHI. RCS analysis also showed that the risk of CKM syndrome tended to increase with decreasing thyroid hormone sensitivity in men. However, these associations in women were not as significant as in men. Age-stratified analysis revealed that older men (>50 years) showed a stronger correlation between thyroid hormone sensitivity and CKM syndrome compared to women. Conclusion This study demonstrated that impaired thyroid hormone sensitivity was significantly associated with the early-stage of CKM syndrome, particularly in older men. These findings provide the evidence of the importance of thyroid hormone sensitivity in CKM syndrome, especially in men over the age of 50.