Relationship between sensitivity to thyroid hormone and cardiovascular-kidney-metabolic syndrome in U.S. adults: Evidence from the 2007–2012 national health and nutrition examination survey

Objective This study investigated the relevance of thyroid hormone sensitivity (THS) to cardiovascular-kidney-metabolic (CKM) syndrome risk in euthyroid U.S. adults, given unclear prior evidence. Methods The cross-sectional study analyzed 8,009 euthyroid adults from NHANES (2007–2012) to assess associations between THS and CKM syndrome. Central THS indices (TSHI, TT4RI, TFQI) and peripheral FT3/FT4 ratio were evaluated. Participants were stratified into five CKM stages (stage 0: no CKM; stages 1–4: increasing severity). Weighted logistic regression examined associations between thyroid sensitivity and CKM stages, while restricted cubic spline (RCS) together with piecewise linear regression models explored nonlinearity and threshold effects. Results In total, 2,381/8,009 participants were classified as CKM syndrome stage 0. TFQI and FT3/FT4 showed a relevance to CKM syndrome stages 1–3 ( P  < 0.05), while no correlation was observed at stage 4 ( P  > 0.05). For each additional unit increase in TFQI and FT3/FT4, the risk of developing CKM syndrome also increased. Compared with low FT3/FT4 levels, high FT3/FT4 level indicated higher odds of developing CKM syndrome stages 1–3. Significant interaction effects (P-interaction < 0.05) emerged across sex/age/ethnicity subgroups stratified by CKM stage 2 ~ 3. Males, older adults ≥ 60y, and Black individuals with elevated FT3/FT4 demonstrated higher progression odds versus respective referent groups. Conclusion THS indices (TFQI, FT3/FT4) are potential biomarkers for CKM risk stratification in euthyroid populations. And there are differences in gender, age and race, which requires further vertical research to verify the causal relationship.