Association between urinary cadmium exposure and metabolic syndrome and the mediating role of thyroid dysfunction:...

This study aims to examine the association between urinary cadmium (U-Cd) exposure and metabolic syndrome (MetS) in U.S. adults and evaluate whether thyroid function (TSH/T4) mediates this relationship. We analyzed National Health and Nutrition Examination Survey 2007-2012 data (n = 4869; age ≥18) to assess the relationship between U-Cd and MetS. U-Cd was measured by ICP-MS, adjusted for creatinine, and log-transformed. We employed weighted logistic regression, restricted cubic splines for nonlinearity, and multivariable models for U-Cd-TSH/T4 relations, with causal mediation analysis for indirect effects, considering demographics and lifestyle factors. Higher U-Cd was associated with greater MetS risk in a dose-response fashion: versus Q1, OR (95% CI) for Q2, Q3, Q4 were 1.84 (1.49-2.26), 2.36 (1.92-2.89), and 2.49 (2.04-3.06); P-trend <.0001. Restricted cubic splines showed a significant overall and nonlinear association (P_overall = .006; P_nonlinear = .036), with relatively flat risk at low exposure and steeper increases beyond a turning point. U-Cd correlated positively with T4 (fully adjusted β ≈ 0.26 ng/dL per unit increase; P <.001) and inversely with TSH. Mediation indicated a small but significant indirect effect via T4 (indirect effect ≈ 0.003; 95% CI, 0.001-0.005; proportion mediated ≈ 8.3%), while TSH and TSH/T4 showed negligible or negative indirect effects; the direct path from U-Cd to MetS predominated. Findings were generally stronger in women, younger adults (<40 years), and those with higher physical activity, and were robust across chronic-disease strata. In a nationally representative sample, U-Cd exposure is positively - and nonlinearly - associated with MetS; this relationship is driven mainly by a direct effect with a modest mediating role of T4, underscoring the metabolic implications of environmental cadmium and the relevance of thyroid pathways.