Associations of the metabolic score for insulin resistance and uric acid with prevalent thyroid nodules: A cross-sectional study with systolic blood pressure mediation analysis and C-TIRADS category-specific analyses

Objective To investigate the associations of metabolic score for insulin resistance (METS-IR) and uric acid (UA) with the odds of prevalent thyroid nodules, including nonlinear associations across C-TIRADS categories; to explore SBP-related indirect associations; and to evaluate the joint association and statistical interaction of METS-IR and UA. Methods Among 12,256 individuals initially screened at the Health Management Center of the First Hospital of Shanxi Medical University between January 2018 and December 2021, 5,232 participants were included in the final complete-case analysis. Data were retrieved from the hospital health examination database on January 25, 2026. METS-IR and UA were categorized into quartiles. Multivariable logistic regression, restricted cubic spline (RCS) regression, exploratory mediation analysis, joint classification analysis, and interaction analyses were performed. Results Compared with the lowest quartile, the highest quartiles of METS-IR and UA were associated with higher odds of prevalent thyroid nodules in the fully adjusted models (METS-IR: OR =3.928, 95% CI : 3.120 to 4.946; UA: OR =3.627, 95% CI : 2.839 to 4.634; both P < 0.001). RCS analyses showed nonlinear associations of METS-IR and UA with C-TIRADS 2–3 and C-TIRADS 4 thyroid nodules (all P for overall association <0.001; all P for nonlinearity ≤0.049). Exploratory mediation analyses yielded outcome-dependent findings: in the overall analysis, the estimated proportions mediated through SBP were 6.62% for METS-IR and 1.44% for UA; no significant indirect associations were observed for C-TIRADS 2–3 nodules, whereas only the indirect association for METS-IR was significant for C-TIRADS 4 nodules. Participants with concurrently elevated METS-IR and UA had the highest adjusted odds of prevalent thyroid nodules ( OR , 4.562; 95% CI , 3.753–5.544; P < 0.001); however, interaction analyses indicated a submultiplicative joint association and no evidence of positive additive interaction. Conclusion METS-IR and UA were associated with higher odds of prevalent thyroid nodules, with nonlinear associations observed across the exposure distributions. Concurrent elevations in METS-IR and UA identified a subgroup with the highest observed odds of thyroid nodules, although interaction analyses did not support positive synergy. Exploratory mediation analyses provided limited and outcome-dependent evidence of SBP-related indirect associations. The cross-sectional design precludes conclusions regarding temporal ordering or causal mediation.