ArticleFrontiers in endocrinology2026
Non-linear association between thyroid scintigraphy-derived thyroid weight and I-131 treatment efficacy in graves' disease: a multicenter restricted cubic spline and threshold analysis.
Article in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objective: Radioactive iodine-131 (I-131) is a standard therapy for Graves' disease (GD), yet predicting therapeutic efficacy remains challenging due to complex biological variables. Conventional linear models often fail to capture the dynamic dose-response relationship between thyroid size and treatment outcomes. This study aimed to characterize the non-linear relationship between thyroid weight and I-131 efficacy and identify critical clinical thresholds influencing therapeutic success. Methods: A retrospective multicenter cohort study was conducted involving 888 records, of whom 612 GD patients received initial I-131 treatment between 2018 and 2024. Thyroid weight was estimated using thyroid scintigraphy. Restricted cubic splines (RCS) were employed to model potential non-linear associations, and piecewise threshold analysis was utilized to determine optimal inflection points regarding the correlation between thyroid weight and treatment non-remission. Results: Among 612 patients (mean age 41.2 ± 12.4 years; 73.9% female), 250 (40.8%) experienced non-remission after initial I-131 therapy. RCS analysis revealed a significant non-linear association between thyroid weight and treatment outcome in both unadjusted (P-nonlinear = 0.034) and DAG-confounder-adjusted models including study center (P-nonlinear = 0.032). In multivariable DAG-based logistic regression, thyroid weight (adjusted OR = 1.025, 95% CI: 1.017-1.034), female gender (adjusted OR = 1.67, 95% CI: 1.09-2.56), disease duration >2 years (adjusted OR = 1.97, 95% CI: 1.30-2.99), and study center (adjusted OR = 0.62, 95% CI: 0.42-0.93) were independent predictors. Piecewise analysis identified an exploratory inflection point at 46 g (adjusted LRT: P = 0.030). Mediation analysis demonstrated that RAIU at 3 h was a modest partial mediator (Sobel Z = 2.43, P = 0.015; mediated proportion: 5.8%). Conclusion: Thyroid weight demonstrates a significant non-linear association with I-131 treatment efficacy in GD, with an exploratory inflection point at approximately 46 g. The association is robust to DAG-based confounder adjustment including study center and is only modestly mediated by radioiodine uptake. These findings support individualized RAI dosing strategies incorporating thyroid weight thresholds.
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