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Non-linear association between thyroid scintigraphy-derived thyroid weight and I-131 treatment efficacy in graves'
Lu Lu1, LeLe Zhang2, Dongyun Meng1
1Department of Nuclear Medicine, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang, China.
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.