Genetic polymorphisms and early responses predict refractory hyperthyroidism during antithyroid drug therapy.

Authors

Xinpan Wang, Mengyi Gong, Jiayan Wang, Qiuyi Wang, Kuanfeng Xu, Qi Fu, Yun Cai, Zhixiao Wang, Xiaoyun Liu, Xinyu Xu, Tao Yang, Xuqin Zheng

Published in

iScience. Volume 29. Issue 11. Pages 117780. Nov 20, 2026. Epub Oct 08, 2026.

Abstract

Antithyroid drugs (ATDs) are the first-line treatment for Graves' disease (GD), but variable outcomes require early risk stratification. We analyzed 578 adults, including 240 in a randomized trial of dose titration versus modified partial block-and-replace therapy and the remainder in a temporal observational cohort. Baseline characteristics, 3-month treatment indicators, and 13 GD-susceptibility single nucleotide polymorphisms (SNPs) were evaluated. An ATD-levothyroxine dose-correction method quantified thyroid function and autoantibody changes, informing clinical and SNP risk score-integrated models. The integrated model achieved areas under the curve (AUCs) of 0.841 in development and 0.805 in temporal validation, outperforming the clinical model (p < 0.001) with good calibration and net benefit. Intermediate-risk patients derived the greatest incremental benefit. Baseline free thyroxine (FT4) was the strongest predictor, and the SNP risk score ranked fourth. No inter-regimen efficacy or safety differences were observed. Restricted cubic spline analysis suggested that ATD therapy beyond 3 years may reduce recurrence risk, whereas modified partial block-and-replace showed no advantage over dose titration.

PMID:
42894817
Bibliographic data and abstract were imported from PubMed on 19 Oct 2026.

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