High TRAb Titer at Diagnosis Predicts Persistent Positivity and Relapse in Graves’ Disease after Prolonged Antithyroid Therapy

Q: How were patients with different TRAb titers defined at diagnosis?

Initial TRAb levels were stratified as low-titer ( 10.5 IU/L), using the upper normal limit (UNL) reference.

Sep 29, 2026

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Background: The relationship between high thyrotropin receptor antibody (TRAb) titers at diagnosis and long-term outcomes after prolonged antithyroid drug (ATD) therapy in Graves’ disease (GD) is unclear. Methods: A retrospective cohort (2018–2021) followed 1,148 eligible patients meeting criteria including TRAb negativity before withdrawal and at least 12 months follow-up. Outcomes assessed TRAb dynamics, treatment duration, and relapse. Results: Higher TRAb titers required longer treatment, showed slower TSH normalization, and had lower TRAb negativity rates. High-titer patients had increased persistent TRAb positivity and relapse risks, with predictive thresholds provided. Conclusion: High TRAb titers strongly forecast persistence and relapse after ATD withdrawal, guiding prognosis and management.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

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Introduction

Background and clinical context

Methods

Retrospective cohort design and inclusion criteria

TRAb titer stratification and outcome measures

Results

Treatment duration and thyroid function normalization

TRAb negativity dynamics and trend patterns

Remission rates, persistent positivity, relapse, and predictive thresholds

Conclusion

Original Article Endocrinol Metab 2025;40:950-960 [https://doi.org/10.3803/EnM.2025.2405](https://doi.org/10.3803/EnM.2025.2405)[ ](https://doi.org/10.3803/EnM.2025.2405)[pISSN 2093-596X](pISSN 2093-596X) · eISSN 2093-5978 High TRAb Titer at Diagnosis Predicts Persistent Positivity and Relapse in Graves’Disease after Prolonged Antithyroid Therapy Zimiao Chen1, *, Jinglu Xu 1, *, Wenrui Kang2, Yang Zhang2, Rujun Chen3, Xiaohua Gong1,4 1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University; 2The First School of Medicine,Wenzhou Medical University; 3Department of Burns, 906 Hospital of the Joint Logistics Team, PLA; 4National Key Clinical Specialty (Wound Healing), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China Background: The association between high thyrotropin receptor antibody (TRAb) titers at diagnosis and long-term outcomes following prolonged antithyroid drug (ATD) therapy in Graves’ disease (GD) remains unclear. This study examined TRAb dynamicsand outcomes in high-titer patients receiving prolonged ATD. Methods: In this retrospective cohort (2018–2021), 1,148 of 3,052 newly diagnosed GD patients met inclusion criteria (≥18-month ATD course, TRAb negativity before withdrawal, and ≥12-month follow-up). Initial TRAb levels were defined as low-titer (<5.25 IU/L, 3×upper normal limit [UNL]), intermediate-titer (5.25–10.5 IU/L), and high-titer (> 10.5 IU/L, 6×UNL) . Outcomes included TRAb dynamics, treatment duration, and relapse. Results: High-titer patients required longer therapy (50 months vs. 30 months vs. 22 months, P<0.001) and slower thyroid-stimulating hormone normalization (6 months vs. 4 months vs. 2 months, both P<0.001) . TRAb negativity at 24/48 months occurred in 91.85%/99.26%(low-titer), 52.38%/75.24%(intermediate-titer), and 12.70%/52.68%(high-titer) (P<0.001) . High-titer patients showed fluctuant (46.20%) or smoldering (28.89%) trends. Remission rates declined with higher TRAb titer (60.45% vs. 42.70% vs. 30.47%, P<0.001). High-titer patients showed increased risk of persistent TRAb positivity (2.17-fold; 95% confidence interval [CI], 1.55 to 3.05) and relapse (1.66-fold; 95% CI, 1.45 to 3.22) . Thresholds of 10.90 IU/L and 16.01 IU/L predicted positivity and relapse, respectively. Definitive therapy post-relapse was more common in high-titer patients (38.29% vs. 16.98% in low-titer, P<0.001) . Conclusion: High TRAb titers strongly predict persistent TRAb positivity and relapse after ATD withdrawal. Cut-off at 10.90 and 16.01 IU/L may guide prognosis and treatment. | Keywords: Graves disease; High TRAb titers at diagnosis; Prolonged course of antithyroid drugs; Long-term follow-up; Relapse | | | --- | --- | | Received: 7 April 2025, Revised: 25 May 2025, Accepted: 7 July 2025
Corresponding authors: Rujun Chen
Department of Burns, 906 Hospital of the Joint Logistics Team, PLA, Fanglekang Street, Wenzhou 325000, China
Tel: +86-13868844888, Fax: +86-057788288168, E-mail: [519973491@qq.com](519973491@qq.com)
Xiaohua Gong
Department of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Shangcaicun Street, Wenzhou 325000, China Tel: +86-13758872020, Fax: +86-057755579381, E-mail: [gxh1204@163.com](gxh1204@163.com)
*These authors contributed equally to this work. | Copyright © 2025 Korean Endocrine Society
This is an Open Access article distributed under the terms of
the Creative Commons Attribution Non-Commercial License ([https://creativecommons.org/licenses/by-nc/4.0/](https://creativecommons.org/licenses/by-nc/4.0/)) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
| 950 [www.e-enm.org](www.e-enm.org) High TRAb Titer at Diagnosis Predicts Outcomes INTRODUCTION Graves’ disease (GD) is a common organ-specific autoimmune disorder with an annual incidence of

FAQs

How were patients with different TRAb titers defined at diagnosis?

Initial TRAb levels were stratified as low-titer (<5.25 IU/L), intermediate-titer (5.25–10.5 IU/L), and high-titer (>10.5 IU/L), using the upper normal limit (UNL) reference.

What outcomes differed most between high-titer and lower-titer patients after prolonged ATD therapy?

High-titer patients required longer therapy, had slower TSH normalization, showed lower TRAb negativity rates over time, and had decreased remission rates compared with low- and intermediate-titer groups.

Which TRAb thresholds predicted persistent positivity and relapse?

The study reported cut-offs of 10.90 IU/L for predicting persistent TRAb positivity and 16.01 IU/L for predicting relapse after ATD withdrawal.

Sep 29, 2026

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