Endocrinol Metab.  2025 Feb;40(1):125-134. 10.3803/EnM.2024.2093.

Unveiling Risk Factors for Treatment Failure in Patients with Graves’ Disease: A Nationwide Cohort Study in Korea

• Kim JA
• Kim KJ
• Choi J
• Kim KJ
• Song E
• Yu JH
• Kim NH
• Yoo HJ
• Seo JA
• Kim NH
• Choi KM
• Baik SH
• Kim SG

• KMID: 2565260
• DOI: http://doi.org/10.3803/EnM.2024.2093

Abstract

Background
Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves’ disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice.
Methods
We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years.
Results
Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi.
Conclusion
ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.

Keyword

Graves disease; Treatment failure; Risk factors7

Figure

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  Fig. 1. Schematic study design. RAI, radioactive iodine; ATD, antithyroid drug; PY, person-year.

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  Fig. 2. Multivariate analysis on risk factors associated with treatment failure according to initial treatment in Graves’ disease patients. These results were analyzed in patients with all available data included in models (290,231 in the antithyroid drug [ATD] group, 1,761 in the radioactive iodine [RAI] group, and 3,700 in the thyroidectomy group). Bold values indicated statistically significant factors. CI, confidence interval.

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  Fig. 3. Association between initial dose of radioactive iodine (RAI) treatment and treatment failure using a restricted cubic spline regression model. Graphs show hazard ratios for treatment failure according to the initial dose of RAI treatment adjusted for age, sex, socioeconomic status, hypertension, diabetes mellitus, dyslipidemia, cardiovascular disease, atrial fibrillation, body mass index, smoking status, and alcohol consumption. Data were fitted by a restricted cubic spline Cox proportional hazards regression model, and the model was conducted with 3 knots at the tertiles of dose (reference is median). Solid lines indicate hazard ratios, and shadow shape indicate 95% confidence intervals (CIs). The rug above x-axis is the density of the population along the initial dose of RAI treatment.

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