When should antithyroid drug therapy to reduce the relapse rate of hyperthyroidism in Graves' disease be discontinued?

Objective: The use of antithyroid drug (ATD) therapy in patients with Graves' disease (GD) hyperthyroidism has been increasing, but ATD therapy is associated with a higher relapse rate. We aimed to evaluate clinical factors for predicting relapse of GD after ATD therapy.

Methods: Patients (n = 149) with newly diagnosed GD who achieved remission of hyperthyroidism after ATD therapy (≥6 months) were followed up for >18 months after ATD withdrawal. We evaluated the predictive factors of relapse during a median of 6.9 years of follow-up.

Results: Disease relapse occurred in 52 patients (34.9%). By multivariate analyses, a duration of the minimum maintenance dose therapy (MMDT) of <6 months was a significant factor in disease relapse (hazard ratio [HR], 2.58; 95% confidence interval [CI], 1.47-4.52; p < 0.001), and a T3/free T4 (fT4) ratio > 120 at ATD withdrawal was significantly more frequent in patients with relapse (HR 2.43; 95% CI, 1.36-4.34; p = 0.002). In the prediction-of-relapse model, the likelihood of relapse was greater in the high-risk group, which had a short MMDT duration and a T3/fT4 ratio ≥120 (HR, 5.81; 95% CI, 2.52-13.39; p < 0.001) and the intermediate-risk group, which had a short MMDT duration or a T3/fT4 ratio < 120 (HR, 2.77; 95% CI, 1.26-6.13; p < 0.001), than in the low-risk group, which had a long MMDT duration and a T3/fT4 ratio < 120.

Conclusion: An MMDT longer than 6 months and a high T3/fT4 ratio at ATD withdrawal were independent predictors of relapse in patients who achieved initial remission after ATD for GD. These factors could be used to determine the optimal time to withdraw ATD during the treatment of GD hyperthyroidism.