Predictors of Treatment Outcomes in Pediatric Graves' Disease

Graves' disease (GD), the most common cause of hyperthyroidism in children, is primarily treated with antithyroid drugs (ATDs). The aim of this study was to evaluate factors that could predict remission, relapse, and the need for persistent high doses of methimazole (MMI) in pediatric GD.

This was a retrospective study of medical records that included GD diagnosed before 19 years of age from January 2004 to December 2023. Remission was defined as maintaining the euthyroid state for more than 6 months after stopping ATDs. The high-dose group was defined as those receiving MMI doses of more than 5 mg/day at last follow-up, regardless of euthyroid status.

Of the 113 patients (95 girls and 18 boys), 47 (41.6%) achieved remission at a mean of 37.17 ± 29.01 months after treatment. Compared to the non-remission group, the remission group showed significant differences in T3, fT4 and thyroid-stimulating hormone-binding inhibitor immunoglobulin (TBII) at diagnosis (330.92 ± 177.72 vs. 413.75 ± 179.09 ng/dL, P = 0.017; 3.31 ± 1.39 vs. 4.12 ± 1.34 ng/dL, P = 0.002; 15.68 ± 14.37 vs. 23.37 ± 16.61 IU/L, P = 0.012, respectively); time to TBII normalization (25.26 ± 29.88 vs. 45.33 ± 37.17 months, P = 0.003); and ratio of 6-month to initial TBII (54.98 ± 42.04 vs. 87.92 ± 55.94%, P < 0.001). Eleven patients (11/47, 23.4%) experienced relapse at a mean of 17.91 ± 16.81 months after remission. Compared to the non-relapse group, the relapse group was predominantly male (5.6 vs. 45.5%, P < 0.001) and exhibited a higher ratio of 12-month to initial TBII (36.64 ± 33.78 vs. 87.18 ± 78.14%, P = 0.025). In the non-remission group, 38/66 patients (57.6%) received persistent high doses of MMI, with a mean dose of 0.39 ± 0.17 mg/kg/day at the last follow-up. Compared to the low-dose group, the high-dose group showed significant differences in time to T3, fT4 and TBII normalization (1.21 ± 0.69 vs. 2.39 ± 1.76 months, P < 0.001; 1.50 ± 0.84 vs. 2.61 ± 2.47 months, P = 0.013; 7.00 ± 2.61vs. 9.55 ± 5.14 months, P = 0.011, respectively) and ratio of 6-month to initial TBII (61.57 ± 36.96 vs. 107.34 ± 59.90%, P < 0.001). Based on the receiver-operating characteristic curve for the ratio of 6-month to initial TBII, the cut-off value for remission was 62.5%, and the cut-off value for persistent high doses of MMI was 82.5%.

Thyroid hormone and TBII levels at diagnosis, time to thyroid hormone and TBII normalization, and the TBII ratio after ATD treatment can be used to predict remission, relapse, and the persistent need for high-dose MMI in pediatric GD patients.