Secular Trends in the Management of Pediatric Graves' Disease: A 25-Year Cohort

Over the past two decades, management of pediatric Graves' disease (GD) has shifted toward prolonged antithyroid drug therapy. Yet, longitudinal data describing how these changes have influenced long-term outcomes remain limited. This study examined secular trends in presentation, treatment strategies, and long-term outcomes of pediatric GD over a 25-year period at a tertiary center.

A retrospective cohort study of children diagnosed with GD between 1999 and 2024. Outcomes included temporal changes in initial therapy, methimazole (MMI) dosing, definitive therapy (radioactive iodine ablation or thyroidectomy), remission and relapse rates, and treatment-related adverse events.

A total of 128 children (79.7% female), median age 13.8 years (IQR 10.0-15.6), median follow-up 6.0 years (IQR 3.3-10.4) were included in the study. Initial management shifted exclusively to MMI, with discontinuation of propylthiouracil after 2009 (p < 0.001). Median initial MMI dose declined progressively over the study period from 30 mg/day in 1999-2004 to 10 mg/day in 2015-2020 (p < 0.001 for the trend), with a parallel reduction in weight-adjusted dosing from 0.59 to 0.32 mg/kg/day (p < 0.001 for trend). Similarly, the use of RAI decreased steadily across calendar periods, from 55.6% in 1999-2004 to 9.8% in 2020-2024 (p < 0.001 for trend). Remission and remission with relapse rates did not differ significantly across calendar periods. Lower FT4 levels at diagnosis were marginally associated with remission (B = 0.41, SE = 0.22, p = 0.06). MMI-related Aes occurred in 20.3% of patients, with severe events in 1.6%.

Over 25 years, pediatric GD management evolved toward lower dose, prolonged MMI therapy with a marked decline in definitive treatment. These secular changes were not associated with worsening remission or relapse rates, supporting the feasibility of a sustained conservative approach without evidence of inferior long-term outcomes.