Long-Term Outcomes of Pediatric Graves Disease Patients Treated with Anti-Thyroid Drugs: Experience from a Taiwan Medical Center

Abstract

2 Graves disease (GD) is the most common cause of thyrotoxicosis in children and 3 adolescents, accounting for 15% of all thyroid diseases during childhood.4 Anti-thyroid drugs (ATD) are recommended as the first-line treatment in children and 5 adolescents. However, the remission rate is lower in children than in adults, and the 6 optimal treatment duration and favorite factors associated with remission remain 7 unknown. We aimed to investigate long-term outcomes of pediatric GD patients 8 receiving ATD. We retrospectively reviewed medical charts of 300 pediatric GD 9 subjects, who were initially treated with ATD and followed up for more than one year, 10 from 1985 to 2017 at MacKay Children's Hospital. The 300 patients comprised 257 11 (85.7%) females and 43 (14.3%) males, median age at diagnosis was 11.6 (range 12 2.7-17.8) years, and median follow-up period was 4.7 (range 1.1-23.9) years. Overall, 13 122 patients achieved the criteria for discontinuing ATD treatment, seventy-nine 14 (39.9%) patients achieved remission, with a median follow-up period of 5.3 (range 15 1.5-20.1) years. Patients in the remission group were more likely to be aged < 5 years 16 (remission vs. relapse vs. ongoing ATD; 11.4 vs. 0 vs. 2.6%, P=0.02), less likely to 17 have a family history of thyroid disease (24.1 vs. 42.1 vs. 52.6 %, P=0.001), and had 4 18 lower TRAb levels (42.8 vs. 53.6 vs. 65.1 %, P=0.02). Conclusion: Long-term ATD 19 remains an effective treatment option for GD in children and adolescents. Pediatric 20 GD patients aged < 5 years, having no family history of thyroid disease and having 21 lower TRAb levels were more likely to achieve remission. 5 22 Introduction 23 Graves disease (GD) is a common disorder in adults, with a prevalence of 24 approximately 0.5-1%. Pediatric patients account for < 5% of the total number of GD 25 patients [1]. However, GD remains the most frequent cause of thyrotoxicosis in 26 children and adolescents, accounting for 15% of thyroid disease during childhood [2].27 The incidence increases gradually from young children and peaks in adolescents [3].28 The optimal treatment option for GD in children and adolescents remains 29 controversial. Current treatment approaches for GD include anti-thyroid drugs (ATD), 30 radioactive iodine and surgery. ATD is usually recommended as the first-line 31 treatment for GD in children and adolescents. However, the remission rate is lower in 32 children than in adults [2, 4, 5]; the optimal treatment duration and the favorite factors 33 associated with remission have not yet been established in children and adolescents 34 [6-8]. 35The issue of how long ATD should be used in pediatric GD is important and 36 warrants further study [5, 9]. In adult GD patients, if remission does not occur after 37 12-18 months of ATD therapy, the chance of remission with prolonged therapy is 38 very low [4, 10]. In the pediatric population, longer treatment duration is associated 6 39 with a higher remission rate. Lipple reported that the median time to remission with 40 ATD was 4...