Background: The aim was to determine prevalence and age at seroconversion of thyroid autoimmunity and relation to islet autoantibodies, gender and HLA-DQ genotypes in children followed from birth because of increased genetic risk for type 1 diabetes.
Methods: In 1874 10-year-old children followed in the Diabetes Prediction in Skåne (DiPiS) study, blood samples were analysed for autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb), glutamic acid decarboxylase 65 (GADA), three variants of Zink transporter 8 (ZnT8R/W/QA), insulinoma-associated protein-2 (IA-2A), insulin (IAA) and HLA-DQ genotypes. Prospectively collected samples from 2 years of age were analysed for TPOAb and TGAb and confirming samples at 11-16 years of age for TPOAb, TGAb, TSH and FT4, in children positive for thyroid autoantibodies at age 10.
Results: The prevalence of thyroid autoimmunity was 6.9%, overrepresented in girls (P<0.001), also having higher TPOAb titers at 10 years (P=0.049). TPOAb was related to GADA (P=0.002), ZnT8R/W/QA (P=0.001), IA-2A (P=0.001) and multiple islet autoantibodies (P<0.001), while TGAb was related to ZnT8R/W/QA (P=0.021) and multiple islet autoantibodies (P=0.039). In boys, TPOAb was related to GADA (P=0.002), IA-2A (P=0.001), ZnT8R/W/QA (P=0.001), IAA (P=0.009) and multiple islet autoantibodies (P=0.001) and TGAb to GADA (P=0.013), IA-2A (P=0.005), ZnT8R/W/QA (P=0.003) and multiple islet autoantibodies (P=0.001). In girls, TPOAb was related to multiple islet autoantibodies (P=0.022), while no other associations were found. Titers of IA-2A were related to both TPOAb (P=0.021, rs 0.36) and to TGAb (P=0.011, rs 0.40). In boys, but not in girls, titers of GADA and TGAb correlated (P=0.009, rs 0.38) as did titers of IA-2A and TPOAb (P=0.013, rs 0.51). Thyroid autoimmunity appeared already at 2 years of age, both frequency and titers increased with age. In the confirming sample, 94% were still thyroid autoantibody positive. Abnormal thyroid function or thyroxine treatment was found at follow-up in 22.3% of the children who were thyroid autoantibody positive at 10 years of age.
Conclusion: Thyroid autoimmunity and high TPOAb titers were more common in girls. However, the relation between thyroid and islet autoantibodies and correlations between titers were stronger in boys. These data suggest that while girls may develop autoimmune thyroid disease independent of islet autoantibodies, the risk for boys to develop thyroid disease may be dependent on concomitant islet autoantibodies and an increased risk for type 1 diabetes
27 - 29 Sep 2018
European Society for Paediatric Endocrinology