Abstract
OBJECTIVE: Clinical autoimmune thyroid disease (AITD), presenting as either hypo- or hyperthyroidism, can occur at any age. Autoantibodies against thyroid peroxidase or thyroglobulin precede the onset of clinical AITD. We aimed to assess factors associated with AITD in children and determine if risk factors for AITD differ among the subset who have developed thyroid autoantibodies. DESIGN: Prospective cohort study. PATIENTS: The TEDDY Study is a cohort of 8676 children with increased genetic susceptibility for type 1 diabetes, followed to age 15 years. MEASUREMENTS: Hypothyroidism and hyperthyroidism clinical diagnoses as well as medications used for treating AITD were reported to study staff at every visit, 2 to 4 times per year. Children were screened for thyroid autoantibodies at ages 9 and 14, and if positive, previously collected samples were retrospectively analyzed to determine the age when autoantibodies first appeared. RESULTS: Of 5203 children screened for thyroid autoantibodies, 99 were diagnosed with AITD. Female sex, human leukocyte antigen (HLA) haplogenotype, and family history of hypothyroidism, hyperthyroidism, type 1 diabetes, and celiac disease were associated with risk of AITD. Among the 575 children positive for thyroid autoantibodies, HLA remained associated with AITD, while the estimates for family history were attenuated, and no association was present for sex. CONCLUSIONS: Female sex, family history of autoimmune disease, and HLA haplogenotype are risk factors for AITD in genetically high-risk children, but these trends differ for progression from thyroid autoimmunity to AITD.