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Jonsdottir, B.* ; Clasen, J.L.* ; Vehik, K.* ; Lernmark, Å.* ; Lundgren, M.* ; Bonifacio, E.* ; Schatz, D.* ; Ziegler, A.-G. ; Hagopian, W.* ; Rewers, M.* ; McIndoe, R.* ; Toppari, J.* ; Krischer, J.* ; Akolkar, B.* ; Steck, A.* ; Veijola, R.* ; Haller, M.J.* ; Elding Larsson, H.* ; Germany clinical center (Gezginci, C. ; Heublein, A. ; Hummel, S. ; Knopff, A. ; Koletzko, S. ; Ramminger, C. ; Roth, R. ; Schmidt, J. ; Scholz, M. ; Stock, J. ; Warncke, K. ; Wendel, L. ; Winkler, C.)

Early appearance of thyroid autoimmunity in children followed from birth for type 1 diabetes risk.

J. Clin. Endocrinol. Metab. 110, 498-510 (2024)

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PURPOSE: Autoantibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) define pre-clinical autoimmune thyroid disease (AITD) which can progress to either clinical hypo- or hyperthyroidism. We determined the age at seroconversion in children genetically at risk for type 1 diabetes. METHODS: TPOAb and TgAb seropositivity were determined in 5066 healthy children with HLA DR3 or DR4 containing haplogenotypes from The Environmental Determinants of Diabetes in the Young (TEDDY) Study. Children seropositive on the cross-sectional initial screen at 8-13 years of age had longitudinally collected samples (from 3.5 months of age) screened retrospectively and prospectively for thyroid autoantibodies to identify the age at seroconversion. First-appearing autoantibody was related to sex, HLA genotype, family history of AITD, and subsequent thyroid dysfunction and disease. RESULTS: The youngest appearance of TPOAb and TgAb was 10 and 15 months of age, respectively. Girls had higher incidence rates of both autoantibodies. Family history of AITD was associated with a higher risk of TPOAb hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.17, 3.08; and TgAb HR 2.55, 95% CI 1.91, 3.41. The risk of progressing to hypo- or hyperthyroidism was not different between TgAb and TPOAb, but children with both autoantibodies appearing at the same visit had a higher risk compared to TPOAb appearing first (HR 6.34, 95% CI 2.72, 14.76). MAIN CONCLUSION: Thyroid autoantibodies may appear during the first years of life, especially in girls, and in children with a family history of AITD. Simultaneous appearance of both autoantibodies increases the risk for hypo- or hyperthyroidism.

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