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. 2025 Jan 21;110(2):498-510.
doi: 10.1210/clinem/dgae478.

Early Appearance of Thyroid Autoimmunity in Children Followed From Birth for Type 1 Diabetes Risk

Berglind Jonsdottir  1   2 , Joanna L Clasen  3 , Kendra Vehik  3 , Åke Lernmark  2 , Markus Lundgren  2 , Ezio Bonifacio  4 , Desmond Schatz  5 , Anette-Gabriele Ziegler  6   7   8 , William Hagopian  9 , Marian Rewers  10 , Richard McIndoe  11 , Jorma Toppari  12   13 , Jeffrey Krischer  3 , Beena Akolkar  14 , Andrea Steck  10 , Riitta Veijola  15 , Michael J Haller  5 , Helena Elding Larsson  2   16 ; TEDDY Study Group
Collaborators, Affiliations

Early Appearance of Thyroid Autoimmunity in Children Followed From Birth for Type 1 Diabetes Risk

Berglind Jonsdottir et al. J Clin Endocrinol Metab. .

Abstract

Context: Autoantibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) define preclinical autoimmune thyroid disease (AITD), which can progress to either clinical hypothyroidism or hyperthyroidism.

Objective: 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 human leukocyte antigen (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 age 8 to 13 years had longitudinally collected samples (from age 3.5 months) screened retrospectively and prospectively for thyroid autoantibodies to identify age at seroconversion. The 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 age 10 and 15 months, 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% CI, 1.17-3.08; and TgAb HR 2.55; 95% CI, 1.91-3.41. The risk of progressing to hypothyroidism 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).

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 hypothyroidism or hyperthyroidism.

Keywords: autoimmune thyroid disease; children; thyroid autoimmunity.

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Figures

Figure 1.
Figure 1.
The algorithm for sample selection for testing of autoantibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) in the TEDDY study. Children actively enrolled and aged 8 years or older in 2016 were screened at the next scheduled clinical visit, while younger children were screened when they reached age 8 years. All children diagnosed with type 1 diabetes were eligible for TPOAb and TgAb testing in the last sample collected at or before diagnosis.
Figure 2.
Figure 2.
Age-specific incidence rates and 95% CIs for autoantibodies to thyroid peroxidase (TPOAb)-first (green), thyroglobulin (TgAb)-first (orange), and both-first (purple) in 1-year intervals among 5066 children in the TEDDY study. The age 1 interval includes 1.0 years to younger than 2 years, and likewise for subsequent intervals. Incidence rates (per 1000 person-years) of TPOAb-first and TgAb-first at age 2 were 2.5 (95% CI, 1.3-4.2) and 6.2 (95% CI, 4.1-8.6), respectively, and at age 6, 2.8 (95% CI, 1.5-4.5), and 8.5 (95% CI. 6.1-11.4), respectively. Ages 10 to 13 years are not shown because estimates are unstable due to small sample sizes at those ages.
Figure 3.
Figure 3.
Sex-stratified cumulative incidence and log-rank test P value among 5066 children in the TEDDY study of A, autoantibodies to thyroid peroxidase (TPOAb)-first; B, thyroglobulin (TgAb)-first; C, both-first, and among 424 children at or before type 1 diabetes diagnosis of D TPOAb-first; E, TgAb-first; and F, both first.
Figure 4.
Figure 4.
Forest plot of hazard ratios and 95% CIs for associations of key covariates with risk of autoantibodies to thyroid peroxidase (TPOAb)-first (green); thyroglobulin (TgAb)-first (orange), and both first (purple) among 5025 children in the TEDDY study.
Figure 5.
Figure 5.
Cumulative incidence and log-rank test P value among 5066 children in the TEDDY study of A, autoantibodies to thyroid peroxidase (TPOA)-first; B, thyroglobulin (TgAb)-first; and C, both first; and among 424 children at or before type 1 diabetes diagnosis of D, TPOA-first; and E, TgAb-first; and F, both first. Stratified by human leukocyte antigen genotype.
Figure 6.
Figure 6.
Cumulative incidence and log-rank test P value among 5025 children in the TEDDY study of A, autoantibodies to thyroid peroxidase (TPOA)-first; B, thyroglobulin (TgAb)-first; and C, both first; and among 403 children at or before type 1 diabetes diagnosis of D, TPOA-first; E, TgAb-first; and F, both first. Stratified by family history of autoimmune thyroid disease.
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