Early appearance of thyroid autoimmunity in children followed from birth for type 1 diabetes risk
Jonsdottir, Berglind; Clasen, Joanna L; Vehik, Kendra; Lernmark, Åke; Lundgren, Markus; Bonifacio, Ezio; Schatz, Desmond; Ziegler, Anette-Gabriele; Hagopian, William; Rewers, Marian; McIndoe, Richard; Toppari, Jorma; Krischer, Jeffrey; Akolkar, Beena; Steck, Andrea; Veijola, Riitta; Haller, Michael J; Elding Larsson, Helena; on behalf of the TEDDY Study Group (2024-07-12)
Oxford University Press
12.07.2024
Berglind Jonsdottir, Joanna L Clasen, Kendra Vehik, Åke Lernmark, Markus Lundgren, Ezio Bonifacio, Desmond Schatz, Anette-Gabriele Ziegler, William Hagopian, Marian Rewers, Richard McIndoe, Jorma Toppari, Jeffrey Krischer, Beena Akolkar, Andrea Steck, Riitta Veijola, Michael J Haller, Helena Elding Larsson, the TEDDY Study Group , Early Appearance of Thyroid Autoimmunity in Children Followed From Birth for Type 1 Diabetes Risk, The Journal of Clinical Endocrinology & Metabolism, Volume 110, Issue 2, February 2025, Pages 498–510, https://doi.org/10.1210/clinem/dgae478
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© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. See the journal About page for additional terms.
https://creativecommons.org/licenses/by/4.0/
© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. See the journal About page for additional terms.
https://creativecommons.org/licenses/by/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202408135354
https://urn.fi/URN:NBN:fi:oulu-202408135354
Tiivistelmä
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.
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.
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