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

TEDDY Study Group; 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

doi:10.1210/clinem/dgae478

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

TEDDY Study Group, 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

Research output: Contribution to journal › Article › Scientific › peer-review

Abstract

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.

Original language	English
Journal	The journal of clinical endocrinology and metabolism
DOIs	https://doi.org/10.1210/clinem/dgae478
Publication status	E-pub ahead of print - 12 Jul 2024
Externally published	Yes
Publication type	A1 Journal article-refereed

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10.1210/clinem/dgae478Licence: CC BY

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TEDDY Study Group, 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. (2024). Early appearance of thyroid autoimmunity in children followed from birth for type 1 diabetes risk. The journal of clinical endocrinology and metabolism. Advance online publication. https://doi.org/10.1210/clinem/dgae478

@article{1c8f9ce746aa4dc09f4c4c86549e47e2,

title = "Early appearance of thyroid autoimmunity in children followed from birth for type 1 diabetes risk",

abstract = "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.",

author = "{TEDDY Study Group} and Berglind Jonsdottir and Clasen, {Joanna L} and Kendra Vehik and {\AA}ke Lernmark and Markus Lundgren and Ezio Bonifacio and Desmond Schatz and Anette-Gabriele Ziegler and William Hagopian and Marian Rewers and Richard McIndoe and Jorma Toppari and Jeffrey Krischer and Beena Akolkar and Andrea Steck and Riitta Veijola and Haller, {Michael J} and {Elding Larsson}, Helena and Suvi Virtanen and Leena Hakola and Heikki Hy{\"o}ty and Sami Oikarinen and Suvi Ahonen and Mari {\AA}kerlund and Markus Mattila and Maria L{\"o}nnrot and Mirva Koreasalo and Kalle Kurppa and Katri Lindfors",

note = "{\textcopyright} The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.",

year = "2024",

month = jul,

day = "12",

doi = "10.1210/clinem/dgae478",

language = "English",

}

TEDDY Study Group, Jonsdottir, B, Clasen, JL, 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, MJ & Elding Larsson, H 2024, 'Early appearance of thyroid autoimmunity in children followed from birth for type 1 diabetes risk', The journal of clinical endocrinology and metabolism. https://doi.org/10.1210/clinem/dgae478

TY - JOUR

T1 - Early appearance of thyroid autoimmunity in children followed from birth for type 1 diabetes risk

AU - TEDDY Study Group

AU - Jonsdottir, Berglind

AU - Clasen, Joanna L

AU - Vehik, Kendra

AU - Lernmark, Åke

AU - Lundgren, Markus

AU - Bonifacio, Ezio

AU - Schatz, Desmond

AU - Ziegler, Anette-Gabriele

AU - Hagopian, William

AU - Rewers, Marian

AU - McIndoe, Richard

AU - Toppari, Jorma

AU - Krischer, Jeffrey

AU - Akolkar, Beena

AU - Steck, Andrea

AU - Veijola, Riitta

AU - Haller, Michael J

AU - Elding Larsson, Helena

AU - Virtanen, Suvi

AU - Hakola, Leena

AU - Hyöty, Heikki

AU - Oikarinen, Sami

AU - Ahonen, Suvi

AU - Åkerlund, Mari

AU - Mattila, Markus

AU - Lönnrot, Maria

AU - Koreasalo, Mirva

AU - Kurppa, Kalle

AU - Lindfors, Katri

PY - 2024/7/12

Y1 - 2024/7/12

N2 - 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.

AB - 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.

U2 - 10.1210/clinem/dgae478

DO - 10.1210/clinem/dgae478

M3 - Article

C2 - 38996042

SN - 0021-972X

JO - The journal of clinical endocrinology and metabolism

JF - The journal of clinical endocrinology and metabolism

ER -

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

Abstract

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