Early Appearance of Thyroid Autoimmunity in Children Followed From Birth for Type 1 Diabetes Risk
Authors: 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 ,   the TEDDY Study Group, Rewers Marian , Bautista Kimberly , Baxter Judith , Felipe-Morales Daniel , Frohnert Brigitte I , Stahl Marisa , Garcia Isabel Flores , Gesualdo Patricia , Hays Sierra , Hoffman Michelle , Johnson Randi , Karban Rachel , Liu Edwin , Loaiza Leila , Norris Jill , O’Donnell Holly , Thorndahl Loana , Steck Andrea , Waugh Kathleen , Toppari Jorma , Simell Olli G , Adamsson Annika , Ahonen Suvi , Åkerlund Mari , Anttila Sirpa , Hakola Leena , Hekkala Anne , Honkanen Tiia , Hurskainen Teija , Hyöty Heikki , Ilonen Jorma , Itoshima Saori , Jokipolvi Minna , Jokipuu Sanna , Karjalainen Taru , Karlsson Leena , Kero Jukka , Korpela Marika , Koskenniemi Jaakko J , Kähönen Miia , Knip Mikael , Koivikko Minna-Liisa , Kokkonen Katja , Koskinen Merja , Koreasalo Mirva , Kurppa Kalle , Kuusela Salla , Kytölä Jarita , Laakso Mia , Laiho Jutta , Latva-aho Tiina , Leisku Siiri , Leppänen Laura , Lindfors Katri , Lönnrot Maria , Mäntymäki Elina , Mattila Markus , Miettinen Maija , Niininen Tiina , Niinistö Sari , Nurminen Noora , Oikarinen Sami , Oinas Hanna-Leena , Ollikainen Paula , Othmani Zhian , Pohjola Sirpa , Raja-Hanhela Solja , Rautanen Jenna , Riikonen Anne , Romo Minna , Rönkä Juulia , Rönkä Nelli , Simell Satu , Tihinen Aino , Tossavainen Päivi , Vähä-Mäkilä Mari , Varjonen Eeva , Veijola Riitta , Viinikangas Irene , Vilmi Silja , Virtanen Suvi M , McIndoe Richard , Schatz Desmond , Hopkins Diane , Haller Michael , Gardiner Melissa , Sharma Ashok , Jacobsen Laura , Gordon Percy , Hosford Jennifer , Maina Sharon , Salmon Chelsea , Ziegler Anette G , Bonifacio Ezio , Gezginci Cigdem , Grätz Willi , Heublein Anja , Hummel Sandra , Knopff Annette , Koletzko Sibylle , Ramminger Claudia , Roth Roswith , Schmidt Jennifer , Scholz Marlon , Stock Joanna , Warncke Katharina , Wendel Lorena , Winkler Christiane , München Helmholtz Zentrum , Diabetes Forschergruppe , der Isar Klinikum rechts , Lernmark Åke , Agardh Daniel , Aronsson Carin Andrén , Bennet Rasmus , Cilio Corrado , Dahlberg Susanne , Tsubarah Malin Goldman , Ericson-Hallström Emelie , Fransson Lina , Halilovic Emina , Hyberg Susanne , Jonsdottir Berglind , Karimi Naghmeh , Larsson Helena Elding , Lindström Marielle , Lundgren Markus , Maziarz Marlena , Melin Jessica , Rahmati Kobra , Ramelius Anita , Salami Falastin , Sjöberg Anette , Amboh Evelyn Tekum , Törn Carina , Ulvenhag Ulrika , Wiktorsson Terese , Wimar Åsa , Hagopian William A , Killian Michael , Crouch Claire Cowen , Skidmore Jennifer , Bender Trevor , Llewellyn Megan , McCall Cody , Meyer Arlene , Meyer Jocelyn , Mulenga Denise , Powell Nole , Radtke Jared , Roy Shreya , Tucker Preston , Becker Dorothy , Franciscus Margaret , Smith MaryEllen Dalmagro-Elias , Daftary Ashi , Klein Mary Beth , Yates Chrystal , Krischer Jeffrey P , Adusumali Rajesh , Austin-Gonzalez Sarah , Avendano Maryouri , Baethke Sandra , Burkhardt Brant , Butterworth Martha , Cadigan Nicholas , Clasen Joanna , Counts Kevin , Gandolfo Laura , Garmeson Jennifer , Gowda Veena , Karges Christina , Liu Shu , Liu Xiang , Lynch Kristian , Malloy Jamie , Mramba Lazarus , McCarthy Cristina , Moreno Jose , Parikh Hemang M , Remedios Cassandra , Shaffer Chris , Smith Susan , Sulman Noah , Tamura Roy , Tewey Dena , Thuma Henri , Toth Michael , Uusitalo Ulla , Vehik Kendra , Vijayakandipan Ponni , Wroble Melissa , Yang Jimin , Young Kenneth , Abbondondolo Michael , Ballard Lori , Brown Rasheedah , Cuthbertson David , Dankyi Stephen , Eberhard Christopher , Fiske Steven , Hadley David , Heyman Kathleen , Hsiao Belinda , Laras Francisco Perez , Lee Hye-Seung , Li Qian , Smith Laura , Hagopian William , Radtke Jared , Tucker Preston , Wasserfall Clive H , Winter William E , Pittman David L , Deigan Chris , Akolkar Beena , Briese Thomas , Brusko Todd , Buckner Teresa , Johnson Suzanne Bennett , McKinney Eoin , Pastinen Tomi , Thorsen Steffen Ullitz , Triplett Eric 
Published: July 2024

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.