GADA positivity at onset of type 1 diabetes is a risk factor for the development of autoimmune thyroiditis.
OBJECTIVE
To evaluate whether the presence of diabetes-specific autoantibodies may predict the development of autoimmune thyroiditis (AIT) in children with type 1 diabetes (T1D).


METHODS
Glutamic acid decarboxylase antibodies (GADA), tyrosine phosphatase IA2 antibodies (IA2A), and insulin autoantibodies (IAA) were determined at T1D onset in 341 children and adolescents. Thyroid antibodies (anti-TG, anti-TPO), thyroid stimulating hormone (TSH), T(3) and T(4) were measured in 335 patients at T1D onset and thereafter annually with a follow-up time of 1-15 yr. In case of thyroid antibody positivity and/or TSH elevation, thyroid gland sonography was performed. Treatment with l-thyroxine was started if persistent elevation of TSH and/or thyroid volume was present.


RESULTS
The majority of patients (92.1%) had at least one T1D antibody (71.6% GADA, 73.0% IA2A, and 44.9% IAA). GADA positive patients were older than those without GADA (p < 0.001). Thyroid autoimmunity was found in 15 of 335 patients (4.5%) at T1D onset with female preponderance (p = 0.013). At the end of follow-up, 70 patients (20.9%) had developed thyroid autoantibodies [cumulative incidence (CI) 0.36 ± 0.06 at 10 yr of T1D]. In 30 patients (9.0%), AIT was diagnosed up to 9.4 yr after T1D onset (CI 0.24 ± 0.06 at 10 yr). AIT incidence was not influenced by IAA or IA2A positivity. In multivariate analysis, GADA positive patients were estimated to have a 3.5-fold increased risk of AIT (CI 0.31 ± 0.11 at 10 yr) compared to those without GADA (p = 0.024).


CONCLUSIONS
Based on the present results, a special focus should be given to GADA positive patients concerning screening for AIT as they are at increased risk to develop autoimmune thyroiditis.
Kordonouri
Olga
O
Diabetes Centre for Children and Adolescents, Children's Hospital at the Bult, Janusz-Korczak-Allee 12, Hannover, Germany. kordonouri@hka.de
Charpentier
Nicola
N
Hartmann
Reinhard
R
D000293:Adolescent; D001323:Autoantibodies / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007223:Infant; D007330:Insulin Antibodies / Q000032:analysis; D007453:Iodide Peroxidase / Q000276:immunology; D008297:Male; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000276:immunology; D012307:Risk Factors; D013954:Thyroglobulin / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000209:etiology* / Q000276:immunology; D013972:Thyrotropin / Q000097:blood / Q000276:immunology; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D001323:Autoantibodies; D007330:Insulin Antibodies; D014284:Triiodothyronine; D013972:Thyrotropin; D013954:Thyroglobulin; D007453:Iodide Peroxidase; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase; D013974:Thyroxine