{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:11:26Z","timestamp":1783487486868,"version":"3.55.0"},"reference-count":39,"publisher":"The Endocrine Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,5,1]]},"abstract":"\n Context and Objective:<\/jats:title>\n The incidence of TSH receptor (TSHR) stimulating autoantibodies (TSAbs) in pediatric Graves' disease (GD) is controversial. This large, multicenter study evaluated the clinical relevance of TSAbs in children with GD both with Graves' orbitopathy (GO) and without orbital disease.<\/jats:p>\n <\/jats:sec>\n \n Design:<\/jats:title>\n We conducted a cross-sectional retrospective study.<\/jats:p>\n <\/jats:sec>\n \n Setting:<\/jats:title>\n Sera were collected in seven American and European academic referral centers and evaluated in a central laboratory.<\/jats:p>\n <\/jats:sec>\n \n Patients and Samples:<\/jats:title>\n A total of 422 serum samples from 157 children with GD, 101 control individuals with other thyroid and nonthyroid autoimmune diseases, and 50 healthy children were studied.<\/jats:p>\n <\/jats:sec>\n \n Main Outcome Measures:<\/jats:title>\n TSAbs were measured using a novel, chimeric TSHR bioassay and a cAMP response element-dependent luciferase. TSH binding-inhibitory Ig (TBII) and parameters of thyroid function were also determined.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n In 82 untreated children with GD, sensitivity, specificity, and positive and negative predictive values for TSAb and TBII were: 100 and 92.68% (P = .031), 100 and 100%, 100 and 100%, and 100 and 96.15%, respectively. TSAb and TBII were present in 147 (94%) and 138 (87.9%) of the 157 children with GD (P &lt; .039), respectively; and in 247 (94%) and 233 (89%) of the 263 samples from this group (P &lt; .0075), respectively. In children with GD and GO, TSAb and TBII were noted in 100 and 96% (P &lt; .001), respectively. Hyperthyroid children with GD and GO showed markedly higher TSAb levels compared to those with thyroidal GD only (P &lt; .0001). No significant differences were noted for TBII between the two groups. After a 3-year (median) medical treatment, the decrease of TSAb levels was 69% in GD vs 20% in GD and GO (P &lt; .001). All 31 samples of euthyroid children with GO were TSAb positive; in contrast, only 24 were TBII positive (P = .016). All children with Hashimoto's thyroiditis, nonautoimmune hyperthyroidism, type 1 diabetes, and juvenile arthritis and the healthy controls were TSAb and TBII negative.<\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n Serum TSAb level is a sensitive, specific, and reproducible biomarker for pediatric GD and correlates well with disease severity and extrathyroidal manifestations.<\/jats:p>\n <\/jats:sec>","DOI":"10.1210\/jc.2013-4026","type":"journal-article","created":{"date-parts":[[2014,2,11]],"date-time":"2014-02-11T17:59:22Z","timestamp":1392141562000},"page":"1648-1655","source":"Crossref","is-referenced-by-count":91,"title":["Clinical Relevance of Thyroid-Stimulating Autoantibodies in Pediatric Graves' Disease\u2014A Multicenter Study"],"prefix":"10.1210","volume":"99","author":[{"given":"T.","family":"Diana","sequence":"first","affiliation":[{"name":"Thyroid Laboratory (T.D., M.K., G.J.K.), Department of Medicine I, Johannes Gutenberg University Medical Center, 55101 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. S.","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Endocrinology (R.S.B., A.H., J.S.), Department of Medicine, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Bossowski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Endocrinology, Diabetology, with the Cardiology Division (A. Bossowski), Medical University in Bialystok, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Segni","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (M.S.), University La Sapienza, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Niedziela","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Rheumatology (M.N.), University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"K\u00f6nig","sequence":"additional","affiliation":[{"name":"Institute of Medical Statistics, Biometry, and Epidemiology (J.K.), Johannes Gutenberg University Medical Center, 55101 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Bossowska","sequence":"additional","affiliation":[{"name":"Department of Cardiology (A. Bossowska), Internal Affair and Administration, Ministry Hospital, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Ziora","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (K.Z.), Silesia Medical University, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Hale","sequence":"additional","affiliation":[{"name":"Division of Endocrinology (R.S.B., A.H., J.S.), Department of Medicine, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Endocrinology (R.S.B., A.H., J.S.), Department of Medicine, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Pitz","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology (S.P.), Johannes Gutenberg University Medical Center, 55101 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Kanitz","sequence":"additional","affiliation":[{"name":"Thyroid Laboratory (T.D., M.K., G.J.K.), Department of Medicine I, Johannes Gutenberg University Medical Center, 55101 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. J.","family":"Kahaly","sequence":"additional","affiliation":[{"name":"Thyroid Laboratory (T.D., M.K., G.J.K.), Department of Medicine I, Johannes Gutenberg University Medical Center, 55101 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613341111200_B1","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1210\/jc.2010-0898","article-title":"Approach to the pediatric patient with Graves' disease: when is definitive therapy warranted?","volume":"96","author":"Bauer","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613341111200_B2","first-page":"50","article-title":"Hyperthyroidism in childhood: causes, when and how to treat","volume":"5","author":"L\u00e9ger","year":"2013","journal-title":"J Clin Res Pediatr Endocrinol"},{"key":"2020071613341111200_B3","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1530\/eje.1.01991","article-title":"Childhood Graves' ophthalmopathy: results of a European questionnaire study","volume":"153","author":"Krassas","year":"2005","journal-title":"Eur J Endocrinol"},{"key":"2020071613341111200_B4","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1515\/JPEM.2006.19.10.1193","article-title":"Thyroid-associated ophthalmopathy in juvenile Graves' disease\u2013clinical, endocrine and therapeutic aspects","volume":"19","author":"Krassas","year":"2006","journal-title":"J Pediatr Endocrinol Metab"},{"key":"2020071613341111200_B5","doi-asserted-by":"crossref","first-page":"176970","DOI":"10.1186\/1687-9856-2010-176970","article-title":"Adverse events associated with methimazole therapy of Graves' disease in children","volume":"2010","author":"Rivkees","year":"2010","journal-title":"Int J Pediatr Endocrinol"},{"key":"2020071613341111200_B6","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1089\/thy.1999.9.871","article-title":"Special features of Graves' disease in early childhood","volume":"9","author":"Segni","year":"1999","journal-title":"Thyroid"},{"key":"2020071613341111200_B7","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1089\/thy.1997.7.755","article-title":"Autoimmune hyperthyroidism in prepubertal children and adolescents: comparison of clinical and biochemical features at diagnosis and responses to medical therapy","volume":"7","author":"Shulman","year":"1997","journal-title":"Thyroid"},{"key":"2020071613341111200_B8","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1089\/thy.2008.0014","article-title":"Pediatric thyroid-associated orbitopathy: the Children's Hospital of Philadelphia experience and literature review","volume":"18","author":"Goldstein","year":"2008","journal-title":"Thyroid"},{"key":"2020071613341111200_B9","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.jaapos.2007.12.011","article-title":"Pediatric Graves' ophthalmopathy: the pre- and postpubertal experience","volume":"12","author":"Holt","year":"2008","journal-title":"J AAPOS"},{"key":"2020071613341111200_B10","doi-asserted-by":"crossref","first-page":"e60","DOI":"10.1056\/NEJMicm0809071","article-title":"Images in clinical medicine. 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ophthalmopathy","volume":"52","author":"Kubo","year":"2005","journal-title":"Endocr J"},{"key":"2020071613341111200_B27","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1507\/endocrj.52.505","article-title":"Assays for thyroid-stimulating antibodies and thyrotropin-binding inhibitory immunoglobulins in children with Graves' disease","volume":"52","author":"Shibayama","year":"2005","journal-title":"Endocr J"},{"key":"2020071613341111200_B28","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1210\/jc.2011-1944","article-title":"Positive impact of long-term antithyroid drug treatment on the outcome of children with Graves' disease: national long-term cohort study","volume":"97","author":"L\u00e9ger","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613341111200_B29","doi-asserted-by":"crossref","first-page":"3817","DOI":"10.1210\/jc.2008-0842","article-title":"Predictors of autoimmune hyperthyroidism relapse in children after discontinuation of 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