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J Clin Endocrinol Metab. 2014 May;99(5):1648-55. doi: 10.1210/jc.2013-4026. Epub 2014 Feb 11.

Clinical relevance of thyroid-stimulating autoantibodies in pediatric graves' disease-a multicenter study.

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Thyroid Laboratory (T.D., M.K., G.J.K.), Department of Medicine I, Johannes Gutenberg University Medical Center, 55101 Mainz, Germany; 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; Department of Pediatrics, Endocrinology, Diabetology, with the Cardiology Division (A. Bossowski), Medical University in Bialystok, 15-089 Bialystok, Poland; Department of Pediatrics (M.S.), University La Sapienza, 00185 Rome, Italy; Department of Pediatric Endocrinology and Rheumatology (M.N.), University of Medical Sciences, 61-701 Poznan, Poland; Institute of Medical Statistics, Biometry, and Epidemiology (J.K.), Johannes Gutenberg University Medical Center, 55101 Mainz, Germany; Department of Cardiology (A. Bossowska), Internal Affair and Administration, Ministry Hospital, 15-089 Bialystok, Poland; Department of Pediatrics (K.Z.), Silesia Medical University, 40-055 Katowice, Poland; and Department of Ophthalmology (S.P.), Johannes Gutenberg University Medical Center, 55101 Mainz, Germany.



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.


We conducted a cross-sectional retrospective study.


Sera were collected in seven American and European academic referral centers and evaluated in a central laboratory. PATIENTS AND SAMPLES: 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.


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.


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 < .039), respectively; and in 247 (94%) and 233 (89%) of the 263 samples from this group (P < .0075), respectively. In children with GD and GO, TSAb and TBII were noted in 100 and 96% (P < .001), respectively. Hyperthyroid children with GD and GO showed markedly higher TSAb levels compared to those with thyroidal GD only (P < .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 < .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.


Serum TSAb level is a sensitive, specific, and reproducible biomarker for pediatric GD and correlates well with disease severity and extrathyroidal manifestations.

[Indexed for MEDLINE]

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