小儿格雷夫斯病中促甲状腺素自身抗体的临床意义——一项多中心研究。

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

机构信息

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.

出版信息

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

DOI:10.1210/jc.2013-4026

PMID:24517152

Abstract

CONTEXT AND OBJECTIVE

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.

DESIGN

We conducted a cross-sectional retrospective study.

SETTING

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.

MAIN OUTCOME MEASURES

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.

RESULTS

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.

CONCLUSIONS

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

摘要

背景与目的

促甲状腺激素受体（TSHR）刺激自身抗体（TSAbs）在儿科格雷夫斯病（GD）中的发生率存在争议。本项大型多中心研究评估了伴有和不伴眼眶疾病的 GD 患儿中 TSAb 的临床相关性。

设计

我们进行了一项横断面回顾性研究。

地点

在美国和欧洲的七个学术转诊中心收集了血清样本，并在一个中心实验室进行了评估。

患者和样本

共研究了 422 份来自 157 例 GD 患儿、101 例其他甲状腺和非甲状腺自身免疫性疾病患者以及 50 例健康儿童的血清样本。

主要观察指标

使用新型嵌合 TSHR 生物测定法和 cAMP 反应元件依赖性荧光素酶测定了 TSAb 和 TSH 结合抑制性 Ig（TBII）。还测定了甲状腺功能的参数。

结果

在 82 例未经治疗的 GD 患儿中，TSAb 和 TBII 的敏感性、特异性、阳性和阴性预测值分别为：100%和 92.68%（P =.031）、100%和 100%、100%和 100%以及 100%和 96.15%。在 157 例 GD 患儿中，TSAb 和 TBII 分别存在于 147 例（94%）和 138 例（87.9%）患儿中（P <.039），在这组患儿的 263 份样本中，TSAb 和 TBII 分别存在于 247 例（94%）和 233 例（89%）样本中（P <.0075）。在患有 GD 和 GO 的患儿中，TSAb 和 TBII 的检出率分别为 100%和 96%（P <.001）。患有 GD 和 GO 的甲状腺功能亢进患儿的 TSAb 水平明显高于仅患有甲状腺 GD 的患儿（P <.0001）。两组间 TBII 无显著差异。经过 3 年（中位）的药物治疗，GD 患儿的 TSAb 水平下降了 69%，而 GD 和 GO 患儿的 TSAb 水平仅下降了 20%（P <.001）。所有 31 例甲状腺功能正常的 GO 患儿的 TSAb 均为阳性，而 TBII 阳性的患儿仅为 24 例（P =.016）。桥本甲状腺炎、非自身免疫性甲状腺功能亢进、1 型糖尿病、青少年关节炎和健康对照儿童的 TSAb 和 TBII 均为阴性。