Laboratory of Clinical Pathology, Dept. of Laboratory Medicine, S. Maria degli Angeli Hospital, Pordenone, Italy.
Autoimmun Rev. 2012 Dec;12(2):107-13. doi: 10.1016/j.autrev.2012.07.003. Epub 2012 Jul 7.
TSH receptor antibodies (TRAb) are the diagnostic hallmark of Graves' disease (GD) and immunoassays for their detection have been available for more than 30 years over three generations of laboratory methods. Despite a growing body of data produced by clinical and laboratory research which demonstrates its elevated sensitivity and specificity, TRAb testing is poorly used for diagnosing GD. The aim of our systematic review and meta-analysis is to verify the diagnostic performance of TRAb detected with 2nd and 3rd generation immunoassay methods.
We searched for English articles using MEDLINE with the search terms "TSH receptor antibody assay", "TSH Receptor antibody tests" and "Graves' disease". We analyzed studies reporting on TSH receptor antibody tests performed by quantitative immunoassays, on untreated patients with GD as the index disease (sensitivity) and on a control group of either healthy subjects or patients affected by other thyroid diseases (specificity). A total of 681 titles were initially identified with the search strategy described. 560 publications were excluded based on abstract and title. Full-text review was undertaken as the next step on 111 publications providing data on TRAb testing; 58 articles were subsequently excluded because they did not include untreated GD patients, or used either bioassays or 1st generation immunoassays. 32 were also excluded because they included data only on sensitivity or only on specificity of the assay, or were duplicates. Finally, 21 articles were selected for meta-analysis. Extraction of data from selected articles was performed by two authors independently, using predefined criteria: the number of patients with GD and the number of healthy or diseased controls; specification of the analytical method used to detect TRAb; sensitivity and specificity of the assay.
The meta-analysis showed that the overall pooled sensitivity and specificity of the 2nd and 3rd generation TRAb assays are 97.1% and 97.4%, and 98.3% and 99.2%, respectively, with little difference between the types of immunoassay methods employed (human or porcine receptor, manual or automated procedure). The likelihood of a TRAb-positive individual to have GD is 1367- to 3420-fold greater (depending upon the type of assay) compared to a TRAb-negative person.
Data from the meta-analysis showed that TRAb measured with 2nd and 3rd generation immunoassay methods have very high sensitivity and specificity in the diagnosis of GD. The difference between 2nd and 3rd generation methods is small and is equally useful. In contrast with recommendations made by clinical endocrinologists who are not familiar with the state of the art in diagnostic technologies of autoimmunology laboratories, we propose a wide application of these tests in clinical practice to screen all hyperthyroid patients.
促甲状腺激素受体抗体（TRAb）是 Graves 病（GD）的诊断标志，用于检测它们的免疫测定法已经在三代实验室方法中使用了 30 多年。尽管临床和实验室研究产生了越来越多的数据，证明其具有较高的灵敏度和特异性，但 TRAb 检测在诊断 GD 中的应用仍很差。我们系统评价和荟萃分析的目的是验证使用第二代和第三代免疫测定法检测到的 TRAb 的诊断性能。
我们使用 MEDLINE 搜索了英文文章，并使用了“TSH 受体抗体测定”、“TSH 受体抗体检测”和“Graves 病”等搜索词。我们分析了报告使用定量免疫测定法检测 TSH 受体抗体的研究，这些研究针对未经治疗的 GD 患者作为索引疾病（灵敏度），以及健康受试者或患有其他甲状腺疾病的患者作为对照组（特异性）。最初使用描述的搜索策略确定了 681 个标题。根据摘要和标题排除了 560 篇出版物。对 111 篇提供 TRAb 检测数据的出版物进行了全文审查；随后由于未包括未经治疗的 GD 患者，或使用生物测定法或第一代免疫测定法，排除了 58 篇文章。由于仅包括检测的灵敏度或特异性数据，或为重复数据，还排除了 32 篇文章。最后，选择了 21 篇文章进行荟萃分析。使用两个作者独立制定的预设标准从选定文章中提取数据：GD 患者的数量和健康或患病对照组的数量；用于检测 TRAb 的分析方法的说明；检测的灵敏度和特异性。
荟萃分析表明，第二代和第三代 TRAb 检测的总体汇总灵敏度和特异性分别为 97.1%和 97.4%，98.3%和 99.2%，使用的免疫测定方法类型（人或猪受体、手动或自动程序）之间差异很小。与 TRAb 阴性个体相比，TRAb 阳性个体患有 GD 的可能性高 1367 至 3420 倍（取决于检测类型）。
荟萃分析数据表明，使用第二代和第三代免疫测定法测量的 TRAb 在 GD 的诊断中具有非常高的灵敏度和特异性。第二代和第三代方法之间的差异很小，同样有用。与不熟悉自身免疫实验室诊断技术最新进展的临床内分泌学家的建议相反，我们建议在临床实践中广泛应用这些检测方法来筛查所有甲状腺功能亢进症患者。
