Department of Endocrinology and Medicine, Aarhus University Hospital, Aalborg, Denmark.
Thyroid. 2010 Feb;20(2):127-33. doi: 10.1089/thy.2009.0105.
The best biochemical marker of Graves' disease (GD) is the presence in serum of autoantibodies to the thyroid-stimulating hormone receptor (hTSHR-Ab). The aim of this study was to evaluate the performances of two sensitive hTSHR-Ab assays with a specific focus on the clinical importance of differences in results. Both assays are competitive in nature but employ quite different types of ligands. In the "M22-pTSHR" assay, hTSHR-Ab competes with a labeled monoclonal antibody (M22*) against the thyrotropin (TSH)-receptor for binding to porcine TSH receptors. In the "bTSH-rhTSHR" assay, hTSHR-Ab competes with labeled bovine TSH for binding to recombinant human TSH receptors.
bTSH-rhTSHR and M22-pTSHR were measured in patients from a population study: 106 had new hyperthyroidism due to GD, 93 had multinodular toxic goiter, 100 had new primary autoimmune hypothyroidism, and 100 were healthy controls.
Receiver operating characteristic curves indicated a high sensitivity and specificity of both assays (area under curve, bTSH-rhTSHR: 0.977 [confidence interval: 0.954-1.00]; M22-pTSHR: 0.979 [confidence interval: 0.957-1.00]). The two assays identified nearly the same patients who were hTSHR-Ab positive, though large differences in hTSHR-Ab values were obtained in a number of individual patients (ratio bTSH-rhTSHR/M22-pTSHR, range: 0.33-6.5 in patients positive with both assays). Values were in average 2.5 times higher with the bTSH-rhTSHR assay compared with the M22-pTSHR assay, corresponding to the difference in recommended clinical cut-off values (1.0 IU/L and 0.4 u/L). The bTSH-rhTSHR assay had a considerably lower intraassay coefficients of variation of 3.8%; for M22-pTSHR, it was 9.5% (p < 0.01).
Both assays had a high sensitivity and specificity for diagnosing GD. hTSHR-Ab values were in average 2.5 times higher with the bTSH-rhTSHR assay compared with the M22-pTSHR assay. In individual patients, the ratio between results obtained using the two assays varied widely. Thus, results obtained using one assay cannot be quantitatively transformed to values obtained using the other assay. bTSH-rhTSHR had a considerably lower intraassay coefficients of variation and it may be better suited for longitudinal studies of hTSHR-Ab.
Graves 病（GD）的最佳生化标志物是血清中存在针对促甲状腺激素受体（hTSHR-Ab）的自身抗体。本研究的目的是评估两种敏感的 hTSHR-Ab 检测方法的性能，特别关注结果差异的临床重要性。两种检测方法均具有竞争性，但使用的配体类型却截然不同。在“M22-pTSHR”检测中，hTSHR-Ab 与针对促甲状腺激素（TSH）受体的标记单克隆抗体（M22*）竞争结合猪 TSH 受体。在“bTSH-rhTSHR”检测中，hTSHR-Ab 与标记的牛 TSH 竞争与重组人 TSH 受体结合。
在一项人群研究中测量了 bTSH-rhTSHR 和 M22-pTSHR：106 例新出现的 GD 引起的甲状腺功能亢进症，93 例多结节毒性甲状腺肿，100 例新发生的原发性自身免疫性甲状腺功能减退症和 100 例健康对照组。
受试者工作特征曲线表明两种检测方法均具有较高的灵敏度和特异性（曲线下面积，bTSH-rhTSHR：0.977[置信区间：0.954-1.00]；M22-pTSHR：0.979[置信区间：0.957-1.00]）。两种检测方法几乎都能识别出 hTSHR-Ab 阳性的患者，但在许多个别患者中获得了 hTSHR-Ab 值的较大差异（两种检测方法均为阳性的患者中 bTSH-rhTSHR/M22-pTSHR 比值范围：0.33-6.5）。与 M22-pTSHR 检测相比，bTSH-rhTSHR 检测的 hTSHR-Ab 值平均高 2.5 倍，这与推荐的临床临界值差异相对应（1.0 IU/L 和 0.4 u/L）。bTSH-rhTSHR 检测的批内变异系数低得多，为 3.8%；而 M22-pTSHR 检测为 9.5%（p<0.01）。
两种检测方法对诊断 GD 均具有较高的灵敏度和特异性。与 M22-pTSHR 检测相比，bTSH-rhTSHR 检测的 hTSHR-Ab 值平均高 2.5 倍。在个别患者中，两种检测方法的结果比值差异很大。因此，一种检测方法获得的结果不能定量转换为另一种检测方法获得的结果。bTSH-rhTSHR 的批内变异系数低得多，可能更适合于 hTSHR-Ab 的纵向研究。
