Department of Medicine I, Molecular Thyroid Research Laboratory, Johannes Gutenberg University Medical Center, Mainz, Germany.
Endocrine Laboratory and Practice, Mainz, Germany.
J Clin Endocrinol Metab. 2019 Jul 1;104(7):2561-2568. doi: 10.1210/jc.2018-02705.
Serum TSH receptor autoantibody (TSH-R-Ab) is a biomarker of Graves disease (GD). Studies have shown that the levels of this TSH-R-Ab have clinical significance.
To differentiate between thyroidal GD only and Graves orbitopathy (GD + GO).
Controlled, follow-up study.
Academic tertiary referral center for GD + GO.
Sixty patients with GD, GD + GO, and controls.
Serial serum dilution analyses with six automated, ELISA, and cell-based assays for TSH-R-Ab.
Differentiation among GD phenotypes.
All undiluted samples of hyperthyroid-untreated GD patients were positive with the six assays but became negative at dilution 1:9 in four of six assays. In contrast, all undiluted samples of hyperthyroid-untreated GD + GO patients remained positive up to dilution 1:81, P < 0.001. At high dilutions 1:243, 1:729, 1:2187, and 1:6561, the rate of stimulating TSH-R-Ab positivity in the bioassay for GD + GO patients was 75%, 35%, 5%, and 0%, respectively (all P < 0.001). The five ELISA and/or automated assays confirmed this marked difference of anti-TSH-R-Ab detection between GD-only and GD + GO. In comparison, the baseline-undiluted samples of GD vs GD + GO showed an overlap in the ranges of TSH-R-Ab levels. Subsequent to 12-month methimazole treatment, samples from euthyroid GD + GO patients were still TSH-R-Ab positive at the high dilution of 1:243. In contrast, all GD samples were negative already at dilution 1:3. A GD patient with TSH-R-Ab positivity at dilution 1:729 developed de novo GO.
TSH-R-Ab titers, as determined by dilution analysis, significantly differentiate between GD and GD + GO.
血清促甲状腺激素受体自身抗体（TSH-R-Ab）是格雷夫斯病（GD）的生物标志物。研究表明，这种 TSH-R-Ab 的水平具有临床意义。
区分单纯甲状腺 GD 和格雷夫斯眼病（GD+GO）。
对照、随访研究。
GD+GO 的学术三级转诊中心。
60 例 GD、GD+GO 和对照组患者。
采用 6 种自动化 ELISA 和基于细胞的 TSH-R-Ab 检测方法进行血清稀释分析。
区分 GD 表型。
未经治疗的甲状腺功能亢进 GD 患者的所有未稀释样本在 6 种检测方法中均为阳性，但在 4 种检测方法中，稀释至 1:9 时变为阴性。相反，未经治疗的甲状腺功能亢进 GD+GO 患者的所有未稀释样本在稀释至 1:81 时仍为阳性，P<0.001。在高稀释度 1:243、1:729、1:2187 和 1:6561 时，GD+GO 患者的生物测定中刺激 TSH-R-Ab 阳性的比例分别为 75%、35%、5%和 0%（均 P<0.001）。五种 ELISA 和/或自动化检测方法证实了 GD 单纯型和 GD+GO 之间抗 TSH-R-Ab 检测的这种显著差异。相比之下，GD 与 GD+GO 的基线未稀释样本在 TSH-R-Ab 水平范围上存在重叠。甲巯咪唑治疗 12 个月后，甲状腺功能正常的 GD+GO 患者的样本仍在高稀释度 1:243 时呈 TSH-R-Ab 阳性。相比之下，GD 样本在稀释度 1:3 时已全部阴性。一名 TSH-R-Ab 稀释度为 1:729 的 GD 患者新发 GO。
通过稀释分析确定的 TSH-R-Ab 滴度可显著区分 GD 和 GD+GO。
