Departments of Medicine I (G.J.K., T.D., J.G., M.K.), Ophthalmology (S.P.), and Institute of Medical Biostatistics, Epidemiology and Informatics (J.K.), Johannes Gutenberg University Medical Center, Mainz, Germany.
J Clin Endocrinol Metab. 2016 May;101(5):1998-2004. doi: 10.1210/jc.2016-1220. Epub 2016 Mar 10.
Thyroid-associated orbitopathy (TAO) rarely occurs in patients with Hashimoto's thyroiditis (HT).
There is evidence that TSH receptor stimulating antibodies (TSAb) play a role in the pathogenesis of TAO. In this report, the prevalence of TSAb in HT patients with and without TAO was studied.
This is a longitudinal observational study.
The study took place in an academic joint thyroid-eye clinic.
A total of 1055 subjects were included.
TSAb was measured with a Food and Drug Administration-cleared bioassay that uses Chinese hamster ovary cells expressing a chimeric TSH receptor and a cAMP response element-dependent luciferase. Results of TSAb activity were reported as percentage of specimen-to-reference ratio (SRR%, cutoff >140%).
We measured the association of TSAb with the risk of TAO in patients with HT.
Of 700 consecutive and unselected patients with HT, 44 (6%) had overt TAO. Patients with HT+TAO were older (P < .001), heavier smokers (P = .032), and clustered less with autoimmune diseases (P = .005). All healthy controls were TSAb negative. In contrast, serum was TSAb positive in 30/44 (68.2%) and 36/656 (5.5%, P < .001) patients with HT+TAO and HT, respectively. Compared to patients with HT only, serum TSAb levels were higher in HT+TAO (median SRR%, 25th and 75th percentiles): 45, 35-65 vs 192.5, 115-455.3, P < .001. Highest TSAb values were noted in patients with active and severe TAO vs those with mild and inactive TAO: 486, 392-592 vs 142, 73-192.5; P < .001. The odds ratio of TSAb positivity for the risk of TAO adjusted for gender and age was 55.9 (95% confidence interval [CI], 24.6-127, P < .0001), whereas the odds ratio per 10-fold change in TSAb SRR% (quantitative TSAb) was 133 (95% CI, 45-390, P < .0001). The area under the receiver operating characteristic curve for qualitative and quantitative TSAb was 87.2% (95% CI, 80.6-93.8) and 89.4% (95% CI, 84.1-94.7), respectively.
TSAb is strongly associated with TAO in HT and TSAb may contribute to the pathophysiology of TAO.
甲状腺相关性眼病（TAO）在桥本甲状腺炎（HT）患者中很少发生。
有证据表明，促甲状腺激素受体刺激抗体（TSAb）在 TAO 的发病机制中起作用。在本报告中，研究了 HT 伴或不伴 TAO 患者中 TSAb 的患病率。
这是一项纵向观察性研究。
研究在一个学术性甲状腺眼病联合诊所进行。
共纳入 1055 例受试者。
使用美国食品和药物管理局批准的生物测定法测量 TSAb，该方法使用表达嵌合 TSH 受体和 cAMP 反应元件依赖性荧光素酶的中国仓鼠卵巢细胞。TSAb 活性的结果以标本与对照比值（SRR%，截断值>140%）的百分比报告。
我们测量了 TSAb 与 HT 患者 TAO 风险的相关性。
在 700 例连续和未经选择的 HT 患者中，44 例（6%）存在明显的 TAO。HT+TAO 患者年龄更大（P<0.001）、吸烟量更大（P=0.032）、自身免疫性疾病聚集程度更低（P=0.005）。所有健康对照者的 TSAb 均为阴性。相比之下，在 HT+TAO 和 HT 患者中，血清分别有 30/44（68.2%）和 36/656（5.5%）（P<0.001）为 TSAb 阳性。与仅 HT 患者相比，HT+TAO 患者的血清 TSAb 水平更高（中位数 SRR%，25%和 75%分位数）：45，35-65 与 192.5，115-455.3，P<0.001。在活动性和严重 TAO 患者中 TSAb 值最高，而在轻度和非活动性 TAO 患者中 TSAb 值较低：486，392-592 与 142，73-192.5；P<0.001。调整性别和年龄后，TSAb 阳性的 TAO 风险比为 55.9（95%置信区间[CI]，24.6-127，P<0.0001），而 TSAb SRR%每增加 10 倍（定量 TSAb）的比值比为 133（95%CI，45-390，P<0.0001）。定性和定量 TSAb 的受试者工作特征曲线下面积分别为 87.2%（95%CI，80.6-93.8）和 89.4%（95%CI，84.1-94.7）。
TSAb 与 HT 中的 TAO 密切相关，TSAb 可能有助于 TAO 的病理生理学。
