Theodoraki A, Jones G, Parker J, Woolman E, Martin N, Perera S, Thomas M, Bunn C, Khoo B, Bouloux P M, Vanderpump M P J
Departments of EndocrinologyClinical ImmunologyClinical Biochemistry, Royal Free Hampstead NHS Trust, London, UK.
Clin Endocrinol (Oxf). 2011 Jul;75(1):127-33. doi: 10.1111/j.1365-2265.2011.04022.x.
UK national guidelines recommend the measurement of TSH receptor antibodies (TRAb) in certain clinical scenarios. A commercial third-generation TRAb autoantibody M22-biotin ELISA assay was introduced in May 2008 in our centre.
To evaluate the diagnostic performance of a TRAb assay in a retrospective and subsequently a prospective cohort in a UK centre.
A retrospective review of patients with thyroid disease followed by a prospective observational study in consecutive patients with newly found suppressed serum thyrotrophin (TSH).
Medical records of 200 consecutive patients with thyroid disorders who had TRAb measured since the introduction of the assay. In a prospective study 44 patients with newly identified hyperthyroidism (TSH < 0·02 mIU/l) had sera assayed for TRAb prior to their clinic appointment at which a final diagnosis was sought.
In the retrospective cohort, the manufacturer's cut-off point of TRAb ≥0·4 U/l resulted in a positive predictive value (PPV) of 95%, sensitivity 85%, specificity 94% and negative predictive value (NVP) 79% to diagnose Graves' disease using defined criteria. Receiver operating characteristic (ROC) analysis determined an optimal cut-off point of TRAb ≥3·5 U/l with a 100% specificity to exclude patients without Graves' disease at the cost though of a lower sensitivity (43%). In the prospective study, the sensitivity, PPV, specificity and NPV were all 96% using the ≥0·4 U/l cut-off. When combining hyperthyroid patients from both cohorts the assay sensitivity and specificity at ≥0·4 U/l cut-off were 95% and 92% respectively. A positive TRAb result increased the probability of Graves' disease for a particular patient by 25-35% and only six (2·5%) patients had a diagnosis of hyperthyroidism of uncertain aetiology after TRAb testing.
The assay studied specifically identifies patients with Graves' disease. It is a reliable tool in the initial clinical assessment to determine the aetiology of hyperthyroidism and has the potential for cost-savings.
英国国家指南建议在某些临床情况下检测促甲状腺素受体抗体（TRAb）。2008年5月，我们中心引入了一种商业化的第三代TRAb自身抗体M22-生物素酶联免疫吸附测定法。
在英国一家中心对一组回顾性病例以及随后的前瞻性队列进行评估，以评价TRAb检测方法的诊断性能。
对甲状腺疾病患者进行回顾性分析，随后对连续的血清促甲状腺素（TSH）水平降低的新确诊患者进行前瞻性观察研究。
自该检测方法引入以来，对200例连续的甲状腺疾病患者的病历进行分析。在前瞻性研究中，44例新确诊的甲状腺功能亢进患者（TSH<0.02 mIU/l）在门诊预约寻求最终诊断前检测血清TRAb。
在回顾性队列中，按照制造商设定的TRAb≥0.4 U/l的临界值，根据既定标准诊断格雷夫斯病的阳性预测值（PPV）为95%，灵敏度为85%，特异性为94%，阴性预测值（NPV）为79%。受试者工作特征（ROC）分析确定TRAb≥3.5 U/l的最佳临界值，其特异性为100%，可排除非格雷夫斯病患者，不过灵敏度较低（43%）。在前瞻性研究中，采用≥0.4 U/l的临界值时，灵敏度、PPV、特异性和NPV均为96%。将两个队列中的甲状腺功能亢进患者合并后，采用≥0.4 U/l临界值时检测的灵敏度和特异性分别为95%和92%。TRAb检测结果呈阳性使特定患者患格雷夫斯病的概率增加25%至35%，TRAb检测后只有6例（2.5%）患者被诊断为病因不明的甲状腺功能亢进。
所研究的检测方法能特异性地识别格雷夫斯病患者。它是初步临床评估中确定甲状腺功能亢进病因的可靠工具，并且具有节省成本的潜力。
