Clinical value of the first automated TSH receptor autoantibody assay for the diagnosis of Graves' disease (GD): an international multicentre trial.

BACKGROUND: Most recently, a new rapid and fully automated electrochemiluminescence immunoassay for the determination of TSH receptor autoantibodies (TRAb) based on the ability of TRAb to inhibit the binding of a human thyroid-stimulating monoclonal antibody (M22) has been established. OBJECTIVE: To evaluate this assay system in clinical routine based on an international multicentre trial and to compare the results with other established TRAb assays. PATIENTS AND MEASUREMENTS: Totally 508 Graves' disease (GD), 142 autoimmune thyroiditis, 107 subacute thyroiditis, 109 nonautoimmune nodular goitre, 23 thyroid cancer patients and 446 normal controls were retrospectively evaluated. RESULTS: ROC plot analysis revealed an area under curve of 0.99 (95% CI: 0.99-1.0) indicating a high assay sensitivity and specificity. The highest sensitivity (99%) and specificity (99%) was seen at a cut-off level of 1.75 IU/l. Here, the calculated positive predictive value was 95%, whereas the negative predictive value was 100%. Applying the ROC plot-derived cut-off of 1.75 IU/l we found a sensitivity for TRAb positivity within the group of newly diagnosed GD patients of 97% which is in accordance to the sum of different nonautomated porcine TSH receptor-based assays with a sensitivity of 94% indicating an excellent analytical performance of the new assay format. Detailed comparison of the automated and the sum of manual assays revealed a near identical specificity. CONCLUSION: Our results demonstrate that this new assay system has a high sensitivity for detecting GD and specificity for discriminating from other thyroid diseases. This assay may represent the future technology for rapid fully automated TRAb detection.

Technical evaluation of the first fully automated assay for the detection of TSH receptor autoantibodies.

BACKGROUND: Graves' disease (GD) is mediated by autoantibodies which bind to the TSH receptor (TRAb). The aim of the present study was to evaluate the technical performance of the first fully automated immunoassay for TRAb detection. METHODS: The Elecsys Anti-TSHR immunoassay utilizes a porcine TSH receptor (TSHR) and the human thyroid stimulating monoclonal TSHR autoantibody M22. RESULTS: Intraassay and total imprecision CV were determined between 1.4%-14.9%, and 2.4%-28.8%, respectively. Using the 20% CV criteria the functional sensitivity was found at 0.73 IU/L. The median CV at the cut-off (1.75 IU/L) was found to be 11%. Comparison studies with five TRAb immunoassays yielded slopes and intercepts between 1.02-1.48, and -0.74-0.56, respectively. Correlation coefficients were determined between 0.895 and 0.978. ROC plot analysis of patients with GD, patients with other thyroid disorders and healthy controls revealed an AUC of 0.99 resulting in a sensitivity of 97% and a specificity of 99% at a TRAb level of 1.75 IU/L. CONCLUSION: The evaluation of the TRAb immunoassay generated homogeneous performance data and demonstrated a high degree of comparability to established TRAb assays. The automated TRAb assay represents a major improvement of thyroid testing in clinical practice.