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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. [ABSTRACT FROM AUTHOR]

Clinical thyrotoxicosis in Graves'' disease patients is caused by thyrotropin receptor (TSHR)-stimulating autoantibodies. The molecular mechanisms of TSHR post-translational modification, TSHR signaling and TSHR–autoantibody interaction are still debatable, and the precise interaction of stimulating and blocking autoantibodies with TSHR is unclear. Recent TSHR epitope studies indicate that binding sites for stimulating and blocking autoantibodies are close together, not on distinct or distant parts of the molecule. Furthermore, new methods to detect TSHR autoantibodies and their clinical use are addressed. Highly sensitive TSHR autoantibody assays are widely available and cost efficient, and their routine clinical use might help in the differential diagnosis of hyperthyroidism and disease outcome prediction in patients with high levels of TSHR autoantibodies. [Copyright &y& Elsevier]

A letter to the editor is presented in response to an article related to Graves' disease and Hashimoto's thyroidities published in a previous issue of the journal.

Abstract: Commercial assays to measure thyroid stimulating hormone (TSH) receptor (TSHR) autoantibodies (TRAb) have been available for the serological diagnosis of autoimmune thyroid diseases (AITD) for several years. The widespread assessment of this parameter has identified Graves'' disease (GD) as a common organ-specific autoimmune disease. Within the present article we aim to review immunobiological and epidemiological aspects as well as diagnostic methods available for the detection of TRAb. Over the last decade, TRAb detection in GD became more sensitive since TRAb assays were being largely improved by named research groups. Therefore, functional assay (fas) and diagnostic sensitivity of current TRAb assays will be discussed. Within the second part of this review we will focus on clinical applications of TRAb measurement for outcome prediction of GD as well as the importance of this method to distinguish GD from other AITD. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]