Measurement of anti-TSH receptor antibodies: what is the correct cut-off value?

Background: Autoantibodies against the thyroid stimulating hormone receptor, thyrotropin receptor autoantibodies (TRAb) are diagnostic for Graves' disease and can be measured by different methods. As antibody concentrations are not comparable between methods, appropriate cut-off values need to be established for every single method. For a third-generation TRAb assay (Phadia, Thermofisher), the manufacturer determined the cut-off value in a study population consisting of Graves' disease (both newly diagnosed and patients under treatment) and non-Graves' disease patients. The aim of this study was to verify whether this cut-off value holds true in our population.

Methods: Retrospective analysis was performed on TRAb measurements collected over a period of six months from all patients referred for TRAb testing. For our study, we included patients that were newly diagnosed with hyperthyroidism including Graves' disease, multinodular goitre, toxic adenoma, and thyroiditis. Furthermore, we included Graves' patients that were under treatment at the time of TRAb measurement.

Results: Whereas all patients with Graves' disease had positive TRAb, few patients with multinodular goitre, toxic adenoma, and thyroiditis scored positive for TRAb. ROC curve analysis revealed a cut-off value of 4.5 IU/l (compared to 3.3 IU/l established by the manufacturer). Newly diagnosed Graves' patients had higher TRAb concentrations compared to patients under treatment.

Conclusion: The cut-off value of this immunoassay should probably be set higher in untreated Graves' patients than proposed by the manufacturer as the cut-off value should be determined in a study population excluding Graves' patients under treatment. The overall clinical picture remains crucial in the diagnosis of Graves' disease.