Analytical and Clinical Validation of Two Commercially Available Immunoassays Used in the Detection of TSHR Antibodies.

BACKGROUND Graves disease is caused by autoantibodies that target the thyroid-stimulating hormone receptor (TSHR). Anti-TSHR autoantibody measurement is routinely performed to differentiate between Graves disease and other causes of hyperthyroidism. We evaluated the clinical performance of a reference laboratory bioassay [the Thyretain thyroid-stimulating immunoglobulin (TSI) Bioassay by Diagnostic Hybrids] and 2 commercially available immunoassays: the TSI Bridge immunoassay by Siemens and the thyroid-stimulating hormone receptor antibody (TRAb) immunoassay by Roche. We further evaluated the analytical performance of the Siemens TSI and Roche TRAb assays. METHODS We performed method comparisons using 125 patient specimens submitted for TSI testing for clinical purposes. Concordance of patient results was assessed between the 3 methods, and chart review was performed to further evaluate samples that generated discordant results. All 3 methods were also evaluated for potential interference caused by human chorionic gonadotropin (hCG). RESULTS The Roche and Siemens assays demonstrated acceptable day-to-day precision, within-run precision, and precision at the clinical decision cutoffs. Despite manufacturer-defined analytical measuring ranges up to 40 IU/L, the Roche and Siemens assays were linear to 20 IU/L and 15 IU/L, respectively. hCG concentrations up to 150000 IU/L did not interfere with any of the methods evaluated. Moderate agreement between methods was observed when testing patient specimens that generated negative (≤1.3) or weakly positive (1.4-3.8) results by the Thyretain assay. One hundred percent agreement was observed when the Thyretain assay was strongly positive (≥3.9). CONCLUSIONS The 3 commercially available anti-TSHR autoantibody measurement methods demonstrated equivalent performance in patients with untreated Graves disease. Discordant results were observed when testing specimens collected from patients undergoing treatment for Graves disease. In these patients, the Siemens TSI assay more frequently generated results consistent with clinical history, results of other laboratory tests, and imaging studies than the Thyretain Bioassay and Roche TRAb assay.