Measuring thyroid-stimulating hormone receptor antibodies using the IMMULITE® 2000 TSI assay is better than using the BRAHMS TRAK assay in an unselected clinical population, but both perform worse than expected: a real-world retrospective observational study

Abstract Background Graves’ hyperthyroidism is caused by stimulatory autoantibodies. Its diagnosis and monitoring are commonly based on measurement of thyrotropin receptor antibodies (TRAb) with unspecific immunoassays, that also detect neutral and blocking antibodies. TRAb analyzed using the Siemens IMMULITE® 2000 TSI immunoassay (TRAb-IM), designed to target stimulatory immunoglobulins, represents a promising alternative. This study aimed to determine the clinical performance of TRAb-IM and the Thermo Fisher BRAHMS TRAK KRYPTOR immunoassay (TRAb-KR) in a real-world setting. Methods Over 3 months, TRAb-IM was analyzed in samples collected to measure TRAb-KR after referral for thyrotoxicosis or at the time of discontinuation of antithyroid drugs (n = 168). Data on thyroid hormones, TRAb-KR, and date of start/discontinuation of antithyroid drugs was collected. Results Agreement analysis for Graves’ disease diagnosis between the assays yielded a Gwet’s AC1 of 0.69 (95% confidence interval [CI] 0.51–0.86) for the samples collected after referral for thyrotoxicosis (n = 122). In this group, sensitivity (95% CI) for TRAb-IM and TRAb-KR was 97% (86–100) and 78% (62–90), respectively, in overt hyperthyroidism (n = 49), and 71% (42–92) and 43% (18–71), respectively, in subclinical hyperthyroidism (n = 46). Specificity was 100% (74–100) for both assays in overt hyperthyroidism, and 97% (84–100) and 100% (89–100), respectively, in subclinical hyperthyroidism. When TRAb-IM and TRAb-KR results were used as predictors for recurrence at the time of discontinuation of antithyroid drugs, the ROC AUC was 0.65 (95% CI 0.47–0.82; p = 0.07) and 0.57 (95% CI 0.41–0.73; p = 0.40), respectively. Conclusions The TRAb-IM assay presented better clinical performance at both diagnosis of Graves’ disease and prediction of its recurrence compared to the TRAb-KR assay. Nonetheless, endocrinologists should be aware that both assays are weak in diagnostic of subclinical cases and in the prediction of recurrence, when used at the time of discontinuation of antithyroid drugs.