Sensitivity of assays for TSH-receptor antibodies

Hashimoto’s patients have in some cases both stimulating and blocking antibodies [2, 3]. It stands to reason that if the patient is hypothyroid, then blocking antibody avidity and/ or titer would dominate irrespective of the presence of stimulating antibodies. There is a growing list of publications that show the prevalence of TSHR stimulating autoantibodies in HT patients using bioassays. Wall et al. [4] found that 22 % (4/17) HT patients without thyroid-associated orbitopathy (TAO) were TSI positive using ThyretainTM TSI Reporter BioAssay. Another clinical study using a different bioassay had similar conclusion and showed 7 % of the HT patients have stimulating autoantibodies [5]. A recent publication by the authors of the subject manuscript showed that 5.5 % of HT patients and 68.2 % of HT patients with TAO were TSI positive when tested with the Thyretain bioassay [6]. Astonishingly, the authors did not test the HT samples with the stimulating bioassay for this study and only tested them with the blocking bioassay. Therefore, we do not know the stimulating autoantibody status of the HT patients. Furthermore, the HT population selected appears to not be random as all tested positive with blocking bioassay. The prevalence of TSHR blocking autoantibodies in HT patients is reportedly 9 % [7]. The IMMULITE TSI assay has a published specificity of 96.4 % when 111 randomly selected HT patients were evaluated [1]. Independent clinical studies have confirmed the high performance of IMMULITE TSI assay showing 100 % sensitivity and 98 % specificity with GD and HT patients [8, 9]. The testing of the HT patients with the Thyretain bioassay may fail to detect all the stimulating antibodies due to its lower sensitivity (92 % according to Thyretain assay package insert) compared to the IMMULITE TSI assay with 98.6 % sensitivity. Stimulating antibody tests that do not rely on bioassay will detect stimulating antibodies even in the presence of blocking antibodies allowing the physician to monitor To the Editor in Chief