Endocrine Abstracts

Objective: The performance of two functional bioassays and two immunoassays for the measurement of TSHR-Ab was assessed in this multicenter study.

Methods: Two-hundred two subjects (median age 54 years, 162 female, 80%), with well-documented thyroid disorders and controls were prospectively enrolled in a consecutive, unselected manner. Antibody measurements were performed in a blinded manner using the Bridge (Siemens, performed at the Dartmouth-Hitchcock Medical Center Laboratory in Lebanon, NH, USA) and Cobas (Roche) automated assays as well as stimulating (TSAb) and blocking (TBAb) TSHR-Ab cell-based bioassays (Quidel) according to manufacturer’s instructions. The Cobas and the two bioassays were performed at the Johannes Gutenberg University, Mainz, Germany.

Results: The four assays were negative in controls (n=10), patients with euthyroid nodular disease (n=11) and non-autoimmune thyrotoxicosis (n=21). In patients with Graves’ disease (GD), independent of disease duration, TSHR-Ab positivity was present in 72/114 (63%), 69 (61%), and 91 (80%) for the Bridge, Cobas immunoassays and TSAb bioassay, respectively (P<0.001). Concordant positive results in the two immunoassays and TSAb bioassay were noted only in 69/114 (61%) patients with GD and TSAb positivity. Of the 45 discordant findings, 26 were TBAb positive as well as Bridge and Cobas positive. One was Bridge positive only, clinically in remission. Of the remaining discordant samples, 18 were TSAb positive, four of which were new diagnoses and untreated; all Bridge negative, one Cobas positive. Eight TSAb positive were on low dose methimazole, but only in two was Cobas positive and in one Bridge positive. Five TSAb positive were clinically in remission, one only Bridge positive. The two immunoassays highly correlated in GD patients (r=0.8, P<0.001), with a lower correlation between the TSAb bioassay and the Bridge- (r=0.49, P<0.001) or Cobas (r=0.52, P<0.001) assays. In 27 patients with Hashimoto’s thyroiditis (HT), four were TSAb positive (15%), of which three and one were Bridge and Cobas positive, respectively. In 160 patients with autoimmune thyroid disease (AITD), TBAb were present in 32 (20%), HT 11/27 (41%) and GD 21/133 (16%). Thirty (94%) and 28/32 (88%) of the TBAb positive samples were also Cobas and Bridge assay positive but TSAb bioassay negative.

Conclusions: Both in newly diagnosed GD and patients on low dose methimazole, substantial differences in sensitivities were observed among the TSHR-Ab assays. Clinically, this may affect initial diagnosis and decisions to discontinue anti-thyroid drugs. In patients with AITD and TSAb negative, both Bridge and Cobas immunoassays were positive in the presence of blocking TSHR-Ab measured in a TBAb bioassay.