Evaluation of a Coated-Tube Assay for Antithyrotropin Receptor Antibodies in Patients with Graves' Disease and Other Thyroid Disorders

The detection of autoantibodies to the thyrotropin-receptor antibody (TRAb) is commonly used in clinical practice for the diagnostic assessment of Graves' disease (GD) and its differential diagnosis from toxic multinodular goiter (MNG) and autonomous adenoma. Additionally, TRAb assays can be useful during antithyroid drug treatment of GD to evaluate the risk of relapse and/or remission. The detection of TRAb was originally performed using a radioreceptor assay based on detergent-solubilized porcine thyroid membranes (TRAb). More recently new assays using purified porcine or recombinant human thyrotropin(TSH) receptor-coated plastic tubes (CT) have been developed (pCT-TRAb or hCT-TRAb). We have evaluated both assays (TRAb and pCTTRAb) in 300 individuals: healthy controls (n = 51); patients with GD before and after treatment (n = 200), patients with MNG (n = 29), and Hashimoto's thyroiditis [HT; n = 20]). All healthy controls and patients with HT had undetectable TRAb using both methods. Patients with active (not treated) GD had higher pCT-TRAb values (mean ± standard deviation [SD], 58.2% ± 20.3%, inhibition of TSH binding) compared to TRAb (41.2% ± 15.4%, p< 0.01, Wilcoxon test). Results (as percent inhibition for both methods) had a positive and significant correlation (r = 0.68, p < 0.001). Moreover TRAb assay had a 97.3% sensitivity and 96.8% specificity; the pCT-TRAb sensitivity was 96.3% and specificity was 98.4% at a cutoff of 1.51 U/L. During treatment of GD, the TRAb method resulted in significantly lower (p < 0.05) values at 12, 24, and 30 months, while pCT-TRAb only exhibited significancy (compared to basal levels) at 30 months. The percent inhibition after 131I treatment of GD was significantly higher for pCT-TRAb (33.7 ± 25.7) compared to TRAb (21.9 ± 17.7, p < 0.01, Wilcoxon test). Only one patient with untreated MNG had a positive pCT-TRAb but negative TRAb value. Patients with MNG treated with 131I were divided into two groups: group 1 (only ¹³¹I) or group 2 (hrTSH preceding ¹³¹I). After MNG radioisotopic ablation, five patients had a positive pCT-TRAb and four had a positive TRAb(group 1) while in group 2, three patients had a positive pCT-TRAb and two had a positive TRAb assay. In conclusion, pCT-TRAb usually had higher percent inhibition values compared to TRAb in untreated GD, had a relatively lower decrease in percent inhibition values during treatment but exhibited a slightly increased sensitivity compared to TRAb. An advantage of the pCT-TRAb assay may be because of the coating system itself that might expose more receptor sites for the antibody.