Clinical evaluation of automated bridging immunoassay TSI in the diagnosis of Graves’ disease and the relationship with hyperthyroidism degree

Background: Accurate and rapid detection of stimulating thyroid-stimulating hormone (TSH) receptor antibody has always been an urgent need for clinical diagnosis and management of thyroid-related diseases. We aimed to evaluate the use of thyroid stimulating immunoglobulin (TSI) assay in the diagnosis of Graves’ disease (GD) and analyze the relationship between TSI and the degree of hyperthyroidism. Methods: 227 new-onset GD patients, 29 Hashimoto thyroiditis, 43 non-autoimmune thyroid diseases and 37 euthyroid controls were consecutively recruited. All participants accepted the measurement of serum thyroid function and thyroid associated antibody including TSI measured by Immulite 2000 bridging immunoassay and TSH receptor autoantibodies (TRAb) measured by third-generation Roche electrochemiluminescence immunoassay. The quantitative consistency between TSI and TRAb detection methods was analyzed by using Passing-Bablock regression and Bland-Altman scatter plot. Diagnostic performance of GD was assessed by receiver operating characteristics (ROC) curve analysis. Results: Among 227 GD patients (174 female, 53 male, with mean age of 39 years old), quantitative TSI was positively correlated with TRAb (r=0.8099). According to the cutoff value proposed by the manufacture (TSI 0.55IU/L, TRAb 1.75IU/L), the positive rates of TSI and TRAb in new-onset GD patients were 96.92% and 95.15%, respectively. Both TSI and TRAb levels positively correlated to FT 4 levels (TSI: r=0.243, TRAb: r=0.317, all P<0.001) and FT 3 levels (TSI: r=0.288, TRAb: r=0.360, all P<0.001) in new-onset GD patients. ROC analysis showed that the optimal cut-off TSI value was 0.577 IU/L for GD diagnosis in this Chinese population, with sensitivity 96.92% and specificity 97.25%, respectively. The optimal cut-off value of TRAb was 1.38 IU/L, with sensitivity 96.92% and specificity 99.08%, respectively. There were no significant differences between the cutoff values obtained through ROC analysis and provided by the manufacturer both for TSI and TRAb when calculating the sensitivity and specificity of GD diagnosis. Among 8 newly GD cases with discordant antibody qualitative results, TSI was more likely to match the clinical diagnosis of GD than TRAb (6 TSI positive, 2 TRAb positive). Conclusion: The automated bridging-based TSI immunoassay was positively correlated with thyroxine levels in newly onset GD patients and more likely to be consistent with the clinical diagnosis of GD than TRAb. The positive cut-off value 0.577IU/L of Immulite 2000 TSI for GD diagnosis in Chinese population were closed to the value recommended by the manufacturer.