Relevance of TSH-receptor antibody levels in predicting disease course in Graves' orbitopathy: comparison of the third-generation TBII assay and Mc4-TSI bioassay

Abstract

Aims: To investigate if TSH-receptor antibody (TRAb) levels measured in early Graves' orbitopathy (GO) stages are predictive of clinical disease course beyond 1 year after initial GO diagnosis and to compare performance of two newly developed TRAb assays (third-generation thyrotropin-binding inhibitor immunoglobulin (TBII) assay vs Mc4-thyroid-stimulating immunoglobulin (TSI) bioassay) in predicting disease course.

Methods: Newly diagnosed, untreated GO patients whose duration of ocular symptoms was less than 6 months were included. One year after initial diagnosis, all patients were classified as presenting either a mild (Group 1) or severe course (Group 2) according to their clinical manifestations. The measurements of two TRAb assays at initial GO diagnosis were used for analysis.

Results: Data from 112 patients were available for analysis. Seventy-three patients (65.2%) were designated as Group 1, and 39 patients (34.8%) as Group 2. Patients with higher initial TRAb levels demonstrated a higher risk of severe disease course upon multiple regression analysis (P<0.01). The cutoff values for the prediction of severe course of the third-generation TBII and Mc4-TSI assays were 10.67 IU/l and 555.10%, respectively, with assay specificities of 84.9 and 89.0%. The TBII assay predictive power (area under the curve (AUC)=0.817; 95% confidence interval (CI) =0.732-0.902) was equivalent to the TSI bioassay (AUC=0.868, 95% CI=0.803-0.934) (P=0.203).

Conclusions: The predictive power of the third-generation TBII assay and Mc4-TSI bioassay are similarly strong. Measurement of TRAb using either third-generation TBII or Mc4-TSI in early GO periods would provide important prognostic information on future GO course.

Figure 1

Schematic representation showing the principles of the third-generation TBII assay and Mc4-TSI bioassay. AC, adenylate cyclase; CRE, cAMP response element; LH-CG, lutropin-choriogonadotropin; TSH, thyroid-stimulating hormone; TRAb, TSH-receptor autoantibody; pTSH-R, porcine thyroid-stimulating hormone receptor; TSI, thyroid-stimulating immunoglobulin; TBI, thyroid-blocking immunoglobulin.

Figure 2

Distribution of TSH receptor autoantibody levels according to mild and severe Graves' orbitopathy, and comparison of the receiver operating characteristic analysis between two different TSH-receptor antibody assays. (a) Distribution of third-generation TBII assay. (b) Distribution of Mc4-TSI bioassay. (c) Comparing areas under the curve for each TRAb assay yielded that the predictive power of the third-generation TBII assay (AUC=0.817, 95% CI=0.732–0.902) was equivalent to that of the Mc4-TSI bioassay (AUC=0.868, 95% CI=0.803–0.934) in predicting severe patient disease outcome using the Delong method (P=0.203).