Detecting TSH-Receptor antibodies with the recombinant TBII assay: Technical and clinical evaluation

We evaluated the technical robustness of the new commercial TBII assay usin g human recombinant TSH-R, and describe its use for the clinician in the ro utine laboratory. The human recombinant TSH-R assay (DYNOtest(R) TRAK human ) was compared to a conventional TBII assay (TSH-REZAK(R)). Specificity was adjusted at 99.1% for both assays by ROC plot analysis including 113 healt hy individuals. Sensitivity in 115 patients with active Craves' Disease (GD ) was 98.2% for the DYNOtest(R) TRAK human compared to 68.4% for the TSH-RE ZAK(R) (p < 0.0001). Comparison of the ROC-calculated cut off confirmed the recommended cut-off for the DYNOtest(R) TRAK human, since 11% inhibition o f tracer equals 1 IU/L, which is recommended as the grey zone. At the recom mended cut-off (2 IU/L, 22% inhibition), the sensitivity is still 93.9% wit h 100% specificity. The ROC plot-derived cut-off of the TSH-REZAK(R) (4.4%, 2 to 10 U/L) is below the grey zone of 10-15 U/L. At the recommended cut o ff of 15 U/L, the sensitivity is 43.0% with a specificity of 100%. Both ass ays showed a good correlation(r = 0.82, p < 0.0001); however, assay compari son revealed a constant bias in favour of the DYNOtest(R) TRAK human. Apply ing the ROC plot-derived cut-off of 11% inhibition 11 (U/L) for the DYNOtes t(R) TRAK human, we found 15 of 50 patients with autoimmune thyroiditis (AI T) and 6 of 23 patients with goitre (all < 1.5 IU/L). These patients would have been missed using the recommended 2 IU/L. The difference in sensitivit y between the DYNOtest(R) TRAK human and the TSH-REZAK(R) was highly signif icant. in the GD group, but not in other groups, indicating that the DYNOte st(R) TRAK human has a higher sensitivity for GD without compromising speci ficity. In summary, the proposed high sensitivity of the new TBII assay usi ng human recombinant TSH-R could be confirmed with the commercial product. This method offers a clear advantage over conventional TBII assays to confi rm or exclude the diagnosis of GD. The recommended cut-off is very stringen t, and until we have more information on the clinical relevance of low-leve l TBII between 1 and 1.5 IU/L, those patients should be monitored for the d evelopment of autoimmune thyroid disease.