title: Detecting TSH-receptor antibodies with the recombinant TBII assay: technical and clinical evaluation.
abstract: We evaluated the technical robustness of the new commercial TBII assay using human recombinant TSH-R, and describe its use for the clinician in the routine laboratory. The human recombinant TSH-R assay (DYNOtest TRAK human) was compared to a conventional TBII assay (TSH-REZAK). Specificity was adjusted at 99.1% for both assays by ROC plot analysis including 113 healthy individuals. Sensitivity in 115 patients with active Graves' Disease (GD) was 98.2% for the DYNOtest TRAK human compared to 68.4% for the TSH-REZAK (p<0.0001). Comparison of the ROC-calculated cut off confirmed the recommended cut-off for the DYNOtest TRAK human, since 11% inhibition of tracer equals 1 IU/L, which is recommended as the grey zone. At the recommended cut-off (2 IU/L, 22% inhibition), the sensitivity is still 93.9% with 100% specificity. The ROC plot-derived cut-off of the TSH-REZAK (4.4%, 2 to 10 U/L) is below the grey zone of 10-15 U/L. At the recommended cut off of 15 U/L, the sensitivity is 43.0% with a specificity of 100%. Both assays showed a good correlation (r = 0.82, p < 0.0001); however, assay comparison revealed a constant bias in favour of the DYNOtest TRAK human. Applying the ROC plot-derived cut-off of 11 % inhibition (1 IU/L) for the DYNOtest TRAK human, we found 15 of 50 patients with autoimmune thyroiditis (AIT) 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 sensitivity between the DYNOtest TRAK human and the TSH-REZAK was highly significant in the GD group, but not in other groups, indicating that the DYNOtest TRAK human has a higher sensitivity for GD without compromising specificity. In summary, the proposed high sensitivity of the new TBII assay using human recombinant TSH-R could be confirmed with the commercial product. This method offers a clear advantage over conventional TBII assays to confirm or exclude the diagnosis of GD. The recommended cut-off is very stringent, and until we have more information on the clinical relevance of low-level TBII between 1 and 1.5 IU/L, those patients should be monitored for the development of autoimmune thyroid disease.
authors.affiliation: Department of Endocrinology, Heinrich-Heine-University, Düsseldorf, Germany. schottmt@uni-duesseldorf.de
authors.forename: M
authors.initials: M
authors.lastname: Schott
authors.forename: J
authors.initials: J
authors.lastname: Feldkamp
authors.forename: C
authors.initials: C
authors.lastname: Bathan
authors.forename: R
authors.initials: R
authors.lastname: Fritzen
authors.forename: W A
authors.initials: WA
authors.lastname: Scherbaum
authors.forename: J
authors.initials: J
authors.lastname: Seissler
mesh_terms: D001323:Autoantibodies / Q000032:analysis*; D001665:Binding Sites / Q000276:immunology; D005500:Follow-Up Studies; D006111:Graves Disease / Q000175:diagnosis* / Q000532:radiotherapy / Q000601:surgery; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D011989:Receptors, Thyrotropin / Q000276:immunology*; D011994:Recombinant Proteins; D012016:Reference Values; D015203:Reproducibility of Results; D013967:Thyroiditis, Autoimmune / Q000175:diagnosis* / Q000532:radiotherapy / Q000601:surgery
chemical_list: D001323:Autoantibodies; D007457:Iodine Radioisotopes; D011989:Receptors, Thyrotropin; D011994:Recombinant Proteins