title: TSH-receptor antibody measurement for differentiation of hyperthyroidism into Graves' disease and multinodular toxic goitre: a comparison of two competitive binding assays.
abstract: OBJECTIVE
  Graves' disease is characterized by stimulating autoantibodies to the TSH-receptor (TRAb). The aim of this study was to compare the performance of a new TRAb assay based on competitive binding to recombinant human TSH-receptors (H-TRAb) with an assay employing purified porcine TSH-receptors (P-TRAb). Furthermore, to evaluate the applicability of the H-TRAb assay to discriminate between patients with hyperthyroidism due to Graves' disease (GD) and multinodular toxic goitre (MNTG).
  
  
  METHODS
  H-TRAb and P-TRAb were measured in patients with newly diagnosed hyperthyroidism due to GD (n = 106) and MNTG (n = 94). For comparison, TRAb was measured in patients with primary autoimmune hypothyroidism, euthyroid subjects with an enlarged thyroid gland by ultrasound, and healthy controls (n = 100 for each group). Patients were consecutively included from a population survey.
  
  
  RESULTS
  If the cut-off values recommended by the manufacturer for TSH-receptor antibody positivity were used for evaluation, the sensitivity of the H-TRAb assay vs. the P-TRAb assay in diagnosing GD was: 95.3/67.9% (P < 0.001). Specificity was (H/P-TRAb): 99/99%. The sensitivity of P-TRAb was increased if the upper 97.5% limit of measurements in controls was used as cut-off (H-TRAb vs. P-TRAb: 95.3/80.2%, P < 0.001). Specificity (H/P-TRAb): 98/98%. The difference between assay performance may partly be due to a better technical performance of the H-TRAb assay with more reliable results in the low range of measurements. However, even in GD patients with clearly measurable TRAb, 25% had a P-TRAb < 50% of the value expected from the H-TRAb measurement. This suggests that a subgroup of patients produce TRAb with a higher affinity for the human than the porcine TSH receptor. A relatively high proportion of patients with MNTG were TRAb positive (H-TRAb/P-TRAb: 17/9%). Characteristics of H-TRAb positive and negative MNTG patients were compared. There was no difference between size of thyroid gland and number of nodules by ultrasonography. H-TRAb positive patients had significantly higher serum T4 and T3 and a greater number were TPO-Ab positive.
  
  
  CONCLUSIONS
  H-TRAb diagnosed Graves' disease with a high sensitivity and specificity than P-TRAb. The high occurrence of TRAb in multinodular toxic goitre might in part reflect an overlap between Graves' disease and multinodular toxic goitre in some patients.
authors.affiliation: Department of Endocrinology and Medicine, Aalborg Hospital, Aalborg, Denmark. ibulow@aas.nja.dk
authors.forename: I B
authors.initials: IB
authors.lastname: Pedersen
authors.forename: N
authors.initials: N
authors.lastname: Knudsen
authors.forename: H
authors.initials: H
authors.lastname: Perrild
authors.forename: L
authors.initials: L
authors.lastname: Ovesen
authors.forename: P
authors.initials: P
authors.lastname: Laurberg
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001667:Binding, Competitive; D003430:Cross-Sectional Studies; D003937:Diagnosis, Differential; D005260:Female; D006044:Goiter, Nodular / Q000175:diagnosis* / Q000276:immunology; D006111:Graves Disease / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay / Q000379:methods; D011989:Receptors, Thyrotropin / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012042:Registries; D012680:Sensitivity and Specificity; D013552:Swine
chemical_list: D001323:Autoantibodies; D011989:Receptors, Thyrotropin; D011994:Recombinant Proteins