title: Accuracy of receptor-based methods for detection of thyrotropin-receptor autoantibodies: a new automated third-generation immunoassay shows higher analytical and clinical sensitivity for the differential diagnosis of hyperthyroidism.
abstract: OBJECTIVE
  Specific autoantibodies acting as TSH receptor agonists (TRAb) are responsible for Graves' disease (GD). In the last 30 years three generations of assay methods for the detection of TRAb have become available. The aim of this multicentre study was to evaluate the analytical sensitivity, precision and diagnostic accuracy of TRAb measurement using a new automated assay in comparison with a second-generation standard method.
  
  
  METHODS
  Serum samples from patients with GD (n=82), autoimmune thyroiditis (AIT, n=57) or hyperthyroidism (HT, n=292), from 106 healthy subjects and from 57 patients with infectious diseases were analysed using a third-generation TRAb immunoassay (anti-TSHR, RAD 120; Radim, Italy) based on the human monoclonal TSH receptor antibody M22.
  
  
  RESULTS
  Using a cut-off value of 1.25 mIU/l, established by ROC curve analysis, 80/82 GD patients (97.5%), 68/292 HT patients (23.2%), and 6/57 AIT patients (10.5%) were TRAb-positive with the M22-based automated assay. The percentages of TRAb positivity were lower in the same patients when the measurements were done with the second-generation method (95.1%, 18.9%, 7.0%, respectively).
  
  
  CONCLUSIONS
  The M22-based automated immunoassay shows high functional sensitivity (0.4 mIU/l) and high diagnostic specificity, is more sensitive than the standard second-generation method and is less time-consuming and labourintensive, and is therefore the up-to-date technology for TRAb detection in clinical practice.
authors.affiliation: Clinical Pathology Laboratory, Beata Vergine delle Grazie Hospital, Latisana, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Tozzoli
authors.affiliation: Clinical Pathology Laboratory, Beata Vergine delle Grazie Hospital, Latisana, Italy.
authors.forename: Graziano
authors.initials: G
authors.lastname: Kodermaz
authors.affiliation: Allergology and Immunology Unit, S. Maria degli Angeli Hospital, Pordenone, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Villalta
authors.affiliation: Department of Internal Medicine, S. Martino Hospital, University of Genua, Genua, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Bagnasco
authors.affiliation: Department of Internal Medicine, S. Martino Hospital, University of Genua, Genua, Italy.
authors.forename: Giampaola
authors.initials: G
authors.lastname: Pesce
authors.affiliation: Clinical Pathology Laboratory, S. Antonio Hospital, Tolmezzo, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Bizzaro
keywords: Automated TRAb immunoassay; Graves’ disease; Hyperthyroidism; Sensitivity; Specificity; TSHR antibodies