title: A TSHR-LH/CGR chimera that measures functional thyroid-stimulating autoantibodies (TSAb) can predict remission or recurrence in Graves' patients undergoing antithyroid drug (ATD) treatment.
abstract: BACKGROUND
  A functional thyroid-stimulating autoantibodies (TSAb) assay using a thyroid-stimulating hormone receptor chimera (Mc4) appears to be clinically more useful than the commonly used assay, a binding assay that measures all the antibodies binding to the thyroid-stimulating hormone receptor without functional discrimination, in diagnosing patient with Graves' disease (GD).
  
  
  OBJECTIVE
  The objective of the study was to investigate whether an Mc4 assay can predict relapse/remission of hyperthyroidism after antithyroid drug (ATD) treatment in patients with GD.
  
  
  METHODS
  An Mc4 assay was used to prospectively track TSAb activity in GD patients treated with ATD over a 5-yr period.
  
  
  METHODS
  GD patients from the Chieti University participated in this study.
  
  
  METHODS
  Interventions included the assessment of patients' sera using the Mc4 assay, the Mc4-derivative assay (Thyretain), and a human monoclonal thyroid-stimulating hormone receptor antibody, M22 assay.
  
  
  METHODS
  The Mc4 assay, a sensitive index of remission and recurrence, was used in this study.
  
  
  RESULTS
  The TSAb levels significantly decreased only in the remitting group as evidenced by Mc4 assay values at the end of ATD (0.96 ± 1.47, 10.9 ± 26.6. and 24.7 ± 37.5 arbitrary units for the remitting, relapsing, and unsuspended therapy groups, respectively). Additional prognostic help was obtained by thyroid volume measurements at the end of treatment. Although not statistically significant, the Mc4 assay has a trend toward improved positive predictive value (95.4 vs. 84.2 or 87.5%), specificity (96.4 vs. 86.4 and 90.9%), and accuracy (87.3 vs. 83.3 and 80.9%) comparing the Mc4, Thyretain, and M22 assays, respectively. Thyretain has a trend toward improved negative predictive value (82.6 vs. 81.8 and 76.9%) and sensitivity (80 vs. 77.8 and 70%) comparing Thyretain, Mc4, and M22 assays, respectively.
  
  
  CONCLUSIONS
  The Mc4 assay is a clinically useful index of remission and relapse in patients with GD. Larger studies are required to confirm these findings.
authors.affiliation: Unit of Endocrinology, Department of Medicine and Sciences of Aging, University "G. D'Annunzio" and Aging Research Center, "Gabriele D'Annunzio" University Foundation, 66013 Chieti-Pescara, Italy.
authors.forename: Cesidio
authors.initials: C
authors.lastname: Giuliani
authors.forename: Dominique
authors.initials: D
authors.lastname: Cerrone
authors.forename: Norikazu
authors.initials: N
authors.lastname: Harii
authors.forename: Mark
authors.initials: M
authors.lastname: Thornton
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Kohn
authors.forename: Nilesh M
authors.initials: NM
authors.lastname: Dagia
authors.forename: Ines
authors.initials: I
authors.lastname: Bucci
authors.forename: Maria
authors.initials: M
authors.lastname: Carpentieri
authors.forename: Barbara
authors.initials: B
authors.lastname: Di Nenno
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Blasio
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitti
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Monaco
authors.forename: Giorgio
authors.initials: G
authors.lastname: Napolitano
mesh_terms: D000328:Adult; D000818:Animals; D013956:Antithyroid Agents / Q000627:therapeutic use; D001323:Autoantibodies / Q000032:analysis / Q000097:blood; D016466:CHO Cells; D002986:Clinical Trials as Topic / Q000379:methods; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005500:Follow-Up Studies; D006111:Graves Disease / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating / Q000032:analysis* / Q000097:blood; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011974:Receptors, LH / Q000032:analysis* / Q000737:chemistry / Q000502:physiology; D011989:Receptors, Thyrotropin / Q000032:analysis* / Q000737:chemistry / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012008:Recurrence; D012074:Remission Induction; D013960:Thyroid Function Tests / Q000379:methods; D055815:Young Adult
chemical_list: D013956:Antithyroid Agents; D001323:Autoantibodies; D018828:Immunoglobulins, Thyroid-Stimulating; D011974:Receptors, LH; D011989:Receptors, Thyrotropin; D011993:Recombinant Fusion Proteins