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
Cesidio Giuliani, Dominique Cerrone, Norikazu Harii, Mark Thornton, Leonard D. Kohn, Nilesh M. Dagia, Ines Bucci, Maria Carpentieri, Barbara Di Nenno, Andrea Di Blasio, Paolo Vitti, Fabrizio Monaco and Giorgio Napolitano
- Author Affiliations

56127 Pisa, Italy

Abstract

Context: 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.

Design: An Mc4 assay was used to prospectively track TSAb activity in GD patients treated with ATD over a 5-yr period.

Setting and Patients: GD patients from the Chieti University participated in this study.

Interventions: 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.

Main Outcome Measures: 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.

Conclusion: The Mc4 assay is a clinically useful index of remission and relapse in patients with GD. Larger studies are required to confirm these findings.