Diagnostic value of a chimeric TSH receptor (Mc4)-based bioassay for Graves' disease

Korean J Intern Med. 2011 Jun;26(2):179-86. doi: 10.3904/kjim.2011.26.2.179. Epub 2011 Jun 1.

Abstract

Background/aims: Graves' disease (GD) is caused by thyroid-stimulating hormone receptor (TSHR) and thyroid-stimulating immunoglobulin (TSI). We used a recently introduced, technically enhanced TSI bioassay to assess its diagnostic value and determine the cut-off in patients in high iodine intake area.

Methods: In a cross-sectional setting, we collected serum from 67 patients with untreated GD, 130 with GD under treatment, 22 with GD in remission, 42 with Hashimoto's thyroiditis, 12 with subacute thyroiditis, 20 with postpartum thyroiditis, and 93 euthyroid controls. TSI was measured using the Thyretain™ bioassay, which is based on Chinese hamster ovary cells transfected with chimeric TSHR (Mc4). TSI levels are reported as a specimen-to-reference ratio percentage (SRR%).

Results: The TSI levels in patients with GD (either treated or not) were significantly higher than those of the remaining patients (p < 0.05). The new bioassay showed a sensitivity of 97.0% and a specificity of 95.9% with a cut-off value of 123.0 SRR% for GD. A weak correlation was found between TSI and thyrotropin-binding inhibiting immunoglobulin (TBII) (r(s) = 0.259, p = 0.03), but no correlation was found between TSI and tri-iodothyronine or free thyroxine.

Conclusions: The Mc4-CHO bioassay showed comparable diagnostic value for GD with the conventional TBII assay. We propose a cut-off of 123.0 SRR% in areas where iodine intake is high.

Keywords: Biological assay; Graves disease; Immunoglobulins, thyroid-stimulating; Receptors, thyrotropin; Thyrotropin-binding inhibitory immunoglobulin.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Adult
  • Animals
  • Biological Assay*
  • Biomarkers / blood
  • CHO Cells
  • Case-Control Studies
  • Cricetinae
  • Cricetulus
  • Cross-Sectional Studies
  • Female
  • Genes, Reporter
  • Graves Disease / diagnosis*
  • Graves Disease / immunology
  • Graves Disease / therapy
  • Hashimoto Disease / diagnosis
  • Humans
  • Immunoglobulins, Thyroid-Stimulating / blood*
  • Luciferases / genetics
  • Luciferases / metabolism
  • Male
  • Middle Aged
  • Postpartum Thyroiditis / diagnosis
  • Predictive Value of Tests
  • Protein Binding
  • Radioimmunoassay
  • Receptors, Thyrotropin / genetics
  • Receptors, Thyrotropin / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Republic of Korea
  • Sensitivity and Specificity
  • Thyroiditis, Subacute / diagnosis
  • Transfection

Substances

  • Biomarkers
  • Immunoglobulins, Thyroid-Stimulating
  • Receptors, Thyrotropin
  • Recombinant Fusion Proteins
  • Luciferases