Korean J Intern Med.  2011 Jun;26(2):179-186. 10.3904/kjim.2011.26.2.179.

Diagnostic Value of a Chimeric TSH Receptor (Mc4)-Based Bioassay for Graves' Disease

• Lee JI
• Jang HW
• Kim SK
• Choi JY
• Kim JY
• Hur KY
• Kim JH
• Min YK
• Chung JH
• Kim SW

• KMID: 1776590
• DOI: http://doi.org/10.3904/kjim.2011.26.2.179

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 Thyretaintrade mark 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) (rs = 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.

Keyword

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

MeSH Terms

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