The cloning and sequencing of thyroid-stimulating hormone (TSH) receptor (TSHR), combined with advances in molecular techniques, have facilitated the understanding of the interaction of the TSHR antibodies (TSHRAbs) with the TSHR at the molecular level and have allowed the delineation of their clinical role. TSHRAbs in vivo are functionally heterogeneous; the stimulating TSHRAbs cause hyperthyroidism and diffuse goiter in patients with Graves' disease, whereas, the blocking TSHRAbs cause hypothyroidism in some patients with autoimmune hypothyroidism and are the cause of transient neonatal hypothyroidism. Measuring TSHRAbs has potential clinical implications in differential diagnosis of Graves' disease, predicting the outcome of Graves' disease after antithyroid drug treatment, and predicting the fetal/neonatal hyperthyroidism or neonatal hypothyroidism. The existence of epitope heterogeneity in a patient, i.e., of stimulating TSHRAbs with epitopes other than on the N-terminal region of the extracellular domain, is significantly associated with favorable long-term clinical response to antithyroid drug treatment. Measuring these subtypes for thyroid-stimulating antibody (TSAb) has potential clinical impli-cations, for example, in predicting responsiveness to treatment in untreated patients with Graves' disease.
Autoantibodies/*immunology ; Epitopes/immunology ; Graves Disease/diagnosis/immunology/therapy ; Humans ; Hyperthyroidism/diagnosis/*immunology/therapy ; Hypothyroidism/diagnosis/*immunology/therapy ; Immunoglobulins, Thyroid-Stimulating ; Receptors, Thyrotropin/*immunology

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.
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