The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
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Diagnostic Value of a Chimeric TSH Receptor (Mc4)-Based Bioassay for Graves' Disease

  • Lee, Ji-In (Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jang, Hye-Won (Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Soo-Kyoung (Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Choi, Joon-Young (Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Ji-Young (Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Hur, Kyu-Yeon (Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Jae-Hyeon (Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Min, Yong-Ki (Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Chung, Jae-Hoon (Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Sun-Wook (Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • Published : 2011.06.01
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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 $Thyretain^{TM}$ 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

References

  1. Brent GA. Clinical practice: Graves' disease. N Engl J Med 2008;358:2594-2605. https://doi.org/10.1056/NEJMcp0801880
  2. Ajjan RA, Weetman AP. Techniques to quantify TSH receptor antibodies. Nat Clin Pract Endocrinol Metab 2008;4:461-468. https://doi.org/10.1038/ncpendmet0886
  3. Smith BR, Bolton J, Young S, et al. A new assay for thyrotropin receptor autoantibodies. Thyroid 2004;14:830-835.
  4. Villalta D, Orunesu E, Tozzoli R, et al. Analytical and diagnostic accuracy of "second generation" assays for thyrotrophin receptor antibodies with radioactive and chemiluminescent tracers. J Clin Pathol 2004;57:378-382. https://doi.org/10.1136/jcp.2003.012294
  5. Ochi Y, Kajita Y, Wu L, Iidaka M, Nagayama Y. Augmentative effect of polyethylene glycol, polyvinyl alcohol and dextran on thyroid-stimulating antibody stimulated cAMP production in FRTL-5 cells and CHO cells expressing human TSH receptor. Horm Res 2000;53:20-25.
  6. Preissner CM, Wolhuter PJ, Sistrunk JW, Homburger HA, Morris JC 3rd. Comparison of thyrotropin-receptor antibodies measured by four commercially available methods with a bioassay that uses Fisher rat thyroid cells. Clin Chem 2003;49:1402-1404. https://doi.org/10.1373/49.8.1402
  7. Hovens GC, Buiting AM, Karperien M, et al. A bioluminescence assay for thyrotropin receptor antibodies predicts serum thyroid hormone levels in patients with de novo Graves' disease. Clin Endocrinol (Oxf) 2006;64:429-435.
  8. Tahara K, Ban T, Minegishi T, Kohn LD. Immunoglobulins from Graves' disease patients interact with different sites on TSH receptor/LH-CG receptor chimeras than either TSH or immunoglobulins from idiopathic myxedema patients. Biochem Biophys Res Commun 1991;179:70-77. https://doi.org/10.1016/0006-291X(91)91335-A
  9. Lytton SD, Ponto KA, Kanitz M, Matheis N, Kohn LD, Kahaly GJ. A novel thyroid stimulating immunoglobulin bioassay is a functional indicator of activity and severity of Graves' orbitopathy. J Clin Endocrinol Metab 2010;95:2123-2131. https://doi.org/10.1210/jc.2009-2470
  10. Kamijo K, Murayama H, Uzu T, Togashi K, Kahaly GJ. A novel bioreporter assay for thyrotropin receptor antibodies using a chimeric thyrotropin receptor (mc4) is more useful in differentiation of Graves' disease from painless thyroiditis than conventional thyrotropin-stimulating antibody assay using porcine thyroid cells. Thyroid 2010;20:851-856. https://doi.org/10.1089/thy.2010.0059
  11. Rakover Y, Sadeh O, Sobel E, Shneyour A, Kraiem Z. A case of transient hypothyroidism: sequential serum measurements of autoantibodies inhibiting thyrotropin-stimulated thyroid cAMP production in a neonate. Acta Endocrinol (Copenh) 1990;123:118-122.
  12. Ueda Y, Sugawa H, Akamizu T, et al. Thyroid-stimulating antibodies in sera from patients with Graves' disease are heterogeneous in epitope recognition. Eur J Endocrinol 1995;132:62-68. https://doi.org/10.1530/eje.0.1320062
  13. Kim WB, Chung HK, Park YJ, Park DJ, Lee HK, Cho BY. Clinical significance of classification of Graves' disease according to the characteristics of TSH receptor antibodies. Korean J Intern Med 2001;16:187-200.
  14. Watson PF, Ajjan RA, Phipps J, Metcalfe R, Weetman AP. A new chemiluminescent assay for the rapid detection of thyroid stimulating antibodies in Graves' disease. Clin Endocrinol (Oxf) 1998;49:577-581. https://doi.org/10.1046/j.1365-2265.1998.00619.x
  15. Evans C, Morgenthaler NG, Lee S, et al. Development of a luminescent bioassay for thyroid stimulating antibodies. J Clin Endocrinol Metab 1999;84:374-377. https://doi.org/10.1210/jc.84.1.374
  16. Grasso YZ, Kim MR, Faiman C, Kohn LD, Tahara K, Gupta MK. Epitope heterogeneity of thyrotropin receptor-blocking antibodies in Graves' patients as detected with wild-type versus chimeric thyrotropin receptors. Thyroid 1999;9:531-537. https://doi.org/10.1089/thy.1999.9.531
  17. Kim JY, Kim KR. Dietary iodine intake and urinary iodine excretion in patients with thyroid diseases. Yonsei Med J 2000;41:22-28.
  18. Kim JY, Moon SJ, Kim KR, Sohn CY, Oh JJ. Dietary iodine intake and urinary iodine excretion in normal Korean adults. Yonsei Med J 1998;39:355-362.
  19. Flynn A, Hirvonen T, Mensink GB, et al. Intake of selected nutrients from foods, from fortification and from supplements in various European countries. Food Nutr Res 2009;53. DOI: 10.3402/fnr.v53i0.2038.

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