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Bedeutung der TSH-Rezeptor-Antikörper für die Diagnose des Morbus Basedow sowie die Prognoseabschätzung der Schilddrüsenüberfunktion und der endokrinen Orbitopathie

Stellungnahme der Sektion Schilddrüse der DGE

Role of TSH Receptor Autoantibodies for the Diagnosis of Graves’ Disease and for the Prediction of the Course of Hyperthyroidism and Ophthalmopathy. Recommendations of the Thyroid Section of the German Society of Endocrinology

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Zusammenfassung

Die Autoimmunhyperthyreose (Synonym Morbus Basedow) ist eine antikörpervermittelte Autoimmunerkrankung, bei der es zu einer Stimulation der Schilddrüse, aber auch anderer Zielgewebe kommt. Neben der Hyperthyreose können extrathyreoidale Manifestationen wie die endokrine Orbitopathie (EO) auftreten.

Zur Diagnosesicherung des Morbus Basedow sollten die TSH-Rezeptor-Autoantikörper (TRAK) bestimmt werden. Aufgrund der deutlich höheren Sensitivität und Spezifität sollten anstelle überholter TRAK-Assays der ersten Generation (Einheiten in U/l) Assays der zweiten Generation (Einheiten in IU/l) verwendet werden. Für einen Teil der Patienten ist eine Prognoseabschätzung des Morbus Basedow mit hoher Wahrscheinlichkeit durch eine Bestimmung der TRAK im Verlauf der Erkrankung möglich, so dass eine Operation bzw. Radiojodtherapie mit hohen TRAK-Werten schon vor Ablauf des 1. Jahres (frühestens nach 6 Monaten bei einem TRAK-Wert von > 10 IU/l) einer thyreostatischen Therapie empfohlen werden kann. Für Patienten mit niedrigeren TRAK-Werten kann keine sichere Vorhersage getroffen werden.

Mittels der TRAK-Bestimmung auf der Basis eines Assays der zweiten Generation kann auch der Verlauf der EO abgeschätzt werden, womit Therapieentscheidungen beeinflusst werden können.

Abstract

Graves’ disease (GD) is the only autoimmune disease where autoantibodies stimulate the target organs. Among the most common clinical manifestations are hyperthyroidism and orbitopathy (GO).

To ensure the diagnosis of autoimmune hyperthyroidism, activity of TSH receptor autoantibodies (TRAb) should be determined. Because of their significantly improved sensitivity and equal specificity, second-generation TRAb assays (activity given in IU/l) should be preferred over first-generation assays (activity given in U/l). During follow-up of antithyroid drug therapy it is possible to predict outcome for some patients with high chances if TRAb levels are high. On this basis, thyreoablative treatment (operation or radioiodine) can already be indicated before the 1st year of antithyroid drug treatment has passed. If TRAb antibody titers are > 10 IU/l, it is possible to predict outcome as early as 6 months after initiation of antithyroid drug therapy. Below a certain threshold, depending on the time point of measurement, no representative risk analyses are available for TRAbs.

TRAb measurement is also helpful to determine the course of GO. This may guide the physician through crucial treatment decisions, especially if the patient is at risk of deterioration.

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Literatur

  1. Ando T, Latif R, Pritsker A, et al. A monoclonal thyroid-stimulating antibody. J Clin Invest 2002;110:1667–74.

    PubMed  CAS  Google Scholar 

  2. Andrade VA, Gross JL, Maia AL, et al. Serum thyrotropin-receptor autoantibodies levels after I therapy in Graves’ patients: effect of pretreatment with methimazole evaluated by a prospective, randomized study. Eur J Endocrinol 2004;151:467–74.

    Article  PubMed  CAS  Google Scholar 

  3. Bahn RS, Dutton CM, Natt N, et al. Thyrotropin receptor expression in Graves’ orbital adipose/connective tissues: potential autoantigen in Graves’ ophthalmopathy. J Clin Endocrinol Metab 1998;83:998–1002.

    Article  PubMed  CAS  Google Scholar 

  4. Bartalena L, Marcocci C, Tanda L, et al. Management of thyroid eye disease. Eur J Nucl Med Mol Imaging 2002;29:Suppl 2:S458–65.

    PubMed  Google Scholar 

  5. Bartalena L, Tanda ML, Bogazzi F, et al. An update on the pharmacological management of hyperthyroidism due to Graves’ disease. Expert Opin Pharmacother 2005;6:851–61.

    Article  PubMed  CAS  Google Scholar 

  6. Benker G, Kotulla P, Kendall-Taylor P, et al. TSH binding-inhibiting antibodies in hyperthyroidism: relationship to clinical signs and hormone levels. Clin Endocrinol (Oxf) 1989;30:19–28.

    Article  CAS  Google Scholar 

  7. Benker G, Vitti P, Kahaly G, et al. Response to methimazole in Graves’ disease. The European Multicenter Study Group. Clin Endocrinol (Oxf) 1995;43:257–63.

    Article  CAS  Google Scholar 

  8. Carella C, Mazziotti G, Sorvillo F, et al. Serum thyrotropin receptor antibodies concentrations in patients with Graves’ disease before, at the end of methimazole treatment, and after drug withdrawal: evidence that the activity of thyrotropin receptor antibody and/or thyroid response modify during the observation period. Thyroid 2006;16:295–302.

    Article  PubMed  CAS  Google Scholar 

  9. Costagliola S, Franssen JD, Bonomi M, et al. Generation of a mouse monoclonal TSH receptor antibody with stimulating activity. Biochem Biophys Res Commun 2002;299:891–6.

    Article  PubMed  CAS  Google Scholar 

  10. Costagliola S, Morgenthaler NG, Hoermann R, et al. Second generation assay for thyrotropin receptor antibodies has superior diagnostic sensitivity for Graves’ disease. J Clin Endocrinol Metab 1999;84:90–7.

    Article  PubMed  CAS  Google Scholar 

  11. Crisp MS, Lane C, Halliwell M, et al. Thyrotropin receptor transcripts in human adipose tissue. J Clin Endocrinol Metab 1997;82:2003–5.

    PubMed  CAS  Google Scholar 

  12. Dunkelmann S, Neumann V, Staub U, et al. [Results of a risk adapted and functional radioiodine therapy in Graves’ disease.] Nuklearmedizin 2005;44:238–42.

    PubMed  CAS  Google Scholar 

  13. Eckstein A, Loesch C, Glowacka D, et al. Euthyroid and primarily hypothyroid patients develop milder and significantly more asymmetric Graves ophthalmopathy. Br J Ophthalmol 2009:67:607–12.

    Google Scholar 

  14. Eckstein AK, Finkenrath A, Heiligenhaus A, et al. Dry eye syndrome in thyroid-associated ophthalmopathy: lacrimal expression of TSH receptor suggests involvement of TSHR-specific autoantibodies. Acta Ophthalmol Scand 2004;82:291–7.

    Article  PubMed  CAS  Google Scholar 

  15. Eckstein AK, Lax H, Losch C, et al. Patients with severe Graves’ ophthalmopathy have a higher risk of relapsing hyperthyroidism and are unlikely to remain in remission. Clin Endocrinol (Oxf) 2007;67:607–12.

    Google Scholar 

  16. Eckstein AK, Plicht M, Lax H, et al. Clinical results of anti-inflammatory therapy in Graves’ ophthalmopathy and association with thyroidal autoantibodies. Clin Endocrinol (Oxf) 2004;61:612–8.

    Article  Google Scholar 

  17. Eckstein AK, Plicht M, Lax H, et al. Thyrotropin receptor autoantibodies are independent risk factors for Graves’ ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab 2006;91:3464–70.

    Article  PubMed  CAS  Google Scholar 

  18. Feldt-Rasmussen U, Schleusener H, Carayon P, et al. Meta-analysis evaluation of the impact of thyrotropin receptor antibodies on long term remission after medical therapy of Graves’ disease. J Clin Endocrinol Metab 1994;78:98–102.

    Article  PubMed  CAS  Google Scholar 

  19. Gerding MN, van der Meer JW, Broenink M, et al. Association of thyrotrophin receptor antibodies with the clinical features of Graves’ ophthalmopathy. Clin Endocrinol (Oxf) 2000;52:267–71.

    Article  CAS  Google Scholar 

  20. Giovanella L, Ceriani L, Garancini S, et al. Clinical applications of the 2nd generation assay for anti-TSH receptor antibodies in Graves’ disease. Evaluation in patients with negative 1st generation test. Clin Chem Lab Med 2001;39:25–8.

    Article  PubMed  CAS  Google Scholar 

  21. Glinoer D, de Nayer P, Bex M, et al. Effects of 1-thyroxine administration, TSH-receptor antibodies and smoking on the risk of recurrence in Graves’ hyperthyroidism treated with antithyroid drugs: a double-blind prospective randomized study. Eur J Endocrinol 2001;144:475–83.

    Article  PubMed  CAS  Google Scholar 

  22. Hensen J, Kotulla P, Finke R, et al. 10 years experience with consecutive measurement of thyrotropin binding inhibiting antibodies (TBIAb). J Endocrinol Invest 1984;7:215–20.

    PubMed  CAS  Google Scholar 

  23. Hermsen D, Broecker-Preuss M, Casati M, et al. Technical evaluation of the first fully automated assay for the detection of TSH receptor autoantibodies. Clin Chim Acta 2009;401:84–9.

    Article  PubMed  CAS  Google Scholar 

  24. Hoermann R, Quadbeck B, Roggenbuck U, et al. Relapse of Graves’ disease after successful outcome of antithyroid drug therapy: results of a prospective randomized study on the use of levothyroxine. Thyroid 2002;12:1119–28.

    Article  PubMed  CAS  Google Scholar 

  25. Kakinuma A, Morimoto I, Kuroda T, et al. Comparison of recombinant human thyrotropin receptors versus porcine thyrotropin receptors in the thyrotropin binding inhibition assay for thyrotropin receptor autoantibodies. Thyroid 1999;9:849–55.

    Article  PubMed  CAS  Google Scholar 

  26. Kamijo K. TSH-receptor antibody measurement in patients with various thyrotoxicosis and Hashimoto’s thyroiditis: a comparison of two two-step assays, coated plate ELISA using porcine TSH-receptor and coated tube radioassay using human recombinant TSH-receptor. Endocr J 2003;50:113–6.

    Article  PubMed  CAS  Google Scholar 

  27. Khoo DH, Ho SC, Seah LL, et al. The combination of absent thyroid peroxidase antibodies and high thyroid-stimulating immunoglobulin levels in Graves’ disease identifies a group at markedly increased risk of ophthalmopathy. Thyroid 1999;9:1175–80.

    Article  PubMed  CAS  Google Scholar 

  28. Laurberg P, Wallin G, Tallstedt L, et al. TSH-receptor autoimmunity in Graves’ disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study. Eur J Endocrinol 2008;158:69–75.

    Article  PubMed  CAS  Google Scholar 

  29. Manji N, Carr-Smith JD, Boelaert K, et al. Influences of age, gender, smoking, and family history on autoimmune thyroid disease phenotype. J Clin Endocrinol Metab 2006;91:4873–80.

    Article  PubMed  CAS  Google Scholar 

  30. Massart C, Orgiazzi J, Maugendre D, et al. Clinical validity of a new commercial method for detection of TSH-receptor binding antibodies in sera from patients with Graves’ disease treated with antithyroid drugs. Clin Chim Acta 2001;304:39–47.

    Article  PubMed  CAS  Google Scholar 

  31. Maugendre D, Massart C. Clinical value of a new TSH binding inihibitory activity assay using human TSH receptors in the follow-up of antithyroid drug treated Graves’ disease. Comparison with thyroid stimulating antibody bioassay. Clin Endocrinol (Oxf) 2001;54:89–96.

    Article  CAS  Google Scholar 

  32. Meller J, Schreivogel I, Bergmann A, et al. [Clinical implications of a new TSH receptor antibody assay (DYNOtest TRAKhuman) in autoimmune thyroid diseases.] Nuklearmedizin 2000;39:14–8.

    PubMed  CAS  Google Scholar 

  33. Morgenthaler N. TSH-receptor autoantibodies. In: Wiersinga W, Drexhage HA, Weetman AP, et al., eds. The thyroid and autoimmunity. Stuttgart-New York: Thieme, 2006:126–32.

    Google Scholar 

  34. Morgenthaler NG, Ho SC, Minich WB, et al. Stimulating and blocking thyroid-stimulating hormone (TSH) receptor autoantibodies from patients with Graves’ disease and autoimmune hypothyroidism have very similar concentration, TSH receptor affinity, and binding sites. J Clin Endocrinol Metab 2007;92:1058–65.

    Article  PubMed  CAS  Google Scholar 

  35. Mourits MP, Prummel MF, Wiersinga WM, et al. Clinical Activity Score as a guide in the management of patients with Graves’ ophthalmopathy. Clin Endocrinol (Oxf) 1997;47:9–14.

    Article  CAS  Google Scholar 

  36. Noh JY, Hamada N, Inoue Y, et al. Thyroid-stimulating antibody is related to Graves’ ophthalmopathy, but thyrotropin-binding inhibitor immunoglobulin is related to hyperthyroidism in patients with Graves’ disease. Thyroid 2000;10:809–13.

    Article  PubMed  CAS  Google Scholar 

  37. Okamoto Y, Tanigawa S, Ishikawa K, et al. TSH receptor antibody measurements and prediction of remission in Graves’ disease patients treated with minimum maintenance doses of antithyroid drugs. Endocr J 2006;53:467–72.

    Article  PubMed  CAS  Google Scholar 

  38. Orgiazzi J, Madec AM. Reduction of the risk of relapse after withdrawal of medical therapy for Graves’ disease. Thyroid 2002;12:849–53.

    Article  PubMed  CAS  Google Scholar 

  39. Perros P, Kendall-Taylor P. Natural history of thyroid eye disease. Thyroid 1998;8:423–5.

    Article  PubMed  CAS  Google Scholar 

  40. Perros P, Kendall-Taylor P, Neoh C, et al. A prospective study of the effects of radioiodine therapy for hyperthyroidism in patients with minimally active Graves’ ophthalmopathy. J Clin Endocrinol Metab 2005;90:5321–3.

    Article  PubMed  CAS  Google Scholar 

  41. Quadbeck B, Hoermann R, Hahn S, et al. Binding, stimulating and blocking TSH receptor antibodies to the thyrotropin receptor as predictors of relapse of Graves’ disease after withdrawal of antithyroid treatment. Horm Metab Res 2005;37:745–50.

    Article  PubMed  CAS  Google Scholar 

  42. Quadbeck B, Roggenbuck U, Janssen OE, et al. Impact of smoking on the course of Graves’ disease after withdrawal of antithyroid drugs. Exp Clin Endocrinol Diabetes 2006;114:406–11.

    Article  PubMed  CAS  Google Scholar 

  43. Reinhardt MJ, Brink I, Joe AY, et al. Radioiodine therapy in Graves’ disease based on tissue-absorbed dose calculations: effect of pre-treatment thyroid volume on clinical outcome. Eur J Nucl Med Mol Imaging 2002;29:1118–24.

    Article  PubMed  CAS  Google Scholar 

  44. Sabri O, Zimny M, Schreckenberger M, et al. [Characterization of therapy failures in radioiodine therapy of Graves’ disease without simultaneous antithyroid agents.] Nuklearmedizin 2001;40:1–6.

    PubMed  CAS  Google Scholar 

  45. Sanders J, Evans M, Premawardhana LD, et al. Human monoclonal thyroid stimulating autoantibody. Lancet 2003;362:126–8.

    Article  PubMed  CAS  Google Scholar 

  46. Schott M, Eckstein AK, Willenberg HS, et al. Improved prediction of relapse of Graves’ thyrotoxicosis by combined determination of TSH receptor and thyroperoxidase antibodies. Horm Metab Res 2007;39:56–61.

    Article  PubMed  CAS  Google Scholar 

  47. Schott M, Feldkamp J, Bathan C, et al. Detecting TSH-receptor antibodies with the recombinant TBII assay: technical and clinical evaluation. Horm Metab Res 2000;32:429–35.

    Article  PubMed  CAS  Google Scholar 

  48. Schott M, Hermsen D, Broecker-Preuss M, et al. Clinical value of the first automated TSH receptor autoantibody assay for the diagnosis of Graves’ disease: an international multicenter trial. Clin Endocrinol (Oxf) 2009:in press.

  49. Schott M, Morgenthaler NG, Fritzen R, et al. Levels of autoantibodies against human TSH receptor predict relapse of hyperthyroidism in Graves’ disease. Horm Metab Res 2004;36:92–6.

    Article  PubMed  CAS  Google Scholar 

  50. Tallstedt L, Lundell G, Torring O, et al. Occurrence of ophthalmopathy after treatment for Graves’ hyperthyroidism. The Thyroid Study Group. N Engl J Med 1992;326:1733–8.

    PubMed  CAS  Google Scholar 

  51. Terwee CB, Prummel MF, Gerding MN, et al. Measuring disease activity to predict therapeutic outcome in Graves’ ophthalmopathy. Clin Endocrinol (Oxf) 2005;62:145–55.

    Article  CAS  Google Scholar 

  52. Wakelkamp IM, Bakker O, Baldeschi L, et al. TSH-R expression and cytokine profile in orbital tissue of active vs. inactive Graves’ ophthalmopathy patients. Clin Endocrinol (Oxf) 2003;58:280–7.

    Article  CAS  Google Scholar 

  53. Weetman AP. Graves’ disease 1835-2002. Horm Res 2003;59:Suppl 1:114–8.

    Article  PubMed  CAS  Google Scholar 

  54. Wiersinga WM, Bartalena L. Epidemiology and prevention of Graves’ ophthalmopathy. Thyroid 2002;12:855–60.

    Article  PubMed  Google Scholar 

  55. Zimmermann-Belsing T, Nygaard B, Rasmussen AK, et al. Use of the 2nd generation TRAK human assay did not improve prediction of relapse after antithyroid medical therapy of Graves’ disease. Eur J Endocrinol 2002;146:173–7.

    Article  PubMed  CAS  Google Scholar 

  56. Zöphel K, Landenberg P von, Roggenbuck D, et al. Are porcine and human TSH receptor antibody measurements comparable? Clin Lab 2008;54:1–8.

    PubMed  Google Scholar 

  57. Zöphel K, Wunderlich G, Koch R, et al. [Measurement of thyrotropin receptor antibodies (TRAK) with a second generation assay in patients with Graves’ disease.] Nuklearmedizin 2000;39:113–20.

    PubMed  Google Scholar 

  58. Zöphel K, Wunderlich G, Kopprasch C, et al. [Predictive value of thyrotropin receptor antibodies using the second generation TRAb human assay after radioiodine treatment in Graves’ disease.] Nuklearmedizin 2003;42:63–70.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Zentrum für Augenheilkunde, Universitätsklinikum Essen, Essen, Germany

    Anja Eckstein

  2. Klinik für Endokrinologie, Universitätsklinikum Essen, Essen, Germany

    Klaus Mann

  3. I. Medizinische Universitätsklinik und Poliklinik Mainz, Mainz, Germany

    George J. Kahaly

  4. Gemeinschaftspraxis Endokrinologie und Diabetologie, Stuttgart, Germany

    Martin Grußendorf

  5. Klinik und Poliklinik für Nuklearmedizin, Universität Würzburg, Würzburg, Germany

    Christoph Reiners

  6. Klinik für Allgemeine Innere Medizin, Endokrinologie und Diabetologie, Städtische Kliniken Bielefeld, Bielefeld, Germany

    Joachim Feldkamp

  7. Praxis für Endokrinologie, Düsseldorf, Germany

    Beate Quadbeck

  8. Klinik für Nuklearmedizin, Universitätsklinikum Essen, Essen, Germany

    Andreas Bockisch

  9. Klinik für Endokrinologie, Diabetologie und Rheumatologie, Universitätsklinikum Düsseldorf, Düsseldorf, Germany

    Matthias Schott

  10. Klinik für Endokrinologie, Diabetologie und Rheumatologie, Universitätsklinikum Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany

    Matthias Schott

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  1. Anja Eckstein
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  2. Klaus Mann
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Eckstein, A., Mann, K., Kahaly, G.J. et al. Bedeutung der TSH-Rezeptor-Antikörper für die Diagnose des Morbus Basedow sowie die Prognoseabschätzung der Schilddrüsenüberfunktion und der endokrinen Orbitopathie. Med Klin 104, 343–348 (2009). https://doi.org/10.1007/s00063-009-1072-0

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  • DOI: https://doi.org/10.1007/s00063-009-1072-0

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