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

Springer Science and Business Media LLC - Tập 104 - Trang 343-348 - 2009
Anja Eckstein1, Klaus Mann2, George J. Kahaly3, Martin Grußendorf4, Christoph Reiners5, Joachim Feldkamp6, Beate Quadbeck7, Andreas Bockisch8, Matthias Schott9
1Zentrum für Augenheilkunde, Universitätsklinikum Essen, Essen, Germany
2Klinik für Endokrinologie, Universitätsklinikum Essen, Essen, Germany
3I. Medizinische Universitätsklinik und Poliklinik Mainz, Mainz, Germany
4Gemeinschaftspraxis Endokrinologie und Diabetologie, Stuttgart, Germany
5Klinik und Poliklinik für Nuklearmedizin, Universität Würzburg, Würzburg, Germany
6Klinik für Allgemeine Innere Medizin, Endokrinologie und Diabetologie, Städtische Kliniken Bielefeld, Bielefeld, Germany
7Praxis für Endokrinologie, Düsseldorf, Germany
8Klinik für Nuklearmedizin, Universitätsklinikum Essen, Essen, Germany
9Klinik für Endokrinologie, Diabetologie und Rheumatologie, Universitätsklinikum Düsseldorf, Düsseldorf, Germany

Tóm tắt

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.

Tài liệu tham khảo

Ando T, Latif R, Pritsker A, et al. A monoclonal thyroid-stimulating antibody. J Clin Invest 2002;110:1667–74. 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. 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. 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. 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. 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. 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. 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. 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. 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. Crisp MS, Lane C, Halliwell M, et al. Thyrotropin receptor transcripts in human adipose tissue. J Clin Endocrinol Metab 1997;82:2003–5. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. Orgiazzi J, Madec AM. Reduction of the risk of relapse after withdrawal of medical therapy for Graves’ disease. Thyroid 2002;12:849–53. Perros P, Kendall-Taylor P. Natural history of thyroid eye disease. Thyroid 1998;8:423–5. 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. 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. 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. 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. 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. Sanders J, Evans M, Premawardhana LD, et al. Human monoclonal thyroid stimulating autoantibody. Lancet 2003;362:126–8. 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. 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. 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. 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. 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. 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. 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. Weetman AP. Graves’ disease 1835-2002. Horm Res 2003;59:Suppl 1:114–8. Wiersinga WM, Bartalena L. Epidemiology and prevention of Graves’ ophthalmopathy. Thyroid 2002;12:855–60. 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. Zöphel K, Landenberg P von, Roggenbuck D, et al. Are porcine and human TSH receptor antibody measurements comparable? Clin Lab 2008;54:1–8. 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. 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.