TRAK-Bestimmung: Aktuelles für die klinische Praxis

Zusammenfassung

Beim Morbus Basedow stimulieren Autoantikörper (Ak) den TSH-Rezeptor (TSH-R) und verursachen so die Hyperthyreose. Der Nachweis der Ak ist daher ein wichtiges Hilfsmittel für Nachweis bzw. Ausschluss eines Morbus Basedow. Die Bestimmung der TSH-R-Ak hat verbreitet Anwendung gefunden und wird in der klinischen Diagnostik meist mittels Radio-Rezeptor-Assays durchgeführt, die TSH-binding-inhibition-Aktivität messen, wobei Schweine-Schilddrüsen-Rezeptoren (für die pTBII-Assay) Verwendung finden. Mit einer neueren Methode, die humane rekombinante TSH-Rezeptoren verwendet, konnte in mehreren Studien, eine signifikant höhere Sensitivität bei gleich bleibend hoher Spezifität zur Diagnose des Morbus Basedow demonstriert werden. Weitere Hauptindikationen sind die Vorhersage eines Rezidivs nach thyreostatischer Therapie und die Bestimmung von Krankheitsaktivität und Schweregrad der endokrinen Orbitopathie. Die vorliegende Arbeit gibt einen Überblick über die wichtigsten methodischen Aspekte mit Darstellung der Konsequenzen für die klinische Praxis.

Abstract

Graves' disease is characterized by autoantibodies (Ab) that stimulate the TSH-Receptor (TSH-R) thereby causing hyperthyroidism. Detection of these Ab is therefore an important tool for confirmation or exclusion of Graves' disease. Determination of TSH-R-Ab has found wide spread use and is mostly performed in clinical routine by radio receptor assays measuring TSH binding inhibitory activity using porcine (pTBII assay). Using a more recent method, applying human recombinant TSH-receptors, many studies revealed a significantly higher sensitivity - without loss of specificity - in diagnosing Graves' disease. Further important indications are prediction of relapse after antithyroid drug therapy and evaluation of disease activity and severity in Graves' ophthalmopathy. This review provides an overview over the most relevant methodological aspects and demonstrates the consequences for clinical practice.

TSH-R-Ak-Assay - Indikationen - Sensitivität - Spezifität

TSH-R-Ab assays - indications - sensitivity - specificity

Literatur

• 1 Adams D D, Purves H D. Abnormal responses in the assay of thyrotropin.  Proceedings of the University of Otago Medical School. 1956;  34 11-12
• 2 Szkudlinski M W, Fremont V, Ronin C, Weintraub B D. Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships.  Physiol Rev. 2002;  82 473-502
• 3 Prabhakar B S, Bahn R S, Smith T J. Current perspective on the pathogenesis of Graves' disease and ophthalmopathy.  Endocr Rev. 2003;  24 802-835
• 4 Rapoport B, Chazenbalk G D, Jaume J C, McLachlan S M. The Thyrotropin (TSH)-Receptor: Interaction with TSH and Autoantibodies.  Endo Rev. 1998;  19 673-716
• 5 Morgenthalter N G. New assay systems for thyrotropin receptor antibodies.  Curr Opin Endocrinol Diabetes. 1999;  6 251-260
• 6 Rees Smith B, Hall R. Binding of thyroid stimulators to thyroid membranes.  FEBS Lett. 1974;  42 301-304
• 7 Shewring G A, Rees Smith B. An improved radioreceptor assay for TSH receptor antibodies.  Clin Endocrinol. 1982;  17 409
• 8 Schott M, Feldkamp J, Bathan C, Fritzen R, Scherbaum W A, Seissler J. Detecting TSH-receptor antibodies with the recombinant TBII assay: technical and clinical evaluation.  Horm Metab Res. 2000;  32 429-435
• 9 Nagayama Y, Kaufman K D, Seto P, Rapoport B. Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor.  Biochem Biophys Res Comm. 1989;  165 1184-1190
• 10 Libert F, Lefort A, Gerard C, Parmentier M, Perret J, Ludgate M, Dumont J E, Vassart G. Cloning, sequencing and expression of the human thyrotropin (TSH) receptor: Evidence for binding of autoantibodies.  Biochem Biophys Res Comm. 1989;  165 1250-1255
• 11 Costagliola S, Rodien P, Many M C, Ludgate M, Vassart G. Genetic immunization against the human thyrotropin receptor causes thyroiditis and allows production of monoclonal antibodies recognizing the native receptor.  J Immunol. 1998;  160 1458-1465
• 12 Costagliola S, Morgenthaler N G, Hoermann R, Badenhoop K, Struck J, Freitag D, Poertl S, Weglöhner W, Hollidt J M, Quadbeck B, Dumont J E, Schumm-Draeger P-M, Bergmann A, Mann K, Vassart G, Usadel K-H. Second generation assay for TSH-receptor antibodies has superior diagnostic sensitivity for Graves' disease.  J Clin Endocrinol Metab. 1999;  84 90-97
• 13 Giovanella L, Ceriani L, Garancini S. Clinical applications of the 2^nd generation assay for anti-TSH receptor antibodies in Graves' disease. Evaluation in patients with negative 1^st generation test.  Clin Chem Lab Med. 2001;  39 25-28
• 14 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
• 15 Zimmermann-Belsing T, Nygaard B, Rasmussen A K, Feldt-Rasmussen U. Use of the 2^nd generation TRAK human assay did not improve prediction of relapse after antithyroid medical therapy of Graves' disease.  Eur J Endocrinol. 2002;  146 173-177
• 16 Pedersen I B, Knudsen N, Perrild H, Ovesen L, Laurberg P. TSH-receptor antibody measurement for differentiation of hyperthyroidism into Graves' disease and multinodular toxic goitre: a comparison of two competitive binding assays.  Clin Endocrinol (Oxf). 2001;  55 381-390
• 17 Meller J, Jauho A, Hüfner M, Gratz S, Becker W. Disseminated thyroid autonomy or Graves' disease: reevaluation by a second generation TSH receptor antibody assay.  Thyroid. 2000;  10 1073-1079
• 18 Wallaschofski H, Kuwert T, Lohmann T. TSH-Receptor Autoantibodies - Differentiation of Hyperthyroidism between Graves' Disease and Toxic Multimodular Goitre.  Exp Clin Endocrinol Diabetes. 2004;  112 171-174
• 19 Davies T F, Evered D C, Ress Smith B D. et al . Value of thyroid-stimulating-antibody determinations in predicting short-term thyrotoxic relapse in Graves' disease.  Lancet. 1977;  1 1181-1182
• 20 Feldt-Rasmussen U, Schleusener H, Carayon P. 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
• 21 Davies T F, Roti E, Braverman L E, DeGroot L J. Thyroid controversy - stimulating antibodies.  J Clin Endocrinol Metab. 1998;  83 3777-3785
• 22 Vitti P, Rago T, Chiovato L, Pallini S, Santini F, Fiore E, Rocchi R, Martino E, Pinchera A. Clinical features of patients with Graves' disease undergoing remission after antithyroid drug treatment.  Thyroid. 1997;  7 369-375
• 23 Rink T, Holle L H, Schroth H J, Garth H. Individuelle Verlaufskontrolle der TSH-Rezeptor-Antikörper-Titer zur Einschätzung der Prognose eines M. Basedow [Individual outcome monitoring of TSH receptor antibody level for predicting the prognosis of Graves' disease].  Nuklearmedizin. 1998;  37 90-94
• 24 Glinoer D, de Nayer P, Bex M. Effects of l-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;  144 475-483
• 25 Dietlein M, Dressler J, Grünwald F, Joseph K, Leisner B, Moser E, Reiners C, Rendl J, Schicha H, Schneider P, Schober O. Leitlinie zur Schilddrüsendiagnostik (Version 2).  Nuklearmedizin. 2003;  42 109-115
• 26 Schott M, Morgenthaler N G, Fritzen R, Feldkamp J, Willenberg H S, Scherbaum W A, Seissler J. Levels of autoantibodies against human TSH receptor predict relapse of hyperthyroidism in Graves' disease.  Horm Metab Res. 2004;  36 92-96
• 27 Laurberg P, Nygaard B, Glinoer D, Grussendorf M, Orgiazzi J. Guidelines for TSH-receptor antibody measurements in pregnancy: results of an evidence-based symposium organized by the European Thyroid Association.  Eur J Endocrinol. 1998;  139 584-586
• 28 Gerding M N, van der Meer J WC, Broenink M, Bakker O, Wiersing W M, Prummel M F. Association of thyrotrophin receptor antibodies with the clinical features of Graves' ophthalmopathy.  Clin Endocrinol (oxf). 2000;  52 267-271
• 29 Eckstein A K, Pflicht M, Lax H. et al . Clinical results of anti-inflammatory therapy in Graves' ophthalmopathy and association with thyroidal antibodies.  Clin Endocrinol (oxf). 2004;  61 612-618
• 30 Morgenthaler N G, Minich W B, Willnich M, Bogusch T, Hollidt J M, Weglohner W, Lenzner C, Bergmann A. Affinity purification and diagnostic use of TSH receptor autoantibodies from human serum.  Mol Cell Endocrinol. 2003;  212 73-79