Horm Metab Res 2004; 36(2): 92-96
DOI: 10.1055/s-2004-814217
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Levels of Autoantibodies against Human TSH Receptor Predict Relapse of Hyperthyroidism in Graves’ Disease

M.  Schott1 , N.  G.  Morgenthaler 4 , R.  Fritzen1 , J.  Feldkamp 3 , H.  S.  Willenberg1 , W.  A.  Scherbaum1 , J.  Seissler 2
  • 1Department of Endocrinology
  • 2German Diabetes Research Institute, Heinrich-Heine-University Duesseldorf
  • 3Department of Internal Medicine, Municipal Hospital Bielefeld
  • 4Research Department, B.R.A.H.M.S. AG, Biotechnology Centre Hennigsdorf, Hennigsdorf nr Berlin, Germany
Further Information

Publication History

Received 17 April 2003

Accepted after revision 18 August 2003

Publication Date:
05 March 2004 (online)

Abstract

The aim of this study was to evaluate the ability of the more sensitive second-generation TSH receptor (TRAb) assay to predict recurrent Graves’ disease (GD) vs. remission depending on TRAb levels. 93 patients with active GD were included in the study. By using a cut-off limit of 1.0 IU/l, all 93 patients were positive for TRAb (median: 4.6 IU/l) at the time of their first visit (single point measurement in median 5.1 months after initial diagnosis). Subsequently, 33 patients went into remission and were euthyroid during follow-up (median follow-up: 21.7 months), whereas 60 patients did not go into remission or developed relapse over the following 24 months. Median TRAb levels in the group of remission were significantly (p < 0.0001) lower than TRAb values in the relapse group (2.1 compared to 8.6 IU/l). Applying ROC plot analysis to compare different TRAb thresholds, a cut-off of 10 IU/l was established. Here, the specificity for relapse was 97 % as only 1 of 29 patients with TRAb values above 10 IU/l went into remission during follow-up, whereas all other 28 patients developed a relapse (positive predictive value for relapse: 96.4 %). In contrast, TRAb values lower than 10 IU/l had no impact on the prediction of remission. In conclusion, our data clearly indicate that TRAb measurement is useful for identifying patients that will not benefit from long-term antithyroid drug treatment.

References

  • 1 Weetman A P. Graves’ disease.  New England Journal of Medicine. 2000;  343 1236-1248
  • 2 Rapoport B, Chazenbalk G D, Jaume J C, McLachlan S M. The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies.  Endocrine Reviews. 1998;  19 673-716
  • 3 Morgenthaler N G. New assay systems for thyrotropin receptor antibodies.  Current Opinion of Endocrinology and Diabetes. 1999;  6 251-260
  • 4 Smith B R, Hall R. Thyroid-stimulating immunoglobulins in Graves’ disease.  Lancet. 1974;  2 427-431
  • 5 Costagliola S, Morgenthaler N G, Hoermann R, Badenhoop K, Struck J, Freitag D, Poertl S, Weglohner 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 thyrotropin receptor antibodies has superior diagnostic sensitivity for Graves’ disease.  Journal of Clinical Endocrinology and Metabolism. 1999;  84 90-97
  • 6 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.  Hormone and Metabolic Research. 2000;  32 429-435
  • 7 Massart C, Orgiazzi J, Maugendre D. 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.  Clinica Chimica Acta. 2001;  304 39-47
  • 8 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.  Clinical Endocrinology. 2001;  54 89-96
  • 9 Giovanella L, Ceriani L, Garancini S. Clinical applications of the 2nd generation assay for anti-TSH receptor antibodies in Graves’ disease. Evaluation in patients with negative 1st generation test.  Clinical Chemistry and Laboratory Medicine. 2001;  39 25-28
  • 10 Zimmermann-Belsing T, Nygaard B, Rasmussen A K, Feldt-Rasmussen U. Use of the 2nd generation TRAK human assay did not improve prediction of relapse after antithyroid medical therapy of Graves’ disease.  European Journal of Endocrinology. 2002;  146 173-177
  • 11 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.  Clinical Endocrinology. 2001;  55 381-390
  • 12 Wallaschofski H, Orda C, Georgi P, Miehle K, Paschke R. Distinction between autoimmune and non-autoimmune hyperthyroidism by determination of TSH-receptor antibodies in patients with the initial diagnosis of toxic multinodular goiter.  Hormone and Metabolic Research. 2001;  33 504-507
  • 13 Morgenthaler N G, Nagata A, Katayama S, Bergmann A, Iitaka M. Detection of low titre TBII in patients with Graves’ disease using recombinant human TSH receptor.  Clinical Endocrinology. 2002;  57 193-198
  • 14 Schleusener H, Schwander J, Fischer C, Holle R, Holl G, Badenhoop K. Prospective multicentre study on the prediction of relapse after antithyroid drug treatment in patients with Graves’ disease.  Acta Endocrinol. 1989;  120 689-701
  • 15 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.  Journal of Clinical Endocrinology and Metabolism. 1994;  78 98-102
  • 16 Wartofsky L, Glinoer D, Solomon B, Nagataki S, Lagasse R, Nagayama Y, Izumi M. Differences and similarities in the diagnosis and treatment of Graves’ disease in Europe, Japan, and the United States.  Thyroid. 1991;  1 129-135
  • 17 McIver B, Rae P, Beckett G, Wilkinson E, Gold A, Toft A. Lack of effect of thyroxine in patients with Graves’ hyperthyroidism who are treated with an antithyroid drug.  The New England Journal of Medicine. 1991;  334 220-224
  • 18 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
  • 19 Michelangeli V, Poon C, Taft J, Newnham H, Topliss D, Colman P. The prognostic value of thyrotropin receptor antibody measurement in the early stages of treatment of Graves’ disease with antithyroid drugs.  Thyroid. 1998;  8 119-124

M. Schott,M. D. 

Department of Endocrinology · Heinrich-Heine-University Duesseldorf ·

Moorenstraße 5 · 40225 Duesseldorf · Germany

Phone: + 49 (211) 811 78 10

Fax: + 49 (211) 811 78 60 ·

Email: schottmt@uni-duesseldorf.de

    >