Horm Metab Res 2007; 39(1): 56-61
DOI: 10.1055/s-2007-957347
Original Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Improved Prediction of Relapse of Graves' Thyrotoxicosis by Combined Determination of TSH Receptor and Thyroperoxidase Antibodies

M. Schott 1 , A. Eckstein 2 , H. S. Willenberg 1 , T-B-T. Nguyen 1 , N. G. Morgenthaler 3 , W. A. Scherbaum 1
  • 1Department of Endocrinology, Diabetes and Rheumatology, University Hospital Duesseldorf, Duesseldorf, Germany
  • 2Department of Ophthalmology, University Hospital Essen, Essen, Germany
  • 3Institut für Experimentelle Endokrinologie und Endokrinologisches Forschungszentrum EnForCé, Charité, Universitäts- medizin Berlin, Campus Mitte, Berlin, Germany
Further Information

Publication History

Received 11. 8. 2006

Accepted 28. 9. 2006

Publication Date:
16 January 2007 (online)


Background: Recently, we and others have demonstrated that high levels of auto-antibodies to the human TSH-receptor (TRAb) predict relapse of hyperthyroidism in Graves' disease (GD). Our objective was to extend the outcome of the prediction by combining TRAb with thyroperoxidase antibody (TPO-Ab) measurement.

Patients and Methods: One hundred and thirty-one GD patients (118 females, 13 males) were analysed, of whom 94 patients (71.8%) had relapse, whereas 37 (28.2%) went into remission. Second generation TRAb and TPO-Ab assays were performed in GD patients with relapse and remission in mean 4.3 months after initial diagnosis.

Results: The mean anti-TPO-Ab levels were similar in all patients with relapse and remission. However, there was a steady decline from 4047 U/ml to 530 U/ml in the remission group that correlated positively with TRAb values (>2 to >10 IU/l). The relapse group remained at consistently high levels. The positive predictive value (PPV) for relapse in patients with TRAbs >6 IU/l and anti-TPO-Abs >5000 U/ml was 100, whereas TRAbs >6 IU/l and anti-TPO-Abs >500 U/ml were associated with a PPV of 93.7 up to 96 (p=0.008). These Ab constellations accounted for about one third of all GD patients. For patients with TRAbs between >2 and <6 IU/l the PPV was 66.7-90.0.

Conclusion: Our follow-up analysis indicates that the prediction of relapse of GD can be improved by a combined measurement of TRAb and TPO-Ab. In patients with moderately increased Abs, determined about 6 months after initial diagnosis, an ablative therapy can be approached without delay.


  • 1 Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, Grimley EJ, Hasan DM, Rodgers H, Tunbridge F. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham survey.  Clin Endocrinol (Oxf). 1995;  43 55-68
  • 2 Weetman AP. Graves' disease.  N Engl J Med. 2000;  343 1236-1248
  • 3 Rapoport B, Chazenbalk GD, Jaume JC, McLachlan SM. The Thyrotropin (TSH) Receptor: Interaction with TSH and autoantibodies.  Endocr Rev. 1998;  19 673-716
  • 4 Schott M, Feldkamp J, Bathan C, Fritzen R, Scherbaum WA, Seissler J. Detecting TSH-receptor antibodies with the recombinant TBII assay: technical and clinical evaluation.  Horm Metab Res. 2000;  32 429-435
  • 5 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.  Clin Chim Acta. 2001;  304 39-47
  • 6 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
  • 7 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.  Clin Chem Lab Med. 2001;  39 25-28
  • 8 Zimmermann-Belsing T, Nygaard B, Rasmussen AK, Feldt-Rasmussen U. 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;  146 173-177
  • 9 Schott M, Morgenthaler NG, Fritzen R, Feldkamp J, Willenberg HS, Scherbaum WA, Seissler J. Levels of autoantibodies against human TSH receptor predict relapse of hyperthyroidism in Graves' disease.  Horm Metab Res. 2004;  36 92-96
  • 10 Quadbeck B, Hoermann R, Roggenbuck U, Hahn S, Mann K, Janssen OE. Sensitive thyrotropin and thyrotropin-receptor antibody determinations one month after discontinuation of antithyroid drug treatment as predictors of relapse in Graves' disease.  Thyroid. 2005;  15(9) 1047-1054
  • 11 Schott M, Minich WB, Willenberg HS, Papewalis C, Seissler J, Feldkamp J, Bergmann A, Scherbaum WA, Morgenthaler NG. Relevance of TSH receptor stimulating and blocking autoantibody measurement for the prediction of relapse in Graves' disease.  Horm Metab Res. 2005;  37(12) 741-744
  • 12 Mariotti S, Caturegli P, Piccolo P, Barbesino G, Pinchera A. Antithyroid peroxidase autoantibodies in thyroid diseases.  J Clin Endocrinol Metab. 1990;  71 661-669
  • 13 Engler H, Riesen WF, Keller B. Anti-thyroid peroxidase (anti-TPO) antibodies in thyroid diseases, non-thyroidal illness and controls. Clinical validity of a new commercial method for detection of anti-TPO (thyroid microsomal) autoantibodies.  Clin Chim Acta. 1994;  225 123-136
  • 14 Gilmour J, Brownlee Y, Foster P, Geekie C, Kelly P, Robertson S, Wade E, Braun HB, Staub U, Michel G, Lazarus JH, Parkes AB. The quantitative measurement of autoantibodies to thyroglobulin and thyroid peroxidase by automated microparticle based immunoassays in Hashimoto's disease, Graves' disease and a follow-up study on postpartum thyroid disease.  Clin Lab. 2000;  46 57-61
  • 15 Rieu M, Raynaud A, Richard A, Laplanche S, Sambor B, Berrod JL. Evidence for the effect of antibodies to TSH receptors on the thyroid ultrasonographic volume in patients with Graves' disease.  Clin Endocrinol (Oxf). 1994;  41 667-671
  • 16 Guo J, Wang Y, Jaume JC, Rapoport B, McLachlan SM. Rarity of autoantibodies to a major autoantigen, thyroid peroxidase, that interact with denatured antigen or with epitopes outside the immunodominant region.  Clin Exp Immunol. 1999;  117 19-29
  • 17 Chapal N, Peraldi-Roux S, Bresson D, Pugniere M, Mani JC, Granier C, Baldet L, Guerrier B, Pau B, Bouanani M. Human anti-thyroid peroxidase single-chain fragment variable of Ig isolated from a combinatorial library assembled in-cell: insights into the in vivo situation.  J Immunol. 2000;  164(8) 4162-4169
  • 18 Chapal N, Chardes T, Bresson D, Pugniere M, Mani JC, Pau B, Bouanani M, Peraldi-Roux S. Thyroid peroxidase autoantibodies obtained from random single chain FV libraries contain the same heavy/light chain combinations as occur in vivo.  Endocrinology. 2001;  142 4740-4750
  • 19 Pichurin P, Guo J, Yan X, Rapoport B, McLachlan SM. Human monoclonal autoantibodies to B-cell epitopes outside the thyroid peroxidase autoantibody immunodominant region.  Thyroid. 2001;  11 301-313
  • 20 Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): national health and nutrition examination survey (NHANES III).  J Clin Endocrinol Metab. 2002;  87(2) 489-499
  • 21 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
  • 22 Laurberg P, Buchholtz Hansen PE, Iversen E, Eskjaer JS, Weeke J. Goitre size and outcome of medical treatment of Graves' disease.  Acta Endocrinol (Copenh). 1986;  111(1) 39-43
  • 23 Hoermann R, Quadbeck B, Roggenbuck U, Szabolcs I, Pfeilschifter J, Meng W, Reschke K, Hackenberg K, Dettmann J, Prehn B, Hirche H, Mann K. 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 1119-1128


M. Schott

Department of Endocrinology

Diabetes and Rheumatology University Hospital Duesseldorf

Moorenstr. 5

40225 Duesseldorf


Phone: +4921181 17 810

Fax: +4921181 17 860

Email: schottmt@uni-duesseldorf.de