Prediction of Remission or Relapse for Graves’ Hyperthyroidism by the Combined Determination of Stimulating, Blocking and Binding TSH-Receptor Antibodies after the Withdrawal of Antithyroid Drug Treatment

Abstract

The most likely reasons for the low predictive value of TSH-receptor antibodies (TRAbs) determinations in previous investigations are the biological heterogeneity of TRAbs and changes of the different stimulating (TSAb) or blocking (TSBAb) antibody bioactivities of TRAbs during the course of Graves’ disease (GD), which have not been taken into account in most previous studies. Furthermore, in a recent study it has been demonstrated that the decline of TRAb values detected with highly sensitive hTBII or TSAB assays is not useful in evaluating remission or relapse of GD at the end of antithyroid drug treatment (ATDT). In order to make a thorough investigation of the predictive values of all different TRAb qualities for the recurrence for GD after the withdrawal, we investigated hTBII, TSAbs and TSBAbs in 54 consecutive patients with GD at the end of ATDT and 12 - 13.5 months after stopping ATDT. Using the TRAb values at the time of reinvestigation in a model, recurrence for GD was better predicted compared to the determination at the time of withdrawal of ATDT. Furthermore, using this model, the combined determination of hTBII, TSAbs, and TSBAbs revealed the highest level of significance for the prediction of remission or relapse of GD (OR = 15; p < 0.0001) compared to the detection of hTBII, TSAbs and TSBAbs alone. Therefore, significant changes of TSAbs after the end of ATDT and the biological heterogeneity of TRAb define the conditions for predicting remission or relapse of GD after ATDT by TRAb determinations. Consequently, our results suggest that the prediction of the individual course of GD can only be improved by combined determinations of all TRAb qualities (hTBII, TSAbs and TSBAbs) after the end of ATDT.

Key words

Thyroid Antibodies - Graves’ Disease - Remission - Relapse

References

• 1 Glinoer D, Hesch D, Lagasse R, Laurberg P. The management of hyperthyroidism due to Graves' disease in Europe in 1986. Results of an international survey.  Acta Endocrinol Suppl (Copenh). 1987;  285 3-23
• 2 Solomon B, Glinoer D, Lagasse R, Wartofsky L. Current trends in the management of Graves' disease.  J Clin Endocrinol Metab. 1990;  70 1518-1524
• 3 Weetman A P. Medical Progress: Graves' Disease.  N Engl J Med. 2000;  343 1236-1248
• 4 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
• 5 Hedley A J, Young R E, Jones S J, Alexander W D, Bewsher P D. Antithyroid drugs in the treatment of hyperthyroidism of Graves' disease: Long-term follow-up of 434 patients. Scottish Automated Follow-Up Register Group.  Clin Endocrinol (Oxf). 1989;  31 209-218
• 6 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
• 7 Schleusener H, Schwander J, Fischer C, Holle R, Holl G, Badenhoop K, Hensen J, Finke R, Bogner U, Mayr W R. Prospective multicentre study on the prediction of relapse after antithyroid drug treatment in patients with Graves' disease.  Published erratum appears in Acta Endocrinol (Copenh). 1989;  120 689-701
• 8 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 69-375
• 9 Benker G, Reinwein D, Kahaly G, Tegler L, Alexander W D, Fassbinder J, Hirche H. Is there a methimazole dose effect on remission rate in Graves' disease. Results from a long-term prospective study? The European Multicentre Trial Group of the Treatment of Hyperthyroidism with Antithyroid Drugs.  Clin Endocrinol (Oxf). 1998;  49 451-457
• 10 Reinwein D, Benker G, Lazarus J H, Alexander W D. A prospective randomized trial of antithyroid drug dose in Graves' disease therapy. European Multicenter Study Group on Antithyroid Drug Treatment.  J Clin Endocrinol Metab. 1993;  76 1516-1521
• 11 Rittmaster R S, Abbott E C, Douglas R, Givner M L, Lehmann L, Reddy S, Salisbury S R, Shlossberg A H, Tan M H, York S E. Effect of methimazole, with or without L-thyroxine, on remission rates in Graves' disease.  J Clin Endocrinol Metab. 1998;  83 814-818
• 12 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
• 13 Cho B Y, Shong Y K, Lee H K, Koh C S, Min H K. Graves' hyperthyroidism following primary hypothyroidism: Sequential changes in various activities of thyrotropin receptor antibodies.  Acta Endocrinol (Copenh). 1989;  120 447-450
• 14 Kung A W, Jones B M. A change from stimulatory to blocking antibody activity in Graves' disease during pregnancy.  J Clin Endocrinol Metab. 1998;  83 514-518
• 15 Banga J P, Harris P E. Potential pathogenicity of autoantibodies to thyrotropin receptor in treated, euthyroid patients with Graves' disease.  Eur J Endocrinol. 1998;  139 139-142
• 16 Leech N J, Dayan C M. Controversies in the management of Graves' disease.  Clin Endocrinol (Oxf). 1998;  49 273-280
• 17 Rapoport B, Chazenbalk G D, Jaume J C, McLachlan S M. The thyrotropin (TSH) receptor: Interaction with TSH and autoantibodies.  Published erratum appears in Endocr Rev Endocr Rev. 1999;  19 673-716
• 18 Wallaschofski H, Paschke R. Detection of thyroid stimulating (TSAB)- and thyrotropin stimulation blocking (TSBAB) antibodies with CHO cell lines expressing different TSH-receptor numbers.  Clin Endocrinol (Oxf). 1999;  50 365-372
• 19 Wallaschofski H, Kaczmarek M, Miehle K, Hentschel B, Paschke R. Differences between thyrotropin receptor antibody bioactivity and inhibition of 125I-bovine thyrotropin binding.  Thyroid. 2000;  10 897-907
• 20 Chazenbalk G D, Pichurin P, McLachlan S M, Rapoport B. A direct binding assay for thyrotropin receptor autoantibodies.  Thyroid. 1999;  9 1057-1061
• 21 Worthington J, Byfield P G, Himsworth R L. Heterogeneity of circulating TSH-receptor antibodies in thyroid disease demonstrated directly by chromatography.  Clin Endocrinol (Oxf). 1991;  34 147-154
• 22 Yamano Y, Takamatsu J, Sakane S, Hirai K, Kuma K, Ohsawa N. Differences between changes in serum thyrotropin-binding inhibitory antibodies and thyroid-stimulating antibodies in the course of antithyroid drug therapy for Graves' disease.  Thyroid. 1999;  9 769-773
• 23 Maugendre D, Gatel A, Campion L, Massart C, Guilhem I, Lorcy Y, Lescouarch J, Herry J Y, Allannic H. Antithyroid drugs and Graves' disease - prospective randomized assessment of long-term treatment.  Clin Endocrinol (Oxf). 1999;  50 127-132
• 24 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.  J Clin Endocrinol Metab. 1999;  84 90-97
• 25 Madec A M, Laurent M C, Lorcy Y, Le G uerrier, Rostagnat-Stefanutti A, Orgiazzi J, Allannic H. Thyroid stimulating antibodies: An aid to the strategy of treatment of Graves' disease?.  Clin Endocrinol (Oxf). 1984;  21 247-255
• 26 Tamai H, Kasagi K, Takaichi Y, Takamatsu J, Komaki G, Matsubayashi S, Konishi J, Kuma K, Kumagai L F, Nagataki S. Development of spontaneous hypothyroidism in patients with Graves' disease treated with antithyroidal drugs: Clinical, immunological, and histological findings in 26 patients.  J Clin Endocrinol Metab. 1989;  69 49-53