Relapse of Graves' disease after successful outcome of antithyroid drug therapy: Results of a prospective randomized study on the use of levothyroxine

Rudolf Hoermann, Brigitte Prehn, Herbert Hirche, I. Szabolcs, C. Clanget, V. Hinke, H. Schatz, K. Takáts, A. Radácsi, I. Foeldes, M. Oó, Beate Quadbeck, A. Ágoston, J. Feldkamp, R. Fritzen, R. Santen, M. Schott, W. A. Scherbaum, L. Tharandt, K. CissewskiJ. Pátkay, T. Trilling, Ulla Roggenbuck, A. Vogel, P. M. Schumm-Draeger, K. Jungheim, D. Freitag, K. H. Usadel, A. Akinci, H. P. Hammes, C. Helfrich, R. G. Bretzel, G. Altenfoerde, István Szabolcs, S. Van Ophemert, W. Becker, M. Huefner, W. Buchinger, W. Langsteger, O. Eber, A. Schindler, K. Spieker, G. Pocsay, M. J. Seibel, Johannes Pfeilschifter, R. Ziegler, A. Gerhardt, D. Kompa, B. Stamm, M. Zeitz, B. Helmich-Kapp, D. Graf, H. Lehnert, M. Weber, D. Engelhardt, Wieland Meng, W. Greil, N. Késmárki, J. Mészáros, E. Heinen, B. Zietz, K. D. Palitzsch, R. Hampel, Z. Bencsik, J. Vadász, Z. Loecsey, Kirsten Reschke, J. Rendl, C. Reiners, Klaus Hackenberg, Juergen Dettmann

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Antithyroid drugs are effective in restoring euthyroidism in Graves' disease, but many patients experience relapse after withdrawal. Prevention of recurrence would therefore be a desirable goal. In a prospective study, patients with successful outcome of 12 to 15 months antithyroid drug therapy were stratified for risk factors and randomly assigned to receive levothyroxine in a variable thyrotropin (TSH)-suppressive dose for 2 years or no treatment. The levothyroxine group was randomized to continue or discontinue levothyroxine after 1 year. End points included relapse of overt hyperthyroidism. Of 346 patients with Graves' disease enrolled 225 were euthyroid 4 weeks after antithyroid drug withdrawal and were randomly assigned to receive levothyroxine (114 patients) or no treatment (controls, 111 patients). Of those not randomized, 39 patients showed early relapse within 4 weeks, 61 endogenous TSH suppression, 7 TSH elevation, and 14 had to be excluded. Dropout rate during the study were 13.3%. Kaplan-Meier analyses showed relapse rates to be similar in the levothyroxine group (20% after 1 year, 32% after 2 years) and the randomized controls (18%, 24%), whereas relapses were significantly more frequent in the follow-up group of patients with endogenously suppressed TSH (33%, 49%). Levothyroxine therapy did not influence TSH-receptor antibody, nor did it reduce goiter size. The best prognostic marker available was basal TSH determined 4 weeks after withdrawal of antithyroid drugs (posttreatment TSH). The study demonstrates that levothyroxine does not prevent relapse of hyperthyroidism after successful restoration of euthyroid function by antithyroid drugs and characterizes posttreatment TSH as a main prognostic marker.

Original languageEnglish
Pages (from-to)1119-1128
Number of pages10
JournalThyroid
Volume12
Issue number12
Publication statusPublished - Dec 1 2002

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Antithyroid Agents
Graves Disease
Thyroxine
Prospective Studies
Recurrence
Drug Therapy
Hyperthyroidism
Goiter
Kaplan-Meier Estimate
Thyrotropin
Therapeutics

ASJC Scopus subject areas

  • Endocrinology

Cite this

Relapse of Graves' disease after successful outcome of antithyroid drug therapy : Results of a prospective randomized study on the use of levothyroxine. / Hoermann, Rudolf; Prehn, Brigitte; Hirche, Herbert; Szabolcs, I.; Clanget, C.; Hinke, V.; Schatz, H.; Takáts, K.; Radácsi, A.; Foeldes, I.; Oó, M.; Quadbeck, Beate; Ágoston, A.; Feldkamp, J.; Fritzen, R.; Santen, R.; Schott, M.; Scherbaum, W. A.; Tharandt, L.; Cissewski, K.; Pátkay, J.; Trilling, T.; Roggenbuck, Ulla; Vogel, A.; Schumm-Draeger, P. M.; Jungheim, K.; Freitag, D.; Usadel, K. H.; Akinci, A.; Hammes, H. P.; Helfrich, C.; Bretzel, R. G.; Altenfoerde, G.; Szabolcs, István; Van Ophemert, S.; Becker, W.; Huefner, M.; Buchinger, W.; Langsteger, W.; Eber, O.; Schindler, A.; Spieker, K.; Pocsay, G.; Seibel, M. J.; Pfeilschifter, Johannes; Ziegler, R.; Gerhardt, A.; Kompa, D.; Stamm, B.; Zeitz, M.; Helmich-Kapp, B.; Graf, D.; Lehnert, H.; Weber, M.; Engelhardt, D.; Meng, Wieland; Greil, W.; Késmárki, N.; Mészáros, J.; Heinen, E.; Zietz, B.; Palitzsch, K. D.; Hampel, R.; Bencsik, Z.; Vadász, J.; Loecsey, Z.; Reschke, Kirsten; Rendl, J.; Reiners, C.; Hackenberg, Klaus; Dettmann, Juergen.

In: Thyroid, Vol. 12, No. 12, 01.12.2002, p. 1119-1128.

Research output: Contribution to journalArticle

Hoermann, R, Prehn, B, Hirche, H, Szabolcs, I, Clanget, C, Hinke, V, Schatz, H, Takáts, K, Radácsi, A, Foeldes, I, Oó, M, Quadbeck, B, Ágoston, A, Feldkamp, J, Fritzen, R, Santen, R, Schott, M, Scherbaum, WA, Tharandt, L, Cissewski, K, Pátkay, J, Trilling, T, Roggenbuck, U, Vogel, A, Schumm-Draeger, PM, Jungheim, K, Freitag, D, Usadel, KH, Akinci, A, Hammes, HP, Helfrich, C, Bretzel, RG, Altenfoerde, G, Szabolcs, I, Van Ophemert, S, Becker, W, Huefner, M, Buchinger, W, Langsteger, W, Eber, O, Schindler, A, Spieker, K, Pocsay, G, Seibel, MJ, Pfeilschifter, J, Ziegler, R, Gerhardt, A, Kompa, D, Stamm, B, Zeitz, M, Helmich-Kapp, B, Graf, D, Lehnert, H, Weber, M, Engelhardt, D, Meng, W, Greil, W, Késmárki, N, Mészáros, J, Heinen, E, Zietz, B, Palitzsch, KD, Hampel, R, Bencsik, Z, Vadász, J, Loecsey, Z, Reschke, K, Rendl, J, Reiners, C, Hackenberg, K & Dettmann, J 2002, 'Relapse of Graves' disease after successful outcome of antithyroid drug therapy: Results of a prospective randomized study on the use of levothyroxine', Thyroid, vol. 12, no. 12, pp. 1119-1128.
Hoermann, Rudolf ; Prehn, Brigitte ; Hirche, Herbert ; Szabolcs, I. ; Clanget, C. ; Hinke, V. ; Schatz, H. ; Takáts, K. ; Radácsi, A. ; Foeldes, I. ; Oó, M. ; Quadbeck, Beate ; Ágoston, A. ; Feldkamp, J. ; Fritzen, R. ; Santen, R. ; Schott, M. ; Scherbaum, W. A. ; Tharandt, L. ; Cissewski, K. ; Pátkay, J. ; Trilling, T. ; Roggenbuck, Ulla ; Vogel, A. ; Schumm-Draeger, P. M. ; Jungheim, K. ; Freitag, D. ; Usadel, K. H. ; Akinci, A. ; Hammes, H. P. ; Helfrich, C. ; Bretzel, R. G. ; Altenfoerde, G. ; Szabolcs, István ; Van Ophemert, S. ; Becker, W. ; Huefner, M. ; Buchinger, W. ; Langsteger, W. ; Eber, O. ; Schindler, A. ; Spieker, K. ; Pocsay, G. ; Seibel, M. J. ; Pfeilschifter, Johannes ; Ziegler, R. ; Gerhardt, A. ; Kompa, D. ; Stamm, B. ; Zeitz, M. ; Helmich-Kapp, B. ; Graf, D. ; Lehnert, H. ; Weber, M. ; Engelhardt, D. ; Meng, Wieland ; Greil, W. ; Késmárki, N. ; Mészáros, J. ; Heinen, E. ; Zietz, B. ; Palitzsch, K. D. ; Hampel, R. ; Bencsik, Z. ; Vadász, J. ; Loecsey, Z. ; Reschke, Kirsten ; Rendl, J. ; Reiners, C. ; Hackenberg, Klaus ; Dettmann, Juergen. / Relapse of Graves' disease after successful outcome of antithyroid drug therapy : Results of a prospective randomized study on the use of levothyroxine. In: Thyroid. 2002 ; Vol. 12, No. 12. pp. 1119-1128.
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title = "Relapse of Graves' disease after successful outcome of antithyroid drug therapy: Results of a prospective randomized study on the use of levothyroxine",
abstract = "Antithyroid drugs are effective in restoring euthyroidism in Graves' disease, but many patients experience relapse after withdrawal. Prevention of recurrence would therefore be a desirable goal. In a prospective study, patients with successful outcome of 12 to 15 months antithyroid drug therapy were stratified for risk factors and randomly assigned to receive levothyroxine in a variable thyrotropin (TSH)-suppressive dose for 2 years or no treatment. The levothyroxine group was randomized to continue or discontinue levothyroxine after 1 year. End points included relapse of overt hyperthyroidism. Of 346 patients with Graves' disease enrolled 225 were euthyroid 4 weeks after antithyroid drug withdrawal and were randomly assigned to receive levothyroxine (114 patients) or no treatment (controls, 111 patients). Of those not randomized, 39 patients showed early relapse within 4 weeks, 61 endogenous TSH suppression, 7 TSH elevation, and 14 had to be excluded. Dropout rate during the study were 13.3{\%}. Kaplan-Meier analyses showed relapse rates to be similar in the levothyroxine group (20{\%} after 1 year, 32{\%} after 2 years) and the randomized controls (18{\%}, 24{\%}), whereas relapses were significantly more frequent in the follow-up group of patients with endogenously suppressed TSH (33{\%}, 49{\%}). Levothyroxine therapy did not influence TSH-receptor antibody, nor did it reduce goiter size. The best prognostic marker available was basal TSH determined 4 weeks after withdrawal of antithyroid drugs (posttreatment TSH). The study demonstrates that levothyroxine does not prevent relapse of hyperthyroidism after successful restoration of euthyroid function by antithyroid drugs and characterizes posttreatment TSH as a main prognostic marker.",
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TY - JOUR

T1 - Relapse of Graves' disease after successful outcome of antithyroid drug therapy

T2 - Results of a prospective randomized study on the use of levothyroxine

AU - Hoermann, Rudolf

AU - Prehn, Brigitte

AU - Hirche, Herbert

AU - Szabolcs, I.

AU - Clanget, C.

AU - Hinke, V.

AU - Schatz, H.

AU - Takáts, K.

AU - Radácsi, A.

AU - Foeldes, I.

AU - Oó, M.

AU - Quadbeck, Beate

AU - Ágoston, A.

AU - Feldkamp, J.

AU - Fritzen, R.

AU - Santen, R.

AU - Schott, M.

AU - Scherbaum, W. A.

AU - Tharandt, L.

AU - Cissewski, K.

AU - Pátkay, J.

AU - Trilling, T.

AU - Roggenbuck, Ulla

AU - Vogel, A.

AU - Schumm-Draeger, P. M.

AU - Jungheim, K.

AU - Freitag, D.

AU - Usadel, K. H.

AU - Akinci, A.

AU - Hammes, H. P.

AU - Helfrich, C.

AU - Bretzel, R. G.

AU - Altenfoerde, G.

AU - Szabolcs, István

AU - Van Ophemert, S.

AU - Becker, W.

AU - Huefner, M.

AU - Buchinger, W.

AU - Langsteger, W.

AU - Eber, O.

AU - Schindler, A.

AU - Spieker, K.

AU - Pocsay, G.

AU - Seibel, M. J.

AU - Pfeilschifter, Johannes

AU - Ziegler, R.

AU - Gerhardt, A.

AU - Kompa, D.

AU - Stamm, B.

AU - Zeitz, M.

AU - Helmich-Kapp, B.

AU - Graf, D.

AU - Lehnert, H.

AU - Weber, M.

AU - Engelhardt, D.

AU - Meng, Wieland

AU - Greil, W.

AU - Késmárki, N.

AU - Mészáros, J.

AU - Heinen, E.

AU - Zietz, B.

AU - Palitzsch, K. D.

AU - Hampel, R.

AU - Bencsik, Z.

AU - Vadász, J.

AU - Loecsey, Z.

AU - Reschke, Kirsten

AU - Rendl, J.

AU - Reiners, C.

AU - Hackenberg, Klaus

AU - Dettmann, Juergen

PY - 2002/12/1

Y1 - 2002/12/1

N2 - Antithyroid drugs are effective in restoring euthyroidism in Graves' disease, but many patients experience relapse after withdrawal. Prevention of recurrence would therefore be a desirable goal. In a prospective study, patients with successful outcome of 12 to 15 months antithyroid drug therapy were stratified for risk factors and randomly assigned to receive levothyroxine in a variable thyrotropin (TSH)-suppressive dose for 2 years or no treatment. The levothyroxine group was randomized to continue or discontinue levothyroxine after 1 year. End points included relapse of overt hyperthyroidism. Of 346 patients with Graves' disease enrolled 225 were euthyroid 4 weeks after antithyroid drug withdrawal and were randomly assigned to receive levothyroxine (114 patients) or no treatment (controls, 111 patients). Of those not randomized, 39 patients showed early relapse within 4 weeks, 61 endogenous TSH suppression, 7 TSH elevation, and 14 had to be excluded. Dropout rate during the study were 13.3%. Kaplan-Meier analyses showed relapse rates to be similar in the levothyroxine group (20% after 1 year, 32% after 2 years) and the randomized controls (18%, 24%), whereas relapses were significantly more frequent in the follow-up group of patients with endogenously suppressed TSH (33%, 49%). Levothyroxine therapy did not influence TSH-receptor antibody, nor did it reduce goiter size. The best prognostic marker available was basal TSH determined 4 weeks after withdrawal of antithyroid drugs (posttreatment TSH). The study demonstrates that levothyroxine does not prevent relapse of hyperthyroidism after successful restoration of euthyroid function by antithyroid drugs and characterizes posttreatment TSH as a main prognostic marker.

AB - Antithyroid drugs are effective in restoring euthyroidism in Graves' disease, but many patients experience relapse after withdrawal. Prevention of recurrence would therefore be a desirable goal. In a prospective study, patients with successful outcome of 12 to 15 months antithyroid drug therapy were stratified for risk factors and randomly assigned to receive levothyroxine in a variable thyrotropin (TSH)-suppressive dose for 2 years or no treatment. The levothyroxine group was randomized to continue or discontinue levothyroxine after 1 year. End points included relapse of overt hyperthyroidism. Of 346 patients with Graves' disease enrolled 225 were euthyroid 4 weeks after antithyroid drug withdrawal and were randomly assigned to receive levothyroxine (114 patients) or no treatment (controls, 111 patients). Of those not randomized, 39 patients showed early relapse within 4 weeks, 61 endogenous TSH suppression, 7 TSH elevation, and 14 had to be excluded. Dropout rate during the study were 13.3%. Kaplan-Meier analyses showed relapse rates to be similar in the levothyroxine group (20% after 1 year, 32% after 2 years) and the randomized controls (18%, 24%), whereas relapses were significantly more frequent in the follow-up group of patients with endogenously suppressed TSH (33%, 49%). Levothyroxine therapy did not influence TSH-receptor antibody, nor did it reduce goiter size. The best prognostic marker available was basal TSH determined 4 weeks after withdrawal of antithyroid drugs (posttreatment TSH). The study demonstrates that levothyroxine does not prevent relapse of hyperthyroidism after successful restoration of euthyroid function by antithyroid drugs and characterizes posttreatment TSH as a main prognostic marker.

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