Skip to main content
Log in

Predictors of long-term remission in patients with Graves’ disease: a single center experience

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Antithyroid drugs (ATDs) remain the first-line therapy in patients with Graves’ disease (GD), despite a high relapse rate. The purpose of this study was to identify the predictors of remission in patients with GD treated with ATDs—retrospective study at an endocrine referral service in Northern Greece. Two-hundred and eleven patients met the study’s criteria. Females (p = 0.049), non-smokers (p = 0.017), patients without ophthalmopathy (p = 0.033), and those developing pharmaceutical hypothyroidism (p = 0.018) experienced longer duration of remission. Duration of remission was positively associated with therapy duration (r s = 0.151, p = 0.030), maximum TSH levels during (r s = 0.241, p = 0.001), at the end (r s = 0.280, p < 0.001) and 3 months after therapy (r s = 0.341, p = 0.003). There was a negative association with free T4 (FT4) (r s = −0.426, p < 0.001) and free triiodothyronine (FT3) (r s = −0.467, p = 0.038) levels at 6 months after ATDs discontinuation. In multiple-regression analysis, only duration of the first ATDs course for more than 24 months independently predicted duration of remission. Female gender, non-smoking, the absence of orbitopathy, treatment duration, pharmaceutical hypothyroidism, higher TSH levels during, at the end and 3 months after ATDs discontinuation, and lower FT4 and FT3 levels 6 months after therapy were associated with longer duration of remission. However, only duration of ATDs therapy for more than 24 months independently predicted predict long-term remission in GD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. G.A. Brent, Graves’ disease. N. Engl. J. Med. 358, 2594–2605 (2008)

    Article  PubMed  CAS  Google Scholar 

  2. M. Schott, W.A. Scherbaum, N.G. Morgenthaler, Thyrotropin receptor autoantibodies in Graves’ disease. Trends Endocrinol. Metab. 16, 243–248 (2005)

    Article  PubMed  CAS  Google Scholar 

  3. A.J. Hedley, R.E. Young, S.J. Jones, W.D. Alexander, P.D. Bewsher, 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) 31, 209–218 (1989)

    Article  CAS  Google Scholar 

  4. D. Cooper, Antithyroid drugs. N. Engl. J. Med. 352, 905–917 (2005)

    Article  PubMed  CAS  Google Scholar 

  5. P. Abraham, A. Avenell, C.M. Park, W.A. Watson, J.S. Bevan, A systematic review of drug therapy for Graves’ hyperthyroidism. Eur. J. Endocrinol. 153, 489–498 (2005)

    Article  PubMed  CAS  Google Scholar 

  6. R.S. Bahn, H.B. Burch, D.S. Cooper, J.R. Garber, M.C. Greenlee, I. Klein, P. Laurberg, I.R. McDougall, V.M. Montori, S.A. Rivkees, D.S. Ross, J.A. Sosa, M.N. Stan, American Thyroid Association, American Association of Clinical Endocrinologists, Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr. Pract. 17, 456–520 (2011)

    Article  PubMed  Google Scholar 

  7. N.S. Glaser, D.M. Styne, Predicting the likelihood of remission in children with Graves’ disease: a prospective, multicenter study. Pediatrics 121, e481–e488 (2008)

    Article  PubMed  Google Scholar 

  8. F. Kaguelidou, C. Alberti, M. Castanet, M.A. Guitteny, P. Czernichow, J. Léger, French Childhood Graves’ Disease Study Group, Predictors of autoimmune hyperthyroidism relapse in children after discontinuation of antithyroid drug treatment. J. Clin. Endocrinol. Metab. 93, 3817–3826 (2008)

    Article  PubMed  CAS  Google Scholar 

  9. A. Allahabadia, J. Daykin, R.L. Holder, M.C. Sheppard, S.C. Gough, J.A. Franklyn, Age and gender predict the outcome of treatment for Graves’ hyperthyroidism. J. Clin. Endocrinol. Metab. 85, 1038–1042 (2000)

    Article  PubMed  CAS  Google Scholar 

  10. H. Schleusener, J. Schwander, C. Fischer, R. Holle, G. Holl, K. Badenhoop, J. Hensen, R. Finke, U. Bogner, W.R. Mayr et al., Prospective multicentre study on the prediction of relapse after antithyroid drug treatment in patients with Graves’ disease. Acta Endocrinol. (Copenh) 120, 689–701 (1989)

    CAS  Google Scholar 

  11. C. Cappelli, E. Gandossi, M. Castellano, C. Pizzocaro, B. Agosti, A. Delbarba, I. Pirola, E. De Martino, E.A. Rosei, Prognostic value of thyrotropin receptor antibodies (TRAb) in Graves’ disease: a 120 months prospective study. Endocr. J. 54, 713–720 (2007)

    Article  PubMed  CAS  Google Scholar 

  12. C. Carella, G. Mazziotti, F. Sorvillo, M. Piscopo, M. Cioffi, P. Pilla, R. Nersita, S. Iorio, G. Amato, L.E. Braverman, E. Roti, Serum thyrotropin receptor antibodies concentrations in patients with Graves’ disease before, at the end of methimazole treatment, and after drug withdrawal: evidence that the activity of thyrotropin receptor antibody and/or thyroid response modify during the observation period. Thyroid 16, 295–302 (2006)

    Article  PubMed  CAS  Google Scholar 

  13. T. Yasuda, Y. Okamoto, N. Hamada, K. Miyashita, M. Takahara, F. Sakamoto, T. Miyatsuka, T. Kitamura, N. Katakami, D. Kawamori, M. Otsuki, T.A. Matsuoka, H. Kaneto, I. Shimomura, Serum vitamin D levels are decreased in patients without remission of Graves’ disease. Endocrine 43(1), 230–232 (2012)

    Article  PubMed  Google Scholar 

  14. M. Feng, H. Li, S.F. Chen, W.F. Li, F.B. Zhang, Polymorphisms in the vitamin D receptor gene and risk of autoimmune thyroid diseases: a meta-analysis. Endocrine, (2012). doi:10.1007/s12020-012-9812-y

  15. H. Allannic, R. Fauchet, J. Orgiazzi, A.M. Madec, B. Genetet, Y. Lorcy, A.M. Le Guerrier, C. Delambre, V. Derennes, Antithyroid drugs and Graves’ disease: a prospective randomized evaluation of the efficacy of treatment duration. J. Clin. Endocrinol. Metab. 70, 675–679 (1990)

    Article  PubMed  CAS  Google Scholar 

  16. A.P. Weetman, A.P. Pickerill, P. Watson, V.K. Chatterjee, O.M. Edwards, Treatment of Graves’ disease with the block-replace regimen of antithyroid drugs: the effect of treatment duration and immunogenetic susceptibility on relapse. QJM 87, 337–341 (1994)

    PubMed  CAS  Google Scholar 

  17. R.V.P.C. Garcia-Mayor, R. Luna-Cano, L.F. Perez-Mendez, J.C. Galofre, A. Andrade, Antithyroid drug and Graves’ hyperthyroidism. Significance of treatment duration and TRAb determination on lasting remission. J. Endocrinol. Invest. 15, 815–820 (1992)

    PubMed  CAS  Google Scholar 

  18. D. Maugendre, A. Gatel, L. Campion, C. Massart, I. Guilhem, Y. Lorcy, J. Lescouarch, J.Y. Herry, H. Allannic, Antithyroid drugs and Graves’ disease–prospective randomized assessment of long-term treatment. Clin. Endocrinol. (Oxf) 50, 127–132 (1999)

    Article  CAS  Google Scholar 

  19. T. Wille, B. Müller, D. Noth, U. Bürgi, P. Diem, Long-term follow up after antithyroid drug treatment in Graves’ disease. Praxis (Bern 1994) 95, 1121–1127 (2006)

    Article  CAS  Google Scholar 

  20. T. Konishi, Y. Okamoto, M. Ueda, Y. Fukuda, I. Harusato, Y. Tsukamoto, N. Hamada, Drug discontinuation after treatment with minimum maintenance dose of an antithyroid drug in Graves’ disease: a retrospective study on effects of treatment duration with minimum maintenance dose on lasting remission. Endocr. J. 58, 95–100 (2011)

    Article  PubMed  CAS  Google Scholar 

  21. S.R. Page, C.E. Sheard, M. Herbert, M. Hopton, W.J. Jeffcoate, A comparison of 20 or 40 mg per day of carbimazole in the initial treatment of hyperthyroidism. Clin. Endocrinol. (Oxf) 45, 511–516 (1996)

    Article  CAS  Google Scholar 

  22. Y.K. Choo, W.S. Yoo, D.W. Kim, H.K. Chung, Hypothyroidism during antithyroid drug treatment with methimazole is a favorable prognostic indicator in patients with Graves’ disease. Thyroid 20, 949–954 (2010)

    Article  PubMed  CAS  Google Scholar 

  23. D. Glinoer, P. de Nayer, M. Bex, Belgian Collaborative Study Group on Graves’ Disease, 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. 144, 475–483 (2001)

    Article  PubMed  CAS  Google Scholar 

  24. F. Bolaños, M. González-Ortiz, H. Durón, C. Sánchez, Remission of Graves’ hyperthyroidism treated with methimazole. Rev. Invest. Clin. 54, 307–310 (2002)

    PubMed  Google Scholar 

  25. K. Hashizume, K. Ichikawa, A. Sakurai, S. Suzuki, T. Takeda, M. Kobayashi, T. Miyamoto, M. Arai, T. Nagasawa, Administration of thyroxine in treated Graves’ disease. Effects on the level of antibodies to thyroid-stimulating hormone receptors and on the risk of recurrence of hyperthyroidism. N. Engl. J. Med. 324, 947–953 (1991)

    Article  PubMed  CAS  Google Scholar 

  26. S.K. Grebe, C.M. Feek, H.C. Ford, J.N. Fagerström, D.P. Cordwell, J.W. Delahunt, R.J. Toomath, A randomized trial of short-term treatment of Graves’ disease with high-dose carbimazole plus thyroxine versus low-dose carbimazole. Clin. Endocrinol. (Oxf) 48, 585–592 (1998)

    Article  CAS  Google Scholar 

  27. G. Benker, D. Reinwein, G. Kahaly, L. Tegler, W.D. Alexander, J. Fassbinder, H. Hirche, 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) 49, 451–457 (1998)

    Article  CAS  Google Scholar 

  28. H. Sato, M. Minagawa, N. Sasaki, S. Sugihara, I. Kazukawa, K. Minamitani, K. Wataki, S. Konda, H. Inomata, K. Sanayama, Y. Kohno, Comparison of methimazole and propylthiouracil in the management of children and adolescents with Graves’ disease: efficacy and adverse reactions during initial treatment and long-term outcome. J. Pediatr. Endocrinol. Metab. 24, 257–263 (2011)

    Article  PubMed  CAS  Google Scholar 

  29. T. Yamada, T. Aizawa, Y. Koizumi, I. Komiya, K. Ichikawa, K. Hashizume, Age-related therapeutic response to antithyroid drug in patients with hyperthyroid Graves’ disease. J. Am. Geriatr. Soc. 42, 513–516 (1994)

    PubMed  CAS  Google Scholar 

  30. P. Vitti, T. Rago, L. Chiovato, S. Pallini, F. Santini, E. Fiore, R. Rocchi, E. Martino, A. Pinchera, Clinical features of patients with Graves’ disease undergoing remission after antithyroid drug treatment. Thyroid 7, 369–375 (1997)

    Article  PubMed  CAS  Google Scholar 

  31. H. Cinemre, C. Bilir, F. Gokosmanoglu, N. Akdemir, B. Erdogmus, R. Buyukkaya, Predictors of time to remission and treatment failure in patients with Graves’ disease treated with propylthiouracil. Clin. Invest. Med. 32, E199–E205 (2009)

    PubMed  CAS  Google Scholar 

  32. Ρ. Prakash, Prediction of remission in Graves’ disease treated with long-term carbimazole therapy: evaluation of technetium-99 m thyroid uptake and TSH concentrations as prognostic indicators. Eur. J. Nucl. Med. 23, 118–122 (1996)

    Article  PubMed  CAS  Google Scholar 

  33. B. Quadbeck, R. Hoermann, U. Roggenbuck, S. Hahn, K. Mann, O.E. Janssen, Basedow Study Group, Sensitive thyrotropin and thyrotropin-receptor antibody determinations one month after discontinuation of antithyroid drug treatment as predictors of relapse in Graves’ disease. Thyroid 15, 1047–1054 (2005)

    Article  PubMed  CAS  Google Scholar 

  34. W.E. Wood, Role of TSH measurements in predicting the outcome of treatment for Graves’ disease following drug therapy. Postgrad. Med. J. 71, 222–223 (1995)

    Article  PubMed  CAS  Google Scholar 

  35. J.N. Talbot, F. Duron, R. Féron, P. Aubert, G. Milhaud, Thyroglobulin, thyrotropin and thyrotropin binding inhibiting immunoglobulins assayed at the withdrawal of antithyroid drug therapy as predictors of relapse of Graves’ disease within one year. J. Endocrinol. Invest. 12, 589–595 (1989)

    PubMed  CAS  Google Scholar 

  36. O. Ishtiaq, S. Waseem, M.N. Haque, N. Islam, A. Jabbar, Remission of Grave’s disease after oral anti-thyroid drug treatment. J. Coll. Physicians Surg. Pak. 19, 690–693 (2009)

    PubMed  Google Scholar 

Download references

Conflict of interest

The authors have no conflict of interest to disclose.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Panagiotis Anagnostis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Anagnostis, P., Adamidou, F., Polyzos, S.A. et al. Predictors of long-term remission in patients with Graves’ disease: a single center experience. Endocrine 44, 448–453 (2013). https://doi.org/10.1007/s12020-013-9895-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-013-9895-0

Keywords

Navigation