Skip to main content
SpringerLink
Log in

An update on the medical treatment of Graves’ hyperthyroidism

  • Short Review
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Medical treatment of Graves’ hyperthyroidism is based on the use of thionamides; namely, methimazole and propylthiouracil. In the past, methimazole was preferred by European endocrinologists, whereas propylthiouracil was the first choice for the majority of their North American colleagues. However, because of the recent definition of a better side-effect profile, methimazole is nowadays the first choice world while. Although thionamides are quite effective for the short-term control of Graves’ hyperthyroidism, a relatively high proportion of patients relapses after thionamide withdrawal. Other possible medical treatments, include iodine and compounds containing iodine, perchlorate, lithium (as an adjuvant in patients undergoing radioiodine therapy), β-adrenergic antagonists, glucocorticoids, and some new molecules still under investigation. Management of Graves’ hyperthyroidism using thionamides as well as the other available medical treatments is here reviewed in detail, with a special mention of situations such as pregnancy and lactation, as well as neonatal and fetal thyrotoxicosis.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa JA, Stan MN (2011) Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid 21:593–646

    Article  PubMed  Google Scholar 

  2. Astwood EB (1943) Treatment of of hyperthyroidism with thiourea and thiouracil. JAMA 122:78

    Article  CAS  Google Scholar 

  3. Cooper DS (2005) Antithyroid drugs. N Engl J Med 352:905–917

    Article  PubMed  CAS  Google Scholar 

  4. Wartofsky L, Glinoer D, Solomon B, Lagasse R (1991) Differences and similarities in the diagnosis and treatment of Graves’ disease in Europe, Japan and the United States. Thyroid 1:129–135

    Article  PubMed  CAS  Google Scholar 

  5. Emiliano AB, Governale L, Parks M, Cooper DS (2010) Shifts in propylthiouracil and methimazole prescribing practices: antithyroid drug use in the United States from 1991 to 2008. J Clin Endocrinol Metab 95:2227–2233

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  6. Glinoer D, Cooper DS (2012) The propylthiouracil dilemma. Curr Opin Endocrinol Diabet Obes 19:402–407

    Article  Google Scholar 

  7. Bahn RS, Burch HS, Cooper DS, Garber JR, Greenlee CM, Klein IL, Laurberg P, McDougall IR, Rivkees SA, Ross D, Sosa JA, Stan MN (2009) The role of propylthiouracil in the management of Graves’ disease in adults: report of a meeting jointly sponsored by the American Thyroid Association and the Food and Drug Administration. Thyroid 19:673–674

    Article  PubMed  CAS  Google Scholar 

  8. Reinwein D, Benker G, Lazarus JH, Alexander WD (1993) A prospective randomized trial of antithyroid drug dose in Graves’ disease therapy. European Multicenter Study Group on Antithyroid Drug Treatment. J Clin Endocrinol Metab 76:1516–1521

    PubMed  CAS  Google Scholar 

  9. Konishi T, Okamoto Y, Ueda M, Fukuda Y, Harusato I, Tsukamoto Y, Hamada N (2011) 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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  11. Kaguelidou F, Alberti C, Castanet M, Guitteny MA, Czernichow P, Léger J (2008) Predictors of autoimmune hyperthyroidism relapse in children after discontinuation of antithyroid drug treatment. J Clin Endocrinol Metab 93:3817–3826

    Article  PubMed  CAS  Google Scholar 

  12. Wartofsky L (1973) Low remission after therapy for Graves’ disease. Possible relation of dietary iodine with antithyroid therapy results. JAMA 226:1083–1088

    Article  PubMed  CAS  Google Scholar 

  13. Solomon BL, Evaul JE, Burman KD, Wartofsky L (1987) Remission rates with antithyroid drug therapy: continuing influence of iodine intake? Ann Intern Med 107:510–512

    Article  PubMed  CAS  Google Scholar 

  14. Barbesino G, Tomer Y (2013) Clinical utility of TSH receptor antibodies. J Clin Endocrinol Metab 98:2247–2255

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Lamberg BA, Salmi J, Wagar G, Makinen T (1981) Spontaneous hypothyroidism after antithyroid treatment of hyperthyroid Graves’ disease. J Endocrinol Invest 4(3):99–402

    Google Scholar 

  16. Feldt-Rasmussen U, Schleusener H, Carayon P (1994) Meta-analysis evaluation of the impact of thyrotropin receptor antibodies on long term remission after medical therapy of Graves’ disease. J Clin Endocrinol Metab 78:98–102

    PubMed  CAS  Google Scholar 

  17. Tripodi PF, Ruggeri RM, Campennì A, Cucinotta M, Mirto A, Lo Gullo R, Baldari S, Trimarchi F, Cucinotta D, Russo GT (2008) Central nervous system vasculitis after starting methimazole in a woman with Graves’ disease. Thyroid 18:1011–1013

    Article  PubMed  CAS  Google Scholar 

  18. Ruggeri RM, Imbesi S, Saitta S, Campennì A, Cannavò S, Trimarchi F, Gangemi S (2013) Chronic idiopathic urticaria and Graves’ disease. J Endocrinol Invest 36:531–536

    PubMed  CAS  Google Scholar 

  19. Weetman AP, McGregor AM, Hall R (1984) Evidence for an effect of antithyroid drugs on the natural history of Graves’ disease. Clin Endocrinol 21:163–172

    Article  CAS  Google Scholar 

  20. Marcocci C, Marinò M (2005) Thyroid directed antibodies. In: Braverman LE, Utiger RD (eds) Werner and Ingbar’s the thyroid: a fundamental and clinical text, 9th edition. Lippincott, Williams & Wilkins, Philadelphia, pp 360–372

  21. Weetman AP, McGregor AP, Hall R (1983) Methimazole inhibits thyroid autoantibody production by an action on accessory cells. Clin Immunol Immunopathol 28:39–45

    Article  PubMed  CAS  Google Scholar 

  22. Weiss I, Davies TF (1981) Inhibition of immunoglobulin-secreting cells by antithyroid drugs. J Clin Endocrinol Metab 53:1223–1228

    Article  PubMed  CAS  Google Scholar 

  23. Rennie DP, McGregor AM, Keast D, Weetman AP, Foord SM, Dieguez C, Williams ED, Hall R (1983) The influence of methimazole on thyroglobulin-induced autoimmune thyroiditis in the rat. Endocrinology 112:326–330

    Article  PubMed  CAS  Google Scholar 

  24. Wenzel KW, Lente JR (1984) Similar effects of thionamide drugs and perchlorate on thyroid-stimulating immunoglobulins in Graves’ disease: evidence against an immunosuppressive action of thionamide drugs. J Clin Endocrinol Metab 58:62–69

    Article  PubMed  CAS  Google Scholar 

  25. Nakamura H, Noh JY, Itoh K, Fukata S, Miyauchi A, Hamada N (2007) Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves’ disease. J Clin Endocrinol Metab 92:2157–2162

    Article  PubMed  CAS  Google Scholar 

  26. Li D, Pei H, Li X, Liu X, Li X, Xie Y (2012) Short-term effects of combined treatment with potassium bromide and methimazole in patients with Graves’ disease. J Endocrinol Invest 35:971–974

    PubMed  CAS  Google Scholar 

  27. Hashizume K, Ichikawa K, Sakurai A, Suzuki S, Takeda T, Kobayashi M, Miyamoto T, Arai M, Nagasawa T (1991) 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

    Article  PubMed  CAS  Google Scholar 

  28. Romaldini JH, Bromberg N, Werner RS, Tanaka LM, Rodrigues HF, Werner MC, Farah CS, Reis LC (1983) Comparison of effects of high and low dosage regimens of antithyroid drugs in the management of Graves’ hyperthyroidism. J Clin Endocrinol Metab 57:563–570

    Article  PubMed  CAS  Google Scholar 

  29. Tamai H, Hayaki I, Kawai K, Komaki G, Matsubayashi S, Kuma K, Kumagai LF, Nagataki S (1995) Lack of effect of thyroxine administration on elevated thyroid stimulating hormone receptor antibody levels in treated Graves’ disease patients. J Clin Endocrinol Metab 80:1481–1484

    PubMed  CAS  Google Scholar 

  30. Rittmaster RS, Zwicker H, Abbott EC, Douglas R, Givner ML, Gupta MK, Lehmann L, Reddy S, Salisbury SR, Shlossberg AH, Tan MH, York SE (1996) Effect of methimazole with or without exogenous l-thyroxine on serum concentrations of thyrotropin (TSH) receptor antibodies in patients with Graves’ disease. J Clin Endocrinol Metab 81:3283–3288

    PubMed  CAS  Google Scholar 

  31. Rizvi A, Crapo LM (1996) Failure of thyroxine therapy for Graves’ disease (letter). Ann Intern Med 124:694

    Article  PubMed  CAS  Google Scholar 

  32. Rittmaster RS, Abbott EC, Douglas R, Givner ML, Lehmann L, Reddy S, Salisbury SR, Shlossberg AH, Tan MH, York SE (1998) Effect of methimazole, with or without l-thyroxine, on remission rates in Graves’ disease. J Clin Endocrinol Metab 83:814–818

    PubMed  CAS  Google Scholar 

  33. Emerson CH, Anderson AJ, Howard WJ, Utiger RD (1975) Serum thyroxine and triiodothyronine concentrations during iodide treatment of hyperthyroidism. J Clin Endocrinol Metab 40:33–36

    Article  PubMed  CAS  Google Scholar 

  34. Marigold JH, Morgan AK, Earle DJ, Young AE, Croft DN (1985) Lugol’s iodine: its effect on thyroid blood flow in patients with thyrotoxicosis. Br J Surg 72:45–47

    Article  PubMed  CAS  Google Scholar 

  35. Chang DC, Wheeler MH, Woodcock JP, Curley I, Lazarus JR, Fung H, John R, Hall R, McGregor AM (1987) The effect of preoperative Lugol’s iodine on thyroid blood flow in patients with Graves’ hyperthyroidism. Surgery 102:1055–1061

    PubMed  CAS  Google Scholar 

  36. Laurberg P, Boye N (1987) Inhibitory effect of various radiographic contrast agents on secretion of thyroxine by the dog thyroid and on peripheral and thyroidal deiodination of thyroxine to tri-iodothyronine. J Endocrinol 112:387–390

    Article  PubMed  CAS  Google Scholar 

  37. DeGroot LJ, Buhler U (1971) Effect of perchlorate and methimazole on iodine metabolism. Acta Endocrinol (Copenh) 68:696–706

    CAS  Google Scholar 

  38. Barzilai D, Sheinfeld M (1966) Fatal complications following use of potassium perchlorate in thyrotoxicosis. Report of two cases and a review of the literature. Isr J Med Sci 2:453–456

    PubMed  CAS  Google Scholar 

  39. Bogazzi F, Giovannetti C, Fessehatsion R, Tanda ML, Campomori A, Compri E, Rossi G, Ceccarelli C, Vitti P, Pinchera A, Bartalena L, Martino E (2010) Impact of lithium on efficacy of radioactive iodine therapy for Graves’ disease: a cohort study on cure rate, time to cure, and frequency of increased serum thyroxine after antithyroid drug withdrawal. J Clin Endocrinol Metab 95:201–208

    Article  PubMed  CAS  Google Scholar 

  40. Martin NM, Patel M, Nijher GM, Misra S, Murphy E, Meeran K (2012) Adjuvant lithium improves the efficacy of radioactive iodine treatment in Graves’ and toxic nodular disease. Clin Endocrinol (Oxf) 77:621–627

    Article  CAS  Google Scholar 

  41. Henderson JM, Portmann L, Van Melle G, Haller E, Ghika JA (1997) Propranolol as an adjunct therapy for hyperthyroid tremor. Eur Neurol 37:182–185

    Article  PubMed  CAS  Google Scholar 

  42. Wiersinga WM (1991) Propranolol and thyroid hormone metabolism. Thyroid 1:273–277

    Article  PubMed  CAS  Google Scholar 

  43. Neumann S, Eliseeva E, McCoy JG, Napolitano G, Giuliani C, Monaco F, Huang W, Gershengorn MC (2011) A new small-molecule antagonist inhibits Graves’ disease antibody activation of the TSH receptor. J Clin Endocrinol Metab 96:548–554

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  44. Ueki I, Abiru N, Kobayashi M, Nakahara M, Ichikawa T, Eguchi K, Nagayama Y (2011) B cell-targeted therapy with anti-CD20 monoclonal antibody in a mouse model of Graves’ hyperthyroidism. Clin Exp Immunol 163:309–317

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  45. Heemstra KA, Toes RE, Sepers J, Pereira AM, Corssmit EP, Huizinga TW, Romijn JA, Smit JW (2008) Rituximab in relapsing Graves’ disease, a phase II study. Eur J Endocrinol 159:609–615

    Article  PubMed  CAS  Google Scholar 

  46. Marcocci C, Kahaly GJ, Krassas GE, Bartalena L, Prummel M, Stahl M, Altea MA, Nardi M, Pitz S, Boboridis K, Sivelli P, von Arx G, Mourits MP, Baldeschi L, Bencivelli W, Wiersinga W (2011) Selenium and the course of mild Graves’ orbitopathy. N Engl J Med 364:1920–1931

    Article  PubMed  CAS  Google Scholar 

  47. Piantanida E, Tanda ML, Lai A, Sassi L, Bartalena L (2013) Prevalence and natural history of Graves’ orbitopathy in the XXI century. J Endocrinol Invest 36:444–449

    PubMed  CAS  Google Scholar 

  48. Bülow Pedersen I, Knudsen N, Carlé A, Schomburg L, Köhrle J, Jørgensen T, Rasmussen LB, Ovesen L, Laurberg P (2013) Serum selenium is low in newly diagnosed Graves’ disease: a population-based study. Clin Endocrinol (Oxf) 79:584–590

    Article  Google Scholar 

  49. Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, Nixon A, Pearce EN, Soldin OP, Sullivan S, Wiersinga W (2011) Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 21:1081–1125

    Article  PubMed  PubMed Central  Google Scholar 

  50. Lazarus JH (2012) Antithyroid drug treatment in pregnancy. J Clin Endocrinol Metab 97:2289–2291

    Article  PubMed  CAS  Google Scholar 

  51. De Groot L, Abalovich M, Alexander EK, Amino N, Barbour L, Cobin RH, Eastman CJ, Lazarus JH, Luton D, Mandel SJ, Mestman J, Rovet J, Sullivan S (2012) Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 97:2543–2565

    Article  PubMed  Google Scholar 

  52. Marchant B, Brownlie BE, Hart DM, Horton PW, Alexander WD (1977) The placental transfer of propylthiouracil, methimazole and carbimazole. J Clin Endocrinol Metab 45:1187–1193

    Article  PubMed  CAS  Google Scholar 

  53. Yoshihara A, Noh J, Yamaguchi T, Ohye H, Sato S, Sekiya K, Kosuga Y, Suzuki M, Matsumoto M, Kunii Y, Watanabe N, Mukasa K, Ito K, Ito K (2012) Treatment of Graves’ disease with antithyroid drugs in the first trimester of pregnancy and the prevalence of congenital malformation. J Clin Endocrinol Metab 97:2396–2403

    Article  PubMed  CAS  Google Scholar 

  54. Ribuffo D, Costantini M, Gullo P, Houseman ND, Taylor GI (2003) Aplasia cutis congenita of the scalp, the skull, and the dura. Scand J Plast Reconstr Surg Hand Surg 37:176–180

    Article  PubMed  CAS  Google Scholar 

  55. Santini F, Chiovato L, Ghirri P, Lapi P, Mammoli C, Montanelli L, Scartabelli G, Ceccarini G, Coccoli L, Chopra IJ, Boldrini A, Pinchera A (1999) Serum iodothyronines in the human fetus and the newborn: evidence for an important role of placenta in fetal thyroid hormone homeostasis. J Clin Endocrinol Metab 84:493–498

    PubMed  CAS  Google Scholar 

  56. Rotondi M, Cappelli C, Pirali B, Pirola I, Magri F, Fonte R, Castellano M, Rosei EA, Chiovato L (2008) The effect of pregnancy on subsequent relapse from Graves’ disease following a successful course of anti-thyroid drug therapy. J Clin Endocrinol Metab 93:3985–3988

    Article  PubMed  CAS  Google Scholar 

  57. Azizi F, Amouzegar A (2011) Management of hyperthyroidism during pregnancy and lactation. Eur J Endocrinol 164:871–876

    Article  PubMed  CAS  Google Scholar 

  58. Zakarija M, McKenzie JM (1983) Pregnancy-associated changes in the thyroid-stimulating antibody of Graves’ disease and the relationship to neonatal hyperthyroidism. J Clin Endocrinol Metab 57:1036–1040

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Michele Marinò, Francesco Latrofa, Francesca Menconi & Paolo Vitti

  2. Endocrinology Unit, University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy

    Michele Marinò, Francesco Latrofa, Francesca Menconi & Paolo Vitti

  3. Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy

    Luca Chiovato

  4. Unit of Endocrinology, Fondazione Salvatore Maugeri IRCCS, Pavia, Italy

    Luca Chiovato

Authors
  1. Michele Marinò
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francesco Latrofa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francesca Menconi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Luca Chiovato
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paolo Vitti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michele Marinò.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Marinò, M., Latrofa, F., Menconi, F. et al. An update on the medical treatment of Graves’ hyperthyroidism. J Endocrinol Invest 37, 1041–1048 (2014). https://doi.org/10.1007/s40618-014-0136-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-014-0136-z

Keywords

Search

Navigation