Journal List > Int J Thyroidol > v.12(2) > 1138973

Chung: Medical Treatment of Graves' Disease


Among the three treatment modalities of Graves' disease which include antithyroid drug (ATD), radioactive iodine and surgery, the ATD is most commonly preferred in Korea due to ease of use and definite curative effects on the thyrotoxic symptoms. However, several uncertainties about ATD remain: for example, the mechanism of actions on immune modulation, differences in the effects of drugs among individuals and associated factors in the view of remission. In recent years, long-term ATD treatment has been confirmed as an effective and safe therapy modality in adults, and several treatment guidelines have been released which accept long-term ATD therapy as an acceptable alternative to ablative therapy in Graves' patients. In this review, we summarize the recent progress in understanding the clinical role of ATD and emerging new antithyroid drugs focusing on immunomodulation.


1. Cho BY. Hyperthyroidism: Graves' disease. Clinical thyroidolgy. 4th ed. Seoul: Korea Medical Book;2014. p. 219–284.
2. Adams DD, Purves HD. Abnormal responses in the assay of thyrotropin. Proc Univ Otago Med Sch. 1956; 34:11–12.
3. Smith BR, Dorrington KJ, Munro DS. The thyroid-stimulating properties of long-acting thyroid stimulator gamma G-globulin subunits. Biochim Biophys Acta. 1969; 192(2):277–285.
4. Hertz BE, Schuller KE. Saul Hertz, MD (1905–1950): a pioneer in the use of radioactive iodine. Endocr Pract. 2010; 16(4):713–715.
5. Astwood EB. Landmark article May 8, 1943: Treatment of hyperthyroidism with thiourea and thiouracil. By E.B. Astwood. JAMA. 1984; 251(13):1743–1746.
6. Astwood EB, Bissell A, Hughes AM. Further studies on the chemical nature of compounds which inhibit the function of the thyroid gland. Endocrinology. 1945; 37:456–481.
7. Codaccioni JL, Orgiazzi J, Blanc P, Pugeat M, Roulier R, Carayon P. Lasting remissions in patients treated for Graves' hyperthyroidism with propranolol alone: a pattern of spontaneous evolution of the disease. J Clin Endocrinol Metab. 1988; 67(4):656–662.
8. Wood LC, Ingbar SH. Hypothyroidism as a late sequela in patient with Graves' disease treated with antithyroid agents. J Clin Invest. 1979; 64(5):1429–1436.
9. Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016; 26(10):1343–1421.
10. Mazza E, Carlini M, Flecchia D, Blatto A, Zuccarini O, Gamba S, et al. Long-term follow-up of patients with hyperthyroidism due to Graves' disease treated with methimazole. Comparison of usual treatment schedule with drug discontinuation vs continuous treatment with low methimazole doses: a retrospective study. J Endocrinol Invest. 2008; 31(10):866–872.
11. Abraham P, Avenell A, Park CM, Watson WA, Bevan JS. A systematic review of drug therapy for Graves' hyperthyroidism. Eur J Endocrinol. 2005; 153(4):489–498.
12. Rotondi M, Capelli V, Coperchini F, Pinto S, Croce L, Tonacchera M, et al. Post-partum and non-post-partum relapsing Graves' hyperthyroidism display different response to anti-thyroid drugs. Eur J Endocrinol. 2018; 178(6):589–594.
13. Solomon BL, Evaul JE, Burman KD, Wartofsky L. Remission rates with antithyroid drug therapy: continuing influence of iodine intake? Ann Intern Med. 1987; 107(4):510–512.
14. Hiraiwa T, Ito M, Imagawa A, Takamatsu J, Kuma K, Miyauchi A, et al. Restriction of dietary Iodine does not ameliorate the early effect of anti-thyroid drug therapy for Graves' disease in an area of excessive iodine intake. J Endocrinol Invest. 2006; 29(4):380–384.
15. Park SM, Cho YY, Joung JY, Sohn SY, Kim SW, Chung JH. Excessive iodine intake does not increase the recurrence rate of graves' disease after withdrawal of the antithyroid drug in an iodine-replete area. Eur Thyroid J. 2015; 4(1):36–42.
16. Kim TY, Park YJ, Park DJ, Chung HK, Kim WB, Kohn LD, et al. Epitope heterogeneity of thyroid-stimulating antibodies predicts long-term outcome in Graves' patients treated with antithyroid drugs. J Clin Endocrinol Metab. 2003; 88(1):117–124.
17. Choo YK, Yoo WS, Kim DW, Chung HK. Hypothyroidism during antithyroid drug treatment with methimazole is a favorable prognostic indicator in patients with Graves' disease. Thyroid. 2010; 20(9):949–954.
18. Prakash R. Prediction of remission in Graves' disease treated with long-term carbimazole therapy: evaluation of technetium-99m thyroid uptake and TSH concentrations as prognostic indicators. Eur J Nucl Med. 1996; 23(2):118–122.
19. Rittmaster RS, Abbott EC, Douglas R, Givner ML, Lehmann L, Reddy S, et al. Effect of methimazole, with or without L-thyroxine, on remission rates in Graves' disease. J Clin Endocrinol Metab. 1998; 83(3):814–818.
20. Vos XG, Endert E, Zwinderman AH, Tijssen JG, Wiersinga WM. Predicting the risk of recurrence before the start of antithyroid drug therapy in patients with Graves' hyperthyroidism. J Clin Endocrinol Metab. 2016; 101(4):1381–1389.
21. Quadbeck B, Hoermann R, Roggenbuck U, Hahn S, Mann K, Janssen OE, et al. Sensitive thyrotropin and thyrotropinreceptor antibody determinations one month after discontinuation of antithyroid drug treatment as predictors of relapse in Graves' disease. Thyroid. 2005; 15(9):1047–1054.
22. Tun NN, Beckett G, Zammitt NN, Strachan MW, Seckl JR, Gibb FW. Thyrotropin receptor antibody levels at diagnosis and after thionamide course predict Graves' disease relapse. Thyroid. 2016; 26(8):1004–1009.
23. Kim WB. Clinical applications of thyrotropin binding inhibitor immunoglobulin (TBII) assays. J Korean Endocr Soc. 2008; 23(3):174–178.
24. Kwon H, Kim WG, Jang EK, Kim M, Park S, Jeon MJ, et al. Usefulness of measuring thyroid stimulating antibody at the time of antithyroid drug withdrawal for predicting relapse of graves disease. Endocrinol Metab (Seoul). 2016; 31(2):300–310.
25. Kahaly GJ, Bartalena L, Hegedus L, Leenhardt L, Poppe K, Pearce SH. 2018 European Thyroid Association guideline for the management of Graves' hyperthyroidism. Eur Thyroid J. 2018; 7(4):167–186.
26. Takasu N, Yamashiro K, Komiya I, Ochi Y, Sato Y, Nagata A. Remission of Graves' hyperthyroidism predicted by smooth decreases of thyroid-stimulating antibody and thyrotropin-binding inhibitor immunoglobulin during antithyroid drug treatment. Thyroid. 2000; 10(10):891–896.
27. Brito JP, Schilz S, Singh Ospina N, Rodriguez-Gutierrez R, Maraka S, Sangaralingham LR, et al. Antithyroid drugs-the most common treatment for Graves' disease in the United States: a nationwide population-based study. Thyroid. 2016; 26(8):1144–1145.
28. Tatara MR, Golynski M, Radzki RP, Bienko M, Krupski W. Effects of long-term oral administration of methimazole on femur and tibia properties in male Wistar rats. Biomed Pharmacother. 2017; 94:124–128.
29. Azizi F, Malboosbaf R. Long-term antithyroid drug treatment: a systematic review and meta-analysis. Thyroid. 2017; 27(10):1223–1231.
30. Leger J, Gelwane G, Kaguelidou F, Benmerad M, Alberti C. French Childhood Graves' Disease Study Group. Positive impact of long-term antithyroid drug treatment on the outcome of children with Graves' disease: national long-term cohort study. J Clin Endocrinol Metab. 2012; 97(1):110–119.
31. Lippe BM, Landaw EM, Kaplan SA. Hyperthyroidism in children treated with long term medical therapy: twenty-five percent remission every two years. J Clin Endocrinol Metab. 1987; 64(6):1241–1245.
32. Azizi F, Amouzegar A, Tohidi M, Hedayati M, Khalili D, Cheraghi L, et al. Increased remission rates after long-term methimazole therapy in patients with Graves' disease: results of a randomized clinical trial. Thyroid. 2019; 29(9):1192–1200.
33. Bandai S, Okamura K, Fujikawa M, Sato K, Ikenoue H, Kitazono T. The long-term follow-up of patients with thionamide-treated Graves' hyperthyroidism. Endocr J. 2019; 66(6):535–545.
34. El Fassi D, Nielsen CH, Bonnema SJ, Hasselbalch HC, Hegedus L. B lymphocyte depletion with the monoclonal antibody rituximab in Graves' disease: a controlled pilot study. J Clin Endocrinol Metab. 2007; 92(5):1769–1772.
35. Pearce SHS, Dayan C, Wraith DC, Barrell K, Olive N, Jansson L, et al. Antigen-specific immunotherapy with thyrotropin receptor peptides in Graves' hyperthyroidism: a phase I study. Thyroid. 2019; 29(7):1003–1011.
36. Furmaniak J, Sanders J, Young S, Kabelis K, Sanders P, Evans M, et al. In vivo effects of a human thyroid-stimulating monoclonal autoantibody (M22) and a human thyroid-blocking autoantibody (K1-70). Auto Immun Highlights. 2012; 3(1):19–25.
Similar articles