Increased Remission Rates After Long-Term Methimazole Therapy in Patients with Graves' Disease: Results of a Randomized Clinical Trial

Thyroid. 2019 Sep;29(9):1192-1200. doi: 10.1089/thy.2019.0180. Epub 2019 Aug 28.


Background: Studies differ regarding whether, compared with courses of conventional duration, longer-term antithyroid drug treatment increases frequency of remission in patients with Graves' hyperthyroidism. We prospectively conducted a randomized, parallel-group study comparing relapse rates in patients receiving longer-term versus conventional-length methimazole therapy. We also sought variables associated with relapse following the latter. Methods: We enrolled 302 consecutive patients with untreated first episodes of Graves' hyperthyroidism. After 18-24 months of methimazole, 258 patients (85.4%) were randomized to an additional 36-102-month courses ("long-term group": n = 130; scheduled total time on methimazole: 60-120 months) or discontinuation of methimazole ("conventional group": n = 128). Patients were followed 48 months postmethimazole cessation. We performed Cox proportional hazards modeling to identify factors associated with relapse after conventional courses. Results: Methimazole was given for 95 ± 22 months in long-term patients and 19 ± 3 months in the conventional group. Fourteen patients experienced cutaneous reactions and 2 liver enzyme elevations during the first 18 months of treatment; no further methimazole-related reactions were observed despite therapy for up to another 118 months. Hyperthyroidism recurred within 48 months postmethimazole withdrawal in 15% (18/119) of long-term patients versus 53% (65/123) of conventional group patients. In the conventional group, older age, higher triiodothyronine or thyrotropin receptor antibody concentrations, lower thyrotropin concentration, or possession of the rs1879877 CD28 polymorphism or the DQB1-05 HLA polymorphism were independently associated with relapse. Conclusion: Administration of low-dose methimazole for a total of 60-120 months safely and effectively treats Graves' hyperthyroidism, with much higher remission rates than those attained by using conventional 18-24-month courses.

Keywords: Graves' disease; long-term; methimazole; remission rates.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antithyroid Agents / therapeutic use*
  • Female
  • Graves Disease / drug therapy*
  • Humans
  • Male
  • Methimazole / adverse effects
  • Methimazole / therapeutic use*
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • Recurrence


  • Antithyroid Agents
  • Methimazole

Associated data

  • IRCT/5143