Comparative effectiveness of therapies for Graves' hyperthyroidism: a systematic review and network meta-analysis

J Clin Endocrinol Metab. 2013 Sep;98(9):3671-7. doi: 10.1210/jc.2013-1954. Epub 2013 Jul 3.


Context: Several treatment options are available for Graves' disease (GD), including antithyroid drugs (ATDs), radioactive iodine (RAI), and thyroidectomy.

Objective: The primary outcome was to determine the relapse rates of various treatment options. The secondary outcome was to present data regarding adverse effects of ATDs.

Data sources: We searched multiple databases through March 2012.

Study selection: Eligible studies were randomized clinical trials and comparative cohort studies in adults that included 2 or more treatment options for GD.

Data extraction: Two reviewers independently selected studies, appraised study quality, extracted outcome data, and determined adverse effect profiles.

Data synthesis: We found 8 studies with 1402 patients from 5 continents. Mean follow-up duration in months was: ATDs, 57; RAI, 64; and surgery, 59. Studies were at moderate to high risk of bias. Network meta-analysis suggested higher relapse rates with ATDs (52.7%; 352 of 667) than RAI (15%, 46 of 304) (odds ratio = 6.25; 95% confidence interval, 2.40-16.67) and with ATDs than surgery (10%; 39 of 387) (odds ratio = 9.09; 95% confidence interval, 4.65-19.23). There was no significant difference in relapse between RAI and surgery. Examination of 31 cohort studies identified adverse effects of ATDs in 692 of 5136 (13%) patients. These were more common with methimazole, mainly owing to dermatological complications, whereas hepatic effects were more common with propylthiouracil use.

Conclusion: We confirm the relatively high relapse rate of ATD therapy in comparison with RAI or surgery, along with a significant side effect profile for these drugs. These data can inform discussion between physicians and patients regarding the choice of therapy for GD. The limited quality of the evidence in the literature underlines the need for future randomized clinical trials in this area.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Review
  • Systematic Review

MeSH terms

  • Antithyroid Agents / therapeutic use*
  • Databases, Factual
  • Female
  • Graves Disease / drug therapy
  • Graves Disease / radiotherapy
  • Graves Disease / surgery
  • Graves Disease / therapy*
  • Humans
  • Iodine Radioisotopes / therapeutic use*
  • Male
  • Recurrence
  • Thyroidectomy
  • Treatment Outcome


  • Antithyroid Agents
  • Iodine Radioisotopes