title: Radioiodine therapy versus antithyroid medications for Graves' disease.
abstract: BACKGROUND
  Graves' disease is the most common cause of hyperthyroidism. Both antithyroid medications and radioiodine are commonly used treatments but their frequency of use varies between regions and countries. Despite the commonness of the diagnosis, any possible differences between the two treatments with respect to long-term outcomes remain unknown.
  
  
  OBJECTIVE
  To assess the effects of radioiodine therapy versus antithyroid medications for Graves' disease.
  
  
  METHODS
  We performed a systematic literature search in the Cochrane Library, MEDLINE and EMBASE and the trials registers ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was September 2015 for all databases.
  
  
  METHODS
  Randomised controlled trials (RCTs) comparing the effects of radioiodine therapy versus antithyroid medications for Graves' disease with at least two years follow-up.
  
  
  METHODS
  Two authors independently screened titles and abstracts for relevance. One author carried out screening for inclusion, data extraction and 'Risk of bias' assessment and a second author checked this. We presented data not suitable for meta-analysis as descriptive data. We analysed the overall quality of evidence utilising the GRADE instrument.
  
  
  RESULTS
  We included two RCTs involving 425 adult participants with Graves' disease in this review. Altogether 204 participants were randomised to radioiodine therapy and 221 to methimazole therapy. A single dose of radioiodine was administered. The duration of methimazole medication was 18 months. The period of follow-up was at least two years, depending on the outcome measured. For most outcome measures risk of bias was low; for the outcomes health-related quality of life as well as development and worsening of Graves' ophthalmopathy risks of performance bias and detection bias were high in at least one of the two RCTs.Health-related quality of life appeared to be similar in the radioiodine and methimazole treatment groups, however no quantitative data were reported (425 participants; 2 trials; low quality evidence). The development and worsening of Graves' ophthalmopathy was observed in 76 of 202 radioiodine-treated participants (38%) and in 40 of 215 methimazole-treated participants (19%): risk ratio (RR) 1.94 (95% confidence interval (CI) 1.40 to 2.70); 417 participants; 2 trials; low quality evidence. A total of 35% to 56% of radioiodine-treated participants and 42% of participants treated with methimazole were smokers, which is associated with the risk of worsening or development of Graves' ophthalmopathy. Euthyroidism was not achieved by any participant being treated with radioiodine compared with 64/68 (94%) of participants after methimazole treatment (112 participants; 1 trial). In this trial thyroxine therapy was not introduced early in both treatment arms to avoid hypothyroidism. Recurrence of hyperthyroidism (relapse) in favour of radioiodine treatment showed a RR of 0.20 (95% CI 0.01 to 2.66); P value = 0.22; 417 participants; 2 trials; very low quality evidence. Heterogeneity was high (I² = 91%) and the RRs were 0.61 or 0.06 with non-overlapping CIs. Adverse events other than development of worsening of Graves' ophthalmopathy for radioiodine therapy were hypothyroidism (39 of 41 participants (95%) compared with 0% of participants receiving methimazole, however thyroxine treatment to avoid hypothyroidism was not introduced early in the radioiodine group - 104 participants; 1 trial; very low quality evidence) and drug-related adverse events for methimazole treatment (23 of 215 participants (11%) reported adverse effects likely related to methimazole therapy - 215 participants; 2 trials; very low quality evidence). The outcome measures all-cause mortality and bone mineral density were not reported in the included trials. One trial (174 participants) reported socioeconomic effects: costs based on the official hospital reimbursement system in Sweden for patients without relapse and methimazole treatment were USD 1126/1164 (young/older methimazole group) and for radioiodine treatment USD 1862. Costs for patients with relapse and methimazole treatment were USD 2284/1972 (young/older methimazole group) and for radioiodine treatment USD 2760.
  
  
  CONCLUSIONS
  The only antithyroid drug investigated in the two included trials was methimazole, which might limit the applicability of our findings with regard to other compounds such as propylthiouracil. Results from two RCTs suggest that radioiodine treatment is associated with an increased risk of Graves' ophthalmopathy. Our findings suggest some benefit from radioiodine treatment for recurrence of hyperthyroidism (relapse) but there is uncertainty about the magnitude of the effect size.
authors.affiliation: Nuclear Medicine, Affiliated XinHua Hospital of Medical School Shanghai Jiaotong University, Kongjiang Road 1665, Shanghai, Shanghai, China, 200092.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.forename: Jiawei
authors.initials: J
authors.lastname: Xie
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Jinsong
authors.initials: J
authors.lastname: Li
authors.forename: Suyun
authors.initials: S
authors.lastname: Chen
mesh_terms: D013956:Antithyroid Agents / Q000627:therapeutic use*; D006111:Graves Disease / Q000628:therapy*; D049970:Graves Ophthalmopathy / Q000209:etiology; D006801:Humans; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*; D008713:Methimazole / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence
chemical_list: D013956:Antithyroid Agents; D007457:Iodine Radioisotopes; D008713:Methimazole