131I-Induced Graves' disease in patients treated for toxic multinodular goitre: systematic review and descriptive analysis

Background Graves' disease (GD) arising after the treatment of toxic multinodular goitre (TMNG) with radioiodine has long been described but it remained unclear whether GD was in fact iodine induced, its incidence, risk factors, natural history and treatment outcomes. Methods: A systematic search using The Cochrane Library, Medline and PubMed Central allowed the pooling of data from 3633 patients with thyroid autonomy, 1340 patients with TMNG, to fill gaps in knowledge, regarding the clinical expression of iodine-induced GD (I-131-IGD) in adults. Results I-131-IGD developed in 0-5.3% of those with thyroid autonomy (first year) and in 5-5.4% of those with TMNG, 3-6 months after treatment. Patients with toxic adenoma were less affected. I-131-IGD was more common in patients with pre-treatment direct or indirect signs of autoimmunity: positive anti-TPO (p < 0.05), glandular hypoechogenicity, TRAbs within reference range, diffuse uptake on 99mTc-pertechnetate scans (p < 0.05), findings that may increase the risk tenfold. I-131-IGD manifested 3 months after I-131, justifying 15.4-29% of cases of relapse. The rate of spontaneous remission was 17-20% (6 months) and the rate of relapse after a second I-131 treatment 22-25%. The use of an uptake-based administered I-131 activity led to a greater proportion of euthyroid patients (78% compared to 25-50% with the mass-based approach). Conclusions GD may be triggered by I-131. The incidence of the condition is low. Several risk factors were consistently identified; some have shown to raise the risk significantly. I-131-IGD seems more treatment resistant than iodine-independent GD and the best resolution rates were achieved with uptake-based selected iodine activities.