Radioactive Iodine Treatment in Hyperthyroidism and Cancer Mortality-A Still Controversial Issue.

Abstract

Hyperthyroidism is a severe condition of thyroid hormone excess.1 Graves disease (GD), toxic multinodular goiter, and toxic adenoma are the most common causes of hyperthyroidism in younger individuals living in areas with iodine sufficiency and in older individuals in iodine-deficient regions.1 Hyperthyroidism has been associated with an increased risk of coronary heart disease mortality and incident atrial fibrillation, even in patients with subclinical hyperthyroidism with an undetectable serum thyroid-stimulating hormone level but particularly in older patients and in those with underlying heart diseases.1 Therefore, fast and effective control of hyperthyroidism is necessary to avoid adverse outcomes. There are currently 3 main treatment options available for hyperthyroidism: (1) medical treatment with antithyroid drugs (ATDs), (2) radioactive iodine (RAI) therapy, and (3) surgery.1 Each treatment has specific benefits and risks, which is why international guidelines for the management of hyperthyroidism support the use of personalized treatment according to clinical conditions, a risk-benefit analysis, and patient preferences.2 Medical treatment with ATDs is the primary treatment in hyperthyroidism caused by GD. Although associated with rare but serious adverse effects, it gives patients a 40% chance of remission.1 In Europe, approximately two-thirds of the members of the European Thyroid Association prefer a first approach with ATDs. RAI therapy or surgery are definitive treatment options that, due to the permanent destruction or removal of the thyroid gland, result in hypothyroidism.1 RAI is used to cure patients with subclinical and overt hyperthyroidism due to toxic multinodular goiter or toxic adenoma, where remission is not feasible.1 Approximately one-third of patients with hyperthyroidism require 2 or more I-131 treatments to be cured. RAI is usually the second-line treatment in patients with GD who relapse after initial thionamide treatment, in those who do not tolerate ATDs, and in those with cardiac diseases. However, RAI is the preferred first-line therapy for GD in the United States and the United Kingdom because it is associated with a higher cure rate and lower relapse rate compared with ATDs.3 In recent years, conflicting data have been published on the risk of malignant neoplasms in patients with hyperthyroidism following RAI.4,5 However, hyperthyroidism itself has been associated with an increased risk of cancer, supporting a potential role of thyroid hormone excess on carcinogenicity.6 In addition, an increased overall risk of cancer and greater cancer mortality has been reported with ATDs therapy when compared with RAI.7 The body of evidence on a potential association between RAI treatment and cancer incidence and mortality in patients with hyperthyroidism is still highly heterogeneous because the biological effects of RAI on different tissues are difficult to assess. On the contrary, 2 recent meta-analyses did not find any association between RAI and the risk of incident cancer4 or cancer mortality5 in patients with hyperthyroidism. Nevertheless, most studies have some important methodological limits, such as the lack of a control group including patients with hyperthyroidism who are treated with therapies other than RAI and the lack of evaluation of some potential confounding factors, such as smoking, obesity, and alcohol consumption. In the first analysis of data from a large multicenter trial, the Cooperative Thyrotoxicosis Therapy Follow-up Study, a modest increased risk of solid cancer was reported in patients with + Related article