Does Radioactive Iodine Therapy for Hyperthyroidism Cause Cancer?

Radioactive iodine has been considered a safe and effective therapeutic option for hyperthyroidism secondary to Graves disease and autonomously functioning thyroid nodules since the mid-20th century. The question of whether I-131 at the doses used for hyperthyroidism might increase the risk of cancer has been investigated in a number of observational cohort studies over the years, with the preponderance of evidence being reassuring as to its safety. In particular, the 1998 Cooperative Thyrotoxicosis Therapy Follow-up Study (CTTFUS) has been widely cited as compelling evidence that I-131 is safe in hyperthyroidism therapy with respect to carcinogenesis. However, in 2019, a study by Kitahara and colleagues re-analyzed the CTTFUS cohort, extending the follow-up time and applying a novel dosimetric model for estimating tissue absorbed doses of radiation. This new analysis concluded that radioactive iodine was associated with an increased risk for mortality from overall cancer, breast cancer, and non-breast solid cancers. Reaction to this study was vociferous and particularly negative in the nuclear medicine literature. This mini-review was inspired by the 2019 CTTFUS controversy, and it is intended to provide the necessary context for clinicians to provide nuanced advice to their patients on the subject. To that end, the pre-2019 literature is surveyed, the 2019 CTTFUS study and a 2020 follow-up are discussed, and lessons from the literature and critical commentaries are considered.

Diagnostic Performance of Kwak, EU, ACR, and Korean TIRADS as Well as ATA Guidelines for the Ultrasound Risk Stratification of Non-Autonomously Functioning Thyroid Nodules in a Region with Long History of Iodine Deficiency: A German Multicenter Trial

Germany has a long history of insufficient iodine supply and thyroid nodules occur in over 30 % of the adult population, the vast majority of which are benign. Non-invasive diagnostics remain challenging, and ultrasound-based risk stratification systems are essential for selecting lesions requiring further clarification. However, no recommendation can yet be made about which system performs the best for iodine deficiency areas. In a German multicenter approach, 1211 thyroid nodules from 849 consecutive patients with cytological or histopathological results were enrolled. Scintigraphically hyperfunctioning lesions were excluded. Ultrasound features were prospectively recorded, and the resulting classifications according to five risk stratification systems were retrospectively determined. Observations determined 1022 benign and 189 malignant lesions. The diagnostic accuracies were 0.79, 0.78, 0.70, 0.82, and 0.79 for Kwak Thyroid Imaging Reporting and Data System (Kwak-TIRADS), American College of Radiology (ACR) TI-RADS, European Thyroid Association (EU)-TIRADS, Korean-TIRADS, and American Thyroid Association (ATA) Guidelines, respectively. Receiver Operating Curves revealed Areas Under the Curve of 0.803, 0.795, 0.800, 0.805, and 0.801, respectively. According to the ATA Guidelines, 135 thyroid nodules (11.1%) could not be classified. Kwak-TIRADS, ACR TI-RADS, and Korean-TIRADS outperformed EU-TIRADS and ATA Guidelines and therefore can be primarily recommended for non-autonomously functioning lesions in areas with a history of iodine deficiency.

Update of Radiofrequency Ablation for Treating Benign and Malignant Thyroid Nodules. The Future Is Now

Thermal and chemical ablation are minimally invasive procedures that avoid removal of the thyroid gland and target symptomatic nodules directly. Internationally, Radiofrequency ablation (RFA) is among one of the most widely used thermal ablative techniques, and is gaining traction in North America. Surgery remains the standard of care for most thyroid cancer, and in the right clinical setting, Active Surveillance (AS) can be a reasonable option for low risk disease. Minimally invasive techniques have emerged as an alternative option for patients deemed high risk for surgery, or for those patients who wish to receive a more active treatment approach compared to AS. Herein, we review the literature on the safety and efficacy of RFA for treating benign non-functioning thyroid nodules, autonomously functioning thyroid nodules, primary small low risk thyroid cancer (namely papillary thyroid cancer) as well as recurrent thyroid cancer.

Ultrasound Assessment of Autonomous Thyroid Nodules before and after Radioiodine Therapy Using Thyroid Imaging Reporting and Data System (TIRADS)

The Thyroid Imaging and Reporting System (TIRADS) allows a sonographic assessment of the malignancy risk of thyroid nodules (TNs). To date, there is a lack of systematic data about the change in ultrasound (US) features after therapeutic interventions. The aim of this study was to characterize the changes in autonomously functioning thyroid nodules (AFTNs) after radioiodine therapy (RIT) by using TIRADS. We retrospectively assessed data from 68 patients with AFTNs treated with RIT between 2016 and 2018 who had available first and second follow-up US imaging. Before RIT, 69.1% of the AFTNs were classified as low-risk TNs when applying Kwak TIRADS (EU-TIRADS 52.9%), 22.1% were intermediate-risk TNs (EU-TIRADS 19.1%), and 8.8% were high-risk TNs (EU-TIRADS 27.9%). Twelve months after RIT, 22.1% of the AFTNs showed features of high-risk TNs according to Kwak TIRADS (EU-TIRADS 45.6%). The proportion of intermediate TNs also increased to 36.8% (EU-TIRADS 29.4%), and 41.2% were low-risk TNs (EU-TIRADS 25%). A significant percentage of AFTNs presented with features suspicious for malignancy according to TIRADS before RIT, and this number increased significantly after therapy. Therefore, before thyroid US, thorough anamnesis regarding prior radioiodine treatment is necessary to prevent unneeded diagnostic procedures.