Hyperthyroidism is a clinical condition characterized by low thyroid-stimulating hormone (TSH) blood levels and normal or higher blood levels of triiodothyronine (FT3) and thyroxine (FT4). Typically nervousness, heat intolerance, palpitations, and weight loss despite increased appetite are the main symptoms and signs of hyperthyroidism affecting female sex in most cases [1, 2]. Graves’ disease can explain the majority of hyperthyroidism diagnosis [3], while autonomously functioning thyroid nodules (AFTN) represent a secondary, but not negligible, cause of hyperthyroidism [4].

Radioactive iodine (RAI) administration and surgery are the main treatment options for AFTN, but recently radiofrequency ablation (RFA) has been proposed as an alternative [5]. Radiofrequency is widely used for the treatment of non-functioning benign thyroid nodules (NFTN) due to its mini-invasive profile, the ability to reduce nodule volume and low rate of complications. However, clinical experience with RFA as a therapy for AFTN is limited, particularly regarding the availability of comprehensive follow-up data [6,7,8,9,10].

RAI therapy is based on the natural capacity of thyroid cells to take iodine trough sodium iodine symporter (NIS) and [131]-iodine β-emission able to induce cell death [11,12,13,14]. RAI is considered a cornerstone for the treatment of hyperfunctioning thyroid diseases right from its introduction in clinical practice to nowadays, acting as a valid alternative to surgery [5, 15,16,17,18]. Some advantages over surgery, stemming from RAI’s good safety and tolerability profile, the theragnostic capability, and the lower healthcare cost, have significantly contributed to its clinical use success [5].

In a recent systematic review and comparative meta‑analysis, Giovanella and co-workers compares RFA to RAI as standard of care [19]. The study included 23 articles comparing the response rate of RAI and RFA for the treatment of AFTN. Hypothyroidism or euthyroidism was defined as primary outcome, while nodule volume reduction and TSH level modification were defined as secondary outcome. Primary and secondary outcomes were evaluated between 3 and 6 months, between 6 and 12 months, and at the end of the follow-up period (if > 12 months). A total of 296 patients treated with RFA and 1042 patients who received RAI therapy for AFTN were included into the statistical analysis. Some studies considered for the meta-analysis carried out by Giovannella and co-workers, including a total of 141 patients, directly compared RAI and RFA. In the pooled data analysis, they found a higher success rate with RAI therapy compared to RFA, along with a greater risk of failure associated with RFA treatment. However, the latter finding did not reach statistical significance.

The analysis of the entire population of 1338 patients revealed a pooled success rate of 94% among those treated with RAI administration, while only 59% of the patients who underwent RFA reached the primary outcome.

This study confirms the superiority of RAI therapy over the newly proposed RFA for the treatment of AFTN. Hyperthyroidism poses a significant threat if left untreated for an extended period and is linked to higher cardiovascular disease risk [20,21,22,23], osteoporosis, and potentially to increased risk of certain tumor development [24,25,26]. Therefore, a prompt correction of this condition is mandatory.

In addition, RFA is hardly free of side effects that are various and not negligible [27,28,29] compared with those related with RAI administration [30,31,32,33]. RFA is a novel introduction in clinical practice requiring technical improvements and a deeper understanding of its potential and limitations. RAI comes with an extensive clinical use along with a large number of treated patients. Several studies have been conducted to better clarify its role, its safety, and efficacy in either AFTN or other thyroid pathologies cure [4, 17, 34,35,36,37]. While radiation exposure can be a point of concern, the overall safety and tolerability of RAI administration along with its specificity and efficacy might easily still make RAI therapy the treatment of choice for AFTN.