Comparison Between Radioiodine Therapy and Single-Session Radiofrequency Ablation of Autonomously Functioning Thyroid Nodules

A Retrospective Study

Rosa Cervelli; Salvatore Mazzeo; Giuseppe Boni; Antonio Boccuzzi; Francesca Bianchi; Federica Brozzi; Pierina Santini; Paolo Vitti; Roberto Cioni; Davide Caramella


Clin Endocrinol. 2019;90(4):608-616. 

In This Article

Abstract and Introduction


Objective: To compare the efficacy of Radioiodine (RI) and Radiofrequency ablation (RFA) in the treatment of autonomously functioning thyroid nodules (AFTNs). End-points: nodule volume reduction (NVR) and thyroid function normalization.

Design, patients and measurements: Twenty-two patients (2:20 M:F; 51.9 ± 13.9 years) affected by 25 AFTNs, treated by RFA were retrospectively compared with 25 patients (8:17 M:F; 57.2 ± 12.8 years) affected by a single AFTN treated by RI. Both group showed analogous characteristics as to age, gender, toxic/pretoxic phase and pretreatment nodule volume (calculated by the ellipsoid formula). Thyroid hormone levels and autoimmune thyroid profile were assessed before treatment. A fixed RI activity of 555 MBq (15 mCi) was administered. RFA was performed with an 18G, single-tipped electrode, by the "modified moving shot technique." Thyroid hormones were assessed and the nodule post-treatment volume calculated 12 months after treatment.

Results: No statistical difference was found between the post-treatment NVR by comparing RI and RFA (P = 0.69). The volume reduction rates were 68.4 ± 28.9% and 76.4 ± 16.9% after RI and RFA, respectively. As to the thyroid function, 5/25 patients developed clinical hypothyroidism after RI. After RFA, all the 22 patients silenced their AFTN and normalized the thyroid hormones. Subclinical hypothyroidism was recorded in two patients after both RI and RFA. Thus, the functional therapeutic success, defined as the restoration of euthyroidism, was achieved in 18/25 (72%) patients treated by RI and in 20/22 (90.9%) treated by RFA.

Conclusions: No statistical difference in NVR was found between RI and RFA. All patients responded to RI but 5/25 were "over-treated" developing hypothyroidism. RFA was effective in all patients with no case of post-treatment clinical hypothyroidism. No radiation exposure and lower risk of post-treatment hypothyroidism might make RFA the favourite option especially for young patients.


The autonomously functioning thyroid nodule (AFTN), also known as Plummer's adenoma, is a predominantly benign neoplasm presenting as a solitary hyperfunctioning nodule, in an otherwise healthy thyroid gland. It is visualized as a "hot spot" by thyroid scintiscan, due to the strong concentration of Iodine-131 (131I) used as radiotracer (dose, 50 μCi), compared with the surrounding thyroid tissue. The prevalence of AFTN ranges from 0.9% up to 9%.[1,2] AFTNs can cause a range of functional abnormalities, from euthyroidism to subclinical hyperthyroidism (pretoxic nodule) and overt hyperthyroidism (toxic nodule).[3] The toxic phase of AFTN is characterized by hormonal abnormalities and clinical hyperthyroid symptoms, whereas in the pretoxic phase free triiodothyronine (fT3) and free thyroxine (fT4) are normal with low/suppressed levels of thyrotropin (TSH). Despite the absence of clinical symptoms, the pretoxic phase may determine long-term adverse effects, particularly on the skeletal bones and cardiovascular system.[4–6] Thus, treatment may be advised when compression of adjacent structures, cosmetic complaints, hyperthyroid symptoms are present, and, also, to avoid progression of hyperthyroidism or to break off the "pretoxic state," in order to evade the enlargement of the thyroid nodule together with long-term consequences. Hemithyroidectomy of the affected lobe is the standard treatment option for AFTNs.[7] However, some patients refuse surgical resection and others are unsuitable for surgery because of high-anaesthesiologic risks; therefore, alternative therapeutic strategies have been proposed.

Radioiodine (RI) treatment has been increasingly used to solve hyperthyroid states, by applying different schemes of RI doses (low or high fixed dose as well as doses calculated on the basis of the nodule size or RI uptake after 123I administration[8,9]). The optimal dose of RI to silence the hyperfunctioning nodule, avoiding the development of hypothyroidism, is still a matter of debate. As demonstrated by Allahabadia et al, patients affected by large nodules (both palpable and visible) were associated with higher risk of treatment failure after a single dose of RI, and often required a second treatment session.[10] As a consequence, RI treatment is suited for small- to medium-sized AFTNs. The absolute contraindications to this therapy are breastfeeding and pregnancy, and another disadvantage is radiation exposure.

Since the 1990s, alternative therapies have been investigated as follows: percutaneous ethanol injection (PEI)[3,11] and later laser ablation (LA)[12] were proposed for the treatment of AFTNs and proved effective techniques and possible treatment options. The PEI main drawbacks are as follows: (a) the low capability to spread into mixed or solid tissues, making the technique less effective in the treatment of solid nodules and (b) the need of multiple treatment sessions.[13] As to LA, several treatment sessions are required to normalize thyroid hormone levels.[14,15] During the last decade, Radiofrequency ablation was introduced as a reliable, minimally invasive procedure to treat symptomatic benign thyroid nodules in patients unwilling to or ineligible for surgery or RI therapy. Moreover, the Korean Society of Thyroid Radiology[16,17] suggests using RFA in patients with nodule-related symptoms, or with cosmetic problems, or in patients who are affected by AFTNs both in the toxic and pretoxic phases. In the Guidelines updated in 2017, the Korean Society stressed the risk of the worsening of pre-existing chronic diseases after surgery or RI therapy, and pointed out the controversy, which remains around the RI effect on childbearing patients. At the same time, also the first Italian opinion statement about indications of RFA included the AFTNs in the group of nodular thyroid diseases which may benefit from the procedure.[18] In particular, the Authors stated that the patients with toxic or pretoxic thyroid nodules, who are contraindicated to or refuse surgery and RI therapy, are eligible for RFA. Finally, the American Thyroid Association Guidelines confirm the RFA procedure as "a welcome novelty in the management of AFTNs".[19]

The aim of this study is to compare the efficacy of RI and RFA in the treatment of AFTNs. End-points to evaluate the efficacy of each treatment are as follows: (a) nodule volume reduction and (b) hyperfunctioning thyroid nodule silencing, to solve the hyperthyroid functional state.