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

Materials and Methods

This study is a retrospective analysis of data collected prospectively. The study was approved by our institutional review board (CEAVNO) on May 19th 2016; an informed consent form to the procedure was signed by all the patients.

From May 2013 to March 2017, 22 consecutive patients (2 males, 20 females; mean age, 51.9 ± 13.9 years; range 26–72 years) affected by a total of 25 AFTNs and treated by RFA were included in our study and compared with 25 patients with a single AFTN treated by the routine practice of RI. To reduce bias in comparing these two therapies, the series of patients included in the RI group were retrospectively selected among the RI treatments performed between January 2015 and January 2017 in our Institution, in order to match them with the RFA group of patients. As a consequence of the matching, it was possible to find out that both groups of patients showed analogous characteristics as to the crucial parameters of age, gender, toxic/pretoxic phases and pretreatment volume of the nodules. The volume of the nodule was calculated according to the ellipsoid formula: a*b*c*π/6; where a, b and c are the diameters measurements. The matching was created by using the chi-square test to compare the selected categorical, non-numerical parameters based on the treatment received (gender, pre-RFA or RI treatment with antithyroid drug therapy, autoimmune thyroiditis, functional phase of the hyperthyroidism). As to the selected continuous numerical parameters (age, pretreatment TSH value, pretreatment nodule volume), the "bivariate statistical analysis" was performed to confirm the appropriate comparison of the RI and RFA groups.

Pretreatment Assessment

The thyroid hormone levels (TSH, fT3, fT4) and the autoimmune profile (thyroid peroxidase antibody—TPOAb and antithyroglobulin antibody—TgAb) were assessed in each patient before the treatment. The TSH normal range was between 0.4 and 4.0 microUI/mL, and a cut-off of <0.1 microUI/mL was chosen to indicate suppressed TSH levels. The reference normal laboratory values ranged between 2.7 and 5.7 ng/mL for fT3, 0.7-1.7 ng/mL for fT4, <30 UI/mL for TPOAb and finally <10 UI/mL for TgAb. If the laboratory tests showed a thyrotoxic phase, the antithyroid drug (ATD) treatment was administered in order to restore euthyroidism.

Thyroid scintiscan. All patients were evaluated by thyroid scintiscan, in order to confirm the strong concentration of the 131I radiotracer into the nodule. The radioiodine scintigraphy with uptake allowed the calculation of the 131I uptake values and the thyroid imaging after the administration per os of 50 μCi of radioiodine. The uptake values were performed on the 3rd and the 24th hour (New Atomlab 950, Biodex Medical System, Urbino, Italy). The thyroid imaging was acquired on the 24th hour using a single-head large field-of-view gamma camera (Omnia TH33, Mediso Ltd., Budapest, Hungary) equipped with high-energy, high-resolution collimators. In our study, the AFTN was assessed as a hyperfunctioning nodule which determines complete suppression of the surrounding thyroid tissue when the scintigraphic examination showed radiotracer uptake exclusively in the nodule area, whereas when the uptake of the radiotracer was still visible, though slightly sparsely, in the whole thyroid gland the nodule was assessed as hyperfunctioning nodule partially suppressing the remnant thyroid tissue (Figure 1).

Figure 1.

A, Exclusive nodule uptake of the radiotracer, with complete suppression of the remaining thyroid parenchyma. B, Prevalent nodule uptake with partial suppression of the remaining thyroid parenchyma

Ultrasound evaluation. A B-mode Ultrasound (US) exam (7.5 MHz, MyLab Twice, Esaote, Italy) was performed to define the nodule texture (solid or mixed) and to calculate the volume of each nodule according to the ellipsoid formula: V = πabc/6 (where V is volume, a is the largest diameter, and b and c are the two other orthogonal diameters). In the RFA group, the contrast-enhanced ultrasound (CEUS) exam was also performed. The CEUS exam is a useful instrument to evaluate the efficacy of the RFA, because the unenhanced pattern is an indirect index of tissue necrosis.[20] Before treatment, a cytological confirmation of the benign nature of all AFTNs was obtained.

RFA Procedure

After conscious sedation and a local lidocaine US-guided injection to achieve thyroid capsular anaesthesia, RFA was performed. When the AFTNs showed a mixed (fluid and solid) structure, a preliminary aspiration of the main fluid component was performed to obtain only predominantly solid lesions (solid component > 75%).

All RFAs were performed using a RF generator (VIVA RF generator, STARmed, Korea), an 18-gauge internally cooled straight type electrode (10-mm active tip) and by applying the "modified moving shot technique".[21] The "modified moving shot technique" was performed in antero-posterior view of the US-guidance and by using a radial movement of the electrode to create a cone-shaped ablative volume. This technique allowed selecting the shorter pathway to the central and deepest portion of the nodule and, as a consequence, to reduce the number of insertion points into the skin. During the procedure, RF power was applied in a range from 30 to 45 Watt. The impedance was carefully monitored to avoid tissue carbonization. The efficacy of RFA was evaluated by performing CEUS examination once or twice before ending the procedure. The ablation was stopped only when the CEUS exam showed complete devascularization of the AFTN, with an unenhanced pattern. In fact, differently from the RFA treatment in benign non-functioning nodules, where the aim is cytoreduction, the RFA goal in AFTNs is the complete necrosis of the nodule, which produces an excess of thyroid hormones. The US-guide allowed monitoring procedural complications during or after RFA. Ice was applied on the patient's neck skin at the end of the procedure, to prevent oedema of the superficial tissue.

All the RFA procedures were performed by a single operator (S.M.), with more than 5 years' experience in RFA of thyroid nodular diseases and with more than 20 years' experience in percutaneous ablative treatments on liver and kidney.

RI Ablation

The RI therapeutic activity administered was 15 mCi (555 MBq) of 131I to all patients independently of the pretreatment nodule volume. It was administered in a "day hospital regimen"; this management was in accordance with the European Council Euratom Directive 97/43 and the Italian Legislative Decree 187/2000, which define the maximum outpatient dose as 16.2 mCi (600 MBq). RI was administered when the TSH level was almost suppressed as a result of the patient's hyperthyroid state, in order to have it concentrated only in the nodule. In fact, if the patient had been previously treated with ATDs, these were discontinued 21–25 days before the patient's RI treatment.


In both groups of patients showing a pretreatment "toxic" phase controlled by ATD, the ATD was discontinued immediately after the chemical or thermal ablation. All patients were asked to repeat TSH and fT3 dosage 30–45 days after treatments to verify the absence of hormonal abnormalities (in particular the absence of the combination of suppressed TSH levels and over-range fT3). Moreover, they were invited to contact our Center if they experienced hyperthyroid symptoms in between treatment and laboratory exams.

Twelve months after treatment TSH, fT3, fT4 were assessed. The nodule volume was calculated by B-mode US, according to the ellipsoid formula. In the RF group, the US examination of the nodule was completed by performing CEUS, to monitor the "necrotic" portion of the nodule (Figure 2).

Figure 2.

A, EchoColor-Doppler US exam of the pretreatment nodule and B, enhanced vascularization by CEUS. C, CEUS exam performed at the end of the RFA procedure, which shows the unenhanced pattern as an indirect index of complete tissue necrosis. The lesion margins are indicated by "+"

Statistical Analysis

All statistical computations were performed with dedicated software packages (JMP statistical software 7.0, SAS; Cary, NC, USA). Continuous variables were reported as means ± SD; categorical variables were reported as frequencies or percentages.

Data of the two groups were compared with the appropriate use of the Fisher exact test and the Wilcoxon rank test. A P value less than 0.05 was considered indicative of a significant difference.