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

Disclosures

Clin Endocrinol. 2019;90(4):608-616. 

In This Article

Discussion

The conventional treatment of AFTNs is the hemithyroidectomy of the affected lobe, which guarantees the preservation of the thyroid function by the contralateral healthy thyroid lobe and decreases the risk of permanent hypocalcemia if the parathyroid glands of the affected side are damaged. However, the risk of permanent unilateral laryngeal nerve injury still remains with a percentage ranging from 0% to 2.1%.[7,21]

The most widely diffused alternative choice of treatment is RI, because of the high percentage of clinical efficacy (thyroid function is normalized in 75%-95% of patients after 3–12 months) and to the low cost of the therapy.[22] However, in pregnant or breastfeeding women RI is absolutely contraindicated. Moreover, in women of childbearing age who develop thyrotoxicosis, the management of possible future pregnancy should be discussed in advance: pregnancy should be delayed until euthyroidism is restored.[23] The options for such functional restoration are as follows: thyroid surgery, ablative therapy using RI, or ATDs. Surgery might cause permanent neck scar, which might discourage young patients. The main disadvantage of RI is the conception delayed at least for 6 months; as to ATDs, they resolve the symptoms, but, when discontinued, the reappearance of the disease is certain. Moreover, due to the ATDs capability to cross the placenta, as well as to modulate foetal thyroid function, the pursuance of this therapy during pregnancy is to be avoided.[24,25] In both male and female young patients, the RI therapy exposes them to radiation; the administered 15 mCi dose of 131I to young men showed a reduced sperm motility, which can, therefore, determine infertility in subjects at risk.[26] Finally, in order to successfully undergo RI therapy, the ATDs should be discontinued for 21–25 days prior to RI therapy, in order to have suppressed levels of TSH, which guarantees the 131I concentration in the AFTNs. However, this management exposes the patients to the risks associated with the symptoms of hyperthyroidism (especially cardiovascular diseases). These disadvantages lead to seeking alternative treatments to RI therapy, especially in these selected groups of patients. The RFA is a possible alternative therapy to RI in the treatment of AFTNs, showing efficacy in restoring euthyroidism, especially in nodules of small dimension.[27] Indeed, in young hyperthyroid patients, both males and females, the RFA can have advantages: (a) rapid efficacy of the therapy without wash-out period in which it is not possible to attempt conception. As demonstrated by Sung et al, no postprocedural aggravation of symptoms was experienced, and, because of the RFA efficacy, the ATDs can be interrupted or significantly reduced immediately after the procedure;[6] (b) low risk of major complications, which include permanent voice change (0%-2.3%), nodule rupture (0.1%), Horner syndrome (0.1%) and spinal accessory nerve injury (0%-2.3%);[6,27–29] (c) finally, the absence of postprocedural scars.[30,31] At the same time, in patients affected by cardiovascular comorbidities, RFA allows the ATDs administration until the day before the procedure.

In our study, 22 patients with 25 AFTNs treated with a single session of RFA, and 25 patients with a single AFTN treated with a dose of 15mCi of 131I were compared. The two groups were homogeneously selected in terms of age, sex, functional phase of hyperthyroidism, ATD administered and pretreatment volume of the nodule. Both procedures proved to be safe. In particular, in the RFA-treated group of patients no complications were recorded: neither transient nor permanent paralysis of the laryngeal nerve, bleeding or protracted pain (more than 24 hours) were experienced. No patient needed to contact the Center in the 30 days between treatment and the first check because of the appearance of clinical symptoms related to hyperthyroidism. The latter datum was particularly important for the group of RFA-treated patients, where a possible adverse effect might have been the uncontrolled release of free thyroid hormones, as a result of the mechanical cell damage induced by ablative therapy. To monitor this hypothetic effect, the first 5 consecutive patients, who underwent RFA, repeated the TSH, fT3 and thyroglobulin (Tg) dosage immediately after the procedure, and then 3 and 24 hours after the procedure. In all 5 cases, there was no uncontrolled variation of TSH or fT3, while a transient over-threshold increase of the Tg value was recorded.

In our study, the end-points to evaluate the efficacy of each therapy were the volume nodule reduction 12 months after the chemical or thermal ablation, and the solution of the hyperthyroid state. As to volume reduction, both RI and RFA were effective, though the decrease was slightly in favour of RFA (76.4% versus 68.4%). These results were in agreement with the Literature, which reports the average of AFTN volume reduction rate of 35%-54% after RI therapy[14,22,32] and of 52.1% and 79.7% after RFA.[6,33] As to RFA, it showed percentage of volume reduction higher than the other minimally invasive procedures applied on the hyperfunctioning thyroid nodules. In fact, Dossing et al reported 6-month post-laser ablation VRR of 44%,[14] whereas results from a series of hyperthyroid patients treated by PEI (in several sessions) showed VRRs at the 12-month check of 72% and 66% in pretoxic and toxic nodules, respectively.[34]

As to the normalization of the thyroid function after treatment, all patients, both those treated with RFA and those with RI, silenced their AFTN. Despite the majority of patients (72%) treated by RI therapy were restored to euthyroidism, 5 patients developed clinical hypothyroidism (ie, TSH values over 9.0 microUI/mL or high TSH values associated with fT4 values lower than the range). Among the 5 post-treatment hypothyroid patients, two of them were in a pretoxic phase when the RI was administered. This condition was characterized by non-suppressed TSH values, which increases the risk of 131I not exclusively concentrating in the AFTN. As a consequence, the 131I may determine damage to the healthy thyroid tissue. Moreover, another of the 5 post-treatment hypothyroid patients had positive TPOAb before RI therapy. High levels of TPOAb can underlay Hashimoto thyroiditis and, as a consequence, can be considered a risk factor for post-treatment hypothyroidism.[35,36] Finally, 2/5 patients showed a prevalent nodule uptake with only partial suppression of the remaining thyroid parenchyma by thyroid scintiscan (one of them was in a functional pretoxic phase). From the nuclear medicine point of view, this condition might be considered risky since the 131I is taken up by the thyroid tissue surrounding the AFTN, damaging the "healthy" gland.[37] As to the patients treated by RFA, none developed clinical hypothyroidism. Two patients showed subclinical hypothyroidism, and one of them required the administration of a low dose (225 mcg/week) of LT4. The thyroid gland surrounding the AFTN of both patients was affected by thyroiditis (Figure 3). The patient who needed LT4 was affected by Hashimoto thyroiditis with positive TPOAb level before RFA treatment. The ablation silenced the affected nodule, restoring the functionality of the surrounding thyroid tissue. For the restoration of normal thyroid hormone function, RF could be considered more effective than RI. The percentage of hypothyroidism after RI in our series was 20%, in agreement with the Literature, where the risk of developing post-RI hypothyroidism is 12%-32% after a year.[38,39] This is most likely due to the perinodular uptake of RI. As to RFA, the substitution medical therapy (LT4) was required in only one patient because the procedure was specifically targeted at the nodule, and it was effective independently of the toxic or pretoxic functional phases. Thus, despite the high cost of the electrode used in RFA—ten times more expensive than the cost of the administered dose of RI—the minimally invasive RFA procedure showed two main benefits: the reduction of the risk of hypothyroidism and the absence of exposure of patients to radiation.

Figure 3.

A, EchoColor-Doppler US exam of the pretreatment nodule and B, enhanced vascularization by CEUS. C, B-mode US exam performed 12 months after RFA and D, the unenhanced pattern showing complete nodule necrosis. The lesion margins are indicated by "+". E, The contralateral "healthy" thyroid lobe in lateral and F, anterior-posterior US view. The lobe is slightly hypoechoic, dimensionally reduced and with intra-parenchymal calcification. The thyroid lobe boundaries are indicated by "+"

One of the limits of our study lies in the retrospective analysis of the data and in the length of the follow-up (1 year). In fact, our research was not a randomized trial, despite the fact the series of patients included in each group were statistically homogeneous in terms of gender, age, functional thyroid phase, medical treatment received before RI or RFA, and the pretreatment nodule volume. Moreover, the series of patients was limited and the operator who performed RFA was the same in all cases. Probably, the reliability of the results would increase if the study were a multicentric one including a higher number of patients. Finally, the post-treatment scintiscan was not performed; all patients were evaluated in the follow-up period, by laboratory tests and US (CEUS in the RFA group) because the goal of the therapy was to solve the hyperthyroid state.

In conclusion, in an era of "personalized medicine," it would be recommendable to adjust the therapy to the individual patient. Cost-effective RI is good for older patients with no serious cardiovascular comorbidities, though the percentage of hypothyroidism after RI treatment in our series was still 20%. On the contrary, RFA did not determine clinical hypothyroidism. Moreover, the absence of radiation exposure, the lower risk of post-treatment hypothyroidism, the possibility to continue ATD therapy until the day before the RFA procedure make RFA the best option for women of childbearing age, young men with moderate to high risk of infertility and patients affected by cardiovascular diseases, for whom a discontinued medical therapy would be risky.

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