Safety and Efficacy of Radiofrequency Ablation of Thyroid Nodules

Expanding Treatment Options in the United States

Iram Hussain; Fizza Zulfiqar; Xilong Li; Shahzad Ahmad; Jules Aljammal


J Endo Soc. 2021;5(8) 

In This Article


Conservative estimates indicate that 100 000 to 150 000 thyroidectomies are performed in the United States annually.[35,36] An estimated 53 000 patients developed thyroid cancer in 2020,[37] indicating that most thyroidectomies are for benign disease.[35] It is well established that high-volume thyroid surgeons have lower complication rates;[36,38] however, 69% to 86% of the thyroidectomies in the United States are not performed by high-volume surgeons.[39–41] Risks include hypoparathyroidism, both transient (8.2%-39%) and persistent (0.7%-3%); severe hypocalcemia necessitating hospitalization (0.5%-12.5%); recurrent laryngeal nerve injury, both transient (3%-8%) and persistent (0.2%-6.6%); and hemorrhage (0.7%-2.1%).[4,42–47] Up to 40% of patients also report transient minor symptoms, including voice change, dysphagia, or choking sensation postoperatively.[42] Conventional thyroidectomy and minimally invasive video–assisted thyroidectomy (MIVAT) both result in a permanent scar on the neck.[9] Clinicians tend to underestimate the negative perceptions that patients have regarding scarring and may not realize that most patients prefer a "scarless" approach.[48] This is especially true among non-White patients who can experience a significant decline in quality of life because of scar-related issues.[48,49]

When radioactive iodine ablation is used for AFTNs (toxic adenomas or toxic multinodular goiters), up to 40% of patients become hypothyroid within 5 to 8 years, and ~21% have persistence or recurrence of hyperthyroidism.[11–13] Furthermore, a higher dose of radioactive iodine (131I) is typically needed to achieve a higher cure rate, especially in toxic multinodular goiters, and this results in a higher rate of hypothyroidism.[50] In a small subset of patients with AFTNs, administration of [131]I may result in development of TSH-receptor antibodies and Graves-like hyperthyroidism.[51] A trend toward increase in solid organ malignancies is also noted in hyperthyroid patients treated with radioactive iodine ablation.[52]

Radiofrequency ablation offers a therapeutic approach that can mitigate some of the above-mentioned disadvantages of surgical treatment or radioactive iodine ablation. The volume reduction achieved in our study (70.8%) is comparable to other studies published in the literature (50%-93.3%), with a similar low complication rate (reported to be 2.4%-3.5% in larger studies), indicating that this is a viable treatment modality in the United States.[23–26,53–70] It is noted that centers with higher experience have greater volume reductions,[20,21,71,72] although it is promising that our study compares favorably with the retrospective reviews from the Mayo Clinic and Columbia University, which are the only other studies that record the US experience.[28,29]

In keeping with previously published data, smaller nodules responded better to RFA, although there was no significant difference in the volume reduction percentage between NFTNs and AFTNs.[73,74] The data indicates the response is on a continuum which precludes defining a size or volume beyond which RFA would not be effective. Large nodules may require more than one RFA session, although most did respond after a single session with corresponding symptomatic and cosmetic improvement, which is also in keeping with the experience of others.[75] The available data suggests that there is an advantage of performing RFA sooner rather than later in case of symptomatic thyroid nodules for best results.

We did not note any significant differences in volume reduction based on the composition (more solid vs more cystic) on ultrasonography, which is somewhat contrary to the findings from a multicenter study in Italy.[57] However, this may be because of low sample size and the somewhat nonuniform interpretation of ultrasound features across different studies.

In our study, more than 50% of patients became euthyroid, in keeping with results from Italy and South Korea,[27,76–78] with significant improvement in thyroid function tests. RFA of AFTNs may be of value to patients who do not want to risk the hypothyroidism that may occur after surgery or radioactive iodine ablation—a reasonable success rate (~75%) is achieved in our study as well as in the literature.[78,79] Of interest, the free T4 decreased significantly in the NFTN group after RFA (although remained within normal range), whereas the TSH did not significantly change. This could be either an early trend toward hypothyroidism after RFA, or a result of a smaller sample size. An increased risk of hypothyroidism secondary to RFA has not been demonstrated in previous studies. Long-term studies with larger samples would be needed to assess whether RFA can cause hypothyroidism in the long term.

Complication rates are also noted to be quite low compared to surgery and are likely to be operator dependent.[69] Fortunately, there were no major complications in our study; however, this may be simply because of relatively low sample size. In addition, a small margin of normal thyroid tissue was preserved while ablating the nodules, which would have helped avoid complications, but conversely would result in lower volume reductions. The regrowth of thyroid nodules after ablation, resulting in the need for multiple procedures, remains a concern; however, no significant regrowth was noted in our study. Two nodules (1 NFTN and 1 AFTN) were noted to have a small increase in volume after previous decrease (Figures 2 and 3); this may be attributed to either differences in measurements due to intra-operator variability, or regrowth. A longer follow-up period may give insight into the relative rates of regrowth and the factors associated with this.

RFA of thyroid nodules is a well-established practice in some countries, with clinical guidelines issued by academic societies in Korea, Italy, Austria, and the United Kingdom, as well the recent recommendations from the European Thyroid Association and Asian Conference on Tumor Ablation Task Force.[31,80–84] In the United States, RFA is mentioned as a treatment option for benign symptomatic thyroid nodules in the 2016 American Association of Clinical Endocrinologists guidelines[85] but is only considered as second-line therapy for metastatic lymph nodes in patients who are not surgical candidates in the American Thyroid Association 2015 guidelines.[2] RFA can be performed in the outpatient setting in the United States under local anesthesia with results similar to those in more experienced international centers as demonstrated by our study.

Barriers to widespread availability of RFA of thyroid nodules in the United States include both a lack of awareness regarding the procedure and a lack of trained operators to perform the procedure. An additional barrier is the cost of the procedure (currently without a CPT code and thus not reimbursed by insurance) which often needs to be paid out-of-pocket by the patient. However, the absolute cost of the procedure (average US cost: $3500-$6000) is favorable when compared with surgery (estimated national average: ~$19 500), which has the additional burden of possible lifelong thyroid hormone replacement and monitoring, along with perioperative risks and complications.[86] In our study, ~65% of patients paid out-of-pocket for their procedure, whereas the rest were able to get a varying amount reimbursed by their insurance company. The main motivating factors for patients choosing RFA over surgery despite the cost included avoiding a surgical scar and thyroid hormone replacement therapy.

To safely perform the procedure, appropriate training programs need to be established in the United States where skills can be practiced under the supervision of experts. Prerequisites to learning how to perform this procedure include a thorough understanding of the anatomy of the neck, ability to perform and interpret neck ultrasonography, and adequate skill in performing fine needle aspiration of the thyroid using the parallel technique. As with other procedural skills, RFA also has a steep learning curve. Physicians who routinely treat thyroid disease, perform diagnostic ultrasound imaging themselves, and routinely do fine needle aspiration biopsies of neck lesions are ideally placed to add this procedure to the list of treatment options they can offer. More awareness regarding thermal ablation techniques and their use in thyroid nodular disease will ultimately lead to greater access and decreased costs for patients. As the procedure becomes more widespread and more data become available, it will become easier to compare long-term outcomes of RFA and surgery to determine which approach may be better.