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Novel Approaches for Treating Autonomously Functioning Thyroid Nodules

Novel Approaches for Treating Autonomously Functioning Thyroid Nodules

Novel Approaches for Treating Autonomously Functioning Thyroid Nodules


Pace-Asciak, Pia, et al. “Novel Approaches for Treating Autonomously Functioning Thyroid Nodules.” Frontiers in Endocrinology, vol. 11, Oct. 2020, p. 565371. (Crossref),



Benign thyroid nodules are exceedingly common in the adult population. Only a small percentage of nodules are toxic or autonomously functioning thyroid nodules (AFTNs). The options clinicians have for treating the symptoms of hyperthyroidism include anti-thyroidal medications, radioactive iodine, or surgery. Depending on the patient population treated, these options may not be suitable or have inherent risks that are undesirable to the patient. On the other hand, untreated hyperthyroidism can lead to osteoporosis, atrial fibrillation, emotional lability, and neurological consequences. Thus, we present a review of two novel safe and effective approaches for treating AFTN; one surgical (transoral endoscopic thyroid surgery) and one non-surgical (radiofrequency ablation), as a means for expanding our treatment armamentarium. Radiofrequency ablation (RFA) is a novel minimally invasive approach that is a potential alternative to surgery for treating symptomatic benign nodules (43) as well as AFTN (44). This approach eliminates the need for a general anesthetic, an incision, radioactive iodine, or prolonged ATD treatment, making it an attractive non-surgical option. With the use of local anesthesia, the RFA probe is introduced into the midline of the anterior neck at the level of the isthmus, and the nodule is approached using the moving shot technique under ultrasound guidance (45). This causes tissue necrosis and fibrosis by introducing a high frequency alternating current, which raises tissue temperatures to 60 to 100 C (46). Over time, there is progressive shrinkage of the ablated nodule. In benign nodules, the volume of the nodule is thought to decrease between 50 and 80% for most patients, although this is operator and tumor dependent (47, 48). RFA has been offered to patients internationally since 2000 and has been used to treat primary and metastatic tumors of the liver, lung, bone, and kidney and to ablate aberrant conduction pathways in the heart (49–53). More recently, RFA has been applied to the head and neck, particularly for thyroid nodules. While the early results have been promising internationally, there is little North American data (47, 48, 54–61). The current international recommendations for treating benign thyroid nodules include patients who are symptomatic or those who have a disfiguring goiter or a nodule that exceeds 2 cm, or if an AFTN is present (43, 44, 57). Prior to RFA treatment of AFTN, confirmation that the nodule is benign on at least one US-guided FNA or core biopsy is recommended, unless there are concerning features on ultrasound in which case two biopsies should be obtained (43, 44). Nodules that are benign on FNA but that have suspicious US features (EU-TIRADS 5), the latest European Thyroid Association Guidelines strongly recommend (moderate quality evidence) against thyroid ablation to avoid potential delay in treatment of a malignant lesion (62).


RFA has shown excellent efficacy and safety in the management of cosmesis related concerns and pressure symptoms (47, 48, 54–61, 63, 64). In a systematic review and meta-analysis of RFA in benign nodules, a pooled proportion of 2.38% for overall RFA complications was noted (95% CI: 1.42–3.34%), with 1.35% for major complications (95% CI: 0.89–1.81%) and no evidence of any life-threatening complications. The most common complaint post treatment was transient or rarely permanent voice changes (35/2,421). Nodule rupture, permanent hypothyroidism 6 months after treatment, and transient brachial plexus injury was only found in one patient out of 2,421 patients (65). Minor complications included pain during or after the procedure (16/2421), hematoma which disappeared after 1–2 weeks (25/2,421), vomiting (9/2,421), skin burns (six patients had first degree burns and 1 patient had second degree burn which recovered after a month) and transient thyroiditis (one patient three months after the treatment) (65). Furthermore, various studies have shown that the volume of a benign symptomatic thyroid nodule can be reduced by more than 50%, and up to 75–97% in long-term follow-ups (60, 66, 67). The American Thyroid Association Guidelines outline that surgery or radioactive iodine (RAI) are effective for the treatment of AFTN (1, 3). These two options are not always acceptable for patients since RAI involves receiving radiation which is controversial in women of childbearing age, or for patients reluctant to endure the long-term risks associated with radiation (3). Additionally, both treatments have potential complications such as hypothyroidism. Even with lobectomy, surgery confers roughly a 30% chance of hypothyroidism, which is generally avoided in RFA-treated patients (10, 11, 68). RFA may gain favor with patients wishing to avoid developing hypothyroidism (55, 57, 58, 69–71). The success rate of RFA is greater when the volume of the AFTN is relatively small in size. Cesareo et al. compared the reduction between medium sized nodules (18 ml) and smaller sized nodules (5 ml), euthyroidism was achieved 86% in small nodules vs. 45% in medium size nodules (75). Similarly, Cappelli et al. report a volume reduction rate of 73% with TSH normalization in 94% of patients treated with RFA with nodules an average of 7 ml (76). An earlier study by Lim et al. confirmed that larger nodules (>20 ml) required repeat RFA treatment compared with smaller nodules to achieve a similar volume reduction in during 4 year follow-up (77). This work has improved our understanding of how to counsel patients with AFTN. RFA offers a non-surgical approach for patients who wish to avoid surgery altogether or are poor surgical candidates.

Key Words

RFA, thyroid nodule,

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