Efficacy of dual-modality ablation for symptomatic cystic thyroid nodules

Introduction

Cystic thyroid nodules are common clinical findings, often identified incidentally on imaging studies or evaluated when they become markedly enlarged and symptomatic. Symptoms associated with large cystic thyroid nodules are primarily compressive, including neck discomfort, dysphagia, dysphonia, and voice change. While surgical resection is a treatment option, minimally invasive modalities such as radiofrequency ablation (RFA) and ethanol ablation (EA) have emerged as effective alternatives. EA is currently the preferred first-line treatment of predominantly cystic thyroid nodules due to its simplicity and lower cost compared to RFA. Compared to a surgical resection, both procedures obviate the need for general anesthesia and a neck incision while offering a shorter recovery time.

Both modalities are effective in reducing thyroid cyst volume and alleviating symptoms (1-4). RFA typically achieves a mean volume reduction ratio (VRR) of approximately 80.0–80.3% (1,2), whereas EA has shown a wider reported range, from 80% to 100% (3,4). Other studies, however, indicate that EA may achieve lower mean VRRs, around 65.8–69.8% (5,6), and is associated with higher recurrence rates (26–33%) compared with RFA (5,6). Several factors may influence the efficacy of these interventions, including the sonographic characteristics of the nodules, patient-specific factors, and procedural parameters (7). RFA utilizes thermal energy to sclerose the cyst wall, while EA uses a chemical irritant, high concentration ethanol (95–99%), to induce sclerosis through protein denaturation and cytoplasmic dehydration (8). Given their distinct mechanisms of action, combining both techniques may provide more effective and durable outcomes.

Cystic thyroid nodules are generally considered benign, and their risk of malignancy can be stratified based on sonographic patterns. Purely cystic nodules with thin, regular walls have a 0% risk of malignancy. Nodules with a spongiform appearance or those containing interspersed cystic spaces without suspicious features carry a malignancy risk of less than 3%. Partially cystic nodules have a higher risk, ranging from 3.3% to 17.5%. These stratifications provide a useful basis for clinical decision-making and support the selection of minimally invasive treatments for symptomatic benign cystic lesions (9,10).

This study aimed to evaluate the outcomes of dual-modality RFA and EA for the treatment of cystic thyroid nodules and to identify potential determinants of treatment success. Changes in cyst volume, complete disappearance, recurrence, post-procedural thyroid function, and complications were examined in detail. We present this article in accordance with the STROBE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0007/rc).

Methods

Study design and patient selection

We conducted a retrospective analysis of 15 patients who underwent combined RFA and EA for predominantly cystic thyroid nodules between 2019 and 2025 at LCMC-East Jefferson General Hospital, LCMC-Tulane Lakeside Hospital. Eligible patients were adults (≥18 years) with symptomatic or large cystic thyroid nodules (>4 cm) causing compressive symptoms, cosmetic concerns, or local discomfort. All nodules were confirmed to be benign by fine-needle aspiration (FNA) cytology prior to treatment.

Combined RFA/EA therapy was selected in part due to the relatively high cost of ethanol in North America. This combined approach was designed to reduce the amount of ethanol required while maintaining effective ablation of the cyst wall and improving overall treatment efficiency. Patients were required to have available clinical and ultrasound follow-up for a minimum of 6–12 months after treatment. Patients with incomplete follow-up data were excluded. All procedures were performed by a single experienced surgeon.

RFA/EA procedure

All procedures were performed under ultrasound guidance using a percutaneous approach. After sterile preparation, local anesthesia was administered at the skin entry site. Cystic fluid was first aspirated under ultrasound guidance to reduce the cyst volume and allow better visualization of the internal architecture. RFA was then performed using the trans-isthmic approach with the moving-shot technique. Hydrodissection with normal saline was used when necessary to protect surrounding critical structures, including the recurrent laryngeal nerve, trachea, and carotid sheath. RFA was primarily applied to the solid component of the nodule and to the inner cyst wall after collapse of the cyst cavity. Power settings were adjusted dynamically based on the development of transient hyperechoic zones on ultrasound, indicating adequate tissue ablation. Following completion of RFA, ethanol was instilled into the deep perimeter of the residual cystic cavity. A standardized ethanol volume of 1 mL was used in order to minimize ethanol exposure while enhancing ablation of the residual cyst wall. The goal of the combined therapy was to decrease the need for the higher ethanol volumes typically required when EA is used alone.

Study variables

Cystic nodule volume and maximum dimensions were measured before and after the procedure. The VRR was calculated as: VRR (%) = [(initial volume − final volume)/initial volume] × 100. The patients were followed at 3-, 6-, and 12-month intervals. Recurrence was defined as >50% reaccumulation from the lowest volume.

Statistical analysis

Descriptive statistics were used to summarize patient characteristics and outcomes. Continuous variables are reported as median with interquartile range (IQR), and categorical variables as frequencies and percentages. All statistical analyses were conducted using SPSS version 28.

Ethical statement

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board of Tulane University School of Medicine (No. 2025-277). Given the retrospective design and use of de-identified data, informed consent was waived by the Institutional Review Board.

Results

Patient and cyst characteristics

The study cohort comprised 9 females (60%) and 6 males (40%), with a mean age of 61.3±17.3 years. Eight patients presented with compressive symptoms, and 2 were hypothyroid (Table 1). All patients underwent dual-modality RFA/EA procedure. Ten cystic nodules (66.6%) were benign, while 5 (33.3%) were non-diagnostic on FNA. The median cyst size was 3.92 cm (IQR, 2.73–6.38 cm), and the median cyst volume was 9.93 mL (IQR, 1.9–40.5 mL). The median follow-up duration was 6 months (Table 1).

Treatment outcomes

At 6-month follow-up, the median cyst volume was 1.3 mL (IQR, 0.23–6.35 mL). The VRR was 62% (IQR, 39–94%) at 3 months, increased to 75.4% (IQR, 34–95.8%) at 6 months, and reached 87% (IQR, 50–97%) by the last follow-up. Complete resolution (VRR 100%) was achieved in 1 patient (6.7%) at 3 months. No cyst progression was observed, although recurrence occurred in 1 patient. Post-RFA thyroid function was notable for 12 of the 13 euthyroid patients (92.3%) remaining euthyroid, and 1 patient developing hypothyroidism requiring levothyroxine supplementation (Table 2).

Complications

Two patients (13.3%) experienced transient discomfort and pain, which fully resolved within 2 weeks. No cases of hematoma, skin burn, infection, transient or permanent voice change, or vascular injuries were observed (Table 2).

Discussion

RFA and EA have each been used as effective, minimally invasive treatments for cystic thyroid nodules, achieving clinically significant symptom resolution and volume reduction rates of 81%. A dual-modality RFA/EA achieved a greater volume reduction, with a median VRR of 87% (IQR, 50–97%) at the final follow-up of 6–12 months. The low incidence of complete resolution of cyst (n=1) is in line with the findings of other studies, where complete resolution of cystic thyroid nodules is relatively rare (6,11,12). However, the low recurrence observed (n=1) during the follow-up period supports sustained efficacy of these treatments. In comparison, recurrence rates range from 14% to 24.1% within 10 months after EA alone, often requiring a repeat EA or RFA to optimize outcomes (6,13). The absence of progression is also an encouraging outcome, indicating that RFA/EA effectively stabilizes treated cysts and prevents recurrence.

The preservation of thyroid function following RFA/EA further supports the benefit of these procedures. Only one patient developed hypothyroidism, whereas postoperative hypothyroidism occurs in approximately 40–50% of patients after thyroid lobectomy. Post-procedural complications were minimal in this study, with only a small number of patients reporting transient discomfort and pain (13.3%). These findings are consistent with the previously published safety profiles of RFA and EA (14,15). Other serious complications such as hematoma, nerve injuries, skin burns, or infections are known to be rare occurrences and were not observed in our study cohort.

EA is a safe, well-tolerated, and effective first-line treatment, particularly for simple cysts and complex cysts with less than 20% solid component. A systemic review has shown that VRR at 6, 12, 24, 36, 60 and 120 months was 77%, 81%, 72%, 68%, 74% and 69%, respectively (11). Its effectiveness decreases as the solid portion increases. For cysts with more than 20% solid component, RFA may provide better long-term outcomes, though EA remains a reasonable initial option. RFA can also be successfully used as salvage therapy after failed EA. Alternative management strategies include surgical resection, which carries higher risks of hypothyroidism and recurrent laryngeal nerve injury, as well as other minimally invasive techniques such as laser ablation, microwave ablation and Polidocanol sclerotherapy. Compared with these modalities, RFA and EA may offer a balance between efficacy and preservation of thyroid function, although direct comparisons are lacking (16,17).

Although the findings of this study are promising, several limitations should be acknowledged. The small cohort size, limited duration of follow-up, absence of a control group, and lack of assessment of the dose-dependent effects of ethanol instillation restrict the generalizability of the results. Future studies should investigate strategies to further enhance the effectiveness of the combined RFA/EA approach, including optimization of the procedural sequence, individualized ethanol dosing based on cyst size or residual cavity volume, and evaluation of whether additional low-dose ethanol instillation at follow-up may further reduce recurrence rates. Studies with larger cohorts and standardized protocols are warranted to refine patient selection and further validate the efficacy of combined RFA/EA in the management of cystic thyroid nodules.

Conclusions

Combined RFA/EA represents an effective, minimally invasive treatment for cystic thyroid nodules, achieving substantial nodule volume reduction and symptomatic improvement with a low risk of complications. Larger, standardized studies are warranted to identify predictors of treatment success and to further refine procedural protocols for optimal outcomes.

Acknowledgments

This work was initially presented as a poster at the American Thyroid Association Annual Meeting, 2025. The authors would like to thank the patients and clinical teams for their support in patient care and data collection.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0007/rc

Data Sharing Statement: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0007/dss

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0007/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0007/coif). E.K. serves as an Editor-in-Chief of Gland Surgery from May 2024 to April 2026. E.K. reports receiving honoraria for educational training courses from BAIRD. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board of Tulane University School of Medicine (No. 2025-277). Given the retrospective design and use of de-identified data, informed consent was waived by the Institutional Review Board.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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