Ultrasound-Guided Percutaneous Ethanol Injection for the Treatment of Cystic and Predominantly Cystic Thyroid Nodules: A Single-Centre Experience

Abstract

Introduction:

Thyroid nodules with cystic and predominantly cystic nodules represent a significant subset. Management strategies range from observation to surgical resection, with minimally invasive options like percutaneous ethanol injection (PEI) emerging as alternative. This study evaluates efficacy and safety of PEI for treating cystic and predominantly cystic thyroid nodules.

Methods:

A retrospective review of 65 euthyroid patients with cystic and predominantly cystic thyroid nodules treated with PEI at a single centre (January 2018–April 2023) was conducted. Pre- and post-procedure nodule volumes were measured, and clinical outcomes were assessed at 1, 3, and 6 months. A volume reduction ratio of greater than 50% defined efficacy, while incidence and severity of adverse events determined safety.

Results:

Out of 65 patients, 25 patients had pure cystic nodules and 40 patients had predominantly cystic nodules. The median largest diameter cyst size was 3.7 cm (range, 1.63–10.5 cm), and the median volume of cystic nodules before PEI was 10 ml (range, 1.29–80 ml). Patients with a volume reduction ratio >50% are termed responders. Sixty (92.3%) patients were responders, and 5 (7.7) were non-responders at 3 months follow-up. The response rate of PEI at end of the study (6 months follow-up) was 100%. The total volume reduction was 86.49 ± 5.85% at the end of 6 months.

Conclusion:

PEI is an effective and safe modality for managing cystic thyroid nodules, offering significant volume reduction with minimal adverse effects and proving its role as a first-line alternative for patients unsuitable for surgery.

INTRODUCTION

Thyroid nodules (TNs) are a frequent finding in clinical practice because of routine use of neck imaging.[1] Use of ultrasound for diagnosis of thyroid nodules has greatly increased their detection rate (20–76%) as compared to clinical palpation (4–7%).[2,3] The risk of malignancy in these nodules ranges from 7% to 15%.[4,5] The management of solid nodules has been delineated in detail in guidelines from professional societies. The management strategies for these cystic and predominantly cystic nodules range from simple observation and minimally invasive procedures to surgical intervention.[6,7] Simple aspiration has been tried, but it provides temporary relief with very high recurrence rates (60–90%).[8] Surgical resection provides definitive solutions, but it carries risks of anaesthesia, hypothyroidism, hypoparathyroidism, and recurrent laryngeal nerve injury.[9] Alternatively, minimally invasive techniques like percutaneous ethanol injection (PEI), laser, radio frequency, and microwave ablation offer an effective alternative. There is an unmet need for a safe, effective, minimally invasive, and cost-effective procedure for management of cystic and predominantly cystic nodules.

PEI is increasingly recognised as a safe and efficient option for treating benign thyroid cysts and predominantly cystic nodules.[10] PEI has shown better results as compared to simple aspiration, while having similar remission rates and safety as compared to other ablations, with added advantages of higher simplicity, lesser cost, and shorter hospital stay.[10,11,12] The data on PEI from India are limited to a single study.[13] The present study is designed to assess PEI’s efficacy and safety for treating cystic and predominantly cystic thyroid nodules.

MATERIALS AND METHODS

Study design

This retrospective study included patients with cystic (>90%) and predominantly cystic (>50% to <90%) thyroid nodules treated with ultrasound-guided PEI at our centre between January 2018 and April 2023.[14] Demographic data and baseline thyroid function tests (TFTs) were recorded for all patients. 1-month TFTs were recorded to check for transient thyrotoxicosis. Patients with a minimum of 6 months of data are considered for evaluation.

Inclusion criteria

The inclusion criteria consisted of clinically and biochemically euthyroid patients with cystic and predominantly cystic (solid content <50% of the nodule size)[15] thyroid nodules (FNAC with Bethesda category 2) with compressive symptoms or cosmetic concerns treated with PEI during the study period.

Exclusion criteria

Patients with predominant solid thyroid nodules, nodules categorised as Bethesda 3 or higher, multinodular goitre, or abnormal thyroid function tests (elevated T3, T4, and/or suppressed TSH) were excluded.

USG-guided PEI procedure

USG neck and thyroid was performed using the Versana active-GE with a high-frequency transducer of 4.0–13.0 MHz. The volume of the simple cystic nodule or the cystic component of the complex cystic nodule was calculated using the ellipsoid equation: length x width x depth x π/6.[11]

Under aseptic precautions, imaging-guided local anaesthesia was given with 2% lignocaine into the skin and subcutaneous tissue, including peri-capsular infiltration. Using an 18G needle, 3-way cannula, and 20 ml syringe, cysts were aspirated in a supine position with the neck extended. Aspiration of the maximal amount of fluid possible was attempted in each patient. In patients with thick fluid not draining with the 18-G needle, hypertonic saline (3%) was administered to the cyst and aspirated.[16] Sterile 99.9% absolute ethanol was injected into the cyst and the solid portion of predominantly cystic nodules by changing the syringe with the needle in situ. The alcohol was left inside the cyst without re-aspiration.[12] The volume of ethanol injected was equal to the fluid aspirated from the cyst. If the patient experienced pain, then the ethanol injection was stopped. Pain experienced during the procedure was documented on a visual analogue scale. Patients were reviewed clinically and by USG at 1 month, 3 months, and 6 months. The volume reduction ratio (VRR) was calculated using the following formula: [(initial volume - final volume) ×100%]/initial volume. The largest diameter and volume of each thyroid nodule were documented at baseline and during follow-ups at 1, 3, and 6 months. The thyroid function test was done at the first follow-up. Adverse events following PEI were noted.

Study endpoints

The primary endpoints of the study were efficacy, assessed by a volume reduction ratio of more than 50% on ultrasound. Secondary endpoints focused on patient-reported subjective cosmetic relief (a decrease in clinically visible swelling during follow-up) and on safety and long-term recurrence rate.

Statistical analysis

Statistical analysis was conducted using SPSS version 22. Categorical variables were presented as frequency (percentage). Normality of continuous variables was assessed using the Shapiro–Wilk test. All normally distributed values were given as mean ± SD. Continuous variables were analysed using t-tests, and discrete variables were analysed using the Chi-square test. P < 0.05 was considered statistically significant.

Ethical aspects

JNMC ethics committee, Jawaharlal Nehru Medical college, approval letter number- MDC/JNMCIEC/187, issued on date 22/03/2024. Informed consent was obtained for participation in the study and use of the patient data for research and educational purposes. The procedures followed the guidelines laid down in Declaration of Helsinki 1964.

RESULTS

A total of 80 patients underwent PEI for cystic and predominantly cystic nodules, out of which 65 patients met the inclusion criteria [Figure 1], of which 89% were women (n = 58). Out of 65 patients, 25 patients had pure cystic nodules, and 40 patients had predominantly cystic nodules. All patients were euthyroid, and PEI was performed as an outpatient procedure in all patients. The median largest diameter cyst size was 3.7 cm (range, 1.63–10.5 cm), and the median volume of the cystic nodules before PEI was 10 ml (range, 1.29–80 ml). Four (6.1%) patients required a second PEI, and one patient required 3 sessions for inadequate response.

Figure 1.

Ultrasound of neck showing reduction in volume of thyroid nodule following ultrasound-guided percutaneous ethanol injection in the left thyroid lobe in a 27-year-old female

Patients with a volume reduction ratio >50% are termed responders. Fifty-five (84.6%) patients were responders at 1-month follow-up. The response rate increased at the 3-month follow-up, with 60 (92.3%) patients being responders. All the patients achieved the primary efficacy endpoint at the end of the study (6 months follow-up). The total volume reduction was 86.49 ± 5.85% at the end of 6 months follow-up, and the volume reduction in cystic and predominantly cystic nodules was not significantly different (92.9 ± 4.2% vs 85.4 ± 5.2%, P = 0.5). Cosmetic relief is considered if the patient reports a reduction in visible neck mass that was a concern for the patient. Cosmetic relief (as reported by the patient) was achieved in 61 (93.8%). Recurrence is labelled if the nodule’s volume increases significantly (>50%) from the size of the 3-month post-ablation or increased vascularity within the treated area on further follow-up. Four (6.1%) patients had a recurrence within 2 years of follow-up.

Baseline characteristics and outcomes of ultrasound-guided PEI of the thyroid nodules before and after treatment are given in Table 1.

Table 1.

Baseline characteristics and outcomes of ultrasound-guided PEI of the thyroid nodules before and after treatment

Variable	Value
Number of nodules	65
Age at the time of PEI (years)	35.6±10.83 (range 19-60)
Females (%)	58 (89%)
Males (%)	7 (11%)
Number of PEI required per patient	1.09
Pre-PEI cyst volume (mL)	18.49±19.30 (range: 1.29-80)
Largest diameter of cyst (cm)	4.23±1.87 (range: 1.63-10.5)
Volume of ethanol injected (mL)	16.8±15.5 (range: 2-30)
Post-PEI cyst volume (mL)
1 month	8.57±13.26 (range: 0.24-44.6)
3 months	5.67±6.02 (range: 0.22-24.76)
6 months	2.37±1.88 (range: 0.52-4.98)
Responders (%)
1 month	84.6
3 months	92.3
6 months	100
Volume reduction (%)
1 month	66.73±16.82% (range: 40.58-94.4)
3 months	70.37±17.16% (range: 32.65-98.58)
6 months	86.49±5.85% (range: 81.4-98.76)
Adverse effects: Pain radiation to the neck Bleeding into the cyst	6 (9.2%) 4 (6.1%) 2 (3.1%)
Pain during procedure (Visual analogue scale for pain)	2.5±1.1
Recurrence rate	4 (6.1%)

PEI: Percutaneous ethanol injection

There were no significant adverse effects, and the procedure was well tolerated by all patients. Adverse effects occurred in 6 patients (9.2%) and were mild and transient (pain radiating to the neck and bleeding into the cyst). There were no severe complications, such as massive haemorrhage, vocal cord paralysis, or transient thyrotoxicosis.

DISCUSSION

In our study, we have evaluated the efficacy and safety of PEI in 65 cystic and predominantly cystic nodules. The response rate at 6 months in terms of the number of patients achieving a volume reduction ratio (VRR) >50% was 100%, and the mean total VRR was 86.49 ± 5.85%. Cosmetic relief was reported by 93.8% of the patients. The pain experienced during the procedure was very minimal (2.5 on a visual analogue scale), mainly because of peri-capsular infiltration with lignocaine. No major side effects were observed in our study.

Efficacy

In our study, a significant volume reduction was noted at each follow-up interval, with a mean reduction ratio of 66.73% at 1 month and 86.49 ± 5.85% at 6 months. In the systematic review by Cesareo et al.,[12] the mean volume reduction ratio (VRR) was 77% at 6 months and sustained efficacy in long-term follow-ups of up to 10 years. Similarly, the Mayo Clinic study observed a median VRR of 76% at 15.5 months.[13,15] Basu et al. showed a similar response rate in pure cystic nodules (74.56%) but a very poor response rate to predominantly cystic nodules (46.67%).[13,15] In contrast, our study revealed higher volume reduction (likely due to non-respiration of ethanol), with similar response rates in both pure cystic and predominantly cystic nodules (92.9 ± 4.2% vs 85.4 ± 5.2%, P = 0.5). This can be attributed to the infiltration of ethanol into the solid part in our study, and the amount of ethanol injected was 90.8% of the baseline as compared to 37.7% in their study. Use of hypertonic saline in selected patients with difficult-to-aspirate thyroid nodules also could have contributed to improved efficacy.

Safety

Safety was another pivotal endpoint in this study, with no serious adverse events reported. None of the procedures was stopped due to pain, and no patient required admission to the hospital due to adverse events. The pericapsular infiltration with xylocaine before the procedure could be the reason for less pain during and post-procedure. The adverse effects were minor and transient, a finding corroborated by Basu et al. and the Mayo Clinic study, which highlighted mild complications such as transient burning and localised discomfort as the most common side effects.[13,15] This safety profile reinforces the preference for PEI over surgical alternatives, which carry risks of hypothyroidism, recurrent laryngeal nerve damage, and other complications. It is noteworthy that larger baseline volumes did not adversely affect the outcome, aligning with previous findings that baseline nodule size does not necessarily predict therapeutic response.[13,15]

The limitations of the study are its retrospective nature, small sample size, and short follow-up. Future studies with extended follow-up periods could further delineate the durability of therapeutic outcomes and optimise procedural protocols.

CONCLUSION

PEI is a safe and effective modality for the management of cystic and predominantly cystic thyroid nodules. Its significant efficacy in reducing nodule volume and low incidence of adverse events make it a viable alternative to surgical interventions, particularly in patients with cosmetic concerns or compressive symptoms.

Author contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by MG and DV. The first draft of the manuscript was written by MG and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Conflicts of interest

There are no conflicts of interest.

Use of artificial intelligence

Artificial intelligence was not used in the making of manuscript.

Data availability statement

The data supporting the findings of this study are available from the corresponding author.

Funding Statement

Nil.