Ultrasound-guided percutaneous radiofrequency ablation for benign thyroid nodules

Evidence-based recommendations on ultrasound-guided percutaneous radiofrequency ablation for treating benign thyroid nodules in adults. This involves using heat energy to destroy tissue in the nodules.

# Recommendations
Current evidence on the safety and efficacy of ultrasoundguided percutaneous radiofrequency ablation for benign thyroid nodules is adequate to support the use of this procedure provided that standard arrangements are in place for clinical governance, consent and audit. Find out what standard arrangements mean on the NICE interventional procedures guidance page.# Indications and current treatments
Thyroid nodules may be cystic, colloid, hyperplastic, adenomatous or cancerous. The majority of thyroid nodules are benign and they are often asymptomatic. There may be a single thyroid nodule (solitary nodule) or multiple thyroid nodules (multinodular goitre). Thyroid nodules can cause an overactive thyroid, which affects the normal production of thyroxine or triiodothyronine.
Treatment of benign thyroid nodules may be necessary if they are symptomatic or causing cosmetic problems. Conventional treatment includes suppressive levothyroxine therapy or surgery. More recently, other approaches that are less invasive than conventional surgery have been introduced, such as ethanol ablation and percutaneous laser ablation.# The procedure
Radiofrequency ablation is a minimally invasive technique that aims to reduce symptoms and improve cosmetic appearance, while preserving thyroid function, and with fewer complications than surgery.
Before treatment, the thyroid nodule is confirmed as benign, typically by the use of 2 fineneedle aspiration biopsies. Ultrasoundguided percutaneous radiofrequency ablation for benign thyroid nodules is usually done in an outpatient setting using local anaesthesia. The patient lies in the supine position with moderate neck extension. A radiofrequency electrode is inserted into the nodule using ultrasound guidance to visualise the electrode during the procedure. Once in position, the radiofrequency electrode is activated to heat and destroy the tissue.# Efficacy
This section describes efficacy outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the interventional procedure overview.
In a systematic review of 284 patients with benign thyroid nodules treated by radiofrequency ablation (RFA), the mean nodule volume reduced by 9.8 ml after the procedure (95% confidence interval  13.83 to 5.72; 9 studies, n=284 nodules; I2=98% ). In a randomised controlled trial (RCT) of 84 patients with benign solid thyroid nodules, the mean nodule volume reduced from 24.5(19.6) ml at baseline to 8.6(9.5) ml at 6month followup (p<0.001) in patients treated by RFA, compared with no volume reduction in patients randomised to no treatment (27.522.1 ml at baseline and 27.822.1 ml at 6month followup). In an RCT of 80 patients with solid, compressive, nonfunctioning benign thyroid nodules treated by RFA or no treatment, the median percentage volume changes were 71% reduction and 3% increase respectively (p=0.0001). In a nonrandomised comparative study of 400 patients with nodular goitre treated by RFA or surgery there was a mean percentage volume reduction of 85(17.1)% after RFA at 12month followup (p=0.002). In a case series of 111 patients with benign, nonfunctioning thyroid nodules there was a mean volume reduction of 91(15.8)% after RFA at 3year followup. In an RCT of 50 patients with a single benign cystic thyroid nodule treated by RFA or ethanol ablation (also included in the systematic review), there were median percentage volume reductions of 93(5.4)% and 97(4.1)% respectively at 6month followup (p value not reported). In a second RCT of 50 patients with predominantly cystic thyroid nodules treated by RFA or ethanol ablation, mean volume reductions were 87.5(11.5)% and 82.4(28.6)% respectively at 6month followup (p=0.710).
In the systematic review of 284 patients there was a reduction in the mean symptom score (measured on a 10point visual analogue scale, with lower scores indicating less severe symptoms) of 2.89 after RFA (95% CI 2.51 to 3.28; 4 studies, n=85; I2=56%). In the RCT of 84 patients the mean pressure symptom score (measured on a 10point visual analogue scale, with lower scores indicating less severe symptoms) reduced from 2.8(3.3) at baseline to 0.4(0.8) at 6month followup (p<0.001) in patients treated by RFA compared with no reduction for patients with no treatment (2.73 at baseline and 2.93.2 at 6month followup). In the RCT of 80 patients the symptom score (on a scale of 0 to 10, with lower scores indicating less severe symptoms) was 0.4(0.7) for patients treated by RFA compared with 3.3(1.7) for patients with no treatment (p=0.0001) at 6month followup. In the case series of 111 patients, the symptom score (assessed on a scale of 0 to 10, with lower scores indicating less severe symptoms) reduced from 4.3(1.6) at baseline to 0.8(0.9) at last followup (mean followup 49 months, p<0.001). In the RCT of 50 patients treated by RFA or ethanol ablation (also included in the systematic review) symptom scores (assessed on a scale of 0 to 10, with lower scores indicating less severe symptoms) were 0.5(0.8) and 0.5(0.7) respectively at 6month followup (p=0.806).
In the systematic review of 284 patients the mean reduction in cosmetic score (scored by a physician from 1 to 4, with lower scores indicating better cosmetic appearance) was 2.02 (95% CI 1.69 to 2.35; 5 studies, n=114; I2=78%) after RFA. In the RCT of 84 patients the mean cosmetic score (assessed on a scale of 1 to 4, with lower scores indicating better cosmetic appearance) reduced from 2.6(0.9) at baseline to 1.7(0.7) at 6month followup (p<0.001) in patients treated by RFA, compared with no reduction for patients with no treatment (2.61.0 at baseline and at 6month followup). In the RCT of 80 patients cosmetic scores (assessed on a scale of 1 to 4, with lower scores indicating better cosmetic appearance) were 1.7(0.8) for patients treated by RFA and 3.5(0.7) for patients with no treatment (p=0.0001) at 6month followup. In the case series of 111 patients the cosmetic score (on a scale of 1 to 4, with lower scores indicating better cosmetic appearance) reduced from 3.2(0.8) at baseline to 1.3(0.6) at last followup (mean followup 49 months, p<0.001). In the RCT of 50 patients treated by RFA or ethanol ablation (also included in the systematic review) cosmetic scores (on a scale of 1 to 4, with lower scores indicating better cosmetic appearance) were 1.1(0.4) and 1.2(0.4) respectively at 6month followup (p=0.682).
In the systematic review of 284 patients, 60 patients with 'hot' nodules were given methimazole at doses sufficient to maintain thyroidstimulating hormone within the normal range before RFA treatment. After RFA treatment, 29 patients continued to need some dose of this medication to maintain euthyroidism based on thyroidstimulating hormone measurements and symptoms (odds ratio 40.34, 95% CI 7.78 to 209.1; 3 studies, n=60; I2=2%).
In the nonrandomised comparative study of 400 patients, no patients treated by RFA needed medication for hypothyroidism compared with 71.5% of patients treated by surgery (p=0.002).
In the case series of 111 patients (126 nodules) the overall recurrence rate (defined as increases in nodule volume of greater than 50% compared with previous ultrasound images at a minimum of 3 years of followup) was 6% (7/126). All nodules were benign on repeat fineneedle aspirate biopsy. Four of the recurrent nodules decreased in size after repeat RFA, 2 were treated with repeat RFA without further followup and 1 patient chose not to have further treatment and was lost to followup.
The specialist advisers listed key efficacy outcomes as reduction in thyroid nodule volume, and improvement in compression symptoms and cosmetic appearance.# Safety
This section describes safety outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the interventional procedure overview.
Nodule rupture was reported in 1 patient treated by radiofrequency ablation (RFA) in a nonrandomised comparative study of 400 patients. Nodule rupture was reported in less than 1% (2/1459) of patients in a case series of 1,459 patients: 1 patient recovered without treatment and 1 patient was admitted to hospital and treated with antibiotics and analgesics. In the same study, 1 patient had nodule rupture with abscess formation: the patient was treated by left thyroidectomy. Nodule rupture was reported in 1 patient in a case series of 40 patients: this occurred 26 days after RFA and was treated with antiinflammatory medication.
Vocal fold palsy was reported in 1 patient in a systematic review of 284 patients. This was diagnosed at 1month followup, but the patient was subsequently lost to followup. Permanent vocal cord palsy with inspiratory stridor without dysphonia was reported in 1 patient treated by RFA in a randomised controlled trial (RCT) of 84 patients.
Voice change immediately after the procedure was reported in 5% (2/42) of patients treated by RFA in the RCT of 84 patients; this resolved completely within 3 hours of the procedure. Transient hoarseness was reported in less than 1% (1/200) of patients treated by RFA and in 1.5% (3/200) of patients treated by surgery in the nonrandomised comparative study of 400 patients. Voice change was reported in 1% (15/1459) of patients in the case series of 1,459 patients; all patients recovered completely, except for 2 patients who were lost to followup.
Brachial plexus injury was reported in 1 patient in the case series of 1,459 patients. The patient had numbness and decreased sensation in the fourth and fifth fingers of the left hand; this gradually recovered during the next 2 months.
Diffuse glandular haemorrhage was reported in 1 patient in the systematic review of 284 patients. This resulted in interruption of the procedure. The patient was given oral analgesics for pain relief for 3 days. Intranodular bleeding was reported in 8% (3/40) of patients in the case series of 40 patients: this was stopped by swift needleelectrode insertion and heat administration. In the same study, pericapsular bleeding was reported in 1 patient, who had extensive neck bruising 5 to 10 days after the procedure. Haematoma was reported in 1 patient in the systematic review of 284 patients and in 1% (15/1459) of patients in the case series of 1,459 patients: most completely disappeared within 1 to 2 weeks.
Postoperative oedema was reported in 1% (3/284) of patients in the systematic review of 284 patients. This was treated with betamethasone medication.
A fullthickness skin burn was described in a case report. The burn took more than 1 month to heal but its final appearance looked almost like the normal skin. Firstdegree skin burns at the puncture sites were reported in less than 1% (4/1459) of patients in the case series of 1,459 patients: all patients recovered from pain and skin colour changes within 7 days without sequelae.
Vasovagal reaction during the procedure was reported in less than 1% of patients in the case series of 1,459 patients. This included sweating, difficulty breathing and hesitation; it was treated by elevation of the patient's legs and stopping the ablation. Vasovagal reaction was reported in 1 patient in the case series of 40 patients. The patient had bradycardia, hypotension, vomiting and defecation; the bed was tilted, ablation was stopped and the patient recovered within a few minutes. The patient had a subsequent RFA session 3 weeks later. Vomiting was reported in less than 1% (9/1459) of patients in the case series of 1,459 patients: this improved within 1 to 2 days after treatment with antiemetics.
Pseudocystic transformation was reported in 1 patient in the case series of 40 patients: the patient had a painful sudden swelling 3 weeks after RFA, which was treated with oral corticosteroids.
Permanent hypothyroidism was reported in 1 patient in the case series of 1,459 patients: the patient had gradual neck bulging and ultrasound showed diffuse enlargement of the thyroid gland without a thyroid nodule.
In addition to safety outcomes reported in the literature, specialist advisers are asked about anecdotal adverse events (events which they have heard about) and about theoretical adverse events (events which they think might possibly occur, even if they have never done so). For this procedure, specialist advisers listed the following theoretical adverse events: oesophageal or tracheal thermal injury, cardiac arrhythmia, and sympathetic or spinal nerve injury.# Further information
For related NICE guidance, see the NICE website.

# Information for patients
NICE has produced information on this procedure for patients and carers. It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.
ISBN: 978-1-4731-1938-3