Hindawi Publishing Corporation

International Journal of Endocrinology

Volume 2013, Article ID 428363, 7 pages
http://dx.doi.org/10.1155/2013/428363

Review Article
Use of Radiofrequency Ablation in Benign Thyroid Nodules:
A Literature Review and Updates

Kai-Pun Wong and Brian Hung-Hin Lang

Division of Endocrine Surgery, Department of Surgery, The University of Hong Kong, Queen Mary Hospital,
Pokfulam Road, Hong Kong

Correspondence should be addressed to Brian Hung-Hin Lang; blang@hku.hk

Received 7 June 2013; Revised 16 September 2013; Accepted 22 September 2013

Academic Editor: Małgorzata Kotula-Balak

Copyright © 2013 K.-P. Wong and B. H.-H. Lang. This is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.

Successful thermal ablation using radiofrequency has been reported in various tumors including liver or kidney tumors.
Nonsurgical minimally invasive ablative therapy such as radiofrequency ablation (RFA) has been reported to be a safe and efficient
treatment option in managing symptomatic cold thyroid nodules or hyperfunctioning thyroid nodules. Pressure and cosmetic
symptoms have been shown to be significantly improved both in the short and long terms after RFA. For hyperfunctioning thyroid
nodules, RFA is indicated for whom surgery or radioiodine are not indicated or ineffective or for those who refuse surgery or radio-
iodine. Improvement of thyroid function with decreased need for antithyroid medications has been reported. Complication rate
is relatively low. By reviewing the current literature, we reported its efficacy and complications and compared the efficacy of RFA
relative to other ablative options such as ethanol ablation and laser ablation.

1. Introduction 25, 29–33]. RFA is a safe percutaneous ablative technique in

treating liver tumors [34, 35]. Since the first reported series
Thyroid nodules are commonly found and they pose one of in 2006 [36], there had been numerous studies showing its
the most common clinical problems for primary physicians efficacy and safety in treating benign cold and hyperfunction-
and specialists. Clinically palpable nodules are found in 5– ing thyroid nodules [5, 11, 14–24]. In this paper, we described
10% of the normal population and nonclinically palpable the basic principles, patient selection, procedure, efficacy, and
nodules such as those found incidentally on ultrasound (US) complications of RFA and its efficacy relative to other ablation
occur in up to 67% [1–3]. With the increasing use of US, it is modalities.
expected that more and more asymptomatic thyroid nodules
would be detected [4].
Although the majority of these nodules are benign and 2. Basic Principles of RFA
may not cause symptoms, some are occasionally associated
with pressure or thyrotoxic symptoms [5, 6]. Surgery is the RFA refers to hyperthermic ablation by high frequency
treatment of choice for these nodules but may be associ- alternating electric current oscillating between 200 and
ated with certain operative morbidity, unsightful scar and 1200 kHz [37]. By applying an electrode into nodule, a high-
permanent hypothyroidism [7–10]. The alternatives include frequency alternating current is generated and passed into
ethanol ablation (EA) [11–13], radiofrequency ablation (RFA) the surrounding tissue. It thus induces rapid vibration of
[5, 11, 14–24], percutaneous laser ablation (PLA) [6, 25], high- surrounding ions and frictional heat. Coagulative necrosis
intensity focused ultrasound (HIFU) [26], and microwave and irreversible damage is induced near the electrode at
ablation [27, 28]. Nonsurgical, minimally invasive modalities, temperature between 50∘ C and 100∘ C [38]. Temperature
like ethanol ablation and laser ablation, have been reported higher than 100∘ C would lead to vaporization and carboniza-
to be an effective option in treating thyroid nodules [12, 13, tion which result in increased impedance of the tissue and
2 International Journal of Endocrinology

thus interrupted the transferal of electric current and heat electrode [22–24]. The electrode is a 14-gauge, 10 cm long,
energy [38]. Beside the frictional heat produced by oscillating four-hook expandable needle [14, 22]. Under US guidance,
ions, conduction of heat causes further damages to the the electrode is inserted along the greatest dimension of the
surrounding remote area in a slower manner [37, 39]. This nodule. The hook is then opened to a maximum of 3.5 cm and
forms the basic principles of RFA. placed with caution so as to avoid injury to vital structures.
The principles of heat conduction have been demon- Each hook is recommended to be 10 mm away from thyroid
strated in one recent experimental study using the pig animal capsule, 5∼6 mm from pseudocapsule of the outer edge of
model [40]. In this experimental study, temperature mea- nodule, and 15 mm from heat-sensitive cervical structures
surements around the RFA electrode in the porcine thyroid [22]. Lidocaine is injected into superficial cervical tissue and
gland were taken. The maximum temperature at a distance of on the thyroid gland capsule under US guidance. Correct
5 mm from the RFA electrode was between 44∘ C and 61∘ C position of electrode tips and hook is assessed by US. With
while, at a distance of 10 mm, a maximum temperature of this technique, a spherical ablative zone is usually achieved.
53∘ C was achieved. Even at this temperature, there were signs After the ablation, the hooks are retracted and the electrode
of irreversible cell death damage in the region of the thermal is slowly withdrawn after the RF energy has been switched off.
lesions [40]. The second technique is called the “moving shot” tech-
nique. This technique was first described by Baek et al. in
Seoul, Korea. In contrast to the fixed ablation technique,
3. Patient Selection a straight internally-cooled electrode is used [15, 16]. The
electrode is usually 15 cm in length and 17 gauge in size
In 2012, the Korean Society of Thyroid Radiology made a con-
with 1 cm active tip [15, 36, 52]. Recent modifications have
sensus statement regarding the treatment of thyroid nodules
allowed even shorter (7 cm shaft length) and smaller (18-
with RFA [41]. Essentially, RFA is indicated either for patients
19 gauge) electrode with active tips around 0.5, 0.7, 1, 1.5,
with nodule-related symptoms or with hyperfunctioning
and 2 cm [6, 16]. With these shorter and smaller electrode,
nodule(s) which is causing thyrotoxicosis. It is important
it allows better control and variation of ablation option
that, before the ablation, the nodule should be confirmed to
in treating small or vital structure closed thyroid nodule.
be benign in nature with at least two separate US-guided
In the “moving shot technique” [15, 16], the target thyroid
fine-needle aspiration cytologies and/or core biopsies [42,
nodule is divided into multiple small conceptual ablation
43]. Report of RFA incompletely treating primary thyroid
units and during the procedure, each conceptual unit is being
carcinoma was present and histological report reviewed the
ablated by the moving ablation electrode tip. The electrode
inadequacy of RFA in treating primary thyroid carcinoma
is inserted through the isthmus under the US guidance.
[44], and there was no evidence in supporting the treatment
As a result, the whole course of electrode could be seen
benefit of RFA in primary thyroid carcinoma. On the other
and that greatly reduces the risk of injury of the nearby
hand, a cytological diagnosis of follicular or indeterminate
structures. The ablation first starts from the deepest layer up
lesion requires histology to exclude malignancy. Therefore,
and so the electrode is slowly withdrawn to the surface. It
the consensus statement did not recommend RFA for fol-
is important that the region close to the trachea-esophageal
licular lesion or a nodule suspicious of malignancy [41]. In
groove be underablated in order to avoid injury to the
general, RFA is a safe procedure. However, we should be
recurrent laryngeal nerve, trachea, and esophagus as this area
cautious in application of RFA in patients who are either
is often referred to as the “danger triangle”.
pregnant or having history of serious heart problems [5, 41,
45–47]. Since there had been reports of cardiac complication
during RFA for liver tumors [45, 48], patients with serious
heart disease should have continuous cardiac monitoring 5. Short- and Long-Term Clinical
during and after RFA of thyroid nodules. Efficacy of RFA
RFA therapy has mainly been aimed at decreasing pressure
4. Procedural Steps symptoms, improving the cosmetic results as well as resolving
thyrotoxic status in hot nodules. Table 1 shows the results
During the procedure, the patient should be positioned in of volume reduction of cold thyroid nodule after RFA [53].
supine with neck slightly extended. Local anesthetic with For cold nodules, the efficacy of RFA has mainly been
lignocaine or xilocaine is then injected underneath the skin evaluated in terms of reduction of nodule volume, pressure
near the cervical-surrounding soft tissue and thyroid capsule symptoms, and cosmetic symptoms. The reported mean
[23, 49, 50]. Some would also administer premedication volume reductions at 1- and 6-month were 33∼53% and
of fentanyl and midazolam to minimize discomfort [51]. 51∼92%, respectively [15, 22]. Most patients have reported
Ground adhesive pads are adhered to both thighs and are improvement in pressure symptoms and cosmetic symptoms
connected to RF generator, and the generator was connected [5, 15, 17, 23, 24, 52]. Faggiano et al. reported a prospective
to RF electrode. study and found that RFA was far superior to conservative
There are two types of RF device and technique for treatment [24]. In this study, 20 patients were assigned to the
thyroid nodules. The first technique is called the “fixed RFA group while the other 20 patients to the control group.
ablation” technique. This technique was popularized by an After 12 months, patients in the RFA group had significantly
Italian group. It involves the use of a multi-tined expandable decreased mean nodule size (13.3 to 1.8 mL, 𝑃 < 0.001)
International Journal of Endocrinology 3

Table 1: Result of volume reduction in patients who underwent radiofrequency ablation for cold thyroid nodule.

Volume Volume
Follow-up Mean initial
Number of Solid Number of reduction at reduction at the
duration Electrode type volume
nodule/patients component session (mean) the 1st month last follow-up
(months) (mL)
(%) (%)
Sung et al. [11] 21/21 <10% 1–6 Internally cooled 1–3 (1.67) 10.2 92
Multitined
Deandrea et al. [22] 10/9 >30% 6 1 38.7 31.7 46.3
expandable
Multitined
Spiezia et al. [23] 66/66 >30% 12–24 1–3 (1.4) 21.1 43.7 76.6
expandable
Lee et al. [52] 27/27 10–50% 6–38 Internally cooled 1–4 (1.6) 14 97
Jang et al. [19] 20/20 <50% 6–43 Internally cooled 1-2 (1.1) 11.3 92
Baek et al. [17] 15/15 >50% 6–8 Internally cooled 1 7.5 49 80
Ha et al. [5] 14/11 >50% 7–92 Internally cooled 9.7 87.2
15/15 1 13.3 40 70.2
Huh et al. [53] >50% 6 Internally cooled
15/15 2 13.0 42.7 78.3
Multitined
Faggiano et al. [24] 10/10 >70% 12 1 13.3 36.5 84.9
expandable
Kim et al. [36] 35/30 0–100% 1–18 Internally cooled 1 6.3 47 64
Jeong et al. [15] 302/236 0–100% 1–41 Internally cooled 1–6 (1.4) 6.1 58 84
Lim et al. [20] 126/111 0–100% 36–81 Internally cooed 1–7 (2.2) 9.8 93.4

while, in the control group, the mean nodule size was nearly these refractory nodules [19, 52]. In predominantly solid or
static (11.2 to 11.8 mL, 𝑃 > 0.05). The symptom score was solid nodule (i.e., >50% solid component), RFA could achieve
also significantly improved in the RFA group (3.4 to 0.6 a 23 to 37% volume reduction at the 1st month and 51 to
out of 6, 𝑃 < 0.001) and there was a trend of worsening 77% reduction at the 6th month [16, 24, 36]. The rate of
symptoms in the control group (3.0 to 4.1 out of 6, 𝑃 > 0.05). volume reduction appears to be maximum after 1–3 months
Furthermore, the effect of RFA appeared to be durable. After and tends to wean off after 6 months [15, 36]. Besides presence
a 2-year follow-up, a mean of 79.4 ± 2.5% decrease in nodule of high cystic content [15–17, 19, 20, 36], low vascularity of
size (baseline size 24.5 ± 2.1 mL) was observed in an Italian nodule [16, 36] and nontoxic status [14] are good predictors
study [23]. Compressive symptoms improved in all patients for volume reduction.
and were completely resolved in 88% patients [23]. Similarly, Table 2 shows the result in patients underwent RFA for
Lim et al. reported a high mean nodule volume reduction hyperfunctioning thyroid nodule. For benign hyperfunc-
(93.5±11.7%) after a mean follow up of 49 months. Regrowth tioning thyroid nodules, RFA not only reduces the volume
of more than 50% was very uncommon (5.6%) [20]. but also improves the functional status. The majority has
However, it would appear that its efficacy solely depends improved thyroid function and reduced the need for antithy-
on the proportion of cystic component within the ablated roid medication [22, 24]. In fact, antithyroid medication
nodule. For cystic nodules with <10% solid component, RFA could be stopped in about 23 to 89% of the patients [16,
could achieve >90% reduction at 6-month after ablation 22]. In a largest reported series of 28 patients, Spiezia et al.
[11, 21, 36]. However, relative to EA, RFA was not superior reported that all patients with pretoxic thyroid nodule and
and required more sessions and was more expensive [11, 21]. 53% of patients with toxic thyroid nodule stopped antithyroid
In a recent randomized study of single-session treatment of medication at 12-month follow up after RFA. Relative to
benign cystic thyroid nodules, the mean volume reduction cold nodules, ablation of hyperfunctioning thyroid nodules
was 96.9% in EA while it was 93.3% in RF ablation (𝑛 = achieves lower volume reduction (60% versus 76% at 12
21 for each) (difference, 3.6%; lower bound of the one- month) [23] and requires more number of sessions (2.2
sided 95% CI of the difference, 1.2%), thus demonstrating versus 1.4) [15, 16]. In addition, it is important to be more
the noninferiority of EA to RFA [21]. The authors concluded cautious during ablation because incomplete ablation leading
that EA may be the first-line treatment modality for cystic to nodule regrowth and hyperthyroid relapse appeared more
thyroid nodules, which has comparable therapeutic efficacy common in ablation of hot nodules. Therefore, more sessions
to, but is less expensive than, RF ablation [21]. Therefore, EA of RFA are generally needed [16].
would still be the first-line ablative measure for cystic nodule.
On the other hand, predominant cystic nodule (10–50% solid 6. Complications
component) might be suitable for RFA as 6.1–21% failure rates
in EA were reported for this type of nodules [19, 54, 55]. Various complications have been described during RFA and
RFA is generally good in treating the solid component of they include pain, voice changes, skin burn, hematoma,
4 International Journal of Endocrinology

Table 2: Result of patients who underwent radiofrequency ablation for hyperfunctioning thyroid nodule.

Stopped Decreased Initial dosage of Dosage at last

Number of Follow-up Initial
antithyroid antithyroid antithyroid follow-up
nodule/patients duration (months) volume (mL)
medication medication medication (mg/d) (mg/d)
Deandrea et al. [22] 23/22 6 22.5 22.7% 77.3% 5.1 2.6∗
Pretoxic: 100%
Spiezia et al. [23] 28/28 12–24 32.7 7.9 4.2∗
Toxic: 53%
Baek et al. [16] 9/9 6–17 15 88.9%
Faggiano et al. [24] 10/10 12 13.3 40% 40% 6.5 2.3∗
∗
𝑃 < 0.05.

nodule rupture, and thyroid function disturbance. Most of RFA, it was inconclusive in causal relationship of RFA and
the patients recover well with proper treatment with very hypothyroidism. Since this patient have elevated antithyroid
few complications [5, 16–18, 23, 24, 33, 56]. In a Korean perioxidase antibody prior RFA, hypothyroidism might be
multicenter study involving 1459 patients, there were 3.3% the progression of Hashimoto’s thyroiditis [16, 18]. Ha et al.
patients with complications and, of these, 1.4% had major reported that RFA did not affect thyroid function even in
complications. patients who had undergone lobectomy [5].
Pain is the most common reported complication during Although there were no fatal complication or ultramajor
the procedure. It occasionally radiates to ear, shoulder, jaw, complication, tracheal injury, esophageal injury, or perma-
and chest [6, 16]. However, it is usually self-limiting and nent voice changes have been reported, it is important to be
resolved soon when the power of RFA has been switched off. cautious during the procedure and always trace the electrode
It is controlled with simple oral analgesic and only 5.5% of tip before starting ablation [60]. There has been a complica-
patients require analgesic for more than 2 days [15, 22, 57]. tion of brachial plexus injury reported in 1459-patient study
Voice change after RFA is uncommon (about 1%) but, [18]. Though rare, to minimize these complications, studying
nevertheless, it is the most fearful and serious complication preventive measures and following the consensus guidelines
[18]. It is likely caused by thermal injury to recurrent laryngeal are essential [41].
nerve or sometime vagal nerve in case of large thyroid
nodule. Most of the patients recover within 3 months [30]. 7. Comparison with Other Ablative Treatment
To reduce this, underablation near tracheoesophageal groove
is recommended. Other than RFA, other minimally invasive ablative modalities
Unlike RFA in liver tumor, there have been no reports of have been described, including EA and PLA. EA has been
skin burn of thigh pads. This is probably because of the lower shown to be more effective in treating predominantly cystic
energy used during ablation [37]. Skin burn at puncture site nodule (>90% cystic component) [12, 13, 29, 30] and less
has been reported and is usually of first degree. Most patients for predominantly solid nodule [61]. Sung et al. tried to
recover from pain and skin color change within 7 days [18, evaluate the opium first-line treatment of thyroid cystic
36]. Application of ice bag to puncture site might prevent skin nodule by comparing ethanol ablation and RFA [11, 21].
burn [18]. After a single treatment session, EA achieved similar and
Haematoma after thyroidectomy is a distress compli- noninferior outcome in terms of nodule volume, symptoms,
cation [58]. It happens after RFA but could be managed and cosmesis, compared to RFA [21]. However, fewer sessions
conservatively with the compression of neck for several of ablation were needed in the EA group, and cost of each
minutes [59]. It is usually caused by injury of perithyroidal session of ablation was also less expensive. Therefore, the
or anterior jugular vessels during electrode insertion. Proper author concluded that ethanol ablation should be the first-
assessment of perithyroidal and anterior neck and use of line treatment for cystic nodule. But there was still a role of
small size needle might prevent mechanical injury during RFA in ethanol refractory thyroid nodules. About 20% of cys-
insertion [59]. tic nodule was refractory to ethanol ablation [12, 19, 54, 55];
Nodule rupture and thyroid function disturbances are additional RFA could effectively treat incompletely resolved
two potential late complications of RFA. Nodule rupture may thyroid nodule [52]. For predominantly cystic nodules (i.e.,
occur 1 month after RFA. It usually presents as a sudden >20% solid component), EA is prone to incomplete ablation
neck bulging and pain at the time of rupture. It is caused by and adding RFA might be needed for improved results [19].
breakdown of thyroid capsule and internal bleeding. These Since the introduction of PLA in 2000, different stud-
patients should be managed with antibiotics and closely ies have assessed its efficacy and safety in the ablation
monitored since abscess formation is a potential sequel of thyroid nodules [25, 31–33]. It has been recommended
requiring subsequent operation [18]. by the guidelines of the American Association of Clinical
Transient thyrotoxicosis immediately after RFA has been Endocrinologists, the Associazione Medici Endocrinologi
reported. All patients were asymptomatic and spontaneously (Italian Association of Clinical Endocrinologists), the Euro-
recovered within 1 month [15, 36]. Though subclinical pean Thyroid Association (AACE-AME-ETA) as a possible
hypothyroidism in one patient was detected 6 month after option for treatment of benign thyroid nodules [57]. PLA
International Journal of Endocrinology 5

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