Thyroid Research and Practice

: 2014  |  Volume : 11  |  Issue : 3  |  Page : 89--93

Non-invasive and percutaneous ablation of nontoxic solid nodules

Narendra Kotwal, Aditi Pandit 
 Department of Endocrinology, Army Hospital Research & Referral, Delhi Cantt, New Delhi, India

Correspondence Address:
Narendra Kotwal
Department of Endocrinology, Army Hospital Researcch & Referral, Delhi Cantt, New Delhi - 110 010


Thyroid nodules (TNs) are commonly seen in the general population with a prevalence of about 4% by palpation and about 10-41% by ultrasound. Most of the TNs are benign. Surgery and radioiodine therapy have been the mainstay of therapy in compressive TNs. Surgery has its own complications and hence, the quest for a non-invasive modality of treatment remains. Radiofrequency ablation, ethanol ablation and laser ablation are the non-invasive methods of treating a benign TN. Also, microwave ablation and high intensity focused ultrasound have recently been tried in the treatment of TNs. In this review, we will be discussing the above newer and emerging modalities in the non-invasive ablation of non-toxic nodules.

How to cite this article:
Kotwal N, Pandit A. Non-invasive and percutaneous ablation of nontoxic solid nodules.Thyroid Res Pract 2014;11:89-93

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Kotwal N, Pandit A. Non-invasive and percutaneous ablation of nontoxic solid nodules. Thyroid Res Pract [serial online] 2014 [cited 2021 Dec 1 ];11:89-93
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Thyroid nodules (TNs) are very commonly seen in general population with a prevalence of about 4% by palpation and up to 10-41% with use of ultrasound. [1] Majority of the TNs are benign [2] and few of the benign nodules warrant treatment for pressure symptoms and for cosmetic reasons. Surgery and radioiodine therapy have been the mainstay of therapy in the compressive TNs but surgical complications have been reported in around 7-10% of cases. [3] Also, the risk of thyroid surgery is definitely more in the elderly population and it is refused by many. Medical therapy using levothyroxine used in non-functioning TNs achieves very little goiter shrinkage and also, the risk of suppressing thyroid stimulating hormone remains. [4] Non-surgical or minimally invasive methods of treating TN are being investigated. Ethanol ablation (EA), percutaneous radiofrequency ablation (RFA), and laser ablation (LA) have been used. Recently, high intensity focused ultrasound (HIFU) and microwave ablation as thermal ablation have been tried. In this review, we will be discussing the non-invasive modes of treating solid TN's.


RFA first tried in the treatment of liver cancer [5] and was introduced in the treatment of TNs in 2006. Kanauchi et al. in 2001 [6] demonstrated in pigs that percutaneous RFA induced necrosis of thyroid tissue. Mallery et al. [7] in 2003 successfully used RFA for treating hyperthyroidism in cats though, the effect was transient.

Principle of RFA

RFA uses the heat generated from high frequency alternating electric current between 200 kHz and 1200 kHz. The radio-frequency waves pass through the electrode and agitate the tissue ions around the electrode. They generate frictional heat and increase the temperature in the tissue, resulting in the destruction of the tissue. Furthermore, the conduction heat from the ablated area can damage the tissue away from the electrode in a slower fashion. Frictional heat and conduction heat are the two basic principles of RFA.


The moving shot technique has been recommended to optimize the efficacy and minimize the complications. The TNs are divided into multiple conceptual units and the nodule is ablated unit by unit. The electrode is placed in the deepest portion of the nodule and then moved backwards in the superficial direction. The extent of the ablated area is determined by the echogenic changes. It is performed under ultrasonographic guidance after local anesthesia usually using the Trans isthmic area. This approach has several advantages like clear view of the electrode in the transverse ultrasound view and minimal heat exposure to the danger area that is near the recurrent laryngeal nerve and/or the esophagus. [8]


Many studies have demonstrated the safety and the efficacy of RFA. [3],[9],[10],[11],[12] In a recently published study in December 2012, demonstrated the efficacy and safety of RFA in both toxic and non-toxic solid nodule compared to no treatment at all. They demonstrated a reduction in TN volume of up to 94% at the end of 9 months and also, reduction in the pressure symptoms. [3] These results were similar to a randomized prospective study by Baek et al. [13] In another follow-up study of 126 benign TNs in 111 patients over 4 years, reported a decrease in the TN volume of up to 93.5% at the end of 4 years. [14] In a large series study of 236 patients demonstrated a volume reduction of up to 84% in 6 months. 91% of nodules were reduced by 50% indicating therapeutic success. [10] The greatest volume reduction was observed in the 1 st month post RFA with further declining volume as the time passes. [10],[13] It has been demonstrated that a single session of RFA is sufficient to decrease the thyroid volume and ameliorate the cosmetic and the pressure symptoms. [13] A recurrence rate of 5.6% was found over a follow-up of 4 years though, none of the nodules grew to a size larger than its initial volume. [14] Complete ablation of periphery is important to prevent the marginal tumor regrowth which may be required in larger nodules and the moving shot technique has been proposed as a suitable method. [9],[13],[15] RFA is also effective in treatment of benign predominantly cystic TNs with a residual solid component in patients whose clinical problems were incompletely resolved after EA. [16] RFA is effective in solid nodules in patients with incompletely resolved clinical problems after EA indicating that RFA is effective for both solid and cystic component. [17] Recently, Korean society of thyroid radiology have published a consensus statement regarding the use of thermal ablation laser and radiofrequency in TNs. [18]


In a retrospective study conducted on 1459 patients who underwent RFA, the complication rate was 3.3% and major complication rate was 1.4%. Major complications were voice change, brachial plexus injury, tumor rupture, and permanent hypothyroidism. Minor complications were hematoma, skin burn, and vomiting. [19] Pain was the most common complaint reported post-procedure and around 5.5% patients required analgesics for the same. [10] Kim et al. reported that recurrent laryngeal nerve injury after RFA was 3.3%. [11] Knowledge of the danger triangle and the variations in the vagus nerve can help prevent the recurrent laryngeal injury. Hematomas can be prevented by local compression. Nodule rupture usually occurs due to hematoma in the TN and can be conservatively managed with antibiotics and/or analgesics.


LA concept was initially described in 1983 by Bown. [20]


Light is delivered interstitially by implanting a laser fiber directly into tissues. Interstitial LA is a thermal technique aiming at conversion by tissue into heat of light produced by sources such as neodymium-yttrium aluminum garnet with a wavelength of 1064 nm or continuous (820 nm) diode laser. The delivered photons cause increase in the temperature followed by the denaturation of the irradiated cells. LA induces a zone of coagulative necrosis with well-defined margins when temperature exceeds 60°C (threshold for protein denaturation) with irreversible tissue destruction and with no viable tissue remaining inside. [21]


Based on experimental studies in animals a first feasibility was conducted in 2000 by Pacella et al. [22] Many uncontrolled trials have demonstrated the efficacy of LA in TNs. [23],[24],[25] In a large series of 122 patients were followed up for a period of 3 years. The thyroid volume decreased by 50% in a wide size range of nodules. [26] In another prospective randomized study by Dossing et al. showed that a single treatment with ultrasound guided LA reduced the thyroid volume by almost 50%. The incremental effect of additional laser was minimal. [27] A randomized controlled trial showed that nodules decreased significantly by 22% after 2 weeks and by 44% after 30 weeks. [28] In another randomized controlled trial demonstrated a volume reduction >50% was found in 33.3% of cases. [29] A study in 2009 demonstrated a dose response relationship of LA. [30] Also, a recent study has demonstrated that only high energy (>400-500 J/ml of nodular tissue to be treated) of laser energy is needed for it to be effective over time. [31] Also, the concern regarding the histopathological changes seen in TN after LA was studied in a series of 22 patients followed up for 18 months. It was demonstrated that LA treatment is safe and can be followed up with fine needle aspiration cytology. [32] Similar results were found by Cakir et al. [33] In comparative study between LA and RFA found that LA as well as RFA are suitable for singular TNs and induces reproducible clinically relevant lesions in an appropriate application time. The maximum inducible lesion volumes by LA are significantly larger than by RFA with the devices used herein. [34]


Complications associated with LA are rare and usually temporary. Transient dysphonia, pain, fever, mild burns and skin infections have been reported. [21]


EA was first used for a successful renal cyst ablation in 1981 [35] and subsequently was demonstrated to be effective in treatment of hepatic cysts, [36] malignant liver lesions, [37] and also primary hyperparathyroidism. [38] Ethanol causes thyroid tissue destruction by complex mechanisms like coagulative necrosis, vascular thrombosis, and hemorrhagic infarction. [39] Livraghi et al. first demonstrated the use of EA in hyper functioning TNs in 1990. [40] Since then, EA has been established as a first line treatment for benign cystic TNs. However, the data regarding use of EA in solid nodules is variable and depends on the nodule size, volume of ethanol instilled, and nodule toxicity. [41],[42],[43] In a recently published study, however, demonstrated a success rate of 60% in solid nodules. Nodular vascularity and the degree of intranodular echo staining after EA on color Doppler sonography were useful in predicting the success rate for benign predominantly solid nodules. [44] Limitations include repeated use of EA, painful despite local anesthesia, fever, periglandular fibrosis or dysphonia. A sudden increase in the intranodal pressure can cause leakage of ethanol extranodally. [45]


Microwave thermal ablation

Microwave ablation uses electromagnetic energy typically operated at 915 MHz or 2.45 GHz causing tissue destruction using thermal energy. When electromagnetic energy is applied over the tissue, the energy is used to force molecules to continuously realign with the applied field. This rotation of molecules represents an increase in kinetic energy and hence, an elevation in local tissue temperatures. [46] Microwave ablation has been used for the treatment of hepatic malignancies, [47] lung malignancies, [48] lung cancer. [49] Its use in TN ablation has been demonstrated recently. In recently published study in January 2013, a total of 477 benign TNs in 222 patients underwent microwave ablation. A volume-reduction ratio greater than 50% was observed in 82.3% of index nodules, and 30.7% of index nodules disappeared 6 month after the ablation. They did not report any major complications. [50] Another study demonstrated a volume reduction ratio of up to 45%. One case report of laryngeal nerve palsy and tracheal cartilage necrosis after microwave ablation has been reported. [51]


HIFU relies on the same principle as ultrasound. When focused ultrasound waves pass through a tissue it causes local rise of temperature to cause tissue necrosis. [52] In 1950 Fry et al. demonstrated the use of HIFU by producing lesions in the brains of cats and monkeys. [53],[54] It has been used in the treatment of benign prostratic hyperplasia, liver cancer. Prostrate cancer. [52] Esnault et al. have conducted the first human feasibility study on 25 patients. Among the 25 patients, 16 patients showed a significant response on ultrasound. They did not report any complications. [55] Though, it appears as an exciting prospect much research is needed yet.


The non-invasive and the percutaneous methods like LA and RFA are a good alternative to benign solid TNs, especially in patients refusing surgery and those with cosmetic problems. EA though, effective in cystic nodules, its use in solid nodules is limited with the conflicting data available. The newer modalities are all an interesting prospect in our never ending search for an ideal alternative to surgery which is minimally invasive, though, further studies need to determine its efficacy in the treatment of TN's.


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