A thyroid nodule is a lesion of the thyroid gland distinct from differentiated from tissue due to abnormal growth of thyroid cells. It may be benign or malignant.

About 95% of thyroid nodules are benign. Thyroid nodules are malignant in about 5% of cases. Among malignant nodules, by far the most frequent are poorly aggressive papillary microcarcinomas (MPTC) (80-90% of malignant tumors).

The thyroid nodule is commonly encountered. While studies conducted in the 1970s based on inspection and palpation had reported a thyroid nodule prevalence of 3 to 7 percent in the total population, the more recent introduction of ultrasonography has revealed that the percentage of thyroid nodules is actually much higher, ranging from a low of 20 percent to a high of 76 percent in the general population. Thyroid nodules detected by ultrasound have a prevalence similar to that described by autopsy studies in the 1950s, namely, that the number of nodules found by ultrasound corresponds to those detectable by examination of glandular tissue, therefore in about 50% of the thyroids examined.

Thyroid nodules are more common in older people, women, individuals from iodine-deficient geographic areas, and those with a history of exposure to ionizing radiation.

Large nodules are usually visibly noticed by the patients themselves or their family members or friends.

Smaller thyroid nodules are often detected incidentally during neck imaging examinations such as carotid artery echo-Doppler, CT scan, MRI, PET scan, and scintigraphy, performed for reasons unrelated to thyroid disease. Only rarely are thyroid nodules recognized by screening ultrasound.

  • Measurement of TSH and circulating thyroid hormones fT3, fT4, anti-thyroid anti-Thyperoxidase and anti-Thyroglobulin antibodies: these blood tests recognize possibly coexisting thyroid dysfunction, hypo- and hyper-thyroidism. The blood tests of most patients with thyroid nodules reveal concentrations within normal limits.
  • Thyroid needle aspiration for cytologic examination (FNAC): this recognizes malignancies. Its blanket use has resulted in increasing increase in diagnoses of thyroid tumors and especially papillary thyroid microcarcinomas (MPTC) in recent years.
  • Thyroid scintigraphy and other imaging tests (CT, MRI, PET) : are useful only in selected cases

The use of thyroid removal surgery has increased enormously in recent years: in 2016, about 40,000 total thyroid removal surgeries were performed in Italy, 80% of the cases on women. Surgical procedures that saved healthy parts of the gland were performed in only 2% of cases.

Small malignant lesions of the thyroid gland (MPTC), are generally devoid of aggressiveness. For this reason, it is sometimes recommended not to perform any type of intervention but to monitor the patient(s): so-called active surveillance. In cases where aggressiveness of the tumor is suspected (extracapsular extension, aggressive cytology, suspected metastasis to lymph nodes), surgical removal of the thyroid is recommended.

Most patients (about 80%) refuse the proposal of “active surveillance”; once carcinoma is diagnosed, most patients prefer to undergo surgery to get rid of the neoplasm for good. Thyroid specialists (endocrinologists, surgeons, others) who follow the most established guidelines offer patients surgery for total or partial removal of the thyroid gland in more than 55% of cases regardless of the aggressiveness of the tumor at the time of diagnosis.

Conventional surgery consists of lobectomy or total thyroidectomy. Transaxillary or transoral robotic surgical variants have also been proposed. Minimally invasive video-assisted surgery, MIVAT (Minimally Invasive Video Assisted Thyroidectomy), has also been practiced. Any surgery involves skin incision and a hospital stay. Most importantly, it involves the sacrifice of a thyroid lobe or the entire thyroid gland.

According to very recent international guidelines, which the TNT Association collaborated in the drafting, the alternative to surgery and simple surveillance are ablative therapies that offer a solution to the fundamental problem by avoiding surgery for partial or total removal of the gland, thus saving the thyroid gland.

Thyroid ablative therapies aim to destroy both benign and malignant nodular tissue by selective tumor removal (ablation) guided by ultrasound imaging (minimally invasive ultrasound-guided surgery). Thyroid ablation is achieved by administering heat directly to benign or malignant nodular cells (thermo-ablation). This is achieved by the ultrasound-guided introduction of heat-delivering devices (radiofrequency, microwave, laser) into the nodule to be destroyed, achieving tumor destruction and annihilation. When the temperature inside the nodule exceeds 60°C for just one second, the cells exposed to this temperture are destroyed.

The delivery of heat inside the nodule can be done with using various devices: radiofrequency (RFA), microwave (MWA), laser light (LA), and high-intensity focused ultrasound (HIFU). Among all these hyperthermic techniques, radiofrequency has emerged to be the most suitable because it is easy to perform and widely applicable in many diagnoses.

Non-hyperthermal ablation techniques are also proposed, such as Irreversible Electroporation (IRE), which, by means of the application of a high-voltage electric field around the nodule opens the micropores on the cell membrane, thus destroying the targeted cells by natural death (apoptosis).

IRE is currently used to treat highly malignant tumors and has not yet been tested on the human thyroid.

Radiofrequency thermal ablation is an outpatient procedure that is performed without the need for surgical incisions by means of a needle-electrode inserted and guided and controlled by ultrasound imaging inside the thyroid nodular tissue. Overheating of the tissue causes ablation.

RFA reduces the volume of benign thyroid nodules by an average of 70-80% within one year. The reduction in nodule volume is generally sufficient to make compressive symptoms disappear and achieve excellent cosmetic results. In the case of hyperfunctioning adenomas (toxic or pretoxic), RFA can normalize thyroid function as well. RFA destroys papillary thyroid microcarcinomas which in 80-100% of the cases no visible traces on an ultrasonography can be detected. Best results are obtained on benign nodules of volume <30 ml (largest diameter <5-6 cm), oval in shape, and spongiform colloid-cystic ecostructure. RFA has been proven to improve the quality of life of patients who have undergone this procedure.

Before surgery, the nature of the thyroid nodule should be determined by ultrasound-guided fine needle aspiration (FNA) and/or thyroid needle biopsy (CNB). If RFA surgery is indicated, the patient should undergo preoperative tests, including thyroid function tests, coagulation tests, blood glucose, transaminases, creatinine, and ECG.

Radiofrequency thermal ablation is prescribed for the treatment of solid or partially cystic benign nodules of the thyroid gland. RFA is also effective in thyroid cysts and Autonomously Functioning Thyroid Nodule (AFTN) adenoma. Papillary malignancies <1 cm in size or lymph node metastasis that are neither responsive to radioiodine nor a candidate for surgery can be successfully treated with RFA.

The most commonly used technique is monopolar radiofrequency. During this procedure, the patient is part of a circuit that includes a radiofrequency generator, a needle-electrode, and two grounding pads placed on the patient’s legs. There is also radiofrequency with bipolar circuit in which the circuit opens and closes at the tip of the needle without traveling through the patient’s body. This produces reduced ablations and should be reserved for patients with pacemakers or implanted defibrillators.

The patient is placed on the bed in a supine position, head hyperextended. The operator administers echo-guided local anesthesia with 2% lidocaine (short-acting) and 10% bupivacaine (long-acting). The anesthesiologist cannulates a vein and sedates the patient with midazolam 3-5 mg followed by Propofol on a slow infusion pump. Oxygenation is maintained by means of “goggles” connected to an oxygen cylinder. Vital parameters including respiration, ECG, partial oxygen pressure, and blood pressure are monitored by the anesthesiologist throughout the procedure. Sedation is necessary to facilitate maneuvers and reduce spontaneous swallowing acts. Sedation causes semi-consciousness and anterograde amnesia. The patient loses all recollection of the procedure and experiences no intraoperative pain while maintaining some responsiveness.

The needle-electrode is introduced into the nodule under ultrasound guidance. Radiofrequency electromagnetic waves emitted by the electrode heat the nodule inducing necrosis of the targeted tissue, which will be replaced by fibrous tissue over time. This results in volume reduction of the thyroid nodule. A saline cooling system at a temperature of -5 °C reduces the temperature at the needle-electrode tip during treatment to avoid the process of carbonization.

No hospitalization is required for the RFA procedure. RFA surgery is performed on an outpatient basis under local sedation and analgesia but without the need for general anesthesia with intubation. The patient is usual awake by the end of the procedure, and after 1-2 hours of observation in the recovery room, the patient is discharged. In the immediate postoperative period, analgesics are administered to reduce pain.

Some physicians prefer to perform the procedure under local anesthesia in an outpatient facility in order to keep costs down and to have direct control over patient voice, which is asked to produce vocal sounds during the ablation procedure. This practice causes stress and discomfort to patients. In the absence of an anesthesiologist, the same operator is called upon, in addition to performing the ablation, to also monitor patient’s vital functions. The intervention of an anesthesiologist/reanimator and the use of an operating room reduce stress for patient and operator, lower discomfort and possible side effects, and provide legal protection for the operator.

The procedure, including set-up time, lasts from a minimum of about 15 to a maximum of 120 minutes depending on the size and number of nodules, as well as other individual patient factors.

RFA is repeatable on particularly large nodules or in cases of recurrence.

At the end of the RFA procedure, steroid (methylprednisolone) and pain-relieving (acetaminophen) therapy is administered intravenously. These therapies prevent inflammation (soft tissue swelling) and pain, respectively. No antibiotics are needed.

Pain is very limited. It is generally restricted to a tight sensation or tenderness in the neck. During RFA procedure, the patient loses all memory of the surgery and does not experience any intraoperative pain while maintaining some responsiveness. Postoperative pain is controlled by acetaminophen and anti-inflammatory drugs. Other analgesics or opioids are very rarly needed to reduce pain.

The patient is usually awake immediately at end of RFA surgery, and is kept under observation in the recovery room for 1-2 hours. Before discharge, a postoperative ultrasound is performed, comparing preoperative and postoperative images. The patient is issued a discharge letter succinctly describing the RFA procedure and its outcomes. A clinical and ultrasound follow-up is performed the day after the RFA procedure.

Thyroid nodules appear near structures in the neck that need to be preserved: common carotid artery, internal jugular vein, vagus nerve, brachial plexus, cervical sympathetic, trachea, recurrent laryngeal nerve, esophagus, muscle fascia and muscles. Ultrasonographic visualization using technologically advanced instrumentation and gentle and precise maneuvers during radiofrequency thermal ablation preserve these structures. The technique of hydrodissection (separation by infusion of cold glucose solution (+2 °C) of the recurrent laryngeal nerve from the thyroid nodule minimizes the risk of dysfunction of the recurrent laryngeal nerve that moves the vocal cord. In selected cases, we propose intraoperative vocal cord monitoring by Fibrolaryngoscopy (FFL) to the patient.

If performed properly this technique has minimal and easily preventable side effects and complications.

They may consist of (the frequency of side effect are highlighted)

  • Sense of discomfort in the neck: common, resolved spontaneously in a short time.
  • Neck pain, sometimes radiating to the jaw: rare, occurs in the immediate postoperative period, has spontaneous resolution or treated with anti-inflammatories in 1-3 days.
  • Cutaneous ecchymosis: frequent, spontaneous resolution in 7-10 days.
  • Punctiform skin burn: very rare, requires dressing.
  • Abscesses or infections: very rare or nonexistent.
  • Pericapsular and intranodular bleeding: rare, they are dominated with external compression (pericapsular hemorrhage) or by RFA itself (intranodular hemorrhage). They result in neck swelling and/or ecchymosis.
  • Dysphonia (drop in vocal tone) from paralysis of a vocal cord: rare if hydrodissection is adopted. Exceptional or absent if intraoperative monitoring with FFL is additionally performed. Dysphonia is usually reversible in hours, days or months, and is caused by overheating of the recurrent laryngeal nerve that mobilizes the vocal cord. Only very rarely does the recurrent laryngeal nerve report an injury that causes permanent vocal cord paralysis.
  • Nerve injury to the brachial plexus or cervical sympathetic (Horner’s syndrome): very rare, partially reversible.
  • Autoimmune hypo/hyperthyroidism/thyroiditis: very rare. They are observed in 1% of cases, are usually transient, have as markers antithyroid antibodies that are checked periodically in every patient.
  • Colliquation and late rupture (10-25 days after ablation): uncommon, occur after ablation of large nodules. To prevent colliquation and rupture anti-inflammatory corticosteroid therapy at home post-RFA is indicated. Therapy is conservative, with drainage if the colliquated mass is large. Healing takes several months but is complete.

Some drugs are prescribed to patients as home postoperative therapy:

  • -Corticosteroids in various doses and durations to reduce postoperative edema and reduce the risk of late colliquation of the treated mass, to be taken orally with breakfast.
  • A pump inhibitor (lansoprazole) to be taken on an empty stomach in the morning with only water 1 hour before breakfast to achieve gastroprotection, for the duration of corticosteroid treatment.
  • Analgesics (paracetamol 1 g) or anti-inflammatories (ketoprofen, ibuprofen, etc.) to be taken as needed in the postoperative period.

Relative to the proposed indications, thermoablative radiofrequency therapy has the same result as surgical intervention while limiting the disadvantages of surgical intervention to a minimum.

  • Disadvantages of surgical therapy
    • Surgical scarring
    • Partial or complete loss of thyroid function
    • Major side effects
    • Recurrent laryngeal nerve injury with transient or permanent dysphonia
    • Hypoparathyroidism with transient or permanent drop in blood calcium
    • General operative risks: hemorrhage, infection
    • Need for general anesthesia, drainage tubes, hospitalization
    • Recovery time of several days
    • Deterioration in quality of life due to the need to take hormone replacement therapy

  • Advantages of ablative therapy
    • Absence of scarring
    • Preservation of normal thyroid gland
    • Preservation of normal thyroid function
    • No need to take any thyroxine replacement therapy
    • Minimal side effects
    • Absence of general anesthesia, drainage tubes, hospitalization
    • Very rapid recovery to daily routine activities
    • Aggressiveness minimized
    • Improved quality of life