Thyroid nodules are one of the most common reasons for an endocrinology consultation today.1, 2 Thyroid nodules, often discovered incidentally during a thyroid ultrasound or on physical examination, are common and usually benign. Between 5 and 15% are at risk of becoming malignant (thyroid cancer).3 It is also common to examine the cervical lymph nodes, as suspected lymphadenopathy and metastatic thyroid cancer can be detected.4, 5

The incidence of thyroid nodules is estimated at around 0.1% per year and almost 10% throughout life.6 Their prevalence ranges from 4 to 8% through palpation and up to 50–70% by ultrasound.7, 8 Thyroid nodules increase linearly with age, with exposure to ionizing radiation, with a family history of thyroid disease or thyroid cancer, as well as in iodine-deficient regions.1, 7, 9 In addition, thyroid nodules are approximately ten times more common in women than in men.7

Most cases of benign thyroid nodules (BTN) remain asymptomatic and can be treated by clinical follow-up. However, some of them may require treatment related to cosmetic issues, pain or local pressure.6, 9 The current standard of care for symptomatic BTN, as well as for thyroid cancer and metastatic cervical adenopathies, is surgery.10, 11 However, patients may have problems with surgery or may be unwilling to undergo these procedures.6, 8 Surgery is not only expensive, but is also associated with a 2–10% risk of complications, such as hypothyroidism, voice change or hypocalcemia.8, 10 In addition, the quality of life and general well-being of the patients can be significantly affected by lifelong dependence on thyroid hormone replacement therapy, metabolic changes, and the presence of a neck scar that can sometimes be unsightly.11

In the last twenty years, other non-surgical image-guided techniques for treatment have been introduced into clinical practice, which are less invasive than surgery and are generally performed on an outpatient basis, such as radiofrequency ablation (RFA) and ultrasound- guided percutaneous ethanol injection (PEI).3, 6, 12 In PEI, 95–99% ethanol is slowly injected into the cyst cavity, inducing small vessel thrombosis and coagulative necrosis in the cyst wall, followed by fibrosis, contraction and consequent reduction in lesion volume.2, 3

PEI is currently used as standard of care in the management of symptomatic BTN (fluid portion > 50%), but it is less common in the treatment of both solid and benign parathyroid nodules.6, 13

The aim of this study was to identify, critically assess and synthesize the available scientific evidence on the clinical effectiveness and safety, as well as on the cost-effectiveness, of PEI for the therapeutic management of people with thyroid nodular pathology or metastatic cervical adenopathies. A further aim was to conduct an economic evaluation to compare the health outcomes and costs of PEI and RFA in patients with predominantly cystic BTN.