Nodular thyroid disease is a very common finding in clinical practice, discovered by ultrasound (US) in about 50 % of the general population, with higher prevalence in women and in the elderly [1–4]. Whereas therapeutic flowchart is quite established and shared for malignant lesions, multiple options are now available for patients presenting with benign thyroid nodules, ranging from simple clinical and US follow-up to thyroid surgery. The majority of thyroid nodules, benign by fine-needle aspiration, are asymptomatic, stable, or slow-growing over time and require no treatment. Nevertheless, large thyroid nodules may become responsible for pressure symptoms, resulting in neck discomfort, cosmetic complaints, and decreased quality of life. Partial/total thyroid surgery has so far constituted the only therapeutic approach for these. Although surgery is widely available, highly effective, and safe in skilled centers, complications (both temporary and permanent) still occur in 2–10 % of cases [5, 6]. Hypothyroidism is an unavoidable effect after total thyroidectomy, requiring lifelong l-thyroxine replacement therapy. Besides, surgery is expensive and may be not recommended for high-risk patients or refused by others. Radioiodine (131I) therapy has been proven to be effective to treat toxic multinodular goiters and autonomously functioning thyroid nodules (AFTN) [7], although they are usually more radioresistant than toxic diffuse goiters [8]. Radioiodine therapy normalizes thyroid function and significantly reduces thyroid volume. However, hypothyroidism often occurs, in up to 60 % of patients, several years after treatment [9]. Otherwise, radioiodine therapy shows only incomplete, weak effects in nonfunctioning cold thyroid nodules. Pretreatment with recombinant human TSH may improve goiter volume reduction by causing a more homogeneous distribution of radioiodine within the gland, especially increasing the uptake of 131I in scintigraphically relatively cold areas [10]. TSH-suppression therapy withl-thyroxine was widely used to achieve nodule shrinkage and to prevent nodule growth and formation, producing, however, controversial results and exposing patients to heart and bone side effects. Therefore, current guidelines do not recommend its routine use in clinical practice, suggesting its usefulness in some cases only [3, 4]. Over the last two decades, nonsurgical, minimally invasive, US-guided techniques have been proposed for the treatment of thyroid nodules [11–16]. Percutaneous ethanol injection (PEI) is recommended for the treatment of relapsing cysts and dominantly cystic thyroid nodules [17]. Because of the limitations of PEI in the management of solid thyroid nodules, hyperthermic methods (laser ablation and radiofrequency ablation) have been introduced afterward for the treatment of solid, benign thyroid lesions [18], achieving marked nodule size reduction and clinical improvement in nodule-related symptoms, in several series from skilled centers, especially in Korea and Italy. Other nonsurgical therapies, such as high-intensity focused-ultrasound (HIFU), microwaves, cryotherapy, and electroporation, are presently under investigation.
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