• Indeterminate Nodule
• Mutational Markers
• Surgery
• Thyroid

Palpable thyroid nodules are common in the adult population, with an estimated prevalence in the United States of 4–7%, resulting in 10 –18 million affected individuals (1–3). The incidence of thyroid nodules detectable by ultrasonography is even higher and may exceed 50% in patients over 65 years old (2, 3). The vast majority of thyroid nodules are benign and can be managed conservatively, whereas approximately 5–15% of nodules examined by ultrasound and fine-needle aspiration (FNA) cytology are malignant. A challenge facing the physician is to distinguish between benign nodules and malignant tumors to ensure that each patient receives timely and appropriate treatment, while minimizing the risk of unnecessary intervention. Fine needle aspiration cytology (FNAC) is the gold-standard modality for determining the nature of a thyroid nodule. However, it fails to yield a conclusive result in a subset of patients, labeling them as having an ‘‘indeterminate diagnosis.’’ In doing so, it compromises the proper triaging of patients to appropriate surgery. This places patients at risk of non-optimal initial surgery: an overly radical total thyroidectomy, or an unnecessary two-stage operation. The aim of this study was to assess the impact of combining gene mutation testing and ultrasonographic (US) features preoperatively on predicting the risk of malignancy in patients with indeterminate nodules, with the goal of offering patients the most appropriate tailored initial surgical intervention.