Background: Thyroid nodules are present in 19–67 % of the population and have a 5–10 % risk of malignancy. Fine needle aspiration biopsies are indeterminate in 20–30 % of patients, often necessitating thyroid surgery for diagnosis. We hypothesized that developing a risk model incorporating factors associated with malignancy could help predict the risk of malignancy in patients with indeterminate thyroid nodules. Methods: We identified 151 patients with a cytologic diagnosis of follicular neoplasm (Bethesda IV) who progressed to surgery. We retrospectively analyzed demographic, clinical, sonographic, and cytological variables in relation to thyroid carcinoma. Results: Of 151 patients, 51 (33.8 %) had a final diagnosis of thyroid carcinoma. Papillary carcinoma was diagnosed in 34 patients (66.7 %), follicular carcinoma in 15 (29.4 %), and Hürthle cell carcinoma in 2 (3.9 %). On univariate analysis, younger age, male gender, tobacco use, larger nodule size, and calcifications on ultrasound, nuclear atypia on cytology, and suspicious frozen section were associated with the presence of malignancy. When determining odds ratios, four factors were most predictive of malignancy: nodule calcification [odds ratio (OR) 6.37, 95 % confidence interval (CI) 1.62–25.1, p < 0.01] and nodule size (OR 1.75, 95 % CI 1.19–2.57, p < 0.01) on ultrasound, nuclear atypia on cytology (OR 4.91, 95 % CI 1.90–12.66, p < 0.01), and tobacco use (OR 4.59, 95 % CI 1.30–16.27, p < 0.02). A multivariable model based on these four factors resulted in a c-statistic of 0.82. Conclusions: A multivariable model based on calcification, nodule size, nuclear atypia, and tobacco use may predict the risk of thyroid cancer requiring a total thyroidectomy in patients with thyroid nodules of indeterminate cytology.
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