The Optimal Age Threshold for Stratifying the Risks of Disease Progression in Patients with Highly Suspicious Sub-centimeter Thyroid Nodules

Purpose The study aimed to identify the value and optimal age cutoff to predict the progression of highly suspicious thyroid nodules ≤ 10 mm during active surveillance (AS), and to reveal distinct risk factors in patients of different ages. Methods A total of 779 patients with highly suspicious thyroid nodules were enrolled and followed up by ultrasonography. Locally weighted scatterplot smoothing (LOWESS) and the package ‘changepoint’ were used to identify the optimal age cutoffs using R. Multivariate Cox regression was performed to identify independent prognostic factors in each patient group divided according to age. Results Age was an independent predictor of nodule progression ( P = 0.038). The optimal age cutoff to stratify the risk of nodule progression was 30 years. Younger patients were more likely to have progression of nodules during AS ( P < 0.001), including enlargement of nodule size ( P = 0.011) and new lesion occurrence ( P < 0.001). Nodule size was identified as a risk factor for disease progression in patients younger than 30 years old ( P = 0.008, OR 7.946, 95% CI 1.715–36.820), while multifocality ( P = 0.018, OR 2.315, 95% CI 1.155–4.639) and thyroiditis ( P = 0.028, OR 2.265, 95% CI 1.092–4.699) were independent predictors in patients over 30 years old. Conclusions Highly suspicious thyroid nodules ≤ 10 mm in young patients tended to be more progressive. The predictors of disease progression were distinct in patients of different ages.