Changes in the Volume and Diameter of Benign Thyroid Nodules: A 10-Year Follow-Up Study

Background: The incidence of asymptomatic thyroid nodules has risen enormously, with > 90% being benign. Despite limited long-term data, significant nodule growth (SNG) is common. Guidelines recommend cytology reevaluation if SNG occurs. Our study aimed to identify the rate and factors associated with SNG, compare diameter and volume-based assessments, and examine the association between SNG and malignancy risk over the long term (10 years). Methods: The retrospective cohort study, conducted at Ankara University, School of Medicine, Department of Endocrinology and Metabolism, included 732 nodules from 376 euthyroid patients, all monitored over a 10-year period by the same experienced sonographer, with evaluations at baseline, 5th and 10th years. The nodules were cytologically benign and/or sonographically in the low-to-intermediate risk category. Size changes at the 5th and 10th years were considered significant if there was a 20% or 2 mm increment in two diameters according to diameter-based criterion (DBC) or 50% increment in volume-based criterion (VBC) designed by the ellipsoid formula. Generalized linear mixed-effects models were used to account for the clustered data structure and analyze factors affecting nodule growth. Nodule growth was the dependent variable, while sex, age at diagnosis, initial TSH level, total nodule count, nodule volume, echogenicity, and localization were independent variables. Results: At the 5th and 10th years, SNG frequencies were higher when calculated using VBC [27.7% (n = 203) and 44% (n = 321), respectively] compared with DBC [19.1% (n = 140) and 35% (n = 256), respectively], with the differences being statistically significant (McNemar test, p < 0.01). Factors associated with SNG included being younger than 45 years of age (VBC OR = 1.704, CI = 1.227-2.366, p = 0.002; DBC OR = 1.913, CI = 1.379-2.656, p < 0.001), having higher number of nodules (VBC: OR = 1.171, CI = 1.061-1.291, p = 0.002; DBC: OR = 1.147, CI = 1.040-1.265, p = 0.006), and having smaller nodule volume (VBC: OR = 0.870, CI = 0.806-0.940, p < 0.001; DBC: OR = 0.912, CI = 0.850-0.978, p = 0.010). Thyroid cancer was diagnosed in four original nodules (0.5%), whereas the malignancy rate in biopsies performed was 1.4% (n = 4). Conclusions: In long-term follow-ups of sonographically and/or cytologically benign thyroid nodules, SNG is not rare. Growth is more likely in younger patients, those with higher number of nodules and smaller nodules. In the follow-up of nodule size, VBCs yield augmented results compared with DBCs. However, malignancy is quite rare in growing nodules. Therefore, adopting flexible long-term follow-up protocols appears to be practical for benign nodular thyroid disease.