Evaluation of the Long-term Growth Potential of Benign Non-toxic Thyroid Nodules by the AgNOR Method; an 11-year Follow-up Study

Abstract

Objective: The classification of benign thyroid nodules as stable or as fast growing may have clinical and economical relevance. The proliferative activity of thyroid cells determined by argyrophilic staining of the nucleolar organizer region (AgNOR) displays significant differences between benign and malignant thyroid lesions. We tested if that parameter can predict the growth potential of benign nodules. Methods:On cytological samples of 106 benign nodules of 89 euthyroid patients, the mean AgNOR number per cell (AgNORc), the mean AgNOR area per cell (AgNORa) and the mean nuclear area were determined. The mean follow-up period was 11.9 years. The initial (V1) and the final (V2) nodule volumes and respective TSH values (TSH1 and TSH2) were determined.Results: 66 nodules (62.2%) increased in volume. The median of V2/V1 was 1.31. V2/V1 correlated significantly with AgNORa, AgNORc, nuclear area and TSH-1. There was no significant correlation between V2/V1 and either age, duration of follow-up or TSH-2. No correlation was found between V2 and any of the parameters. We found on both forward and backward stepwise analysis that AgNORc values and initial TSH levels were significant determinates of the increase in volume size, i.e. both higher AgNORc values and higher initial TSH levels carry a greater risk for nodule growth. Conclusions:The determination of AgNORc during FNA evaluation may contribute to the estimation of growth potential of thyroid nodules. Further studies using other enzyme techniques or new molecular methods are justified to achieve a better discrimination between stable and growing nodules.