Endocrine Abstracts

Introduction: The surgical approach is the first line treatment for patients with an indeterminate nodule, both without and with nuclear atypia (TIR3A and TIR3B, respectively, as defined by Italian Consensus for thyroid cytology). However, there are no prospective studies about the feasibility of active surveillance in patients with indeterminate thyroid nodules.

Methods: Eighty-six consecutive patients who decided to undergo active surveillance for at least one indeterminate nodule, diagnosed with fine needle aspiration cytology, were enrolled in this prospective study, and were consequently submitted to neck ultrasound every 6-12 months. Disease progression was defined as detection of nodule enlargement in two consecutive evaluations (at least 3 mm in all diameters) and/or of a metastatic lymph-node. In such cases, patients were submitted to surgery. Molecular analysis was performed in a subgroup of samples.

Results: The median age at enrollment was 43 years (9-77 years, IQR 24). 78/86 patients exhibited a single indeterminate nodule: 20/78 (25.6%) TIR3A and 58/78 (74.4%) TIR3B. The remaining 8/86 patients had two indeterminate nodules. At baseline, median biggest diameter was 13 mm (5-58 mm, IQR 8). After a median follow-up of 24.5 months only 3/86 patients (3.5%) showed an increase in dimensions after 20, 36 and 37 months, respectively: two of them were submitted to surgery and their final diagnosis was minimally invasive follicular carcinoma; they were both cured during a follow-up of 29 and 4 months. The third patient is waiting for surgery. 8/86 (9.3%) patients were recently submitted to surgery due to their choice, without any evidence of disease progression: 2/8 (25%) presented a papillary thyroid carcinoma while the other 6 had a benign final diagnosis. The molecular analysis of 25/94 (26.0%) nodules showed that 12/25 (48%) were negative, 12/25 (48%) had one of the RAS gene family mutations (5/25 NRAS, HRAS 4/25 and KRAS 3/25) and 1/25 (4%) a BRAF^K601E. Despite the small number of analyzed cases, no correlation was observed between the presence of a gene alteration and the disease progression.

Conclusions: This study suggests that active surveillance is feasible for patients with indeterminate nodules. In our group, only 3.5% of patients demonstrated disease progression during a median follow-up of 24 months and their outcome was optimal despite the delayed surgery. Moreover, our data confirm the higher prevalence of RAS gene mutation (HRAS, NRAS and KRAS) and the absence of BRAF^V600E mutation in indeterminate nodules without any correlation with the progression of the nodule.