Endocrine Abstracts

Aim: Functional neuroendocrine tumors (NETs) represent a specific diagnostic and therapeutic challenge, since hormonal clinical syndrome can severely complicate clinical picture and affect treatment. Our aim was to analyze characteristics and survival of functional pancreatic NETs.

Materials and methods: We retrospectively analyzed data from 272 patients with pancreatic NETs treated at our department from the year 2005 till 2023. The patients underwent standard radiological, pathohistological and hormonal evaluation. All tumors were graded according to current ENETS guidelines. Disease stage was defined according to the ENETS/AJCC TNM staging system. Differences between continuous variables were analyzed by non-parametric tests and differences between frequencies by χ²-test. Overall survival was analyzed by Kaplan–Meier method, and differences by Cox-regression analysis. Statistical analysis was performed by SPSS software.

Results: Functional tumors were diagnosed in 61 patients (22.4%): 24 insulinomas (8.7%), 11 serotoninomas (18%), 8 gastrinomas (13.1%), 6 patients with ectopic Cushing’s syndrome (9.8%), 3 patients PTHrP secretion (4.9%), 2 glucagonomas (3.3%), and 1 VIP-oma (1.6%), while the remaining 6 patients had combinations of 2 or more aforementioned hormonal hypersecretions. Majority of functional NETs were well differentiated (NET G1 29.5%, NET G2 41.0%, NET G3 13.1%, NEC G3 1.6%, MiNEN 1.6%), and better differentiated compared to nonfunctional NETs (P=0.018). Functional tumors were significantly smaller (P<0.05), more related to MEN1 syndrome (P=0.005), and with lower disease stage than nonfunctional (P=0.011). Median overall survival of functional NETs was 104.0 months (95%CI 100.2–206.8). This was not different to nonfunctional tumors (P=0.259), except that NET G3 functional NETs had a tendency towards shorter survival. There was significant difference in survival within a group of functional NETs (P<0.05), with patients with insulinomas having the longest, and patients with ectopic Cushing’s syndrome having the shortest survival. Patients with insulinomas had significantly longer survival when compared to nonfunctional NETs overall (P=0.013), but this was due to insulinomas being exclusively grade G1 and G2 (55.6% and 44.4% respectively), and of lower stage (SI and SII 73.7%). When G1 and G2 insulinomas were compared to respective nonfunctional tumors, there was no significant difference in survival (P=0.326 and P=0.909 respectively). On the other hand, patients with ectopic Cushing’s syndrome had significantly shorter survival compared to nonfunctional NETs irrespectively of grade or stage (P=0.008 and P=0.007 respectively).

Conclusion: Almost one quarter of patients with pancreatic NETs have a recognizable hormonal syndrome. Despite some more favorable features compared to nonfunctional tumors, certain hormonal profiles independently affect survival.