Endocrine Abstracts

Introduction: Hormonal syndromes are significant cause of morbidity in patients with neuroendocrine tumors (NET), requiring special treatment, rarely completely efficient. Effect on mortality is also presumed. Our aim was to investigate epidemiological characteristics of NET with hormonal production in our group of patients.

Patients and methods: We analyzed 822 patients with NET of various primary tumor sites, treated at our department during period of 2004–2017. Tumors were graded and staged according to pathohistological characteristics, and extent of dissemination. Hormonal analyses were done routinely according to clinical presentation. Immunohistochemical staining for specific hormonal products was performed in tumors with proven clinical syndrome, and in gastro-entero-pancreatic (GEP) NET irrespective of presence of clinical syndrome. Statistical analysis was done with SPSS software.

Results: A total of 155 patients (18.9%) had hormonal clinical syndrome in our group of patients with NET. Immunohistochemical positivity without clinical syndrome was verified in additional 63 patients with GEP NET, making it a total of 218 (26.5%) tumors producing some type of hormonal product. Serotonin production was most frequently detected (126 tumors, 15.3%), followed by insulin in 21 tumors (2.6%), gastrin in 20 tumors (2.4%), ACTH in 15 tumors (1.8%), somatostatin in 10 tumors (1.2%), and calcitonin in 8 tumors (1.0%). Less frequently, ghrelin, glucagon, GHRH, VIP, PTHrP and ADH production was detected (in less than 1.0% each). In 39 patients without carcinoid syndrome, serotonin immunopositivity was detected in tumor tissue. Conversely, 6 patients with clinical carcinoid syndrome stained negative for serotonin. Same was observed in about 50% of patients with clinical ectopic Cushing’s syndrome. Only one patient immuno-positive for somatostatin actually presented with clinical syndrome. Hormonal clinical syndrome was most frequently present in patients with intestinal NET (47 patients, 30.3%), followed by pancreatic (46 patients, 29.7%), and lung NET (26 patients, 16.8%). Significant proportion consisted of tumors of unknown primary site (30 patients, 19.4%). Clinical syndrome was rarely present in poorly differentiated NET, only in 11 patients with grade 3 tumors. Overall survival in patients with hormonal syndromes was 126.0 months (95%CI 61.6–190.4), with 5-year survival of 62.5%. This was not significantly different when compared to non-functioning grade 1 and grade 2 NET (P=0.929). Only presence of Cushing’s syndrome significantly affected survival (median 4.0 monhs, 95%CI 0.0–12.1)

Conclusion: Clinical hormonal syndrome in patients with NET has a significant impact on overall morbidity, but seems not to affect survival, except in case of ectopic Cushing’s syndrome.