Incidence and prognostic value of serotonin secretion in pancreatic neuroendocrine tumours

Abstract

Background

Serotonin secretion occurs in approximately 1-4% of patients with a pancreatic neuroendocrine tumour (PNET), but the incidence is not well defined. The aim of this study is to determine the incidence of serotonin secretion with and without carcinoid syndrome, and the prognostic value for overall survival (OS).

Methods

Data were collected from 255 patients with a PNET if 24-hour urinary 5-hydroxyindoleacitic acid excretion (5-HIAA) was assessed. Patients were diagnosed with serotonin secretion if 24-hour urinary 5-HIAA excretion was more than 3x the upper limit of normal (ULN) of 50 μmol/24 hours during follow-up. The effect of serotonin secretion on OS was estimated with uni- and multivariate analyses using a Cox-regression.

Results

2 (0.8%) patients were diagnosed with carcinoid syndrome and another 20 (7.8%) had a serotonin-secreting PNET without symptoms. These patients mostly had ENETS stage IV disease with high chromogranin A (CgA). Serotonin secretion was a negative prognostic factor in univariate analysis (HR 2.2, 95% CI: 1.27-3.81), but in multi-variate analysis only CgA >10x ULN (HR: 1.81, 95% CI 1.10-2.98) and neuron-specific enolase (NSE) >ULN (HR: 3.51, 95% CI 2.26-5.46) were predictors for OS. Immuohistochemical staining for serotonin was positive in 28.6% of serotonin-secreting PNETs (1 with carcinoid syndrome) and negative in all controls.

Conclusion

carcinoid syndrome is rare in patients with a PNET, but serotonin secretion occurs often. This is a negative prognostic factor for overall survival, but after correction for CgA and NSE it is no longer a predictor and probably only a "not-so innocent bystander" in patients with high tumour burden.

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