Elevated Serum Bioactive Ghrelin Levels in Patients with Metastatic Neuroendocrine Tumors Maintains Body Weight

Abstract

Purpose: Ghrelin is the first and only circulating gut-brain peptide shown to have orexigenic effects. In patients with neuroendocrine tumors (NETs), we have observed weight preservation despite widely disseminated disease and hypothesize that elevated ghrelin levels in these patients accounts for maintenance of BMI. In this study, we sought to establish ghrelin levels in patients with NETs and to evaluate for differences in ghrelin levels in NETs with and without hepatic metastases. Methods: The study was conducted as a single-center, prospective trial enrolling 31 patients with NETs. Bioactive ghrelin levels were measured and analyzed for differences by two-tailed unpaired Student's t test (P < 0.05) between subgroups including patients with and without metastases, patients on and off concurrent octreotide therapy, patients on and off concurrent proton pump inhibitor therapy, carcinoid tumors versus pancreatic NETs, multiple endocrine neoplasia type I (MEN I) versus non-MEN I, and Zollinger-Ellison versus non Zollinger-Ellison. Results: Bioactive ghrelin levels in patients with NET and hepatic metastases (591±275 pg/ml) were significantly (P = .03) elevated compared to the group of NET patients without hepatic metastases (387±234 pg/ml). The former had a mean weight of 176lbs compared to a mean of 163lbs for the latter. These higher ghrelin levels correlated with serum chromogranin A levels. Bioactive ghrelin in patients on long-acting octreotide and on proton pump inhibitor therapy differed significantly (P = .04 and. 03, respectively) from untreated patients. No significant differences in ghrelin levels were seen between any other subgroup analysis. Conclusions: These data suggest that there is a correlation in the levels of ghrelin and the presence of metastatic NETs. The elevations in serum ghrelin observed correlate with the aggressive nature of the disease as determined by measurements of biochemical markers. These data support the possibility that ghrelin is co-released from NETs and exerts an orexigenic effect in patient with NETs.