Elevated Pancreatic Polypeptide Levels in Pancreatic Neuroendocrine Tumors and Diabetes Mellitus: Causation or Association?

摘要

Pancreatic neuroendocrine tumors (PNETs) that secrete primarily pancreatic polypeptide (PP) are rare and usually nonfunctional. There are approximately two-dozen reports of PP-secreting PNETs, and three that have been associated with diabetes mellitus (DM). None suggest a mechanism for the association between PP-secreting PNETs and DM. We describe five patients with PP-producing tumors who were diagnosed with DM at the same time as their PNETs, review the literature on PP, and consider its role in the pathophysiology of diabetes mellitus. The cases discussed were extracted from our surgical neuroendocrine tumor database. We examined all patients with PP-predominant PNETs—both with DM (n=5) and without (n=8). The five patients with DM at the time of PNET diagnosis demonstrated improvement or resolution of their DM post-operatively. In the patients with PP-secreting PNETs but no diagnosis of DM pre-operatively, one became hypoglycemic post-operatively, and two others developed post-operative DM. The five cases discussed in detail raise the question of whether the hypersecretion of PP in PNETs might be an important event leading to the development of diabetes mellitus. Although the literature does not provide a mechanism for this association, it may be related to the role of PP in hepatic glucose regulation.