Gastrinoma, insulinoma, VIPoma, glucagonoma, and somatostatinoma account for the vast majority of pancreatic islet-cell tumors; their characteristics are shown in Table 71-3. The tumors are named for the dominant hormone they produce. They are generally slow-growing and produce symptoms related to hormone production. Gastrinomas and peptic ulcer disease constitute the Zollinger-Ellison syndrome. Gastrinomas are rare (4 cases per 10 million population), and in 25-50%, the tumor is a component of a multiple endocrine neoplasia type 1 (MEN 1) syndrome.

Insulinoma may present with Whipple's triad: fasting hypoglycemia, symptoms of hypoglycemia, and relief after IV glucose. Normal or elevated serum insulin levels in the presence of fasting hypoglycemia are diagnostic. Insulinomas may also be associated with MEN 1.

Verner and Morrison described a syndrome of watery diarrhea, hypokalemia, achlorhydria, and renal failure associated with pancreatic islet tumors that produce vasoactive intestinal polypeptide (VIP). VIPomas are rare (1 case per 10 million) but often grow to a large size before producing symptoms.

Glucagonoma is associated with diabetes mellitus and necrolytic migratory erythema, a characteristic red, raised, scaly rash usually located on the face, abdomen, perineum, and distal extremities. Glucagon levels >1000 ng/L not suppressed by glucose are diagnostic.

The classic triad of somatostatinoma is diabetes mellitus, steatorrhea, and cholelithiasis.

Provocative tests may facilitate diagnosis of functional endocrine tumors: tolbutamide enhances somatostatin secretion by somatostatinomas; pentagastrin enhances calcitonin secretion from medullary thyroid (C cell) tumors; secretin enhances gastrin secretion from gastrinomas. If imaging techniques fail to detect tumor masses, angiography or selective venous sampling for hormone determination may reveal the site of tumor. Metastases to nodes and liver should be sought by CT or MRI.