Pancreatic islet cell tumors are divided into two types: (1) an endocrine type that elaborates excessive gastrointestinal tract hormones, causing specific clinical syndromes, and (2) a nonfunctioning type that is characterized by symptoms related to the size, location and invasion of the tumor mass. Pancreatic islet cell tumors have a better prognosis than those associated with ductal cell adenocarcinoma. They may be diagnosed by the classic clinical manifestation, by the detection of hormones in the serum and by dynamic CT scan with intravenous and oral contrasts.

Several pancreatic islet cell tumors have been identified. These tumors tend to elaborate a variety of biologically active peptides, resulting in a variety of clinical presentations. These peptides include glucagon, insulin, gastrin, vasoactive intestinal peptide (VIP), somatostatin and pancreatic polypeptide (PP).

Insulinoma is the most common neoplasm of the endocrine pancreas. The insulinoma syndrome is associated with Whipple's triad, which includes symptoms of (1) fasting hypoglycemia (confusion, seizures, personality changes, in addition to palpitation, tremulousness and diaphoresis), with (2) a low serum glucose level, and (3) a relief of symptoms by the administration of glucose. The diagnosis can be made by the demonstration of high serum insulin and low blood sugar, and an elevation in the insulin-to-glucose ratio (IG). The tumor may be localized by dynamic CT scan. Treatment includes surgery to remove the tumor if it is well localized or amenable to surgery, and a combination chemotherapy including streptozocine, doxorubicin and 5-fluorouracil.

Glucagon-secreting tumors (glucagonomas) arise from the alpha cells of the pancreas. Patients commonly present with mild diabetes, dermatitis, delayed gastric emptying, stomatitis, ileus and constipation. The dermatitis is manifested by a skin rash termed necrolytic migratory erythema, commonly appearing over the lower extremities. The diagnosis is established by the demonstration of elevated plasma glucagon levels that increase, paradoxically, with challenge by intravenous tolbutamide. Glucagonoma tends to present with large tumors and can be demonstrated by dynamic CT scan.

Gastrin-secreting tumors (gastrinomas; Zollinger-Ellison syndrome) arise from nonbeta islet cells. They are frequently malignant and tend to be multiple. They commonly present with recurrent severe peptic ulceration accompanied by marked gastric acid hypersecretion and occasionally diarrhea. The diagnosis is established by the demonstration of marked fasting hyper-gastrinemia and marked gastric acid hypersecretion. In patients who have borderline increases in gastrin, provocative testing with secretin is indicated. Following secretin stimulation, gastrin levels increase in patients with gastrinoma, whereas in patients with common duodenal ulcer, gastrin levels may show a minimal increase, a decrease or no change. High levels of gastrin may be present in a condition known as G-cell hyperplasia. This can be distinguished from gastrinoma by the sharp rise of gastrin levels (> 200%) in response to meals. Patients with gastrinoma show minimal or no rise in gastrin levels.

Vasoactive intestinal peptide-secreting tumors (VIPoma; Werner-Morrison syndrome) produce the pancreatic cholera syndrome, which is characterized by severe diarrhea, hypokalemia and hypochlorhydria or achlorhydria. Fluid secretion may exceed 3-5 L, with a loss of 200-300 mEq of potassium daily. Although the diagnosis is established by the demonstration of high levels of VIP, other substances, such as prostaglandins and secretin-like substances, may contribute to this syndrome.

Somatostatin-producing tumors (somatostatinomas) are the least common of pancreatic islet cell tumors, so by the time of diagnosis they tend to be malignant and have usually metastasized. They commonly present with mild diabetes mellitus, gallstones with a dilated gallbladder, anemia, hypochlorhydria and malabsorption. The diagnosis is established by the demonstration of high serum levels of somatostatin.

Pancreatic polypeptide-producing tumors have not been shown to produce any clinically defined syndrome.

Pancreatic endocrine tumors are ideally treated by resection. Unfortunately, despite all our available techniques, up to 40% of these tumors tend to escape localization. These tumors tend to be single or multiple and may be located in any portion of the pancreas or ectopically in the duodenum or any other part of the gastrointestinal tract. It appears that endoscopic ultrasonography may play an important role in tumor localization, but this technique is operator dependent and is not widely used.

Recently, octreotide scintigraphy has shown promise in detecting endocrine islet cell tumors, which appear to have somatostatin receptors. Radiolabeled somatostatin analogues bind to these receptors and can be demonstrated by a gamma camera scintigraphy. This test offers some hope in differentiating endocrine from ductal cell tumors. It may assist the surgeon in delineating and removing the tumor and possibly the metastatic lesions.