(See also Overview of Pancreatic Endocrine Tumors.)
Glucagon is a hormone normally secreted by the pancreas when blood glucose levels fall. Glucagon stimulates glycogenolysis in the liver and thus increases blood glucose. Glucagonomas are a type of pancreatic endocrine tumor that arises from the alpha cells of the pancreas. Glucagonomas are very rare but similar to other islet cell tumors in that the primary and metastatic lesions are slow-growing: 15-year survival is common. Eighty percent of glucagonomas are malignant. The average age at symptom onset is 50 years; 80% of patients are women. A few patients have multiple endocrine neoplasia type 1.
Because glucagonomas produce glucagon, which raises blood sugar, the symptoms are the same as the symptoms of diabetes. Frequently, weight loss, normochromic anemia, hypoaminoacidemia, and hypolipidemia are present, but the most distinctive clinical feature is a chronic eruption involving the extremities, often associated with a smooth, shiny, vermilion tongue and cheilitis. The exfoliating, brownish red, erythematous lesion with superficial necrolysis is termed necrolytic migratory erythema.
Most patients with glucagonoma have glucagon levels > 1000 pg/mL (> 1000 ng/L; normal is < 200 pg/mL [< 200 ng/L]). However, moderate elevations occur in renal insufficiency, acute pancreatitis, severe stress, and fasting. Correlation with symptoms is required.
Patients should have abdominal CT followed by endoscopic ultrasonography; MRI or positron emission tomography (PET) may be used if CT is unrevealing.
Resection of the tumor alleviates all symptoms.
Unresectable, metastatic, or recurrent tumors are treated with combination streptozocin and doxorubicin, which may decrease levels of circulating immunoreactive glucagon, lessen symptoms, and improve response rates (50%) but are unlikely to improve survival. Newer chemotherapies under investigation for glucagonoma include temozolomide-based regimens, everolimus, or sunitinib.
Octreotide injections partially suppress glucagon production and relieve the erythema, but glucose tolerance may also decrease because octreotide decreases insulin secretion. Octreotide may quickly reverse anorexia and weight loss caused by the catabolic effect of glucagon excess. Patients who respond may be converted to a long-acting octreotide formulation given 20 to 30 mg IM once a month. Patients using octreotide may also need to take supplemental pancreatic enzymes because octreotide suppresses pancreatic enzyme secretion.
Locally applied, oral, or parenteral zinc may cause the erythema to disappear, but resolution may occur after simple hydration or IV administration of amino or fatty acids, suggesting that the erythema is not solely caused by zinc deficiency.