Glucagonoma - Pancreatic cancers

• Tumors of the Gastrointestinal tract • • Pancreatic cancers • Jan 20, 08

A glucagonoma is a pancreatic α-cell tumor that secretes glucagon, producing hyperglycemia and a characteristic skin rash. Diagnosis is by elevated glucagon levels and imaging studies. Tumor is localized with CT and endoscopic ultrasound. Treatment is surgical resection.

Glucagonomas are very rare but similar to other islet cell tumors in that the primary and metastatic lesions are slow-growing: 15-yr survival is common. Eighty percent of glucagonomas are malignant. The average age at symptom onset is 50 yr; 80% of patients are women. A few patients have multiple endocrine neoplasia type I.

Symptoms and Signs
Because glucagonomas produce glucagon, the symptoms are the same as those 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.

Diagnosis
Most patients with glucagonoma have glucagon levels > 1000 pg/mL (normal

< 200). 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 ultrasound; MRI may be used if CT is unrevealing.

Treatment
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. 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 administered 20 to 30 mg IM once/mo. 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.

Eric J. Szilagy, MD and Asim Farid, MD, FRCS(Edin)
Current Treatment Options in Gastroenterology 2001, 4:275-279
Current Medicine Group LLC ISSN 1092-8472

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