A glucagonoma is a pancreatic alpha-cell tumor that secretes glucagon, causing hyperglycemia and a characteristic rash. Diagnosis is by elevated glucagon levels and imaging studies. Tumor is localized with CT and endoscopic ultrasound. Treatment is surgical resection.
(See also Overview of Gastrointestinal and Pancreatic Neuroendocrine Tumors .)
Glucagon is a hormone normally secreted by the pancreas when blood glucose levels fall. It 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. They 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. Most glucagonomas are malignant.
The average age at symptom onset is 50 years; 80% of patients are female (1). A few patients have multiple endocrine neoplasia type 1.
Довідковий матеріал загального характеру
1. Song X, Zheng S, Yang G, et al: Glucagonoma and the glucagonoma syndrome. Oncol Lett 15(3):2749–2755, 2018. doi:10.3892/ol.2017.7703
Symptoms and Signs of Glucagonoma
Because glucagonomas produce glucagon, which raises blood glucoses, the symptoms are the same as symptoms of diabetes.
Frequently, weight loss, normochromic anemia, hypoaminoacidemia, and hypolipidemia are present.
The most distinctive clinical feature is a chronic eruption involving the extremities, often associated with a smooth, shiny, vermilion tongue and cheilitis. The exfoliating, erythematous lesion with superficial necrolysis is termed necrolytic migratory erythema.
Diagnosis of Glucagonoma
Serum glucagon level
CT and endoscopic ultrasound to localize
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 ultrasound; MRI or positron emission tomography (PET) may be used if CT is unrevealing.
Patients with necrolytic migratory erythema may have low levels of amino acid, zinc, and essential fatty acids.
Treatment of Glucagonoma
Surgical resection for localized disease
Chemotherapy for metastatic disease
Octreotide or lanreotide to suppress glucagon production
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. Chemotherapies under investigation for glucagonoma include temozolomide-based regimens, everolimus, sunitinib, and cabozantinib (1).
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.
Довідковий матеріал щодо лікування
1. Chan J, Geyer S, Ou F-S, et al. LBA53 Alliance A021602: Phase III, double-blinded study of cabozantinib versus placebo for advanced neuroendocrine tumors (NET) after progression on prior therapy (CABINET). Ann Oncol 34 (Suppl 2): S1292, 2023.
