Glucagonoma

Glucagonoma is a rare pancreatic neuroendocrine tumor that arises from alpha cells and secretes glucagon. Most cases are malignant and present in middle-aged adults, often with liver metastases at diagnosis.

The glucagonoma syndrome is characterized by a combination of symptoms, with necrolytic migratory erythema as the most distinctive sign. This erythema presents as painful, blistering, erythematous plaques that typically favor the face, perineum, and extremities. Other common features include weight loss, diabetes or glucose intolerance, stomatitis, cheilitis, anemia, venous thromboembolism, and neuropsychiatric symptoms.

Pathophysiology involves sustained hyperglucagonemia, which causes hyperglycemia and a catabolic state leading to nutrition deficiency and dermatitis. The clinical picture often reflects both hormonal excess and tumor burden.

Diagnosis is suggested by the presence of necrolytic migratory erythema in combination with diabetes or weight loss. Fasting plasma glucagon levels are typically markedly elevated (often >500 pg/mL). Localizing the tumor relies on imaging such as CT or MRI, with somatostatin receptor imaging (for example, Ga-68 DOTATATE PET/CT). Confirmation is by biopsy showing a glucagon-producing neuroendocrine tumor.

Treatment depends on stage. Localized glucagonomas may be cured by surgical resection. Metastatic or unresectable disease is managed with somatostatin analogs (octreotide or lanreotide) to control symptoms and glucagon secretion, and may involve peptide receptor radionuclide therapy (Lutetium-177 DOTATATE) or targeted therapies such as everolimus or sunitinib. Supportive care addresses nutritional status, glycemic control, dermatitis, and thromboembolism risk.

Prognosis varies with disease extent; long-term survival improves with early detection and appropriate systemic therapy, but metastatic disease carries a poorer prognosis.