glucagonoma

Glucagonoma is a functional pancreatic neuroendocrine tumor (PNET) derived from alpha cells of the islets of Langerhans that autonomously secretes excess glucagon. It is part of the MEN1 syndrome spectrum in some cases (associated with parathyroid, pituitary, and pancreatic tumors) but most occur sporadically, typically in adults 40-70 years old. Pathophysiology: Excess glucagon promotes glycogenolysis and gluconeogenesis, leading to hyperglycemia/diabetes mellitus. Glucagon also causes amino acid catabolism, resulting in hypoaminoacidemia, which is thought to contribute to necrolytic migratory erythema (NME)—a characteristic serpiginous, erythematous rash with central clearing and blistering, typically affecting the perineum, groin, and extremities. Clinical features (4 D's mnemonic): Dermatitis (NME, seen in ~70% of patients), Diabetes (mild, new-onset hyperglycemia), DVT/thromboembolism (due to hypercoagulable state), and Depression/psychiatric disturbances. Additional findings include weight loss, glossitis, cheilitis, anemia, and diarrhea. Diagnosis: Markedly elevated serum glucagon levels (>500-1000 pg/mL is highly suggestive), along with imaging (CT/MRI, somatostatin receptor scintigraphy or PET) to localize the tumor, which is often large (>5 cm) and metastatic (60-70% of cases) at diagnosis, most frequently to the liver. Skin biopsy of NME lesions shows characteristic necrolysis of the upper epidermis. Treatment: Surgical resection is the treatment of choice for localized disease. Octreotide (somatostatin analog) can control symptoms, particularly the rash, by suppressing glucagon secretion. Chemotherapy (e.g., streptozocin-based regimens) may be used for metastatic disease. Prognosis is variable; 5-year survival is around 50-60% due to frequent metastatic spread at diagnosis, though the tumor grows slowly.