Pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PNETs) are hormone-secreting tumors of the pancreas that derive from neuroendocrine cells. The most important types are glucagonomas, VIPomas, somatostatinomas, insulinomas (treated in a separate article), and gastrinomas (treated in a separate article). With the exception of insulinomas, PNETs typically manifest with diarrhea, weight loss, and normal or elevated blood glucose levels; insulinomas do not affect bowel movements and manifest instead with weight gain and hypoglycemia. Diagnosis involves laboratory studies to identify excess hormone levels and imaging to detect the primary tumor and metastases. Surgical resection is the first-line treatment. Octreotide is the treatment of choice for inoperable tumors.

For more information, see “Insulinoma” and “Gastrinoma.”

• Definition: a rare neuroendocrine tumor of the pancreatic α-cells that secretes glucagon. In > 50% of cases, metastasis is present at diagnosis.
• Clinical features
  • Weight loss
  • Impaired glucose tolerance or diabetes mellitus (75–95%)
  • Necrolytic migratory erythema
    • A cutaneous paraneoplastic syndrome that is mainly associated with pancreatic tumors secreting glucagon, but also hepatitis B, C, and bronchial carcinoma
    • Occurrence of multiple areas of centrifugally spreading erythema, located predominantly on the face, perineum, and lower extremities
    • Develop into painful and pruritic crusty patches with central areas of bronze-colored induration
    • Tend to resolve and reappear in a different location
    • Skin biopsy shows epidermal necrosis
  • Chronic diarrhea
  • Deep vein thrombosis
  • Depression
• Diagnostics: requires a high index of suspicion to make the diagnosis
  • Laboratory findings: ↑ glucagon > 500 pg/mL, ↑ blood glucose levels, normocytic normochromic anemia
  • Imaging (CT): to locate the tumor
• Treatment
  • Glycemic control
  • Tumor resection
  • Octreotide (if tumor is inoperable)

“Wait for 6 Days until the GLUe (glucagonoma) is dry:” Decreasing weight, Diabetes, Dermatitis, Diarrhea, DVT, Depression.

Reference:^[2]

• Definition: a rare neuroendocrine tumor of δ-cell (D-cell) origin that is usually located in the pancreas or gastrointestinal tract and secretes somatostatin.
  • ↑ Somatostatin → ↓ secretion of the following hormones:
    • Secretin
    • Cholecystokinin
    • Glucagon
    • Insulin
    • Gastrin
    • Gastric inhibitory peptide
• Clinical features
  • Abdominal pain
  • Weight loss
  • Classic triad
    • Glucose intolerance/diabetes
    • Cholelithiasis
    • Steatorrhea
  • Achlorhydria
• Diagnostics
  • Laboratory findings: ↑ somatostatin, ↑ blood glucose levels
  • Imaging: locate the tumor
• Treatment
  • Tumor resection: curative if no metastases are present
  • Octreotide (if tumor is inoperable)
  • Chemotherapy

Reference:^[3]

• Definition: : a neuroendocrine tumor that secretes VIP (vasoactive intestinal polypeptide)
• Etiology: associated with MEN1 syndrome (5% of cases)
• Pathophysiology
  • Excess VIP → ↑ relaxation of gastric and intestinal smooth muscles and cAMP activity (similar to cholera toxin) → secretory diarrhea and inhibition of gastric acid production
  • VIP also stimulates vasodilation, bone resorption, and glycogenolysis
• Tumor location: The primary tumor is most frequently found in the pancreas.
• Clinical features
  • WDHA syndrome (watery diarrhea, hypokalemia, achlorhydria): tea-colored watery diarrhea (> 700 mL/day) → dehydration
  • Weight loss
  • Abdominal pain, nausea, vomiting
  • Achlorhydria → ↓ iron and B₁₂ absorption → anemia
• Diagnostics
  • ↑ Serum VIP concentration (> 75 pg/mL)
  • Hypokalemia
  • Hypercalcemia ^[4]
  • Hyperglycemia
  • Gastric achlorhydria or hypochlorhydria
  • CT scan to localize the primary tumor
• Treatment
  • Tumor resection
  • Octreotide (inhibits VIP secretion)