What is a Somatostatinoma?

A somatostatinoma is an extremely rare neuroendocrine tumor (NET) that secretes excessive somatostatin, leading to a triad of diabetes, gallstones, and diarrhea/steatorrhea. It is the rarest of the functional pancreatic NETs.

Key Facts:

• Extremely Rare: <1 in 40 million per year (rarer than other functional NETs)
• Location:
  • Pancreas (55%): Usually head
  • Duodenum/Ampulla of Vater (44%)
  • Rarely: jejunum, other locations
• Malignant in 70-90%: Often metastatic at diagnosis
• Large at Diagnosis: Often >5 cm
• Many are Non-Functional: Found incidentally (don't produce enough somatostatin to cause syndrome)

How Does High Somatostatin Cause Symptoms?

• Somatostatin: "Master inhibitor" hormone—suppresses many other hormones and functions
• Effects of Excess Somatostatin:
  • Inhibits Insulin and Glucagon: Mild diabetes (usually insulin predominates → diabetes)
  • Inhibits Gallbladder Contraction: Bile stasis → gallstones
  • Inhibits Pancreatic Enzymes and Bicarbonate: Malabsorption, diarrhea, steatorrhea (fatty stools)
  • Inhibits Gastric Acid and Motility: Dyspepsia, achlorhydria

Classic Triad (Often Incomplete):

1. Diabetes Mellitus (70-90%): Usually mild
2. Cholelithiasis (Gallstones) (65-90%)
3. Diarrhea/Steatorrhea (35-90%): Fatty, foul-smelling stools from malabsorption

Note: Full triad is present in only ~10% of patients; many have incomplete or no symptoms (non-functional tumors)

Symptoms:

• Diabetes Mellitus: Mild hyperglycemia, often easy to control
• Gallstones: May be asymptomatic or cause biliary colic, cholecystitis
• Diarrhea/Steatorrhea: Fatty stools, malabsorption, weight loss
• Weight Loss
• Abdominal Pain: From tumor mass or gallstones
• Achlorhydria: Low stomach acid
• Hypochlorhydria-Induced Anemia: From reduced B12/iron absorption
• Jaundice: If tumor obstructs bile duct (especially duodenal/ampullary tumors)

Many Patients Are Asymptomatic:

• Tumor discovered incidentally on imaging or during surgery for other reasons

Associations:

• Neurofibromatosis Type 1 (NF1): ~50% of duodenal somatostatinomas occur in NF1 patients (ampullary location)
• von Hippel-Lindau (VHL) Syndrome: Rarely associated

Diagnosis:

1. Serum Somatostatin:

• Normal: <25 pg/mL
• Somatostatinoma: Elevated (often >100-1000 pg/mL)
• Diagnostic but often not measured (tumor often discovered by imaging/surgery before somatostatin checked)

2. Chromogranin A:

• Tumor marker for all NETs
• Usually elevated

3. Imaging:

• CT or MRI Abdomen: Large pancreatic or duodenal mass, liver metastases common
• Endoscopic Ultrasound (EUS): Visualize tumor, can biopsy
• Gallium-68 DOTATATE PET/CT: Somatostatin receptor imaging (most somatostatinomas are receptor-positive)
• Abdominal Ultrasound: Detect gallstones
• ERCP (if duodenal/ampullary tumor): Evaluate biliary obstruction

4. Labs:

• Fasting Glucose, HbA1c: Assess diabetes
• Fecal Fat: Steatorrhea (>7 g/day)
• Liver Enzymes, Bilirubin: If bile duct obstruction

5. Histology (Biopsy or Surgical Specimen):

• Immunohistochemistry positive for somatostatin, chromogranin, synaptophysin

Treatment:

1. Surgery (If Resectable):

• Tumor Resection: Potentially curative
• Pancreatic Tumors: Pancreaticoduodenectomy (Whipple procedure) if in head; distal pancreatectomy if tail
• Duodenal/Ampullary Tumors: Local excision or Whipple procedure
• Cholecystectomy: Remove gallbladder (often done concurrently due to high gallstone rate)
• Cure Rate: <30% (often metastatic at diagnosis)

2. For Metastatic/Unresectable Disease:

• Somatostatin Analogs (Octreotide, Lanreotide):
  • Slow tumor growth
  • Paradoxically, may NOT help symptoms (already too much somatostatin), but can control tumor progression
• Peptide Receptor Radionuclide Therapy (PRRT): Lutetium-177 DOTATATE (Lutathera®)
• Everolimus (Afinitor®): mTOR inhibitor; slows tumor progression
• Chemotherapy: Streptozocin-based regimens
• Liver-Directed Therapies: Embolization, RFA for liver mets

3. Symptomatic Treatment:

• Diabetes Management: Diet, metformin, insulin as needed (usually mild)
• Pancreatic Enzyme Replacement: For steatorrhea, malabsorption (pancrelipase/Creon®)
• Bile Acid Sequestrants: For diarrhea
• Fat-Soluble Vitamin Supplementation: Vitamins A, D, E, K (if malabsorption)
• Cholecystectomy: If symptomatic gallstones

Prognosis:

• Slow-Growing but Often Malignant
• 5-Year Survival:
  • Localized: 50-70%
  • Metastatic: 30-50%
• Many patients have metastases at diagnosis
• Duodenal somatostatinomas (associated with NF1) tend to have better prognosis than pancreatic