• Information
  1. Insulinoma
  2. Glucagonoma
  3. Somatostatinoma
  4. Other Islet Cell Tumors

A. Insulinoma

1. Symptoms
   1. Hypoglycemia, usually fasting
   2. Exertional hypoglycemia
   3. Inappropriate plasma insulin levels
2. Diagnosis
   1. Tumors >2cm can be detected with CT, MRI, or ultrasound
   2. Radiographic techniques have ~25% sensitivity for tumors <2cm
   3. Pancreatic arteriography - previously done without calcium stimulation
   4. Portal Venous sampling
   5. Intra-arterial calcium stimulation with insulin detection >85% sensitive [1]
   6. Measurement of plasma glucose, insulin, and C-peptide levels (during symptoms)
3. Treatment
   1. Surgical resection
   2. Dietary management - high carbohydrate load
   3. Octreotide (Somatostatin analog) - Controls symptoms in ~50% of cases [3]
   4. Diazoxide suppresses insulin release and may also be used
   5. Majority (~90%) of tumors are benign
   6. Chemotherapy for maligant tumors - streptozotocin + fluorouracil (or doxorubicin)

B. Glucagonoma

1. Symptoms
   1. Glucose intolerance, hyperglycemia, mild diabetes
   2. Migratory necrolytic erythematous rash - often on much of body
   3. Severe muscle wasting
   4. Hypoaminoacidemia and hypocholesterolemia
2. Diagnosis
   1. Measure plasma glucagon levels
   2. Rule out other causes of high glucagon: chronic pancreatitis, uremia, cirrhosis, trauma
   3. CT or MRI study
   4. Tumor has usually (~75%) metastasized to liver or bone at diagnosis
3. Treatment
   1. Somatostatin analog Octreotide (Sandostatin®)
   2. Surgical Resection - usually debulking
   3. Most tumors are slow growing
   4. Chemotherapy of minimal benefit - usually DTIC given

C. Somatostatinoma

1. Somatostatin
   1. Produced by delta cells in the pancreatic islets
   2. Polypeptide hormone with major suppressive acitivty on gut hormone release
   3. Suppressed hormones include:
   4. Islets: insulin, glucagon, somatostatin itself
      1. Pancreatic parenchyma: gastrin, secretin, cholecystokinin, motilin
   5. Blocks gastric acid secretion and increased gut motility
2. Symptoms
   1. Diabetes
   2. Diarrhea and steatorrhea
   3. Cholelithiasis
   4. Hypoochlorhydria
   5. Weight Loss
3. Diagnosis
   1. Majority have metastasized at diagnosis
   2. Increased levels of circulating somatostatin
   3. CT or MRI localization: primary tumors occur in pancreas or intestine
4. Treatment
   1. Chemotherapy of minimal efficacy - streptozotocin + fluorouracil
   2. Surgical resection - rarely curative
   3. Sandostatin (Octreotide®) [3]

D. Other Islet Cell Tumors

1. VIPoma
2. Nonfunctional Islet Cell Tumors
   1. Usually presnt as mass causing abdominal pain or obstruction
   2. Often found after metastasis to liver
   3. Pancreatic polypeptide, enolase (neuron specific), HCG may be produced
3. Gastrinoma
4. Hypercalcemia [4]
   1. May be present with any of the islet cell carcinomas
   2. In small series, 8 of 10 patients with islet cell Ca had increased PTHrP
   3. PTHrP levels fall with treatment of islet cell tumors

References

1. Axelrod L. 1995. Ann Intern Med.123(4):311
2. Doppman JL, Chang R, Fraker DL, et al. 1995. Ann Intern Med. 123(4):269
3. Lamberts SWJ, van der Lely AJ, de Herder WW, Hofland LJ. 1996. NEJM. 334(4):246
4. Wu TJ, Lin CL, Taylor RL, et al. 1997. Mayo Clin Proc. 72(12):1111