What is the characteristic of insulinomas (tumors of the pancreas that produce excess insulin)?

Characteristics of Insulinomas

Insulinomas are mostly benign (approximately 90%) and can be cured surgically in the majority of cases. 1

Key Characteristics of Insulinomas

• Benign vs. Malignant: Approximately 90% of insulinomas are benign and can be cured surgically 1, 2
• Number: Most insulinomas are solitary when sporadic, while familial tumors are more likely to be multiple 3
• Location: Insulinomas are evenly distributed throughout the pancreas (head, body, and tail) 4
• Association with MEN1: Insulinomas occur in approximately 10% of patients with Multiple Endocrine Neoplasia Type 1 (MEN1) syndrome 1

Diagnostic Approach

The diagnosis of insulinoma requires:

1. Demonstration of Whipple's triad:

   • Symptoms consistent with hypoglycemia
   • Low plasma glucose measured during symptoms
   • Relief of symptoms when glucose is raised to normal 4

2. A 48-72 hour supervised fast (gold standard diagnostic test) showing:

   • Blood glucose below threshold
   • Inappropriately elevated insulin levels
   • Elevated C-peptide and proinsulin levels 1

Localization Studies

• Endoscopic Ultrasonography (EUS): Preferred localization method with approximately 82% success rate 1
• CT/MRI: Should be performed to rule out metastatic disease 1
• Newer Techniques: Glucagon-like peptide 1 receptor PET/CT or PET/MRI for occult insulinomas 4

Surgical Management

The primary treatment for localized insulinomas is surgical resection, with approach determined by tumor location:

• Exophytic or peripheral insulinomas: Enucleation (can be performed laparoscopically for tumors in body and tail) 3
• Head of pancreas tumors:
  • If enucleation not possible: Pancreatoduodenectomy 3
  • Small peripheral tumors: Enucleation or local excision with lymph node dissection 3
• Body/tail tumors: Distal pancreatectomy with preservation of the spleen when possible 3

Management of Unresectable or Metastatic Disease

For patients not suitable for surgery or with metastatic disease:

• Diazoxide or somatostatin analogs for symptom control 1
• Newer targeted therapies: Everolimus, sunitinib, pasireotide 2
• Peptide receptor radionuclide therapy (PRRT) for metastatic disease 2
• Cytotoxic chemotherapy for higher-grade tumors 2

Important Clinical Pearls

• Early referral to a specialized neuroendocrine multidisciplinary team is critical for optimal management 1
• Untreated insulinomas can cause significant morbidity due to recurrent hypoglycemic episodes 1
• Laparoscopic procedures are increasingly used with good outcomes 1
• Octreotide should be used with caution as it can potentially worsen hypoglycemia by suppressing counterregulatory hormones 1
• Insulinomas are less consistently octreotide-avid than other pancreatic NETs 1

The 5-year survival rate for patients with indolent (non-metastatic) insulinomas is excellent at 94-100%, while those with aggressive (metastatic) insulinomas have survival rates of 24-67% 4.