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

Characteristics of Insulinomas

Insulinomas are predominantly benign (approximately 90%) pancreatic neuroendocrine tumors that are typically solitary and can arise in any part of the pancreas. 1, 2

Key Characteristics of Insulinomas

Distribution and Benign Nature

• Approximately 90% of insulinomas are benign and can be cured surgically 1, 2
• Insulinomas are not predominantly located in the head of the pancreas but are distributed throughout the organ 1
• They typically present as small (<2 cm), well-demarcated, solitary nodules 2
• Distribution is relatively even between the head, body, and tail of the pancreas 3

Association with MEN1 Syndrome

• Only about 10% of insulinomas are associated with Multiple Endocrine Neoplasia Type 1 (MEN1) syndrome 4
• When associated with MEN1, there is a higher likelihood of multiple tumors 5
• The typical pattern is:
  • 80% of patients have a single benign tumor
  • 10% have multiple tumors (high association with MEN1)
  • 10% have metastatic malignant insulinoma 5

Clinical Behavior

• Insulinomas typically pursue an indolent course with excellent outcomes after resection 1
• The 5-year survival rate for patients with non-metastatic ("indolent") insulinomas is 94-100% 4
• For metastatic ("aggressive") insulinomas, the 5-year survival rate drops to 24-67% 4

Diagnostic Approach

Clinical Presentation

• Symptoms result from hypoglycemia and include Whipple's triad:
  1. Symptoms consistent with hypoglycemia
  2. Low plasma glucose measured during symptoms
  3. Relief of symptoms when glucose is raised to normal 4
• Symptoms are often intermittent and can be misdiagnosed as neurologic or psychiatric disorders 5

Laboratory Findings

• Diagnosis requires demonstration of:
  • Hypoglycemia (glucose ≤40 mg/dL) during symptoms
  • Inappropriate insulin secretion (insulin >6 μIU/mL) during hypoglycemia
  • Elevated C-peptide and proinsulin levels 6, 5
• A 48-72 hour supervised fast is the gold standard diagnostic test 6

Treatment Approaches

Surgical Management

• Surgical resection is the primary treatment for localized insulinomas 6, 1
• Options include enucleation, partial pancreatectomy, or pancreaticoduodenectomy depending on tumor location 1, 3
• Laparoscopic procedures are increasingly used with good outcomes 1

Medical Management

• For patients not suitable for surgery or with metastatic disease:
  • Diazoxide or somatostatin analogs for symptom control 2
  • Newer targeted therapies include everolimus, sunitinib, and pasireotide 2
  • Peptide receptor radionuclide therapy (PRRT) for metastatic disease 2, 4

Important Caveats

• Octreotide should be used with caution in insulinoma patients as it can worsen hypoglycemia by suppressing counterregulatory hormones 6, 1
• Insulinomas are less consistently octreotide-avid than other pancreatic NETs 6, 1
• Early referral to a specialized neuroendocrine multidisciplinary team is critical for optimal management 2
• Despite their typically benign nature, untreated insulinomas can cause significant morbidity due to recurrent hypoglycemic episodes 5