What is the recommended treatment for insulinoma?

Treatment of Insulinoma

Surgical resection is the optimal treatment for locoregional insulinomas, with a cure rate of 90% in most cases. 1, 2

Preoperative Management

• Before surgical excision, symptoms of hormonal excess must be treated to stabilize the patient 1
• Glucose levels should be stabilized using:
  • Dietary management 1, 2
  • Diazoxide - first-line medical therapy for managing hypoglycemia due to hyperinsulinism 1, 2, 3
  • Everolimus can be considered as an alternative for preoperative stabilization 1, 2
• Somatostatin analogs (octreotide, lanreotide) should be used with extreme caution in insulinoma patients as they can:
  • Suppress counterregulatory hormones like growth hormone, glucagon, and catecholamines 1
  • Precipitously worsen hypoglycemia, potentially resulting in fatal complications 1, 2
  • Should only be administered to patients whose tumors are somatostatin receptor scintigraphy-positive 1

Surgical Approach

• Surgical options depend on tumor location and size 1, 4:
  • Enucleation - primary treatment for exophytic or peripheral insulinomas, especially for benign, solitary tumors (most common procedure, used in 56% of cases) 1, 5
    • Can be performed laparoscopically for localized tumors within the body and tail of the pancreas 1
  • Distal pancreatectomy with preservation of the spleen - for tumors in the body/tail that cannot be enucleated 1, 5
  • Pancreatoduodenectomy - for tumors in the head of the pancreas that are deep, invasive, or close to the main pancreatic duct 1
• Laparoscopic procedures are safe for selected patients with insulinomas and may be associated with shorter hospital stays 1
• Open surgical approach remains the most common method (90% of cases) 5

Management of Unresectable or Metastatic Disease

• For patients who are not surgical candidates due to comorbidities, high surgical risk, or metastatic disease: 1, 6
  • Medical therapy with diazoxide is the primary approach for symptom control 2, 3, 6
  • Newer targeted therapies can be considered: 6, 7
    • Everolimus (mTOR inhibitor) - particularly effective as it causes hyperglycemia while having antitumor effects 6
    • Sunitinib (tyrosine kinase inhibitor) 6, 8
    • Pasireotide (multisomatostatin receptor ligand) - in selected cases 6
  • Minimally invasive procedures for selected cases: 6, 7
    • Ethanol ablation
    • Radiofrequency ablation
    • Tumor embolization
  • For metastatic disease, peptide receptor radionuclide therapy (PRRT) can control tumor growth 6, 8
  • Cytotoxic chemotherapy for higher-grade tumors 6

Common Complications and Pitfalls

• Pancreatic fistula is the most frequent surgical complication 4, 5
• Recurrence occurs in approximately 7% of cases after surgery 5
• Metachronous tumors may develop, particularly in patients with MEN-1 syndrome 4
• Proton pump inhibitors can cause falsely elevated chromogranin A levels, complicating diagnosis 2
• Diazoxide may displace bilirubin from albumin, which should be considered when treating newborns with increased bilirubinemia 3
• Diazoxide may interact with other medications including coumarin anticoagulants and antihypertensive agents 3

Special Considerations

• Multiple insulinomas are found in 10% of cases, often associated with MEN-1 syndrome 8, 4
• Intraoperative ultrasound is recommended to avoid missing lesions in patients with multiple insulinomas 4
• Aggressive surgical approach is indicated for malignant insulinoma patients when feasible 4
• Regular monitoring is required during diazoxide treatment, including urine glucose and ketones, blood glucose, and serum uric acid levels 3