insulinoma

Epidemiology

• 2nd most common endocrine tumor of the pancreas

Pathology

• rarely malignant; 10% malignant
• single neoplasm, unless associated with MEN-1

Genetics

• implicated genes: GNAL, CRTC2, INSM1

Clinical manifestations

• Whipple's triad
  • fasting hypoglycemia
  • glucose < 50 mg/dL during symptoms
  • relief with oral or IV glucose
• weight gain
• symptoms of hypoglycemia
  • cholinergic symptoms
    • sweating
  • adrenergic symptoms
    • anxiety
    • hunger
    • diaphoresis
    • tachycardia
    • tremulousness
    • PVC's
    • irritability
    • hyperthermia
    • palpitations
    • hypothermia
  • neurologic symptoms
    • headache
    • behavioral changes (combativeness, agitation)
    • cognitive change
    • seizures
    • coma
    • hemiparesis
    • aphasia
    • visual changes
    • Babinski's sign

Laboratory

• elevated plasma insulin
  • inappropriately high plasma insulin during hypoglycemia
  • plasma insulin > 6 mU/mL in association with plasma glucose < 50 mg/dL in males & < 40 mg/dL in females indicates hyperinsulinemia
• decreased fasting serum glucose
• elevated C-peptide (obtain when glucose is < 50 mg/dL)
  • C-peptide > 0.2-0.4 nM suggests a beta-cell lesion
• elevated pro-insulin > 20 pM
• C-peptide suppression test
  • elevated C-peptide after administration of insulin to induce hypoglycemia demonstrates autonomous production of endogenous insulin
• glucagon tolerance panel, for insulinoma
• insulin-induced C-peptide suppression panel
• insulin:glucose ratio > 0.3 uU/mg
• inhibited ketosis: plasma beta-hydroxybutyrate < 2.7 mM after a lengthy fast
• transhepatic sampling of portal vein & pancreatic veins for insulin & C-peptide (requires special expertise)
• see ARUP consult

Diagnostic procedures

• endoscopic pancreatic ultrasonography (90% sensitivity)

Radiology

• computed tomography of abdomen
  • 1st diagnostic test after biochemical diagnosis
    • tumor is small
    • generally not visible with CT or US
    • lesions must be larger than 1.0-1.5 cm for visualization
• magnetic resonance imaging (MRI)
  • generally offers no benefit over CT
• nuclear scanning with isotopically labeled somatostatin analogues not an effective diagnostic tool because insulinomas do not produce enough somatostatin receptors to render scintigraphy diagnostically useful
• imaging studies only after laboratory confirmation of hypoglycemia & hyperinsulinemia

Differential diagnosis

• surreptitious use of sulfonylureas
• insulin antibodies

Management

• surgical excision or distal pancreatectomy
• diazoxide for persistent disease
  • inhibits insulin secretion
  • alternative agents:
    • phenytoin
    • propranolol
    • verapamil
    • octreotide
• chemotherapy for maligant persistent or recurrent disease
  • sunitinib & everolimus are active
  • capecitabine plus temozolomide is active
  • older recommendationc
    • streptozocin
    • fluorouracil

More general terms

• islet cell tumor