Insulinoma

KEY FEATURES

Essentials of Diagnosis

• Hypoglycemic symptoms—frequently neuroglycopenic (confusion, blurred vision, diplopia, anxiety, convulsions)

• Immediate recovery upon administration of glucose

• Blood glucose 40–50 mg/dL (2.2–2.8 mmol/L) with a serum insulin level of ≥ 6 mcU/mL or more

General Considerations

• Fasting hypoglycemia in otherwise healthy adults most commonly due to adenoma of the islets of Langerhans

• Adenomas can be familial

• 90% of tumors are single and benign

• Multiple benign adenomas can occur, as can malignant tumors with functional metastases

• Multiple adenomas can occur with tumors of parathyroids and pituitary in multiple endocrine neoplasia type 1 (MEN 1)

• Over 99% of adenomas are located within the pancreas and < 1% in ectopic pancreatic tissue

CLINICAL FINDINGS

Symptoms and Signs

• Whipple triad is characteristic of hypoglycemia regardless of the cause

  • A history of hypoglycemic (neuroglycopenic) symptoms

  • An associated low plasma glucose level (40–50 mg/dL)

  • Relief of symptoms upon ingesting fast-acting carbohydrates in approximately 15 minutes

• Symptoms often develop in the early morning, after missing a meal, or occasionally after exercise

• Initial central nervous system (CNS) symptoms include

  • Blurred vision or diplopia

  • Headache

  • Feelings of detachment

  • Slurred speech

  • Weakness

• Personality changes vary from anxiety to psychotic behavior

• Neurologic deterioration can result in convulsions or coma

Differential Diagnosis

• Hyperinsulinism from surreptitious insulin or sulfonylureas

• Extrapancreatic tumors

• Postprandial early hypoglycemia: alimentary disorders (dumping syndrome, postgastrectomy)

• Postprandial late hypoglycemia: functional (increased vagal tone), occult diabetes mellitus

• Delayed insulin release resulting from B-cell dysfunction

  • Counterregulatory deficiency

  • Idiopathic

• Alcohol-related hypoglycemia

• Immunopathologic hypoglycemia: antibodies to insulin receptors, which act as agonists

• Pentamidine-induced hypoglycemia

DIAGNOSIS

• Diagnostic criteria for insulinoma after a 72-hour fast are listed in Table 29–12

Laboratory Tests

• Diagnosis of insulinoma requires

  • Low plasma glucose (< 45 mg/dL) (or when patient has neuroglycopenic symptoms)

  • Concomitant inappropriately elevated serum insulin, proinsulin, and C-peptide levels

• Factitious use of insulin

  • Triad of hypoglycemia, high immunoreactive insulin and suppressed plasma C-peptide is pathognomonic of exogenous insulin administration

  • The insulin/C-peptide ratio (pmol/L) will be > 1

  • Elevated circulating proinsulin level when there is fasting hypoglycemia is characteristic of most B cell adenomas ...