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Key Features

Essentials of Diagnosis

  • Fasting hypoglycemia rather than postprandial hypoglycemia

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

  • Immediate recovery upon administration of glucose

  • Blood glucose < 45 mg/dL (2.5 mmol/L) with a serum insulin level of 6 microunit/mL or more

  • Hypoglycemic unawareness is common

General Considerations

  • Insulinoma is generally an 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

  • Patients adapt to chronic hypoglycemia by increasing their efficiency in transporting glucose across the blood–brain barrier, which masks awareness that their blood glucose is approaching critically low levels

    • Counterregulatory hormonal responses as well as neurogenic symptoms such as tremor, sweating, and palpitations are blunted during chronic hypoglycemia

Clinical Findings

Symptoms and Signs

  • Whipple triad is characteristic of hypoglycemia regardless of the cause

    • A history of hypoglycemic 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 CNS symptoms include

    • Blurred vision or diplopia

    • Headache

    • Feelings of detachment

    • Slurred speech

    • Weakness

  • Convulsions or coma may occur

  • Personality changes vary from anxiety to psychotic behavior

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


  • Diagnostic criteria for insulinoma after a 72-hour fast are listed in Table 27–12

Table 27–12.Diagnostic criteria for insulinoma after a 72-hour fast.

Laboratory Tests

  • C-peptide levels (by ICMA) of > 200 pmol/L and proinsulin levels (by RIA) of > 5 pmol/L are characteristic of insulinomas

  • Plasma beta-hydroxybutyrate levels are suppressed ...

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