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For further information, see CMDT Part 27-06: The Hypoglycemic States

Key Features

Essentials of Diagnosis

  • Symptoms begin at plasma glucose levels of ∼60 mg/dL (3.3 mmol/L), brain function impairment at ∼50 mg/dL (2.8 mmol/L)

  • Two types of spontaneous hypoglycemia: fasting and postprandial

    • Fasting: Often subacute or chronic; usually presents with neuroglycopenia

    • Postprandial: Relatively acute, with symptoms of neurogenic autonomic discharge (sweating, palpitations, anxiety, tremulousness)

General Considerations

Fasting hypoglycemia

  • Endocrine disorders (eg, hypopituitarism, Addison disease, myxedema)

  • Liver malfunction (eg, acute alcoholism, liver failure)

  • End-stage chronic kidney disease on dialysis

  • In absence of endocrine disorders, rule out hyperinsulinism due to

    • Either pancreatic B-cell tumors, iatrogenic, or surreptitious administration of insulin or sulfonylurea

    • Hypoglycemia caused by extrapancreatic tumors

  • Alcohol-related hypoglycemia

    • Due to hepatic glycogen depletion combined with alcohol-mediated inhibition of gluconeogenesis

    • Most common in malnourished alcohol abusers

    • However, can occur in anyone unable to ingest food after an acute alcoholic episode followed by gastritis and vomiting

Postprandial (reactive) hypoglycemia

  • May be seen after gastrointestinal surgery and is particularly associated with the dumping syndrome after gastrectomy and Roux-en-Y gastric bypass surgery

  • Occult diabetes very occasionally presents with postprandial hypoglycemia

  • Rarely, it occurs with islet cell hyperplasia–the so-called noninsulinoma pancreatogenous hypoglycemia syndrome

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

  • Weight gain can result from overeating to relieve symptoms

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

  • Because of hypoglycemic unawareness, autonomic symptoms may be mild or late and the initial symptoms are due to neuroglycopenia

    • Blurred vision

    • Headache

    • Feelings of detachment

    • Slurred speech

    • Weakness

  • Personality changes may occur and range from anxiety to psychotic behavior

  • Convulsions or coma may occur if symptoms are ignored and untreated

Differential Diagnosis

  • Fasting hypoglycemia

    • Hyperinsulinism: pancreatic B-cell tumor and surreptitious insulin or sulfonylureas

    • Extrapancreatic tumors

  • Postprandial early hypoglycemia: alimentary (eg, 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

  • Islet hyperplasia (noninsulinoma pancreatogenous hypoglycemia syndrome)

Diagnosis

Laboratory Tests

  • An elevated circulating proinsulin level (> 5 pmol/L) in the presence of fasting hypoglycemia is characteristic of most B-cell adenomas and does not occur in factitious hyperinsulinism

  • In patients with epigastric distress, history of renal calculi, or menstrual or erectile dysfunction, obtaining a serum calcium, gastrin, or prolactin level may be useful in screening for MEN-1 associated with insulinoma

  • Obtain samples of plasma glucose, insulin, C-peptide, ...

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