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Difficulty: Very hardEndocrinology and Metabolism

An endocrinologist is reviewing the results of 72-hour fasting tests for five adult patients who developed neuroglycopenic symptoms with concurrent plasma glucose levels < 50 mg/dL. Match each patient's specific plasma laboratory profile, drawn at the precise time of symptomatic hypoglycemia, to the most likely underlying pathophysiologic etiology.

  • Insulin markedly elevated, C-peptide suppressed, beta-hydroxybutyrate suppressed, oral hypoglycemic screen negativeFactitious exogenous insulin administration
  • Insulin elevated, C-peptide elevated, proinsulin disproportionately elevated, beta-hydroxybutyrate suppressed, oral hypoglycemic screen negativeAutonomous pancreatic beta-cell neoplasm (Insulinoma)
  • Insulin elevated, C-peptide elevated, proinsulin normal, beta-hydroxybutyrate suppressed, oral hypoglycemic screen positiveSurreptitious sulfonylurea or meglitinide ingestion
  • Insulin suppressed, C-peptide suppressed, beta-hydroxybutyrate suppressed, IGF-II to IGF-I ratio > 10Non-islet cell tumor hypoglycemia (NICTH)
  • Insulin suppressed, C-peptide suppressed, beta-hydroxybutyrate markedly elevated, serum cortisol < 3 µg/dLPrimary adrenal insufficiency (Addison disease)

Answer

The laboratory profiles uniquely differentiate the mechanisms of fasting hypoglycemia based on endogenous insulin secretion (C-peptide), beta-cell maturation (proinsulin), alternative insulin-receptor agonists (IGF-II), secretagogue presence, and the ketotic versus non-ketotic nature of the hypoglycemia.
Each laboratory profile distinctly aligns with a specific pathophysiologic mechanism of hypoglycemia. Factitious exogenous insulin provides the hormone without C-peptide. Insulinomas secrete mature insulin, C-peptide, and large amounts of proinsulin autonomously. Sulfonylureas drive normal endogenous secretion (increasing both insulin and C-peptide). NICTH relies on IGF-II activating insulin receptors systemically, which suppresses true insulin, C-peptide, and ketones. Finally, adrenal insufficiency causes hypoglycemia via impaired gluconeogenesis; the resulting appropriately suppressed insulin allows for unimpeded ketogenesis.

Step-by-Step Solution

1
Analyze insulin and C-peptide levels to differentiate exogenous from endogenous hyperinsulinism.
High insulin with suppressed C-peptide indicates an exogenous source, while high insulin with elevated C-peptide indicates an endogenous source.
C-peptide is co-secreted with endogenous insulin in equimolar amounts but is absent in pharmaceutical insulin preparations.
2
Differentiate endogenous hyperinsulinism etiologies using drug screens and proinsulin levels.
A positive screen confirms secretagogue use; a negative screen with disproportionately high proinsulin strongly points to an insulinoma.
Beta-cell neoplasms are less efficient at processing proinsulin to mature insulin compared to healthy beta cells stimulated by drugs.
3
Evaluate beta-hydroxybutyrate (ketone) levels to determine if the hypoglycemia is insulin-mediated.
Suppressed ketones indicate active suppression of lipolysis by an insulin-like effect (hyperinsulinism or IGF-II), whereas high ketones indicate appropriate insulin suppression (e.g., hypocortisolism).
Insulin strongly inhibits hormone-sensitive lipase, preventing ketone body formation.

Key Concept

Differential diagnosis of adult fasting hypoglycemia using the 72-hour fasting test.
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Topics

Endocrinology and Metabolism

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