Whipple’s Triad:

1. Symptoms consistent with hypoglycemia
2. Documented low plasma glucose when symptoms present
3. Relief of symptoms following resolution of hypoglycemia

Physiological response to hypoglycemia:

Endogenous Insulin Synthesis:

• Endogenous insulin is formed as two insulin chains (A & B) linked by C-peptide.  Measurement of C-peptide can help distinguish from endogenous versus exogenous insulin.

Causes of Hypoglycemia:

1. Drugs (insulin, sulfonylureas, alcohol)
2. Critical illness (hepatic failure, sepsis, etc.)
3. Hormone deficiency (cortisol, glucagon, etc.)
4. Non-islet cell tumor ~ increased production of IL-GF2 resulting increased glucose utilization
5. Endogenous insulin
   • Insulinoma
   • Non-insulinoma Pancreatogenous Hypoglycemic Syndrome (NIPHS)
   • Post-gastric bypass hypoglycemia
   • Antibody to insulin / Antibody to insulin receptor

Interpretation of 72 hour glucose fast data:

*Remember the only way to distinguish between insulinoma, NIPHS, PGBH and a sulfonylurea ingestion is with a urine sulfonylurea toxicity screen!