A 45-year-old man with Type 2 diabetes presents with recurrent hypoglycemia despite stopping sulfonylureas. Fasting serum insulin is 48 µIU/mL (normal <25), C-peptide is 8.2 ng/mL (normal <3.0), and proinsulin is markedly elevated. Plasma sulfonylurea screen is negative. CT pancreas shows a 1.8 cm hypoenhancing lesion in the body. Which of the following criteria definitively distinguishes this from exogenous insulin administration?
- A Elevated C-peptide
- B Negative sulfonylurea screen
- C Elevated proinsulin ✓
- D Hypoglycemia suppressed by diazoxide
Explanation
Markedly elevated proinsulin (>22% of total immunoreactive insulin or absolute elevation) is the most specific marker for insulinoma; beta cells co-secrete proinsulin in excess amounts from these tumors. Exogenous insulin suppresses endogenous insulin and C-peptide, making elevated C-peptide useful but not definitive alone (sulfonylureas also raise C-peptide). Proinsulin elevation essentially rules out exogenous insulin and points to autonomous beta-cell secretion, fulfilling the biochemical triad of insulinoma: hypoglycemia + elevated insulin + elevated proinsulin/C-peptide.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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