A clinician is evaluating four non-diabetic adult patients who presented with recurrent ep… — USMLE Step 2 CK

A clinician is evaluating four non-diabetic adult patients who presented with recurrent episodes of neuroglycopenia. A 72-hour fasting test was performed for each patient. Match each patient's laboratory profile obtained during the symptomatic hypoglycemic episode (glucose $<55\text{ mg/dL}$ ) to the most likely underlying etiology.

Glucose $35\text{ mg/dL}$ ; Insulin $18\text{ \mu U/mL}$ (High); C-peptide $2.5\text{ ng/mL}$ (High); Elevated proinsulin; Negative secretagogue screen.Insulinoma (pancreatic neuroendocrine tumor)
Glucose $40\text{ mg/dL}$ ; Insulin $22\text{ \mu U/mL}$ (High); C-peptide $0.05\text{ ng/mL}$ (Low); Suppressed proinsulin; Negative secretagogue screen.Factitious exogenous insulin administration
Glucose $38\text{ mg/dL}$ ; Insulin $15\text{ \mu U/mL}$ (High); C-peptide $2.8\text{ ng/mL}$ (High); Normal proinsulin; Positive sulfonylurea screen.Unintentional or factitious secretagogue ingestion
Glucose $32\text{ mg/dL}$ ; Insulin $1\text{ \mu U/mL}$ (Low); C-peptide $0.04\text{ ng/mL}$ (Low); Suppressed proinsulin; Elevated IGF-II to IGF-I ratio.Non-islet cell tumor hypoglycemia (NICTH)

Answer

Profile 1 matches Insulinoma; Profile 2 matches Exogenous insulin; Profile 3 matches Secretagogue ingestion; Profile 4 matches Non-islet cell tumor hypoglycemia.

Each patient's hypoglycemia etiology is systematically determined by evaluating the presence of endogenous insulin production (C-peptide), precursor processing (proinsulin), and exogenous secretagogues.

Step-by-Step Solution

Evaluate serum insulin levels during the hypoglycemic episode.

Profiles 1, 2, and 3 show high insulin (insulin-mediated). Profile 4 shows low insulin (non-insulin-mediated).

This differentiates hyperinsulinemic states from causes like severe liver failure, adrenal insufficiency, or NICTH where insulin is appropriately suppressed.

Analyze C-peptide levels in the hyperinsulinemic profiles.

Profile 1 and 3 have high C-peptide. Profile 2 has low C-peptide.

C-peptide is co-secreted with endogenous insulin. High insulin with low C-peptide proves the insulin came from an exogenous source.

Check the secretagogue screen and proinsulin levels for profiles with high C-peptide.

Profile 1 has a negative screen and high proinsulin. Profile 3 has a positive screen.

This step distinguishes between autonomous tumoral secretion of insulin (insulinoma) and pharmacologically stimulated endogenous secretion (sulfonylureas/meglitinides).

Key Concept

Diagnostic evaluation of fasting hypoglycemia using the insulin, C-peptide, and oral hypoglycemic agent screen axis.

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