A patient with hypoglycemia has high insulin, high C-peptide, and high proinsulin. What is the most likely diagnosis?

• A. Insulinoma.
• B. Exogenous insulin administration.
• C. Sulfonylurea usage.
• D. Glucagonoma.

Answer: (A)

The key concept is distinguishing endogenous from exogenous insulin secretion during hypoglycemia by looking at insulin, C-peptide, and proinsulin levels. When insulin is elevated in the setting of low blood sugar, a simultaneously high C-peptide indicates the insulin is being produced by the body's own pancreas rather than injected from outside. The presence of elevated proinsulin makes this endogenous source even more likely, because insulinomas—tumors that secrete insulin and its precursors—tend to release higher amounts of proinsulin along with insulin.

In contrast, if insulin is high but C-peptide is low, the insulin is exogenous. Sulfonylurea use can also raise endogenous insulin and C-peptide, but proinsulin is not typically elevated to the same degree, and clinical history may reveal drug exposure. Glucagonoma usually presents with hyperglycemia and weight loss; its typical profile does not match hypoglycemia driven by high insulin.

Thus, the combination of high insulin, high C-peptide, and high proinsulin during hypoglycemia best points to an insulin-secreting tumor of the pancreas, i.e., insulinoma.