Interpretation

Normal individuals will have proinsulin concentrations below the upper limit of the normal fasting reference range (22 pmol/L) when hypoglycemic (blood glucose <60 mg/dL). Conversely, most (>80%) insulinoma patients will have proinsulin concentrations above the upper limit of the reference range. The sensitivity and specificity for a diagnosis of insulinoma during hypoglycemia are approximately 75% and near 100%, respectively, at the 22 pmol/L cutoff. A higher sensitivity (>95%) can be achieved using a 5 pmol/L cutoff, which is recommended by Mayo Clinic's highly-experienced hypoglycemia team to avoid missing cases. However, the lower cutoff results in reduced specificity (approximately 40%), emphasizing the need for a combination of different tests to assure accurate biochemical diagnosis.

Patients with prohormone convertase 1/3 deficiency have low, or sometimes undetectable, insulin levels and substantially elevated proinsulin levels, exceeding the upper limit of the reference range substantially in the fasting state and rising even higher after food intake. Many other hormonal abnormalities are also present, including cortisol deficiency (because of lack of processing of pro-opiomelanocortin to adrenocorticotropic hormone and other peptides), infertility, and, often, obesity.