Beta-cell adenomas without hyperinsulinemia with use of highly specific insulin radioimmunoassays: case report and review of literature.

Objective: To report a case of a proinsulin-secreting islet cell adenoma in which the diagnosis was obscured by an ultraspecific insulin assay.

Methods: We describe the case of a 46-year-old woman, who presented with fasting hypoglycemia and appropriately low insulin values.

Results: A prolonged supervised fast produced symptomatic hypoglycemia (20 mg/dL) after only 7 hours. During the entire fasting test, highly specific insulin remained at <3 mIU/L, with a median value (and interquartile range) of 0.9 (0.8 to 2.3) mIU/L, when the glucose concentration was <50 mg/dL. The serum C-peptide level remained high normal (mean +/- SD, 2.7 +/- 0.6 ng/mL; normal fasting levels, 0.8 to 3.9), and no evidence of sulfonylurea use was detected in the patient's urine. Circulating proinsulin levels were persistently high (>200 pmol/L in all determinations when hypoglycemia was present; expected value, <5 pmol/L). Magnetic resonance imaging and endoscopic ultrasonography confirmed the presence of a 2.5-cm tumor in the head of the pancreas. A proinsulin-secreting islet cell tumor was diagnosed. Surgical resection of the tumor was successfully accomplished, but diabetes mellitus developed 4 months postoperatively.

Conclusion: The diagnosis of a hypoglycemia-producing pancreatic adenoma can be missed when an ultraspecific insulin assay is used. The direct measurement of proinsulin established the diagnosis in this case.