Diffuse nesidioblastosis as a cause of hyperinsulinemic hypoglycemia in adults: a diagnostic and therapeutic challenge.

Hyperinsulinemic hypoglycemia is caused by uncontrolled insulin release either from neoplastic pancreatic β-cells or from functionally defective β-cells. The latter disorder, which is usually seen in newborns, has been called nesidioblastosis and is divided histopathologically into a focal and diffuse type. In adults, nesidioblastosis is rare, and therefore its histopathologic and clinical features are not well known. In our institution, 4 of 128 adult patients (>3%) suffering from hyperinsulinemic hypoglycemia were found to have diffuse nesidioblastosis. The remaining patients had an insulinoma resected successfully in all but one patient. The diagnosis of diffuse nesidioblastosis was established histopathologically after removing a segment of the distal pancreas. Resection of up to 90% of the pancreas relieved 2 of the 4 patients of their symptoms. We conclude that diffuse nesidioblastosis is rare in adults but may account for more than 3% of patients with hyperinsulinemic hypoglycemia. The histopathologic diagnosis relies predominantly on demonstration of β-cell hypertrophy. The cause of the disease is not known but may be related to defects in the glucose recognition system of the β-cell. Treatment consists of operative reduction of the β-cell mass, but the extent of pancreatic resection required is hard to judge, and there is a thin line between successful treatment, persistence of the disease, and pancreatic endocrine insufficiency.