Diagnosis and localization of insulinoma after negative laparotomy by hyperinsulinemic, hypoglycemic clamp and intra-arterial calcium stimulation

Abstract

A 40-year-old woman with recurrent episodes of hypoglycemia was referred because of suspected insulinoma. Prolonged fasting was discontinued after 24 h due to symptomatic hypoglycemia (29 mg/dl, glucose/insulin-ratio 0.34). Magnetic resonance tomography showed a small 0.3 cm lesion in the body of the pancreas. During subsequent surgery a pancreatic tumor could not be detected, neither by manual palpation nor intraoperative ultrasonography. A hyperinsulinemic, sequentially eu- and hypoglycemic clamp confirmed the biochemical diagnosis of endogenous hyperinsulinemia and intra-arterial calcium stimulation localized calcium responsive tissue in the feeding distribution of the superior mesenteric artery. An octreotide scan was negative. During relaparotomy, six weeks after the initial surgery, the pancreatic body and tail were resected and a approximately 1 cm non-malignant insulinoma was found. Although the use of highly sensitive, and more sophisticated and expensive methods for the diagnosis and localization of insulinomas are not generally suggested, we recommend application of intra-arterial calcium stimulation if the tumor is not detected using conventional diagnostic procedures.

Figure 1

Plasma glucose (A), insulin (B) and C-peptide concentrations (C) during a hyperinsulinemic, sequentially eu- and hypoglycemic clamp experiment in the patient. Human insulin was infused at 20 (0 to 90 min) and 80 mU/kg/h (90 - 270 min), while the glucose infusion rate (glucose 20%) was adjusted to first create normoglycemic and then hypoglycemic conditions. Hyperinsulinemic hypoglycemia fails to suppress C-peptide concentrations (see arrow: C-peptide in control subjects).

Figure 2

Plasma insulin (A) and C-peptide (B) concentrations after selective intra-arterial calcium injection in the patient. Calcium injections were separated by periods of 15 minutes to allow hormone concentrations to return to baseline values.