A Case Report Of Insulinima In The Pancreas With An Unusual Clinical Presentation And The Investigation On Its Underlying Mechanism

Aims: Report a case of insulinoma in the pancreas with an unusual clinical presentation, investigate its possible underlying mechanism and discuss its clinical significances.Materials and Methods: The patient had a history of recurrent attacks of severe hypoglycemia in the past 6 years, which usually occurred 2-4 hours after meal and never in a postabsorptive state at night or in the early morning. She took nitrindepine orally 10mg, two times a day for hypertension in the past 6 years. After an explorative operation and the postoperative histological study, the diagnosis of insulinoma was confirmed. Before the operation, a series of biochemical tests were performed, including the 24-hour plasma glucose, insulin and C-peptide test (one point per hour) with the diet as usual, the oral glucose tolerance and insulin release tests (OGTT) in the morning and at night respectively, intra-vein glucose tolerance and insulin release test (IGTT) and the euglycemic-hyperinsulinemic clamp test. Then we analyzed the results of these tests and their time relationship with meal and themedication of nitrindepine. A series of perfusion studies were performed in vitro to investigate the insulin release responses of insulinoma and normal rat pancreatic islets to the different concentrations of glucose and calcium ion, and the effects of Verapamil on the above processes.Results: The 24-hour serum glucose, insulin and C-peptide test showed that the hypoglycemia usually occurred 2-4 hours after the meal, accompanied with hyerinsulinemia. In the daytime (8AM-12PM), the average serum glucose level was 2.08mmol/L and the average serum C-peptide (C-P) level was 3.10nmol/L and they were 5.76mmol/L and 0.50nmol/L at night (12PM-8AM) respectively. The results of the OGTT-insulin release test at 7AM-11 AM and 3AM-7AM are quite different. In the euglycemic-hyperinsulinemic clamp test, the serum C-P concentration was 3.92nmol/L when the exogenous insulin infusions rate was 8 mU/kg.min. The perfusion studies in vitro showed that the high concentration of extracellular glucose and calcium ions both could make either insulinoma or normal SD rat pancreatic islets release insulin higher than the basal level and Verapamil can inhibit the insulin release response to glucose but not to calcium ions. Conclusions: 1. The effects of the nitrindepine to the insulin release of pancreas islets may be the underlying mechanism of the unusual presentation of the patient.2.The calcium ion-channel blockers (CCB) may be a drug on choice for the patients with malignant insulinomas or those will not or cannot . undergo surgery.3.More investigations on the effects the calcium ion-channel blockers on the insulin release of human islets and its mechanisms are necessary because theses drugs are widely used in the patient with hypertension.4.An exploratory operation is necessary if insulinoma issuspected on the results of the biochemical studies.