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Insulinoma

INTRODUCTION

Low blood glucose concentrations were recognized as a feature of several diseases in the 19th century. However, it was not until insulin became available for the treatment of diabetes mellitus in the early 1920s that clinical events similar to those arising from overtreatment with insulin were identified in nondiabetic persons. This observation led to the postulation of a new disease entity called hyperinsulinism [1].

Support for the existence of hyperinsulinism was provided by finding a malignant pancreatic islet-cell tumor in a patient who had episodes of severe hypoglycemia in 1927 [2]. Extracts of the tumor caused marked hypoglycemia in rabbits. The first cure of hyperinsulinism by removal of an insulinoma was reported in 1929 [3].

The clinical features, diagnosis, and treatment of insulinomas will be reviewed here. The causes and evaluation of hypoglycemia, and the management of metastatic neuroendocrine tumors are discussed separately. (See "Diagnostic approach to hypoglycemia in adults" and "Overview of hypoglycemia in adults" and "Management of metastatic gastroenteropancreatic neuroendocrine tumors", section on 'Treatment'.)

CLINICAL FEATURES

The common clinical manifestation of an insulinoma is fasting hypoglycemia, with discrete episodes of neuroglycopenic symptoms that may or may not be preceded by sympathoadrenal (autonomic) symptoms. However, postprandial hypoglycemia may be a feature or even the sole manifestation of hypoglycemia in some patients. In a retrospective review of 237 patients with surgically confirmed insulinoma, managed over the period 1987 to 2007, 21 percent reported both fasting and postprandial symptoms and 6 percent reported only postprandial symptoms [4]. The hypoglycemia in persons with insulinoma is primarily due to reduced hepatic glucose output rather than increased glucose utilization [5]. (See "Overview of hypoglycemia in adults" and "Physiologic response to hypoglycemia in normal subjects and patients with diabetes mellitus".)

Evidence suggests that insulinomas arise from cells of the ductular/acinar system of the pancreas rather than from neoplastic proliferation of islet cells [6]. The mechanism by which insulinomas maintain high levels of insulin secretion in the presence of hypoglycemia is unknown. However, one study reported that a variant of insulin mRNA with increased translation efficiency is present in high amounts in insulinomas when compared to normal islets [7]. (See "Insulin secretion and pancreatic beta-cell function".)
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References Top
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