the islets of Langerhans cells (pancreatic endocrine tumours). Estimates of malignancy (metastases) range from 5 to 30%. Over 99% of insulinomas originate in the pancreas, with rare cases from ectopic pancreatic tissue. About 5% of cases are associated with tumours of the parathyroid glands and the pituitary (multiple endocrine neoplasia type 1) and are more likely to be multiple and malignant. Most insulinomas are small, less than 2 cm. History Hypoglycemia was first recognized in the 19th century. In the 1920s, after the discovery of insulin and its use in the treatment of diabetics, hyperinsulinism was suspected to be a cause of hypoglycemia in nondiabetics. A pioneering description of hyperinsulinism as a cause of hypoglycemia was published by Seale Harris in 1924. The first report of a surgical cure of hypoglycemia by removing an islet cell tumour was in 1929. An insulinoma removed from a woman in Munich provided insulin mRNA that was used in the first human gene cloning experiment. In 1979, Axel Ulrich cloned this gene into E. coli. Most therapeutic insulin used today derives from this woman's tumour. Additional images See also Causes of hypoglycemia Metastatic Insulinoma References Further reading External links Endocrine neoplasia Rare cancers Amyloidosis