Mahvash Disease: Pancreatic Neuroendocrine Tumor Syndrome Caused by Inactivating Glucagon Receptor Mutation

Human tumor syndromes are usually caused by inherited or de novo mutations in tumor suppressor genes or oncogenes within the cells that give rise to the tumors [1,2]. In some occasions, the cells that give rise to tumors do not have intrinsic abnormalities in cell differentiation or proliferation but are forced into a hyperplastic state secondarily by neural or humoral factors. The latter phenomenon is especially relevant to certain endocrine tumors that arise in a hyperplastic background. Thyrotroph adenoma of the pituitary can arise from hyperplastic thyrotrophs in profound primary hypothyroidism; gastric carcinoids can arise from hyperplastic enterochromaffin-like cells in chronic atrophic gastritis or gastrinoma; and parathyroid adenoma can arise from hyperplastic parathyroid chief cells in chronic renal failure [3-5]. We here review a novel pancreatic neuroendocrine tumor syndrome arising in a background of pancreatic α cell hyperplasia caused by inactivating glucagon receptor mutation.