Glucagon receptor gene mutations with hyperglucagonemia but without the glucagonoma syndrome  

作　　者：Helen C Miller Mark Kidd Irvin M Modlin Patrizia Cohen Roberto Dina Panagiotis Drymousis Panagiotis Vlavianos Günter Klöppel Andrea Frilling 

机构地区：[1]Department of Surgery and Cancer,Imperial College London,London W12 0HS,United Kingdom [2]Department of Surgery,Yale University,New Haven,CT 06510,United States [3]Emeritus Yale University,School of Medicine,New Haven,CT 06510,United States [4]Department of Histopathology,Imperial College London,London W12 0HS,United Kingdom [5]Department of Gastroenterology,Imperial College London,London W12 0HS,United Kingdom [6]Department of Pathology,Technical University of Munich,81675 Munich,Germany

出　　处：《World Journal of Gastrointestinal Surgery》2015年第4期60-66,共7页世界胃肠外科杂志（英文版）（电子版）

摘　　要：Pancreatic neoplasms producing exclusively glucagon associated with glucagon cell hyperplasia of the islets and not related to hereditary endocrine syndromes have been recently described. They represent a novel entity within the panel of non-syndromic disorders associated with hyperglucagonemia. This case report describes a 36-year-old female with a 10 years history of nonspecific abdominal pain. No underlying cause was evident despite extensive diagnostic work-up. More recently she was diagnosed with gall bladder stones. Abdominal ultrasound, computerised tomography and magnetic resonance imaging revealed no pathologic findings apart from cholelithiasis. Endoscopic ultrasound revealed a 5.5 mm pancreatic lesion. Fine needle aspiration showed cells focally expressing chromogranin, suggestive but not diagnostic of a low grade neuroendocrine tumor. Octreo Scan was negative. Serum glucagon was elevated to 66 pmol/L(normal: 0-50 pmol/L). Other gut hormones, chromogranin A and chromogranin B were normal. Cholecystectomy and enucleation of the pancreatic lesion were undertaken. Postoperatively, abdominal symptoms resolved and serum glucagon dropped to 7 pmol/L. Although H and E staining confirmed normal pancreatic tissue, immunohistochemistry was initially thought to be suggestive of alpha cell hyperplasia. A count of glucagon positive cells from 5 islets, compared to 5 islets from 5 normal pancreata indicated that islet size and glucagon cell ratios were increased, however still within the wide range of normal physiological findings. Glucagon receptor gene(GCGR) sequencing revealed a heterozygous deletion,K349_G359del and 4 missense mutations. This case may potentially represent a progenitor stage of glucagon cell adenomatosis with hyperglucagonemia in the absence of glucagonoma syndrome. The identification of novel GCGR mutations suggests that these may represent the underlying cause of this condition.Pancreatic neoplasms producing exclusively glucagonassociated with glucagon cell hyperplasia of the isletsand not related to hereditary endocrine syndromes havebeen recently described. They represent a novel entitywithin the panel of non-syndromic disorders associatedwith hyperglucagonemia. This case report describesa 36-year-old female with a 10 years history of nonspecificabdominal pain. No underlying cause was evidentdespite extensive diagnostic work-up. More recentlyshe was diagnosed with gall bladder stones. Abdominalultrasound, computerised tomography and magneticresonance imaging revealed no pathologic findings apartfrom cholelithiasis. Endoscopic ultrasound revealed a 5.5mm pancreatic lesion. Fine needle aspiration showedcells focally expressing chromogranin, suggestive butnot diagnostic of a low grade neuroendocrine tumor.OctreoScan？ was negative. Serum glucagon was elevatedto 66 pmol/L （normal： 0-50 pmol/L）. Other gut hormones,chromogranin A and chromogranin B were normal.Cholecystectomy and enucleation of the pancreatic lesionwere undertaken. Postoperatively, abdominal symptomsresolved and serum glucagon dropped to 7 pmol/L.Although H and E staining confirmed normal pancreatictissue, immunohistochemistry was initially thought to besuggestive of alpha cell hyperplasia. A count of glucagonpositive cells from 5 islets, compared to 5 islets from 5normal pancreata indicated that islet size and glucagoncell ratios were increased, however still within the widerange of normal physiological findings. Glucagon receptorgene （GCGR） sequencing revealed a heterozygous deletion,K349_G359del and 4 missense mutations. This case may potentially represent a progenitor stage of glucagon cell adenomatosis with hyperglucagonemia in the absence of glucagonoma syndrome. The identification of novel GCGR mutations suggests that these may represent the underlying cause of this condition.

关 键 词：Hyperglucagonemia Glucagon receptorgene MUTATION Adenomatosis PANCREAS 

分 类 号：R735.9[医药卫生—肿瘤]