Glucagon receptor gene mutations with hyperglucagonemiabut without the glucagonoma syndrome

• Published in: 世界胃肠外科杂志：英文版（电子版） 2015 (4), p.60-66
• Main Author: Helen C Miller Mark Kidd Irvin M Modlin Patrizia Cohen Roberto Dina Panagiotis Drymousis Panagiotis Vlavianos Günter Kl？ppel Andrea Frilling
• Format: Article
• Language: English
• Subjects: Adenomatosis; Glucagon; Hyperglucagonemia; Mutation; Pancreas; receptorgene
• ISSN: 1948-9366; 1948-9366

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.