Glucagonoma With Necrolytic Migratory Erythema: Metabolic Profile and Detection of Biallelic Inactivation of DAXX Gene

• DOI: 10.1210/jc.2017-02646
• Publication Date: 2018-04-23T18:04:36Z
• Authors: Ai Tamura; Tatsuki Ogasawara; Yoichi Fujii; Hiyori Kaneko; Akitoshi Nakayama; Seiichiro Higuchi; Naoko Hashimoto; Yui Miyabayashi; Masanori Fujimoto; Eri Komai; Takashi Kono; Ikki Sakuma; Hidekazu Nagano; Sawako Suzuki; Hisashi Koide; Koutaro Yokote; Kozue Iseki; Rena Oguma; Hiroyuki Matsue; Hiroyuki Nojima; Kensuke Sugiura; Hideyuki Yoshitomi; Masayuki Ohtsuka; Bahityar Rahmutulla; Atsushi Kaneda; Naoko Inoshita; Seishi Ogawa; Tomoaki Tanaka
• Keywords: Glucagonoma; Hyperglucagonemia; Hyperinsulinemic hypoglycemia

Necrolytic migratory erythema (NME) occurs in approximately 70% of patients with glucagonoma syndrome. Excessive stimulation metabolic pathways by hyperglucagonemia, which leads to hypoaminoacidemia, contributes NME pathogenesis. However, the molecular pathogenesis and relationships between abnormalities clinical symptoms remain unclear. A 53-year-old woman was referred our hospital a generalized rash weight loss. diagnosed histopathological examination skin biopsy tissue. Laboratory tests revealed diabetes, marked insulin resistance, severe ketosis, anemia. Enhanced computed tomography scans detected 29-mm pancreatic hypervascular tumor, eventually as glucagonoma. Preoperative treatment octreotide long-acting release reduced glucagon level, improved amino acid profile, produced remission. Surgical tumor excision normalized status led remission symptoms, including NME. Whole-exome sequencing (WES) subsequent targeted capture sequencing, followed Sanger pyrosequencing, identified biallelic alteration death-domain associated protein (DAXX) combination loss heterozygosity frameshift mutations (c.553_554del:p.R185fs c.1884dupC:p.C629fs) Consistently, immunohistochemistry confirmed near-absence DAXX staining cells. Tumor expression somatostatin receptor subtype 2 3 messenger RNA markedly upregulated. This is report inactivation determined WES. The manifested syndrome case showed relationship hypoaminoacidemia status. Further investigations are required elucidate underlying mechanisms onset tumorigenesis.