Heterogeneity of glucagonomas due to differential processing of proglucagon-derived peptides

Endocrinology, Diabetes & Metabolism Case Reports

article

Benjamin G Challis¹  Nicolai J Wewer Albrechtsen³  Vishakha Bansiya²  Keith Burling¹  Peter Barker¹  Bolette Hartmann³  Fiona Gribble¹  Stephen O¹  Jens J Holst³  Helen L Simpson² 

[1] Wellcome Trust–MRC Institute of Metabolic Science, University of Cambridge;Wolfson Diabetes and Endocrinology Clinic, Institute of Metabolic Science, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital;Department of Biomedical Sciences, Faculty of Health and Medical Sciences;Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen

关键词: Adult;    Female;    Male;    White;    United Kingdom;    Pancreas;    Endocrine-related cancer;    GLP-1;    GLP-2;    Glucagon;    Insulin;    Oxyntomodulin;    Glucagonoma;    Constipation;    Bloating;    Appetite reduction/loss;    Rash;    Nausea;    Vomiting;    Weight loss;    Hypoglycaemia;    Necrolytic migratory erythema;    Tachycardia;    Splenomegaly;    Hepatomegaly;    Hypotension;    Oedema;    Normochromic normocytic anaemia;    Hypoalbuminaemia;    Diarrhoea;    Abdominal pain;    Hyperglycaemia;    Hyperglucagonaemia;    Hypertrophy;    Pancytopaenia;    Hyperinsulinaemia;    CT scan;    Liver biopsy;    Histopathology;    Immunohistochemistry;    GLP-1;    GLP-2;    Glucagon;    Synaptophysin;    SPECT scan;    Octreotide scan;    Chromogranin A;    Gastrin;    Insulin;    Gut hormones (fasting);    Glucose (blood);    Insulin;    Pancreatic polypeptide;    Zinc;    Octreotide;    Somatostatin analogues;    Lanreotide;    Dermatology;    Gastroenterology;    Oncology;    Insight into disease pathogenesis or mechanism of therapy;    December;    2015;   

DOI  :  10.1530/EDM-15-0105

学科分类：血液学

来源: Bioscientifica Ltd.

【 摘 要 】

Pancreatic neuroendocrine tumours (pNETs) secreting proglucagon are associated with phenotypic heterogeneity. Here, wedescribe two patients with pNETs and varied clinical phenotypes due to differential processing and secretion of proglucagonderived peptides (PGDPs). Case 1, a 57-year-old woman presented with necrolytic migratory erythema, anorexia,constipation and hyperinsulinaemic hypoglycaemia. She was found to have a grade 1 pNET, small bowel mucosal thickeningand hyperglucagonaemia. Somatostatin analogue (SSA) therapy improved appetite, abolished hypoglycaemia and improvedthe rash. Case 2, a 48-year-old male presented with diabetes mellitus, diarrhoea, weight loss, nausea, vomiting and perinealrash due to a grade 1 metastatic pNET and hyperglucagonaemia. In both cases, plasma levels of all measured PGDPs wereelevated and attenuated following SSA therapy. In case 1, there was increased production of intact glucagon-like peptide 1(GLP-1) and GLP-2, similar to that of the enteroendocrine L cell. In case 2, pancreatic glucagon was elevated due to apancreatic a-cell-like proglucagon processing profile. In summary, we describe two patients with pNETs and heterogeneousclinical phenotypes due to differential processing and secretion of PGDPs. This is the first description of a patientwith symptomatic hyperinsulinaemic hypoglycaemia and marked gastrointestinal dysfunction due to, in part,a proglucagon-expressing pNET.

【 授权许可】

CC BY-NC-ND