J Cutan Med Surg 2017 Jun 1:1203475417719051. Epub 2017 Jun 1.

1 Department of Dermatology, Saint-Luc Hospital, Montreal University, Montréal, QC, Canada.

Background: Necrolytic migratory erythema (NME) is most commonly a paraneoplastic condition. It is the dermatologic manifestation classically associated with glucagonoma pancreatic neuroendocrine tumour. Glucagonoma syndrome has been defined by the constellation of secreting tumour associated with overproduction by the α-cells in the pancreatic islets of Langerhans, abnormally elevated blood level of glucagon, and skin findings of NME. Read More

Rev Med Suisse 2017 May;13(565):1158-1162

Service d'endocrinologie, diabétologie, hypertension et nutrition, HUG, 1211 Genève 14.

An endocrine disease can be associated with glucose intolerance or diabetes mellitus, and the latter can falsely be considered as type 2 diabetes. Glycemic imbalance can be a direct or indirect consequence of excessive hormone production. Endocrine diseases such as acromegaly, Cushing's syndrome and pheochromocytoma can increase glucose production and cause insulin resistance. Read More

Case Rep Dermatol 2017 Jan-Apr;9(1):69-73. Epub 2017 Mar 17.

Division of Dermatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Necrolytic acral erythema (NAE) is a distinctive skin disorder. The exact cause and pathogenesis is still unclear. Most studies report an association of NAE with hepatitis C virus (HCV) infection. Read More

Intern Med 2017 1;56(11):1375-1381. Epub 2017 Jun 1.

Department of Diabetes and Endocrinology, Osaka Red Cross Hospital, Japan.

A 53-year-old woman developed end-stage renal failure during a 15-year clinical course of primary hyperparathyroidism and was referred to our hospital for evaluation of suspected multiple endocrine neoplasia type 1 (MEN1). Genetic testing revealed a novel deletion mutation at codon 467 in exon 10 of the MEN1 gene. Systemic and selective arterial calcium injection (SACI) testing revealed hyperglucagonemia and hypergastrinemia with positive gastrin responses. Read More

Dermatol Ther 2017 Jul 16;30(4). Epub 2017 May 16.

Unidad de Gestión Clínica de Dermatología, Hospital Universitario Puerta del Mar, Cádiz, Spain.

Arch Med Sci 2017 Apr 1;13(3):515-524. Epub 2016 Jun 1.

Department of Endocrinology, Poznan University of Medical Sciences, Poznan, Poland.

Gastroenteropancreatic neuroendocrine tumors (GEP/NET) are unusual and rare neoplasms that present many clinical challenges. They characteristically synthesize store and secrete a variety of peptides and neuroamines which can lead to the development of distinct clinical syndrome, however many are clinically silent until late presentation with mass effects. Management strategies include surgery cure and cytoreduction with the use of somatostatin analogues. Read More

N Engl J Med 2017 Mar;376(10):e18

Iowa Methodist Medical Center, Des Moines, IA

Endosc Ultrasound 2017 Jan-Feb;6(1):49-54

Medical Department, Caritas-Krankenhaus, Uhlandstr. 7 D-97980 Bad Mergentheim, Germany; Sino-German Research Center of Ultrasound in Medicine, The first Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background And Objectives: Imaging of the pancreas for detection of neuroendocrine tumors is indicated as surveillance in multiple endocrine neoplasia type 1 (MEN1) or if typical clinical symptoms combined with hormone production raise the suspicion of a neuroendocrine tumor. Endoscopic ultrasound (EUS) is considered the best imaging modality to detect small pancreatic tumors. However, little is known about how small pancreatic neuroendocrine tumors (pNETs) present on EUS. Read More

J Pathol 2017 May 27;242(1):90-101. Epub 2017 Mar 27.

INSERM U1052, Lyon, France.

Foxa2, known as one of the pioneer factors, plays a crucial role in islet development and endocrine functions. Its expression and biological functions are regulated by various factors, including, in particular, insulin and glucagon. However, its expression and biological role in adult pancreatic α-cells remain elusive. Read More

Transl Gastroenterol Hepatol 2016 19;1:70. Epub 2016 Sep 19.

Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

A 60-year-old male patient was admitted due to protracted systemic pruritus and erythema for 3 years without an obvious dermatologic cause, which exacerbated in the past 3 months, along with weight loss and diarrhoea. He had significant fasting hyperglycemia and dramatically elevated serum glucagon level in biochemical examination. Elevated chromogranin A (CgA) and neuron-specific enolase (NSE) levels were also manifested, whereas carbohydrate antigen 19-9 (CA-199) and carcinoembryonic antigen (CEA) were unremarkable. Read More

Diabetes 2017 Feb;66(2):235-240

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Glucagon is usually viewed as an important counterregulatory hormone in glucose metabolism, with actions opposing those of insulin. Evidence exists that shows glucagon is important for minute-to-minute regulation of postprandial hepatic glucose production, although conditions of glucagon excess or deficiency do not cause changes compatible with this view. In patients with glucagon-producing tumors (glucagonomas), the most conspicuous signs are skin lesions (necrolytic migratory erythema), while in subjects with inactivating mutations of the glucagon receptor, pancreatic swelling may be the first sign; neither condition is necessarily associated with disturbed glucose metabolism. Read More

Endocrinol Diabetes Metab Case Rep 2016 21;2016. Epub 2016 Nov 21.

Metabolic Disease Research , Novo Nordisk A/S, Måløv , Denmark.

Glucagon stimulates hepatic glucose production by activating specific glucagon receptors in the liver, which in turn increase hepatic glycogenolysis as well as gluconeogenesis and ureagenesis from amino acids. Conversely, glucagon secretion is regulated by concentrations of glucose and amino acids. Disruption of glucagon signaling in rodents results in grossly elevated circulating glucagon levels but no hypoglycemia. Read More

Abdom Radiol (NY) 2017 Apr;42(4):1113-1131

Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler St., Houston, TX, 77030, USA.

Gastrointestinal secretory tumors, or gastroenteropancreatic neuroendocrine tumors, encompass a wide array of endocrine cell tumors. The significance of these tumors lies in their ability to alter physiology through hormone production as we well as in their malignant potential. Functioning tumors may present earlier due to symptomatology; conversely, non-functioning tumors are often diagnosed late as they reach large sizes, causing symptoms secondary to local mass effect. Read More

Surgery 2017 Mar 15;161(3):727-734. Epub 2016 Nov 15.

Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.

Background: Distal pancreatectomy is the most frequent operation for insulinomas complicating multiple endocrine neoplasia type 1 insulinoma, although there are conditions for which a different operative approach might be preferable. In this article, we report the operative experience of a referral center for multiple endocrine neoplasia type 1 insulinoma.

Methods: Twelve patients underwent operations between 1992 and 2015: 8 underwent a distal pancreatic resection, and 4 underwent a pancreatoduodenectomy. Read More

Oncotarget 2016 11;7(46):74415-74426

Center for Neuropathology, Ludwig-Maximilians University, Munich, Germany.

Amplification or overexpression of MYCN is involved in development and maintenance of multiple malignancies. A subset of these tumors originates from neural precursors, including the most aggressive forms of the childhood tumors, neuroblastoma and medulloblastoma. In order to model the spectrum of MYCN-driven neoplasms in mice, we transgenically overexpressed MYCN under the control of the human GFAP-promoter that, among other targets, drives expression in neural progenitor cells. Read More

Endocr Pract 2017 Jan 15;23(1):116. Epub 2016 Sep 15.

From the 1Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, India.

Biomedica 2016 Jun 3;36(2):176-81. Epub 2016 Jun 3.

Grupo de Microbiología Molecular, Facultad de Medicina, Universidad de La Sabana, Chía, Colombia.

Necrolytic migratory erythema is a rare paraneoplastic dermatosis that may be the first clinical manifestation of the glucagonoma syndrome, a disorder characterized by mucocutaneous rash, glucose intolerance, hypoaminoacidemia, hyperglucagonaemia and pancreatic glucagonoma. The clinical case of a 45-year-old woman is presented. She had been experiencing weight loss, polydipsia, polyphagia, postprandial emesis, excessive hair loss and abdominal pain for two months. Read More

Med Clin (Barc) 2017 Apr 24;148(8):e45. Epub 2016 Aug 24.

Servicio de Anatomía Patológica, Hospitales Universitarios Virgen del Rocío, Sevilla, España.

Endocr Relat Cancer 2016 Sep 26;23(9):R423-36. Epub 2016 Jul 26.

Oxford Center for DiabetesEndocrinology and Metabolism, University of Oxford, Oxford, UK.

Although recent epidemiological evidence indicates that the prevalence of non-functioning gastroenteropancreatic (GEP) neuroendocrine tumours (NETs) is rising, a significant number of GEP-NETs still present with symptoms related to the secretion of biologically active substances leading to the development of distinct clinical syndromes. In the past, these syndromes were associated with substantial morbidity and mortality due to the lack of specific therapies; however, since the introduction of long-acting somatostatin analogues and medications such as proton pump inhibitors, their control has been greatly improved. As a result, nowadays, the main cause of morbidity and mortality in GEP-NETs is mostly directly related to tumour growth and the extent of metastatic disease. Read More

Cir Esp 2016 Oct 19;94(8):473-80. Epub 2016 Jul 19.

Servicio de Cirugía, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, España.

Introduction: The aim of this study was to analyze prognostic factors for survival and recurrence in patients with resected pancreatic neuroendocrine tumors (PNT).

Methods: Medical records of 95 patients with resected PNT were retrospectively reviewed. The variables studied were: age, sex, form of presentation (sporadic/familial tumors), functionality, type of tumor, localization, type of surgery, tumor size, multifocal tumors and recurrent rate. Read More

J Eur Acad Dermatol Venereol 2016 Dec 16;30(12):2016-2022. Epub 2016 Jul 16.

Dermatology and Pathology, Rutgers-New Jersey Medical School, Newark, NJ, USA.

Glucagonoma syndrome is defined by the presence of an alpha-cell secreting tumour of the pancreas, elevated levels of glucagon, and a characteristic rash called necrolytic migratory erythema (NME). NME is usually a specific and often initial finding of glucagonoma syndrome, but it may occur in other settings unassociated with an alpha-cell pancreatic tumour (pseudoglucagonoma syndrome). Glucagonoma syndrome must be distinguished from pseudoglucagonoma syndrome. Read More

Cutis 2016 Jun;97(6):E6-7

Rochester Skin Lymphoma Medical Group, New York, USA.

Hosp Pract (1995) 2016 Aug 18;44(3):109-19. Epub 2016 Jul 18.

a Department of Internal Medicine, Division of Gastroenterology and Hepatology , University of Utah School of Medicine, Huntsman Cancer Center , Salt Lake City , Utah , USA.

Pancreatic neuroendocrine tumors (PNETs) are neoplasms that arise from the hormone producing cells of the islets of Langerhans, also known as pancreatic islet cells. PNETs are considered a subgroup of neuroendocrine tumors, and have unique biology, natural history and clinical management. These tumors are classified as 'functional' or 'non-functional' depending on whether they release peptide hormones that produce specific hormone- related symptoms, usually in established patterns based on tumor subtype. Read More

Nutr Metab (Lond) 2016 7;13:46. Epub 2016 Jul 7.

Section of Cell Biology and Functional Genomics, Division of Diabetes Endocrinology and Metabolism, Department of Medicine, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith Hospital, du Cane Road, London, W12 0NN UK.

Background: The human SLC30A8 gene encodes the secretory granule-localised zinc transporter ZnT8 whose expression is chiefly restricted to the endocrine pancreas. Single nucleotide polymorphisms (SNPs) in the human SLC30A8 gene have been associated, through genome-wide studies, with altered type 2 diabetes risk. In addition to a role in the control of insulin release, recent studies involving targeted gene ablation from the pancreatic α cell (Solomou et al. Read More

Arch Biochem Biophys 2016 Dec 7;611:113-119. Epub 2016 Jun 7.

Department of Dermatology, Faculty of Medicine, University of Yamanashi, Yamanashi, 409-3898, Japan.

Of all tissues, the skin has the third highest abundance of zinc in the body. In the skin, the zinc concentration is higher in the epidermis than in the dermis, owing to a zinc requirement for the active proliferation and differentiation of epidermal keratinocytes. Here we review the dynamics and functions of zinc in the skin as well as skin disorders associated with zinc deficiency, zinc finger domain-containing proteins, and zinc transporters. Read More

Surg Oncol Clin N Am 2016 Apr 18;25(2):363-74. Epub 2016 Feb 18.

Department of Surgery, Helen F. Graham Cancer Center, 4701 Ogletown-Stanton Road, S-4000, Newark, DE 19713, USA.

Pancreatic neuroendocrine tumors are a rare group of neoplasms that arise from multipotent stem cells in the pancreatic ductal epithelium. Although they comprise only 1% to 2% of pancreatic neoplasms, their incidence is increasing. Most pancreatic neuroendocrine tumors are nonfunctioning, but they can secrete various hormones resulting in unique clinical syndromes. Read More

Case Rep Surg 2016 14;2016:1484089. Epub 2016 Feb 14.

Department of Radiology, King Hussein Medical Center, Amman 11831, Jordan.

The rarity of glucagonoma imposes a challenge with most patients being diagnosed after a long period of treatment for their skin rash (months-years). Awareness of physicians and dermatologists of the characteristic necrolytic migratory erythema often leads to early diagnosis. Early diagnosis of glucagonoma even in the presence of resectable liver metastases may allow curative resection. Read More

Best Pract Res Clin Endocrinol Metab 2016 Jan 23;30(1):3-17. Epub 2015 Oct 23.

Yale University School of Medicine, New Haven, CT, USA.

The discovery of neuroendocrine tumours of the gastrointestinal tract and pancreas started in 1870, when Rudolf Heidenhain discovered the neuroendocrine cells, which can lead to the development of these tumours. Siegfried Oberndorfer was the first to introduce the term carcinoid in 1907. The pancreatic islet cells were first described in 1869 by Paul Langerhans. Read More

Bosn J Basic Med Sci 2016 Feb 1;16(1):1-7. Epub 2016 Feb 1.

1: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark 2: Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.

Pancreatic islet α-cell tumours that overexpress proglucagon are typically associated with the glucagonoma syndrome, a rare disease entity characterised by necrolytic migratory erythema, impaired glucose tolerance, thromboembolic complications and psychiatric disturbances. Paraneoplastic phenomena associated with enteric overexpression of proglucagon-derived peptides are less well recognized and include gastrointestinal dysfunction and hyperinsulinaemic hypoglycaemia. The diverse clinical manifestations associated with glucagon-expressing tumours can be explained, in part, by the repertoire of tumorally secreted peptides liberated through differential post-translational processing of tumour-derived proglucagon. Read More

Dermatol Online J 2016 Sep 15;22(9). Epub 2016 Sep 15.

Hofstra Northwell School of Medicine, Department of Dermatology, Hempstead.

We report a 48-year-old woman with a past medical history of psoriasis, nonalcoholic steatohepatitis (NASH), and type II diabetes mellitus, who presented to the emergency department with a 1 week history of erosive annular plaques with associated atrophy and telangiectasias on her legs bilaterally, thighs and buttock, histopathologically consistent with necrolytic migratory erythema. Although classically associated with a pancreatic glucagonoma, this patient experienced this figurate erythema in the setting of fatty liver disease with no glucagonoma. The rarity of pseudoglucagonoma syndrome, or necrolytic migratory erythema occurring in the absence of a glucagonoma, warranted the discussion of this case. Read More

Pancreas 2016 08;45(7):947-52

From the *Department of Surgery and Oncology, †Department of Anatomic Pathology, and ‡Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Objectives: Pancreatic neuroendocrine tumors (PNETs) are known to have heterogeneity in terms of their ability to produce multiple hormones. The aim of this study was to evaluate the heterogeneity of PNETs from the viewpoint of hormonal expression.

Methods: The expressions of 4 representative hormones, gastrin, insulin, glucagon, and somatostatin, in both primary and metastatic lesions, were analyzed by immunohistochemical staining in 20 patients with metastatic PNETs (6 gastrinomas, 1 insulinoma, 1 glucagonoma, and 12 nonfunctioning PNETs [NF-PNETs]). Read More

Int J Dermatol 2016 Nov;55(11):1272-1274

Department of Dermatology, The Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.

Int J Surg Case Rep 2015 23;17:167-9. Epub 2015 Nov 23.

H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA. Electronic address:

Introduction: Pancreatic VIPomas are exceedingly rare, with an annual incidence of less than 1 per million. Most VIPomas are metastatic at diagnosis, with the liver being the most common site of spread.

Presentation Of Case: We describe a highly unusual case of a metastatic pancreatic VIPoma to an ovary in a 54 year-old patient. Read More

Pediatr Dermatol 2016 Mar-Apr;33(2):e43-7. Epub 2015 Dec 9.

Division of Pediatric General, Thoracic and Fetal Surgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Necrolytic migratory erythema (NME) is a rare cutaneous finding characterized by painful, pruritic, scaly red patches and plaques, bullae, and superficial erosions. Typically NME is a paraneoplastic phenomenon associated with glucagonoma. We report the exceptional case of an infant who developed iatrogenic NME arising secondary to glucagon therapy for congenital hyperinsulinism. Read More

Oncol Lett 2015 Aug 27;10(2):1113-1116. Epub 2015 May 27.

The Pancreas Center of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.

Necrolytic migratory erythema (NME), diabetes mellitus and glucagon-secreting tumors form the hallmarks of glucagonoma syndrome, and represent the major clinical manifestations of glucagonoma. NME is usually presented as the initial complaint of patients. Due to the rare incidence of glucagonoma, its diagnosis is often delayed, which leads to its progression. Read More

Br J Dermatol 2016 May 20;174(5):1092-1095. Epub 2016 Jan 20.

Arizona Transplant Associates, 2218 N. 3rd Street, Phoenix, AZ, 85004, U.S.A.

Glucagonoma syndrome is an extremely rare pancreatic neuroendocrine tumour often associated with necrolytic migratory erythema. While glucagonomas are neoplasms of adulthood, we report the first case in a paediatric patient. We present the case of a 15-year-old girl with a 4-year history of a rash, consistent with necrolytic migratory erythema, found to have a localized glucagonoma. Read More

JAMA Dermatol 2016 Mar;152(3):345-6

Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Nihon Naika Gakkai Zasshi 2015 11;104(11):2394-8

Pancreas 2016 Apr;45(4):533-40

From the Departments of *Medical Sciences, and †Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden.

Objectives: Progranulin (PGRN) promotes cell growth and cell cycle progression in several cell types and contributes to tumorigenesis in diverse cancers. We have recently reported PGRN expression in islets and tumors developed in an MEN1 transgenic mouse. Here we sought to investigate PGRN expression and regulation after exposure to hypoxia as well as its effects on pancreatic islet cells and neuroendocrine tumors (NETs) in MEN1(+/−) mice. Read More

J Gastrointest Cancer 2016 Dec;47(4):466-467

Jewish Hospital, Cincinnati, OH, USA.

Intern Med 2015 1;54(19):2475-81. Epub 2015 Oct 1.

Department of Diabetes and Endocrinology, Osaka Red Cross Hospital, Japan.

A 35-year-old obese diabetic man presented with recurrent primary hyperparathyroidism during a three-year outpatient follow-up. He was clinically diagnosed with multiple endocrine neoplasia type 1 (MEN1) due to the presence of a pituitary adenoma and multiple glucagonomas. The glucagonomas may have affected his glycemic control. Read More

Front Horm Res 2015 14;44:24-39. Epub 2015 Aug 14.

Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Neuroendocrine tumors are usually slow-growing tumors. Many of these are capable of secreting peptide hormones or biogenic amines that may lead to endocrine syndromes. Nonfunctioning tumors can either secrete no hormones at all, or secrete hormones not giving rise to endocrine symptoms, such as chromogranin A, chromogranin B or pancreatic polypeptide. Read More

Rev Assoc Med Bras (1992) 2015 May-Jun;61(3):203-6

Universidade de Fortaleza, Fortaleza, CE, Brazil.

Introduction: glucagonoma is a pancreatic neuroendocrine tumor derived from alpha-cells of the islets of Langerhans. It is marked by tumoral autonomous production of glucagon and characterized, among other symptoms, by necrolytic migratory erythema, an erythematous circinate lesion with areas of necrosis and sloughing. This is a rare disease with worldwide incidence estimated at 1 case per 20 million people. Read More

Clin Nucl Med 2015 Nov;40(11):877-9

From the Department of Diagnostic Imaging, Cross Cancer Institute, Edmonton, Alberta, Canada.

A 56-year-old man presented with a history of 2 prior resections of a recurrent pancreatic glucagonoma in the past 4 years. Workup revealed new liver and abdominal nodal metastases with a rising serum glucagon level. He was started on peptide receptor radionuclide therapy with Lu DOTATATE, and his disease stabilized, while his glucagon levels decreased and also stabilized. Read More

Clin J Gastroenterol 2014 Jun 9;7(3):255-9. Epub 2014 Apr 9.

Department of Clinical Oncology, Osaka City General Hospital, Osaka, Japan,

Necrolytic migratory erythema (NME) is a classical paraneoplastic symptom observed in patients with pancreatic glucagonoma. We report a 46-year-old Japanese woman with glucagonoma who presented with mucocutaneous manifestations 1 year prior to the diagnosis of the pancreatic neoplasm with multiple liver metastases. She was treated with octreotide long-acting release, a somatostatin analog, which resulted in a dramatic improvement of NME within 2 weeks after the start of treatment. Read More

Rev Prat 2015 Apr;65(4):461-5

Neuroendocrine pancreatic tumors are rare tumors which require specific diagnosis and management. They are characterized by complex histopathologic criteria, large differences in secretory profile and évolutivity, and be associated to hereditary endocrine disease as NEM1 or VHL. Therapeutic strategy is currently discussed throught the regional or national pluridisciplinary workups organized by the 17 experts centers of the French RENATEN network. Read More

World J Gastrointest Surg 2015 Apr;7(4):60-6

Helen C Miller, Panagiotis Drymousis, Andrea Frilling, Department of Surgery and Cancer, Imperial College London, London W12 0HS, United Kingdom.

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 non-specific abdominal pain. Read More