Genetic disorders and insulinoma/glucagonoma. Insulinoma and glucagonoma are two rare functioning neoplasms of the neuroendocrine cells of the pancreas, respectively, characterized by an uncontrolled over-secretion of insulin or glucagon, responsible for the development of the hypoglycemic syndrome and the glucagonoma syndrome. They prevalently arise as sporadic tumors; only about 10% of cases develop in the context of rare inherited tumor syndromes, such as multiple endocrine neoplasia type 1 (MEN1), neurofibromatosis type 1 (NF1), and tuberous sclerosis complex (TSC), being the result of an autosomal-dominant germline heterozygous loss-of-function mutation in a tumor-suppressor gene. Here, we reviewed the main epidemiological and clinical aspects of insulinoma and glucagonoma in the context
Characteristics and treatment options of glucagonomas: a national study from the French Group of Endocrine Tumors and ENDOCAN-RENATEN network. Glucagonoma is a very rare functional pancreatic neuroendocrine tumor (PanNET). We aimed to provide data on the diagnosis, prognosis, and management of patients with glucagonoma. In this retrospective national cohort, we included all patients with glucagonoma, defined by at least one major criterion (necrolytic migratory erythema (NME) and/or recent-onset diabetes and/or weight loss ≥ 5 kg) associated with either glucagonemia >2xULN or positive glucagon immunostaining. Antisecretory efficacy was defined as partial/complete resolution of glucagonoma symptoms. Antitumor efficacy was assessed according to the time to next treatment (TTNT). Thirty-eight
Emerging therapies for advanced insulinomas and glucagonomas. Pancreatic neuroendocrine neoplasms (panNENs) are rare relatively malignancies that, despite their frequently slow-growing pattern, have the ability to metastasize. Metastatic and/or advanced Malignant insulinomas and glucagonomas are functioning panNENs emerging from the pancreas displaying unique peculiarities, depending action. Similarly, advanced and/or metastatic glucagonomas management also follows the panNENs therapeutic algorithm, but the clinical syndrome has to be addressed by aminoacid infusion and by first-generation SSAs to improve patient' performance status. PRRT seems to be an effective treatment when surgery and SSAs fail. The application of these therapeutic modalities has been shown to be efficacious
Glucagonoma syndrome with severe erythematous rash: A rare case report. Glucagonoma is a rare neuroendocrine tumor of the pancreas. Glucagonoma syndrome is often misdiagnosed as other skin lesions by clinicians due to a typical clinical sign of necrolytic migratory erythema (NME) with severe erythematous rash. A 48-year-old female patient was admitted to our department because she presented with unclear recurrent severe erythematous rash. The patient was diagnosed as skin disease. Histopathologic examination revealed a pancreatic glucagonoma. Immnohistochemical staining of tumor tissue was positive for glucagon. The distal pancreatectomy plus splenectomy was performed in 2017. The skin lesions disappeared after surgery. She was followed up and showed no recurrence until now. Clinicians should
Spleen-preserving distal pancreatectomy and lymphadenectomy for glucagonoma syndrome: A case report. Glucagonoma is a rare type of functional pancreatic neuroendocrine tumor that is characterized by distinctive clinical manifestations; among these, necrolytic migratory erythema represents the hallmark clinical sign of glucagonoma syndrome and is usually presented as the initial complaint calcification in plain scanning images and uneven enhancement in strengthening periods. In addition, laboratory tests indicated elevated fasting blood glucagon (1109 pg/mL, normal range: 50-150 pg/mL) levels. Glucagonoma syndrome was ultimately diagnosed in clinical. Spleen-preserving distal pancreatectomy was conducted and postoperative pathology revealed the presence of glucagonoma. The patient recovered
Glucagonoma and the glucagonoma syndrome Glucagonoma is an extremely rare pancreatic α-islet cell tumor and is often accompanied by certain clinical symptoms including necrotizing migratory erythema (NME), diabetes, weight loss and anemia. The objectives of the current review were to discern the clinical features, diagnosis, treatment and prognosis of glucagonoma by evaluating 623 reported cases older than those without metastasis (average age, 54.0 years old vs. 50.8 years old). The average time between symptoms and diagnosis of glucagonoma was 31.4 months. Glucagonoma is a very rare disease. It is important for clinicians to learn more about this disease to be able to diagnose and treat it as early as possible, thus improving patient prognosis.
Glucagonoma with necrolytic migratory erythema: metabolic profile and detection of biallelic inactivation of DAXX gene. Necrolytic migratory erythema (NME) occurs in approximately 70% of patients with glucagonoma syndrome. Excessive stimulation of metabolic pathways by hyperglucagonemia, which leads to hypoaminoacidemia, contributes to NME pathogenesis. However, the molecular pathogenesis of glucagonoma and relationships between metabolic abnormalities and clinical symptoms remain unclear. A 53-year-old woman was referred to our hospital with a generalized rash and weight loss. NME was diagnosed by histopathological examination of skin biopsy tissue. Laboratory tests revealed diabetes, hyperglucagonemia, marked insulin resistance, severe hypoaminoacidemia, ketosis, and anemia. Enhanced computed
A review of cutaneous manifestations within glucagonoma syndrome: necrolytic migratory erythema. Necrolytic migratory erythema (NME) is a rare skin disorder that is a cutaneous manifestation of the glucagonoma syndrome. It presents with annular eruptions of migrating erythematous papules and plaques with superficial epidermal necrosis, central flaccid bullae, and crusted erosions located primarily in the intertriginous areas. Treatment with the long-acting somatostatin analog Octreotide is a potential therapy to help ameliorate skin symptoms. We present a case of a patient with a 1-year history of a pancreatic glucagonoma that developed an ulcerated, plaque-like, weeping rash over multiple areas of their body despite current treatment with Octreotide and stable pancreatic tumor staging
Glucagonoma and Glucagonoma Syndrome: A Case Report with Review of Recent Advances in Management 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. Herein, we present a typical case of glucagonoma treated at our center and review the literature pertinent to its management.
Glucagonoma syndrome with serous oligocystic adenoma: A rare case report. Glucagonoma and pancreatic serous oligocystic adenoma (SOA) are rare neuroendocrine and exocrine tumors of the pancreas, respectively. The coexistence of glucagonoma syndrome (GS) and SOA is a rare clinical condition and has not yet been reported. Additionally, necrolytic migratory erythema (NME), a hallmark clinical sign for the hepatic nodular lesion. One week after surgery, the glucagon concentration decreased to near normal levels. The cutaneous lesions spontaneously resolved within 4 weeks after surgery. Because almost all glucagonomas are malignant or have malignant potential, their early recognition and correct diagnosis are very important for a better prognosis, especially in cases with NME as the only manifestation
Malignant transformation of glucagonoma with SPECT/CT In-111 OctreoScan features: A case report. Glucagonoma is an uncommon disease but it has been associated with a pattern of symptoms defined as glucagonoma syndrome. These symptoms, if promptly recognized, could help to speed up the diagnosing process. We report a case of a 68-year-old woman with a pancreatic glucagonoma. Her symptoms at the onset were typical of the glucagonoma syndrome. After a significant weight loss, she underwent a computer tomography scan of the abdomen, which showed a hypervascular lesion of the tail of the pancreas and hypervascular lesions of the liver. An ultrasound guided biopsy was performed and pathology was consistent with glucagonoma. Her blood glucagon levels were elevated. She was treated
Glucagonoma syndrome: a review and update on treatment. 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. Prompt recognition of NME and subsequent workup for a glucagonoma can allow for an earlier diagnosis and enhance the chances of a favourable outcome. In particular, metastases occur late, so early recognition of glucagonoma syndrome before liver metastases can be life-saving. Surgical
Glucagonoma syndrome: report of one case 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
Do glucagonomas always produce glucagon? 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
Glucagon receptor gene mutations with hyperglucagonemia but without the glucagonoma syndrome 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 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
Pediatric Necrolytic Migratory Erythema as a Presenting Sign of Glucagonoma Syndrome. 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. Immediately following resection of the tumour, there was complete resolution of her rash and systemic symptoms. Detection of the cutaneous rash of necrolytic migratory erythema can aid in the early diagnosis of a glucagonoma, as well as the prevention of metastatic disease. To our knowledge, this is the first reported paediatric patient
Heterogeneity of glucagonomas due to differential processing of proglucagon-derived peptides Pancreatic neuroendocrine tumours (pNETs) secreting proglucagon are associated with phenotypic heterogeneity. Here, we describe two patients with pNETs and varied clinical phenotypes due to differential processing and secretion of proglucagon-derived peptides (PGDPs). Case 1, a 57-year-old woman