Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinicopathologic correlation of five cases of glucagon-positive pancreatic tumours is reviewed. Two cases with the typical glucagonoma syndrome but with atypical manifestations in the central nervous system are presented. These neurological manifestations might constitute a new paraneoplastic syndrome. The last three cases illustrate how glucagon positivity can be present in pancreatic endocrine tumours other than in the classical glucagonoma.
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PMID:Clinico-pathological correlation of glucagon-positive pancreatic endocrine tumours: a presentation of five cases. 766 14

We report a rare case of symptomatic hypoglycemia in a patient with intra-abdominal recurrence of a previously resected gastrointestinal stromal tumor (GIST). The patient is a 65-year-old woman who underwent resection of a large abdominal mass arising from the stomach, histologically diagnosed as a high-grade leiomyosarcoma. She was lost to follow up. Five years later, the mass recurred; core biopsy demonstrated a CD 117-positive, spindle-cell tumor, consistent with a GIST. She was placed on Gleevec, as there was evidence of multifocal disease, but imaging revealed only mild improvement. Subsequently, her clinical status deteriorated, and she was hospitalized for dehydration, vomiting, and mental status changes. Her blood glucose on admission was 22 mg/dL, and a dextrose infusion (50%) was necessary to maintain adequate blood glucose levels. Measurements of insulin, proinsulin, c-peptide, beta-hydroxybutyrate, and thyroid-stimulating hormone were normal, as were cosyntropin stimulation and glucagon response tests. Suspicions arose for tumor-secreted insulin-like factor. She underwent resection of the dominant 44-cm recurrence, with immediate rebound hyperglycemia, followed by complete normalization of her blood glucose levels. She was discharged on postoperative Day 5 without symptoms or insulin, and is alive with disease at 20 months. Paraneoplastic syndromes occur in only 15 per cent of patients with known malignancies (e.g., lung cancer and metastatic carcinoid), and are rarely reported in the setting of GIST. Hypoglycemia is most often observed in presence of insulinoma and only isolated case reports in GIST patients exist. Overexpression of insulin-like growth factor II is thought to be the mechanism of action. Supportive management and palliative resection or debulking is recommended when possible.
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PMID:Hypoglycemia in the setting of advanced gastrointestinal stromal tumor. 1721 25

Biochemical markers are applied in gastroenteropancreatic neuroendocrine tumours (GEP-NETs) for diagnostic, prognostic or predictive purposes. Chromogranin A is the most important general marker and it is recommended to be measured in every patient with a suspected NET, whereas Neuron Specific Enolase is elevated mainly in poorly differentiated NETs. Pancreatic Polypeptide is used in the diagnosis of pancreatic non-functioning NETs, whereas Chorionic Gonadotrophin has an adjunctive role. In the case of functioning tumours, specific markers should be sought and monitored during follow up. Endogenous hyperinsulinemia is suggested in the presence of non-suppressible insulin and proinsulin levels during hypoglycemia, whereas high fasting or stimulated gastrin levels along with elevated gastric acid output are diagnostic for the Zollinger-Ellison syndrome. Glucagon, vasoactive intestinal polypeptide (VIP) and somatostatin are markers for glucagonoma, VIP-oma and somatostatinoma syndromes respectively. In case of ectopic paraneoplastic syndrome, the relevant hormone serves as a diagnostic and prognostic marker.
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PMID:Biochemical markers for gastroenteropancreatic neuroendocrine tumours (GEP-NETs). 2358 19

Necrolytic migratory erythma (NME) is an obligatory paraneoplastic syndrome. Here we describe a woman admitted to the dermatology ward with NME which was later found to be associated with glucagonoma, a slow-growing, rare pancreatic neuroendocrine tumor. Even more rarely, the tumor was located in the pancreas head, while most of such lesions are located in the distal pancreas. The diagnosis of this rare tumor requires an elevated serum glucagon level and imaging confirming a pancreatic tumor. After surgical removal of the tumor, the patient's cutaneous and systemic features resolved. It is therefore imperative that clinicians recognize NME early in order to make an accurate diagnosis and to provide treatment for this rare tumor.
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PMID:Necrolytic migratory erythema as the first manifestation of pancreatic neuroendocrine tumor. 2502 13

A 61-year-old male was admitted from the outpatient setting for treatment of severe hyperglycemia. Five months earlier, his hemoglobin A1c had been 5 mmol/mol. At presentation, hemoglobin A1c was 11.3 mmol/mol and he required insulin therapy at discharge. Later magnetic resonance imaging (MRI) identified bilateral renal masses, previously seen on ultrasound during workup for chronic kidney disease, as being suspicious for renal cell carcinoma (RCC). He underwent partial nephrectomy and cryoablation with pathology showing papillary type RCC. Hyperglycemia resolved after resection and insulin therapy was discontinued, requiring only an oral hypoglycemic. Hyperglycemia as a paraneoplastic syndrome related to RCC is rare. The cause of this acute hyperglycemia is not understood, though previously suggested mechanisms include ectopic glucagon production, autoimmune causes and interleukin-6 (IL-6) mediated pathways. Severe, new-onset hyperglycemia in the absence of common causes and with a renal mass on imaging may represent an uncommon paraneoplastic syndrome secondary to RCC.
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PMID:New onset hyperglycemia attributed to renal cell carcinoma. 2986 57

Lipase hypersecretion syndrome (LHS) is a paraneoplastic syndrome seen exclusively as a result of pancreatic acinar cell carcinoma (ACC). In LHS, acinar enzymes (lipase, trypsin and chymotrypsin) which are normally secreted to the duodenum for digestive purposes, are instead released to the blood by the carcinoma cells. In a way, it is "endocrine-ization" of an "exocrine" function. These circulating enzymes, especially lipase, exerts its digestive action on other tissues, especially on the subcutaneous tissues in the pressure poins of legs, creating a picture often mistaken as erythema nodosum or rheumatic nodules. The bone and joints may also be effected, which mostly appears to be secondary to the complications and super-infection of the skin lesions. Eosinophilia also often accompanies this syndrome. The accurate diagnosis of LHS requires the identification of the pancreatic primary as well as its correct classification as acinar because a variety of pancreatic tumors can be associated with skin lesions, ranging from rare metastasis of adenocarcinoma to the necrolytic migratory erythema caused by glucagon-producing neuroendocrine tumors. Towards this differential, the diagnostic characteristics of acinar cell carcinomas that have been better elucidated in the past decade often need to be employed in increasingly smaller specimens and the liver, especially since most LHS cases also have liver metastasis (presumably due to the by-pass of the "first-pass" liver metabolism phenomenon). ACC (and LHS) occur in patients in their 60's. The pancreatic mass is often large, round, demarcated and closely resemble neuroendocrine and solid-pseudopapillary neoplasms but are more atypical/proliferative, and commonly show single prominent nucleoli and a distinctive chromophilia. Immunostaining with trypsin/chymotrypsin, negativity of beta-catenin help in the differential; as a caveat, neuroendocrine differentiation is common in ACCs. In conclusion, LHS is a rare type of paraneoplastic syndrome specific to ACC. The accurate diagnosis requires attention to their subtle diagnostic characteristics.
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PMID:Lipase hypersecretion syndrome: A distinct form of paraneoplastic syndrome specific to pancreatic acinar carcinomas. 3130 Feb 57

Glucagonoma is a hormonally active rare pancreatic neuroendocrine tumour causing an excess of glucagon. This is a narrative review based on a multidisciplinary approach of the tumour. Typically associated dermatosis is necrolytic migratory erythema (NME) which is most frequently seen at disease onset. Insulin-dependent diabetes mellitus, depression, diarrhoea, deep vein thrombosis are also identified, as parts of so-called 'D' syndrome. Early diagnosis is life saving due to potential aggressive profile and high risk of liver metastasis. NME as paraneoplastic syndrome may be present for months and even years until adequate recognition and therapy; it is remitted after successful pancreatic surgery. Thus the level of practitioners' awareness is essential. If surgery is not curative, debulking techniques may improve the clinical aspects and even the outcome in association with other procedures such as embolization of hepatic metastasis; ablation of radiofrequency type; medical therapy including chemotherapy, targeted therapy with mTOR inhibitors such as everolimus, PRRT (peptide receptor radiotherapy), and somatostatin analogues (including combinations of medical treatments). Increased awareness of the condition involves multidisciplinary practitioners.
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PMID:Glucagonoma: From skin lesions to the neuroendocrine component (Review). 3290 95