Glucagonoma

Obtain fasting plasma glucagon in a patient with necrolytic migratory erythema (NME), particularly when accompanied by progressive weight loss, diabetes or glucose intolerance, anemia, glossitis, cheilitis, stomatitis, diarrhea, or venous thrombosis. NME may begin in intertriginous or perineal areas and migrate to the extremities or perioral region; its recognition should prompt biochemical testing even when blood glucose is normal. ScienceDirect+3ScienceDirectGlucagonoma - an overview | ScienceDirect TopicsPubMedGlucagonoma - StatPearls - NCBI BookshelfPubMedDiagnostic challenge of glucagonoma: case report and literature review - PubMedPubMedDiagnostic characteristics, treatment outcomes, and prognostic factors in glucagonomas - PMC

Assess immediately for complications that change near-term management: dehydration or clinically important hyperglycemia, severe nutritional decline, anemia, and venous thromboembolism. Thromboembolic events account for more than half of deaths directly attributed to glucagonoma in one summary, supporting a low threshold to evaluate compatible symptoms with venous imaging and to use perioperative deep-vein-thrombosis prophylaxis. ScienceDirect+1ScienceDirectGlucagonoma - an overview | ScienceDirect TopicsPubMedPancreatic neuroendocrine tumors: biology, diagnosis, and treatment

Elicit personal and family features of multiple endocrine neoplasia type 1 (MEN1), because approximately one-fifth of glucagonomas are associated with MEN1. In a patient with glucagonoma plus personal or family history suggestive of parathyroid, pituitary, or other pancreatic endocrine tumors, evaluate for a hereditary endocrine syndrome rather than treating the pancreatic lesion as definitively sporadic. PubMed+2PubMedGlucagonoma - StatPearls - NCBI Bookshelf - NIHPubMedGlucagonoma - StatPearls - NCBI BookshelfPubMedDiagnosis and Management of Functional Pancreatic Neuroendocrine Tumors in Children—A Systematic Review

Draw glucagon in the fasting state. A level greater than 500 pg/mL is commonly observed in glucagonoma and is a practical threshold for a strongly suspicious result in the appropriate syndrome; a level greater than 1,000 pg/mL is diagnostic when glucagonoma syndrome is present. Some references define the diagnosis using a greater-than-10-fold elevation above a normal value below 50 pg/mL, underscoring the need to interpret the result against the assay-specific reference range. ScienceDirect+4ScienceDirectGlucagonoma - an overview | ScienceDirect TopicsPubMedDiagnosis of Pancreatic Neuroendocrine TumorsGastroenterologyGastrointestinal Neuroendocrine Tumors: Pancreatic Endocrine ...PubMedPancreatic neuroendocrine tumors: biology, diagnosis, and treatmentPubMedDiagnosis and Management of Functional Pancreatic Neuroendocrine Tumors in Children—A Systematic Review

Do not use glucagon as a stand-alone tumor marker. Mild elevations occur with diabetes mellitus, diabetic ketoacidosis, acute or chronic pancreatitis, renal failure, cirrhosis or chronic hepatic failure, sepsis or bacteremia, Cushing syndrome, acute trauma, burns, portocaval shunting, and other neuroendocrine neoplasms. In these settings, correlate the fasting result with NME or other glucagon-excess manifestations and structural imaging before assigning a glucagonoma diagnosis. PubMed+2PubMedGlucagon & Glucagonoma Syndrome - Endotext - NCBI BookshelfPubMedPancreatic neuroendocrine tumors: biology, diagnosis, and treatmentPubMedDiagnosis and Management of Functional Pancreatic Neuroendocrine Tumors in Children—A Systematic Review

At the initial biochemical evaluation, document the consequences of hormone excess and nutritional compromise with glucose assessment and HbA1c, complete blood count, albumin, and liver testing. In a patient with a pancreatic NET and symptoms of hormonal excess, fasting assessment of other potentially secreted peptides, including insulin, proinsulin, pancreatic polypeptide, gastrin, VIP, and somatostatin, can identify mixed secretion or an alternative functional pancreatic NET syndrome. PubMed+3PubMedAn Overview of Pancreatic Neuroendocrine Tumors and an Update on Endoscopic Techniques for Their ManagementPubMedDiagnosis of Pancreatic Neuroendocrine TumorsPubMedDiabetes Mellitus Secondary to Endocrine Diseases: An Update of Diagnostic and Treatment ParticularitiesPubMedPancreatic neuroendocrine tumors: biology, diagnosis, and treatment

Perform multiphasic, three-phase CT or MRI of the pancreas for primary-tumor localization and liver staging. Glucagonomas are usually pancreatic, frequently arise in the distal pancreas, and are often large at diagnosis; contrast-enhanced CT commonly demonstrates a hypervascular pancreatic lesion and can identify hypervascular liver metastases. PubMed+3PubMedGlucagon & Glucagonoma Syndrome - Endotext - NCBI BookshelfScienceDirectScintigraphic long-term follow-up of a patient with metastatic glucagonoma - ScienceDirectPubMedDiagnosis and Management of Functional Pancreatic Neuroendocrine Tumors in Children—A Systematic ReviewPubMedGlucagonoma-associated dilated cardiomyopathy refractory to somatostatin analogue therapy

Add somatostatin receptor imaging, preferably PET/CT with gallium-68-labeled DOTATATE, DOTANOC, or DOTATOC, to define receptor-positive metastatic disease. These PET techniques have the highest sensitivity for metastases from grade 1 to 2 and some grade 3 pancreatic NETs; somatostatin receptor scan positivity has been reported in up to 97% of glucagonoma patients. If PET is unavailable, indium-111 pentetreotide SPECT/CT can demonstrate receptor expression, although it is an older modality. Wolters Kluwer+3Wolters KluwerMalignant transformation of glucagonoma with... : MedicinePubMedGlucagon & Glucagonoma Syndrome - Endotext - NCBI BookshelfPubMedAn Overview of Pancreatic Neuroendocrine Tumors and an Update on Endoscopic Techniques for Their ManagementPubMedDiagnosis of Pancreatic Neuroendocrine Tumors

Obtain core biopsy of a metastatic lesion or primary tumor when tissue will establish diagnosis, determine differentiation, and provide Ki-67 grading before systemic therapy. Expected supportive immunophenotype in a well-differentiated glucagonoma includes neuroendocrine-marker positivity such as chromogranin and synaptophysin with glucagon positivity; pathology should distinguish well-differentiated pancreatic NET from poorly differentiated neuroendocrine carcinoma because treatment strategy differs. Wolters Kluwer+2Wolters KluwerMalignant transformation of glucagonoma with... : MedicinePubMedGlucagon & Glucagonoma Syndrome - Endotext - NCBI BookshelfPubMedGlucagonoma-associated dilated cardiomyopathy refractory to somatostatin analogue therapy

Translate staging into a resectability decision in a pancreatic NET multidisciplinary setting. Localized pancreatic disease is potentially curable with surgery. For liver involvement, hepatic resection is considered when liver disease is not widespread, extrahepatic disease is not diffuse, and liver function is adequate; diffuse metastatic disease instead requires disease-control and symptom-control planning. PubMedPubMedGlucagonoma - StatPearls - NCBI Bookshelf

Address hyperglycemia according to its severity while recognizing that successful suppression or removal of glucagon-secreting tumor can improve glucose control. Monitor glucose and HbA1c during treatment because somatostatin analogs suppress hormone secretion but may also affect insulin secretion; treatment response should be judged by symptoms and glycemic trajectory as well as glucagon concentration. PubMed+1PubMedDiabetes Mellitus Secondary to Endocrine Diseases: An Update of Diagnostic and Treatment ParticularitiesPubMedPancreatic neuroendocrine tumors: biology, diagnosis, and treatment

Treat NME and catabolic decline as manifestations of hormone excess and nutritional compromise rather than as isolated dermatitis. Initiate nutritional assessment and repletion in patients with weight loss, hypoalbuminemia, mucositis, or severe cutaneous disease; preoperative nutrition support is specifically reported as part of multidisciplinary glucagonoma management. NME often improves when glucagon levels decline after tumor resection, cytoreduction, or somatostatin analog therapy. PubMed+2PubMedAn Overview of Pancreatic Neuroendocrine Tumors and an Update on Endoscopic Techniques for Their ManagementPubMedDiabetes Mellitus Secondary to Endocrine Diseases: An Update of Diagnostic and Treatment ParticularitiesPubMedPancreatic neuroendocrine tumors: biology, diagnosis, and treatment

Maintain heightened vigilance for venous thromboembolism. Obtain diagnostic testing for new dyspnea, chest pain, unilateral limb symptoms, or otherwise unexplained clinical deterioration, and use routine perioperative deep-vein-thrombosis prophylaxis when surgery is undertaken. ScienceDirect+1ScienceDirectGlucagonoma - an overview | ScienceDirect TopicsPubMedPancreatic neuroendocrine tumors: biology, diagnosis, and treatment

Refer localized glucagonoma for pancreatic resection because surgery is the only potentially curative treatment. Resection type is determined by tumor location. In patients without metastases, surgery alone has been associated with postoperative 5-year survival greater than 85%; resection also reduces glucagon concentration and can substantially improve NME. ScienceDirect+1ScienceDirectGlucagonoma - an overview | ScienceDirect TopicsPubMedGlucagonoma - StatPearls - NCBI Bookshelf

For selected hepatic metastases, consider combined or staged resection of the primary and liver metastases when disease is not widespread, diffuse extrahepatic metastases are absent, and hepatic functional reserve is adequate. Cytoreductive surgery can reduce tumor burden and glucagon levels, but it is not equivalent to cure in disseminated disease; preoperative nutritional optimization and thrombosis prophylaxis are important perioperative components. PubMed+1PubMedGlucagonoma - StatPearls - NCBI BookshelfPubMedPancreatic neuroendocrine tumors: biology, diagnosis, and treatment

For unresectable, locally advanced, or metastatic receptor-positive glucagonoma, use a somatostatin analog as first-line hormone-control therapy and as part of tumor-control management. Somatostatin analogs suppress glucagon secretion and are associated with improvement in NME and other glucagonoma-syndrome manifestations. Specific agent selection and dose should follow current pancreatic NET labeling and multidisciplinary guidance because glucagonoma-specific dosing data are limited. PubMed+3PubMedGlucagon & Glucagonoma Syndrome - Endotext - NCBI BookshelfPubMedDiagnostic characteristics, treatment outcomes, and prognostic factors in glucagonomas - PMCPubMedDiabetes Mellitus Secondary to Endocrine Diseases: An Update of Diagnostic and Treatment ParticularitiesPubMedPancreatic neuroendocrine tumors: biology, diagnosis, and treatment

If disease progresses or tumor burden requires additional control, select therapy by differentiation, Ki-67 grade, disease tempo, somatostatin receptor expression, prior treatment, and patient comorbidity. Guideline-based pancreatic NET sequencing includes targeted therapy, peptide receptor radionuclide therapy with radiolabeled somatostatin analogs for receptor-positive disease, and cytotoxic chemotherapy for clinically high disease burden. Everolimus and sunitinib are indicated to improve progression-free survival in progressing pancreatic NETs; lutetium-177 DOTATATE is an option for somatostatin receptor-positive gastroenteropancreatic NETs. PubMed+1PubMedGlucagon & Glucagonoma Syndrome - Endotext - NCBI Bookshelfcdn clinicaltrials[PDF] P R O T O C O L C O V E R P A G E - ClinicalTrials.gov

Use PRRT only after confirming somatostatin receptor positivity and coordinating care through an experienced NET team. Cohort evidence in receptor-positive glucagonomas suggests lutetium-177 DOTATATE may improve disease and symptom control, but direct glucagonoma-specific comparative data remain limited. PubMed+1PubMedGlucagon & Glucagonoma Syndrome - Endotext - NCBI BookshelfPubMedDiagnostic characteristics, treatment outcomes, and prognostic factors in glucagonomas - PMC