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Glucagonoma Workup

  • Author: Luigi Santacroce, MD; Chief Editor: George T Griffing, MD  more...
 
Updated: May 14, 2015
 

Laboratory Studies

Determining the level of glucagonemia by means of radioimmunoassay (RIA) testing is mandatory. A positive test result for glucagonoma exceeds 1000 pg/mL (reference range is 50-200 pg/mL).

Performing a fasting blood sugar and/or glucose tolerance test to establish the presence of diabetes is important. A complete blood count (CBC) with a differential count is important for evaluating whether anemia is present. Because glucagonoma can, in rare cases, be a part of multiple endocrine neoplasia type 1 syndrome, also check serum levels of fasting insulin, glucagon, prolactin, calcium, and VIP.

Performing a study of the nutritional status of the patient is important in order to correct nutritional deficits; this test must evaluate the level of serum concentration of amino acids, zinc, and essential fatty acids.

Determining the level of transaminases, bilirubinemia, and alkaline phosphatase is important in order to detect hepatic metastases. The serum level of chromogranin A (CgA) has been proposed as and demonstrated to be a type of sensitivity marker (albeit a nonspecific one) for determining the presence of glucagonoma. Stimulation tests with arginine, secretin, or tolbutamide, which rapidly stimulate plasmatic glucagon levels in patients affected by glucagonoma, are of little additional help.

The detection of telomerase and the quantification of the human telomerase reverse transcriptase (hTERT) protein subunit have been proposed for distinguishing clinically benign from malignant endocrine tumors. In reported cases, primary endocrine malignant tumor showed telomerase activity. The quantification of hTERT messenger ribonucleic acid (mRNA) has been used in clinical practice to exclude malignancy.

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Imaging Studies

In patients with functioning islet cell tumors, the radiologist must localize the lesion. Knowing the tumor size and location, especially with hepatic metastases, is fundamentally important when deciding on treatment.

As with other endocrine tumors of the pancreas, the diagnosis requires localization by 1 of several modalities, including angiography, computed tomography (CT) scanning, and magnetic resonance imaging (MRI). CT and MRI of the pancreas can help to characterize the precise site of the tumor (localized in the pancreatic tail in 86-88% of cases).[10] In 95% of cases, the tumor appears as a single mass, with a diameter varying from 1-30 cm.

Selective angiography of the celiac tripod can localize the center of the tumor with high reliability simultaneously characterizes hepatic metastases. The tumor usually appears as a prominent, hypervascular area. The combination of abdominal CT and angiography provides an acceptable preoperative assessment.[10]

MRI is useful in characterizing islet cell tumors, which have marked increased signal intensity on T2-weighted images. Gadolinium enhancement in the nonnecrotic or nondegenerated areas of the tumor shows a characteristic pattern that allows differentiation of islet cell tumors from the more common pancreatic adenocarcinoma, which is hypovascular and has lower signal intensity on T2 images.

Metaiodobenzylguanidine (MIBG) scintigraphy may be helpful in detecting the primary tumor.

Positron emission tomography (PET) scanning and scintigraphic study with indium-111 octreotide (111 In-D-Phe1-octreotide) or C-11 L-dihydroxyphenylalanine (11 C-L - DOPA) have been used, but, because of the small number of patients with glucagonoma, estimating the real reliability of these imaging techniques has not been possible. Because the lymph node metastasizes and the primary tumor in the pancreatic tail cannot be observed with ultrasonography, CT scanning, or angiography, this diagnostic tool might be useful in selected patients. Practically all glucagonomas studied have been somatostatin receptor positive.[11, 12]

Endoscopic ultrasonography can be used for early localization of the tumor.

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Procedures

Correctly performing a biopsy of the skin during an advanced phase of the disease allows for a diagnosis of necrolytic migratory erythema. Different stages of the cutaneous lesions may be present simultaneously. Performing repetitive, multiple, and random sampling of the lesions is very helpful for diagnosis.

Based on radiologic features, a Tru-cut biopsy or laparotomy could be performed in order to obtain histologic samples.

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Histologic Findings

Usually, glucagonomas arise from alpha-2 cells of the pancreatic islets and grossly appear as a single mass (80%). In approximately 80% of cases, glucagonoma is a carcinoma, and it is an adenoma in 20% of cases. Although the tumor is most frequently localized in the tail of the pancreas, finding it in other areas of the organ is not rare (24% in the body of pancreas, 10% in the head of the pancreas, and 20% in the whole pancreas is interested with multiple foci). Glucagonoma is rarely found in a gastric or duodenal location.

The tumor appears as a solid, single mass of 5 cm or more that is well demarcated from the surrounding parenchyma and is capsulated, with a rich vascular network that differentiates it from pancreatic adenocarcinomas. More rarely, a number of neoplastic lesions can be found. The tumor cells are occasionally organized in nests and strands and appear strongly glucagon-positive on immunohistochemical staining. A strong cellular affinity for betacellulin, a member of the family of epidermal growth factors (EGFs), has been reported. Electron microscopy shows secretory granules and an extended rough endoplasmic reticulum (RER).

The basic skin damage seems to consist of small blisters, which contain acantholytic epidermal cells, neutrophils, and lymphocytes. The surrounding epidermis is usually intact, and the dermis contains a lymphocytic perivascular infiltrate. Skin samples from the areas with early necrolytic migratory erythema show lymphocytic infiltration of the dermis, while examination of the epidermis shows focal dyskeratosis and lymphocytes. Later, lymphocytic infiltration of the dermis with neutrophils and eosinophils can be found, while the epidermis shows diffuse parakeratosis, acanthosis, loss of the granular layer, and necrosis of the superficial layers.

Metastases that are histologically similar to the primitive tumor may be in the liver (60-90%).

Images are included below.

A section of a glucagonoma mass with several fiber A section of a glucagonoma mass with several fiber bundles and solid cellular strands (125 X). Courtesy of Professor Pantaleo Bufo, University of Foggia, Italy.
A section of a glucagonoma mass with irregular asp A section of a glucagonoma mass with irregular aspects of fiber bundles and cellular strands (400 X). Courtesy of Professor Pantaleo Bufo, University of Foggia, Italy.
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Staging

No detailed or generally accepted staging system for glucagonoma exists.

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Contributor Information and Disclosures
Author

Luigi Santacroce, MD Assistant Professor, Medical School, State University at Bari, Italy

Disclosure: Nothing to disclose.

Coauthor(s)

Mini R Abraham, MD Consulting Staff, Overland Park Medical Specialists

Mini R Abraham, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society

Disclosure: Nothing to disclose.

Laura Diomede University of Bari School of Medicine, Italy

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

Frederick H Ziel, MD Associate Professor of Medicine, University of California, Los Angeles, David Geffen School of Medicine; Physician-In-Charge, Endocrinology/Diabetes Center, Director of Medical Education, Kaiser Permanente Woodland Hills; Chair of Endocrinology, Co-Chair of Diabetes Complete Care Program, Southern California Permanente Medical Group

Frederick H Ziel, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Federation for Medical Research, American Medical Association, American Society for Bone and Mineral Research, California Medical Association, Endocrine Society, International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

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A section of a glucagonoma mass with several fiber bundles and solid cellular strands (125 X). Courtesy of Professor Pantaleo Bufo, University of Foggia, Italy.
A section of a glucagonoma mass with irregular aspects of fiber bundles and cellular strands (400 X). Courtesy of Professor Pantaleo Bufo, University of Foggia, Italy.
Bland embolization of the right hepatic artery in a patient with metastatic neuroendocrine tumors: Part 1. Courtesy of Memorial Sloan-Kettering Cancer Center.
Bland embolization of the right hepatic artery in a patient with metastatic neuroendocrine tumors: Part 2. Courtesy of Memorial Sloan-Kettering Cancer Center.
Postprocedure computed tompgraphy scans after bland embolization of the right hepatic artery in a patient with metastatic neuroendocrine tumors. Courtesy of Memorial Sloan-Kettering Cancer Center.
 
 
 
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