Pancreatic endocrine tumours are heterogeneous with varying tumour biology and prognosis. They are classified as non-functional or functional if they are associated with a hormone-related clinical syndrome caused by hormone release from the tumour. The glucagonoma syndrome is a rare paraneoplastic phenomenon identified as a slow-growing alpha cell tumour of the pancreatic islets of Langerhans, which produces a state of chronic hyperglucagonaemia.
Glucagonoma was first described by Becker, Kahn and Rothman in 1942, and these tumours are thought to cause 1 % of all pancreatic neuroendocrine tumours with an incidence of one in 20 million.
The presentation is often with the typical skin disorder : necrolytic migratory erythema. Weight loss and diabetes mellitus are two other prevalent characteristics of this syndrome, and it is estimated that people with glucagonoma have a 66%-83% chance of developing diabetes mellitus.
Patients with glucagonoma usually are middle-aged (53+/-5 years, range 43-71); the excess of glucagon in these patients enhances blood glucose levels, because of the effects this hormone has on gluconeogenesis and lipolysis. The net result is hypoaminoacidemia, anaemia and weight loss of 5-15 kg.
It is important to note that either diabetes (66% of patients) or necrolytic migratory erythema (NME, 83%) are usually present in these patients. NME is a classical symptom that may be observed in limbs and areas of greater friction, and it is resistant to steroid treatment, both oral and topical. NME, along with anemia, may be caused by the low aminoacid levels in blood.
Diarrhoea (33%), deep vein thrombosis (DVT, 33%), glossitis and stomatitis (33%) are other symptoms associated with glucagonoma; the thrombosis does not respond to anticoagulant therapy. As might be expected, when considering the rarity and complexity of the syndrome, diagnosis of this tumour is often delayed.
Investigation is based on blood tests, radiological exams and biopsies.
Blood tests include: - complete blood count (anemia normocytic); - erythrocyte sedimentation rate (raised ESR); - glucose tolerance test (to establish the presence of Diabetes Mellitus); - fasting and random blood glucose levels (hyperglycemia); - serum glucagon levels by means of radioimmunoassay (RIA) (a positive result for glucagonoma exceeds 1000 pg/mL; normal range 50-150 pg/mL). - Radiological investigations are helpful in knowing the size and location of the tumor, especially with hepatic metastasis and fundamentally important when deciding on treatment.
These investigations are mainly:
- abdominal US: essential for detection of tumor mass; ;
- CT/MRI/endoscopic US: needed for the localization of the tumor;
Axial contrast-enhanced CT image obtained in the arterial phase shows a 9.5-cm heterogeneously hyperattenuating mass that contains calcification (arrowhead) and multiple foci of decreased attenuation (arrows), a finding due to areas of cystic degeneration. Obstruction of the main pancreatic duct (*) and atrophy also are seen and are a result of mass effect. - - selective celiac axis arteriography is helpful because the tumour has a rich vascular supply. It is required to localize the tumour when the CT is negative, and is considered to be the gold standard for the localization of the tumour and detection of liver metastasis. - - indium labeled-DTPA can also be used since it is a very sensitive in diagnosis of glucagonoma. - MIBG scintigraphy and PET scanning are used if the primary tumor cannot be detected on US, CT or angiography.
Radiological and histological findings. (A) Axial and (B) coronal CT scan revealing a 5-7 cm nodular mass in the tail of her pancreas (*)(C) Histological examination of the mass showing an alpha-cell pancreatic tumor (hematoxylin and eosin ×20). (D) Inmunostaining revealed numerous glucagon-positive cells (×20).
Other procedures include the biopsy of skin in advanced stage of the disease (allows the diagnosis of necrolytic migratory erythema). Based on radiological features, a Tru-Cut biopsy or laparotomy can be performed in order to obtain histological samples.
The mainstay of treatment is surgical resection of the primary tumour. Most patients show significant clinical improvement even with incomplete resection of metastasis. Increased level of glucagon secretion can be treated with octreotide, a somatostatin analog.
In advanced metastasis and non resectable disease, chemotherapeutic agents such as doxorubicin, streptozotocin and 5-fluorouracil have also been used successfully to selectively damage alpha cells of pancreatic islet. These do not destroy the tumour but help to minimize the symptom progression.
In patients with glucagonoma, providing a supplemental protein supply in order to furnish amino acids is useful. In more severe cases, such supplementation can be administered intravenously. The administration of essential fatty acids (i.e. olive oil), zinc, vitamins and minerals is also helpful.[a]
^ Ishaq M, Khan RA, Mujtaba G – Glucagonoma Syndrome - Journal of Pakistan Association of Dermatologists 2009; 106-108
^ This web page was created by Rodolfo Calarco, Gabriele Brunotti and Virginia Coradini, medical students at Sapienza University Of Rome.