GlucagonomD13.7

Rare, glucagon-producing malignant, slow-growing pancreatic tumor belonging to the family of neuroendocrine tumors, which is usually already metastasized at the time of diagnosis (lymph nodes, liver, more rarely metastases are found in bone).

Glucagonomas are islet cell tumors that develop from the alpha cells of the Langerhans islets of the pancreas.

Sporadic glucagonomas (>95% of glucagonoma patients)

Syndromal glucagonomas (partial symptom of multiple endocrine neoplasia type 1 (MEN1).

Very rare; incidence not known; w:m=4:1.

The average age when the first symptoms appear is 50 years.

Glucagonomas are usually located in the tail area of the pancreas.

Initially uncharacteristic with continuous performance loss, weight loss, unexplained normochromic anemia, hypoaminoacidemia and hypolipidemia.

Clinically typical is the combination of hyperglycaemia, often associated with a recurrent, therapy-resistant, scaly, sometimes pustular, often perioral, but also inguinal localized dermatitis(erythema necrolyticum migrans). Furthermore, cheilitis and atrophic glossitis. Psychological changes are not rare.

Glucagon level > 1000 pg/ml (normal < 200). The determination of other neuroendocrine hormones (insulin, gastrin) is important, since an islet cell tumour can have several hormonal activities.

Remark: Moderate increases of glucagon levels occur in renal insufficiency, acute pancreatitis and during fasting.

Blood sugar determination: Hyperglycemia

Decrease of the amino acid concentration in the blood.

Combination of hyperglycaemia (in non-obese people) and migratory necrolytic dermatitis. Determination of serum glucagon levels.

Imaging procedures: By means of upper abdominal sonography, endosonography, CT, MRT or PET detection of visible masses in the pancreas. The tumour can be very small, but also relatively large. It is not uncommon for there to be enlargement of the lymph nodes in the upper abdomen and possibly liver metastases at the time of the noticeable clinical symptoms.

The spread of the glucagonoma in the body is recorded by an octreotide scintigraphy.

Histological detection by means of fine needle biopsy or biopsy of a larger foci.

Chemotherapy (success is unsatisfactory): Non-resectable, metastatic or recurrent tumors are treated with a combination of streptozotocin and doxorubicin, this may reduce circulating immunoreactive glucagon levels, decrease symptoms and increase response rates (50%), but overall survival is unlikely to improve.

Alternative: chemotherapy with a temozolomide-based regime

Alternative: everolimus or sunitinib.

Supplementary symptomatic:

• Octreotide (somatostatin analogue). Octreotide injections partially suppress glucagon production and relieve erythema, but glucose tolerance may also decrease as octreotide also reduces insulin secretion (Note: Octreotide is only effective in glucagon-forming tumors. Tumours that produce little or no glucagon do not benefit from octreotide as it has no antiproliferative effect.) Octreotide also reduces the catabolic effect of excess glucagon. In the long term, patients are switched to a long-acting octreotide preparation (20-30 mg i.m. 1x/ month). Patients on octreotide medication often need to take pancreatic enzymes as octreotide also inhibits the secretion of pancreatic enzymes.
• Oral or parenteral zinc can lead to an improvement in the accompanying dermatitic symptoms.
• Amino or fatty acids: in addition, the application of amino or fatty acids leads to an improvement (these experiences suggest that dermatitis is not exclusively caused by a zinc deficiency.

Therapeutic guidelines according to AWMF Guideline 2018:

All NF-pNET >2cm without diffuse distant metastasis should be resected unless significant comorbidity argues against surgery.

In case of suspected malignancy of the glucagonoma (<10%; large tumors and/or V.a. nodular infestation) without evidence of distant metastases, complete resection with formal pancreatic resection and lymphadenectomy should be performed.

In the presence of malignant glucagonoma with resectable distant metastases, the complete removal of the primary tumor and metastases should be attempted. If liver metastases are present, hepatic (chemo)embolization with the controlled, available procedures should be performed.

In the case of malignant glucagonomas with surgically incurable distant metastases, removal of the primary tumor and debulking of the distant metastases to improve the hyperglycemia symptoms should be considered.

Blind resection of pancreatic tissue without intraoperative tumor detection should not be performed.

80% of glucagonomas are malignant. The prognosis is relatively good in terms of quality of life and long-term survival due to slow growth and newer treatment options.

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