Pancreatic glucagonoma.

Glucagonoma is an A-cell pancreatic tumor that produces glucagon and is clinically manifested by a combination of characteristic skin changes and metabolic disorders. The glucagonoma syndrome was deciphered in 1974 by C. N. Mallinson et al. In 95% of cases, the tumor is located intrapancreatically, in 5% - extrapancreatically. Only cases of solitary tumors have been observed.

In more than 60% of patients it is malignant. Sometimes glucagonoma produces other peptides - insulin, PP. The diagnosis is established by increasing glucagon levels and instrumental studies. The tumor is identified by CT and endoscopic ultrasound. Treatment of glucagonoma consists of surgical resection.

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Symptoms of glucagonoma

Because glucagonomas secrete glucagon, the symptoms of glucagonoma are similar to those of diabetes mellitus. Weight loss, normochromic anemia, hypoaminoacidemia, and hypolipidemia are common, but the major distinguishing clinical feature is a chronic rash affecting the extremities, often associated with a smooth, shiny, bright red tongue and cheilitis. The scaling, hyperpigmentation, erythematous lesions with superficial necrolysis are called necrolytic migratory erythema.

In most cases, patients have characteristic migratory necrolytic erythema. It begins as maculopapular erythema, then turns into bulbous dermatosis. Moreover, the blister-like rising upper layers of the epidermis are destroyed. New elements appear next to the old ones. Healing occurs through hyperpigmentation. Skin rashes appear more often in the abdomen, thighs, and shins. The pathogenesis of skin changes is unclear. Their connection with hyperglycemia and hypoacidemia observed in patients with glucagonoma is not excluded. Both hyperglycemia and hypoacidemia are a consequence of increased gluconeogenesis in the liver caused by an increased level of glucagon, and plasma amino acids are also converted into glucose.

Pathological glucose tolerance is caused by the hyperglycemic effect of glucagon due to both the formation of glucose and increased glycogenolysis.

Patients often develop very painful glossitis and stomatitis. Their pathogenesis is unclear. There is also pronounced stasis in the small and large intestines, associated with the inhibition of intestinal motility by the peptide.

Diagnosis of glucagonoma

The decisive evidence of glucagonoma (in the presence of appropriate clinical manifestations) is the detection of high concentrations of glucagon in the plasma (normal value is below 30 pmol/l). However, moderate increases in the hormone can be observed in renal failure, acute pancreatitis, severe stress and starvation. Correlation with symptoms is necessary. Patients should undergo abdominal CT and endoscopic ultrasound; if CT is uninformative, MRI can be used.

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Treatment of glucagonoma

Radical removal of glucanoma is possible in only one out of three patients with glucagonoma. Tumor resection results in symptom regression. Treatment of glucagonoma with streptozotocin and/or 5-fluorouracil without prior surgical intervention yields disappointing results.

Inoperable tumors, presence of metastases or recurrent tumors are subject to combined treatment with streptozocin and doxorubicin, which reduce the levels of circulating immunoreactive glucagon, lead to regression of symptoms and improve the condition (50%), but are unlikely to affect survival time. Octreotide injections partially suppress glucagon secretion and reduce erythema, but glucose tolerance may also decrease due to decreased insulin secretion. Octreotide quite quickly leads to the disappearance of anorexia and weight loss caused by the catabolic effect of excess glucagon. If the drug is effective, patients can be transferred to prolonged octreotide at 20-30 mg intramuscularly once a month. Patients taking octreotide should additionally take pancreatic enzymes due to the suppressive effect of octreotide on the secretion of pancreatic enzymes.

There are reports of successful reduction of liver metastases using embolization of hepatic arteries with gelatin foam directly injected during catheterization.

Zinc preparations are prescribed to treat skin changes. Topical, oral, or parenteral zinc causes regression of erythema, but the erythema may resolve with simple hydration or intravenous administration of amino or fatty acids, suggesting that the erythema is definitely not caused by zinc deficiency.

What is the prognosis for glucagonoma?

Glucagonoma is rare, but like other islet cell tumors, the primary tumor and metastatic lesions are slow growing: survival is usually about 15 years. Eighty percent of glucagonomas are malignant. The average age at onset of symptoms is 50 years; 80% are women. Some patients have multiple endocrine neoplasia type I.