Glucagonoma
Introduction
Introduction to glucagonoma Glucagonoma (GCGN) is an islet A (2) cell tumor that secretes excessive glucagon, mainly characterized by skin migration, necrotic erythema, diabetes, anemia, tongue and angular cheilitis, vulva Vaginitis, low amino acidemia, etc., also known as hyperglycemia skin disease syndrome. More malignant, often early metastasis. The diameter of the tumor is generally 1.5 to 3 cm, and sometimes the entire pancreas is a tumor. After early surgical removal of the tumor, skin damage and diabetes can quickly disappear. The disease is more common in middle-aged and elderly people aged 40 to 70. Women are more common than men, and most of them are menopausal women. Most cases last for more than 1 year, and some are more than 12 years. basic knowledge The proportion of illness: 0.005%-0.008% Susceptible people: no special people Mode of infection: non-infectious Complications: anemia, keratitis, malnutrition, dementia, optic atrophy, nystagmus, ataxia
Cause
Cause of glucagonoma
Islet A cell proliferation (20%)
Most of the glucagonomas are single-shot, 60% of which are malignant. Occasionally, the disease can be caused by pancreatic islet A cell proliferation. The tumor is distributed with the most pancreatic tail, followed by the pancreas and the pancreatic head.
Pathogenesis
Glucagon is secreted by islet A (2) cells and is a single-chain polypeptide consisting of 16 amino acids with a molecular weight of 3485. Glucagon is synthesized on the 2 cell core protein body and receives a coating from the Golgi apparatus to form 2. Granules, glucagon may have a larger molecular weight precursor when synthesized in 2 cells, called pre-glucagon, and islet 2 cells secrete glucagon about 1 mg per day. Recently, human plasma was measured by immunological methods. Glucagon is present in several different molecular sizes, about 55% is high molecular weight glucagon called glucagon, molecular weight is about 160,000 Da; 35% is "true" glucagon, molecular weight is 3500 Da The other, called glucagon, has a molecular weight of 9000 Da, which is only a small amount and may be a proglucagon precursor.
The normal level of glucagon in normal human plasma is 50-100pg/ml. In patients with glucagonoma, the basic level of plasma glucagon is often significantly increased, often above 1000pg/ml, in most patients. The increase in plasma glucagon levels comes from "true" glucagon, sometimes high molecular weight proglucagon (9000Da) is also increased, the pathophysiological basis of glucagonoma is excessive pancreas Glucagon catabolism; glucagon activates liver phosphorylase, promotes the breakdown of glycogen into glucose; it also promotes gluconeogenesis, hepatic glycogen cloning and hepatic glycogenolysis The effect is elevated blood sugar, glucose tolerance is reduced, fat decomposition is often antagonized by secondary increased insulin secretion without excessive ketone body formation, plasma free fatty acid levels are still in the normal range, but protein catabolism is often obvious For low amino acidemia and malnutrition, the occurrence of dermatitis is similar to the skin changes after long-term injection of exogenous pancreatic hyperglycemia. After removal of glucagonoma, dermatitis can heal without recurrence. This formation is associated with low amino acidemia after excessive catabolism of glucagon, and is also a cause of dermatitis. In addition, stomatitis, cheilitis, glossitis and anemia are also associated with hypoamino acidemia. Symptoms such as dermatitis, cheilitis, and cheilitis can be alleviated after application of various amino acid solutions.
According to Binnick (1977), 19 cases were detailed in 19 cases, 10 cases of pancreatic tail (47.6%), 5 cases of pancreatic body (23.8%), 2 cases of pancreatic body and tail, 1 case of pancreatic head and pancreatic neck, pancreas In 1 case of neck, about 60% of cases have metastasized. The most common part is liver, followed by lymph nodes, which are transferred to the spine and left adrenal gland. The cells under light microscope are polygonal or columnar, and their sizes are different. Nuclear fission is rare. The tumor cells are arranged in a nest or reticular structure. Some places are daisy-like or acinar-like. There are fibrous tissues between the cells. The malignant tissues are rich in blood vessels. Under the electron microscope, the characteristics of 2 cells are round. Dense secretory granules, but other cells contain different granules. Indirect fluorescent immunoassay can confirm that glucagon is contained in tumor cells, and immunofluorescence reaction of glucagon antibody can confirm the diagnosis. The most obvious skin lesions are under the microscope. The histological changes were necrotic and lysis of the upper layer of the epidermal hair layer, and resulted in bullous rupture. There was mild lymphocytic infiltration around the blood vessels in the epidermis. In the long-formed lesions, non-specific dermatitis-like changes were observed. Acanthosis There spongiosis, Clostridium keratinocytes with pyknotic nuclei, no acantholysis, immunofluorescence negative.
Prevention
Glucagonoma prevention
Life is regular. Pay attention to the combination of work and rest, maintain an optimistic, positive attitude towards life, and avoid alcohol and tobacco. There are no special effective preventive measures for this disease. Early detection and early diagnosis are the key to prevention and treatment of this disease.
Complication
Glucagonoma complications Complications anemia keratitis dystrophy dementia optic atrophy nystagmus acne ataxia
1. Weight loss, fatigue, glossitis and angular cheilitis, anemia is very common, and its mechanism is related to the consumption of tumors and the enhancement of glucagon catabolism and metabolism, which leads to malnutrition.
2. A small number of patients have a history of mental neurosis, such as dementia, optic atrophy, sputum eating, nystagmus, ataxia, and abnormal reflection.
Symptom
Glucagonoma Symptoms Common Symptoms Glucocorticoids Secreted Polysaccharide Urine Partial Leukamouric Acid Acidosis
The prominent symptoms are rash and diabetes. The rash has certain characteristics. It is called necrotic migratory erythema (NME). It is mainly regional erythema, but also desquamate red papules and plaques. The rash is often ring-shaped or curved. It can be a bullous, smashed and crusted. It is easily infected by bacteria and yeast, and there is necrotic and soluble bullous rash. When the initial lesion begins to heal, the pigment remains in the healing area. Sinking, the lesion can be displaced from one part to another, and the erythema can occur in all parts of the body, but the upper part of the trunk, lower abdomen, groin, buttocks, perineum, lower limbs and face are more common, while the upper limbs Less, the lesion needs to be cured for 1 to 2 weeks. The skin lesions in the same case may be erythema, bullae, scarring, normal, etc. The skin lesions are not easy to cure, and the tiny wounds or medical adhesives can be contacted with the skin. Causes skin lesions. Early cases are all diagnosed by dermatologists due to long-lasting skin lesions. The pathogenesis of glucagonoma skin lesions may be due to pancreas Increased secretion of glucagon, resulting in increased catabolism of nutrients, resulting in low amino acidemia, malnutrition through low amino acidemia, skin lesions or damage, or due to zinc deficiency, also known as glucagon Or the direct effect of certain substances secreted by the tumor on the skin, the skin lesions can completely disappear after the tumor is removed.
More than 95% of patients have symptoms of diabetes, non-insulin-dependent, and milder symptoms, often controlled by diet or oral medication; occasionally the condition is heavier and requires high-dose insulin injection to control, never seen Reports of patients with ketoacidosis are likely to offset the effects of glucagon because most patients are accompanied by elevated plasma insulin.
Weight loss, fatigue, glossitis and angular cheilitis, anemia and other symptoms are also common, the mechanism of which is related to tumor consumption and glucagon catabolism and nutrient enhancement, resulting in malnutrition, 50% of cases may have diarrhea It is also one of the reasons for weight loss.
1/5 to 1/3 of the cases occurred without clotting abnormal blood vessels, jaundice is rare, found in the head of the pancreas tumor compression of the common bile duct.
A small number of patients have a history of mental neurosis, such as dementia, optic atrophy, sputum eating, nystagmus, ataxia, abnormal reflexes, etc., the neurological symptoms are caused by extensive central nervous system dysfunction, and a large number of glucagons Related to the central nervous system.
Examine
Examination of glucagonoma
1. General laboratory tests: Low amino acidemia, positive urine glucose, elevated blood glucose or decreased glucose tolerance, increased erythrocyte sedimentation rate, positive hemoglobinemia in the positive cells, and tumor cells in the duodenal juice of the pancreatic head tumor.
2. Plasma glucagon radioimmunoassay
(1) The basic determination of glucagon is significantly increased, which can exceed 1000pg/ml, which is 5-10 times normal, and the normal value is 50-100pg/ml. The literature records the plasma glucagon in patients with glucagonoma. Up to 380 ~ 9600pg / ml, oral or intravenous glucose can not inhibit the secretion of glucagon.
(2) Plasma glucagon stimulation test: In cases where it is difficult to determine the diagnosis, pancreatic A cell secretagogues such as arginine and alanine may be used, and plasma glucagon is increased after injection, but this reaction is also Found in primary or secondary islet A cell proliferation, this test is not a specific diagnostic method for glucagonoma.
3. Tolbutamide (D860) test Normal intravenous injection of tolbutamide can stimulate insulin secretion and inhibit glucagon, lowering blood glucose. In patients with glucagonoma, intravenous injection of tolbutamide On the contrary, it can cause a significant increase in glucagon, insulin also slowly rises, but the blood glucose drop is not obvious or only slowly decline, this test suggests the possibility of glucagonoma.
4. Response to exogenous glucagon After intravenous injection of 0.25-0.5 mg of glucagon in normal humans, plasma insulin and blood glucose levels were significantly increased, but in patients with glucagonoma, due to long-term plasma endogenous Glucagon is increased, it is not sensitive to exogenous glucagon. Although intravenous glucagon, the reaction of plasma glucose concentration is still very slow, the slow response of this method can be useful for the diagnosis of glucagonoma. Method, but sensitive people can not rule out the disease.
5. Barium meal examination and duodenal hypotension angiography only help the diagnosis of islet cell tumor of the pancreas, which is reflected in the inner wall of the descending segment of the duodenum, but the disease occurs in the head of the pancreas. In some cases, the jejunum and the ileum are thick and wrinkled, and the reason is unclear.
6. Celiac artery and pancreatic artery angiography can diagnose more than 70% of islet cell tumors, but it is not clear which cells the tumor is from.
7. Liver and pancreatic ultrasound scan and CT scan can diagnose the primary lesion of the pancreas and whether the liver has metastatic lesions.
8. Tumor tissue electron microscopy observation of tumor cells in line with the characteristics of islet A cells; tumor tissue contains high concentrations of glucagon.
Diagnosis
Diagnosis and diagnosis of glucagonoma
diagnosis
According to clinical manifestations, typical specific skin lesions are very similar in all cases, diabetes, weight loss, tongue and angular cheilitis, diarrhea, etc., combined with laboratory and other ancillary examinations.
Differential diagnosis
Glucagonoma has skin damage and elevated plasma glucagon levels, so cases with skin lesions and increased glucagon levels should be identified:
Skin damage
(1) skin damage in patients with glucagonoma is necrotic and catabolic erythematous changes; should be associated with benign familial pemphigus, deciduous pemphigus, diffuse pustular psoriasis, toxic epidermal necrolysis and other diseases Identification.
(2) Patients with skin lesions and tumors at the same time should be differentiated from dermatomyositis, black acanthosis, and acquired ichthyosis.
2. The increase in plasma glucagon is significantly increased in islet A cell tumors, but mildly elevated in the following conditions and diseases: protein intake, starvation, insulin cessation, acidosis, uremia, infection, strenuous exercise , diabetes, cirrhosis, Cushing's syndrome, acromegaly, pheochromocytoma, acute pancreatitis and treatment with adrenal cortex should be identified.
