Insulinoma

Introduction to insulinoma Insulinoma (lusulinoma) is an islet B cell tumor, also known as endogenous hyperinsulinemia, which is a common cause of organic hypoglycemia, accounting for 70-75% of islet cell tumors. Most are benign, malignant accounted for 10 to 16%, insulinoma can occur at any age, but more common in young and middle-aged, about 74.6% of patients occurred in 20 to 59 years old, more men than women, the ratio of men to women is 1.4 to 2.1. basic knowledge The proportion of illness: 0.02% Susceptible people: no special people Mode of infection: non-infectious Complications: pituitary tumors headaches coma

Insulinoma etiology

Insulin capacity decreased (30%):

The main defect of insulinoma is storage. Insulin cells can synthesize insulin and can also respond to various stimuli, but partially or completely lose the ability to store insulin. Under normal physiological conditions, the maintenance of normal blood glucose concentration mainly depends on insulin. And the regulation of glucagon secretion, blood sugar level is an important factor in controlling insulin release. When blood glucose concentration drops, it can directly promote the secretion of glucagon, inhibit the secretion of insulin, when the blood sugar drops to 1.96mmol / L (35mg% When insulin secretion is almost completely stopped, this normal physiological feedback phenomenon is lost in patients with insulinoma, so that insulin continues to escape from islet cells and inhibits glycogen decomposition beyond blood glucose levels. The requirement to cause hypoglycemia syndrome.

Hypoglycemia (40%):

After hypoglycemia occurs, the body should maintain blood sugar levels, compensatory acceleration of adrenaline secretion, increase phosphorylase activity, and promote the conversion of glycogen to glucose, so the blood and urine adrenaline content of patients can be increased, in low blood sugar Early and comatose clinical manifestations of accelerated pulse, increased blood pressure, sympathetic sweating and other sympathetic nerves. Therefore, the main metabolic change of insulinoma is hypoglycemia, which forms a central nervous disorder and even coma and sympathy due to hypoglycemia. The clinical sign of the adrenal gland system is excited.

Pathological change

Insulinoma can occur in any part of the pancreas. The incidence of pancreatic head, body and tail is basically the same. It occurs in the tail of the pancreas. The pancreatic head and the uncinate part are not easy to find. The tumor volume is generally small, and the tumor diameter is small. Generally between 0.5 and 5 cm, but more than 80% of tumors are less than 2 cm in diameter, which makes it difficult to locate the diagnosis. Most of them are spherical. Most of the tumors have clear boundaries but no obvious envelope. Some tumors have envelopes or The pseudo-envelope is softer than normal tissue and rich in blood supply. The living tumor seen in the operation is reddish brown or blue-violet, and the postoperative tumor section is dark red or reddish. The insulinoma is in various islet cell tumors. The most common type, about 50% of the tumors are simple -cell tumors, but some are mixed tumors containing -, -, PP and G cells. The -cell proliferation is diffuse and nodular. Species, sometimes associated with small adenomas, it is difficult to identify specific types of tumor cells, whether by light or electron microscopy. Insulinoma is composed of tumor cells, connective tissue and amyloid deposits between tumor cells and capillaries. Light mirror Now the volume of the local islets is increased or increased. The tumor cells under the microscope are quite similar to the normal -cells. It can be seen that the tumor cells are arranged in a cord-like or agglomerate shape, which are islet B cells of different sizes, and the cytoplasm is light. Dyeing, containing particles, polygonal, cuboidal or columnar, the nucleus is round or oval, nuclear fission is rare, there are abundant functional organelles in the tumor cells under electron microscope, mitochondria in the cytoplasm is abundant, and tumors in some tumors The cells also contain typical -cell secretory granules, but since not all insulinoma cells contain secretory granules inside, and other types of islet cells can also have high-density secretory granules, it is still difficult to judge tumors under electron microscope. The specific type of cell.

Insulinoma prevention

There is no effective preventive measure for this disease. Early detection and early diagnosis are the key to the prevention and treatment of this disease. Hypoglycemia is the basic cause of various clinical manifestations. Hypoglycemia or hypoglycemia coma is caused by an increase in blood insulin concentration, more than early morning, fasting, fatigue, and emotional stress, early every few days, weeks Or it occurs once in a few months. Therefore, we must actively prevent the occurrence of hypoglycemia.

Insulinoma complications Complications pituitary tumor headache coma

When patients have multiple endocrine adenomas (insulin-dependent type), they can coexist with pituitary tumors, thyroid tumors, adrenal adenomas and hyperparathyroidism. In addition to symptoms of hypoglycemia, there are headaches, bone pain, polyuria, etc. symptom.

1. Hypoglycemia: Insulinoma can develop paroxysmal hypoglycemia or hypoglycemia coma, manifested as: cold sweat, palpitations, shaking hands and feet, thirst, tachycardia and so on.

2. In some cases, chronic hypoglycemia occurs. Patients often have unconscious personality changes, memory loss, loss of reason, unstable gait, unclear vision, arrogance, hallucinations, abnormal behavior, and even misdiagnosis as mental illness.

Symptoms of insulinoma Common symptoms Skin pale diarrhea gait instability trembling hypoglycemia convulsion liver enlargement coma tachycardia tachycardia

The typical clinical manifestation of insulinoma is the Whipple "triple syndrome" or insulinoma triad, namely:

1. Paroxysmal hypoglycemia or coma, often occurring when hunger or fatigue.

2. Blood glucose is less than 2.8mmol/L (50mg%) in acute attacks.

3. After oral or intravenous glucose, the symptoms are relieved.

Hypoglycemia is the basic cause of various clinical manifestations. Hypoglycemia or hypoglycemia coma is caused by increased blood insulin concentration, more than early morning, fasting, after exertion and emotional stress, early every few days, weeks Or a few months of seizures, the seizures are frequent and prolonged when the blood sugar drops rapidly. When the blood sugar drops rapidly, the body compensatory mechanism promotes the glycogen decomposition and increases the adrenaline secretion. Therefore, the symptoms of sympathetic overexcitability appear: weakness, weakness, cold sweat , heart palpitations, shaking hands and feet, pale skin, thirst, tachycardia, hunger, nausea, vomiting, etc. When blood sugar continues to decline, the body loses compensatory response, brain cells are insufficiently supplied with sugar, generally involving the cerebral cortex Neuropsychiatric symptoms, accompanied by mental disorders, blindness of consciousness, convulsions, facial twitching, angular arch reversal, foaming at the mouth, closed jaws, incontinence, unresponsiveness, disorientation, blurred vision, diplopia or Vision, transient hemiplegia, positive pyramidal tract sign, reflex disappearance, coma, etc., light can be expressed as straight eyes, dementia, slow response In severe cases, there may be arrogance, gibberish, disfigurement, even auditory hallucinations, hallucinations and delusions, and then mental disorders, which in turn involve the diencephalon, the midbrain, the pons and the cerebral meditation, the midbrain, the pons and the cerebral infarction. When there is a coma, if multiple episodes of hypoglycemia can cause degenerative changes in the brain, chronic symptoms such as mania, depression, dementia, muscle contraction, etc.

In some cases, chronic hypoglycemia is characterized by atypical symptoms. Patients often have unconscious personality changes, memory loss, loss of reason, unstable gait, unclear vision, sometimes arrogance, hallucinations, and abnormal behavior, which are misdiagnosed. For mental illness, rare peripheral neuropathy and progressive muscle atrophy; some to avoid hunger or relieve symptoms, and frequent eating, so "obesity" can occur.

Patients with insulinoma have a long course of disease, slow progress, mild symptoms at the initial onset, and short time, 1 or 2 times a year. It seems to be accidental. After the onset of daily frequency, the symptoms are heavy, even several times a day, such as long-term cerebral hypoglycemia. Seizures can cause irreversible damage to the nervous system, causing the patient to be mentally retarded during remission, behavioral abnormalities, dementia, and loss of labor.

Some cases with Zollinger-Ellison syndrome, about 10% of patients with peptic ulcer, but it must be pointed out that any kind of hypoglycemia can have a variety of symptoms, many patients to prevent hypoglycemia The seizure and more diet, eventually caused by excessive intake of calories, cancer patients, rapid progression of the disease, liver enlargement, hard, thin, abdominal pain, diarrhea and other symptoms of severe hypoglycemia.

Insulin tumor examination

1. Blood glucose measurement: When the clinical symptoms occur, blood glucose is measured. If the blood glucose is lower than 40mg/dl, it can be used as an important diagnostic basis, but blood is drawn at a later time, sometimes due to fluid regulation and compensation. Can not reflect a serious hypoglycemia state.

2. Qualitative diagnosis

(1) Hunger test: The method is simple and easy, the positive rate can reach 80%95%, the clinical symptoms are not typical, and the fasting blood glucose>2.8mmol/L (50mg/dl) can be used for this test, generally in fasting 12 After ~18h (except water) can induce hypoglycemia episodes; fasting 24h positive rate is 85%; fasting 48h positive rate is more than 95%, fasting 72 hours is 98%, increase exercise-induced hypoglycemia, especially blood sugar level Decreased, and plasma insulin levels do not decline, have diagnostic significance, such as those who have not induced hypoglycemia after 72h fasting, may be excluded from the disease, this test must be carried out under close observation, and prepared rescue measures to prevent accidents, Continuously three times of examination, fasting blood glucose 2.8mmol / L (50mg%) or less, can be diagnosed as insulinoma, mild patients, fasting can be extended to 24 ~ 48h or more, patients with hypoglycemic coma, convulsions, may be Increase the damage of brain nerve cells, so in patients with typical symptoms, it is not appropriate to do this stimulation test, in the course of the examination, once the symptoms appear, you should immediately intravenously inject 50% glucose solution to relieve the symptoms.

Blood glucose, insulin and C-peptide levels are measured once every 4 to 6 hours. If the episode of hypoglycemia is severe, the blood glucose 2.5mmol/L (45mg/dl) should be terminated immediately and intravenously injected with 50% glucose 60-80ml. Especially with liver disease and pituitary-adrenal dysfunction can also induce severe hypoglycemia, must be vigilant.

(2) Oral glucose tolerance test (OGTT): multiple determination of fasting blood glucose, and <2.8mmol / L (50mg / d), it has important diagnostic value for insulinoma, after oral glucose 100g, blood sugar rise is not high, no more than 5.6mmol / L (100mg%), or rose to a high level and rapidly decreased to a low level of 2 ~ 3h and maintained for 5 ~ 7h, due to the independent secretion of insulin, no reactivity after glucose load, so the plasma insulin concentration can be Normal, increased or decreased, different from normal reactivity, it is generally considered that early hypoglycemia 1h after taking sugar, or hypoglycemia 2~3h and always showed a low level curve, this is because insulin secretion is increased, making blood sugar rapid When transformed and utilized, insulinoma or islet tissue hyperplasia, with autonomous secretion, may be more frequent, sometimes less, even temporarily stop secretion, so that the inhibition of normal -cell function has not recovered, at this time may appear diabetes curve, necessary When the needle was placed in the vein, the blood sample was taken once for 30 minutes for 5 hours. It is considered that the oral glucose tolerance test has little value for the diagnosis of this disease.

(3) Determination of insulin and proinsulin: In addition to fasting and onset of blood glucose below 2.2mmol / L (40mg / dl), the following tests can be used:

1 Determination of plasma insulin during fasting episodes: normal human fasting venous plasma insulin concentration, generally in the range of 5 ~ 20mU / L, rarely more than 30mU / L, but this disease often has autonomous secretion of hyperinsulinemia, when the patient About 80% of patients in the morning after 12~14 hours of fasting may have hypoglycemia with relatively high plasma high insulin levels. For patients with both hypoglycemia and hyperinsulinemia, plasma C-peptide determination can help distinguish Anthropogenic iatrogenic hypoglycemia caused by insulin-derived insulin, 95% of patients with insulinoma have a C-peptide level of 300pmol/L. However, hypoglycemia cannot be ruled out by C-peptide due to sulfonylurea-induced drugs. Detection is necessary, but obesity, acromegaly, hypercortisolism, late pregnancy, oral contraceptives can cause hyperinsulinemia, pancreatic islet -cell hypoglycemia, most proinsulin levels are elevated In particular, in patients with hypoglycemia, when measuring the inconsistency between insulin and C-peptide data, it is necessary to determine proinsulin, and it is diagnosed for the identification of hypoglycemia caused by endogenous insulin and exogenous insulin. The value, but not only the increase in proinsulin, but the diagnosis of hypoglycemia, C peptide and insulin secretion, and C peptide is antigenic, so the use of radioimmunoassay C peptide can reflect the secretion function of islet cells, When insulinoma or islet B cells proliferate, serum and urinary C-peptide increase. Since exogenous insulin does not contain C-peptide, it does not interfere with C-peptide determination. Therefore, in patients with diabetes treated with insulin, such as insulinoma at the same time, this test has very Great value.

2 insulin release test: tolbutamide (D860) test can stimulate the islet release of insulin, producing a significant hypoglycemia lasting 3 ~ 5h, normal people on the fasting intravenous injection of 1g of D860 (or 20 ~ 25mg / kg dissolved in saline Intravenous injection of 20ml caused a transient increase in plasma insulin to 60-130u/ml at 5min, and gradually decreased blood glucose after 20-30min, and returned to normal after 1.5~2h, while the insulinoma patient responded 5~15 minutes after injection. Strengthened, and after 2 to 3 hours, hypoglycemia still does not recover. After the tumor is resected, the abnormal reaction disappears to determine the function state of islet cells. Since the insulin secretion of insulin can be intermittent, suspicious patients need to be re-examined regularly. The glucose tolerance curve for patients with various diseases can vary significantly.

A. The specific methods are as follows:

a. Intravenous method: 25g glucose intravenous glucose tolerance test can be used. If the curve shows that the insulin level exceeds 150mU/L at one point in each time point, it also supports the diagnosis of this disease. Intravenous injection D860 1g, every injection 2, 5, 10, 30, 60min blood draw, acute hypoglycemia reaction in patients with insulinoma, often within 30 to 60 minutes after injection, blood glucose dropped below 1.6mmol / L, hypoglycemia can last more than 180min, normal people no In the spontaneous hypoglycemia reaction, plasma IRI was significantly increased.

b. Oral method: glucose tolerance test can be performed after oral administration of 75g glucose. Blood glucose level is taken at the same time to measure insulin level. The glucose tolerance curve of this disease is mostly low, but the insulin curve is relatively high, such as each time point. One of the peaks above 150mU/L is helpful for the diagnosis of this disease. After blood tests for blood glucose in the morning, oral D860 2g, followed by blood every 1/2h, insulinoma patients often appear within 3 to 4 hours. Significant hypoglycemia, and blood glucose showed a low blood sugar curve after taking the drug, the degree of hypoglycemia is obvious, and the duration is not easy to recover, and hypoglycemia coma can also be induced.

B.D860 test should pay attention to the following points:

a. The patient's fasting blood glucose <2.7mmol / L, should not be tested.

b. In the trial, the test is stopped as soon as the loss of consciousness or symptoms of hypoglycemia occurs, and the glucose is administered orally or intravenously.

c. The D860 test is more dangerous. After the injection of D860, the saline solution is connected to keep the infusion smooth. In the event of hypoglycemia, glucose or glycoside can be injected in time.

3. L- leucine test : After oral administration of L-leucine 2% solution 150 mg/kg for about half an hour, the patient's blood glucose dropped to less than 60% of the fasting blood glucose level, and then gradually rose again, and the plasma insulin content increased. No blood sugar decreased after taking the service, the positive rate was 50% to 60%.

4. Glucagon test : intravenous glucagon 1mg (injection within 2min), followed by determination of plasma insulin and blood glucose levels within 30min, blood glucose can be increased rapidly, while plasma insulin concentration can be decreased, but glucagon injection After 1 to 1.5 hours, blood glucose decreased to normal. After 2 hours, hypoglycemia showed 2.52 mmol/L to 2.8 mmol/L (45 mg% to 50 mg%), and insulin content increased. If blood glucose was lower than 2.52 mmol/L (45 mg%), Plasma insulin is greater than 100u/ml, the diagnosis can be confirmed, the positive rate of this test can reach 80%, so this test has diagnostic value for insulinoma caused by insulin. This test is safer than metobutamide, and the accuracy is greater. Normal people have no hypoglycemia.

5. Calcium challenge test: intravenous calcium gluconate 5mg/kg·h for 2h, blood glucose gradually decreased after 15~30 minutes of input, plasma insulin content increased, no significant change in normal or functional hypoglycemia patients. .

6. The ratio of plasma proinsulin (or pre-insulin) to insulin : when B cells secrete insulin, which contains insulin, C-peptide and proinsulin, the ratio of normal plasma proinsulin to insulin does not exceed 25%, in patients with insulinoma The plasma proinsulin content increased almost without exception, and some can be as high as 10 times or more (normal value is less than 0.25 ng/ml). The ratio of proinsulin to insulin is increased, and it is more obvious when there is malignant transformation.

7. Plasma IRI measurement and IRI/G ratio: normal human fasting plasma immune response insulin (IRI) concentration is less than 24u / ml, insulin tumor patients moderately elevated blood concentration, but due to insulin secretion is often periodic, peripheral blood The peak value and the lowest value can differ by a factor of five. In addition, hyperglycemia can occur in obese people, acromegaly, Cushing syndrome, and late pregnancy. Therefore, insulinoma cannot be diagnosed based on IRI alone, and the ratio of IRI to glucose concentration is calculated. IRI/G) has a greater diagnostic value. The normal IRI/G value is less than 0.3. 95% of patients with insulinoma have a fasting 24h IRI/G>0.3. If they are fasted to 72h, all cases are positive, Tarrer et al. Corrected IRI/G" calculation method: IRI × 100/G-3, the normal person's morning fasting time ratio <50, such as correction IRI / G> 50, almost certainly the diagnosis of insulinoma.

8. Inhibition test : Creutzfeldt et al. used a computer-controlled glucose infusion system to determine the amount of glucose required to maintain a blood glucose level of 4.5 mmol/L. The normal person is about 25 mg/min, and the value of insulinoma patients is greatly increased. In the second stage, the instillation system is maintained, and the injection of insulin inhibiting somatostatin (SRIH) and diazoxide is performed, and the glucose infusion required to maintain blood glucose of 4.5 mmoL/L is calculated. In normal people, this value is significantly lower than that of the control when the insulin secretion is reduced. However, the insulinoma has a certain resistance to the inhibition of the two drugs, so the value is unchanged or only slightly decreased, and the malignant insulinoma is more normal. The drug that inhibits insulin secretion is not reactive, so this test can not only be used as a diagnostic test for insulinoma, but also to judge benign or malignant insulinoma before surgery, and can help to judge whether the clinical treatment with SRIH is effective or not.

9. Medical imaging diagnosis : Before the localization diagnosis, it should be further confirmed after repeated evaluation of biochemical diagnosis.

(1) Selective angiography: Selective functional angiography is helpful for localization, but this method has vascular injury and lack of sensitivity to abdominal angiography. The gastroduodenal, superior mesenteric artery, splenic artery and dorsal pancreatic artery can be performed separately. Intubation angiography, observing the capillary capillaries of the tumor, because the tumor is rich in blood vessels, the contrast agent can show smaller tumors, the positive expression is tumor filling and staining, the blood vessel distortion is increased, the positive rate is 20% to 80% (average 63%) If this method and the splenic portal vein blood sampling to determine the insulin value, can improve the accuracy of intraoperative tumor localization.

(2) B-mode ultrasonography: Although B-ultrasound is safe, but due to the small size of the tumor, the positioning is less than 50%. In the surgical exploration, intraoperative ultrasound can be used for further diagnosis. Aligning the pancreas can better distinguish tumors from normal tissues. The lesions are circular or elliptical solid dark areas on the sonogram. The boundary is clear and smooth, and the boundary between normal and pancreatic tissues is clear. When the malignant insulinoma is present, the tumor volume is better. Large, often bleeding, necrosis, and local infiltration, but only according to its ultrasound image performance is difficult to distinguish from pancreatic cancer, B-sensitivity to insulinoma is about 30%, the general tumor is less than 1.5cm diameter when B-ultrasound Hard to find.

(3) CT examination: for insulin tumors larger than 2cm in diameter, the detection rate of CT can reach more than 60%. For tumors with diameter less than 2cm, although the CT positioning ability is slightly stronger than that of B-ultrasound, its sensitivity is still only 7 %~25%; the level of sensitivity is related to the type of machine and the examination method. Scanning must be performed when examining insulinoma with CT, and enhanced dynamic scanning should be used as much as possible. Only in this way can some small insulin tumors be obvious. Intensive and detected, although the detection rate of CT is not high, but because it is a non-invasive examination, and can detect multiple lesions and liver metastasis at the same time, it is one of the most commonly used methods for preoperative positioning of insulinoma. CT scan can improve the display rate of insulinoma. Because insulinoma is a multi-transplant tumor, when a iodinating agent is applied, a bright region can appear in normal pancreatic tissue, and the positive rate is about 40%.

(4) MRI: The current clinical comparison shows that the ability of MRI to locate insulinoma is not as good as that of CT, and its sensitivity is 20% to 50%. The detection rate of liver metastasis is not as good as CT, so MRI is generally not used. Preoperative positioning examination.

2. Selective percutaneous hepatic vein blood sampling Selective percutaneous hepatic vein blood sampling combined with plasma insulin determination, through the insulin gradient changes to clear the pancreatic head, body, tail local hyperinsulinemia has been clinically applied, 1 must Experience in the selection of venous catheterization surgery, 2 postoperative intra-abdominal hemorrhage, infection, high incidence of bile leakage, 3 pairs of some uncommon cases, such as multiple adenoma with hyperplasia, this method can not be accurately located in the spleen When sampling the portal vein system, because the blood flow rate is fast, the blood sample is diluted, resulting in a negative result of low plasma insulin. 4 The drug that inhibits insulin secretion is stopped for at least 24 hours before sampling, so that the patient can relapse with hypoglycemia.

3. Endoscopic ultrasonography: This technique can be the best imaging technique before surgery, which can diagnose approximately 95% of pancreatic islet cell tumors, but it requires a fairly skilled operating technician. Pancreatic radionuclide scanning, endoscopic retrograde cholangiopancreatography, digital subtraction and other techniques are helpful in the diagnosis of this tumor.

4. Recently, the 8 peptide labeled with 125I-tyrosine complex was used as a scanning drug to locate islet cell tumors and their metastases, and it was found to have a special somatostatin receptor. This method may locate the tumor before surgery. helpful.

Diagnostic diagnosis of insulinoma

diagnosis

The doctor can diagnose the patient based on the patient's history of the disease, reference to clinical symptoms, and laboratory findings.

Differential diagnosis

Patients with insulinoma must be identified with other diseases that cause fasting hypoglycemia. This disease is often misdiagnosed as epilepsy, cerebrovascular accident, rickets, schizophrenia, orthostatic hypotension, meningitis, encephalitis, brain tumor and diabetic acidosis, hyperosmolar coma, hepatic encephalopathy, hypopituitarism, Addison disease, hypothyroidism, autoimmune hypoglycemia, drug-induced hypoglycemia, non-insulinoma hypoglycemia, etc. The glucose tolerance curve of patients with various diseases can be significantly different, and the corresponding glucose tolerance test should be carried out, and several common hypoglycemia identification points should be identified to observe the curve shape and hypoglycemia caused by various causes. Differential diagnosis provides a reference.

1. Functional hypoglycemia, also known as neurogenic hypoglycemia, is mainly seen in some people with autonomic dysfunction or anxiety, and is a common type of hypoglycemia. High-glucose diets are more likely to cause hypoglycemia. Berglund (1922) first found that after 2.5 to 4.5 hours of eating a large amount of glucose (or sucrose), arteriovenous blood glucose was lower than fasting blood glucose, and each episode lasted 15 to 20 minutes or longer. Afterwards, it can recover on its own. This type of functional hypoglycemia has a long history, mild symptoms, and little loss of consciousness. The blood sugar is rarely lower than 2.2mmol/L. In addition, the blood sugar level is often inconsistent with the symptoms, sometimes the blood sugar level is low but asymptomatic. .

2. Insufficient hormone secretion for hyperglycemia

(1) hypothyroidism, due to decreased thyroxine secretion, sugar absorption in the intestinal tract is slow, glycogen decomposition is also weakened, and adrenal cortical function can be slightly lower, fasting blood glucose can be as low as 3.3mmol / L, but low blood sugar The state is not serious, the disease is mainly caused by general malaise, cold, yellow and dry skin, edema, hair loss, unresponsiveness, constipation, menstrual cycle disorder in female patients, anemia, etc., which is the performance of various hypothyroidism.

(2) Chronic adrenal insufficiency, about half of which may have hypoglycemia symptoms, mostly in fasting, morning or pre-feeding, sometimes reactive hypoglycemia 1 to 2 hours after a meal, because the patient is sensitive to insulin, blood sugar is easy to decline, at the same time Significant symptoms can occur with a blood glucose level of about 3.3 mmol/L. However, the disease has a special pigmentation, as well as fatigue, weight loss and hypotension.

(3) anterior pituitary dysfunction, some cases may have paroxysmal hypoglycemia; secondary adrenal insufficiency and hypothyroidism, decreased growth hormone. The clinical features are hypothyroidism, adrenal insufficiency and hypogonadism.

3. Hypoglycemia with hyperinsulinemia except

(1) Early stage of diabetes: Some patients with early diabetes may have elevated blood glucose and diabetes, and the clinical manifestations of mild spontaneous hypoglycemia often 3 to 5 hours after eating are due to the delayed delayed response of B cells to glucose-stimulated insulin secretion. When the insulin is released in a large amount after eating, the absorption of sugar in the intestinal lumen is nearing completion. However, this disease is feasible to determine the glucose tolerance test.

(2) giant tumors or malignant tumors other than islets: generally refers to large tumors in the thoracic and abdominal cavity. Laurante counts 222 cases of hypoglycemia produced by extra-pancreatic tumors, and its distribution is stromal tumors (more common is fibroma, fibrosarcoma). Located in the retroperitoneum and mediastinum accounted for 45%, liver cancer accounted for 23%, adrenal cancer 10%, gastrointestinal cancer 3%, lymphoma 6%, other (ovary, lung, kidney) accounted for 8%; hypoglycemia caused by tumor Insulin-like substances, or hypoglycemia caused by excessive consumption of glucose by large tumors, and tumors are calculated in kilograms. Therefore, it is not difficult to find the lesions in clinical attention. If necessary, it can be confirmed by special examination such as X-ray.

(3) In chronic liver disease and cirrhosis, the function of regulating blood glucose concentration in the liver is insufficient, and in addition to insufficient insulin insufficiency, resulting in fasting hypoglycemia, plasma IRI is normal or increased. However, only in the case of diffuse hepatocyte damage and severe hepatic insufficiency, in addition to postprandial hyperglycemia, the reduction of glucose tolerance, is also the most basic metabolic disorder of cirrhosis, so identification is not difficult. In the case of glycogen deposition, hypoglycemia can also be caused by defects in glycogenolytic enzymes, which is more common in children, and there is a significant swelling of the liver and spleen in the clinic.

(4) central nervous system lesions, encephalitis, subarachnoid hemorrhage, and diencephalic lesions can also cause hypoglycemia, need to pay attention to identification.

(5) blood sugar lowering drugs and drinking: exogenous insulin and other hypoglycemic drugs such as D860, phenformin (hypoglycemia), salicylate can reduce blood sugar. Drinking a lot of alcohol, alcohol metabolism needs to consume coenzyme NADP, causing gluconeogenesis disorders, and metabolism to produce lactic acid, causing lactic acidosis, so that insulin action is enhanced, hypoglycemia occurs.

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