Islet cell hyperplasia

(1) Overuse of insulin or failure to reduce insulin promptly after improvement of the condition.

(2) Delayed eating or snacks due to reasons such as conferences, visits to places, late breakfast, and late work.

(3) Significant increase in activity without corresponding increase in snacks or reduction in insulin dose.

(4) Decreased food intake without timely reduction of insulin.

(5) Improper ratio of mixed insulin injection (PZI is 1-2 times more than RI) and large dose, often with more urine sugar during the day and hypoglycemia at night.

(6) Failure to eat on time or have a snack before the peak effect of insulin.

(7) When the mood changes from being very tense to relaxed and cheerful.

(8) After the onset of ketosis, the dose of insulin increases, while the amount of food intake decreases.

(9) Overuse of PZI.

(10) Medications that exacerbate hypoglycemia.

    Patients with islet cell hyperplasia mainly present with palpitations, fatigue, excessive sweating, hunger, hand tremors, convulsions, incontinence of urine and feces, and disturbance of consciousness, with coma in severe cases. The disease generally has no other complications.

　　1. Chief Complaint:

　　Patients mainly present with palpitations, fatigue, excessive sweating, hunger, hand tremors, convulsions, incontinence of urine and feces, and disturbance of consciousness, with coma in severe cases. The disease generally has no other complications.

　　2. Clinical manifestations:

　　1. Main manifestations

　　The onset of symptoms is often related to the rate of blood glucose decrease. When blood glucose decreases rapidly, it is usually manifested as sympathetic nervous system excitation, with symptoms such as palpitations, fatigue, hunger, pallor, cold sweat, and tremors of hands and feet. When blood glucose decreases slowly, it presents as a neuroglycopenic syndrome, characterized by inattention, dullness of thought and language, restlessness, dizziness, blurred vision, unsteady gait, and sometimes mania, abnormal sensation, and behavior. Severe hypoglycemia can lead to coma, disappearance of the pupillary light reflex, seizures, hemiplegia, and various pathological reflexes. When blood glucose decreases for a long time, both types of symptoms can appear sequentially.

　　Patients may present with typical Wipple triad: ①Spontaneous periodic episodes of hypoglycemic symptoms, coma, and mental and neurological symptoms, which occur during fasting or after exercise; ②Blood glucose level below 2.8 mmol/L during episodes; ③Symptoms can be immediately relieved after oral or intravenous glucose administration.

　　(1) Symptoms of sympathetic nervous system excitation are common, such as dizziness, headache, weakness, pale complexion, sweating, tachycardia, palpitations, and hunger.

　　(2) Psychiatric symptoms such as dizziness, amnesia, abnormal sensations, memory loss, disorientation, incontinence of urine and feces, drowsiness, visual impairment, confusion, mania, loss of consciousness, somnolence, and coma, etc.

　　(3) Neurological symptoms such as clonic convulsions, increased patellar reflexes, pathological reflexes, positive corticospinal tract signs, opisthotonos, hemiplegia, etc.

　　2, Secondary manifestations

　　Some patients may have symptoms such as vomiting, abdominal pain, diarrhea, and other gastrointestinal symptoms, and long-term hypoglycemia can also lead to fever.

    Islet cell hyperplasia seriously affects the patient's daily life, so it should be actively prevented. However, there is currently no effective preventive method for this disease, so early detection and early treatment are of great significance for the treatment of the disease.

　　First, primary examination

　　1, General laboratory examination

　　(1) Blood glucose measurement: Clinically, the blood glucose level is generally expressed by the concentration of venous plasma glucose. Blood glucose measurement is the most basic examination for diagnosing islet cell hyperplasia, and is usually measured during fasting or during an episode of hypoglycemia, with the best time for blood glucose measurement being during an episode of symptoms.

　　(2) Oral glucose tolerance test: The main value of this test lies in distinguishing various causes of hypoglycemia.

　　(3) Plasma insulin measurement: The concentration of fasting plasma immunoreactive insulin (IRI) in normal people is 5~10mU/L, rarely exceeding 30mU/L, and the concentration in plasma increases when islet cell hyperplasia occurs.

　　(4) C-peptide measurement and plasma proinsulin measurement: The insulin/proinsulin ratio in normal people

　　2, Provocation test

　　(1) Fasting and exercise test: The patient is fasting after dinner, and the blood glucose level is measured at 8 am the next morning. If there is no obvious hypoglycemia, continue to fast and closely observe, measuring blood glucose every 4 hours or when symptoms occur. If hypoglycemia still does not occur, perform 2 hours of exercise after fasting for 12, 24, 36, and 48 hours respectively to promote an attack. If there is no attack after fasting for 72 hours, the possibility of this disease is very small.

　　(2) Glucagon test: Intravenous injection of glucagon 1mg, 50% to 75% of insulinoma cases show a serum insulin level of more than 160mU/L within 5 minutes after injection, or an increase of more than 60, 40, and 20mU/L respectively at 30, 40, and 60 minutes after injection compared to before injection. At the same time, the blood glucose level does not increase significantly, and hypoglycemia often persists for a long time after the test.

　　(3) Leucine test: Intravenous injection of leucine at a dose of 200mg/kg within 30 minutes, if the blood glucose level decreases by more than 1.39mmol/L, the plasma insulin level increases by more than 30mU/L, or the plasma insulin levels increase by 20, 15, and 10mU/L at 30, 60, and 90 minutes respectively, it strongly suggests the diagnosis of insulinoma. About 80% of patients with this disease show an exaggerated response to leucine.

　　(4) D860 test: Intravenous injection of 1g D860 within 2 minutes, and then measure blood glucose and insulin every 15 minutes in the first hour, and every 30 minutes in the second and third hours. Plasma insulin should also be measured every 5 minutes in the first 15 minutes. The following three indicators suggest insulinoma: ① Plasma glucose decreases to below 65% of the baseline or less than 1.67 mmol/L; ② Blood glucose decreases to below 2.22 mmol/L and remains below this level for more than 3 hours (if hypoglycemia occurs, terminate this test); ③ Plasma insulin increases, increasing to 195 mU/L or persistently elevated within the first 15 minutes, increasing by 50 mU/L compared to the baseline at 30 minutes, increasing by 25 mU/L at 45 minutes, and increasing by 15 mU/L at 60 minutes.

　　2. Secondary Examinations

　　The pathological changes in islet cell hyperplasia in the histopathological examination are islet cell hyperplasia, showing islet cell hyperplasia under the microscope, and there are some islet cells that are hypertrophied, accompanied by mild lymphocytic infiltration. There is an irregular degenerative area in the center. Experienced pathologists can judge whether there is islet cell hyperplasia from this.

　　3. Matters to be noted in the examination

　　1. When the fasting or onset blood glucose level is below 3.33 mmol/L (60 mg/dl) and cannot be ruled out clinically, the fasting blood glucose level should be measured for more than 5 consecutive days. If the blood glucose level is below 2.22 mmol/L (40 mg/dl) multiple times, the possibility of diagnosis is relatively high.

　　2. Since insulin secretion is often cyclical and pulsatile, the peak and minimum values in peripheral blood can differ by 5 times, so a single plasma insulin measurement may not show an increase; in addition, individuals with obesity, acromegaly, Cushing's syndrome, late pregnancy, and those taking oral contraceptives can also have hyperinsulinemia. Therefore, islet cell hyperplasia cannot be diagnosed solely based on plasma insulin measurements.

　　3. In pediatric cases, the leucine test cannot differentiate between islet cell hyperplasia and insulinoma. Normal individuals who have mistakenly taken sulfonylurea drugs can also have a positive leucine test.

　　4. The following points should be noted for the D860 test: ① The fasting blood glucose level of the patient

　　5. When all imaging examinations show no abnormalities, the possibility of islet cell hyperplasia should be considered.

     The diet of islet cell hyperplasia patients should be light and easy to digest, with an emphasis on eating more vegetables and fruits, and a reasonable diet should be maintained. In addition, patients should also pay attention to avoiding spicy, greasy, and cold foods.

　　1. Treatment Principles

　　Islet cell hyperplasia is primarily treated with surgery, with medical treatment as an adjunct.

　　2. Specific Treatment Methods

　　To alleviate symptoms, consume more carbohydrates, increase the frequency and quantity of meals, and take glucose orally or intravenously before the expected onset time. The clinical treatment methods for islet cell hyperplasia include surgery and medication.

　　1. Once a functional diagnosis is made, surgery should be performed as soon as possible. Delayed surgery may result in permanent central nervous system damage due to long-term hypoglycemia, or obesity due to excessive eating, which may increase the difficulty of future surgery.

　　(1) Relative indications: Patients with frequent attacks and severe symptoms that meet the above diagnostic criteria, without a cause of spontaneous hypoglycemia outside the pancreas, should undergo surgical treatment.

　　(2) Contraindications: non-functional benign hyperplasia, patients who cannot tolerate surgery.

　　(3) Surgical methods: include subtotal or distal pancreatectomy, local resection of the pancreas at the site, and pancreaticoduodenectomy. In cases of islet hyperplasia, subtotal or distal pancreatectomy can be performed, but the spleen should be preserved as much as possible.

　　Acute pancreatitis after surgery is mainly caused by surgical trauma, especially damage to larger pancreatic ducts or blood vessels that cause pancreatitis. Pancreatic fistula is a common complication after insulinoma resection, with an incidence rate of about 14.5%, mainly due to the extensive incision of pancreatic tissue or damage to the pancreatic duct.

　　2. Drug treatment mainly acts by reducing insulin secretion and peripheral glucose utilization.

　　(1) Indications: ① Alleviate hypoglycemia symptoms; ② As preoperative preparation; ③ Refuse surgical treatment or have contraindications to surgery.

　　(2) Specific medication selection:

　　Diazoxide: a derivative of thiazide diuretics. The therapeutic dose for adults is determined according to individual responsiveness, ranging from 25-200mg, two to three times a day, taken orally. The pediatric dose is 12mg/kg per day. The common dose of diazoxide is 300-400mg/d, sometimes up to 1000mg/d, with 2-8mg/d of dichlorothiazide taken orally. This drug is often used as preoperative medication and stopped 2 days after surgery. The drug can cause edema and sodium retention, gastrointestinal discomfort, and hirsutism, so it is often used with the diuretic trichlormethiazide, not only to prevent edema but also to enhance the inhibitory effect of diazoxide on B cells.

　　Octreotide: a somatostatin analog that can inhibit insulin secretion. Generally, 50-150μg per dose, three times a day, subcutaneous injection, with a maximum dose of 450μg per dose, three times a day. However, these drugs can only be used for a short period of time.

　　Third, treatment precautions

　　The most ideal treatment method is to surgically remove the focus. Rebound hyperglycemia is a sign of surgical success. Octreotide often inhibits insulin secretion and can be used for acute phase treatment. Since octreotide also inhibits the secretion of glucagon and growth hormone, it may worsen hypoglycemia. Chemotherapy drugs have significant adverse reactions when used in high doses and should not be used for a long time.