Excessive secretion of catecholamines
Introduction
Introduction Pheochromocytoma can be called catecholamine. Pheochromocytoma originates from the pheochromic tissue of the adrenal medulla, sympathetic ganglia, paraganglia or other sites. Because of the paroxysmal or persistent secretion of a large amount of norepinephrine and adrenaline, tumor cells are clinically present with paroxysmal or persistent hypertension, headache, sweating, palpitations and metabolic disorders. If you can get early treatment, you can cure.
Cause
Cause
The pheochromocytoma is located in the adrenal gland, which accounts for 80% to 90%, and is mostly one-sided. The extra-adrenal tumors are mainly located in the extraperitoneal and abdominal aorta (10% to 15%), and a few are located in the renal and hepatic hilum. , special parts such as the bladder and rectum. Multi-benign, malignant accounted for 10%. As with most tumors, the etiology of sporadic pheochromocytoma remains unclear. Familial pheochromocytoma is genetically related. It has been reported that pheochromocytoma in multiple endocrine neoplasia (MEN-2A, MEN-2B) has a short arm of chromosome 1 and it has been found that both of them have a chromosome 10 REI proto-oncogene. A germ-line mutation, MEN2A exhibits a mutation in exon RET10, which encodes a cysteine residue in the extracellular protein ligand binding region, thereby affecting the tyrosine kinase receptor on the cell surface. MEN-2B has a mutation in chromosome 8 RETB proto-oncogene that affects the tyrosine kinase catalytic site of the protein-binding region in the cell. Tyrosine kinases are involved in the regulation of cell growth and variation. This leads to the onset of susceptible populations.
Phenotype cytoma in von Hippel-Lindau syndrome, gene damage exists in the VHL gene (also known as tumor suppressor gene) of 3p25~26, mutations are diverse, and three exons (exons 1, 2, 3) Mutations can occur as nonsense mutations, missense mutations, frameshift mutations or deletion mutations, and pheochromocytoma is associated with missense mutations. When a gene is mutated, cell growth is out of control and a tumor is formed. The VHL gene germ cell line mutation determines the tumor susceptibility and disease status of the VHL family, and the VHL gene somatic cell line mutation is related to the malignant tendency of the tumor. In multiple neurofibromas (types I and II), pheochromocytoma is only associated with type I, and its basic genetic damage is an inactivating mutation of the RF1 gene of chromosome 17. This gene is also a tumor suppressor gene, which, when lost, can lead to the development of pheochromocytoma and other tumors.
Examine
an examination
Related inspection
Urinary catecholamine challenge test monoamine oxidase
Pheochromocytoma accounts for about 0.5 to 1% of the cause of hypertension. More than 90% of patients can be cured by surgery. Because this disease has the risk of causing an emergency accident, and some of them are malignant pheochromocytoma, it should be diagnosed early. However, because patients often have intermittent episodes, it brings certain difficulties to some experiments and examinations. Therefore, the selection of examination methods should be considered comprehensively.
Laboratory examination
General laboratory tests are not specific. The sugar tolerance decreased, the basal metabolism increased, and the blood scorpion protein combined with iodine politicians had reference significance. Determination of blood, urine catecholamines, and metabolites is usually performed as a specific test.
Adrenaline and norepinephrine are first degraded to metanephrine in the metabolic process and eventually degraded to 3-methylamino 4-hydroxymandelic acid (VMA). Therefore, urine meta-adrenalin and VMA will be measured in the laboratory as a diagnostic indicator of functional pheochromocytoma. However, the adrenal glands and VMA can be affected by certain drugs, such as monoamine oxidase inhibitors, chlorpromazine, lithium preparations, and foods such as coffee, bananas, etc., which affect the results. Urine mourning is the completeness of stagnation and whether it is in the attack period, which can affect the measurement results. These factors should be given enough attention.
Urinary catecholamine determination is more sensitive and reliable, but the technical requirements are higher. It is believed to be the most sensitive indicator of catecholamine secretion in the short term. The diagnostic value of the adrenaline-predominant is higher.
In recent years, the application of sensitive and specific radioimmunoassay has been carried out to determine the blood norepinephrine, adrenaline, and dopamine. Although the experimental conditions are high and expensive, it is the most sensitive for the diagnosis of pheochromocytoma. The method, in particular by means of this examination, can be found in normal blood pheochromocytoma.
In recent years, Kuchel et al found that the three components of catecholamines, norepinephrine, adrenaline, and dopamine exist in the blood circulation in two ways, namely, free state and combined state. 80% of norepinephrine and adrenaline in the peripheral blood circulation are in a bound state, while almost 100% of dopamine is in a bound state. In the past, all the catecholamines in the free state were determined in the laboratory. The binding state of catecholamine was determined and found.
2. Pharmacological test
Pharmacological tests are not specific and have certain false negatives, false positives and side effects. However, it is of diagnostic significance to apply a drug test to patients who are suspicious and have no abnormalities in catecholamine determination.
There are two broad categories of pharmacological tests, namely blockade of alpha adrenergic receptor blockers, such as phentolamine (regitine), for the onset of persistent hypertensive patients or patients with paroxysmal hypertension. If blood pressure is due to excessive secretion of norepinephrine and adrenaline. Blood pressure decreased rapidly within 2 minutes after intravenous injection of benzylamine. The systolic blood pressure drops more than 4.65 kPa (35 mmHg), and the diastolic blood pressure drops more than 3.3 kPa (25 mmHg), and is maintained positive for 3 to 5 minutes or more. Sedatives and blood pressure lowering drugs should be discontinued for 1 week before the test, so as not to affect the accuracy of the determination.
It has been reported that clonidine can be used for inhibition assays. After oral clonidine, blood catecholamines in non-pheochromocytoma hypertensive patients were inhibited and decreased; whereas in patients with pheochromocytoma, the release of tumor-autonomous catecholamines could not be inhibited, so blood catecholamine levels were unchanged.
The challenge test is the induction of stimulation in patients with paroxysmal hypertension without episodes and low blood pressure using histamine. Two minutes after intravenous injection of histamine, the systolic blood pressure increased by more than 6.65 kPa (50 mmHg), and the diastolic blood pressure increased by more than 3.99 kPa (30 mmHg), which was positive. In normal people and patients with essential hypertension, blood pressure can be decreased after injection, and facial flushing, headache, and nausea are also present. This test has certain risks, and benzyl oxazoline should be prepared during the test. This test has certain risks. Benzyl oxazoline should be prepared during the test so that it can be used when blood pressure is too high. For those with a history of myocardial infarction, cerebral hemorrhage, and heart failure, this test is banned.
Glucagon stimulates the release of catecholamines from adrenal medullary pheochromocytoma, causing hypertension, but not in normal and essential hypertension patients. Its side effects are much smaller than histamine and safer.
3. Positioning diagnosis
B-mode ultrasound and CT scan have high diagnostic accuracy for pheochromocytoma and are non-invasive, and conditions should be the preferred method of examination. Tumors above 1.5cm can be accurately located by CT scan. It is more difficult to be less than 1cm. It needs to be combined with other examinations for comprehensive analysis. CT scan can not only locate and measure the size of the tumor, but also determine whether it has infiltration or metastasis according to the tumor boundary and other conditions, so as to select appropriate treatment methods.
Segmental blood sampling of the vena cava, the location of pheochromocytoma, especially for small tumors, ectopic tumors or other tumors that failed to locate the tumor, has a high value, can provide a certain reference for CT scan.
The 131I-meta-iodobenzidine (131I-MIBG) angiography, which has been carried out in recent years, provides an important method for the diagnosis and localization of pheochromocytoma. The principle is that MIBG is chemically similar to norepinephrine and can be taken up by adrenal medulla and pheochromocytoma. Therefore, it is specific for pheochromocytoma examination and can identify whether the tumor in other parts of the adrenal gland or adrenal gland is pheochromocytoma. It has the advantages of safety, specificity and high accuracy.
Diagnosis
Differential diagnosis
Many diseases have similar pheochromocytoma manifestations, so differential diagnosis is important.
Essential hypertension
Some patients with essential hypertension exhibit high sympathetic excitability, manifested as palpitations, hyperhidrosis, anxiety, and increased cardiac output. However, the patient's urinary catecholamines are normal. In particular, the determination of catecholamines during urine exacerbation is more helpful in excluding pheochromocytoma.
2. Intracranial disease
In the case of intracranial disease with high intracranial pressure, symptoms such as severe headaches like pheochromocytoma can occur. Patients often have signs of other neurological damage to support the primary disease. However, you should also be alert to pheochromocytoma complicated with cerebral hemorrhage.
3. Neuropsychiatric disorders
It is easily confused with the onset of pheochromocytoma in anxiety episodes, especially with hyperventilation. But blood pressure is usually normal at an anxiety attack. If blood pressure also rises, it is necessary to measure blood and urine catecholamines to aid identification. Seizures are also similar to pheochromocytoma, sometimes blood catecholamines can also be elevated, but urinary catecholamines are normal. There are auras before seizures, abnormal EEG, and effective antiepileptic treatment to help exclude pheochromocytoma.
4. Menopausal syndrome
Women in the menopausal transition period will have a variety of symptoms caused by estrogen deficiency, such as hot flashes, sweating, irritability, mood swings, etc., similar to the onset of pheochromocytoma, through the understanding of menstrual history, sex hormones and CA The assay can be helpful in identification.
5. Other
Hyperthyroidism presents with high metabolic symptoms and high blood pressure. However, the diastolic blood pressure is normal and the catecholamines are not increased. Coronary heart disease angina pectoris, acute myocardial infarction, etc. need to be differentiated from pheochromocytoma. Generally, it can be distinguished according to the change of electrocardiogram at the time of onset and the improvement of the treatment of myocardial blood supply.
