Pheochromocytoma
Introduction
Introduction to pheochromocytoma Phenochromocytoma (PHEO) is a tumor formed by chromaffin cells. Extrapyretic pheochromocytoma can occur anywhere from the carotid body to the pelvis. Can lead to abnormal blood pressure (often manifested as hypertension) and metabolic disorders, some patients may cause serious heart, brain, kidney damage or sudden high blood pressure caused by chronic hypertension, life-threatening, but such as It can be diagnosed and treated in a timely and early manner, and it is a curable secondary hypertension. basic knowledge The proportion of illness: 0.003%-0.04% Susceptible people: no special people Mode of infection: non-infectious Complications: arrhythmia, hypertension, heart failure, hypertensive encephalopathy
Cause
The cause of pheochromocytoma
(1) Causes of the disease
Pheochromocytoma is located in the adrenal gland, accounting for 80% to 90%, and mostly one-sided; extra-adrenal tumors are mainly located in the extraperitoneal, adjacent to the abdominal aorta (10% to 15%), a few are located in the renal hilum, hepatic hilum , bladder, rectum and other special parts, benign, malignant accounted for 10%, like most tumors, the cause of sporadic pheochromocytoma is still unclear, family pheochromocytoma is genetically related, has been reported Pheochromocytoma in multiple endocrine neoplasia (MEN-2A, MEN-2B) has a short arm of chromosome 1 and it has been found that both have a germline of the chromosome 10 REI proto-oncogene (germ) -line) mutation, MEN2A is 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, whereas MEN-2B There is a mutation in the RTEB proto-oncogene of chromosome 10, which affects the tyrosine kinase catalytic site of the protein-binding region in the cell, and tyrosine kinase is involved in the regulation of cell growth and mutation, resulting in the onset of susceptible population, von Hippel- Chromaffin cells in Lindau syndrome Tumor, gene damage exists in 3p25 ~ 26 VHL gene (also known as tumor suppressor gene), mutations are diverse, 3 exons (exons 1, 2, 3) can be mutated, can be expressed as non-sense Mutation, missense mutation, frameshift mutation or deletion mutation, etc., pheochromocytoma is related to its missense mutation; when the gene is mutated, the cell growth is out of control and the tumor is formed, and the VHL gene germ cell line mutation determines the tumor of the VHL family. Sense of quality and morbidity, and the somatic cell line mutation of VHL gene is related to the malignant tendency of the tumor. In multiple neurofibromatosis (type I and type II), pheochromocytoma is only related to type I. The basic genetic damage is the inactivating mutation of the RF1 gene of chromosome 17, which is also a tumor suppressor gene, which can lead to the occurrence of pheochromocytoma and other tumors after loss of expression.
(two) pathogenesis
Pathology
Pheochromocytoma is derived from the pheochromic tissue of the sympathetic nervous system and is divided into two types: sporadic and familial. The sporadic pheochromocytoma is often single, 80% to 85% of the tumors are located in the adrenal gland, and the right side is slightly more. On the left side, a small number of tumors are located in the chromaffin tissue outside the adrenal gland. Familial pheochromocytoma is often multiple, mostly located in the adrenal gland, involving the bilateral adrenal glands, rare in the adrenal gland, in children, extra-adrenal and The incidence of pheochromocytoma in the bilateral adrenal gland is higher. The diameter of pheochromocytoma in the adrenal gland is often less than 10cm, mostly 3~5cm, and the average weight is about 10g. The large tumor occasionally can exceed 1000g, and the tumor is mostly round. Or elliptical, very few dumbbells; the tumor surface is gray or tan, or variegated, often bleeding, necrosis, cystic or calcification, visible under the light microscope, larger, polygonal The composition of chrome cells, under the electron microscope, there are dense eosinophils rich in epinephrine and norepinephrine around the nucleus. The diameter of malignant pheochromocytoma is larger than that of benign tumors. Significant difference, malignant people may have infiltration of the capsule, blood vessels may have tumor thrombus formation, but it is difficult to identify by microscopic observation, mainly to observe whether there is local infiltration and distant metastasis, the main part of metastasis is often liver , bones, lymph nodes and lungs, familial pheochromocytoma is often bilateral hyper-small, multi-center lesions, the incidence of malignancy and recurrence rate is higher than diffuse pheochromocytoma.
Extra-adrenal pheochromocytoma (or paraganglioma) accounts for 15% to 20% of pheochromocytoma, and extra-adrenal tumors are often less than 5cm in diameter and weigh between 20 and 40g. Tumors can be in sympathetic nerves. Intra- or extra-segmental, consistent with the anatomical distribution of extra-adrenal pheochromic tissue; most of the abdomen, located in the anterior retroperitoneal abdominal aorta, left and right lumbar paravertebral space, the opening of the inferior mesenteric artery, and the chromosome adjacent to the aorta ( Zuckerkandl) can also be seen in the carotid body, jugular sinus, suprarenal pole, renal hilum, hilar, between the liver and inferior vena cava, celiac plexus, near the head of the pancreas, axillary or proximal axillary vascular , in the ovary, in the bladder, after the rectum, etc.; the tumor of the chest is often located on the sympathetic trunk after mediastinum, but also in the pericardium or heart; tumors in the cauda equina and other parts are rare, about 20% of extra-adrenal pheochromocytoma is multiple The incidence of malignant extra-adrenal pheochromocytoma is relatively large, manifested as recurrence and distant metastasis after tumor resection, extra-adrenal pheochromocytoma has multiple, multi-focal characteristics, should pay attention to look carefully to prevent omission.
Like other endocrine gland tumors, the pathological diagnosis of adrenal medullary tumors cannot be based solely on morphological manifestations. In addition to hormone determination and clinical manifestations, attention must be paid to the evaluation of the biological behavior (hormone synthesis, secretion and infiltration ability) of tumor cells.
In terms of hormone synthesis and secretion ability, the following hormones can be identified from tumor cells by immunohistochemistry: adrenaline, norepinephrine, dopamine, serotonin, acetylcholine, enkephalin, CGRP, CRH, VIP, PACAP, ANP, AM, SS, neuropeptide Y, substance P, galanin, etc., the polyphenol secretion of pheochromocytoma of the adrenal medulla is generally more obvious than that of the adrenal gland.
In genetics, the genetic markers of sporadic pheochromocytoma are unknown, while familial (such as MEN 2A) have significant genetic defects. Recent studies have shown that pheochromocytoma and paraganglioma have a common chromosome. Defects, using genome-to-comparison hybridization, found that the copy number changes were similar. Both tumors had loss and other changes in 1 cen-p3l (82%) and 11q22-25 (41%), in histopathological morphology. In terms of the diagnosis of simple cell morphology, especially the basis for the identification of benign and malignant, it must be limited by immunohistochemistry. The tumor cells are chromogranin, Leu7, S-100 protein positive reaction only indicates that it is The source of extraneural embryonic layer can not identify its benign and malignant, sometimes in the growth of cells, the infiltration behavior is ambiguous. When the diagnosis is difficult, it can be diagnosed by flow cytometry. If it is still difficult, it depends on the long-term follow-up observation.
The general histopathological diagnosis principles and methods of this disease can be referred to the diagnostic draft published by the Cancer Society of the National College of Pathologists.
Adrenal medulla hyperplasia mainly refers to the increase in the number of chromaffin cells, according to the ratio of adrenal medulla / cortical thickness, such as > 1: 10 that there may be medullary hyperplasia, adrenal medulla hyperplasia may be simple or accompanied by MEN-II. Most of the simple adrenal medulla hyperplasia is bilateral adrenal medulla hyperplasia, a small number of unilateral hyperplasia, it has been reported that vitamin D3 increases the number of adrenal medullary chromaffin cells through its role in promoting mitosis, in addition, 21-hydroxylation In addition to adrenal hyperplasia, the enzyme deficiency has adrenal medullary dysfunction and medullary hyperplasia. The clinical manifestations of adrenal medulla hyperplasia are similar to those of pheochromocytoma, with paroxysmal hypertension and episode hypertensive crisis. Blood, urine catecholamine and its metabolite levels can be increased, but B-ultrasound, CT and MRI can not find adrenal mass, 131I-MIBG can be bilateral or one side (proliferative side) adrenal medulla intake of MIBG increased, confirmed diagnosis By pathological examination, the pathological changes are multiple nodular hyperplasia or diffuse hyperplasia, and blood pressure can return to normal after surgery.
Some immunohistochemical indicators can be used to determine the biological behavior of tumor cells. For example, the rate of monoclonal antibody MIB1 positive cells varies greatly in benign and malignant pheochromocytoma, and the positive rate of MIB1 in benign tumor cells of the adrenal gland is low (0.81%). ), malignant time is high (3.30%); outside the adrenal gland, this difference is more obvious (0.44% vs 5.1%), so when the MIB positive cell rate is >2%, it is highly suspected of malignant pheochromocytoma.
2. Biochemical changes
(1) Synthesis, storage and release of catecholamines: synthesis and release of catecholamines in pheochromocytoma cells are different from chromaffin cells in normal adrenal medulla, but chromogranular granules in pheochromocytoma cells are in morphology And physiologically functionally identical to the chromaffin particles in the normal adrenal medulla, the chromaphilic particles are rich in epinephrine and norepinephrine, but the ratio between the two is not the same in different chromaffin particles, due to adrenaline ( E) There must be a high concentration of glucocorticoids during synthesis. Therefore, in addition to the adrenaline in the adrenal gland and the chromatin in the aorta, the tumor cells in other parts can only synthesize norepinephrine. (NE), this feature is helpful for the localization diagnosis of tumors, probably because the feedback inhibition of tyrosine hydroxylase is impaired, the synthesis regulation of catecholamines is changed, and the level of catecholamine synthesis by tumor cells is more or less The ground is higher than the normal chromaffin cells, and the pheochromocytoma is not like the normal, adrenal medulla is innervated, the release of catecholamines and nerve impulses Inconsistent movements, changes in tumor blood flow, direct compression, chemical and drug stimulation, and an increase in angiotensin-2 can cause catecholamine release in tumor cell tissues, but the mechanism is not well understood.
(2) Excretion of catecholamines: Unlike chromogranular granules (about 85% of adrenaline) in normal adrenal medulla, most of the pheochromocytoma in pheochromocytoma contain more NE than epinephrine, so most of them The patient's urine is dominated by norepinephrine, and all of them are adrenaline, which is clinically characterized by -receptor-exciting syndromes such as tachycardia and hypermetabolism, unless the adrenaline in urine is measured separately. And norepinephrine, most patients can not infer the type of excreted catecholamines from clinical features, because of its atypical clinical manifestations, the secretion and excretion of adrenaline pheochromocytoma is difficult to diagnose, tumor cells only synthesize and secrete the adrenal gland The mechanism of element (E) is unknown. Phenylethanolamine-N-methyltransferase (PNMT) is the only rate-limiting enzyme that catalyzes the conversion of NE to E. These tumor cells express large amounts of PNMT and are compared with other types of pheochromocytoma. PNMT is expressed only in tumor cells secreting E and is expressed together with 17-hydroxylase and its receptor protein, suggesting that PNMT, which controls the amount of adrenaline production, is secreted in the adrenaline. Tumor cells were overexpressed, and the reason is the over-expression of Egr-1 and cortisol rich content.
In patients with familial pheochromocytoma, tumor cells contain large amounts of catecholamines, but levels of catecholamines and catecholamine metabolites in the blood and urine are rarely increased, especially in multiple endocrine neoplasia syndromes, in plasma and in urine. Adrenaline increase is only a biochemical change, generally does not cause clinical symptoms, the mechanism is still unclear, at this time the diagnosis is often very difficult.
In addition to the Zuckerkandl pheochromocytoma, extra-adrenal pheochromocytoma typically secretes only adenine, adrenaline, but it has been reported that pheochromocytoma in the thoracic cavity can also produce adrenaline, in the early stages of pheochromocytoma, dopamine and The excretion of dopamine metabolites such as high vanillic acid (HVA) is often normal. If the excretion of dopamine and HVA in the urine increases, it is more likely to be malignant.
(3) tumor size and catecholamine level: the size of the tumor is related to the conversion of free catecholamine to catecholamine metabolites. Small pheochromocytoma, the concentration of catecholamine in the tumor is low, but its discharge is much, so the VMA in urine The proportion of CA is low; on the contrary, large pheochromocytoma, the concentration of catecholamine in the tumor is high, but the discharge is small, the ratio of VMA to catecholamine in urine is high, because the small tumor discharge rate is high, so the unmetabolized catecholamine is secreted, which has biological activity. It can produce clinical manifestations. These tumors are often diagnosed at a very small time. On the contrary, for tumors that can store more catecholamines, catecholamines can be converted into their metabolites in tumors, and less bioactive catecholamines are secreted. Before the onset of clinical symptoms, the tumor is already large. Understanding the synthesis and metabolic processes of CA will help us to have a clear understanding of CA's biochemical sources, material composition and metabolites, and its CA anabolic pathway.
CA plays a role in stimulating receptors in the body. Its related adrenergic receptors are divided into , and DA receptors (DACs), which are further divided into 12, 12 and DAC1 DAC2 receptors. The physiological response of the body when stimulated.
(4) Other substances produced by tumors: In addition to the synthesis of adrenaline and NE, pheochromocytoma can also synthesize or secrete some peptides, and these peptides can also be increased in the circulation, including the adrenal cortex. Hormone (ACTH), corticotropin releasing hormone (CRH), growth hormone releasing hormone (GHRH), calcitonin gene-related peptide (CGRP), parathyroid hormone-related peptide (PTHrP), atrial natriuretic peptide (ANP), It seems that the mechanism of synthesis and secretion of these peptide hormones is unknown, such as vasopressin (VIP), neuropeptide substance Y (NPY), somatostatin, erythropoietin and adrenomedullin (AM), -MSH, etc. Not due to nerve stimulation, may be related to the increased reflex activity of the chromogranin secretory channel. The effect of these peptide hormones on clinical manifestations is not very clear, but some peptides can cause special endocrine syndromes, such as FTHrP. Secretion can cause secondary hypercalcemia, and increased secretion of erythropoietin leads to secondary polycythemia.
3. Family pheochromocytoma and related diseases
(1) Multiple endocrine neoplasia syndrome: in multiple endocrine neoplasia type I (MEN-1, Wermer syndrome), pheochromocytoma is not common, multiple endocrine neoplasia type II (MEN-2A, Sipple Syndrome) includes pheochromocytoma, medullary thyroid carcinoma and parathyroid adenoma; about 40% to 50% of MEN-2A individuals can develop pheochromocytoma, which is derived from adrenal medulla hyperplasia, often multiple Bilateral, there may be hyperplastic changes around the tumor [diffuse and / or nodular hyperplasia], extra-adrenal pheochromocytoma is rare; the hormone secreted by the tumor is mainly adrenaline, so early clinical symptoms can be atypical, only There are changes in blood or urine biochemistry, multiple endocrine neoplasia type III (MEN-2B) consists of ganglion neuroma phenotype (mafan body type, multiple mucosal neuroma), medullary thyroid carcinoma and pheochromocytoma The incidence of pheochromocytoma is 40% to 50%.
(2) von Hippel-Lindau syndrome (VHL syndrome): von Hippel-Lindau syndrome is an autosomal dominant genetic disease, consisting of retinal hemangioma, central vascular reticuloma, kidney cancer, kidney and pancreas Cysts and multiple cystadenoma, the incidence of pheochromocytoma accounts for 10% to 20%, often multiple, the incidence of pheochromocytoma in different families is different, up to 90% in some families And it happens often earlier.
The etiology and pathogenesis of this syndrome have been basically ascertained. The chromosome 3p25 region contains tumor suppressor gene (TSG). Vascular tumors (benign) and cysts (liver, kidney, pancreas) can be caused by mutation or deletion of TSG. Etc.) and the formation of cystadenoma, about 70% of patients may be associated with renal clear cell carcinoma, the apparent rate of pheochromocytoma varies greatly, but in recent years there have been more reports that the intrinsic easy to merge with endolymphatic sac Endolymphtic sac tumors are one of the important causes of tinnitus and deafness. Clinically, when encountering familial retina, hemangioblastoma of the brain tissue or multiple pancreatic cysts, it is necessary to think of VHL syndrome, but with epididymis alone or Renal cysts cannot be diagnosed as VHL. For those without a family history, they must have two or more retinal and/or brain vascular reticuloma, or have a vascular reticuloma with a visceral tumor. The clinical diagnosis of VHL can only be made. The diagnosis depends on the molecular biological examination of the TSG gene mutation or the deletion of the 3p 25 region. All family members must be screened for DNA or 3P 25 deletion. Tests, positive carriers must undergo close follow-up observations.
The TSG gene (also known as the VHL gene) contains three exons encoding two mRNAs. About 20% of patients with Southerner analysis can detect germline mutations (which involve all cells), and 27% have nonsense mutations or frameshifts. (frameshift) mutation, the positive detection rate of VHL family members is about 80%, the family suffering from pheochromocytoma (VHL2 type) accounts for about 7% to 20%, VHL in most VHL 2 family, the gene is non-sense Mutation, while the VHL gene of the VHL type 1 family (without pheochromocytoma) is completely or partially deficient (due to the early appearance of the stop codon), and the clinical heterogeneity of VHL is derived from genetic defects and penetrance. Heterogeneity, sometimes associated with the presence of chimeric chromosomes in tumor cells.
The adrenal medulla and sympathetic nervous system originate from the sympathetic neurons of the embryonic stage and become differentiated into sympathetic ganglion cells and chromaffin cells. These cells are abnormally differentiated to form neuroblastoma, ganglionoma and PHEO. Differentiation and evolution process.
(3) Multiple neurofibromatosis and other related diseases: There are two subtypes of multiple neurofibromatosis (type I and type II), and pheochromocytoma is only associated with type I, and its incidence is in multiple neurofibromas. The population varies in height, 1% to 50%, in the Carney complex. It is often characterized by functional extra-adrenal paraganglioma, and often associated with pheochromocytoma in Sturge-Weber syndrome. .
Yokoyma et al used the metoclopramide (gastric ampoules) test as a challenge test for suspicious patients to identify the nature of adrenal masses. Of the 7 patients with pheochromocytoma, 3 were positive, 3 were negative, and 1 was false negative. Its sensitivity and specificity are similar to those of 24h urinary catecholamine and MIBG, but the specificity is 100%. The negative result is not the test insensitivity, but the disease itself has heterogeneous biological characteristics. It was thought that it was considered to be methoxychlor Amine (gastric ampoules) can promote the secretion of AVP (ADH), but Coiro et al used 1 mg intravenous injection of metoclopramide (gastric ampoules), no change in plasma AVP, Hsu et al found that pheochromocytoma (6/7) showed a positive reaction. In addition to the increase in blood pressure, it was more diagnostic to observe changes in plasma and urinary catecholamine before and after the test, but drugs that interfere with CA secretion should be discontinued before the test.
Prevention
Pheochromocytoma prevention
Because of the diverse clinical manifestations of patients with pheochromocytoma, the diagnosis is difficult, but the possibility of pheochromocytoma should be considered first when:
1, patients with paroxysmal or persistent hypertension, accompanied by headache, palpitations, excessive sweating, pale, chest, abdominal pain, nervousness, anxiety, sudden death and other symptoms and high metabolic status;
2. Children, young people with acute or malignant hypertension;
3, unexplained shock; high, low blood pressure repeated alternating attacks; paroxysmal arrhythmia; body position changes or large, urinating induced blood pressure significantly increased;
4, during surgery, anesthesia, pregnancy, childbirth, sudden increase in blood pressure or shock, and even sudden cardiac arrest; massage or squeeze bilateral renal area or abdomen to induce hypertension;
5, taking conventional antihypertensive drugs, blood pressure is not satisfactory, or only b-adrenergic receptor blockers.
The etiology of sporadic pheochromocytoma is still unclear, so there is no clear related prevention. Family pheochromocytoma is related to heredity and can be related to genetics.
1. In the diagnosis and treatment of patients with hypertension, be highly alert to the possibility of the disease, should master its clinical characteristics before early diagnosis, minimize missed diagnosis and misdiagnosis.
2. Once the diagnosis is confirmed, the surgical treatment is the first choice.
3. Pay attention to keeping the blood pressure relatively stable during the treatment of the disease to avoid accidents.
Complication
Pheochromocytoma complications Complications arrhythmia hypertension heart failure hypertensive encephalopathy
Pay attention to the occurrence of complications, such as heart failure, arrhythmia, hypertensive encephalopathy, pulmonary infection and other abnormal changes. If pheochromocytoma crisis occurs, blood should be taken immediately to determine urea nitrogen, creatinine, blood sugar, etc. Avoid rolling the tumor.
The following complications can be combined:
1. Cardiovascular complications, catecholaminergic heart disease, arrhythmia, shock.
2. Cerebrovascular complications Stroke, transient ischemic attack (TIA), hypertensive encephalopathy, mental disorders.
3. Others such as diabetes, ischemic enterocolitis, cholelithiasis, etc.
Symptom
Symptoms of pheochromocytoma Common symptoms Catecholamine excretion palpitations with hypertension Heart enlargement nausea arrhythmia Anxiety thin skin Pale shock Functional tremor
Most of them are 20 to 50 years old. Most of the main symptoms are paroxysmal hypertension, with varying time and frequency. Usually blood pressure is not high, the systolic blood pressure can reach 200 ~ 300mmHg, diastolic pressure 130 ~ 180mmHg, with headache, pale, sweating, tachycardia, discomfort in the precordial area, nausea and vomiting, blurred vision. After the termination of the attack, there may be symptoms such as cheeks and skin flushing, systemic fever, runny nose, dilated pupils, and increased urine output. Some may be characterized by persistent hypertension, or persistent hypertension with paroxysmal aggravation and sympathetic excitability as described above. If you have low blood pressure or high blood pressure fluctuations when standing, you should be suspected of this disease. Individuals may present with hypotension, shock, or alternating hypertension and hypotension.
1. Cardiovascular system performance
Because a large amount of catecholamines intermittently enter the blood circulation, the blood vessels contract, the peripheral resistance increases, the heart rate increases, and the cardiac output increases, resulting in a high blood pressure paroxysmal stimuli, systolic blood pressure up to 26.6kPA (200mmHg), and diastolic blood pressure. Significantly elevated. The attack may be accompanied by palpitations, shortness of breath, chest depression, headache, pale complexion, excessive sweating, blurred vision, etc. In severe cases, hypertensive crisis such as cerebral hemorrhage or pulmonary edema may occur. After the onset of remission, the patient is extremely tired and weak, and skin flushing such as the face may occur. Attacks can be triggered by sudden changes in body position, emotional agitation, strenuous exercise, coughing, and urination. The frequency and duration of seizures vary widely and are not positively correlated with tumor size.
Some patients can present with persistent hypertension. It is reported that about 90% of children have persistent hypertension, and about 50% of adults have persistent hypertension. The difference is that there is excessive expression of adrenaline or norepinephrine. A small number of patients may have symptoms such as paroxysmal hypotension and shock. A small number of patients may have episodes of hypotensive hypotension, shock, etc., which may be related to tumor necrosis, intratumoral hemorrhage, catecholamine release, or severe cardiac accidents. In this case, the prognosis is often worse.
In 1958, Szakas proposed the concept of catecholamine cardiomyopathy, which is characterized by direct toxic effects of catecholamines on the myocardium, resulting in cardiac hypertrophy, edema, focal hemorrhage, intimal hypertrophy, and inflammatory cell infiltration. Clinical manifestations like myocarditis, severe heart failure and severe arrhythmia.
2. Metabolic disorders
Catecholamine stimulates islet alpha-receptors, which reduces insulin secretion, acts on the liver alpha, beta receptors and muscle beta receptors, increases gluconeogenesis and glycogenolysis, reduces the use of sugar by surrounding tissues, and thus increases blood sugar or sugar. The tolerance is reduced. Catecholamine can also promote the secretion of pituitary TSH and ACTH, increase the secretion of thyroxine and adrenocortical hormone, leading to increased basal metabolism, increased blood stasis, accelerated fat decomposition, and caused weight loss. A small number of patients may have hypokalemia.
3. Other performance
Catecholamine can relax gastrointestinal smooth muscle and weaken gastrointestinal motility, which can cause constipation and sometimes stubbornness. Severe contraction of the gastrointestinal arterioles can cause gastrointestinal mucosal ischemia, occasional necrotic perforation and other symptoms. Due to the oppression of tumor growth on adjacent organs, clinical manifestations can occur.
Examine
Examination of pheochromocytoma
Physical examination
Patients with intermittent episodes have no obvious signs, or only the heart is enlarged, and a few can be abducted and abdominal masses. Increased blood pressure during the attack, may have wet skin, pale complexion, pulse rate, arrhythmia, diplopia and so on.
Laboratory inspection
1. Determination of blood, urine catecholamine and its metabolites
(1) Urinary CA, vanillyl mandelic acid, 3-methoxy adrenergic (MN) and methoxy norepinephrine (NMN) and their sum (TMN) can be elevated, often at normal high limits. More than twice, paroxysmal is only higher than normal after the onset, therefore, pre-prepared urinary storage (with 5ml of 6nmol / L HCl), collecting blood pressure during the episode (3 ~ 24h) during the episode The examination is the key to timely obtaining the diagnosis basis. At the same time, the amount of creatinine is measured, and the excretion is calculated per mg of creatinine. Simultaneous determination of norepinephrine and its metabolite dihydroxyphenylpropanol (DHPG) can improve its diagnosis. Specificity, due to many drugs and foods such as tetracycline, erythromycin, aspirin, caffeine, levodopa, guanethidine, clonidine, lishepine, bromocriptine and tea, coffee, cola, bananas, etc. The above indicators need to be deactivated first, the urinary CA is normal circadian rhythm, and the displacement increases during the activity, most patients with pheochromocytoma have a significant increase in urinary CA, often greater than 1500nmol / d ( 250 g).
(2) Determination of plasma CA and DHPG: Plasma CA value is significantly higher than normal in the sustained or paroxysmal attack of this disease, only reflects the blood CA level immediately, so the diagnostic value is not higher than the CA level in the urine 24h. more meaningful.
2. Pharmacological tests are divided into excitation and inhibition tests:
(1) Inflammatory test: Only for paroxysmal patients, the above examination can not be diagnosed, it is considered to be adopted, there is a certain risk, especially for those who have persistent hypertension or older age, it is not suitable for the stimulation test to avoid accidents, even if there is indication The cold-pressurization test should also be performed first to observe the patient's vascular reactivity and to prepare an alpha blocker (phentolamine) for severe hypertension or hypertensive crisis that may occur after challenge.
1 Cold-pressurization test: The antihypertensive drug was stopped for 1 week before the test, and the sedative was at least 48h. The blood pressure of the normal person after immersing in the ice water was 12/11mmHg30/25mmHg compared with the control. If the blood pressure is >160/110mmHg, it is not suitable. Do other excitation tests.
2 glucagon stimulation test: the side effects of histamine and tyramine are lighter, should be listed as the first choice, should be used for cold compression test, after the blood pressure is stable, 3 minutes after the injection of glucagon 1mg, such as plasma CA level It is more than 3 times higher or the blood pressure is higher than the highest value of the cold pressurization test by 20/15mmHg or more, and it can be diagnosed as pheochromocytoma.
(2) Inhibition test: It is suitable for the episode of persistent hypertension or paroxysmal hypertension, or the blood pressure is obviously increased after the above-mentioned stimulation test. It is mainly used for differentiation with other causes of hypertension or essential hypertension. The following test can be applied when the blood pressure is 170/110 mmHg or the plasma CA level is 5.9 to 11.8 nmol/L (1000 to 2000 pg/ml).
1 phentolamine (regitine) test: phentolamine is a short-acting alpha-adrenergic receptor blocker, which can be used to determine whether hypertension is caused by high levels of CA.
If the blood pressure within 2 to 3 minutes after phentolamine injection is lower than 35/25mmHg and lasts for 3 to 5 minutes or longer, it is positive, which is highly suggestive of pheochromocytoma. If blood CA changes are measured at the same time, such as Consistent with changes in blood pressure, it is more conducive to the establishment of a diagnosis.
2 clonidine test: clonidine is a central 2 adrenergic receptor agonist, can reduce the release of CA from neurons, but does not inhibit the release of CA in pheochromocytoma, so it can be identified, this test is safe, However, it is only suitable for patients with elevated plasma CA before the test. Most patients with hypertension without this disease may have lower blood pressure, and those with primary hypertension may be inhibited to the normal range or at least 50% of the original level. While most patients with pheochromocytoma have unchanged plasma CA levels, or more often, they may have a few false negative or false positive cases, which may be combined with a glucagon challenge test or repeated if necessary.
Film degree exam
1. Adrenal CT scan
For the first time, when CT is performed, due to postural changes or injection of venous contrast agents can induce hypertensive seizures, -adrenergic receptor blockers should be used to control hypertension, and phentolamine should be prepared at any time during the scan. In case of urgent need.
2. Magnetic resonance imaging (MRI)
It can display the anatomical relationship and structural characteristics of the tumor and surrounding tissues, and has a high diagnostic value.
3.B Ultra
Convenient, easy, low price, but the sensitivity is not as good as CT and MRI, it is not easy to find smaller tumors, and it can be used as a means of initial screening and localization.
4.131I-m-iodobenzylamine (MIBG) scintillation scan
The location of extra-adrenal, multiple or malignant metastatic pheochromocytoma has a high diagnostic value, and has qualitative and localized significance, but it is poorly imaged for low-function tumors, and is affected by a variety of drugs such as lishepine. Cocaine, tricyclic antidepressants, etc., cause false negatives, so should be stopped 1 week before the examination, and take compound iodine to protect the thyroid before the examination.
In recent years, 11-carbon hydroxyephedrine, octreotide imaging or PET has been used to diagnose this disease.
5. Adrenal vein cannulation
Blood sampling for plasma CA When clinical manifestations and biochemical tests support the disease, but the above non-invasive imaging examination failed to locate the tumor, it may be considered, the operation may induce hypertensive crisis, phentolol should be prepared Ming is ready for emergency use.
Diagnosis
Diagnosis and differentiation of pheochromocytoma
Diagnosis can be based on medical history, clinical symptoms, and laboratory tests.
Differential diagnosis
Many diseases have similar pheochromocytoma manifestations, so differential diagnosis is important.
1. Essential hypertension Some patients with essential hypertension exhibit high sympathetic excitability, manifested as palpitations, hyperhidrosis, anxiety, increased cardiac output, but the patient's urinary catecholamines are normal, especially in anxiety episodes. When urine is administered to determine catecholamines, it is more helpful to exclude pheochromocytoma.
2. Intracranial disease In the case of intracranial disease combined with high intracranial pressure, there may be symptoms such as severe headache caused by pheochromocytoma. Patients usually have signs of other nervous system damage to support the primary disease, but they should also be alert to Chromoblastoma complicated by cerebral hemorrhage.
3. Neuropsychiatric disorders are easily confused with episodes of pheochromocytoma in anxiety episodes, especially with hyperventilation, but blood pressure is usually normal in anxiety attacks. If blood pressure also rises, it is necessary to measure blood and urine catecholamines. Help identification, seizures are similar to pheochromocytoma, sometimes blood catecholamines can also be elevated, but urinary catecholamines are normal, there are aura before seizures, abnormal EEG, anti-epileptic treatment, etc. to help exclude chromogranin cells tumor.
4. Menopausal women in the menopausal transition period will have a variety of symptoms caused by estrogen deficiency, such as hot flashes, sweating, impatience, mood swings are difficult to control, etc., similar to the onset of pheochromocytoma, by understanding the history of menstruation, The determination of sex hormones and CA can be helpful in identification.
5. Other hyperthyroidism presents high metabolic symptoms, accompanied by hypertension, but diastolic blood pressure is normal, and catecholamines do not increase, coronary heart disease angina pectoris, acute myocardial infarction, etc. need to be differentiated from pheochromocytoma, generally according to ECG changes at the time of onset To improve the effective treatment of myocardial blood supply, etc., the most critical is the determination of urinary catecholamine.
Coronary heart disease angina pectoris; anxiety caused by other causes; unstable primary hypertension; diseases with paroxysmal hypertension, such as brain tumors; menopausal syndrome; hyperthyroidism.
