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Pheochromocytoma (chromaffinoma): information overview
Last reviewed: 23.04.2024
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Chromaffinoma (benign and malignant), pheochromocytoma, pheochromoblastoma are synonyms of a tumor that develops from special cells located in the adrenal medulla, sympathetic ganglia and paraganglia.
Pheochromocytoma is a catecholamine-secreting tumor of chromaffin cells, typically located in the adrenal gland. Causes permanent or paroxysmal hypertension. Diagnosis is based on measuring the products of catecholamines in the blood or urine. Visualization, especially CT or MRI, helps to localize tumors. Treatment is to remove the tumor as much as possible. Drug therapy for controlling blood pressure includes a-blockers, possibly in combination with beta-blockers.
Cells and emerging tumors derive their name from the ability to stain in the brown (phaios) color when processing histological sections with chromium salts (chromos). Vnenadococcal tumors of chromaffin tissue are sometimes called paragangliomas, and non-functioning formations of the same genesis, regardless of location, are chemodectomes. In most cases, tumors of chromaffin tissue secrete catecholamines, which determines their clinical course.
Pheochromocytoma is found in approximately 0.3-0.7% of patients with arterial hypertension. According to other data, 20 patients are expected per 1 million people, and according to autopsy results of patients who died from hypertension, chromaffinoma occurs in 0.08% of cases.
Pheochromocytoma is described in all age groups, from newborns to the elderly, but is most often found between the ages of 25 and 50 years. Among almost 400 patients with chromaffinoma, operated at the Institute of Experimental Endocrinology and Chemistry of Hormones of the Russian Academy of Medical Sciences, children aged 5 to 15 years were 10%, patients from 25 to 55 years old - 70%, over 55 years - 15%. Over 60% of adult patients are women. Among boys from 5 to 10 years old boys predominate, while among older children - girls.
[What causes pheochromocytoma?
The secreted catecholamines include noradrenaline, adrenaline, dopamine and dopa in various proportions. About 90% of pheochromocytomas are found in the adrenal medulla, but they can also be found in other tissues, the derivatives of nerve cells; the possible places include the sympathic chain of the paranglegia, located retroperitoneally along the aorta, in carotid bodies (the organ of Zukerkundl), in the place of aortic bifurcation, in the genitourinary system, in the brain, in the pericardial sac, in the dermoid cysts.
The pheochromocytoma in adrenal medulla is equally common in men and women, 10% of cases is bilateral (20% in children), malignant in more than 10% of cases. Of extradrenal tumors, 30% are malignant. Although pheochromocytomas occur at any age, most often occur in 20-40 years.
The pheochromocytoma varies in size, but on average it is 5-6 cm in diameter. They weigh 50-200 g, but tumors weighing several kilograms were also noted. Rarely, they are large enough to be accessible by palpation or cause symptoms of constriction or obstruction. Regardless of the histological structure, the tumor is considered benign if the capsule has not sprouted and metastasized, although there are exceptions.
The pheochromocytoma can be part of the family multiple endocrine neoplasia syndrome (MEN), IIA and IIBtypes, in which other endocrine tumors can coexist or develop sequentially. Pheochromocytoma develops in 1% of patients with neurofibromatosis (Recklinghausen's disease) and can be observed with hemangiomas and renal cell carcinomas, as in Hippel-Lindau disease. Family pheochromocytomas and tumors of carotid bodies can be associated with a mutation of the enzyme succinate dehydrogenase.
The causes and pathogenesis of pheochromocytoma (chromaffinoma)
Symptoms of pheochromocytoma
Hypertension, which is paroxysmal in 45% of patients, is a leading symptom. Pheochromocytoma occurs in 1 of 1000 patients with hypertension. Common symptoms and signs include tachycardia, increased sweating, postural hypotension, tachypnea, cold and wet skin, severe headaches, fluttering of the heart, nausea, vomiting, epigastric pain, visual disturbances, dyspnea, paresthesia, constipation, anxiety. Paroxysmal seizures can be provoked by palpation of the tumor, changing the posture, squeezing the stomach or massage, introducing anesthesia, emotional trauma, blockade (which paradoxically increases pressure by blocking mediated vasodilation), urination (if the tumor is in the bladder). In elderly patients, severe weight loss with persistent hypertension may indicate pheochromocytoma.
In a physical examination, if it is carried out outside the paroxysmal seizure, there is usually no deviation, other than the presence of hypertension. Retinopathy and cardiomegaly are often less severe than might be expected with a given degree of hypertension, but specific catecholamine cardiomyopathy may develop.
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Diagnosis of fechromocytoma
Pheochromocytoma can be suspected in patients with typical symptoms or in the presence of sudden severe unexplained hypertension. Diagnosis involves the determination of high levels of catecholamine products in serum or urine.
Blood test
Free metanephrine plasma has a sensitivity of up to 99%. This study is more sensitive than the definition of circulating adrenaline and norepinephrine, as plasma metanephrine rises continuously, and epinephrine and norepinephrine are secreted intermittently. However, a significantly elevated plasma norepinephrine level makes the diagnosis highly probable.
Urine examination
The determination of metanephrine in the urine is less specific than the free plasma metanephrine, the sensitivity is about 95%. Two or three normal results make the diagnosis unlikely. The definition of epinephrine and norepinephrine in urine is almost as reliable. The main products of the metabolism of epinephrine and norepinephrine in urine are Vanillilmindal (VMC) and homovaniline (HVA) metanephrins. In healthy people, very small amounts of these substances are excreted. Normal data for 24 hours are as follows: free adrenaline and norepinephrine <100 μg (<582 nmol), total metanephrine <1.3 mg (<7.1 μmol), IUD <10 mg (<50 μmol), HVC <15 mg <82.4 μmol). With pheochromocytoma and neuroblastoma, renal excretion of epinephrine and norepinephrine is increased. However, increased release of these substances can occur with other disorders (eg, coma, dehydration, sleep apnea) or severe stress; in patients taking alkaloids rauwolfia, methyldopa, catecholamines; after consumption of food containing large amounts of vanilla (especially in the presence of kidney failure).
Other studies
The blood volume is limited, there may be a false increase in hemoglobin and hematocrit levels. There may be hyperglycemia, glucosuria, manifest diabetes mellitus, elevated muscle-free levels of free fatty acids and plasma glycerin. The level of plasma insulin is very low relative to the level of glucose. After removal of pheochromocytoma, hypoglycemia may occur, especially in patients taking oral antihyperglycemic drugs.
Provocative tests with histamine and tyramine are dangerous and should not be used. Histamine (0.51 mg, injected rapidly intravenously) causes an increase in blood pressure of more than 35/25 mm Hg. Art. Within 2 minutes of normotonics with pheochromocytomas, but at the present time is not necessary. For the relief of the hypertensive crisis, the presence of phentolamine mesylate is necessary.
The main approach is to use the 24 hour excretion of catecholamines with urine as a screening test and avoid the use of provocative tests. In patients with elevated plasma catecholamine levels, a suppressive test using clonidine or phenothamine intravenously can be used, but is rarely necessary.
Visualization for tumor localization is necessary in patients with abnormal screening results. CT or MRI of the chest and abdominal cavity with or without contrast should be used. When using isotonic contrast agents, there is no need for blockade of a-drenoreceptors. PET is also used quite successfully. Repeated determinations of the concentration of catecholamines in plasma samples during catheterization of the vena cava with blood sampling at various sites, including adrenal veins, help localize the tumor: an increase in norepinephrine level will be detected in the vein draining the tumor. The ratio of norepinephrine levels to adrenaline in the adrenal vein can help to find a small-volume adrenal source of catecholamines. In the localization of pheochromocytoma, the use of radiopharmaceuticals with nuclear imaging is also effective. 123-1-metaiodobenzylguanidine (MIBH) is most commonly used outside the United States; 0.5 mCy is administered intravenously, the patient is scanned on day 1,2,3. Normal adrenal tissue practically does not accumulate the drug, and pheochromocytomas accumulate in 90% of cases. The image is usually positive only if the focus is large enough to detect CT or MRI, but can help in confirming that the adrenal mass is probably the source of catecholamines. 131-1-MIBG is a less sensitive alternative.
It is necessary to search for associated genetic disorders (for example, "coffee stains with milk" in neurofibromatosis). Patients should be screened for MEN from the serum (and, possibly, calcitonin) and other studies shown by clinical data.
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Treatment of fechromocytoma
The method of choice is surgical removal. The operation is usually delayed until control of hypertension is achieved with a combination of beta blockers (usually phenoxybenzamine 20-40 mg orally 3 times a day and propranolol 20-40 mg orally 3 times a day).
Blockers should not be used until an adequate blockade is achieved. Some blockers, like doxazosin, can be quite effective, but are better tolerated. The most effective and safe blockade is phenoxybenzamine 0.5 mg / kg intravenously in 0.9% physiological saline for 2 hours in each of the 3 days before surgery. Sodium nitroprusside can be administered in hypertensive crisis preoperatively or intraoperatively. When detecting or suspecting bilateral tumors (as in patients with MEN), a sufficient dose of hydrocortisone (100 mg intravenously twice a day) is necessary before and during surgery to avoid acute glucocorticoid insufficiency due to bilateral adrenalectomy.
Most pheochromocytomas can be removed laparoscopically. Continuous monitoring of blood pressure through the intra-arterial catheter, as well as control of the bcc should be performed. Introduction to anesthesia should be performed with non-arrhythmogenic drug (eg, thiobarbiturate), then continue with enflurane. During the operation, paroxysms of hypertension should be controlled by injections of 15 mg of phentolamine intravenously or by sodium nitroprusside infusions [24 μg / (kghmin)], and tachyarrhythmia with propranolol 0.52 mg intravenously. If a muscle relaxant is needed, it is preferable to use a drug that does not release histamine. Preoperative use of atropine should be avoided. To avoid blood loss, a blood transfusion (12 units) must be performed before the tumor is removed. If blood pressure was well controlled before surgery, a high salt diet is recommended to increase BCC. If hypotension develops, it is necessary to begin infusion of a dextrose solution containing norepinephrine 412 mg / l. In some patients with hypotension in the absence of effect on Levarterenol, hydrocortisone 100 mg intravenously may be effective.
Malignant metastatic pheochromocytoma is treated with a- and beta-blockers. The tumor can be painless and exist for a long time. It is necessary to monitor blood pressure. The use of 1311metoyodobenzylguanidine (MIBG) for the treatment of residual disease phenomena prolongs survival. Radiation therapy can reduce bone pain, chemotherapy is rarely effective, but can be used in the case of ineffectiveness of other methods.