Pheochromocytoma of the adrenal glands: what is it and what is the prognosis of life. What is pheochromocytoma and how life-threatening is it? Pheochromocytoma Treatment

Pheochromocytoma- a tumor of the adrenal medulla that secretes catecholamine hormones: adrenaline or norepinephrine. An increased level of these substances causes: a persistent increase in pressure, palpitations, chest pain, nausea, vomiting, nervous excitement. Mostly the disease manifests itself in the form of hypertensive crises.

Pheochromocytoma is a rather rare disease: 2 cases per 1 million population. The average age of patients is 20-50 years, but 10% are children. In childhood, boys are more likely to get sick, but among adult patients, the majority of women.

Pheochromocytoma is a tumor that has good circulation and is surrounded by a capsule. Its dimensions can vary from 0.5 to 14 cm. It increases by 3-7 mm annually. In 90% of cases, pheochromocytoma is a benign tumor, but in 10% it is a malignant neoplasm consisting of cancer cells.

The tumor can be localized on the adrenal gland itself or nearby. Outside the adrenal gland, pheochromocytoma secretes norepinephrine only. At the same time, the symptoms of the disease are less pronounced, since this hormone has a milder effect on the body. In the vast majority of patients, the tumor is diagnosed on one adrenal gland, in 1/10 the lesion is bilateral.

What are the adrenal glands?

Adrenal function- the production of hormones that regulate metabolism and facilitate the adaptation of the body to adverse conditions.

The adrenal glands have 2 layers:

• cortical substance - located on the surface;
• the medulla is the inner part of the adrenal gland.

Causes of Pheochromocytoma

• hereditary predisposition. In 10% of cases, patients have relatives with an adrenal tumor. The disease is associated with mutations in the gene responsible for the functioning of the adrenal glands. As a result, the cells of the adrenal medulla grow uncontrollably.


• Multiple endocrine neoplasia Type 2A (Cipple's syndrome) and Type 2B (Gorlin's syndrome). These are hereditary diseases that are characterized by the proliferation of cells of the endocrine glands. In addition to the adrenal glands, a number of other organs are affected: the thyroid and parathyroid glands, mucous membranes and the musculoskeletal system.

Pheochromocytoma Symptoms

Mostly pheochromocytoma manifests itself in the form of hypertensive attacks that last from 5 minutes to several hours.

An increase in pressure in 95% of cases is manifested by three symptoms:

• headache
• heartbeat
• increased sweating

Diagnosis of pheochromocytoma

Stimulation tests

Test with α-blockers - phentolamine or tropafen. These drugs block the effect of adrenaline and norepinephrine on the body. The test is carried out for people whose blood pressure is stable over 160/110 mm. Hg

Intravenously injected 1 ml of 1% phentolamine or 2% solution of tropafen. If within 5 minutes the pressure decreased by 40/25 mm Hg, then this gives reason to assume pheochromocytoma. To prevent the development of side effects (orthostatic collapse), patients should lie down for 2 hours after the test.

The remaining stimulating tests pose a danger to the health of patients, therefore they are not used.

Laboratory tests

1. General blood analysis

   During an attack, there are changes in the blood associated with contraction of the smooth muscles of the spleen under the influence of catecholamines.

   • leukocytes are increased: over 9.0x10 9 /l
   • lymphocytes are increased: over 37% of the total number of leukocytes
   • eosinophils are elevated: over 5% of the total number of leukocytes
   • erythrocytes are increased: over 5.0 10 12 / l
   • glucose level is increased: over 5.55 mmol / l
2. Determination of the level of catecholamines in blood plasma

   Norm:

   • adrenaline: 10 - 85 pg / ml.
   • norepinephrine: 95 - 450 pg / ml.
   • dopamine: 10 - 100 pg / ml.

• The level of hormones is increased by tens and hundreds of times during attacks. The rest of the time it can be normal or low. With hypertension, the level of hormones is increased by 2 times.
• Norepinephrine levels are higher than adrenaline levels.
• Dopamine levels are significantly elevated in adrenal cancer.

For analysis, urine is taken within 3 hours after the crisis or daily.

1. Daily urinalysis. All urine during the day is collected in a container of at least 2 liters. The container must be stored in a refrigerator. 10 ml of a 30% H2SO4 solution is added as a preservative. The last portion of urine is taken at the same time as the first. The volume of urine is recorded. The contents of the container are shaken and poured into a sterile container of 100 ml for research.
2. Analysis of a three-hour portion of urine. The most accurate result can be obtained during an attack, but at this point, urine collection may be difficult. Therefore, the sample is taken within 3 hours after the attack.

• The norm of catecholamines is 200 mcg / dl. With pheochromocytoma, the level is increased several times.
• There are casts in the urine.
• Increased glucose level: over 0.8 mmol / l.
• Increased protein level: over 0.033 g / l.

Outside of seizures, urinalysis is normal.

Determination of the total concentration of metanephrines (metananephrine and normetanephrine) in plasma and urine Hormones are rapidly destroyed in the blood and bind to receptors, and metanephrine and normetanephrine (the breakdown products of adrenaline and noradrenaline) persist for 24 hours. The sensitivity of the method is 98%.

Symptoms pheochromocytomas:

The level of metanephrines in blood plasma:

• metanephrine over 2-3690 pg / ml.
• normetanephrine over 5-3814 pg / ml.

• metanephrine over 345 mcg / day.
• normetanephrine over 440 mcg / day.

Instrumental research methods

Non-invasive and safe examination of internal organs based on the properties of ultrasonic waves. Tissues reflect ultrasound differently, and the machine analyzes the results and compiles an image. The accuracy of the study is 80-90%. The effectiveness increases if the size of the tumor exceeds 2 cm.

A hydrogel is applied to the skin, which allows ultrasound to pass through the tissue. The sensor sends ultrasonic waves and picks up their reflection from the organs. Pheochromocytoma differs in density and structure from the tissue of the adrenal glands, so it is clearly visible on the monitor screen.

Target diagnostics: to determine the localization and size of the tumor.

Symptoms:

• small rounded formation at the upper pole of the adrenal glands
• the capsule is clearly visible
• smooth borders of the tumor
• acoustic density is increased - pheochromocytoma looks like a light spot
• inside the tumor there are cavities (areas of necrosis) filled with fluid
• areas of calcium deposition

Computed tomography is a study during which the patient is given a series of x-rays from different angles. With the help of computer equipment, their results are compared to obtain a layered image of the internal organs. With the introduction of an intravenous contrast agent, you can get more information about the tumor and its vessels. The effectiveness of such a study in pheochromocytoma approaches 100%.

Purpose of the study- evaluate the size of the adrenal tumor and clarify its nature. Mandatory research in preparation for surgery.

Symptoms:

• round or oval formation
• structure is heterogeneous. The tumor may have a capsule or areas of calcium deposition, hemorrhage, cavities
• with the introduction of a contrast agent, numerous vessels feeding the tumor are visible
• the rate of removal of the contrast agent from pheochromocytoma more than 50% in 10 minutes
• tumor - an area of ​​increased density (25-40 units)

A non-X-ray research method that allows visualization of the adrenal glands and other organs of the retroperitoneal space. In a constant magnetic field, hydrogen atoms in cells create electromagnetic oscillations that are captured by sensitive sensors. A contrast agent is injected intravenously to visualize the vessels that feed the adrenal gland and the tumor itself.

The patient lies on the table, and around him, inside the tunnel of the apparatus, the scanner takes readings. The results obtained are summed up and layer-by-layer images (slices) of the area of ​​interest are created.

With the help of MRI, it is possible to detect a pheochromocytoma from 2 mm and accurately determine its location. Typically, an MRI is ordered if contrast-enhanced CT scans do not provide a definitive diagnosis. The accuracy of the study is 90-100%.

Symptoms:

• rounded formation from a few mm to 15 cm;
• in a benign course, the contours are correct; in cancer of the adrenal cortex, the contours are fuzzy;
• may have a capsule;
• the structure is heterogeneous, may have solid inclusions or cystic cavities filled with fluid.

Adrenal scintigraphy

Isotopes of substances (iodcholesterol, scintadren) are injected intravenously, which accumulate in the tissue of the adrenal glands. After that, their presence is recorded using a scanner - a detector gamma camera.

This method allows you to identify pheochromocytoma, which are located not only on the adrenal gland itself, but also in its vicinity, as well as tumor metastases in the malignant course of the disease.

Symptoms:

• asymmetric accumulation of the radioisotope in the adrenal glands;
• accumulation of the isotope in the area of ​​the adrenal medulla;
• accumulation of the isotope outside the adrenal gland.

If the pheochromocytoma does not have a characteristic appearance on CT and MRI, then a fine needle biopsy is required. Local anesthesia of the area is carried out with novocaine or lidocaine. Under the control of ultrasound or CT, a needle is inserted into the tumor and, by pulling the syringe plunger, the material is taken for examination under a microscope.

Target biopsy - to differentiate pheochromocytoma from an inflammatory process or a malignant tumor, to determine which cells the tumor consists of. Is it benign or is it cancer of the adrenal glands.

Symptoms pheochromocytomas:

• cells of the cortex and medulla of the adrenal gland
• blood cells
• colloidal liquid
• atypical malignant cells indicating a cancerous nature of the tumor

Pheochromocytoma Treatment

Medical treatment of pheochromocytoma

Surgery for pheochromocytoma

Indications for the operation:

• hormonally active pheochromocytoma;
• hormonally inactive tumor more than 4 cm.

• blood clotting disorders;
• excessively high or low pressure that cannot be corrected;
• severe condition of the patient;
• age over 70 years old.

Operation efficiency. Many doctors consider surgery the only effective treatment. It quickly eliminates the symptoms of the disease and reduces the risk of strokes. In 90% of patients, the pressure returns to normal immediately after removal of the pheochromocytoma. The risk of tumor recurrence is minimal.

Prolonged arterial hypertension and hypercatecholaminemia lead to changes in the myocardium (catecholamine myocardial dystrophy) and can cause non-coronary myocardial necrosis. Excessive intake of catecholamines into the blood provokes the development of spasm of peripheral vessels with hypovolemic arterial hypertension, centralization of blood circulation, and also causes ischemic atrophy of the canal epithelium of the kidneys.

Catecholamines are responsible for the manifestation of an adaptive stress response, during which the sympathetic nervous system is activated, and the body prepares for increased physical and emotional stress.

The uncontrolled growth of hormone-producing cells in pheochromocytoma leads to the fact that the concentration of catecholamines in the blood exceeds the threshold level. If the tumor secretes a biologically active substance constantly, persistent increase in blood pressure. If the release of the hormone occurs episodically, a catecholamine crisis develops.

Pheochromocytomas can be either benign or malignant (the latter account for about 10% of all tumors). Both of them must be removed surgically in full, because frequent crises or a constant increase in the level of catecholamines in the blood causes secondary damage to the myocardium, nervous system and other organs. The disappointing moment is that in almost half of the observations (as a result of on time or ineffective examinations), the diagnosis of pheochromocytoma is established posthumously.

The reasons

The specific causes and symptoms of pheochromocytoma are unknown. In some cases heredity plays a role Approximately 10% of patients have a family history of the disease. Pheochromocytoma may also be a manifestation of multiple endocrine metaplasia syndrome. In other cases, it is believed that the cause of pheochromocytoma was the impact of nonspecific carcinogenic factors.

The cause of the crisis in the paroxysmal form can be any kind of stress: physical or emotional overload, hypothermia, drinking alcohol, coffee or smoking, as well as sudden movement.

Classification

Chromaffin cells are present not only in the adrenal cortex, but also in the sympathetic ganglions; therefore, pheochromocytoma can be located both in the adrenal gland and in other organs and tissues. Extra-adrenal localization is characteristic of hereditary tumors.

Distinguish benign and malignant pheochromocytomas. The latter occur in no more than 10% of cases. They are usually located outside the adrenal glands and produce predominantly.

When making a diagnosis, a clinical classification is used, according to which the disease is divided into 3 groups.

Silent signs of pheochromocytoma, with no obvious manifestations of hypercatecholaminemia. They, in turn, are divided into:

• asymptomatic, in which clinical manifestations are completely absent throughout the patient's life, and the tumor is not diagnosed; in this case, along with the hormone, the tumor cells produce an enzyme that turns it into an inactive metabolite, so symptoms do not appear;
• latent (exchange) symptoms of pheochromocytoma appear only with very strong stressful influences, with a normal rhythm of life, there is a slight increase in the level of metabolism and, in rare cases, emotional lability.

With a characteristic clinical picture, they are divided into:

• paroxysmal - an increase in pressure and other symptoms caused by an excess of adrenaline in the blood, appear only during an attack, there are no symptoms in the interictal period;
• persistent - manifested by a stable increase in blood pressure.

With uncharacteristic clinical symptoms of pheochromocytoma, which are similar to manifestations of other diseases. They can manifest as a cardiovascular, psychoneurovegetative, abdominal or endocrine-metabolic syndrome.

Symptoms

The paroxysmal form of the disease is characterized by a complete absence of symptoms in the interictal period. Hypersecretion of adrenaline can be provoked by any extreme effect on the body:

• hypothermia or overheating;
• emotional stress;
• viral infection;
• alcohol intake;
• excessive consumption of coffee;
• smoking.

An attack can occur without an external cause.

During a paroxysm, systolic and diastolic pressure rises by 40-60 units, the skin turns pale. The person is shivering, body temperature may rise, pain and heaviness in the chest and upper abdomen are felt, nausea is observed, ending in vomiting. The attack can last from 5-10 minutes to several hours. At the end of the paroxysm, all physiological parameters return to normal: pressure and body temperature decrease, the skin acquires a normal shade. Profuse sweat may come out, a large amount of unconcentrated urine is excreted. The frequency of attacks varies from several times a day to once a year.

With a high intensity of symptoms or a prolonged course of an attack, complications from adrenaline-dependent organs (or) are possible.

In the persistent form of pheochromocytoma, the pressure remains constantly elevated. Therefore, arterial hypertension often becomes the primary diagnosis for such patients. Persistent hypercatecholaminemia leads to the development of complications on the part of the organs concerned. The heart suffers first: dysmetabolic and rhythm disturbances are present in almost all patients with a persistent form.

With a masked form of pheochromocytoma, clinical manifestations can resemble a heart attack or angina pectoris, and also mimic neuropsychiatric disorders. Perhaps the appearance of pain in the abdomen like acute or endocrine disorders, similar to the clinic or diabetes.

Diagnostics

Diagnosis of a pheochromocytoma tumor is based on hormonal studies and radiation methods, which make it possible to directly visualize the neoplasm. Each of these two areas is responsible for its part of the survey. The purpose of hormonal studies is to detect the production of an excess amount of catecholamines, radiation methods detect or exclude the presence of a tumor in the adrenal gland and other areas of the body.

The clinical manifestations of pheochromocytoma are very diverse, so it is impossible to diagnose and start treatment of pheochromocytoma based on complaints and clinical examination data. The most difficult thing is to make a differential diagnosis with arterial hypertension. In favor of an adrenal tumor, the following signs indicate:

• the young age of the patient and the short duration of the disease with pheochromocytoma;
• signs of increased basal metabolism during normal functioning of the thyroid gland;
• decreased glucose tolerance or diabetes mellitus;
• marked weight loss since the onset of symptoms.

To confirm the diagnosis, a biochemical analysis of blood and urine is performed for the content of catecholamines and their biologically inactive methylated derivatives.

A test for the content of catecholamines in the blood or urine makes sense to carry out with a persistent form of pheochromocytoma. or immediately after an episode of high blood pressure (compared to baseline). Only a part of the biologically active substances produced by the tumor enters the bloodstream unchanged.

Neoplasm cells also produce a certain amount of an enzyme that converts active adrenaline and norepinephrine into inactive forms: metanephrine and normetanephrine. This makes possible the existence of a paroxysmal and asymptomatic form of pheochromocytoma, and also makes it difficult to diagnose it by determining the level of catecholamines in the blood and urine.

Determination of the level of methylated derivatives of catecholamines (MPC) in the blood and urine has an extremely high diagnostic value. A negative result of this test makes it possible to exclude pheochromocytoma, and the obtained results make it possible to make an assumption about the localization and degree of differentiation of tumor tissues and adjust the surgical treatment plan.

If a pathology was diagnosed based on a biochemical analysis, it is necessary to determine the location of the tumor in order to subsequently treat pheochromocytoma with the correct method. For this apply:

• Ultrasound of the adrenal glands; in this case, only large tumors located in the adrenal glands are detected, so the diagnostic value of this method is low;
• CT or MRI retroperitoneal space or the whole body; using these methods, it is possible to detect tumor foci with a diameter of up to 1 mm of adrenal and extra-adrenal localization;
• scintigraphy- the most accurate research method; at the same time, a special substance containing labeled is introduced into the human body, it accumulates in chromaffin cells and practically does not enter normal tissues; the localization of the tumor is determined using a special sensor that recognizes the accumulation of labeled atoms; in this way it is possible to find metastases in malignant pheochromocytoma;
• PAT(positron emission tomography) - this study has the greatest diagnostic value and allows you to localize tumors that have not been detected using other research methods.

Treatment

With pheochromocytoma, recovery is possible only with complete removal of the tumor. Therefore, the main treatment for pheochromocytoma is surgery. Medications in the treatment of fetochromocytoma are used for emergency care during an attack and to prepare the patient for surgery.

Removal of the tumor significantly improves blood pressure in the vast majority of patients and reduces the risk of myocardial infarction, stroke, myocardial hypertrophy and other complications. However, an operation performed on an unprepared patient with high blood pressure (if the latter has persistent hypertensive crises or high blood pressure) can cause the development of life-threatening complications during the operation - cardiac arrhythmias, uncontrolled hemodynamics syndrome, vascular intraoperative strokes.

The provision of emergency care is reduced to lowering blood pressure with the help of adrenergic blockers, since vasodilators with an excess of catecholamines are ineffective.

Preparation for surgery includes:

• enhanced nutrition with increased energy value to restore depleted body reserves;
• a regimen with the complete elimination of emotional stress, physical exertion and other factors provoking an attack;
• the introduction of adrenoblockers to normalize blood pressure and prevent intraoperative complications.
• In malignant pheochromocytoma, a course of chemotherapy is performed before surgery.

Surgical treatment for single tumors of the adrenal localization is carried out by an open or endoscopic method. In the first case, a scar remains from the skin incision, but the surgeon gets the opportunity to visually examine the organ and remove the adjacent tissue if the tumor turns out to be malignant. Histological examination can be performed intraoperatively.

Endoscopic surgery is less invasive and easier to tolerate by patients, but is associated with certain technical difficulties and does not provide a complete overview of the surgical field.

There is no standard surgical technique for the removal of extraadrenal tumors. A priority - complete removal of the tumor only in this case the treatment will be successful.

Prevention

Measures of specific prevention of pheochromocytoma are unknown, timely detection and appointment of adequate treatment are of great importance.

Forecast

With complete surgical removal of a benign pheochromocytoma, the prognosis is favorable. In most cases, a decrease in blood pressure to normal levels and regression of additional symptoms is achieved. The recurrence rate is not higher than 15%.

In malignant forms of pheochromocytoma, the prognosis is less favorable. With a full course of chemotherapy and complete surgical removal of the tumor, a five-year survival rate is less than 50%.

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Among all hormone-producing tumors, pheochromocytoma occupies a special place, which not only has a significant effect on many organs and tissues, but also can lead to serious and deadly complications.

The source of the tumor is the so-called chromaffin cells concentrated mainly in the adrenal medulla. In addition, chromaffin tissue is found along the aorta, in the zone of the gates of the liver and kidneys, in the solar plexus, mediastinum, heart and other parts of the body.

Patients with pheochromocytoma are usually young and middle-aged people, from 30 to 50 years old, more often women, every tenth patient is a child. Up to 90% of cases are neoplasia of adrenal localization, much less often it grows in the area of ​​the aortic paraganglion, very rarely in the abdominal cavity, head and neck.

Cells of chromaffin tissue produce norepinephrine, epinephrine, dopamine, without which the normal functioning of the body, adaptation to stress, maintaining pressure, and many metabolic processes are impossible. In a healthy body, they are constantly formed by the adrenal glands, and their concentration increases during stressful situations, injuries and other adverse conditions.

The release of adrenaline provokes an increase in blood pressure, frequency and strength of cardiac impulses, leads to a spasm of small vessels of the skin, gastrointestinal tract, and an increase in blood glucose levels. Norepinephrine in action is in many ways similar to adrenaline, but it also causes a variety of vegetative symptoms - agitation, fear, tachycardia, sweating, etc. Dopamine is responsible for the psycho-emotional state and vegetative.

If the effects of these hormones are normally realized under stress and contribute to a better adaptation to adverse conditions, then in pheochromocytoma their number is not adequate to the situation. An excess of catecholamines provokes hypertension, degenerative changes in the myocardium and renal epithelium, vasospasm and various autonomic disorders.

Severe symptoms and a high risk of serious complications require early diagnosis and timely treatment, usually surgical, although even after elimination of tumor growth foci, hypertension and other disorders may not completely disappear.

Causes and essence of pheochromocytoma

The causes of pheochromocytoma are not fully understood and remain a mystery in most patients. Approximately 10% of cases are chromosomal abnormalities, then they talk about the family form. The disease is transmitted in a dominant way, so among close relatives there may be a significant number of patients.

Often, pheochromocytoma is combined with other endocrine neoplasms, being part of the syndrome of multiple endocrine neoplasia. Its growth is possible with neurofibromatosis, medullary thyroid carcinoma. These cases are also familial.

Externally, pheochromocytoma resembles a node surrounded by a capsule, the dimensions are usually within five centimeters., but more is possible, while the amount of hormones synthesized by tumor cells does not depend on its size. In addition to catecholamines, the tumor can secrete serotonin, calcitonin, adrenocorticotropic hormone.

Adrenaline-predominantly synthesizing neoplasia is usually dark brown, while norepinephrine-secreting tumors are lighter in color (yellow, light brown). The tumor itself has a soft texture, is rich in blood vessels, and is prone to hemorrhages, which is why it acquires a rather characteristic appearance. Necrosis is possible, after the resorption of which cavities remain, and the pheochromocytoma has a cystic character.

In the absolute majority of cases, the neoplasm has a unilateral type of lesion, about a tenth of which are bilateral tumors, the same number are extra-adrenal pheochromocytomas. Depending on the characteristics of tumor cells and their behavior, it is customary to isolate benign and malignant pheochromocytoma, which is also called pheochromoblastoma.

A malignant chromaffin tumor, more often than a benign variety, is localized outside the adrenal glands and synthesizes a large amount of dopamine. It is capable of metastasizing to the lymph nodes, liver, bones, and lungs. Metastasis, and not the degree of cell differentiation, is the main predictor of pheochromoblastoma.

Manifestations of a tumor

Pheochromocytoma is a hormone-producing neoplasia, therefore its manifestations are associated with the effect of their excess on organs and tissues. Among all such neoplasms, pheochromocytoma is distinguished by the most serious disorders of blood circulation, the work of the heart and kidneys.

Depending on the current, there are several forms of the disease:

1. Paroxysmal.
2. Permanent.
3. Mixed.

The paroxysmal form of pheochromocytoma accounts for up to 85% of cases. It is characterized by hypertensive crises, in which patients complain of severe headache, dizziness, shortness of breath, pain and discomfort in the heart area. Patients look frightened from a feeling of fear, similar to that which accompanies many heart diseases, trembling, restless, pale. Sweating appears, the pulse quickens, nausea, dry mouth, convulsions, fever, and large amounts of urine are possible.

In almost all patients, a combination of headache, palpitations and sweating becomes an indispensable manifestation of a crisis. These symptoms of pheochromocytoma are combined into the so-called Carney triad.

Excessive physical activity, errors in diet, alcohol intake, stress, and even urination can provoke a crisis. You should not try to probe the tumor yourself, as this can also lead to a sharp jump in pressure.

The crisis can last several minutes, and in severe cases - 2-3 hours or more. Characteristic is its sudden ending with the release of a large amount of urine (sometimes up to five liters), profuse sweating, the patient feels tired and very weak.

classic manifestations of pheochromocytoma

The permanent variant of the course of pheochromocytoma is characterized by a consistently high level of blood pressure and proceeds similarly to primary hypertension. Patients feel weak, emotionally unstable, prone to metabolic disorders, especially diabetes. At mixed form against the background of chronically high blood pressure, periodic hypertensive crises occur (with excitement, stress and other provoking conditions).

A very dangerous type of tumor course is considered to be a situation where the pressure is either high or low and changes unpredictably. This phenomenon is called catecholamine shock and is considered a life-threatening condition that is diagnosed in every tenth patient, somewhat more often in children.

Serious complications of a hypertensive crisis with pheochromocytoma are cerebral hemorrhage, heart attack, pulmonary edema, acute kidney failure.

It can be difficult to suspect pheochromocytoma in its atypical course. So, the tumor can "simulate" a heart attack, acute pathology in the abdomen, stroke, thyrotoxicosis, kidney disease, and sometimes it is completely asymptomatic.

Frequency asymptomatic forms tumors are difficult to establish, because such patients do not seek help due to the absence of complaints. A case is described when neoplasia reached several kilograms of weight, while the patient did not experience any autonomic disorders or hypertension, and the only concern was back pain.

Meanwhile, the asymptomatic course is quite dangerous, because the patient can die suddenly from a sharp hemodynamic disorder, hemorrhage into the tumor. With a tumor not diagnosed in time, any stress, physical activity, surgery or childbirth can be fatal due to severe hypotension and shock.

Diagnosis of pheochromocytoma

Diagnosis of pheochromocytoma is complex and requires not only a thorough assessment of the patient's complaints and symptoms of the disease, but also a series of laboratory and instrumental tests. Biochemical blood tests are considered an obligatory component in order to confirm changes in hormonal status.

After examining and talking with the patient, he is sent for tests, including the determination of catecholamines in the blood and urine. If necessary, it is possible to study other hormones (cortisol, parathyroid hormone, adrenocorticotropic hormone). To obtain more reliable results, provocative tests are carried out with the introduction of histamine, clonidine, glucagon, etc.

Mandatory general and biochemical blood tests with a study of sugar levels, counting the number of formed elements. With a tumor, glucose rises, the numbers of leukocytes and lymphocytes increase, and eosinophils increase.

pheochromocytoma on CT

Among the instrumental methods, ultrasound, computed and magnetic resonance imaging, X-ray examination of the chest, and excretory urography are of great diagnostic value. These diagnostic methods allow you to determine the exact location, size and anatomical features of the tumor formation.

Given the changes in the organ of vision, patients need to consult an ophthalmologist, and the negative impact of the disease on the heart and blood vessels requires regular electrocardiography. If there is doubt about the structure of the tumor, a fine-needle biopsy may be prescribed, but the procedure is used relatively rarely due to the risk of complications.

Video: pheochromocytoma on CT

Treatment

Treatment for pheochromocytoma consists of surgical removal and drug therapy. Since the neoplasm is accompanied by high blood pressure, it is very important to stabilize it at an acceptable level, which will allow the operation to be carried out as safely as possible.

Conservative therapy

Medical therapy includes:

• Alpha-blockers (tropafen, phentolamine);
• Beta-blockers (propranolol, atenolol);
• calcium antagonists.

The drug phenoxybenzamine, which has adrenoblocking properties, is quite effective in pheochromocytoma. It is prescribed according to a scheme that involves a gradual increase in dosage from 10 mg to 40 mg in two to three doses daily. The dose may be even higher if it provides stable blood pressure.

During treatment, not only pressure is controlled, but also cardiac activity: for two weeks there should be no deterioration in the ST segment and T wave on the ECG, and the number of extrasystoles should not exceed one per 5 minutes of observation.

Catapressan and raunatin allow to reduce pressure between crises in patients with pheochromocytoma, which, however, do not save from hypertensive crises and cause only a decrease in systolic pressure.

Prazosin, tetrazosin are considered more selective alpha-blockers. Acting directed at specific receptors, prazosin causes fewer adverse reactions, does not contribute to tachycardia, and a faster action allows you to choose an effective dose in a shorter period of time. In addition, with the appointment of prazosin, the likelihood of hypotension in the postoperative period is lower.

In pheochromocytoma with rare hypertensive crises, preference is given to agents from the group of calcium antagonists - nifedipine, verapamil, diltiazem. These drugs do not contribute to severe hypotension and may even be given prophylactically if the tumor occurs without hypertension. Beta-blockers are indicated for concomitant heart disease, severe tachycardia.

It is important to note that the scheme for maintaining optimal blood pressure is selected individually for each patient, taking into account the form of the disease and the characteristics of its course, so there are no identical prescriptions for different patients.

If surgical treatment of adrenal pheochromocytoma is not possible, conservative therapy with drugs that can reduce the amount of circulating catecholamines in the blood is used. The possibilities of such treatment are limited by the high risk of complications and side effects, so it is used quite rarely.

The drug alpha-methyltyrosine is able to reduce the level of catecholamines by 80%, and its maximum dose should not exceed 4 g. When prescribing this drug, the possibility of disorders of the digestive tract (diarrhea), as well as neurological and mental adverse reactions, must be taken into account.

Alpha-methylparatyrosine is considered safer, which sharply inhibits the formation of hormones by the tumor itself and, accordingly, reduces their release into the blood. It can be prescribed in preparation for surgical treatment to reduce the risks of surgery.

With malignant transformation of pheochromocytoma or the initial growth of pheochromocytoma, cytostatics are used - vincristine, cyclophosphamide.

Surgery

Surgical treatment consists in removing the adrenal gland with a neoplasm. Its complexity is due to the need for extremely careful manipulations in the surgical field, since even touching the tumor can provoke a sharp release of hormones. It is important to provide free access to the affected tissues and the possibility of reviewing the internal organs to exclude extra-adrenal foci of tumor growth. To remove pheochromocytoma, transperitoneal, extraperitoneal accesses, through the chest cavity, or a combined approach are used.

With multiple pheochromocytoma, the situation is even more complicated. If other tumor foci are found, they are removed as much as possible. If a single operation is not possible, the treatment is carried out in several stages. Leaving an ectopic tumor tissue is considered an extreme case, for which there must be good reasons - too high a risk for the patient or lack of technical ability to remove the neoplasm.

The operation itself consists in laparotomy access to the tumor (laparoscopy is not used due to possible complications), its removal along with the adrenal gland (total adrenalectomy). With a bilateral lesion, the surgeon excised both adrenal glands, and if other growth foci are found, they also remove them. The operation is performed under careful control of blood pressure and other hemodynamic parameters.

adrenalectomy - surgical removal of the adrenal glands

If the patient is a pregnant woman, then pheochromocytoma "will not allow" to bear and give birth to a child without a huge risk to health, first of all, to the expectant mother. In such cases, doctors have no other choice but to terminate the pregnancy (abortion or caesarean section for a long time) and then remove the neoplasm.

Video: an example of a laparoscopic operation to remove a pheochromocytoma

After surgical removal of a pheochromocytoma, some complications are possible. If the pressure does not fall, but remains high, then there is a possibility of a violation of the operating technique when the renal artery was accidentally ligated. Another reason may be the presence of areas of pheochromocytoma, especially with multicentric growth, as well as the presence of primary hypertension as a comorbidity.

Severe hypotension is another possible complication of treatment, the causes of which may be internal bleeding, insufficient control of circulating blood volume, the continued effect of antihypertensive drugs prescribed in the preparatory period or during the operation itself.

In benign pheochromocytoma, surgical treatment leads to an almost complete cure for most patients. There is no need to talk about complete healing, since the tumor significantly changes the state of other organs. The probability of recurrence does not exceed 12%, and in the case of a unilateral lesion, the risk of involvement of the second adrenal gland is very small. A poorer prognosis in patients with multiple pheochromocytoma, especially if the surgeon was not able to excise all the foci of the neoplasm.

In the postoperative period, some of the symptoms of the tumor may persist. This is due to the long-term effect of catecholamines on the heart and kidneys, which managed to undergo secondary changes. In this regard, persistent hypertension and/or tachycardia are considered as consequences of the presence of a tumor, and they may appear some time after the operation.

Summing up, I would like to note that the operation is not only the most radical method of treatment, but also the only way to save the life of the patient, therefore, in no case should it be abandoned. Even if it is not possible to completely remove the tumor tissue, and hypertension still develops in the postoperative period, these consequences are incommensurably safer than the presence of pheochromocytoma in the adrenal glands.

The author selectively answers adequate questions from readers within his competence and only within the limits of the OncoLib.ru resource. Face-to-face consultations and assistance in organizing treatment are not currently provided.

Pheochromocytoma (chromaffinoma) is that which is formed during the pathological growth of chromaffin cells and is characterized by hormonal activity. It most often originates from the adrenal medulla, and can be either benign or malignant.

Pheochromocytomas often develop in young and mature people (20-40 years old), and the prevalence among men and women is approximately the same. In childhood, the incidence is higher among boys. The tumor produces an excessive amount of peptides and biogenic amines (dopamine, adrenaline and norepinephrine), resulting in catecholamine crises.

Less than 10% of the total number of diagnosed pheochromocytomas falls on the share of malignant tumor varieties (pheochromoblastomas). For such tumors, the location outside the adrenal glands is very characteristic. Secondary foci (metastases) are formed in regional lymph nodes, liver, distant organs (lungs) and tissues (muscle and bone).

Etiology

As a rule, the true cause of chromaffinoma formation remains unclear.

Every tenth patient has a genetic predisposition. During the collection of anamnesis, it turns out that these tumors were previously diagnosed in the parents. Geneticists believe that the pathology is inherited in an autosomal dominant manner.

Often, pheochromocytoma is one of the manifestations of a hereditary disease - multiple endocrine neoplasia syndrome. It also affects other organs of the endocrine system - the thyroid and parathyroid glands.

Pathogenesis

Pheochromocytoma can occur not only from the adrenal medulla, but also from the aortic lumbar paraganglion (in such cases they speak of paragangliomas). Neoplasms of this type are also detected in the pelvic area, chest and abdominal cavity. In the rarest cases, chromaffinoma is found in the head and neck area. Cases of tumor localization in the pericardium and cardiac muscle are described.

Active substances that can be synthesized by chromaffinoma:

Pheochromocytoma is capable of producing neuropeptide Y, which is characterized by pronounced vasoconstrictive properties.

The level of hormonal activity does not depend on the size of the neoplasm (they are variable and can reach 5 cm). The average weight of a pheochromocytoma is 70 g. Rich vascularization is characteristic of these encapsulated tumors.

Symptoms of adrenal pheochromocytoma

Symptoms are determined by an excess of one or another substance. Hypersecretion of catecholamines by pheochromocytoma leads to the development of. Tumors are detected in approximately one in 100 patients with persistently elevated diastolic (“lower”) pressure.

The course of hypertension can be stable or paroxysmal. Periodic crises are accompanied by disorders of the cardiovascular and nervous systems, as well as digestive and metabolic disorders.

During a crisis, blood pressure rises sharply, and in the intervals between paroxysms, it is consistently high or returns to normal values.

Symptoms of a crisis with pheochromocytoma:

• up to 200 mm. rt. Art. and more;
• unmotivated feeling of anxiety and fear;
• intense;
• skin blanching;
• (excessive sweating);
• cardialgia ();
• cardiopalmus;

During an attack in the peripheral blood, increased and leukocytosis is noted.

The duration of paroxysm ranges from several minutes to an hour or more. Their frequency varies from single attacks within a few months to 10-15 per day. The crisis is characterized by a sharp spontaneous relief, which is accompanied by a sharp drop in blood pressure. The patient has profuse sweat and increased urine output (up to 5 liters) with a low specific gravity. He complains of general weakness and a feeling of "brokenness" throughout the body.

Crisis factors:

• general overheating or hypothermia of the body;
• significant physical activity;
• psycho-emotional;
• taking certain pharmacological agents;
• alcohol consumption;
• abrupt movements;
• medical manipulations (deep palpation of the abdomen).

The most severe outcome of an attack is catecholamine shock. It is characterized by uncontrolled hemodynamics - episodes and hypertension are randomly replaced and are not amenable to medical correction. In severe hypertensive crisis caused by chromaffinoma, complications such as exfoliating, development of functional are not excluded. Retinal hemorrhages are often noted. Paroxysms pose a great danger to women during pregnancy.

With a stable course, the patient has consistently high blood pressure, against which, over time, pathologies of the heart muscle and kidneys develop, as well as changes in the fundus. Patients with pheochromocytoma are characterized by mental lability (mood swings and high psycho-emotional excitability), periodic cephalgia, and increased physical and mental fatigue.

Among metabolic disorders, in particular, is an increase in blood glucose levels (hyperglycemia), which often causes development.

Important:with pheochromoblastomas (malignant chromaffinomas), the patient is observed (a sharp decrease in body weight) and abdominal pain appears.

Diagnosis of pheochromocytoma

In the course of a general examination in patients, palpitations, pallor of the skin of the face, neck and chest, and increased blood pressure are detected. Orthostatic hypotension is also characteristic (when a person stands up, the pressure drops sharply).

Important:palpation examination (palpation) of the neoplasm can provoke catecholamine paroxysm.

One of the important diagnostic criteria is an increase in the content of catecholamines in the urine and blood of the subject. In serum, the level of chromogranin-A (universal transport protein), adrenocorticotropic hormone, calcitonin and trace elements - calcium and phosphorus - is also determined.

Nonspecific changes in, as a rule, are determined only during the crisis.

With pheochromocytomas, there are often concomitant pathologies - arterial circulation disorders in the extremities (Raynaud's syndrome) and hypercortisolism with the development of the syndrome.

In a significant proportion of the examined, damage to the retinal vessels (retinopathy) caused by hypertension is found. All patients with suspected pheochromocytoma should undergo additional examination by an ophthalmologist.

During the differential diagnosis of chromaffin, provocative (stimulating) and suppressive tests with histamine and tropafen are used, but there is a possibility of obtaining false positive and false negative test results.

Of the hardware diagnostic methods, ultrasound scanning and tomographic examination (and) of the adrenal glands are considered the most informative. They allow you to specify the size and location of the neoplasm. Additionally, they resort to selective arteriography and adrenal glands, as well as chest organs (to confirm or exclude intrathoracic localization of chromaffinoma).

Pathologies with which differential diagnosis is carried out:

• paroxysmal;
• some kinds.

Note: in pregnant women, the symptoms of pheochromocytoma are masked as late toxicosis (gestosis) and the most severe forms of their course - eclampsia and preeclampsia.

It is far from always possible to reliably establish the malignancy of a tumor at the preoperative stage. It is possible to speak with confidence about pheochromoblastoma if there are such clear signs as invasion (germination) into nearby structures or distant secondary foci.

Treatment and prognosis

If pheochromocytoma is detected, drug therapy is carried out, the purpose of which is to reduce the severity of clinical symptoms and stop paroxysmal seizures.. Conservative measures involve the appointment of drugs from the group α-blockers(Phentolamine, Phenoxybenzamine, Tropafen, and in the preoperative period - Doxazosin) and β-blockers(Metoprolol, Propranolol). In crises, additionally introduced Sodium nitroprusside. A very effective drug for lowering catecholamine levels is A-methyltyrosine, but its regular intake can provoke mental disorders and digestive disorders.

Then a surgical intervention is performed - a total adrenalectomy. During the operation, the affected adrenal gland is removed along with the tumor. Since the location of the pheochromocytoma outside the adrenal gland and the presence of multiple neoplasms is high, preference is given to the “classic” laparotomy approach, but possibly less traumatic.

Multiple endocrine neoplasia is an indication for resection of both adrenal glands.

When diagnosing pheochromocytoma in a pregnant patient, depending on the period, an artificial interruption is performed or, and then the tumor is removed.

When establishing the malignant nature of the neoplasm and detecting distant secondary foci, it is indicated. Such patients need course treatment with cytostatic drugs - Dacarbazine, Vincristine or Cyclophosphamide.

In most cases, after resection of a benign neoplasm, blood pressure indicators normalize, and other clinical signs regress. If hypertension persists, there is reason to assume the presence of ectopic tumor tissue, incomplete removal, or accidental damage to the renal artery.

A single standard for surgical interventions for multiple tumors has not been developed. Sometimes it is advisable to carry out a resection in several stages.

The 5-year survival rate after surgery for benign chromaffinoma is 95%. After resection of pheochromoblastoma, the prognosis is less favorable.

These hormonally active tumors tend to recur in about 12% of cases. All patients undergoing surgery are strongly recommended to be examined annually by an endocrinologist.

Plisov Vladimir, medical commentator

Before starting at least some kind of treatment, irrefutable evidence of an existing ailment is required, otherwise doctors risk harming the patient.

To eliminate the symptoms of pheochromocytoma, it is necessary to conduct laboratory and differential diagnostics, take blood tests for metanephrines, conduct ultrasound and other examinations.

Only having established the correctness of the conclusion, you can begin to actively eliminate the problem of increasing catecholamines in the blood.

In general, the diagnosis of pheochromocytoma begins with an assessment of the symptoms and complaints of the patient. We wrote about this in the article. But they are so non-specific that they require additional examination methods, which you will learn about now.

Pheochromocytoma and laboratory diagnostics

The basis of laboratory diagnostics is the determination of the amount of catecholamines and their metabolites in urine and blood. The catecholamines include:

• adrenalin
• norepinephrine
• dopamine

The end products of the breakdown of catecholamines are collectively known as metanephrines. As a result of metabolism, adrenaline is converted into metanephrine and vanillylmandelic acid (VMA), norepinephrine is converted into normetanephrine and vanillylmandelic acid, and dopamine is converted into homovanillic acid.

Of the metabolites, vanillylmandelic acid (VMA) and total metanephrine, which includes metanephrine and normetanephrine, are determined. To determine the indicators, daily urine is examined, and not blood, as many people think, because the determination process is very complicated and there is a high probability of error.

Watching the hormones themselves (adrenaline and noradrenaline) does not make practical sense, because they are destroyed very quickly, and some pheochromocytomas do not release the hormones themselves into the blood, and in the adrenal tissue they attach a methyl group to the hormone molecule, thereby turning into metabolites that first into the blood and then into the urine.

Preparation for testing for pheochromocytoma

• 48 hours before the analysis, beer, chocolate, cheese, coffee, tea, avocados and bananas are excluded from food, stressful situations and physical exertion are avoided.
• Stop taking teracycline antibiotics, quinidine, reserpine, tranquilizers, adrenoblockers, MAO inhibitors within 4 days before passing the urine test.
• Refrain from smoking while collecting urine.

How to collect daily urine?

At 6 am, urinate in the toilet. During the day, until 6 am the next day, drain all urine into a jar. The six-hour urine of the next day should also go into the jar, not down the toilet.

For research, daily urine is collected, the vessel is stored in a dark place. Before passing the analysis, urine is mixed and poured about 100 ml into a separate jar. Should be sent to the lab immediately.

What are the norms of metanephrines in urine?

Below is a table of norms for total metanephrine.

And this is the norm for normetanephrine.

What other blood tests should be taken when diagnosing pheochromocytoma?

In addition to daily urine for metanephrines, it will be necessary to do a blood test for:

• chromogranina A
• aldosterone
• renin
• calcitonin
• blood cortisol

Chromogranin A is a transport protein that is released by any neuroendocrine tumors, which is pheochromocytoma. An increase in this indicator once again confirms the diagnosis of "pheochromocytoma" or "paraganglioma" (extra-adrenal localization of the tumor).

Instrumental methods for diagnosing pheochromocytoma

In addition to laboratory tests, instrumental methods are needed to confirm the diagnosis, as well as to visualize the tumor. In other words, we have proven that pheochromocytoma exists, now it needs to be found. Most often it is located in one or both adrenal glands, but sometimes the localization of the tumor is in another place.

For the diagnosis of pheochromocytoma, methods such as:

• ultrasound examination (ultrasound)
• computed tomography (CT) and magnetic resonance imaging (MRI)
• radioisotope scanning
• angiography with blood sampling from the inferior vena cava

Ultrasound for the diagnosis of pheochromocytoma

The ultrasound method is the cheapest and easiest diagnostic method, but it is not always possible to see the tumor, so doctors do not particularly trust this method.

On ultrasound, the tumor looks like this: round or oval with clear and even boundaries, the capsule is well defined, the acoustic density is increased, in most tumors there are cavities (necrosis) with liquid, there may be calcifications.

Computed tomography and MRI

CT and MRI are more informative methods, sensitivity up to 95%. The examination is carried out necessarily with contrast, so that the percentage of successful detection of pheochromocytoma is high.

The method is based on the difference between native adrenal density (before contrast injection), density during the arterial and venous phase (during contrast injection), and delayed density (after full contrast injection). This knowledge can give doctors information about the possible nature of the tumor.

For example, malignant tumors have a high initial density, they accumulate a pharmaceutical preparation very well and retain it in their tissue for a long time. And benign pheochromocytomas, on the contrary, have a low initial density, quickly accumulate the drug, but at the same time, the contrast of their tissue is quickly washed out.

radioisotope scanning

Radioisotope scans are performed with J131 (iodine 131), metaiodobenzylguanidine (MIBG).

The advantage of the method is that it allows, along with tumors of the adrenal gland, to detect tumors that are outside the adrenal gland, which, by the way, occupy 10% of the frequency of occurrence, as well as metastases. But this method is not the main one and is not often used.

Angiography for pheochromocytoma

Angiography has not found wide application, because tumors are poorly vascularized, i.e., they are supplied with blood. Therefore, this method is used to take blood from veins, according to the maximum content of catecholamines in which, one can judge the approximate localization of the tumor.

Which specialist should I contact to diagnose the symptoms of pheochromocytoma?

Pheochromocytoma is an endocrinological disease, which means that all diagnostics should be carried out by an endocrinologist. Treatment is carried out by surgeons-endocrinologists.

Differential diagnosis of pheochromocytoma

Differential diagnosis allows you to exclude other diseases that may have a similar course with pheochromocytoma. So, pheochromocytoma should be distinguished from:

• hypertension
• renovascular hypertension
• toxic goiter
• diabetes mellitus associated with hypertension
• hypothalamic vegetative vascular crisis