Pheochromocytoma: symptoms, diagnosis, treatment
Among all hormoneproducing tumors occupies a special place pheochromocytoma, which not only has a significant impact on many organs and tissues, but can lead to severe and deadly complications.
The source of the tumor are so-called chromaffin cells, are concentrated mainly in the adrenal medulla. In addition, chromaffin tissue is found in the course of the aorta, in the area of the gate of the liver and kidneys, solar plexus, mediastinum, heart and other parts of the body.
Patients with pheochromocytoma – usually young and middle age, from 30 to 50 years old, often women, every tenth patient is a child. Up to 90% of cases is adrenal neoplasia localization, much more rarely it grows in the region of the aortic paraganglia, very rarely – in the abdominal cavity, head and neck.
The cells of the chromaffin tissue to form norepinephrine, epinephrine, and dopamine, which are essential for the normal functioning of the body adapting to stress, maintaining pressure, many metabolic processes. In a healthy organism, they are formed by adrenal glands constantly, and their concentration is increased in stressful situations, injuries and other adverse conditions.
Adrenaline triggers an increase in blood pressure, frequency and strength of heart tremors, leads to spasm of small blood vessels of skin, gastrointestinal tract, increased levels of glucose in the blood. Norepinephrine by the action is similar to adrenaline, but also causes a variety of autonomic symptoms – anxiety, fear, tachycardia, sweating, etc. Dopamine is responsible for emotional state and vegetatation.
If the effects of these hormones in check is usually implemented with stress and contribute to a better adaptation to adverse conditions, in pheochromocytoma, their number is not adequate. Excess of catecholamines causes hypertension, degenerative changes in the myocardium and renal epithelium, the vascular spasm and a variety of autonomic disorders.
Severe symptoms and high risk of serious complications require early diagnosis and timely treatment, usually surgical, although even after the elimination of foci of tumor growth, hypertension and other disorders may not disappear completely.
The causes and nature of pheochromocytoma
Causes of pheochromocytomas until the end are unknown and remain a mystery in most patients. Approximately 10% of cases occur in chromosomal abnormalities, then talking about family form. The disease is transmitted by dominant, so among close relatives may be a significant number of patients.
Pheochromocytoma is often combined with other endocrine neoplasms as part of the syndrome multiple endocrine neoplasia. Possible growth in neurofibromatosis, medullary carcinoma of the thyroid gland. These cases are family related.
Externally pheochromocytoma reminiscent of a node, surrounded by a capsule, sizes typically in the range of five centimeters, but possibly more, while the number of synthesized by tumor cells of hormones does not depend on its size. In addition to catecholamines, the tumor may secrete serotonin, calcitonin, adrenocorticotropic hormone.
Neoplasia, synthesizing mainly adrenaline, usually dark brown, and a norepinephrine-secreting tumor is colored a light (yellow, light brown). The tumor itself has a soft texture, rich in blood vessels prone to hemorrhage, which becomes quite distinctive in appearance. Possible necrosis, after resorption which remain oral, and of pheochromocytomas is cystic in nature.
In most cases the tumor is unilateral type of lesion, approximately one-tenth part of the bilateral tumors, the same vanadocene pheochromocytoma. Depending on the characteristics of tumor cells and their behavior, it is customary to distinguish benign and malignant pheochromocytoma, which is also called the feohromoblastomy.
Malignant chromaffin tumors are most often benign species is localized outside the adrenal gland synthesizes large amounts of dopamine. It is able to metastasize to lymph nodes, liver, bones and lungs. Metastasis, not the degree of cell differentiation is a major prognostic indicator feohromoblastomy.
Manifestations of the tumor
Pheochromocytoma – hormone-producing neoplasia, so the symptoms associated with the effects of their abundance on the organs and tissues. Among all such tumors, pheochromocytoma is the most serious circulatory disorders, heart and kidneys.
Depending on the flow there are several forms of the disease:
The share of paroxysmal form of pheochromocytoma accounts for up to 85% of cases. It is characterized by a hypertensive crisis, in which patients complain of severe headache, dizziness, shortness of breath, pain and discomfort in the heart area. Patients seem frightened because of a fear similar to that which accompanies heart disease, trembling, restless, pale. Appears sweating, quickened pulse, nausea, dry mouth, seizures, fever, the release of large amounts of urine.
Almost all patients an essential manifestation of the crisis becomes a combination of pain in the head, palpitations and sweating. These symptoms of pheochromocytoma are combined in the so-called Carney triad.
To provoke the crisis can excessive physical activity, errors in diet, alcohol intake, stress, and even urination. Not worth it to try to test the tumor as it can also lead to a spike pressure.
The crisis may last for several minutes, and severe – 2-3 hours or more. Characteristic think his sudden end with the release of large amounts of urine (sometimes up to five litres), profuse sweating, patient feels tired and very weak.
The permanent version of the current of pheochromocytoma is characterized by consistently high blood pressure levels and flows similar to primary hypertension. Patients experience weakness, emotionally unstable, prone to metabolic disorders, especially diabetes mellitus. At the mixed form the background of chronically high blood pressure periodic hypertensive crises occur (in case of anxiety, stress and other triggering conditions).
A very dangerous kind of tumor flow consider the situation when the pressure is high, the low and unpredictable changes. This phenomenon is called kateholaminami shock and consider life-threatening condition that is diagnosed in every tenth patient, a few more – the children.
Serious complications of hypertensive crisis in pheochromocytoma are brain hemorrhage, heart attack, pulmonary edema, acute renal failure.
Suspect pheochromocytoma can be difficult when it is atypical for. So, the tumor may simulate a heart attack, acute pathology in the abdomen, stroke, hyperthyroidism, renal disease, and sometimes runs completely asymptomatic.
The frequency of asymptomatic forms of the tumor is difficult to establish, because such patients do not seek help due to lack of complaints. When the neoplasm has reached several kilograms of weight, the patient did not experienced any autonomic disorders or hypertension, and the only concern was lower back pain.
Meanwhile, asymptomatic quite dangerous, because the patient may suddenly die from sudden hemodynamic instability, hemorrhage into the tumor. If not diagnosed in time the tumor any stress, physical exercise, surgery or childbirth can be fatal due to severe hypotension and shock.
Diagnosis of pheochromocytoma.
Diagnosis of pheochromocytoma is complicated and requires not only careful assessment of the patient’s complaints and symptoms, but also carrying out a number of laboratory and instrumental tests. A required component considered biochemical blood analysis for the confirmation of hormone changes.
After inspection and conversations with the patient he was sent for tests, including determination of catecholamines in blood and urine. If necessary, possible research and other hormones (cortisol, parathyroid hormone, adrenocorticotropic hormone). To obtain more reliable results are provocative tests with the introduction of histamine, clonidine, glucagon, etc.
Compulsory General and biochemical blood tests examination of blood sugar, by counting the number of formed elements. When the tumor increases glucose, growing numbers of leukocytes and lymphocytes, increased eosinophils.
Among the instrumental methods of greater diagnostic value are the ultrasound, computed and magnetic resonance tomography, x-ray examination of chest organs, excretory urography. These methods of diagnostics allow to determine the exact location, size and anatomic features of tumor formation.
Given the changes in the organ of vision, patients should consult an ophthalmologist, as the negative impact of the disease on the heart and blood vessels requires a regular electrocardiography. If in doubt regarding the structure of the tumor, you can assign fine-needle biopsy, but the procedure is used relatively seldom because of the risk of complications.
Video: pheochromocytoma on CT
Treatment of pheochromocytomas consists in its removal by surgery and drug therapy. Because the tumor is accompanied by high blood pressure, it is very important is to stabilize it at an acceptable level, which will allow to safely perform the surgery.
Drug therapy includes:
- Alpha-blockers (tropafen, phentolamine);
- Beta-blockers (propranolol, atenolol);
- Calcium antagonists.
The drug phenoxybenzamine, with adrenoblokiruyuschim properties, very effective in pheochromocytoma. It is prescribed under the scheme, involving a gradual increase in dosage from 10 mg to 40 mg in two or three doses daily. The dose may be even higher, if it will provide a stable blood pressure.
In the treatment is controlled not only pressure, but also heart activity: during the two weeks should not be deterioration from the ST segment and T wave on the ECG, and the number of extrasystoles should not exceed one per 5 minutes of observation.
Lowering the pressure in the period between the crises in patients with pheochromocytoma allow catapresan and raunatin, which, however, does not protect against hypertensive crises and cause a decrease in only systolic blood pressure.
More selective alpha blockers are prazosin, terazosin. Directed by acting on specific receptors, prazosin causes fewer adverse reactions, is not conducive to tachycardia, more rapid action allows you to choose an effective dose for a shorter period of time. In addition, when you assign the probability of prazosin hypotension in the postoperative period below.
Rare in pheochromocytoma with hypertensive crises the preference means from the group of calcium antagonists – nifedipine, verapamil, diltiazem. These medications do not contribute to strong hypotension and can even be administered prophylactically if the tumor occurs without hypertension. Beta-blockers indicated for concomitant pathology of the heart, the expressed tachycardia.
It is important to note that the scheme maintaining optimal blood pressure is chosen individually for each patient taking into account the form of the disease and peculiarities of its course, so the same assignments of different patients does not happen.
In case of impossibility of surgical treatment of pheochromocytomas of the adrenal gland used conservative therapy with drugs that can reduce the amount of circulating catecholamines in the blood. Of the possibility of such treatment is limited by high risk of complications and side effects, so it is used rarely.
The drug alpha-methyltyrosine able to reduce catecholamine levels by 80%, and the maximum dose should not exceed 4 g in the appointment this means you need to consider the likelihood of disturbances from the digestive tract (diarrhea), and neurological and psychiatric adverse reactions.
Safer is considered alpha methylparathion, which dramatically inhibits the formation of hormones by the tumor and consequently reduces their release into the blood. It can be prescribed in preparation for surgical treatment to reduce the risk of the operation.
During the malignant transformation of pheochromocytoma or original growth feohromoblastomy used citostatic – vincristine, cyclophosphamide.
Surgical treatment consists in removing the adrenal gland with the tumor. Complexity due to the need for a very careful manipulation in the operating field, as even the touch of the tumor could trigger a sudden release of hormones. It is important to provide free access to the diseased tissues and an overview of the internal organs to exclude vanadocene foci of tumor growth. For removing pheochromocytomas use transparency, extraperitoneal access through the thoracic cavity or a combined approach.
With multiple pheochromocytoma, the situation is even more complex. If other tumor foci are detected, they are removed. In case of impossibility of simultaneous operation, the treatment is carried out in several stages. The extreme case is considered abandonment actophilornis tumor tissue, which must be a good reason – too high a risk for the patient or lack the technical ability to remove tumors.
The surgery itself is laparotomies access to tumors (laparoscopy does not apply because of possible complications), removing it along with the adrenal gland (total adrenalectomy). When bilateral lesions, the surgeon excised both adrenal glands, and the discovery of other pockets of growth – and removes them. The operation is performed under careful control of blood pressure and other hemodynamic parameters.
If the patient is a pregnant woman, pheochromocytoma «,» carry and give birth to a child without a huge risk to the health, first of all, the expectant mother. In such cases, doctors have no other choice but to terminate the pregnancy (abortion or cesarean section for a longer period) and after that to remove the tumor.
Video: example of a laparoscopic surgery to remove the pheochromocytoma.
After surgical removal of pheochromocytoma may be some complications. If the pressure is not falling, but remains high, that is, the probability of violation of the operating equipment, when the accident was tied to the renal artery. Another reason could be the abandonment of sites of pheochromocytoma, especially in multicentric growth, as well as the presence of primary hypertension as a concomitant disease.
Sudden hypotension is another possible complication of treatment, reasons which may be internal bleeding, a lack of control of circulating blood volume, the continuing effect of antihypertensive medications prescribed during the preparatory period or during the operation itself.
In benign pheochromocytoma surgical treatment leads to almost complete cure of most patients. A «healing» can not speak, as the tumor significantly changes the condition of other organs. The likelihood of relapse does not exceed 12%, and in the case of unilateral lesions, the risk of involvement of the second adrenal gland is very small. A worse prognosis in patients with multiple pheochromocytoma, especially if the surgeon was unable to resect all the lesions of the tumor.
In the postoperative period, symptoms of tumor can remain. This is due to the prolonged action of catecholamines on the heart and kidneys, which have undergone secondary changes. In this regard, persistent hypertension and/or tachycardia are seen as consequences of the presence of the tumor, however, they can appear after some time from the moment of the operation.
Summing up, we note that the operation is not only the most radical method of treatment, but the only option to save the patient’s life, so in any case can not abandon it. Even if it is not possible to completely remove the tumor tissue and in the postoperative period will develop hypertension, these effects are immeasurably safer the presence of pheochromocytomas in the adrenal glands.