Pheochromocytoma is a tumor with a predominant localization in the adrenal medulla, consisting of chromaffin cells and secreting large amounts of catecholamines. Disease is manifested by arterial hypertension and catecholamine hypertensive crises. In order to diagnose pheochromocytoma, provocative tests are carried out, determination of the content of catecholamines and their metabolites in blood and urine, ultrasound of the adrenal glands, CT and MRI, scintigraphy, selective arteriography. Treatment consists in performing an adrenalectomy after appropriate medical preparation.
ICD 10
D35.0 Benign neoplasm of the adrenal gland
Meaning
Pheochromocytoma (chromaffinoma) is a benign or malignant hormone-active tumor of chromaffin cells of the sympathetic-adrenal system, capable of producing peptides and biogenic amines, including norepinephrine, adrenaline, dopamine. In 90% of cases, pheochromocytoma develops in the medullary layer of the adrenal glands; in 8% of patients it is localized in the aortic lumbar paraganglia; in 2% of cases – in the thoracic or abdominal cavity, in the pelvis; extremely rarely (less than 0.1%) – in the head and neck.
Clinical endocrinology describes pheochromocytomas with intrapericardial and myocardial localization, with a predominant location in the left heart. Pheochromocytoma is usually detected in persons of both sexes at the age of 20-40 years; in children it is more common among boys (60% of observations). Pheochromocytoma is a common cause of arterial hypertension and is detected in about 1% of cases in patients with persistently elevated diastolic blood pressure.
Malignant pheochromocytomas account for less than 10% of cases, they usually have extrarenal localization and produce dopamine. Metastasis of malignant pheochromocytomas occurs in regional lymph nodes, muscles, bones, liver and lungs.
Causes
Quite often, pheochromocytoma is a component of the syndrome of multiple endocrine neoplasia types 2A and 2B, along with medullary thyroid carcinoma, hyperparathyroidism and neurofibromatosis. In 10% of cases, there is a familial form of the disease with an autosomal dominant type of inheritance and a high degree of variability in the phenotype. In most cases, the etiology of chromaffin tumors remains unknown.
Pathogenesis
The clinical symptoms of pheochromocytoma are associated with the effect of catecholamines excessively produced by the tumor on the body. In addition to catecholamines (norepinephrine, adrenaline, dopamine), pheochromocytoma can secrete ACTH, calcitonin, serotonin, somatostatin, vasoactive intestinal polypeptide, the strongest vasoconstrictor – neuropeptide Y and other active substances that cause diverse effects.
Pheochromocytoma is an encapsulated tumor with good vascularization, about 5 cm in size and an average weight of up to 70 g. There are pheochromocytomas of both large and smaller sizes; at the same time, the degree of hormonal activity does not depend on the size of the tumor.
Pheochromocytoma symptoms
The most constant symptom of pheochromocytoma is arterial hypertension, occurring in a crisis (paroxysmal) or stable form. During a catecholamine hypertensive crisis, blood pressure rises sharply, during the inter-crisis period it stays within the normal range or remains stably elevated. In some cases, pheochromocytoma proceeds without crises with constantly high blood pressure.
Hypertensive crisis with pheochromocytoma is accompanied by cardiovascular, gastrointestinal, neuropsychiatric manifestations, metabolic disorders. The development of the crisis is characterized by anxiety, a sense of fear, trembling, chills, headache, pallor of the skin, sweating, convulsions. There are heart pains, tachycardia, rhythm disturbances; dry mouth, nausea and vomiting occur. Characteristic changes on the part of the blood in pheochromocytoma are leukocytosis, lymphocytosis, eosinophilia, hyperglycemia.
The crisis can last from several minutes to 1 or more hours; typically, its sudden end with a sharp decrease in blood pressure up to hypotension. The end of the paroxysm is accompanied by profuse sweating, polyuria with the release of up to 5 liters of light urine, general weakness and weakness. Crises can be provoked by emotional disorders, physical exertion, overheating or hypothermia, deep palpation of the abdomen, sudden body movements, taking medications or alcohol, and other factors.
The frequency of seizures varies: from one for several months to 10 – 15 per day. The outcome of a severe crisis with pheochromocytoma may be retinal hemorrhage, stroke, pulmonary edema, myocardial infarction, renal failure, delaminating aortic aneurysm, etc. Malignant pheochromocytoma (pheochromoblastoma) is accompanied by abdominal pain, significant weight loss, metastasis to distant organs.
Complications
The most severe complication of the clinical course of pheochromocytoma is catecholamine shock, manifested by uncontrolled hemodynamics – a disorderly change of episodes of hyper- and hypotension that cannot be corrected. In pregnant women, pheochromocytoma disguises itself as pregnancy toxicosis, preeclampsia and eclampsia and often leads to an unfavorable outcome of childbirth.
The stable form of pheochromocytoma is characterized by persistently high blood pressure with the gradual development of changes from the kidneys, myocardium and fundus, mood variability, increased excitability, fatigue, headaches. Metabolic disorders (hyperglycemia) in 10% of patients lead to the development of diabetes mellitus. Diseases often associated with pheochromocytoma are GI, Recklinghausen’s disease (neurofibromatosis), Cushing syndrome, Raynaud’s syndrome, etc.
Diagnostics
When assessing the physical data of patients with pheochromocytoma, attention is drawn to increased blood pressure, orthostatic hypotension, tachycardia, pallor of the skin of the face and chest. An attempt to palpate a bulky formation in the abdominal cavity or in the neck area can provoke a catecholamine crisis. In 40% of patients with arterial hypertension, hypertensive retinopathy of varying degrees is detected, therefore, patients with pheochromocytoma should be consulted by an ophthalmologist. The diagnostic standard includes:
- Laboratory tests. Biochemical criteria for pheochromocytoma are an increase in the content of catecholamines in urine, catecholamines in blood, chromogranin A in serum, blood glucose, in some cases – cortisol, calcitonin, parathyroid hormone, ACTH, calcium, phosphorus, etc.
- Pharmacopoeia. Provocative and suppressive pharmacological tests have an important differential diagnostic value. The tests are aimed either at stimulating the secretion of catecholamines by pheochromocytoma, or at blocking the peripheral vasopressor action of catecholamines, however, when conducting tests, both false positive and false negative results can be obtained.
- Methods of instrumental diagnostics. For the purpose of topical diagnosis of pheochromocytoma, ultrasound of the adrenal glands and tomography (CT or MRI) of the adrenal glands, intravenous urography, selective arteriography of the renal and adrenal arteries, adrenal scintigraphy, X-ray or chest X-ray (to exclude the intra-thoracic location of the tumor) are performed. ECG changes are nonspecific, diverse and usually temporary, being detected during seizures.
Differential diagnosis of pheochromocytoma is carried out with hypertension, neurosis, psychosis, paroxysmal tachycardia, thyrotoxicosis, CNS diseases (stroke, transient cerebral ischemia, encephalitis, TBI), poisoning.
Pheochromocytoma treatment
Conservative therapy
The main method of treatment of pheochromocytoma is surgical. Before planning the operation, medical treatment is carried out, aimed at relieving the symptoms of the crisis, reducing the severity of the manifestations of the disease. To relieve paroxysms, normalize blood pressure and stop tachycardia, a combination of a-blockers (phenoxybenzamine, tropafen, phentolamine) and b-blockers (propranolol, metoprolol) is prescribed. With the development of a hypertensive crisis, the introduction of phentolamine, sodium nitroprusside, etc. is indicated. With malignant pheochromocytoma with widespread metastases, chemotherapy (cyclophosphamide, vincristine, dacarbazine) is prescribed.
Surgical treatment
During the operation for pheochromocytoma, only laparotomic access is used due to the high probability of multiple tumors and extrarenal localization. Throughout the intervention, hemodynamic control (CVD and BP) is carried out. Usually, with pheochromocytoma, a total adrenalectomy is performed. If the pheochromocytoma is part of multiple endocrine neoplasia, bilateral adrenalectomy is resorted to, which avoids recurrence of the tumor on the opposite side.
Usually, after pheochromocytoma removal, blood pressure decreases; in the absence of a decrease in blood pressure, one should think about the presence of ectopic tumor tissue. In pregnant women with pheochromocytoma, after stabilization of blood pressure, termination of pregnancy or cesarean section is performed, and then removal of the tumor.
Forecast
Removal of benign pheochromocytomas leads to normalization of blood pressure, regression of pathological manifestations. The 5-year survival rate after radical treatment of benign adrenal tumors is 95%; with pheochromoblastoma – 44%. The recurrence rate of pheochromocytoma is about 12.5%. For the purpose of early detection of relapses, patients are shown to be monitored by an endocrinologist with an annual necessary examination.
