Diagnosis of pheochromocytoma (chromaffinoma)

The diversity of clinical manifestations of phechromocytoma has forced us to look for the most characteristic symptoms, the presence of which would allow us to make a diagnosis with the greatest probability. In the last decade, a triad of signs has been proposed - tachycardia, sweating and headache. Indeed, the detection of these symptoms turned out to be very specific for chromaffinoma - 92.8%, but the presence of all three signs in one patient occurs only in 6.6% of cases. The greatest probability of phechromocytoma exists in thin or thin patients with cold extremities and a purple-red tint of the skin on the hands, forearms, feet, shins, in the area of the knee joints, with pronounced sweating and a crisis course of arterial hypertension, especially if their history includes short-term episodes of an increase in blood pressure above 200/100 mm Hg. Art., accompanied by a sharp headache, pronounced pallor, sweating, tachycardia (rarely bradycardia), nausea and vomiting, weakness (symptoms are given in descending order).

Currently, there is no doubt about the diagnostic value of quantitative determination of catecholamines in blood and urine, but the debate about what is more conclusive - the study of catecholamine precursors or products of their metabolism - still continues. We believe that the most accurate method of diagnostics and differential diagnostics of chromaffinoma is the study of 3-hour excretion of adrenaline (A), noradrenaline (NA) and their main metabolite - vanillylmandelic acid (VMA) after spontaneous or provoked hypertensive crisis. Determination of only daily excretion of catecholamines and vanillylmandelic acid leads to false negative conclusions in almost 25% of cases, which is one of the main sources of diagnostic errors.

It should be especially emphasized that the study of catecholamines should not be carried out against the background of patients taking dopegit. As a rule, in such cases a significant (sometimes tens of times) increase in the level of excretion of catecholamines is detected, while the excretion of vanillylmandelic acid remains within the normal range.

With prolonged treatment with dopegit, especially in large doses, increased excretion of adrenaline and noradrenaline may persist for a month or more. 3-5 days before the study, patients are not recommended to consume citrus fruits, bananas, products containing vanillin (chocolate and some confectionery products), and it is undesirable to take analgin or other drugs that contain it. With the fluorometric method of determining vanillylmandelic acid, analgin significantly distorts the results of the study towards a false-positive diagnosis.

Pharmacological tests for diagnostics and differential diagnostics of pheochromocytoma are based either on the ability of drugs to stimulate secretion of catecholamines by the tumor or to block the peripheral vasopressor action of the latter. The danger of conducting tests lies in the unpredictability of the magnitude of the hyper- or hypotensive response. In the literature of previous years, there are reports of severe consequences of pharmacological tests, sometimes fatal outcomes. Conducting provocative tests in case of suspected chromaffinoma is indicated in patients with any form of hypertension with an initial systolic blood pressure of no more than 150 mm Hg and normal or slightly increased daily excretion of catecholamines and vanillylmandelic acid. A test, for example, with histamine is carried out by rapid intravenous administration of 0.1-0.2 ml of a 0.1% solution in 2 ml of physiological sodium chloride solution. Arterial pressure is measured every 30 sec during the first 5 min and every other minute during the following 5 min. As a rule, 30 seconds after the introduction of histamine, a decrease from the initial systolic and diastolic blood pressure by 5-15 mm Hg is observed. The greatest increase in blood pressure is observed between 60 and 120 s. In patients with a tumor from chromaffin tissue, the increase in systolic blood pressure is (82 ± 14) mm Hg, and diastolic - (51 + 14) mm Hg, while in patients with hypertension of other etiology this value does not exceed, respectively, (31 ± 12) and (20 ± 10) mm Hg. Considering the possibility of a pronounced hypertensive reaction during a provocative test, alpha-blocking drugs should always be ready. A mandatory condition for conducting tests is a study of the 3-hour excretion of catecholamines and vanillylmandelic acid after them, regardless of the nature of the change in blood pressure during the test.

In addition to histamine, drugs such as tyramine and glucagon have a similar stimulating property, but the latter, unlike histamine, does not cause vegetative reactions in the form of hot flashes and sweating, and is therefore much easier to tolerate.

The most common pharmacological tests that block the peripheral vasopressor action of catecholamines include tests with rezhitin and tropafen. Intravenous administration of 10-20 mg of tropafen to a patient with chromaffinoma at the time of an attack reduces arterial pressure within 2-3 minutes by at least 68/40 mm Hg, while in patients with hypertension of other genesis - by no more than 60/37 mm Hg, therefore tropafen, in addition to its diagnostic value, is used in the symptomatic treatment of catecholamine crises caused by the tumor process.

Topical diagnostics of pheochromocytoma. The presence of a catecholamine-producing neoplasm proven by the results of clinical and laboratory studies is the basis for the next stage of diagnostics - identifying the location of the tumor or tumors, taking into account that in 10% of cases, bilateral or extra-adrenal localization of chromaffinoma is possible. For topical diagnostics, the greatest difficulties are cases of extra-adrenal location of neoplasms. It is known that in 96% of cases, chromaffinoma is localized within the abdominal cavity and retroperitoneal space: from the diaphragm to the small pelvis (adrenal glands, para-aortic, Zuckerkandl's organ, aortic bifurcation, bladder, uterine ligaments, ovaries). In the remaining 4% of cases, chromaffinomas can be located in the chest cavity, neck, pericardium, skull, spinal canal.

Palpation of the abdominal cavity under the control of arterial pressure for the purpose of localizing phechromocytoma has long been abandoned as the most inaccurate and dangerous diagnostic method.

Conventional radiography or fluoroscopy of the chest organs in direct and, if necessary, lateral and oblique projections allows to identify or exclude the intrathoracic location of phechromocytoma.

Among the invasive methods, adrenal tomography using gas (oxygen, nitrous oxide, carbon dioxide) introduced presacral into the retroperitoneal space was widely used until comparatively recently. At present, it has almost lost its significance mainly due to its traumatic nature, as well as due to the introduction of more advanced and safer research methods into clinical practice. Another disadvantage of retropneumoperitoneography is its limitation in establishing the metastatic process and identifying neoplasms of extra-adrenal localization. Excretory urography can serve as a significant addition to this method, allowing one to differentiate the shadow of the kidney from the shadow of the tumor, as well as to detect chromaffinoma of the organ of Zuckerkandl by its characteristic deviation of the left ureter.

Arteriographic methods (aortography, selective arteriography of the renal and, if possible, adrenal arteries) have not found wide application due to the low vascularization of most neoplasms.

Venous catheterization is mainly used to determine the levels of catecholamines in blood samples along various outflow pathways along the inferior and superior vena cava, the maximum content of which in the blood can indirectly indicate the approximate localization of a functioning tumor. As for retrograde adrenal venography, it is usually performed on the left and with great difficulty on the right, in addition, retrograde injection of contrast agent into the tumor can lead to a severe hypertensive crisis during the examination.

Among the non-invasive methods of topical diagnostics of phechromocytoma, the most recognized are echography and computed tomography, the parallel use of which allows for the localization, size, prevalence and malignancy (metastases) of the tumor process to be determined in almost all patients before surgery. Some difficulties arise with echography in patients with recurrent phechromocytoma and with neoplasms up to 2 cm in diameter, located in the area of the left adrenal gland, and the errors are mainly of a false-positive nature.

Recently, among the radiological methods of studying the adrenal glands (cholesterol, gallium), gamma topography using methylbenzylguanidine has been widely introduced into everyday practice. The latter, as shown by numerous studies, is a substance tropic to chromaffin tissue, which allows, along with adrenal tumors, to identify neoplasms of extra-adrenal localization, as well as distant metastases.

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