HROMAFFINOMA (chromaffino-ma) — a katekholaminprodutsiruyushchy tumor, coming from marrow of an adrenal gland or extraadrenal chromaffin fabric.
Hromaffinoma consist of the chromaffin cells cosecreting catecholamines (see) — adrenaline
(see), holes adrenaline (see) and dopamine. Because hromaffinoma can also develop serotonrsh and substance, similar to adrenocorticotropic hormone of a hypophysis, carry them to apudoma (see AP UD-system, t. 20, additional materials). Hromaffinoma happen high-quality (pheochromocytomas) and malignant (pheochromoblastomas).
For the first time the chromaffin tumor was described in 1886 by F. Fran-kel. In the USSR H. N. Anichkov in 1924 for the first time mentioned tumors of chromaffin fabric in the review devoted to tumors of a sympathetic nervous system. The first description of their structure is made in 1929
by A. A. Krylov. Hromaffinoma, both high-quality, and malignant, meet rather seldom. According to 62 024 openings which are carried out in various clinics, hromaffinoma are found in 25 cases that makes 0,04%. Among patients with arterial hypertension of a hromaffinom, according to different researchers, it is observed in 0,04 — 2% of cases. Hromaffinoma meets at aged people from 20 to 50 years more often, however cases at children of 3 months are described, and also at persons 80 years are more senior. In recent years in connection with improvement of diagnosis their more frequent identification is noted.
Etiology and pathogeny. The etiology is unknown. Members of one family have messages on detection of a tumor; it allows to assume that in development of a disease the genetic factor matters. Inheritance happens on autosomal dominantly type to high degree of penetrance. At family forms of a disease of a number of researchers the frequent combination of a hromaffinoma to tumors of other closed glands — medullary cancer of a thyroid gland, tumors of epithelial bodies is noted (so-called multiple endocrine a neoplasia of I and II types). In an experiment the role of hormonal disturbances in an origin of a tumor is found. So, at introduction to rats and Guinea pigs of somatotropic hormone of a hypophysis and estrogen in some cases their hromaffinoma was developed.
Quantity the cosecreted tumor of adrenaline, noradrenaline and dopamine, their ratio, reaction of an organism to contents them in blood, influence of these catecholamines on various bodies and systems define variety of symptoms at a hromaffinoma. Adrenaline influences a myocardium, increasing its contractility and excitability, increasing number of reductions of heart, promoting increase in the ABP (preferential systolic), to disturbance of oxidizing processes in a myocardium, causing the expressed dystrophic changes of a muscle of heart. Besides, it promotes disturbance of different types of a metabolism. Standard metabolism and heat generation raise, processes of disintegration of a glycogen in a liver and muscles in this connection tolerance to carbohydrates decreases amplify; there are more intensive processes of a lipolysis that is followed by increase in content in blood free fat to - t, receipt them in a liver and disturbance of its functions; removal of potassium from cells in intercellular space increases that causes muscular weakness and partly dysfunction of a myocardium. Noradrenaline has effect, similar to adrenaline, however is more expressed - but influences peripheral vessels and is less expressed — on exchange processes. Adrenaline and noradrenaline cause sharp increase in activity of century of N of page, break conductivity of nervous impulses in sympathetic nodes that causes variety nevrol. symptoms at a hromaffinoma. Dopamine, also as adrenaline, increases cordial emission. Catecholamines exert impact on other hemadens: exponentiate effect of thyroid hormones, actively influence secretion of hormones of a hypothalamus and a hypophysis.
Pathological anatomy. Hro-maffinoma is in most cases localized in adrenal glands. Usually this unilateral education, however a tumor can affect also both adrenal glands (in case of a family disease). In 5 — 20% of cases the tumor is located out of adrenal glands — in the fabrics containing chromaffin cells. So, in 96% of cases of extraadrenal localization the tumor is found in a sympathetic chain on the course of a ventral aorta and the lower mesenteric artery, Tsukkerkandl's body located in the place of an otkhozhdeniye from an aorta of the lower mesenteric artery and other paragangliya (see) in a bladder. More rare, in 4% of cases, it can be found in a thorax (including in heart), in a neck, in a head cavity, the spinal channel. In some cases the multiple tumors which are located at the same time both in adrenal glands and out of them are observed. The sizes chromaffin from 1 to 16 cm in the diameter. Their weight (weight) usually fluctuates from 1 to 75 g, sometimes reaches 3 kg. The chromaffin tumor of a soft consistence, brown or grayish coloring on a section, has a solid or cystous structure with the centers of hemorrhages and (or) a necrosis, as a rule, plentifully vaskulyarizirova-on, is surrounded with the capsule. Histologically the hromaffinoma (both high-quality, and malignant) is presented by the polygonal spindle-shaped or roundish cells reminding cells of marrow of an adrenal gland. They form fields, tyazh, nests, alveolar structures divided by connective tissue layers with blood vessels of sinusoidal type. Cellular kernels differ in polymorphism; cells of a tumor have plentiful pale basphilic or oxyphilic cytoplasm, contain the grains giving characteristic coloring at impact on them salts of chrome (from here the name chromaffin) and silver. In them neurosecretory granules different the forms and sizes containing adrenaline or noradrenaline are had. Frequency malignant chromaffin (pheochromoblast) makes, according to different researchers, from 2 to 40% of all chromaffin. Such difference in indicators is connected with the fact that rather accurate criteria of a zlokachestvennost of a tumor are absent. The main criterion of a zlokachestvennost of a tumor is availability of hormone of lno-active metastasises in places where chromaffin fabric normal is absent. Signs of a zlokachestvennost are also germination of the capsule of a tumor, an invasion of cells of a tumor in vessels, the centers of a necrosis in fabric of a tumor and a figure of a mitosis in its cells. Cells of a pheochromoblastoma contain the same structural elements, as at a high-quality hromaffinoma (pheochromocytoma). The closest metastasises of a pheochromoblastoma are located in regional limf, nodes, remote — in a pancreas, a liver, a thyroid gland, lungs, bones (e.g., a metastasis in a head of a humeral bone), is rare — in a brain and the spinal channel.
The clinical picture is various and caused not so much by a high level of a katekholaminemiya, how many reaction of all organism, including a-and R-adrenoceptors, on the increased maintenance of catecholamines in blood. Clinically high-quality and malignant hromaffinoma are shown equally. Initial symptoms of a disease are not specific. Usually patients complain of weakness, tachycardia, headaches, dizziness, emotional instability, abdominal pains, perspiration, a loss of appetite, weight loss. As a rule, at patients the cold snap of extremities, pallor of skin, a bug-rovo-cyanochroic shade of skin of a dorsum of brushes, feet and shins is noted. All specified symptoms can be constants or have pristupoobrazny character (against the background of the normal ABP). Duration of an initial stage varies from 1 year to several years, and only at a part of patients with the first symptom of a disease katekholamino-vy crisis with sharp increase in the ABP is, to-ry can result from an injury (including mental), after inf. diseases, alcohol intake, etc. The main display of a tumor in the heat of a disease are catechols - new crises. Katekholaminovy crisis is characterized by the sharp raising of the ABP exceeding usually 200/100 mm of mercury., a severe headache (it is frequent in occipital area), pallor of skin, strengthening of a crimson and cyanochroic shade of skin of brushes, shins and feet (that reminds livors mortis), perspiration (from a moderate hyperhidrosis to a pouring cold clammy sweat), tachycardia (is more rare bradycardia), nausea, vomiting, weakness, the trembling of a body and extremities very similar to a tremor at a thyrotoxicosis (see), heartaches, in a stomach, deterioration in sight up to a blindness. Crisis can be followed by a leukocytosis, a lymphocytosis, an eosinophilia, a hyperglycemia, an albuminuria, a cylindruria, heavy long crises — a glucosuria. Crisis can be complicated by disturbance of cerebral circulation, a myocardial infarction, an acute left ventricular failure that considerably worsens the forecast of a disease.
Crisis can proceed also with hypotension, is extremely rare — against the background of not changed ABP that is connected with a state and - and p-adrenoceptors.
Depending on features of a current distinguish two main forms of a disease: paroxysmal and
constant. Seldom the asymptomatic form diagnosed usually on section meets.
The paroxysmal form is characterized by developing of crisis against the background of the normal ABP. The paroxysm can arise after the physical tension, meal, at defecation, a palpation of a stomach and other provocative moments. As a rule, crises short-term (from 5 to 30 min.), seldom they last to an hour, and extremely seldom duration of crisis is estimated for days. At the beginning of a disease paroxysms arise seldom — 1 time in several months and even years. Further they repeat more often, and the wedge, manifestations become more expressed.
The constant form is characterized by the stable arterial hypertension reminding a severe form of an idiopathic hypertensia. Crises at this form have typical a wedge, a picture (see above), or proceed with scanty symptomatology (an insignificant headache, perspiration).
At children of a hromaffinom meets more often at the age of 10 — 11 years. Features its wedge, currents at children's age are stable arterial hypertension, visual disturbances up to rough changes of a retina, sharp increase in standard metabolism. Children are pale, potliva, avoid games, bystry movements, lose flesh, appetite is sharply reduced. Crisis at children proceeds the same as at adults, but can be followed also by psychological frustration (spasms, a loss of consciousness, an involuntary urination). At a number of children crisis is characterized only by strengthening of perspiration and increase in the ABP.
Hromaffinoma at pregnant women and women in labor can clinically be shown by increase in the ABP and body temperature, headaches; in some cases the eclamptic attacks (see the Eclampsia) which are quite often leading to a lethal outcome are noted. In a puerperal period development of shock is possible.
The diagnosis is made on the basis of characteristic a wedge, by pictures of catechol-minovogo of crisis and data a lab. researches. The most reliable sign is considerable (in tens, hundreds and more time) increase in maintenance of catecholamines and their main metabolite — vanililmin-dalny to - you in a three-hour portion of urine, collected after the spontaneous or provoked crisis. By a reliable method lab. diagnoses, especially at a constant form of a disease, also definition of catecholamines and vanililmin-dalny acid in daily urine is. At patients from hromaffinomy daily excretion of catecholamines, as a rule, exceeds 200 mkg (normal adrenaline 1 — 15 mkg, noradrenaline — 6 — 40 mkg is allocated), daily excretion va-nililmindalny to - you exceeds
7,5 mg (it is normal of 1,5 — 6 mg). Determination of content of catecholamines and their predecessors of dio-xyphenylalanine (see) and dopamine in daily urine less informatively, determination of content of catecholamines in urine against the background of reception of a dopegit in most cases yields a false positive take. In diagnosis of a disease
pharmacological tests were widely adopted, the purpose to-rykh is decrease in the ABP or provoking of katekholaminovy crisis during the mezhpristupny period. Indications for use of test with decrease in the ABP is high persistent hypertensia (especially at small expressiveness of others simpto
m) or the crises which are followed by sharp increase in the ABP. Apply and - adrenoblockers: domestic
drug Tropaphenum and foreign — Regitinum. At intravenous administration of 10 mg of Tropaphenum at patients with hromaffinomy systolic the ABP decreases during 30 — 90 sec. not less than by 60 mm of mercury., diastolic — on 40 mm of mercury.; at intravenous administration of 5 mg of Regitinum systolic the ABP decreases during 30 — 90 sec. not less than by 35 mm of mercury., diastolic more than on 25 mm of mercury. Modification of test with Regitinum is simultaneous determination of content of glucose and insulin in blood. At the same time rather convincing diagnostic criteria of existence of a hromaffinoma are decrease in sugar in blood not less than on 18 mg! 100 ml and increase in content of insulin in plasma not less than on 13 mked/ml.
The indication for provocative tests is the paroxysmal form of hypertensia when the ABP does not exceed 150/100 mm of mercury., and the maintenance of catecholamines and vanililmin-dalny to - you in daily urine — within norm or is slightly increased. The most specific and the least dangerous is test with tyramine, to-ry enter intravenously in a dose 1000 mkg. Test is considered positive if systolic the ABP increases in 30 — 90 sec. more than by 20 mm of mercury. Intravenous administration of a glucagon is rather specific provocative test, however it is necessary to remember its expressed hypertensive action. Apply also test with intravenous administration of a histamine, edges, however, not always is reliable. Tests with adrenaline and cold tests in a crust, time do not apply. Carrying out pharmakol. tests it is inexpedient against the background of reception of sedatives, drugs of Rauwolfia. Pharmakol. tests have only auxiliary value since approximately in 15% of cases yield false positive or false negative takes. It is necessary to remember their danger in view of unpredictability of degree of hypertensive or hypotensive effect at administration of the listed drugs.
The most effective methods of topical diagnosis of tumors are a computer tomography (see the Tomography computer), ultrasonic investigation (see. Ultrasonic diagnosis), an angiography (see), and also a pneumoretroperitoneum (see) with a simultaneous tomography (see), urography (see). The blood analysis from the lower and upper venas cava (taken at various levels) on the maintenance of catecholamines can help in a nek-swarm of degree with diagnosis of extraadrenal localization of a tumor. The listed methods, except for a computer tomography and ultrasonic investigation, can provoke katekholamino-vy crisis therefore they should be seen off with care under careful control of the ABP.
Differential diagnosis. Hromaffinoma is called by «the great simulator» since her wedge, the picture can remind about hundred diseases, including diseases of cardiovascular system, went. - kish. a path, kidneys, at pregnant women — obstetric pathology, and also (in connection with ability of a tumor to produce serotonin and AKTG-like substances) — diseases of endocrine system (Itsenko's disease — Cushing, an aldosteronism, a thyrotoxicosis, a diabetes mellitus, etc.). More often hromaffinoma should be differentiated with an idiopathic hypertensia (see), symptomatic hypertensia of renal genesis, vegeto-vascular dystonia (see Dystonia vascular), is more rare — with aldosteromy (see Adrenal glands, tumors), a diffusion toxic craw (see the Craw diffusion toxic).
At an idiopathic hypertensia unlike the symptomatic arterial hypertension caused hromaffinomy, as a rule, the positive effect from adequate hypotensive therapy is noted, the maintenance of catecholamines and vani-lilmindalny to - you in urine do not exceed norm.
Differential diagnosis of symptomatic hypertensia of renal genesis and the arterial hypertension caused by hromaffinomy is based on results of a research of urine, including on catecholamines and their metabolites, and also on the germinated tool researches and renal arteries.
At vegeto-vascular dystonia raising of the ABP is more often observed at night, arterial hypertension of Ne reaches high figures, crisis is followed by a hyperemia of the person, fear of death, feeling of shortage of air, a polyuria.
At an aldosteroma crises are followed by more expressed weakness without perspiration. At patients constant thirst (polydipsia), a polyuria, a nocturia, alkali reaction of urine, a hypopotassemia is noted. Characteristic signs of an aldosteroma are considerable decrease of the activity of a renin of plasma and increase in maintenance of Aldosteronum in blood; the normal maintenance of catecholamines and vanililmindalny to - you in urine is noted.
Differential diagnosis of a diffusion toxic craw and a hromaffinoma is based on determination of content of hormones of a thyroid gland in blood; characteristic of a hromaffinoma to the katekholamino-Vyya crises at a diffusion toxic craw are not observed.
Treatment high-quality and malignant chromaffin in the absence of the remote metastasises operational. In the course of preoperative preparation, especially at persistent high arterial hypertension, apply and - adrenoblo-katory (phentolamine) and $ - adrenoblockers (Obsidanum), to-rye, however, do not guarantee a stable hemodynamics during operation (excess of these drugs in an organism can have in some cases adverse effect on a hemodynamics in the postoperative period). During operation, and also in the postoperative period carry out correction of the circulator frustration caused by a hypovolemia (introduction of Polyglucinum, Ringer's solution — Locke, hemotransfusion). Use of corticosteroids in time and after operation is shown at a single-step oncotomy of both adrenal glands or at repeated second adrenal gland operation (see Adrenal glands). During operation the lethal outcome from massive bleeding is possible, in particular at germination by a tumor of a wall of a vena cava or renal vessels. Emergence of a recurrence, by data Ying-that experimental endocrinology and chemistry of hormones of the USSR Academy of Medical Sciences, is observed approximately in 10%.
Bolnykhm with nonresectable tumors carry out a symptomatic treatment and - adrenoblockers (phentolamine) and R-adrenoblockers (Obsidanum), to-rye enter orally or (at crises) intravenously. Abroad apply and - the methyl-paratiro-zin (a-MRT) blocking formation of catecholamines at the initial stages of biosynthesis, to-ry appoint 300 — 1000 mg, gradually increasing a dose to 1200 — 2500 mg. However the therapeutic effect remains only during administration of drug, besides, the expressed side effect limits its use. Radiation therapy is inefficient.
The forecast at a pheochromocytoma is defined by features its wedge, currents; early establishment of the diagnosis and a timely oncotomy allow to recover working ability of the patient. At a pheochromoblastoma the forecast adverse. Bibliography: Kazeevk. N and Zephyrs and G. S. Klinika and diagnosis of a pheochromocytoma, Klin, medical, t. 43, No. 6, page 91, 1965; Krylova. A. K to casuistry per-
eternal tumors of a medulla of epinephral gland, Kazansk. medical zhurn., No. 6, with, 627, 1929; N and to about l and e in O. V., etc. Pheochromocytoma, M., 1965, bibliogr.;
F r a n k e I F. Ein Fall von doppelseitigem, vollig latent verlaufendem Nebennierentu-mor und gleichzeitiger Nephritis mit Ve-randerungen am Circulationsapparat und Retinitis, Virchows Arch. path. Anat., Bd 103, S. 244, 1886; H u m e D. M. Pheo-chromocytoma in the adult and in the child, Amer. J, Surg., v. 99, p. 458, 1960; Manger W. M. a. G i f f o r d R. W. Pheo-chromocytoma, N, Y, 1977; P at r a 1 a K., Pitkanen E. To i vonen S. Al-pha-methyl-p-tyrosine in the symptomatic treatment of patients with malignant phaeo-chromocytoma. Ann. Med. intern. Fenn., v. 57, p. 65, 1968; S p r e g e 1
G. a. o. A modified phentolamine test for the diagnosis of pheochromocytoma, J. Amer. med. Ass., v. 211, p. 266, 1970. To. H. Kazeev,
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