Symptoms of pheochromocytoma (chromaffinoma)

Patients with chromaffinoma can be divided into two groups. The first is cases of so-called silent tumors. Similar formations are found at the autopsy of patients who died from various causes, without hypertension in the anamnesis. It is also possible to refer conditionally to patients with hypertensive crisis as the first and last sign of the disease, because it was provoked by some circumstance, for example, tooth extraction, panaric opening, trauma, and resulted in death as a result of cardiovascular or cerebrovascular complications. In vivo non-functioning tumors of chromaffin tissue are most often detected accidentally, after surgery for a "stomach tumor," when only a morphological study establishes the true origin of the removed neoplasm. The second group of the clinical course of chromaffinoma includes patients with functioning tumors in which the disease lasted from several months to 10-15 years or more and was completed either by successful removal of the tumor or sudden death of the patient from cardiovascular insufficiency or stroke.

[1], [2],

Disorders of the cardiovascular system

In the vast majority of patients, the clinical picture of catecholamine-producing neoplasms is characterized by crisis hypertension, with crises occurring both against normal and elevated blood pressure. Persistent hypertension without crises is an exceptional phenomenon. Very rarely a catecholamine attack is characterized by an antihypertensive reaction or occurs against a background of normal blood pressure. The frequency of hypertensive crises varies: from 1-2 times per month to 12-13 times a day and, as a rule, increases with the duration of the disease. The duration of the crises varies in fairly wide ranges: from a few minutes to 1-2 days, although the latter, apparently, is due to the state of uncontrolled hemodynamics. Usually the same catecholamine attack lasts within 10-30 minutes, while the blood pressure in most patients exceeds 180-200 / 100-110 mm Hg. Art.

Chronic hyperkatecholamineemia and hypertension lead to significant changes in the myocardium, which is manifested by ECG tachycardia, rhythm disturbance, ischemic-metabolic changes, up to non-coronary necrosis. Sometimes these signs are so similar to the picture of myocardial infarction that it is extremely difficult to differentiate them. Hence, numerous diagnostic, and therefore, tactical errors. ECG changes include: ST segment reduction, reduced or negative T wave, high T wave. All this can be observed with angina pectoris, therefore ECG is not significant in differential diagnosis of chromaffinoma. The most pronounced changes in the myocardium are observed in patients with persistent hypertension outside the catecholamine crises.

Violations of the rhythm are well detected with daily monitoring of patients. In this case, one can observe sinus tachycardia, ventricular extrasystole, supraventricular extrasystole, migration of pacemaker, and in the same patient different forms of its disturbance are revealed. Monitoring is very demonstrative in surgical intervention, especially at the time of tumor isolation.

[3], [4], [5], [6], [7]

Abdominal syndrome

This variant of the clinical manifestation of chromaffinoma is known for a long time, but it is still difficult to diagnose it. The disease can proceed according to the type of chronic gastrointestinal lesion, but is more often manifested by the symptoms of an "acute" abdomen. Symptoms of abdominal syndrome include abdominal pain without a clear localization and, as a rule, not related to the nature and timing of food intake, nausea, vomiting. All this manifests itself against the background of hypertensive crises, accompanied by pallor, sweating. It is these cases that lead to numerous diagnostic errors and in vain surgical interventions, often resulting in a fatal outcome. With a mildly expressed symptomatology of the gastrointestinal tract in the form of a decrease in appetite, mild dyspepsia, chronic constipation, adult patients are usually observed and treated for cholecystitis, hepatocholecystitis, and children - helminthic invasion.

[8], [9], [10]

Chromaffinoma in pregnancy

The first report of a tumor in a woman in childbirth was published 60 years ago: a 28-year-old woman dies of an unexplained shock 3 hours after birth. Chromaffinoma was found on the section.

The most common disease occurs under the mask of toxicosis of pregnancy, pre-eclampsia, atypical toxemia. During childbirth, clinical manifestations often lead to erroneous diagnosis of internal bleeding, and soon after birth - rupture of the uterus and air embolism. High mortality of mothers and fetuses allowed a number of authors to put forward a provision according to which in women successfully carrying pregnancy and childbirth, the probability of chromaffinoma is excluded. However, our own experience and literature data indicate a possible favorable outcome of labor in the presence of a catecholamine-producing tumor, even with repeated pregnancy. Nevertheless, despite advances in modern medicine, chromaffinoma in pregnant women presents a serious diagnostic and tactical problem, from the successful decision of which the health and life of the mother and child depend. Thus, with the purposeful and timely diagnosis of chromaffinoma, the mortality of mothers decreases from 58 to 12%, and from 56 to 40%. However, many questions of preparation and treatment, the timing of the operation, depending on the timing and nature of the course of pregnancy, still remain unresolved. Practically only one thing is clear: with chromaffinoma, childbirth naturally represents an extreme danger for both the mother and the child.

[11], [12], [13], [14], [15], [16]

Disorders of carbohydrate metabolism

The influence of catecholamines on carbohydrate metabolism became known even more than 80 years ago. Hyperglycemia was considered one of the cardinal signs characteristic of the catecholamine crisis. Adrenaline and to a lesser degree norepinephrine cause the formation of cyclic monophosphate, which is an activator of the mechanism of glycogenolysis in the liver and muscles. It is also known that catecholamines inhibit the secretion of insulin, and adrenaline in addition to this inhibits its hypoglycemic effect.

Approximately 10% of patients with chromaffinoma are diagnosed with diabetes mellitus, for the compensation of which more than half of them, along with diet therapy, need the appointment of insulin or oral sugar reducing agents.

[17], [18]

Chromaffinoma in children

The first report on chromaffinoma in the child refers to 1904. Currently, there are cases of catecholamine-producing neoplasms in newborns, infants, but more often the disease occurs over the age of 8 years. According to the IEE and ICH of the USSR Academy of Medical Sciences, of the 36 children, 28 belonged to this age group. Boys are sick more often than girls.

Early signs of the disease are nonspecific: fast fatigue, weakness, excessive sweating, headaches of varying intensity, accompanied by nausea, sometimes vomiting, decreased appetite, weight loss, pale skin. Later, among the seemingly relatively satisfactory condition, there is a severe hypertensive crisis, accompanied by severe headache, severe pallor, profuse sweating, nausea, vomiting, severe tachycardia. In some children, the crisis occurs with loss of consciousness, meningeal symptoms, seizures, foam from the mouth, involuntary urination. The duration of the attack usually varies from 10-15 minutes to 1-2 hours; it rarely lasts 1-2 minutes or a day. The value of blood pressure reaches 170-270 / 100-160 mm Hg. Art. In the next few days, persistent moderate hypertension, tachycardia and sweating are noted. A recurrent crisis occurs after 1-6 months with a rise in blood pressure to 300/260 mm Hg. Art. And tachycardia to 200 beats per minute. In the future, such conditions are increased to 2-3 times a week, and some children are repeated several times a day. Along with the general pallor of the skin on the skin of the back surface of the hands and feet, the phenomenon of Raynaud is noted in the area of the elbow and knee joints: violet-spotted color, reminiscent of especially severe cases of cadaveric stains.

On ECG almost all children have sinus tachycardia recorded, more than half of patients have a negative T wave in their pectoral leads, in some cases it is possible to observe a periodic nodal rhythm, an extrasystole, an intraventricular or intra-atrial conduction disorder. A third of patients have indications of an overload of the left ventricle. In half the cases, ischemic-metabolic changes in the myocardium are detected.

In the study of the fundus, only a few patients (slightly more than 15%) have mild angiopathy, while in the remaining children the changes in the fundus are severe, most of them already in the form of angioynoretinopathy.

Violations of carbohydrate metabolism in the glucose-tolerant test are detected in almost all patients, however, only one third of them have an obvious diabetes mellitus.

It should be specially emphasized that in the vast majority of observations, the arterial pressure in children was measured in isolated cases and, as a rule, only a year after the onset of obvious clinical manifestations of the disease.

[19], [20]

Chromaffinoma and multiple endocrine neoplasia

In 1961, Sipple noted the non-random nature of the coincidence of two rare neoplasms in themselves: tumors from chromaffin tissue and medullary thyroid cancer. With the development of the APUD concept, this combination, now recognized as Sipple's syndrome, has been theoretically substantiated. Later, the scope of the syndrome was expanded by such manifestations as hyperparathyroidism, neurinoma of the mucous membranes and a marfan-like phenotype of patients.

The most common syndrome Sippl, or MEN-2, takes place in the family form of chromaffinoma, so the identification of one of its signs dictates the need for a targeted examination of family members of the patient.

Catecholamine shock is the most severe complication of the clinical course of chromaffinoma, which occurs in about 10% of patients, and in children it is somewhat more frequent than in adults. At the present time, there are no signs that could be used to predict the likelihood of a shock. Its development, apparently, on the one hand, is due to a sudden change in the sensitivity of adrenoreceptors, and on the other, to the "breakdown" of the mechanisms of inactivation and metabolism of catecholamines.

In addition to the main symptoms of the hypertensive crisis, manifested in the most acute form, these patients have a new qualitative condition, called "uncontrolled hemodynamics". The latter is characterized by a frequent and erratic change of hyper- and hypotensive episodes, which are poor or not amenable to any therapy at all. The tendency to hypotension is a formidable precursor of the lethal outcome and, as a rule, is no longer corrected by the introduction of vasopressors, steroids, cardiac agents or the use of other anti-shock measures.

Despite the extreme severity and danger of catecholamine shock, experience indicates a possible independent favorable outcome of this complication, however, high mortality among patients and the inability to predict the outcome in each specific case force the maximum number of measures to be taken as soon as possible to arrest the shock. There are two tactics for treating this complication: medication for 3-4 hours does not lead to the desired result.

The complexity of surgical treatment of patients with catecholamine shock is the absence of any data on the localization of tumors, therefore the search for chromaffinoma is usually carried out through a wide longitudinal or transverse laparotomy of the abdominal cavity, considering that the overwhelming majority of tumors are localized within it.

A special surgical problem in the state of uncontrolled hemodynamics is the parturient women, since the uterus with the fetus is a significant obstacle for the intraoperative detection of chromaffinoma, and even more so the technical implementation of the intervention. Therefore, first in such situations it is recommended to perform cesarean section, and only after contraction of the uterus is the search and removal of the tumor.

[21], [22]