Symptoms of pheochromocytoma (chromaffinoma)

Patients with chromaffinoma can be divided into two groups. The first are cases of so-called silent tumors. Such formations are found during autopsy of patients who died from various causes, without a history of hypertension. This group also includes patients in whom a hypertensive crisis was the first and last sign of the disease, since it was provoked by some circumstance, such as tooth extraction, opening of a panaritium, trauma, and led to a fatal outcome due to cardiovascular or cerebrovascular complications. Non-functioning tumors of chromaffin tissue during life are most often detected accidentally, after operations for an "abdominal tumor", when only a morphological study establishes the true origin of the removed neoplasm. The second group of clinical course of chromaffinoma includes patients with functioning tumors, in whom the disease before diagnosis lasted from several months to 10-15 years or more and ended either with successful removal of the tumor or sudden death of the patient from cardiovascular failure or stroke.

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Cardiovascular disorders

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

Chronic hypercatecholaminemia and hypertension lead to significant changes in the myocardium, which are manifested on the ECG by tachycardia, rhythm disturbances, 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 the numerous diagnostic and, consequently, tactical errors. ECG changes include: lowering of the ST segment, reduced or negative T wave, high T wave. All this can be observed in angina pectoris, therefore, ECG is not of significant importance in the differential diagnosis of chromaffinoma. The most pronounced myocardial changes are observed in patients with constant hypertension outside catecholamine crises.

Rhythm disturbances are well detected during daily monitoring of patients. In this case, sinus tachycardia, ventricular extrasystole, supraventricular extrasystole, and migration of the pacemaker can be observed, and various forms of its disturbance are detected in the same patient. Monitoring is very demonstrative during surgical intervention, especially at the time of tumor isolation.

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Abdominal syndrome

This variant of clinical manifestation of chromaffinoma has been known for a long time, but it is still difficult to diagnose. The disease can proceed as a chronic gastrointestinal lesion, but more often it manifests itself with symptoms of "acute" abdomen. Symptoms of abdominal syndrome include pain in the abdominal cavity without clear localization and, as a rule, not associated with the nature and time 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 unnecessary surgical interventions, often ending in death. With mild symptoms of the gastrointestinal tract in the form of decreased appetite, mild dyspepsia, chronic constipation, adult patients are usually observed and treated for cholecystitis, hepatocholecystitis, and children - helminthic invasion.

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Chromaffinoma in pregnancy

The first report of a tumor in a woman in labor was published 60 years ago: a 28-year-old woman died of unexplained shock 3 hours after giving birth. A chromaffinoma was found at autopsy.

Most often, the disease occurs under the guise of toxicosis of pregnancy, preeclampsia, atypical toxemia. During childbirth, clinical manifestations often lead to erroneous diagnosis of internal bleeding, and soon after childbirth - rupture of the uterus and air embolism. High mortality of mothers and fetuses allowed a number of authors to put forward the position that in women who have successfully undergone pregnancy and childbirth, the probability of chromaffinoma is excluded. However, our own experience and literature data indicate a possible favorable outcome of childbirth in the presence of a catecholamine-producing tumor, even in repeated pregnancies. Nevertheless, despite the successes of modern medicine, chromaffinoma in pregnant women is a serious diagnostic and tactical problem, the successful solution of which determines the health and life of the mother and child. Thus, with targeted and timely diagnosis of chromaffinoma, maternal mortality decreases from 58 to 12%, and fetal mortality - from 56 to 40%. However, many issues of preparation and treatment, timing of the operation depending on the timing and nature of the pregnancy remain unresolved. Only one thing is practically clear: with chromaffinoma, natural childbirth is extremely dangerous for both the mother and the child.

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Disorders of carbohydrate metabolism

The influence of catecholamines on carbohydrate metabolism became known more than 80 years ago. Hyperglycemia was considered one of the cardinal signs characteristic of a catecholamine crisis. Adrenaline and, to a lesser extent, noradrenaline cause the formation of cyclic monophosphate, which is an activator of the glycogenolysis mechanism in the liver and muscles. It is also known that catecholamines inhibit insulin secretion, and adrenaline additionally 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, require the administration of insulin or oral hypoglycemic agents.

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Chromaffinoma in children

The first report of chromaffinoma in a child dates back to 1904. Currently, cases of catecholamine-producing neoplasms in newborns and infants are known, but the disease is more common in people over 8 years of age. According to the IEEiCG of the USSR Academy of Medical Sciences, 28 out of 36 children belonged to this age group. Boys are more often affected than girls.

Early signs of the disease are non-specific: rapid fatigue, weakness, increased sweating, headaches of varying intensity, accompanied by nausea, sometimes vomiting, loss of appetite, weight loss, pale skin. Later, in the midst of a seemingly relatively satisfactory condition, a severe hypertensive crisis occurs, accompanied by a severe headache, severe pallor, profuse sweating, nausea, vomiting, and severe tachycardia. In some children, the crisis occurs with loss of consciousness, meningeal symptoms, convulsions, foaming at the mouth, and 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 blood pressure reaches 170-270/100-160 mm Hg. In the next few days, persistent moderate hypertension, tachycardia, and sweating are noted. A repeated crisis occurs after 1-6 months with an increase in blood pressure to 300/260 mm Hg and tachycardia to 200 beats/min. Later, such conditions become more frequent up to 2-3 times a week, and in some children they recur several times a day. Along with the general pallor of the skin, the Raynaud phenomenon is observed on the skin of the back of the hands and feet, in the area of the elbow and knee joints: a purple-spotted coloration, reminiscent of cadaveric spots in especially severe cases.

Sinus tachycardia is registered on ECG in almost all children, more than half of the patients have a negative T wave in the chest leads, in some cases periodic nodal rhythm, extrasystole, and intraventricular or intraatrial conduction disturbances can be observed. A third of patients have indications of left ventricular overload. In half of the cases, ischemic-metabolic changes in the myocardium are detected.

When examining the fundus, only some patients (slightly more than 15%) show mild angiopathy, while in the remaining children the changes in the fundus are severe, and in most of them it is already in the form of angioneuroretinopathy.

Disturbances in carbohydrate metabolism are detected in almost all patients according to the glucose tolerance test, but overt diabetes mellitus occurs in only a third of them.

It should be especially emphasized that in the overwhelming majority of observations, blood 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.

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Chromaffinoma and multiple endocrine neoplasia

In 1961, Sipple noted the non-random nature of the coincidence of two neoplasms rare in themselves: a tumor of chromaffin tissue and medullary thyroid cancer. With the development of the APUD concept, this combination, currently recognized as Sipple syndrome, received a theoretical justification. Subsequently, the framework of the syndrome was expanded by such manifestations as hyperparathyroidism, mucosal neuromas, and a Marfan-like phenotype of patients.

Most often, Sipple syndrome, or MEN-2, occurs in the familial form of chromaffinoma, therefore, the detection of one of its signs dictates the need for a targeted examination of the patient's family members.

Catecholamine shock is the most severe complication of the clinical course of chromaffinoma, which occurs in approximately 10% of patients, and in children somewhat more often than in adults. At present, no signs have been established on the basis of which the probability of shock occurrence could be predicted. Its development is apparently caused, on the one hand, by a sudden change in the sensitivity of adrenoreceptors, and on the other hand, by a “breakdown” of the mechanisms of inactivation and metabolism of catecholamines.

In addition to the main symptoms of hypertensive crisis, which manifest themselves in the most acute form, these patients have a new qualitative condition, which is called "uncontrolled hemodynamics." The latter is characterized by frequent and disorderly alternation of hyper- and hypotensive episodes, which are poorly or not at all amenable to any therapy. The tendency to hypotension is a formidable harbinger of a fatal 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 shows that this complication can have an independent favorable outcome, but the high mortality rate among patients and the impossibility of predicting the outcome in each specific case force us to take the maximum number of measures in the shortest possible time to stop the shock. There are two tactics for treating this complication: drug treatment for 3-4 hours does not lead to the desired result.

The difficulty of surgical treatment of patients with catecholamine shock is the lack of any data on the localization of neoplasms, therefore the search for chromaffinoma is usually carried out through a wide longitudinal or transverse laparotomy of the abdominal cavity, given that the overwhelming majority of neoplasms are localized within its limits.

Particular surgical problem in the state of uncontrolled hemodynamics is presented by women in labor, since the uterus with the fetus is a significant obstacle to the intraoperative detection of chromaffinoma, and even more so to the technical implementation of the intervention. Therefore, in such situations, it is recommended to first perform a cesarean section, and only after the uterus has contracted, the tumor is searched for and removed.

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