Pheochromocytoma, catecholamine crisis: causes, symptoms, diagnosis, treatment

Catecholamine crisis is a life-threatening emergency condition. It develops mainly in pheochromocytoma (chromaffinoma) - a hormone-producing tumor of chromaffin tissue.

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Causes of Pheochromocytoma

The incidence of pheochromocytoma in the population is 1-3 cases per 100,000 people; and among patients with arterial hypertension - 0.05-0.2%. In about 10% of cases, pheochromocytoma is a familial disease and is inherited in an autosomal dominant manner. Less than 10% of pheochromocytomas are malignant. They are usually localized outside the adrenal glands and secrete dopamine. Pheochromocytoma usually secretes both adrenaline and noradrenaline, but predominantly noradrenaline. Very rarely, dopamine is the predominant catecholamine. In addition to catecholamines, pheochromocytoma can produce: serotonin, ACTH, VIP, somatostatin, opioid peptides, a-MSH, calcitonin, parathyroid hormone-like peptides, and neuropeptide Y (a strong vasoconstrictor).

A catecholamine crisis can be caused by an overdose of street drugs such as cocaine and amphetamines.

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Symptoms of Pheochromocytoma

Patients most often complain of headache, sweating, palpitations, irritability, weight loss, chest pain, nausea, vomiting, weakness or fatigue. Less common are visual disturbances, sensation of heat, dyspnea, paresthesia, hot flashes, polyuria, polydipsia, dizziness, nausea, convulsions, bradycardia (noted by the patient), sensation of a lump in the throat, tinnitus, dysarthria, retching, painless hematuria.

Common complaints include pain in the epigastric region, impaired intestinal peristalsis, and constipation. Sometimes ischemic colitis, intestinal obstruction, and megacolon are observed. Pheochromocytoma increases the risk of cholelithiasis. Narrowing of the vessels of the extremities under the influence of catecholamines can cause pain and paresthesia, intermittent claudication, Raynaud's syndrome, ischemia, and trophic ulcers.

The leading symptom of pheochromocytoma is a change in blood pressure (in 98% of patients). Moreover, hypertensive crises can be replaced by arterial hypotension.

Other signs of excess catecholamines: sweating, tachycardia, arrhythmia, reflex bradycardia, increased apical impulse, pale skin of the face and trunk, agitation, anxiety, fear, hypertensive retinopathy, dilated pupils: very rare - exophthalmos, lacrimation, pallor or hyperemia of the sclera, no reaction of the pupil to light. Patients are usually thin; body weight does not correspond to height; tremor, Raynaud's syndrome, or mottled skin are characteristic. In children, sometimes - edema and cyanosis of the hands; moist, cold, clammy and pale skin of the arms and legs; "goose bumps", cyanosis of the nail beds. Palpation of a space-occupying lesion found in the neck or abdominal cavity can cause an attack.

Catecholamine crises in pheochromocytoma occur at least once a week in approximately 75% of patients. Over time, attacks occur more frequently, but their severity does not increase. The duration of an attack is usually less than an hour, but some attacks can last a whole week. The attacks are characterized by the same symptoms: palpitations and shortness of breath, cold and clammy hands and feet, pale face, and a sharp increase in blood pressure. Severe or prolonged attacks are accompanied by nausea, vomiting, visual disturbances, chest or abdominal pain, paresthesia, convulsions, and an increase in body temperature.

Attacks can be caused by mental excitement, physical exertion, changes in posture, sexual intercourse, sneezing, hyperventilation, urination, etc. Attacks can be provoked by certain smells, as well as by the consumption of cheese, beer, wine and strong alcoholic beverages. Attacks can also be provoked by medical examinations (palpation, angiography, tracheal intubation, general anesthesia, childbirth and surgical interventions). They also occur against the background of taking beta-blockers, hydralazine, tricyclic antidepressants, morphine, naloxone, metoclopramide, droperidol, etc.

Massive release of norepinephrine, as well as dopamine and serotonin during an overdose of cocaine or amphetamines can cause the development of not only severe arterial hypertension in adolescents, but also acute coronary syndrome, myocardial infarction, cardiac arrhythmias, intracerebral hemorrhages, pneumothorax, non-cardiogenic pulmonary edema, intestinal necrosis, and malignant hyperthermia.

Diagnosis of pheochromocytoma

The main criterion for the diagnosis of pheochromocytoma is an elevated level of catecholamines in urine or plasma. It is necessary to visualize the tumor (CT and MRI).

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Emergency medical care for catecholamine crisis

The most reliable method of treating pheochromocytoma is its removal, especially in the case of ineffectiveness of hypotensive therapy within 3 hours after repeated administration of a non-selective alpha1,2-adrenergic receptor blocker - tropodifen - at a dose of 2-4 mg (or phentolamine 2-5 mg) intravenously by jet stream every 5 minutes.

Sodium nitroprusside [0.5-8 mcg/(kg x min) until the effect is achieved] is also used to reduce blood pressure. To prevent or eliminate arrhythmias against the background of alpha-adrenergic receptor blockade, propranolol 1-2 mg intravenously every 5-10 minutes or esmolol [0.5 mg/kg intravenously, then as an infusion at a rate of 0.1-0.3 mg/(kg x min)] is used. Labetalol, captopril, verapamil or nifedipine can be prescribed to stabilize hemodynamics. In the case of effective alpha-adrenergic receptor blockade, replenishment of the circulating blood volume may be required. To determine the required amount of fluid, the pulmonary artery wedge pressure is measured.

The long-acting alpha-adrenoblocker phenoxybenzamine is initially prescribed at 10 mg 2 times a day, then the dose is gradually increased daily by 10-20 mg and brought to 40-200 mg/day. No less effective is prazosin (a selective alpha1-adrenoblocker), usually prescribed at a dose of 1-2 mg 2-3 times a day.

If surgery is not possible due to the patient’s serious condition or in the presence of metastases of malignant pheochromocytoma, metyrosine, a tyrosine hydroxylase inhibitor, is used.

In metastatic pheochromocytomas secreting VIP and calcitonin, somatostatin is effective. In malignant pheochromocytoma, treatment is with cyclophosphamide, vincristine, and dacarbazine."

In case of cocaine or amphetamine overdose, nitroglycerin is used orally or intravenously, sodium nitroprusside [0.1-3 mcg/(kg x min)], phentolamine, calcium channel blockers (amlodipine 0.06 mg/kg, nifedipine 10 mg 3-4 times a day), benzodiazepines (diazepam 0.1 mg/kg intravenously and repeatedly - within 0.3-0.5 mg/kg, midazolam 0.1-0.2 mg/kg). It should be borne in mind that the introduction of beta-blockers can lead to deterioration of the condition and death due to worsening coronary spasm, myocardial ischemia and paradoxical arterial hypertension (prevalence of alpha-adrenergic activation).

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