Pheochromocytoma

Pheochromocytoma

Pheochromocytoma is a benign or malignant tumor consisting of chromaffin cells that synthesize catecholamines. Chromaffin cells are localized predominantly in the adrenal medulla (90% of cases), but they are also found in the sympathetic ganglia, paraganglia, and other organs. The cells of the adrenal medulla produce adrenaline and norepinephrine; Chromaffin cells located outside the adrenal glands synthesize only norepinephrine.

• • Sipple’s syndrome is characterized by multiple pheochromocytomas and medullary thyroid carcinoma, and hyperparathyroidism is possible.
  • Neurofibromatosis and Lindau disease may be associated with

pheochromocytoma.

Frequency – 0.3-0.7% of the population suffering from severe arterial hypertension; in 0.05% of all patients with arterial hypertension. Genetic aspects. In 10% of cases, a familial form is observed (*171300, 1p, RSHC gene mutation, R). Both extra-adrenal forms of pheochromocytoma (171350, R) and a combination of pheochromocytoma and islet cell tumors (171420, R) are inherited as a dominant trait. Pathogenesis. The manifestations of pheochromocytoma are due to elevated levels of circulating catecholamines. Pathological anatomy. Most pheochromocytomas are single tumors of the adrenal medulla. However, 10-20% is located outside the adrenal glands, and 1-3% – in the chest or in the neck. About 20% are multiple and 10% are malignant.

Clinical picture

• • Arterial hypertension, in the majority of cases, having the character of crises. Attacks typically last less than 1 hour, worse with exercise, anesthesia, urination (suggesting bladder pheochromocytoma), and deep abdominal palpation
  • Headache
  • sweating
  • heartbeat
  • Hyperexcitability and tremor
  • Weight loss
  • Abdominal syndrome (pain that does not have a clear localization and is not associated with eating, in combination with nausea and vomiting), often imitating the picture of an acute abdomen
  • Other signs (fever, constipation, hyperglycemia, orthostatic hypotension, increased metabolism).

Diagnostics. Pheochromocytoma is suspected much more often than it is subsequently diagnosed.

• • In confirmed cases, the content of catecholamines and their metabolites in the urine is increased.
  • The most informative tests are the determination of the excretion of metarenaline in the daily urine, free catecholamines in the urine (adrenaline and norepinephrine) and the concentration of vanillylmandelic acid.
  • Stress increases the concentration of catecholamines in healthy individuals by about 2 times, if more, then a suspicion of pheochromocytoma arises.
  • The content of catecholamines in the blood is very variable and much more difficult to interpret than the results of a study of daily urine.
  • In patients with a mild increase in catecholamines, a clonidine inhibition test is useful. After 3 hours after oral administration of 0.3 mg of clonidine, the content of norepinephrine in the blood decreases to normal levels in most healthy individuals, but remains elevated in patients with pheochromocytoma.

Special Studies

• • ECG – ST segment depression, negative T wave
  • CT or MRI reveals up to 90% of tumors, because they traditionally exceed 1 cm in diameter
  • Adrenal scan with |3|1-benzylguanidine: Locate tumors outside the adrenal glands
  • Examination of blood samples from the vena cava. If the localization of pheochromocytoma still could not be identified, it is possible to examine the content of hormones in the blood taken through a catheter at various levels of the inferior vena cava or other veins.

Treatment:

Drug therapy Drugs of choice

• • A combination of a- and B-blockers (if the operation is postponed for clinical reasons).
  • First, a-blocker phenoxybenzamine is prescribed at a dose of 10 mg/day, increasing the dose by 10–20 mg/day after 2 days until blood pressure normalizes and paroxysms are relieved (up to 0.5–1.0 mg/kg every day).
  • Then a B-blocker is added – propranolol (anaprilin) ​​10 mg after 6 hours, gradually increasing the dose until the tachycardia stops (up to 60 mg / day). A B-blocker should not be used without an a-blocker due to the risk of increasing arterial hypertension.
  • With a hypertensive crisis in the preoperative period or during surgery – phentolamine (1-5 mg IV) or sodium nitroprusside (2-4 mg / kg / h IV), with attacks of tachyarrhythmia – propranolol (anaprilin) ​​0.5- 2 mg IV, with ventricular arrhythmias – lidocaine 50-100 mg IV.
  • If bilateral localization of pheochromocytoma is suspected or in case of familial polyendocrine adenomatosis for the prevention of acute adrenal insufficiency before and during surgery, hydrocortisone (100 mg IV 2 times a day).
  • For anesthesia, it is necessary to use products that do not have arrhythmogenic activity, for example, sodium thiopental and enflurane.

Contraindications. B-blockers – with bronchial asthma, sinus bradycardia and AV blockade (except for AV blockade of the 1st degree), chronic heart failure. Precautions

• • B-blockers are initially prescribed in low doses due to the risk of developing pulmonary edema in patients with catecholamine cardiomyopathy
  • The appointment of B-blockers with adrenomimetic activity is not recommended.
  • a-blockers can cause orthostatic collapse
  • Atropine should not be used for sedation before surgery. Alternative Products
  • a-blockers – prazosin, doxazosin
  • B-Adrenergic blockers – nadolol, atenolol, metoprolol
  • a- and B-blockers – labetalol, starting with 200 mg / day orally.

Surgery

• • Preoperative preparation includes adrenergic blockade with both a- and B-blockers.
  • Operation
  • During the operation, control of blood pressure and CVP is necessary. In the elderly and those with heart disease, a Sudhn-Ganz catheter should be used.
  • In all cases, access is performed by laparotomy, tk. the likelihood of multiple and extra-adrenal tumors is very high
  • In pheochromocytomas, the operation of choice is total adrenalectomy.
  • Special situations
  • Malignant pheochromocytomas are excised. If the tumor is unbelievably removed completely, it is excised as much as possible. In the future, the excess of catecholamines is corrected with the help of drug therapy. With widespread metastases, chemotherapy is used
  • If pheochromocytoma is an integral part of polyendocrine adenomatosis, a bilateral total adrenalectomy should be performed. When only one gland is removed, the recurrence rate on the opposite side is very high.
  • To prevent vascular instability, patients are treated with a-blockers for at least 1 week before surgery. In the presence of arrhythmias, B-blockers are additionally prescribed a few days before the operation.

Observation

• • Daily blood pressure measurement before surgery
  • Hemodynamic control during surgery
  • 2 weeks after the operation – collection of daily urine to measure the content of catecholamines and metanephrines, if the content is normal, then annual testing is required for 5 years. Complications
  • Orthostatic hypotension – when taking a-blockers
  • Pulmonary edema – when taking B-blockers
  • Hypertensive crisis – during surgery.

The prognosis is good after removal of a benign pheochromocytoma. With malignant pheochromocytoma, the 5-year survival rate is less than 50%. Age-related features in babies. Pheochromocytoma is most commonly seen in boys over 8 years of age. Tumors are often malignant, multiple. Persistent arterial hypertension without crises, poorly amenable to antihypertensive therapy, is characteristic. Concomitant pathology

• • Diabetes mellitus (in 10% of patients)
  • Neurofibromatosis
  • Familial polyendocrine adenomatosis
  • Landau disease.

Synonyms

• Chromaffinoma
• Pheochromoblastoma See also Hypertension, arterial; tumor, radiation therapy; Tumor, markers, Tumor, methods of treatment; Tumor, ITB stage D35.0 Benign neoplasm of the adrenal glands