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Pheochromocytoma (chromaffinoma) - Information Overview
Last reviewed: 12.07.2025
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Chromaffinoma (benign and malignant), pheochromocytoma, pheochromoblastoma are synonyms for a tumor that develops from special cells located in the adrenal medulla, sympathetic ganglia and paraganglia.
Pheochromocytoma is a catecholamine-secreting tumor of the chromaffin cells typically located in the adrenal glands. It causes persistent or paroxysmal hypertension. Diagnosis is based on measuring catecholamine products in the blood or urine. Imaging, especially CT or MRI, helps localize the tumors. Treatment is surgical removal of the tumor when possible. Drug therapy for blood pressure control includes alpha-blockers, possibly in combination with beta-blockers.
The cells and the neoplasms arising from them received their name due to their ability to stain brown (phaios) when histological sections are treated with chromium salts (chromos). Extra-adrenal tumors from chromaffin tissue are sometimes called paragangliomas, and non-functioning formations of the same genesis, regardless of localization, are called chemodectomas. In most cases, tumors of chromaffin tissue secrete catecholamines, which determines their clinical course.
Pheochromocytoma is found in approximately 0.3-0.7% of patients with arterial hypertension. According to other data, there are 20 patients per 1 million people, and according to the results of autopsy of patients who died from hypertension, chromaffinoma occurs in 0.08% of cases.
Pheochromocytoma has been described in all age groups, from newborns to the elderly, but is most common in the 25-50 age group. Among almost 400 patients with chromaffinoma operated on at the Institute of Experimental Endocrinology and Hormonal Chemistry of the Russian Academy of Medical Sciences, children aged 5 to 15 years accounted for 10%, patients aged 25 to 55 years accounted for 70%, and those over 55 years accounted for 15%. More than 60% of adult patients are women. Among children aged 5 to 10 years, boys predominate, while among older children, girls predominate.
[ What causes pheochromocytoma?
Secreted catecholamines include norepinephrine, epinephrine, dopamine, and dopa in varying proportions. About 90% of pheochromocytomas are located in the adrenal medulla, but they may also be located in other tissues, derivatives of nerve cells; possible sites include the paraganglia of the sympathetic chain located retroperitoneally along the aorta, in the carotid bodies (Zuckerkandl's organ), at the bifurcation of the aorta, in the genitourinary system, in the brain, in the pericardial sac, in dermoid cysts.
Pheochromocytoma in the adrenal medulla occurs equally often in men and women, is bilateral in 10% of cases (20% in children), and is malignant in more than 10% of cases. Of extraadrenal tumors, 30% are malignant. Although pheochromocytomas occur at any age, they are most common in the 20-40 age group.
Pheochromocytomas vary in size but average 5-6 cm in diameter. They weigh 50-200 g, but tumors weighing several kilograms have also been reported. Rarely are they large enough to be palpated or to cause symptoms of compression or obstruction. Regardless of histology, a tumor is considered benign unless it has invaded the capsule or metastasized, although there are exceptions.
Pheochromocytoma may be part of the familial multiple endocrine neoplasia (MEN) syndrome, types IIA and IIB, in which other endocrine tumors may coexist or develop sequentially. Pheochromocytoma occurs in 1% of patients with neurofibromatosis (Recklinghausen disease) and may be seen with hemangiomas and renal cell carcinomas, as in von Hippel-Lindau disease. Familial pheochromocytomas and carotid body tumors may be associated with mutations in the enzyme succinate dehydrogenase.
Symptoms of Pheochromocytoma
Hypertension, which is paroxysmal in 45% of patients, is the leading symptom. Pheochromocytoma occurs in 1 in 1000 patients with hypertension. Common symptoms and signs include tachycardia, increased sweating, postural hypotension, tachypnea, cold and clammy skin, severe headaches, palpitations, nausea, vomiting, epigastric pain, visual disturbances, dyspnea, paresthesia, constipation, anxiety. Paroxysmal attacks can be provoked by palpation of the tumor, change in posture, abdominal compression or massage, induction of anesthesia, emotional trauma, blockade (which paradoxically increases pressure by blocking mediated vasodilation), urination (if the tumor is in the bladder). In elderly patients, severe weight loss with persistent hypertension may indicate pheochromocytoma.
Physical examination, when performed outside of a paroxysmal attack, is usually unremarkable other than hypertension. Retinopathy and cardiomegaly are often less severe than would be expected given the degree of hypertension, but a specific catecholamine cardiomyopathy may develop.
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Diagnosis of phechromocytoma
Pheochromocytoma may be suspected in patients with typical symptoms or sudden severe unexplained hypertension. Diagnosis involves measuring high levels of catecholamine products in serum or urine.
Blood test
Free plasma metanephrine has a sensitivity of up to 99%. This test is more sensitive than circulating epinephrine and norepinephrine because plasma metanephrine levels rise continuously, while epinephrine and norepinephrine are secreted intermittently. However, a significantly elevated plasma norepinephrine level makes the diagnosis highly probable.
Urine test
Urine metanephrine is less specific than plasma free metanephrine, with a sensitivity of about 95%. Two or three normal results make the diagnosis unlikely. Urine epinephrine and norepinephrine are almost as reliable. The major metabolic products of epinephrine and norepinephrine in urine are the metanephrines vanillylmandelic acid (VMA) and homovanillic acid (HVA). Healthy individuals excrete very small amounts of these substances. Normal 24-hour values are as follows: free epinephrine and norepinephrine < 100 μg (< 582 nmol), total metanephrine < 1.3 mg (< 7.1 μmol), VMA < 10 mg (< 50 μmol), HVA < 15 mg (< 82.4 μmol). Renal excretion of epinephrine and norepinephrine is increased in pheochromocytoma and neuroblastoma. However, increased excretion of these substances may be observed in other disorders (eg, coma, dehydration, sleep apnea) or severe stress; in patients taking rauwolfia alkaloids, methyldopa, catecholamines; after consuming food containing large amounts of vanilla (especially in the presence of renal failure).
Other studies
Blood volume is limited, and hemoglobin and hematocrit levels may be falsely elevated. Hyperglycemia, glucosuria, overt diabetes mellitus, and elevated fasting plasma free fatty acid and glycerol levels may be present. Plasma insulin levels are very low relative to glucose levels. Hypoglycemia may occur after pheochromocytoma removal, especially in patients taking oral antihyperglycemic agents.
Histamine and tyramine provocation tests are dangerous and should not be used. Histamine (0.51 mg given rapidly intravenously) produces a BP increase of >35/25 mmHg within 2 minutes in normotensive patients with pheochromocytomas, but is not currently necessary. Phentolamine mesylate is necessary to treat hypertensive crisis.
The general approach is to use 24-hour urinary catecholamine excretion as a screening test and to avoid provocative testing. In patients with elevated plasma catecholamine levels, a suppression test using oral clonidine or intravenous phentolamine may be used but is rarely necessary.
Imaging for tumor localization may be needed in patients with abnormal screening results. CT or MRI of the chest and abdomen, with or without contrast, should be used. Alpha-blockade is not necessary with isotonic contrast agents. PET has also been used with some success. Repeated catecholamine measurements in plasma samples by vena cava catheterization with blood drawn at various sites, including the adrenal veins, may help localize the tumor: norepinephrine will be elevated in the vein draining the tumor. The norepinephrine/epinephrine ratio in the adrenal vein may help identify a small adrenal source of catecholamines. Radiopharmaceuticals with nuclear imaging have also been effective in localizing pheochromocytoma. 123-1-Metaidobenzylguanidine (MIBG) is most commonly used outside the United States; 0.5 mCi is given intravenously, the patient is scanned on days 1,2,3. Normal adrenal tissue does not accumulate the drug, but pheochromocytomas do so in 90% of cases. Imaging is usually positive only if the lesion is large enough to be detected by CT or MRI, but may help confirm that the adrenal mass is likely to be the source of the catecholamines. 131-1-MIBG is a less sensitive alternative.
Associated genetic abnormalities (eg, café-au-lait spots in neurofibromatosis) should be sought. Patients should be screened for MEN with serum Ca (and possibly calcitonin) and other tests as indicated by clinical data.
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Treatment of phechromocytoma
Surgical removal is the treatment of choice. Surgery is usually delayed until hypertension is controlled with a combination of beta blockers (usually phenoxybenzamine 20-40 mg orally 3 times daily and propranolol 20-40 mg orally 3 times daily).
Blockers should not be used until adequate blockade has been achieved. Some blockers, such as doxazosin, may be effective but are better tolerated. The most effective and safe block is phenoxybenzamine 0.5 mg/kg intravenously in 0.9% saline for 2 hours on each of the 3 days before surgery. Sodium nitroprusside may be given preoperatively or intraoperatively for hypertensive crisis. If bilateral tumors are identified or suspected (as in patients with MEN), adequate hydrocortisone (100 mg intravenously twice daily) should be given before and during surgery to avoid acute glucocorticoid failure due to bilateral adrenalectomy.
Most pheochromocytomas can be removed laparoscopically. Continuous blood pressure monitoring via an intra-arterial catheter and volume control should be maintained. Anesthesia should be inducible with a nonarrhythmogenic drug (eg, thiobarbiturate), then continued with enflurane. During surgery, hypertension should be controlled with phentolamine 15 mg intravenously or sodium nitroprusside infusions [24 mcg/(kg-min)], and tachyarrhythmias with propranolol 0.52 mg intravenously. If a muscle relaxant is required, a nonhistamine-releasing agent is preferred. Preoperative use of atropine should be avoided. Blood transfusion (12 units) should be given before tumor removal to prevent blood loss. If blood pressure has been well controlled preoperatively, a high-salt diet is recommended to increase volume. If hypotension develops, an infusion of dextrose solution containing norepinephrine 412 mg/L should be started. In some patients with hypotension who do not respond to levarterenol, hydrocortisone 100 mg intravenously may be effective.
Malignant metastatic pheochromocytoma is treated with alpha- and beta-blockers. The tumor may be painless and persist for a long time. Blood pressure should be controlled. The use of 1311-metaiodobenzylguanidine (MIBG) to treat residual disease prolongs survival. Radiation therapy may relieve bone pain, chemotherapy is rarely effective but may be used if other methods are ineffective.
Drugs