What Is Pheochromocytoma?

Pheochromocytoma is a rare, usually benign tumor that arises from chromaffin cells in the adrenal medulla. These cells produce catecholamines, including epinephrine and norepinephrine, which regulate heart rate and blood pressure. When a pheochromocytoma develops, it can release large amounts of these hormones into the bloodstream, leading to episodes of severe hypertension and a classic triad of symptoms: headache, palpitations, and sweating.

Though pheochromocytoma most commonly occurs within the adrenal glands, a similar tumor arising outside the adrenals is called a paraganglioma. Both belong to the broader category of catecholamine-secreting tumors. Early detection is crucial, because uncontrolled catecholamine release can cause dangerous complications such as stroke, heart attack, or hypertensive crisis.

Who Gets Pheochromocytoma?

Pheochromocytoma can occur at any age, but it is most frequently diagnosed between the third and fifth decades of life. About one in every 500 people with hypertension who have no obvious cause may harbor a pheochromocytoma. The tumor can be sporadic or hereditary. Hereditary pheochromocytoma is associated with several genetic syndromes, including multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and neurofibromatosis type 1.

Because of the genetic links, some guidelines recommend genetic testing for anyone diagnosed with pheochromocytoma or paraganglioma, regardless of family history. This can help identify relatives at risk and allow earlier surveillance.

Signs and Symptoms

The most characteristic presentation of pheochromocytoma involves episodic spells known as paroxysms. During a paroxysm, the tumor releases catecholamines, causing a sudden surge of symptoms. These episodes can occur unpredictably or be triggered by physical activity, stress, certain foods, or medications.

• Severe, pounding headache
• Palpitations and rapid heart rate
• Profuse sweating and facial pallor
• Dramatic spikes in blood pressure
• Nausea, vomiting, or abdominal pain
• Anxiety or a sense of impending doom

Between episodes, blood pressure may be completely normal. A substantial number of patients, however, have sustained hypertension. In some individuals, pheochromocytoma produces only vague symptoms, and the tumor is discovered incidentally during abdominal imaging for an unrelated condition. Such tumors are often called adrenal incidentalomas.

Diagnosis

Diagnosis of pheochromocytoma is based on biochemical confirmation followed by imaging localization. No single symptom or sign is entirely dependable, so laboratory testing is essential.

Biochemical Testing

Doctors typically measure plasma or urinary metanephrines, the breakdown products of catecholamines. Fractionated metanephrines measured in a 24-hour urine collection or in plasma provide the most sensitive markers. Elevated levels strongly suggest the presence of a catecholamine-secreting tumor. Measurement of vanillylmandelic acid is an older test and is less sensitive.

Imaging Studies

Once biochemical testing indicates pheochromocytoma, imaging is needed to locate it. CT or MRI of the abdomen and pelvis are commonly performed first because most tumors are in the adrenal glands. If a tumor is not found there, functional imaging with radionuclide tracers may help detect additional or extra-adrenal lesions. Options include metaiodobenzylguanidine (MIBG) scintigraphy, somatostatin receptor imaging, or positron emission tomography with radiotracers that target catecholamine pathways.

Biopsy Considerations

Needle biopsy of a suspected pheochromocytoma is generally avoided. Biopsy can precipitate a hypertensive crisis and does not reliably distinguish benign from malignant disease. The diagnosis is instead confirmed by biochemical testing and imaging. If surgery is planned, tissue confirmation occurs after the tumor is removed.

Treatment

Preoperative Medical Management

Before any surgical procedure, blood pressure and heart rate must be stabilized. This step is critical to prevent intraoperative hypertensive crises. Treatment usually begins with alpha-blockade, such as phenoxybenzamine or doxazosin, to counteract the effects of norepinephrine. After adequate alpha-blockade is achieved, a beta-blocker may be added to control reflex tachycardia and arrhythmias. It is never appropriate to begin beta-blockade before alpha-blockade, as unopposed alpha stimulation can dangerously raise blood pressure.

Surgical Resection

The definitive treatment for pheochromocytoma is complete surgical removal, called adrenalectomy. Laparoscopic adrenalectomy is the preferred approach for most localized tumors, as it is associated with less pain and a shorter recovery time. For large or invasive tumors, an open approach might be necessary. The entire tumor is removed along with the affected adrenal gland if there is no possibility of preserving normal adrenal function.

Malignant Pheochromocytoma

Malignant pheochromocytoma is defined by the presence of metastases in sites where chromaffin tissue is not normally present, such as lymph nodes, liver, bone, or lungs. Because it is impossible to reliably predict malignancy based on the appearance of the primary tumor alone, lifelong follow-up is recommended. Malignant disease may require additional treatment, including iodinated MIBG therapy, chemotherapy, or external beam radiation. Other emerging systemic therapies are under investigation.

Prognosis and Follow-Up

Most pheochromocytomas are benign, and surgery offers an excellent prognosis. Hypertension resolves completely in roughly two-thirds of patients after successful tumor removal; in the remainder, blood pressure may improve but still require medication. Recurrence is possible, especially in patients with hereditary forms of the disease, so periodic surveillance is advised.

After surgery, most experts recommend annual biochemical testing for at least ten years, with imaging whenever symptoms or catecholamine levels suggest recurrence. Family members of those who are found to carry a hereditary genetic mutation may also undergo screening.

Important Resources

For more information about pheochromocytoma and related disorders, the National Cancer Institute provides patient-oriented summaries and current treatment overviews. Additional educational materials may be found through the MedlinePlus health information service. Written guidance is also available from the UK Adrenal Tumour Network, an independent patient education charity, and from the Endocrine Society, a professional medical organization.