Pheochromocytoma

What a pheochromocytoma does

The adrenal glands sit on top of the kidneys. Their inner part, the medulla, normally releases adrenaline (epinephrine) and noradrenaline (norepinephrine) in response to stress. A pheochromocytoma produces these hormones in excess, either constantly or in bursts. This drives the "fight or flight" response: a fast heart, constricted blood vessels, high blood pressure, sweating and raised blood sugar.

Tumors outside the adrenal glands, along the nerve chains of the abdomen, pelvis, chest or neck, are called paragangliomas. Some of these produce no hormones.

Symptoms

Spells

Spells last minutes to an hour and may occur several times a day or only occasionally:

• severe, pounding headache
• heavy sweating
• palpitations and a racing heart
• pale skin (more often than flushing)
• tremor and anxiety, a sense of doom
• chest or belly pain, nausea

Spells can be triggered by exercise, pressure on the abdomen, surgery, childbirth, certain foods rich in tyramine, and medicines such as beta-blockers started without an alpha-blocker, metoclopramide, glucocorticoids and some antidepressants.

Between spells

• high blood pressure, constant in about half of people, sometimes resistant to medicines
• dizziness on standing (orthostatic hypotension)
• weight loss, high blood sugar and constipation

Some tumors are found by chance on scans without any symptoms.

Causes and genetics

About 30 to 40% of pheochromocytomas and paragangliomas are caused by inherited gene mutations, the highest rate of any tumor type. Associated syndromes include:

• multiple endocrine neoplasia type 2 (RET gene), with medullary thyroid cancer
• von Hippel-Lindau disease
• neurofibromatosis type 1
• SDH gene mutations (hereditary paraganglioma syndromes), with a higher risk of malignancy
• other genes such as TMEM127 and MAX

The Endocrine Society recommends genetic testing for everyone diagnosed.

Diagnosis

Biochemical testing

• plasma free metanephrines (blood test, ideally drawn after lying down for 30 minutes) or 24-hour urine fractionated metanephrines. Metanephrines are breakdown products of adrenaline and noradrenaline, and are high in almost all hormone-producing tumors
• results several times above normal strongly suggest a tumor
• some medicines (tricyclic antidepressants, certain antipsychotics, levodopa) and stress can cause false positives

Imaging

• CT or MRI of the abdomen and pelvis to locate the tumor
• functional imaging (such as DOTATATE PET or MIBG scans) to look for multiple tumors or spread

Biopsy is avoided because it can trigger a hypertensive crisis.

Distinguishing from other conditions

Spells can resemble panic attacks, hyperthyroidism, migraine, menopause hot flashes, carcinoid syndrome or drug effects. Pheochromocytoma is rare, but testing is simple.

Treatment

Preparation before surgery

To prevent dangerous blood pressure surges during surgery:

• alpha-blockers (phenoxybenzamine or doxazosin) for at least 1 to 2 weeks
• beta-blockers added only after alpha blockade, to control heart rate
• high-salt diet and fluids to restore blood volume
• calcium channel blockers in some cases

Surgery

• laparoscopic adrenalectomy is the standard, with removal of the whole tumor
• partial adrenalectomy may be considered for hereditary or bilateral tumors to preserve adrenal function
• after surgery, blood pressure often normalizes, and low blood sugar and low blood pressure are monitored

Metastatic disease

About 10% of pheochromocytomas, and more paragangliomas, are malignant or spread. Treatment options include surgery to reduce tumor burden, radioactive therapies (such as MIBG or lutetium-based treatment), chemotherapy, targeted drugs, and medicines to block catecholamine effects.

Follow-up

Metanephrine levels are checked a few weeks after surgery and then yearly for life, because tumors can recur, sometimes many years later. Family members of people with hereditary mutations are offered testing and screening.

Frequently asked questions

What are the symptoms of pheochromocytoma?

The classic symptoms are spells of severe headache, heavy sweating and a racing or pounding heart, usually with high blood pressure. Others include anxiety, tremor, pale skin, nausea, weight loss and high blood sugar. Some people have no symptoms.

How is pheochromocytoma diagnosed?

Doctors first measure metanephrines in the blood or a 24-hour urine collection. If levels are high, a CT or MRI scan locates the tumor. Genetic testing is recommended for everyone diagnosed, because many cases are inherited.

Is pheochromocytoma cancer?

Most pheochromocytomas are benign and cured by surgery. About 1 in 10 can spread, more often with certain gene mutations or paragangliomas outside the adrenal gland. Because recurrence is possible, lifelong follow-up is recommended.

Can pheochromocytoma be mistaken for anxiety?

Yes. Spells of racing heart, sweating, trembling and a sense of doom can look like panic attacks. Very high blood pressure during spells, severe headaches, or hard-to-control hypertension are clues that testing for pheochromocytoma is worthwhile.

Why do you need medicine before pheochromocytoma surgery?

Handling the tumor during surgery can release large amounts of adrenaline, causing dangerously high blood pressure and heart rhythm problems. Taking alpha-blockers for 1 to 2 weeks beforehand, plus fluids and salt, makes surgery much safer.