Pheochromocytoma

A pheochromocytoma, or a “pheo,” is a type of neuroendocrine tumor found in adrenal glands. These two glands sit above the kidneys. They make the hormones epinephrine (adrenaline) and norepinephrine (noradrenaline), which control heart rate and blood pressure.

Pheochromocytomas develop in the center of the adrenal gland, an area called the adrenal medulla. They form in chromaffin cells — the same cells involved with many paragangliomas (“paras”), related neuroendocrine tumors found in other body areas. They can interfere with hormone levels in dangerous ways.

Most pheochromocytomas grow slowly, and many are benign (noncancerous). Less often, pheos are malignant (cancerous). Doctors see such cases more commonly in people with inherited genetic mutations placing them at higher risk for pheos and paras. Some people develop both pheos in the adrenal gland and paras in other parts of the body.

Even if they don’t turn cancerous, most pheochromocytomas still require treatment.

Sometimes pheochromocytoma symptoms aren’t very noticeable. More often, the tumors cause a classic set of signs that typically last for 15 to 20 minutes at a time. They may occur up to several times a day and include:

• Headaches
• Heart palpitations, marked by pounding, fluttering or beating rapidly
• Hypertension (high blood pressure), though levels may rise and fall and sometimes even drop too low
• Pale appearance
• Sweating
• Tremors, or shaking

The signs are tied to the adrenaline and noradrenaline chromaffin cells make. Those hormones (known as catecholamines) are neurotransmitters, sending signals from nerves to the heart and blood vessels. Pheochromocytomas often cause the adrenal glands to release more catecholamines than normal, raising blood pressure and heart rate.

Less commonly, pheochromocytomas can cause:

• Anxiety, nervousness or panic attacks
• Pain in the stomach
• Unintended weight loss

We often don’t know why pheochromocytoma forms. For the most part, researchers haven’t identified factors that might raise the risk of developing one.

Up to 40 percent of pheochromocytomas result from genetic mutations (also known as variants) inherited from parents. If either parent carries a known variant, you have a 50-50 chance of inheriting it. But inheriting one of these genes doesn’t guarantee you’ll develop pheochromocytoma. The chances vary depending on the specific variant and other factors.

In addition to causing pheochromocytoma, mutations can also influence how the disease behaves. Some mutations (in RET, VHL, NF1 and TMEM127 genes) can cause tumors in both adrenal glands. And some mutations can make tumors more likely to turn cancerous and more likely to return after treatment.

These variants can also cause other rare tumors in the nerves, eyes, skin, uterus, kidneys, thyroid, pancreas, brain and spinal cord. Some variants cause larger syndromes with additional symptoms and medical conditions.

Genetic mutations involved include:

• FH, also connected to hereditary paraganglioma
• MAX
• NF1, tied to neurofibromatosis type 1
• RET, tied to multiple endocrine neoplasia type 2, or MEN2 (associated pheochromocytomas can represent part of the syndrome or develop separately)
• SDHx
• TMEM127
• VHL, tied to von Hippel-Lindau syndrome and some pancreatic neuroendocrine tumors

We offer genetic testing for neuroendocrine tumors as well as genetic counseling for individuals and families affected by pheochromocytomas and related conditions. Identifying risk helps us create personalized screening plans to find the disease early and make successful treatment more likely.

Most people are diagnosed with pheochromocytoma between the ages of 30 and 50. Sometimes, a pheochromocytoma is found during a scan given for another reason. More often, people come to us with symptoms or known genetic risks.

Unfortunately, many of the people who come to us have spent several years seeking an accurate diagnosis. Pheochromocytoma symptoms overlap with many other conditions, and they find that knowledge of the tumor varies.

At Penn, our team is well-equipped to make that evaluation. We recommend genetic testing for all people with pheochromocytoma to identify which variants may be involved. Results help us determine which scans and treatments to recommend.

Pheochromocytoma testing

In addition to genetic testing, our evaluation typically includes:

• Family health history: We ask whether relatives have had a pheochromocytoma or a related tumor or are known to carry a connected genetic mutation.
• Blood or urine testing: We look for markers in the blood and urine left behind by catecholamines.
• Imaging: Scans help us determine the number of tumors, the location and the size. We start with either CT (X-rays from multiple angles) or MRI (using radio waves and a computer). If there’s a chance of multiple tumors or cancer that has metastasized (spread), we also use a special scanning approach called functional imaging. This nuclear medicine tool shows tumors’ behavior and uses molecules with low radiation.

We bring together a full range of specialists, providing care through a focused program within the larger Penn Neuroendocrine Tumor Program. Our providers hold deep experience, seeing 200 people with paragangliomas and pheochromocytomas each year.

At our program, you’ll find:

• Collaboration: Our providers work together to find the best plan, and most join the weekly neuroendocrine tumor board. Learn more about our tumor board and Neuroendocrine Tumor Program.
• Expertise: Our team specializes in pheochromocytoma, with years of experience treating these tumors. Many of our providers are nationally recognized experts, publishing research and giving talks about pheochromocytomas genetics, nuclear medicine and blood pressure control.
• Innovation: We run clinical trials to find new therapies, particularly for pheochromocytomas that metastasize (spread). Our ongoing project to analyze tumor samples is finding more clues about these challenging tumors and additional treatment targets.
• Options: We provide highly technical treatments not widely available, including surgery that can spare a section of the adrenal gland when needed.
• Top recognition: We hold a Center of Excellence designation from the Pheo Para Alliance, the leading advocacy and research organization for pheochromocytomas and paragangliomas. It recognizes our personalized care, range of specialists and research projects. We’re one of only nine such centers in the world, seven in the U.S. and the only program east of the Appalachians.
• Support: A nurse coordinator helps answer your questions, schedule appointments and attend to other needs. We remove as much stress and difficulty as we can. Throughout your treatment, we offer a range of additional support for neuroendocrine tumors.