How Pheochromocytoma Is Diagnosed

Pheochromocytoma is a rare type of tumor that develops in the adrenal glands, small glands on the top of the kidneys. These tumors can be benign (noncancerous) or malignant (cancerous).

Pheochromocytomas typically produce an excess amount of fight-or-flight hormones called catecholamines, which, in turn, causes symptoms like high blood pressure, headaches, anxiety, and an impending sense of doom.

If suspicious symptoms are noted, or if a person has a family history of a genetic disorder associated with this type of tumor, the first step to reaching a diagnosis usually is a blood or urine test to detect increased levels of the hormones that these tumors secrete. Imaging studies and additional testing may also be needed.

This article will review the diagnostic processes for pheochromocytoma.

Doctor holding a blood test

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Self-Checks/At Home Testing

There are currently no self-screening procedures or at-home tests that are of benefit in diagnosing a pheochromocytoma.

While there are no guidelines, blood pressure monitoring may be useful in finding a pheochromocytoma if present. Signs that suggest a pheochromocytoma include episodes in which blood pressure is very high followed by normal readings (called paroxysms) or blood pressure that is chronically much higher than average.

Very high blood pressure levels, especially if you are taking blood pressure medication, should also be noted and discussed with your healthcare provider.

Physical Examination

If a pheochromocytoma is suspected, your healthcare provider will take your medical history and your family medical history. Your healthcare provider may ask if anyone in your family has ever had endocrine (occurring in the system of glands in your body) conditions or tumors.

One study found that a family history of genetic syndromes was present in 9.5% of those diagnosed with pheochromocytoma. It is also estimated that up to 40% of pheochromoctyoma cases occur in people who have a germline cancer mutation (mutation in a gene that is inherited and present from birth).

During the physical exam, your healthcare provider will take your vitals, noting any blood pressure elevation and changes in heart rate (pulse). They will also look for physical signs of a pheochromocytoma episode, including tremors and heavy sweating.

For those who have a pheochromocytoma associated with a genetic syndrome, additional signs may be noted, such as café au lait spots (patches of darker skin anywhere on the body) or neurofibromas (fatty-feeling tumors under the skin anywhere on the body).

Physical Signs of a Pheochromocytoma

  • A pale face, followed by facial flushing as the episode ends
  • A mottled bluish appearance (cyanosis) of the lips, neck, around the eyes, and fingers
  • Elevated blood pressure reading
  • Rapid pulse
  • Sweating

Labs and Tests

A pheochromocytoma secretes the catecholamines epinephrine, norepinephrine, and dopamine. These hormones can be measured in the plasma, the part of a blood sample in which the red and white blood cells and platelets have been removed, and the urine.

Blood catecholamines test: This is usually the first test recommended for people who are at higher risk for having a pheochromocytoma. This includes people who have a genetic syndrome associated with the condition or whose imaging tests have shown an adrenal mass.

However, any kind of physical or emotional stress can result in the release of catecholamines from the adrenal glands, so testing for plasma catecholamines is done carefully. A person is asked to lie down and an intravenous needle is inserted. This is then left in place for at least 20 minutes before drawing blood.

Urine catecholamine (24-hour urine): Before being excreted by the body, catecholamines are broken down. It is therefore the breakdown products that are examined in a urine sample. Urine analysis is recommended as the first test for people who are not at an increased risk for having a pheochromocytoma.

With a urine catecholamine test, people are given a bucket and tray that fits in the toilet to catch urine. All urine is collected over a period of 24 hours and returned to the lab.

Interpreting Blood and Urine Catecholamine Results

Blood and urine tests can be challenging with a pheochromocytoma due to a relatively high incidence of false positives (tests whose results are positive when a condition does not actually exist) and need to be interpreted carefully.

Fortunately, levels of catecholamines are often very high when a pheochromocytoma is present (2 to 3 times normal levels). Most of the time, levels that are only slightly elevated are normal (though an abnormal result always needs to be followed and rechecked).

Recap

Blood catecholamines are usually ordered for people who have an increased risk of pheochromocytomas (such as a genetic syndrome or an adrenal tumor).

Urine catecholamines are usually ordered for people at average risk.

Genetic Testing and Screening

Many healthcare professionals believe that all people who are diagnosed with a pheochromocytoma should have genetic testing for the genetic syndromes and gene mutations that are associated with the tumor.

According to guidelines, genetic testing should be a shared decision between the healthcare provider and patient. It's important for people to understand both the risks and benefits of testing.

For most people, the benefits of genetic testing far outweigh the risks both for managing the pheochromocytoma and anticipating any associated conditions that may occur. Testing can also help alert family members to be aware or have testing done themselves.

For people who have a genetic syndrome or carry a gene mutation associated with pheochromocytoma, periodic screening may be recommended. This option, as well as the frequency of screening, may vary between syndromes. For example, one syndrome carries a 20% risk of developing a pheochromocytoma, whereas other syndromes are associated with a much lower risk.

Imaging

Imaging studies are done after a positive result has been found on blood or urine testing for catecholamines. The reason for this order of testing is that incidental masses in the adrenal gland are very common, being found on roughly 4% of abdominal CT (computed tomography) scans.

Computed tomography (CT): A CT scan combines multiple X-ray images into a 3-dimensional picture of the organs and soft tissues of a specific body area.

Magnetic resonance imaging (MRI): With MRI, a strong magnetic field is used to construct an image of the inside of the body. An MRI may be used instead of a CT scan to look for a pheochromocytoma when exposure to radiation is of concern (such as in children). MRI is also a better option if a pheochromocytoma has spread (metastasized) beyond the adrenal gland (called metastatic disease).

Scintigraphy (MIBG scan): Most of the time, a pheochromocytoma can be detected with a CT or MRI. If neither of these imaging studies shows a tumor, but lab tests confirm that one is present, MIBG scintigraphy may be used.

In this procedure, radioactive MIBG (Iodine 123 (1231)-metaiodobenzylguanidine) is injected into a vein. Pheochomoctyoma (or paraganglioma) cells take up the MIBG. Scans that detect radioactivity are then done over a few days to look for a tumor anywhere in the body.

A MIBG scan may also be helpful if multiple tumors are suspected. This test also is typically done three months after surgery to remove a pheochromocytoma to look for any evidence of recurrence or spread (metastases).

Recap

A CT scan—or possibly an MRI—is the recommended first imaging test after lab tests indicate there is a significant likelihood that a pheochromocytoma is present.

Staging

There is no standard staging system for pheochromoctyomas and they aren't divided into four stages (stage 1 to stage 4) like many cancers. Instead, they are usually described as belonging to one of three stages (with local being by far the most common), as follows:

  • Local, when the tumor is confined to the area in which it began
  • Regional, when the tumor has spread to nearby tissues or lymph nodes
  • Metastatic, when a tumor has spread to the liver, bones, lungs, or distant lymph nodes

Differential Diagnosis

There are a number of conditions that may resemble a pheochromocytoma either because they cause similar symptoms or because thy cause tumors in the adrenal glands.

Some conditions can mimic the symptoms of a pheochromocytoma. These include:

  • Thyrotoxicosis (severe hyperthyroidism): This can usually be differentiated with lab tests (such as a TSH) or physical exam (looking for a goiter or characteristic eye changes).
  • Renovascular hypertension: This type of blood pressure may also appear suddenly and can be difficult to control. It is more common in younger (less than age 30) or older (over the age of 55) people.
  • Anxiety and panic attacks: With panic attacks, there is often a clear immediate cause for the attack, such as fear, whereas anxiety is excessive worry, fear, or dread.
  • Withdrawal from the ADHD (attention deficit hyperactivity disorder) medication clonidine: This causes similar symptoms as a pheochromocytoma, as does alcohol withdrawal in some cases.
  • Illegal drugs: This includes cocaine, PCP, LSD, and amphetamines.
  • Carcinoid syndrome: This results in facial flushing, often due to another endocrine tumor.
  • Baroreflex failure: Baroreflex failure can have similar erratic levels of blood pressure, but with this condition, people often have a history of head or neck surgery or radiation.
  • Preeclampsia/eclampsia (toxemia of pregnancy): Toxemia of pregnancy can appear much like pheochromocytomas, including with very high blood pressure. With toxemia, however, a pregnancy is usually obvious.
  • Some types of strokes (such as those involving the lateral ventricles). When small, these strokes may not be recognized.
  • Other uncommon tumors: This includes neuroblastoma, ganglioneuroblastomas, and ganglioneuromas.

Other causes of an adrenal mass: There are several adrenal masses that can resemble a pheochromocytoma, and many are asymptomatic, including:

  • Adenomas: These are benign lesions on the adrenal glands (the most common cause).
  • Metastases: Cancer starts somewhere else (for example in the lungs) and has spread to the adrenal glands. With these, there is often evidence of the original tumor.
  • Adrenocortical carcinomas: These cancers may have symptoms due to the hormones they secrete.
  • Other benign tumors: Included are adrenolipomas, leiomyomas, and lymphangiomas.

Summary

Pheochromocytomas are often discovered incidentally during imaging scans for another condition. If a tumor is suspected, your healthcare provider will take your medical and family histories and perform a physical exam. Blood tests and 24-hour urine analysis are the first tests ordered to detect heightened levels of catecholamines. Imaging tests, including CT scans, MRI, and scintigraphy, may also be used to confirm the presence of a tumor and see if and where it has spread.

A Word From Verywell

While it is becoming more common to detect pheochromocytomas in abdominal scans done for another reason, the diagnosis remains challenging due to the overlap of symptoms with many common disorders.

If you are being evaluated for a possible pheochromocytoma, you may feel anxious while you await results. After all, anxiety is one of the symptoms that may lead to a workup being done in the first place. Fortunately, the tests outlined above can diagnosis most of these tumors, with additional options available if a diagnosis is uncertain.

Whether you are being evaluated for a pheochromocytoma or another condition, it's important to ask questions. Healthcare providers encourage people to ask why a test is being done and what they expect to find. Being your own advocate puts you in the driver's seat and helps ensure you get the best care possible.

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6 Sources
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