WHAT IS

pheochromocytoma

A pheochromocytoma (fee-o- kroe-moe- sy-TOE- muh) is a rare, usually noncancerous (benign) tumor that develops in cells in the center of an adrenal gland. You have two adrenal glands, one above each kidney.  Your adrenal glands produce hormones that give instructions to virtually every organ and tissue in your body.

Pheochromocytoma is characterized by the presence of an excess amount of hormones called catecholamines (defined by 1,2-dihydroxybenzene group-not methylated hydroxyl groups), which include norepinephrine (noradrenaline), epinephrine (adrenaline), and dopamine. If you have a pheochromocytoma, the tumor releases hormones that can cause persistent or episodic high blood pressure and other symptoms. If left untreated, a pheochromocytoma can result in severe or life-threatening damage to other body systems, especially the cardiovascular system.

Most people with a pheochromocytoma are between the ages of 20 and 50, but the tumor can develop at any age. Surgical treatment to remove a pheochromocytoma usually returns blood pressure to normal.

THE SYMPTOMS

signs to look for

Pheochromocytoma can occur at any age, but most commonly affects people between the ages of 20 and 50. While very rare, pheochromocytoma often causes a range of symptoms that when recognized can help with diagnosis. If you experience the symptoms below, you should see a doctor to get an accurate diagnosis, as many of these symptoms can be caused by multiple other conditions as well.

These signs and symptoms usually occur in brief spells of 15 to 20 minutes. Spells can happen several times a day or less often. Your blood pressure may be within the normal range or remain elevated between spells.

Signs + Symptoms
Triggers of Symptomatic Spells
When to see a Doctor
Signs + Symptoms
Signs or symptoms of pheochromocytomas may include:
  • High blood pressure
  • Rapid or forceful heartbeat
  • Profound sweating without any reason
  • Severe, throbbing headache
  • Tremors
  • Paleness in the face
  • Shortness of breath
  • Sensation of panic
Less common signs or symptoms may include:
  • Anxiety or sense of doom
  • Abdominal pain
  • Constipation
  • Weight loss
Triggers of Symptomatic Spells
Spells may occur spontaneously or may be triggered by such factors as:
  • Physical exertion
  • Anxiety or stress
  • Changes in body position
  • Bowel movement
  • Labor and delivery
  • Surgery and anesthesia
  • Caffeine
  • Certain drugs such as steroids, decongestants, psychiatric drugs such as phenelzine, tranylcypromine, and isocarboxazid
  • Stimulants, such as amphetamines or cocaine
Foods high in tyramine, a substance that affects blood pressure, also can trigger a spell. Tyramine is common in foods that are fermented, aged, pickled, cured, overripe or spoiled. These foods include:
  • Some cheeses
  • Some beers and wines
  • Dried or smoked meats
  • Avocados, bananas and fava beans
  • Pickled fish
  • Sauerkraut or kimchi
Certain medications that can trigger a symptomatic spell include:
  • Decongestants
  • Monoamine oxidase inhibitors (MAOIs), such as phenelzine (Nardil), tranylcypromine (Parnate) and isocarboxazid (Marplan)
  • Stimulants, such as amphetamines or cocaine
 
When to see a Doctor
The signs and symptoms of pheochromocytoma can be caused by a number of different conditions.

If any of the listed signs or symptoms are paroxysmal, you should see a doctor. It’s important to get a prompt diagnosis.

Although high blood pressure is a primary sign of a pheochromocytoma, most people with high blood pressure don’t have a pheochromocytoma, and not all patients with a pheochromocytoma have hypertension. Talk to your doctor if any of the following factors are relevant to you:

  • Difficulty controlling high blood pressure with current treatment plan
  • A family history of pheochromocytoma
  • A family history of a related genetic disorder: multiple endocrine neoplasia, type II (MEN II); von Hippel-Lindau disease; familial paraganglioma or neurofibromatosis 1 (NF1)

SOURCE: https://www.mayoclinic.org/

Our Doctor Tracker is a great resource if you’re looking for a trusted pheochromocytoma specialist.

 

DIAGNOSIS

preparing for your appointment

You’re likely to start by seeing your family doctor or a general practitioner. However, you may then be referred to a doctor who specializes in hormonal disorders (an endocrinologist).
What you can do

Before your appointment, make a list that includes the following:

  • Signs or symptoms — or any changes from normal— that may be causing concern
  • A record of the frequency and duration of symptoms
  • Recent changes or stresses in your life
  • All medications — including over-the- counter drugs and dietary supplements — and doses you take
  • A log of typical food and beverage consumption
  • Family history of medical conditions
Tests that examine the blood and urine are used to detect (find) and diagnose pheochromocytoma.

The following tests and procedures may be used:

Physical exam and history:

An exam of the body to check general signs of health, including checking for signs of disease, such as high blood pressure or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.

Twenty-four-hour urine test:

A test in which urine is collected for 24 hours to measure the amounts of catecholamine in the urine. Substances caused by the breakdown of these catecholamines are also measured. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. Higher-than-normal amounts of certain catecholamines may be a sign of pheochromocytoma.

Blood catecholamine studies:

A procedure in which a blood sample is checked to measure the amount of certain catecholamines released into the blood. Substances caused by the breakdown of these catecholamines are also measured. An unusual (higher than or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. Higher-than-normal amounts of certain catecholamines may be a sign of pheochromocytoma.

CT scan (CAT scan):

A procedure that makes a series of detailed pictures of areas inside the body, such as the neck, chest, abdomen, and pelvis, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.

MRI (magnetic resonance imaging):

A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body such as the neck, chest, abdomen, and pelvis. This procedure is also called nuclear magnetic resonance imaging (NMRI).

For more detail:

Biochemical diagnosis of pheochromocytomas and paragangliomas: A guide for patients

What biochemical tests are used for diagnosis of pheochromocytomas and paragangliomas?

Biochemical tests used for diagnosis of pheochromocytomas and paragangliomas include measurements in blood or urine of the catecholamines and various breakdown products (metabolites) of the catecholamines. The metabolites most commonly measured include normetanephrine, the breakdown product of noradrenaline, and metanephrine, the breakdown product of adrenaline. These two metabolites, normetanephrine and metanephrine, are commonly referred to in the plural form as the “metanephrines”. It is incorrect to refer to these metabolites in their single form as “normetanephrines” and “metanephrines”. In addition to normetanephrine and metanephrine, some laboratories also measure methoxytyramine, which is the breakdown product of dopamine. Another biochemical test still offered by some laboratories involves measurements in urine of vanillymandelic acid (commonly referred to as VMA), which represents the final major breakdown product of both noradrenaline and adrenaline. Measurements of plasma chromogranin A (CgA) are another test sometimes used to diagnose pheochromocytomas and paragangliomas. Chromogranin A is not a catecholamine or a catecholamine metabolite, but is secreted by the same cells that secrete catecholamines.

SOURCE: Graeme Eisenhofer PhD, Professor & Chief, Division of Clinical
Neurochemistry, Institute of Clinical Chemistry & Laboratory Medicine
and Department of Medicine, University Hospital Dresden, Dresden, Germany

Treatment Overview

exploring your options

Pheochromocytoma, if detected early, can be successfully treated and managed in the vast majority of cases. The treatment of choice for the condition is pheochromocytoma removal, which will involve surgery. Chemotherapy or radiotherapy are also treatment options in some cases and there are clinical trials ongoing as well. However, if left untreated, the tumor is likely to be fatal due to high blood pressure, heart failure, stroke, arrhythmias, or metastatic disease (where the cancer spreads to other organs or bones).

Treatment OPTIONS

Surgery
Radiation therapy
Chemotherapy
Ablation therapy
Embolization therapy
Targeted therapy
New types of treatment are being tested in clinical trials
Surgery
Surgery

Surgery to remove pheochromocytoma is usually an adrenalectomy (removal of one or both adrenal glands). During this surgery, the tissues and lymph nodes inside the abdomen will be checked and if the tumor has spread, these tissues may also be removed. Drugs may be given before, during, and after surgery to keep blood pressure and heart rate normal.

After surgery to remove the tumor, catecholamine levels in the blood or urine are checked. Normal catecholamine levels are a sign that all the pheochromocytoma cells were removed.

If both adrenal glands are removed, life-long hormone therapy to replace hormones made by the adrenal glands is needed.

Before Surgery

Prior to pheochromocytoma surgery, all patients should receive medications to minimize any surgery-related complications. The main goal of the administration of these medications is to normalize blood pressure and heart rate and to protect the patient from the effects of high levels of hormones (catecholamines) released during surgery. The medications used include α-adrenergic antagonists, β-adrenergic antagonists, calcium channel blockers, and catecholamine synthesis inhibitors. Generally, it is not recommended that tumor biopsy be performed prior to surgery.

After Surgery: Follow-Up

A pheochromocytoma urine test and/or plasma tests should be repeated 4-8 weeks after surgery to check for any remaining disease. Long-term regular follow-up is recommended for all patients after that. Yearly urine or plasma tests for pheochromocytoma should be performed for life to detect remaining disease, return of the disease, or the development of metastases. For most people, follow-up CT or MRI is not needed if urine and plasma test results are normal unless a genetic cause was identified.

Radiation therapy
Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy:

  • External radiation therapy uses a machine outside the body to send radiation toward the cancer.
  • Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer.

The way the radiation therapy is given depends on the type of cancer being treated and whether it is localized, regional, metastatic, or recurrent. External radiation therapy and 131I-MIBG therapy are used to treat pheochromocytoma.

Pheochromocytoma is sometimes treated with 131I-MIBG, which carries radiation directly to tumor cells. 131I-MIBG is a radioactive substance that collects in certain kinds of tumor cells, killing them with the radiation that is given off. The 131I-MIBG is given by infusion. Not all pheochromocytomas take up 131I-MIBG, so a test is done first to check for this before treatment begins.

 
Chemotherapy
Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Combination chemotherapy is treatment using more than one anticancer drug. The way the chemotherapy is given depends on the type of cancer being treated and whether it is localized, regional, metastatic, or recurrent. 

Ablation therapy
Ablation therapy

Ablation is a treatment to remove or destroy a body part or tissue or its function. Ablation therapies used to help kill cancer cells include:

  • Radiofrequency ablation: A procedure that uses radio waves to heat and destroy abnormal cells. The radio waves travel through electrodes (small devices that carry electricity). Radiofrequency ablation may be used to treat cancer and other conditions.
  • Cryoablation: A procedure in which tissue is frozen to destroy abnormal cells. Liquid nitrogen or liquid carbon dioxide is used to freeze the tissue. 
 
Embolization therapy
Embolization therapy

Embolization therapy is a treatment to block the artery leading to the adrenal gland. Blocking the flow of blood to the adrenal glands helps kill cancer cells growing there.

 
Targeted therapy
Targeted therapy

Targeted therapy is a treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Targeted therapies are used to treat metastatic and recurrent pheochromocytoma. 

Sunitinib (a type of tyrosine kinase inhibitor) is a new treatment being studied for metastatic pheochromocytoma. Tyrosine kinase inhibitor therapy is a type of targeted therapy that blocks signals needed for tumors to grow. 

 
New types of treatment are being tested in clinical trials
New types of treatment are being tested in clinical trials:

Information about clinical trials is available from the NCI website: https://www.cancer.gov/about-cancer/treatment/clinical-trials/search

Cancerous Pheochromocytoma

In 15%-25% of the cases of pheochromocytoma, the disease is cancerous and has spread to other organs.

 The prognosis for these patients is affected by the location of these tumors. If tumors have spread to the liver and lungs, a patient may have a significantly shorter lifespan than those with tumors in the bones. There are currently no cures for cancerous pheochromocytoma. However, in some cases, the existing treatment options may reduce the tumors and prolong survival.

Current treatment options for cancerous pheochromocytoma include:
  • Surgical removal and tumor size reduction (surgical debulking)
  • 131I-MIBG
  • Chemotherapy
  • Radiotherapy
  • External-beam irradiations of bone metastases
  • Tumor embolization
  • Radiofrequency ablation
  • Cryoablation (killing of tumor by tissue freezing)

GENETIC COMPONENT

why and how

Most pheochromocytoma tumors (approximately 65%) are sporadic, meaning their cause is unknown, but some genetic diseases are known to predispose patients to these tumors. It has been suggested that all patients diagnosed with a pheochromocytoma be urged to consider genetic testing because the incidence of a hereditary syndrome, including those in apparently sporadic cases, is 25%.

Testing for genetic mutations simply involves a blood test and sending the sample to a lab. Historically, there were several factors that lead doctors to perform genetic testing, including early age onset; family history of tumors; having multiple tumor locations; and having head and neck paraganglioma(s). These factors all increase the chances of a hereditary syndrome being involved.

The following inherited syndromes or gene changes increase the risk of pheochromocytoma:
Multiple endocrine neoplasia 2 syndrome, types A and B (MEN2A and MEN2B)

Multiple endocrine neoplasia, type II (MEN II) is a disorder resulting in tumors in more than one part of the body’s hormone-producing (endocrine) system. The locations of other tumors associated with MEN II include the thyroid, parathyroid, lips, tongue and gastrointestinal tract.

Multiple Endocrine Neoplasia, Type 2 (MEN2) is an inherited condition that is caused by genetic mutations in the RET gene on chromosome 10. When normal, these genes signal when to turn on cell growth and division. A mutation in RET causes the cell growth and division signal to always be on, which increases the risk for specific types of tumors.

MEN2 is classified into three subtypes: MEN2A and MEN2B. All subtypes involve high risk for development of medullary carcinoma of the thyroid and an increased risk for pheochromocytoma; MEN2A has an increased risk for parathyroid adenoma or hyperplasia (excessive growth). Additional features in MEN2B include bumps (neuromas) of the lips and tongue; enlarged lips; and ganglioneuromas (a specific type of polyp within the gastrointestinal tract). In addition, patients with MEN2B tend to be slender with long limbs.   About 5% of MEN2A patients and 50% of MEN2B patients have the disease because of a de novo (new) mutation that was not inherited from their parents. If an individual has a RET mutation, then each of his or her children will have a 50% chance of having MEN2, as well. Visit the AMEND support group for more information on MEN2 and the RET gene.

von Hippel-Lindau (VHL) syndrome

Von Hippel-Lindau disease can result in tumors at multiple sites, including the central nervous system, endocrine system, pancreas and kidneys.

VHL is an inherited condition caused by genetic mutations in the VHL gene on chromosome 3. When normal, this gene helps stop tumors from developing.  A mutation in the VHL gene increases the risk for many types of benign and cancerous tumors in the brain, spinal cord, eye, ear, kidneys, adrenal glands, and other parts of the body.  If an individual has a VHL mutation, each of his or her children will have a 50% chance of having VHL as well. Over 90% of patients with this genetic mutation will develop disease by the age of 65. Approximately 20% of VHL patients will develop pheochromocytoma. Some mutations in the VHL gene primarily increase the risk for developing Pheo. The severity of symptoms varies widely between individuals. Visit the NIH online for more information on VHL.

Neurofibromatosis type 1 (NF1)

Neurofibromatosis 1 (NF1) results in multiple tumors in the skin nerves or deeper nerves in the body (neurofibromas), pigmented skin spots and tumors of the optic nerve.

NF1 is an inherited condition caused by genetic mutations in the NF1 gene on chromosome 17. When normal, these genes help stop tumors from developing. A mutation in NF1 increases the risk for multiple café au lait spots; axillary and inguinal freckling; multiple cutaneous (skin) neurofibromas; and iris Lisch nodules. Learning disabilities are present in at least 50% of individuals with NF1. Less common but potentially more serious manifestations include plexiform neurofibromas; optic nerve and other central nervous system gliomas; malignant peripheral nerve sheath tumors; scoliosis; tibial dysplasia; and vasculopathy.

If an individual has an NF1 mutation, each of his or her children will have a 50% chance of having NF1 as well. Visit the NIH online for more information on NF1.

Hereditary Pheochromocytoma Syndrome

Hereditary Pheochromocytoma Syndrome is an inherited disorder that result in pheochromocytoma and can be associated with tumors in the kidney and GI tract as well.

Mutations in the Succinate Dehydrogenase Subunit Genes (SDH) increase risk of developing pheochromocytoma. These genes have a role in the energy cycle in our cells and typically act to prevent tumors from forming but when mutated, can lead to tumor formation. Patients with mutations in any of the SDH genes are at increased risk for pheochromocytoma and also increased risk of cancerous tumors in the kidney and GI tract.

Other genetic causes of pheochromocytoma and paraganglioma are being studied. For example, germline mutations in the gene TMEM127 and MAX have been shown to increase risk of developing pheochromocytoma.

Other genes are currently being studied to see if they too may cause pheos and paras. Researchers are still studying the hereditary patterns and penetrance of these mutations. The Genetics Home Reference page is a good resource to find updated information on new genes as it becomes available.

Pregnancy + Pheo

what you need to know.

Having a pheochromocytoma tumor during pregnancy can be dangerous for the mother-to-be and the baby. Uncontrolled high blood pressure can damage the kidneys, restrict oxygen to the baby and/or cause premature labor. During the stress of labor, a paraganglioma can release massive amounts of catecholamines that may cause hypertensive crisis in the mother and/or complicate the delivery. Therefore, patients with a suspected paraganglioma should be monitored closely during pregnancy and have their blood pressure controlled with medication and ideally managed in centers which have experience with the diagnosis and treatment of paraganglioma in pregnancy. Consultation with a paraganglioma expert is essential for the best possible outcome.

Source- MayoClinic.org
Source: National Cancer Institute: https://www.cancer.gov/types/pheochromocytoma

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