About Pheo Para

Pheochromocytoma is commonly referred to as “The Great Mimic” because its symptoms are often mistaken for other conditions. The incidence of pheochromocytoma is 2 to 8 per million people per year. Less than 1% of high blood pressure cases are due to pheochromocytoma, and only 5% of patients found to have adrenal masses incidentally are diagnosed with pheochromocytoma; given these statistics, it is considered a rare disease. Unfortunately, rare diseases are often misdiagnosed, with dire consequences. This guide will explore the symptoms, genetic causes, diagnosis, and treatment options for pheochromocytoma and paraganglioma.

Disclaimer: This guide is offered strictly for informational purposes. Please contact your doctor for specific medical information and advice.

First, a Little Background

Pheochromocytomas (pheos) and extra-adrenal paragangliomas (paras) are neuroendocrine tumors. They occur in both men and women equally, and they affect every race of people. They can occur at any age, but the peak incidence occurs in the third to fifth decade in life.

During embryonic development, neural crest tissue forms our nervous system, including the central nervous system, the sympathetic nervous system (which includes the adrenal medulla, the Organ of Zuckerkandl located at the bifurcation of the aorta, and other sympathetic ganglia along the sympathetic nervous system), and the parasympathetic nervous system (which includes the carotid body, and other paraganglia along the parasympathetic nervous system). The sympathetic nervous system is primarily made of up of chromaffin cells, which release adrenaline (epinephrine), noradrenaline (norepinephrine), a little dopamine and enkephalins; and is responsible for our “flight or fight” response (increased heart rate, dilated pupils, constriction of blood vessels in many parts of the body, slowed digestion, inhibited saliva production, tunnel vision, shaking). The parasympathetic nervous system is primarily made up of glomus cells and is responsible for our “rest and digest” response. Glomus cells release dopamine, noradrenaline, acetylcholine, substance P, vasoactive intestinal peptide and enkephalins.

The most recent World Health Organization classification uses the term “pheochromocytoma” exclusively for tumors arising from the adrenal medulla and the term “extra-adrenal paraganglioma” for similar tumors that arise from other locations regardless of cell structure or hormone release patterns. Historically there has been debate over this nomenclautre and as a result you might find that not all articles, researchers, and physicians will use these terms according to this definition. They are often used interchangeably.

Pheochromocytoma tumors arising from the chromaffin cells of the adrenal medulla and extra-adrenal paragangliomas arising from the sympathetic nervous system will typically secrete excess adrenalin (epinephrine) and noradrenalin (norepinephrine). These two neurotransmitters or hormones are called the catecholamines. On the other hand, extra-adrenal paragangliomas arising from the glomus cells of the parasympathetic nervous system are typically found in the head and neck region and may not release hormones at all.

It is important to note that when pheo/para tumors are biochemically silent, meaning they do not secrete neurotransmitters, they will not be detected through standard lab tests. It follows that tumors that are biochemically silent also will not have any symptoms associated with them because they are not releasing any hormones.

In most pheo cases (approximately 75% to 95%), a single adrenal tumor presents itself in a patient, and the underlying cause is unknown. Once the tumor is removed, catecholamine levels stabilize and the patient can resume normal life. Patients with single, localized tumors should experience a survival rate similar to age-matched disease-free individuals. When the origin of the tumor(s) is unknown and there is no known genetic mutation in the patient, the cause is referred to as sporadic.

Of patients with initial single, localized tumors, 6.5% to 16.5% will develop a recurrence, usually 5 to 15 years after initial surgery. Although this statistic is fairly low, the consequences of missing a recurrence could be catastrophic, so continued follow-up after the first tumor is vital. In addition, it has recently been proposed that all patients diagnosed with a pheochromocytoma or paraganglioma undergo genetic testing because the incidence of a hereditary syndrome in apparently sporadic cases is as high as 25%. Early identification of a hereditary syndrome allows for early screening for other associated tumors and identification of family members who are at risk.

Although recurrent disease is rare, approximately 50% of patients with recurrent disease will experience distant metastasis. The 5-year survival in the setting of metastatic disease (whether identified at the time of initial diagnosis or identified postoperatively as recurrent disease) is 40% to 45%. There has been debate among medical professionals about whether pheo/para tumors are considered benign versus malignant; however, it is generally accepted that malignant pheo/para tumors occur when tumors arise where chromaffin/glomus tissue does not normally exist in the body (such as the liver, lungs, and bones) or when there is spread of a tumor to distant sites such as distant lymph nodes or bone. Multiple tumors along the sympathetic or parasympathetic nervous system are not considered to be malignant. Malignant and multiple pheo/para tumors are often associated with a genetic mutation in the patient; however, sporadically occurring disease may also be malignant and/or recurrent.

Symptoms

Many symptoms are associated with pheo/para tumors. A patient may experience all, some, or none of these “typical” pheo/para symptoms. Patients with a pheochromocytoma or extra-adrenal sympathetic paraganglioma may present with these symptoms because of the release of excess catecholamines. These symptoms often occur during “episodes” which typically last 20 to 60 minutes and are not sustained; however 50% to 60% of pheochromocytoma patients do have sustained hypertension. Symptoms from catecholamine release can be spontaneous or induced by a variety of events including exercise, trauma, labor and delivery, anesthesia induction, surgery, certain foods and medications, or urination (if the bladder wall is involved).

Parasympathetic extra-adrenal paragangliomas usually do not secrete catecholamines and usually present as a neck mass with symptoms related to compression (pain) or are incidentally discovered on an imaging study performed for an unrelated reason or because of screening in patients with genetic mutations.

Common symptoms of catecholamine release associated with Pheochromocytoma

  • Heart palpitations
  • Racing heart rate, even while resting
  • High blood pressure
  • Excessive sweating
  • Attacks similar to panic/anxiety attacks (these may occur in response to exercise or for no apparent reason)
  • Chest/abdominal pain
  • Headache
  • Vomiting
  • Fever
  • Pallor
  • Flushing
  • Muscle weakness
  • Visual disturbances

Genetic Causes

Most pheochromocytoma tumors (approximately 75%) are sporadic, meaning their cause is unknown, but some genetic diseases are known to predispose patients to these tumors. Extra-adrenal paragangliomas have a higher association with genetic mutations than pheochromocytomas. It has been suggested that all patients diagnosed with a pheochromocytoma or paraganglioma be urged to consider genetic testing because the incidence of a hereditary syndrome even in apparently sporadic cases is as high as 25%.

Testing for genetic mutations simply involves drawing blood and sending it to a lab. Historically, there were several factors that lead doctors to perform genetic testing, including early age of 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.

Types of Genetic Mutations Identified to Date:

Multiple Endocrine Neoplasia Type 2 (MEN2A, MEN2B, and FMTC)

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, MEN2B, and FMTC (familial medullary thyroid carcinoma). All three subtypes involve high risk for development of medullary carcinoma of the thyroid; MEN2A and MEN2B have an increased risk for pheochromocytoma (a specific type of tumor in the adrenal gland); 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, patient’s 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.

Neurofibromatosis Type 1 (NF1)

NF1 is an inherited condition caused by genetic mutations in the NF-1 gene on chromosome 17. When normal, these genes help stop tumors from developing. A mutation in NF-1 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 NF-1 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.

Von-Hippel Lindau (VHL)

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. The severity of symptoms varies widely between individuals. Visit the NIH online for more information on VHL.

Hereditary Paraganglioma Syndrome

Hereditary Paraganglioma Syndrome is an inherited condition caused by genetic mutations in the SDHD, SDHB, SDHC, SDHA, and SDHAF2 (SDH5) genes. When normal, these genes help stop tumors from developing. A mutation in one of these genes increases the risk for paragangliomas (tumors that occur in nervous and endocrine tissues) and pheochromocytomas (paragangliomas on the adrenal gland, which is on top of the kidney). This disorder can present due to de novo (new) mutations; therefore, the absence of a family history of paraganglioma, pheochromocytoma or other features of these syndromes does not eliminate the chance that an individual has a hereditary syndrome. Other tumor types can also occur.

If an individual has an SDH mutation, each of his or her children will have a 50% chance of having the same mutation. Individuals with mutations in SDHD only may develop pheo/para if they inherit the mutation from their father. Individuals with mutations in SDHB or SDHC may develop pheo/para regardless of which parent they inherit the mutation from. A single mutation in the SDH genes increases the risk that an individual will develop the disease associated with it. However, an additional mutation that deletes the normal copy of the gene is needed to cause tumor formation. This second mutation, called a somatic mutation, is acquired during a person’s lifetime and is present only in tumor cells. Visit the NIH online for more information on Hereditary Paraganglioma Syndrome.

Other genetic causes of pheochromocytoma and paraganglioma are being studied. For example, germline mutations in the gene TMEM127 on chromosome 2q11 have been shown to be present in approximately 30% of affected patients with familial disease and in about 3% of patients with apparently sporadic pheochromocytomas without a known genetic cause. Similar to the SDH genes, TMEM127 is a tumor-suppressing gene.

More recently, the TMEM127, MAX, HIF2A, EGLN1, KIF1B, and H-RAS were added to the list of susceptibility genes implicated in the development of paragangliomas/pheochromocytomas. Researchers are still studying the hereditary patterns and penetrance of these mutations. The Genetics Home Reference page is a good resource too find updated information on new genes as it becomes available. 

Carney Triad and Carney-Stratakis Diad

Carney Triad is a rare disease that causes three different tumor types to develop: functioning paragangliomas, pulmonary chondromas (benign cartilaginous lung tumors), and GISTs (gastrointestinal stromal tumors). GISTs may occur anywhere inside the digestive tract, but the stomach is the most common area; they may be multifocal. Carney Triad affects more women than men; up to 80% of patients are women. Even though a gene mutation has not been discovered, it is strongly suspected that Carney Triad is genetic.

Carney-Stratakis Diad is similar to Carney Triad; however, gene mutations causing this condition have been identified. Patients with the condition have been found to have mutations in the SDHB, SDHC, and SDHD genes. The condition is characterized by paraganglioma tumors and GIST (no pulmonary chondromas as with Carney Triad). Carney-Stratakis Diad is autosomal dominant.

Diagnosis

If pheochromocytoma or paraganglioma is suspected, biochemical testing is the first step to confirm or rule out the diagnosis. Simple lab tests for pheo/para will determine whether scans are necessary. If an active, secreting pheo or para tumor is present, the catecholamine levels in the body will be elevated. Generally, two tests are used to measure the levels of catecholamines:

  • Twenty-four-hour urine collection: This test measures catecholamine levels (e.g., epinephrine, norepinephrine, and dopamine) as well as fractionated metanaphrines (e.g., metanephrine and normetanephrine) in the urine. Patients will collect their urine for 24 hours and return it to the lab. Typically a preservative is used and/or the sample is kept cold during the testing period.
  • Plasma-free fractionated metanephrines (PFM): This test measures fractionated metanaphrine levels in the blood. For best results, the patient should lie supine for 30 minutes before the blood draw.

The 24-hour urine collection has a relatively low sensitivity (77-90%) which means it can miss the diagnosis approximately 10-25% of the time and therefore may need to be repeated if there is a strong suspicion of pheochromocytoma/paraganglioma but the first test results come back negative. The sensitivity for this test is however very good (98%), which means there are very few false positives. In contrast, the sensitivity of the PFM test is very good (97-99%) but a relatively low specificity (85%), so false positives are fairly common. Ideally both tests should be used to confirm or refute the pheo diagnosis. The PFM test should be done first to increase certainty of the tumor’s presence, followed by the 24-hour urine test for confirmation.

Certain foods and drugs may affect the outcome of these tests. Patients should avoid caffeine, bananas, chocolate, and acetaminophen (Tylenol) for at least 24 hours before the test (and during the collection). In addition, stress and sleep apnea can affect the results.

A mildly elevated catecholamine or metanephrine level is usually the result of drug interactions or other factors. Patients with symptomatic pheo/para almost always have increases in catecholamines or metanephrines of at least two to three times higher than the upper limits of reference ranges.

Provocative testing (e.g., using glucagon) can be dangerous, adds no value to other current testing methods, and is not recommended.

If the catecholamine levels measured in these tests are elevated, the next step is to order scans to localize the tumor(s). CT (computed tomography) or MRI (magnetic resonance imaging) of the pelvis and abdomen (at least up to the bifurcation of the aorta) are generally accepted as the first set of scans used to locate pheo/para. Both have similar sensitivities (90-100%) and specificities (70-80%). Additional imaging may be necessary if CT and MRI fail to localize the tumor. Several types of scans are used to detect pheochromocytoma and paraganglioma tumors, including CT, MRI, (131)I-MIBG, (123)I-MIBG, (111)In-octreotide and (18)F-flurodeoxyglugose PET scans. MIBG, octreotide and PET scans are special types of scans that involve injecting the patient with a radioactive tracer. Pheo and para tumors will absorb the tracer and light up on the scan if they have the receptors for the tracers on their cell walls. Please note that not all pheo/para tumors show up on MIBG and octreotide scans. Some tumors don’t take up the radioactive tracers.

Diagnosis of Non-Functioning Tumors

Although epinephrine and norepinephrine are the biologically active hormones secreted by pheos and paras, the secretory pattern may be variable and occur in spells. In contrast, metanephrine and/or normetanephrine are produced continuously within chromaffin tumors, and measurement of these circulating metabolites has become the gold standard for diagnosis of pheochromocytoma or functioning paraganglioma. Diagnosis of “silent” tumors. “Silent” tumors are typically diagnosed either as an incidental imaging finding, or by surveillance in a genetically susceptible individual. Both scenarios have become more common in the past two decades with increased imaging frequency and increased knowledge about genetics. Silent tumors are those that don’t produce any pheo/para symptoms. There are two types of silent tumors: those that are producing catecholamines but either the body’s receptors are not responding to the high levels of hormones or the hormone release is not sufficient to cause symptoms; and those that are truly non-functioning (not secreting any hormones at all). Non-functioning PGLs are challenging tumors for clinicians. They are rare and usually asymptomatic until their size is sufficient to produce symptoms of compression on adjacent organs (pain). Sometimes these non-functioning PGLs are discovered as a palpable mass. Non-functioning head and neck PGLs may have the following symptoms: pulsatile tinnitus, palpable mass, hearing loss, hoarseness of voice and difficulty swallowing. Because these tumors are not secreting any hormones, they do not produce any typical pheo symptoms associated with them and will not show up on lab tests. In many cases, diagnosis can only be confirmed after excision.

Treatment Options

While there is no known preventive measure for pheochromocytoma or paraganglioma, there are many effective treatment options once a tumor has been discovered. If the tumor can be surgically removed, either open or laparoscopically, it is the preferred method of treatment.

Before undergoing any surgical procedure, the patient must be adequately “blocked” with medication. This involves taking an alpha blocking medication for at least 2 to 3 weeks before the surgery and monitoring the patient’s blood pressure carefully. The most common medication for blocking patients is Phenoxybenzamine (Dibenzyline). A beta blocker may be used in conjunction.

Going under anesthesia without being blocked is highly dangerous for pheo/para patients. The anesthesia drugs can have a negative influence on the tumors and cause them to release massive amounts of catecholamines. Manipulation of the tumor during surgery can also cause this release, which may result in a hypertensive crisis and even death. It is extremely important that the practitioners involved in the care of the patient have experience with pheo/para surgery and that patients be “blocked” for the best possible outcome.

In most pheo cases (approximately 75% to 95%), a single adrenal tumor presents itself in a patient, and the underlying cause is unknown. Once the tumor is surgically removed, catecholamine levels stabilize and the patient can resume normal life. Patients with single, localized tumors with no known genetic mutation should experience a survival rate similar to age-matched disease-free individuals.

When surgery is not an option due to multiple tumor sites, malignant disease, or the location of a tumor, the treatment depends on several factors and is best determined by doctors who are experienced with pheo/para tumors. The following treatments have been used for pheo/para tumors with variable outcomes. They can be categorized into two groups: local therapy (resection, radiation, radio-frequency ablation, transarterial embolism) and systemic therapy (radionucleotide therapy [MIBG and radiolabeled somatostatin analogs], octreotide, cytoxic chemotherapy, molecular targeted therapy).

Surgical Resection (laprascopic or open surgery)

In most cases (approximately 75 to 95%), a single adrenal pheo tumor presents itself in a patient and the underlying cause is unknown. Once the tumor is removed, catecholamine levels stabilize and the patient can resume normal life. Patients with single, localized tumors should experience a survival rate similar to age-matched disease-free individuals. Of patients with initial single, localized tumors, 6.5% to 16.5% will develop a recurrence, usually 5 to 15 years after initial surgery. If all identifiable disease is resectable, including a limited number of distant metastases, surgery can provide occasional long-term remission. However, if disease is unresectable, surgical debulking will not improve survival. It may still be considered to control symptoms. Being treated by experienced pheo/para physicians is critical; and, as discussed above, being “blocked” before surgery is essential.

Radiotherapy

External beam radiation has been successful in treating a variety of cancers, but it has mixed results with pheo/para tumors. It can be effective as a method of pain control, but it may not eliminate the tumor cells. Side effects include fatigue, skin burns at the site of radiation, nerve damage, and arthritis (long term).

Radio Frequency Ablation (RFA)

RFA is a relatively new procedure that involves inserting a needle directly into the tumor and destroying the cells with radio waves. This procedure is not effective on large tumors. RFA should not be used on tumors in the head and neck or near nerves because of potential damage to surrounding structures. As with surgery, the patient must be blocked with an alpha blocker for at least 2-3 weeks before the procedure. Side effects include pain and swelling at the site of the procedure.

Transarterial embolization (TAE)

TAE is used for liver tumors that are too large for RFA (typically over 5cm). In this procedure, a catheter (a thin, flexible tube) is put into an artery through a small cut in the inner thigh and threaded up into the hepatic artery in the liver. A dye is usually injected into the bloodstream at this time to help the doctor monitor the path of the catheter via angiography. Once the catheter is in place, small particles are injected into the artery to plug it up and cut off the blood supply.

MIBG (I-131 metaiodobenzylguanidine)

This is the same radioactive tracer that is used during scans to locate tumors, but in a much higher dose. In order to receive MIBG as a therapy, the pheo/para tumors must be MIBG positive, meaning they will absorb, or “take up,” the tracer. Precautions must be taken to protect the patient’s thyroid. Side effects of this treatment include fatigue, nausea, and a decrease in blood platelets, especially in high-dose treatments or with several treatments over time.

Radiolabeled Somatostatin Analogues

Symptomatic improvement may occur with all of the various (111)In, (90)Y, or (177)Lu-labelled somatostatin analogues that have been used. Since tumor size reduction was seldom achieved with (111)Indium labelled somatostatin analogues, radiolabelled somatostatin analogues with beta-emitting isotopes like (90)Y and (177)Lu were developed. Reported anti-tumor effects vary considerably between various studies. The side effects are few and mostly mild from these treatments. However, like MIBG, the tumors must be receptive to the agents being considered for use. Not all patients will be candidates for these therapies because their tumor cells won’t “take up” the tracer elements.

Octreotide

Octreotide is a synthetic octapeptide that mimics somatostatin but is a more potent inhibitor of growth hormone, glucagon, and insulin than natural somatostatins. Like the radio labeled somatostatin analogues, Octreotide can also be labelled with a variety of radionuclides, such as yttrium-90 or lutetium-177, to enable peptide receptor radionuclide therapy (PRRT) for the treatment of unresectable pheo/para.

Cytoxic Chemotherapy

The type of chemotherapy used for pheo/para tumors is a mix of three drugs: Cyclophosphamide (Cytoxan), Vincristine, and Dacarbozine (DTIC). This type of chemo is referred to as CVD. Typically, patients will remain on CVD for an extended period of time. A common error with this therapy is to stop the therapy too soon, resulting in further tumor growth. Once CVD chemotherapy has been stopped it typically cannot be started again. It is recommended that patients stay on chemo for 20 or more rounds. An experienced physician should manage this protocol. Patients with the SDHB mutation in particular seem to respond well to this treatment. Side effects include fatigue, nausea, hair loss, decreased white and red blood cell counts, and low platelets. If the patient has bone metastases, a bone-strengthening drug (bisphosphonate) may also be administered with the chemo.

Molecular Targeted Therapy

Understanding the molecular pathway changes responsible for malignant paras will hopefully guide future molecular-targeted therapies. These therapies work by interfering with specific molecular targets along the signaling pathways in the cell that are responsible for carcinogenesis and tumor growth. To date, both benign and malignant PGLs gene mutations are part of two distinct molecular pathways leading to tumorigenesis:

  • Cluster 1 includes mutations of VHL, SDHB, and SDHD and is associated with pseudohypoxia and aberrant VEGF signaling, leading to abnormal hypoxia inducible factor (HIF) activation and overexpression of angiogenic factors.
  • Cluster 2 includes mutations of RET, NF1, TMEM127, and MAX and is associated with abnormal activation of kinase-signaling pathways such as PI3kinase/AKT, RAS/RAF/ERK, and mTOR1/p70s6K, leading to abnormal cell growth and lack of apoptosis capacity.

This all sounds really complex, and it is, but what researchers are attempting to do is keep these cells from malfunctioning by interfering with their abnormal activities somewhere along these pathways.

HIF1a inihbitors are drugs targeted at interfering with HIF hypoxia-driven transcription pathway. These agents have shown marked anti-tumor activity in mice models and seem to be promising for malignant paras, but more studies are needed.

The mTOR inhibitor everolimus (RAD001) in combination with octreotide LAR has been evaluated for low- and intermediate-grade neuroendocrine tumors, with good results. However, when everolimus was evaluated in malignant para patients, all patients experienced disease progression. Researchers concluded that further studies on the PI3K/AKT/mTOR pathway have to be conducted to find a more specific molecular target in its signalling.

Several studies have demonstrated overexpression in malignant pheo/para of angiogenic molecules, such as VEGF, angiopoietin-2, and the endothelin receptors ETA and ETB, suggesting that targeting this pathway with antiangiogenic therapies could represent a new promising treatment option. As a result, sunitinib, a receptor tyrosine kinase inhibitor that acts on several targets (VEGF, PDGF, and c-KIT), and has antiangiogenic and antitumor activity, has been used in the treatment of malignant pheo/para, with mixed but promising results.

Imatinib, another tyrosine kinase inhibitor already used for hematologic and gastrointestinal stromal tumors, has not been found effective for malignant pheo/para treatment.

Thalidomide, by targeting VEGF and basic fibroblast growth factor, is an antiangiogenic agent that has been evaluated in combination with Temozolomide in neuroendocrine tumors. Although there was an objective biochemical response rate (40%) and a radiologic response rate in 33% of malignant pheo/paras, lymphopenia occurred in about 70% of treated patients.

Activators of prolyl hydroxylase (PHD) (such as ERBB2 inhibitors) are now being evaluated as promising antineoplastic therapies. These molecules decrease the expression levels of some angiogenic factors, such as VEGF, acting on HIF pathway, by activating the PHD, thus increasing HIF hydroxylation, and promoting its degradation. More studies are required on these agents.

Molecular targeted therapies are promising strategies, but, due to the complexity of the tumor pathogenesis, further studies on tumor biology, discovery of novel targeted drugs, and new trials are needed to achieve more effective treatments.

Pregnancy and Pheo/Para

Having a pheochromocytoma or paraganglioma 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, or cause premature labor. During the stress of labor, a pheo or para tumor can release massive amounts of catecholamines that may cause hypertensive crisis in the mother and/or complicate the delivery. Therefore, patients with a suspected pheo/para tumor should be monitored closely during pregnancy and have their blood pressure controlled with medication. Consultation with a pheo/para expert is essential for the best possible outcome.

Information last reviewed by a medical professional and updated: May 2014.