Types of Pheochromocytoma: What Patients and Families Need to Know

Pheochromocytoma is a rare but treatable tumor that can be both life-altering and frightening for those affected. Pheochromocytoma is usually benign, but can sometimes be cancerous. 

This rare tumor has a significant impact on both physical and emotional health due to its excessive hormone production and the effects of these chronically elevated hormones.

Understanding pheochromocytoma, including the different types and how they function, helps patients and their families to navigate diagnosis, treatment, and long-term care. 

This article discusses the different types of pheochromocytoma to help patients and their families understand the condition better. It also explains how understanding the distinctions between types can improve outcomes by helping people make more informed decisions about diagnosis and treatment. 

Whether you're newly diagnosed or supporting a loved one, having a clear understanding of pheochromocytoma can provide a sense of empowerment in managing this condition.

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What is Pheochromocytoma?

Pheochromocytoma is a rare tumor that forms in the adrenal glands, which are located on top of the kidneys. Specifically, a pheochromocytoma is a tumor of specialized cells deep in the adrenal gland that produce catecholamines, or chemicals that act as both neurotransmitters and hormones.

Even though they can be very small, a pheochromocytoma can produce enough catecholamines to overwhelm a person’s body. Catecholamines include adrenaline and noradrenaline (also called epinephrine and norepinephrine), and they regulate various functions, including blood pressure and stress response. 

A pheochromocytoma can be either benign or malignant, and some are associated with hereditary conditions. Sporadic cases of pheochromocytoma are a rare cause of high blood pressure, affecting about 0.2% of patients with uncontrolled hypertension.

Pheochromocytomas are most commonly diagnosed in people between 20 and 40 years old. 

A pheochromocytoma overproduces catecholamines, disrupting the normal balance of hormones involved in the stress response. This overproduction of hormones like adrenaline and noradrenaline leads to significant health issues.

Symptoms of Pheochromocytoma

Symptoms of pheochromocytoma are caused by excessive catecholamine production. 

Norepinephrine, which is often secreted continuously by the tumor, causes persistent and often severe high blood pressure that often remains high despite trying multiple blood pressure medications.

Epinephrine, on the other hand, is typically released in bursts, causing intermittent episodes of tachycardia and anxiety.

The most common symptoms of pheochromocytoma include:

• High blood pressure, which may be severe and sudden. Blood pressure that remains high despite multiple blood pressure medications can be a key sign leading healthcare providers to investigate pheochromocytoma as a possible cause.

• Headaches

• Sweating

• Heart palpitations

• Anxiety or feelings like you’re having a panic attack

These symptoms can come and go in waves, which can make pheochromocytoma overwhelming for the patient and challenging for the clinician to diagnose. In some cases, symptoms are mistaken for more common conditions like anxiety or hypertension.

Importance of Early Detection

Early detection of pheochromocytoma is critical. Left untreated, this tumor can cause serious complications such as heart attack, stroke, and organ damage due to consistently high blood pressure. 

For patients with malignant pheochromocytoma, early intervention is key to preventing the spread of cancer to other parts of the body.

Types of Pheochromocytoma

Pheochromocytomas come in different forms, each with unique characteristics. Understanding the differences helps guide diagnosis, treatment, and long-term management.

Benign Pheochromocytomas

Benign pheochromocytomas are non-cancerous, slow-growing tumors that remain confined to the adrenal glands. Most pheochromocytomas are benign, meaning they don’t spread to other parts of the body, and only about 10% become malignant.

Though not malignant, these tumors can still cause significant health problems due to the excess hormone production.

Characteristics

Benign pheochromocytomas tend to grow slowly, especially smaller pheochromocytomas, and are less aggressive than their malignant counterparts. They generally stay in one location and do not spread to other organs.

Symptoms and Impact on Health

While benign, these tumors can still cause the hallmark symptoms of pheochromocytoma, including high blood pressure and episodes of severe headaches and sweating. 

Persistently elevated blood pressure despite medication use is a sign to investigate for pheochromocytoma.

Diagnostic Approaches

Diagnosing benign pheochromocytoma primarily involves biochemical testing, such as measuring plasma or urinary metanephrines and catecholamines, to detect excess hormone production.

Imaging studies, including CT, MRI, or functional scans like PET, are used to locate and assess the tumor for accurate diagnosis.

Malignant Pheochromocytomas

Malignant pheochromocytoma is a rare, catecholamine-producing tumor that can spread to other parts of the body, including the liver, lungs, bones, and lymph nodes. 

While most pheochromocytomas are benign and curable with surgery, malignant cases are more aggressive, difficult to predict, and lack curative treatments. 

Characteristics

Metastatic pheochromocytoma spreads to areas like the liver, lungs, bones, or lymph nodes. It may develop years after the primary tumor is removed, and while treatments can help manage symptoms and reduce tumor size, there is no cure. 

Patients often experience very high levels of stress hormones, leading to severe high blood pressure and potential heart damage. 

Symptoms and Progression

In addition to the symptoms of benign pheochromocytomas, malignant forms may cause more intense and frequent symptoms as the tumor grows. Metastatic spread can result in pain and dysfunction in affected organs.

Prognosis and Treatment Options

Treatment for malignant pheochromocytoma often includes surgery, chemotherapy, radiation therapy, or targeted drug treatments. The prognosis depends on how early the tumor is detected and how aggressively it is treated.

While not curative, surgery can reduce tumor burden, lower hormone levels, and alleviate symptoms. It may be used to remove primary tumors or metastases in vital areas.

Familial Pheochromocytomas

Familial pheochromocytoma is a hereditary condition found in about 25% of cases. It’s linked to genetic mutations in disorders such as Neurofibromatosis type 1 (NF1), Multiple Endocrine Neoplasia type 2 (MEN2), and Von Hippel-Lindau (VHL). 

These inherited tumors are often detected at a younger age, tend to be located in multiple areas, and may occur outside the adrenal glands compared to non-hereditary cases. While these tumors can be benign, there is a higher risk of them becoming malignant in certain conditions.

Since there’s no treatment to prevent the tumors, early diagnosis and regular monitoring are key to managing the condition effectively.

Genetic Links

Familial pheochromocytomas are linked to inherited genetic mutations:

• Neurofibromatosis type 1 (NF1): NF1 is a genetic disorder caused by mutations in the NF1 gene on chromosome 17. It leads to skin features like café-au-lait spots, neurofibromas, freckling, and Lisch nodules on the eyes. About 1-3% of NF1 patients develop pheochromocytomas, which are usually found in the adrenal glands. Malignant cases are rare.

• Multiple Endocrine Neoplasia type 2 (MEN2): MEN2, caused by mutations in the RET gene, has two types: MEN2A and MEN2B. It is linked to Medullary Thyroid Carcinoma (MTC), and around 50% of patients develop pheochromocytomas, typically in the adrenal glands and often on both sides. These tumors are rarely malignant.

• Von Hippel-Lindau (VHL): VHL is a genetic condition from mutations in the VHL gene on chromosome 3. It can cause various tumors, including pheochromocytomas, hemangioblastomas, and renal cell carcinoma. VHL type 1 usually doesn’t involve pheochromocytomas, while type 2 frequently does, often in both adrenal glands. Malignant pheochromocytomas are uncommon in VHL.

• Paraganglioma Syndrome type 4: mutations in the SDHB gene are linked to Paraganglioma Syndrome type 4 (PGL4) and familial pheochromocytoma. People with SDHB mutations are more likely to develop tumors outside the adrenal glands, which have a higher chance of being cancerous. These tumors tend to appear earlier in life and are often more aggressive.

Risk Factors and Screening for Families

If pheochromocytoma runs in a family, genetic counseling and regular screenings are necessary for early detection. Family members with a known genetic mutation should be monitored closely through annual blood tests and imaging to catch any tumors early.

Causes and Risk Factors for Different Types

Understanding what causes pheochromocytomas can help identify those at risk and inform treatment strategies.

Genetic Mutations

Genetic mutations in NF1, RET, VHL, and SDHB, are known risk factors for developing pheochromocytomas, often leading to a higher likelihood of tumor formation and, in some cases, more aggressive or malignant tumors. 

Regular screening and genetic counseling are important for those with a family history of these conditions.

Family History

A family history of genetic syndromes like MEN2, VHL, or NF1 significantly increases the risk of developing pheochromocytoma. Regular screening and early intervention are recommended for individuals with a family history of these conditions.

Environmental and Lifestyle Factors

A key factor in the development of pheochromocytoma is oxidative stress, which occurs when there's an imbalance between harmful molecules (prooxidants) and the body's antioxidants. 

This stress damages cells, especially in the mitochondria, and can trigger tumor formation by disrupting normal energy production processes and activating pathways that promote cancer growth. 

Mutations in certain genes, like SDHB, further enhance oxidative stress, contributing to the development and aggressiveness of these tumors.

Diagnosis and Screening for Pheochromocytoma

A clinician who suspects pheochromocytoma will often begin by ordering blood or urine tests or both.

Diagnostic Tools

Diagnostic tools include blood and urine testing and imaging to determine whether a catecholamine-secreting tumor is present. Often, genetic testing is recommended as well, especially in younger patients and in patients with recurrent pheochromocytoma.

• Biochemical Testing: doctors first test blood and urine for high levels of catecholamines and their byproducts, called metanephrines. This confirms if the tumor is causing excess hormone production.

• Correct Positioning: blood samples should be taken while the patient is lying down, as sitting can cause false positives by increasing metanephrine levels.

• Imaging Scans: once hormone levels are confirmed, doctors use CT scans or MRIs to locate the tumor. If there is a risk of the cancer spreading, PET scans or MIBG scans (a special imaging test used to detect pheochromocytomas) may be used to get more detailed images.

• Genetic Testing: since some pheochromocytomas are inherited, genetic testing is recommended, especially in younger patients, those with tumors in both adrenal glands, or if there’s a family history of related conditions. Recurrent benign pheochromocytomas, especially in young patients, also suggest a possible underlying genetic syndrome. 

Monitoring Malignancy Risk

For patients with a history of benign pheochromocytomas, regular follow-up tests are necessary to assess for the development of new tumors and detect any signs of malignant transformation.

Treatment Options for Pheochromocytoma

The following treatments may be recommended by medical providers:

Surgical Removal

Surgery is the most common treatment for pheochromocytoma. In many cases of benign pheochromocytoma, complete removal of the tumor resolves symptoms.

Indications and Techniques

Most pheochromocytomas are treated surgically. Generally, laparoscopic adrenalectomy is the preferred approach for most cases. 

For benign tumors, surgery is typically curative, while malignant tumors may require additional treatments. 

Risks and Benefits

Before surgery, patients are given medication to lower the risk of complications like high blood pressure during the procedure.

Surgical risks include infection, bleeding, and long-term adrenal insufficiency. While surgery can cure benign tumors, malignant (cancerous) pheochromocytomas might require additional treatments such as chemotherapy or radiation.

Medical Management

For patients who cannot undergo surgery or who have malignant pheochromocytoma, medications can help manage hormone levels and control blood pressure.

Malignant Pheochromocytoma Therapies

In cases of malignant pheochromocytoma, treatments often include chemotherapy, radiation, or newer therapies like MIBG therapy or drugs like sunitinib, which slow the tumor's growth by blocking blood vessel formation.

Treatment for Familial Pheochromocytomas

Patients with a family history of pheochromocytoma need special care, including regular screenings and sometimes preventative surgeries to stop tumors from developing. Genetic testing and regular monitoring is recommended to catch the disease early.

Living with Pheochromocytoma: What Patients & Families Need to Know

It’s important to discuss the implications of a diagnosis of pheochromocytoma with your doctor. While some pheochromocytomas are sporadic, others may have a genetic component that can require long-term monitoring. 

Impact on Daily Life

Living with a genetic tendency for pheochromocytoma may require lifestyle modifications. Reducing stress, following a healthy diet, and adhering to prescribed medications can help reduce oxidative stress, manage symptoms, and prevent complications.

Genetic Counseling and Family Support

Genetic counseling is essential for families affected by familial pheochromocytomas. It helps them understand their risk and navigate decisions about screening and treatment.

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FAQs: Common Questions About Pheochromocytoma

These FAQs provide a quick resource to get essential questions about pheochromocytoma answered. 

How is Pheochromocytoma Diagnosed?

Diagnosis typically involves imaging and biochemical testing to measure hormone levels.

What Are the Symptoms of Malignant Pheochromocytoma?

Malignant pheochromocytomas often cause more severe symptoms like chronic pain, rapid heart rate, and more frequent episodes of high blood pressure.

Is Pheochromocytoma Hereditary?

Yes, some types of pheochromocytoma are hereditary and linked to genetic mutations.

Can a Benign Pheochromocytoma Become Malignant?

While rare, benign pheochromocytomas can potentially become malignant over time.

What Are the Treatment Options for Malignant Pheochromocytoma?

Treatment options include surgery, chemotherapy, radiation, and targeted drug therapies.