Pheochromocytoma: Causes, Symptoms, Diagnosis and Treatment

Pheochromocytomas are uncommon neuroendocrine tumors that typically grow slowly. They originate from cells in the adrenal medulla, the adrenal gland’s core. Often, pheochromocytoma can be effectively treated and controlled if caught early. Although there are choices, surgery to remove the tumor or tumors is the preferred course of treatment when it is feasible. Usually, surgical intervention reduces symptoms and brings blood pressure back to normal.

What is Pheochromocytoma?

A rare tumor that develops in an adrenal gland is called a pheochromocytoma. The tumor is not usually cancerous, which is also termed a benign tumor. There is one adrenal gland on top of each kidney. The hormones produced by the adrenal glands aid in regulating vital bodily functions, including blood pressure. A pheochromocytoma often affects just one adrenal gland. However, cancers can develop in any of the two adrenal glands.

Hormones released by a pheochromocytoma tumor might result in a variety of symptoms. These include headaches, perspiration, elevated blood pressure, and panic attack symptoms. Serious or even fatal harm to other bodily systems may result from untreated pheochromocytomas.

There are three stages of pheochromocytoma:

• Local Pheochromocytoma: The tumor is still inside the adrenal gland where it first appeared and has not spread.
• Regional Pheochromocytoma: Adjacent tissues or lymph nodes may have been affected by the tumor.
• Metastatic Pheochromocytoma: The tumor has extended to other locations.

Causes

The exact cause of pheochromocytoma remains unclear in many cases. However, several factors and conditions have been linked to its development. These include genetic mutations, hereditary syndromes, and abnormal growth of specific cells in the adrenal glands.

1. Genetic Mutations

Pheochromocytomas can arise due to genetic mutations that trigger uncontrolled cell growth. Changes in specific genes involved in regulating cell function and hormone production can lead to tumor formation. Genetic alterations affecting tumor-suppressor genes or those responsible for cell division can result in abnormal chromaffin cell proliferation, which forms the tumor.

2. Hereditary Syndromes

In about 30% of cases, pheochromocytomas are linked to inherited genetic syndromes. Individuals with these hereditary conditions have a higher likelihood of developing the tumor. Some of the common syndromes associated with pheochromocytoma include:

• Multiple Endocrine Neoplasia (MEN): A genetic disorder that leads to tumors in multiple endocrine glands, including the adrenal glands.
• Von Hippel-Lindau (VHL) Syndrome: A condition that results in the growth of tumors and cysts in different organs, including the adrenal glands.
• Neurofibromatosis Type 1 (NF1): A genetic disorder that causes tumors to form on nerve tissue, occasionally involving the adrenal glands.
• Hereditary Paraganglioma-Pheochromocytoma Syndrome: This condition leads to tumors in the adrenal glands or along nerve tissue in the head, neck, and torso.

3. Chromaffin Cell Abnormalities

Pheochromocytomas originate from chromaffin cells, which are responsible for releasing adrenaline and noradrenaline. In a healthy body, these hormones are released during stressful situations, triggering the fight-or-flight response. However, in individuals with pheochromocytoma, the tumor causes excessive and uncontrolled hormone production, even in the absence of stress. This abnormal hormonal release leads to symptoms such as high blood pressure, rapid heartbeat, and anxiety.

4. Sporadic Occurrence

In some cases, pheochromocytomas develop sporadically without any known genetic or hereditary link. These tumors occur randomly and are not associated with family history. While the exact trigger for sporadic cases is not fully understood, factors such as age, lifestyle, and environmental influences may play a role.

5. Rare Cases of Malignant Transformation

Although most pheochromocytomas are benign, in rare instances, they can become malignant. The cause of this transformation is not well understood but may involve genetic mutations that promote aggressive tumor growth. Malignant pheochromocytomas can spread to other organs, making treatment more complex.

Understanding the potential causes of pheochromocytoma can aid in early detection, particularly for individuals with a family history of genetic syndromes. Genetic counseling and regular monitoring are recommended for those at risk.

Symptoms

Pheochromocytomas might sometimes cause no symptoms at all. The following symptoms of pheochromocytoma are frequently present:

• High blood pressure
• Prolonged perspiration
• Quick heartbeat
• Restless shaking in certain individuals
• Pale skin
• Breathing difficulty
• Symptoms similar to a panic attack, such as sudden, overwhelming terror
• Fear or a feeling of impending calamity
• Issues with vision
• Constipation
• Loss of weight

Risk Factors

Multiple factors can heighten the risk of pheochromocytoma development:

1. Genetic Mutations: Inherited conditions, such as multiple endocrine neoplasia (MEN), Von Hippel-Lindau syndrome, and neurofibromatosis type 1, raise the likelihood of developing pheochromocytoma.
2. Age Group: The condition is more common in individuals between 30 and 50 years old, although it can occur at any age.
3. Paraganglioma Syndrome: People with this syndrome, which causes tumors along nerve pathways, have a higher risk of pheochromocytoma.
4. Previous Tumors: Individuals with a history of adrenal or paraganglioma tumors are at greater risk of recurrence.
5. Chronic Hypertension: Long-term high blood pressure increases the risk of adrenal gland abnormalities, including pheochromocytoma.

Identifying these risk factors can help with early detection and timely intervention.

Diagnosis

Diagnosis of pheochromocytoma will include the following.

• Genetic Tests: The healthcare provider may advise genetic testing to determine whether a pheochromocytoma is associated with a hereditary disorder. This will include several tests the doctor will carry out to assess pheochromocytoma.
• 24-hour Urine Analysis: For 24 hours, a urine sample is required for analysis to determine the correct diagnosis of the condition.
• Blood Test: A medical practitioner draws blood to be examined in the laboratory.
• Lab Tests: The hormones noradrenaline and adrenaline, as well as chemicals known as metanephrines that might result from these hormones, are measured in these tests. There is a greater likelihood of elevated metanephrine levels in pheochromocytoma patients.
• Imaging Tests: Imaging studies are required if the lab test results reveal evidence of a pheochromocytoma. The doctor may request one or more of these tests to determine a tumor. Among these tests are the following:
• MRI
• M-iodobenzylguanidine (MIBG) imaging
• Positron emission tomography, or PET scans
• CT Scan

Treatment

The size of the tumor affects the treatment options for pheochromocytoma, among other things.

• Whether the tumor is malignant or benign
• Elevated catecholamine symptoms
• If the tumor is localized or has metastasized, that is, it has spread to other parts of your body
• If the tumor has recurred or has been diagnosed for the first time

The treatment options for pheochromocytoma are:

• Medications: The doctor may prescribe medicine to treat symptoms if pheochromocytoma is causing an overabundance of adrenal hormones. For instance, medications will be advised to maintain normal blood pressure and heart rate.
• Surgery: The primary therapy for pheochromocytoma is surgery. Ninety percent of pheochromocytomas can be surgically removed with success. To determine whether the tumor has spread, the surgeon will examine the lymph nodes and surrounding tissue during the procedure. After surgery, the doctor will measure the catecholamine levels in blood or urine following surgery. A normal level of catecholamines indicates the complete removal of pheochromocytoma cells.
• Radiation Treatment: Strong beams of energy are focused during radiation therapy to either kill or stop the growth of cancer cells while preserving as much surrounding healthy tissue as feasible. There are two types of radiation therapies:
  • External Radiation Therapy
  • Internal Radiation Therapy
• Ablation Therapy: One safe therapeutic approach for tumor destruction is ablation therapy, which employs extremely high or extremely low temperatures. The following ablation techniques can aid in the death of cancerous and aberrant cells:
  • Cryoablation
  • Radiofrequency Ablation
• Embolization Treatment: Embolization therapy is a type of pheochromocytoma treatment in which the artery that supplies the adrenal gland is blocked. The cancer cells that are proliferating in the adrenal glands can be killed by cutting off the blood supply to them.
• Targeted Therapy: One type of treatment called targeted therapy involves using drugs or other substances to target particular cancer cells while sparing healthy ones. Medical professionals treat recurring and metastatic pheochromocytomas using targeted medicines.

Prevention

Pheochromocytoma cannot be prevented. However, individuals with a family history of the condition or related genetic syndromes can take proactive steps for early detection. Genetic counseling and testing can assist in detecting the risk by screening for hereditary conditions like:

• Multiple endocrine neoplasia type 2 (MEN2)
• Von Hippel-Lindau (VHL) disease
• Neurofibromatosis type 1 (NF1)
• Hereditary paraganglioma syndrome
• Carney-Stratakis dyad
• Carney triad

If you have close relatives with pheochromocytoma or any of these genetic conditions, consult your healthcare provider for regular screening and monitoring. Early diagnosis can help manage the condition more effectively.

Conclusion

Although phaeochromocytoma is an uncommon tumor, it’s vital to be aware of the risk of receiving this diagnosis since the symptoms and indications of these tumors can be harmful. Even while heart palpitations, anxiety, and high blood pressure are frequent symptoms, it’s crucial to consult a doctor if they happen simultaneously, particularly during episodes.

Acquiring knowledge about pheochromocytoma symptoms might facilitate the diagnosis process. Comprehending the situation will aid in making appropriate inquiries and obtaining care.

When Should I Contact a Doctor?

Speak with a doctor if you have headaches and elevated blood pressure, which are signs of pheochromocytoma. Pheochromocytoma is uncommon, therefore treating high blood pressure is crucial even if the chance of developing it is minimal.

Frequently Asked Questions