Shall we talk about the rare tumor called Pheochromocytoma today?

Do you sometimes have sudden high blood pressure? Or do you just sweat? Do you get a headache with a pounding heart? Don't be too quick to assume that a few of these things are a serious illness. However, if these symptoms persist, especially with high blood pressure that is difficult to control, it is a good idea to be a little concerned. Today we are going to talk about a condition that is a bit rare, but if properly diagnosed, can be treated very well. That is called pheochromocytoma.

What is Pheochromocytoma? Let's understand it simply.

Simply put, a pheochromocytoma is a tumor that develops in the middle part of the adrenal glands, the adrenal medulla. These tumors are formed by a special type of cell called chromaffin cells. These cells produce and release hormones into the bloodstream that are necessary for our body's "fight or flight" response. Think about it, when you are suddenly scared or face a lot of stress, the changes that happen in your body - your heart rate increases, you sweat, your body shakes - these hormones are responsible for this.

Pheochromocytoma usually develops in only one adrenal gland. However, sometimes it can develop in both glands. It is possible to have more than one tumor in one gland.

Importantly, most pheochromocytomas are benign (not malignant) . This means they do not spread to other parts of the body. However, between 10% and 15% can be cancerous. If this is a cancerous condition, it is described in several main categories, depending on how it has spread:

• Localized pheochromocytoma: The tumor is located in only one or both adrenal glands.
• Regional pheochromocytoma: The cancer has spread to lymph nodes near the adrenal glands or to other tissues.
• Metastatic pheochromocytoma: The cancer has spread to distant organs such as the liver, lungs, or bones.
• Recurrent pheochromocytoma: The cancer has come back after treatment. It can be in the same place it was before or in a different place.

What are these adrenal glands in our body? What is their function?

We have two adrenal glands. They are located at the back of our abdomen, above our kidneys, like a cap. They are part of our endocrine system. Each adrenal gland has two main parts. The outer layer is called the adrenal cortex, and the middle part is called the adrenal medulla.

Our adrenal medulla produces a group of hormones called catecholamines. These hormones control several very important processes in our body:

• Heart rate
• Blood pressure
• Blood sugar level `(Blood glucose)`
• How our body responds to stress (the "fight or flight" response)

The main types of catecholamines are:

• Dopamine
• Epinephrine (Adrenaline) `(Epinephrine / Adrenaline)`
• Norepinephrine (Noradrenaline) `(Norepinephrine / Noradrenaline)`

When a pheochromocytoma is present, it can release more of these hormones, adrenaline and noradrenaline, into the bloodstream than necessary. That's when various symptoms begin to appear.

What is the difference between Pheochromocytoma and Paraganglioma?

These are two very similar, rare types of tumors. Both arise from the same chromaffin cells that we discussed earlier. However, pheochromocytoma arises in the middle part of the adrenal gland (the adrenal medulla), while paraganglioma arises in other places outside the adrenal gland .

Who is most likely to develop this condition? How common is it?

Pheochromocytoma can develop at any age, but is most common in people between the ages of 30 and 50. Approximately 10% of cases are reported in childhood.

This is a very rare tumor . It is difficult to say exactly how many people have this condition. Because some people do not show any symptoms, the disease may go undiagnosed. It is estimated that less than 1% of people with high blood pressure have a pheochromocytoma.

What symptoms does someone with pheochromocytoma show?

Pheochromocytoma symptoms occur when the tumor releases too much of the hormones adrenaline (epinephrine) or noradrenaline (norepinephrine) into the bloodstream. However, some tumors do not produce too much of these hormones and may be asymptomatic.

The most commonly seen symptoms are:

• High blood pressure (Hypertension): This is the main symptom. Sometimes it is difficult to control.
• Headache: It can be a severe, sudden headache.
• Excessive sweating for no reason.
• Palpitations are a feeling of rapid, irregular, or pounding heartbeat.
• Feeling like your body is shaking.

Less common symptoms:

• Chest and/or abdominal pain.
• The skin suddenly becomes paler than usual.
• Nausea and/or vomiting.
• Diarrhea.
• Constipation.
• Orthostatic hypotension is a sudden drop in blood pressure when you stand up. This means that you feel dizzy when you stand up suddenly from a sitting position.
• Weight loss for no reason.

These symptoms may appear or worsen after certain events. For example:

• Intense physical activity.
• Physical injury or severe mental stress.
• Childbirth.
• Obtaining anesthesia.
• Performing surgery.
• Eating foods rich in tyramine (e.g. red wine, chocolate, cheese).

Are the symptoms always there? Or do they come and go?

A person with pheochromocytoma may have persistent high blood pressure, or it may come and go .

Some people may experience "paroxysmal attacks," or sudden attacks of symptoms. This means that there is a sudden increase in blood pressure, accompanied by symptoms such as severe headache, increased heart rate, and excessive sweating. These "attacks" can occur several times a day, or even once or twice a month.

Important: If you have any of these symptoms, especially sudden high blood pressure, headache, sweating, and palpitations, it is very important to seek medical advice.

Why does pheochromocytoma develop? What are the causes?

In most cases, no specific cause can be found for pheochromocytoma. It occurs randomly.

However, in 25% to 35% of cases, this condition is related to hereditary conditions. Some of the main ones are:

• Multiple endocrine neoplasia 2 syndrome, types A and B (MEN2A and MEN2B)
• Von Hippel-Lindau (VHL) disease
• Neurofibromatosis type 1 (NF1)
• Hereditary paraganglioma syndrome
• Carney-Stratakis dyad [paraganglioma and gastrointestinal stromal tumor (GIST)]
• Carney triad (paraganglioma, GIST and pulmonary chondroma)

In addition to these genetic conditions, pheochromocytoma can also develop due to mutations in at least 10 different genes.

How is this disease diagnosed? (Diagnosis)

Pheochromocytoma can be difficult to diagnose because it is a rare tumor and sometimes causes no symptoms. Sometimes, the tumor is discovered incidentally during a test done for another reason.

There are several reasons why a doctor might suspect this disease:

• Your detailed medical history , especially whether anyone in your family has ever had pheochromocytoma.
• A complete physical and medical examination.
• Some specific symptoms , for example the "paroxysmal attacks" we talked about and high blood pressure that is not controlled by normal treatments.

What kind of tests are done?

The doctor may recommend the following tests to confirm whether you have pheochromocytoma:

• 24-hour urine test: This involves collecting your urine throughout the day and measuring the amount of catecholamines in it. It also measures the substances that are produced when these hormones break down. If these levels are higher than normal, it could be a sign of pheochromocytoma.
• Blood catecholamine tests: These measure the levels of catecholamines in the blood. Like urine tests, they also look for substances produced by the breakdown of hormones.
• CT scan (Computer Tomography scan): This takes a series of X-rays to create detailed pictures of the inside of your body. Your doctor may recommend this to look at your adrenal glands.
• MRI scan (MRI - Magnetic Resonance Imaging): This uses a magnet, radio waves, and a computer to make detailed pictures of the inside of the body. It is also used to examine the adrenal glands.

Once the disease is confirmed, further tests may be done to determine whether the tumor is cancerous (malignant) or benign (benign), and whether it has spread to other parts of the body.

Why is Genetic Testing Important?

If you are diagnosed with pheochromocytoma, your doctor will likely recommend genetic counseling and testing to determine if you have an inherited syndrome that puts you at risk for developing other cancers.

Genetic testing may be recommended in cases like these:

• If you or someone in your family has symptoms associated with hereditary pheochromocytoma or paraganglioma syndrome.
• If you have tumors in both of your adrenal glands.
• If there is more than one tumor in one adrenal gland.
• If there are symptoms of increased levels of catecholamines in the blood.
• If pheochromocytoma is diagnosed before the age of 40.

If a genetic test finds a gene change, the genetic counselor may recommend that other members of your family (those who are asymptomatic but at risk) also undergo this test.

What are the treatments for Pheochromocytoma?

The best treatment for this is to surgically remove the tumor, if possible .

The choice of treatment depends on several factors:

• The size of the tumor.
• Whether the tumor is cancerous (malignant) or benign (benign).
• Whether there are symptoms due to an increase in catecholamine hormones.
• Is the tumor confined to one location, or has it spread to other parts of the body? (Metastasised)
• Whether the disease was diagnosed for the first time, or whether it has recurred after previous treatment.

If you have symptoms due to increased adrenal hormones, your doctor may prescribe medications to control those symptoms. For example:

• Medications to keep blood pressure at a normal level, such as alpha-blockers.
• Medications to keep the heart rate at a normal level, such as beta-blockers.
• Medications that block the effects of hormones released in excess by the adrenal gland.

The main treatment options for pheochromocytoma are:

• Surgery
• Radiation therapy
• Chemotherapy
• Ablation therapy
• Embolization therapy
• Targeted therapy

Together, you and your medical team will determine the treatment plan that is best for you.

Main treatment methods

• Surgery:

This is the main treatment for pheochromocytoma. Approximately 90% of tumors can be successfully removed surgically .

Your doctor may recommend surgery to remove one or both of your adrenal glands (adrenalectomy). During the surgery, the surgeon will examine the surrounding tissue and lymph nodes to see if the tumor has spread. If it has, they will remove that tissue, if possible.

After surgery, your blood or urine will be tested for catecholamine levels. If the levels return to normal, it means that all of the pheochromocytoma cells have been removed.

If both adrenal glands are removed, you will have to take hormone therapy for the rest of your life to replace the hormones produced by the adrenal glands.

• Radiation therapy:

This is a treatment that is used to either kill cancer cells or stop them from growing. This is done in a way that does not harm healthy tissue as much as possible.

There are two types of radiation therapy:

• External radiation therapy: Radiation is delivered to the cancer site from a machine outside the body.
• Internal radiation therapy: A radioactive substance is packed into needles, seeds, wires, or catheters and inserted by a doctor into or near the site of the cancer.

The type of radiation therapy depends on whether the cancer is localized, regional, metastatic, or recurrent. Malignant pheochromocytoma is most often treated with external beam radiation therapy and/or 131I-MIBG therapy. 131I-MIBG is a radioactive substance that attaches to some cancer cells and kills them.

• Chemotherapy:

This uses drugs to kill cancer cells, stop them from dividing and multiplying, or stop the growth of cancer. These drugs are usually given intravenously. Although this is a successful treatment, it can have side effects.

• Ablation therapy:

This is a minimally invasive treatment. It uses extreme heat or extreme cold to destroy the tumors.

• Radiofrequency ablation: Radiofrequency ablation uses radio waves to heat and destroy cancer cells and abnormal cells.
• Cryoablation: Uses liquid nitrogen or liquid carbon dioxide to freeze and destroy cancer cells and abnormal cells.

• Embolization therapy:

In this, the artery that supplies blood to the adrenal gland is blocked. This stops blood flow to the gland, and the cancer cells growing there die.

• Targeted therapy:

This uses drugs or other substances that specifically attack only cancer cells without harming healthy cells. This treatment is used for metastatic and recurrent pheochromocytoma.

A tyrosine kinase inhibitor called sunitinib is being studied for metastatic pheochromocytoma. These drugs inhibit tumor growth.

Can this disease be prevented?

Unfortunately, there is no way to prevent pheochromocytoma. However, if you are at risk for developing this disease due to hereditary syndromes and genes, genetic counseling can help with screening and early detection.

If any of your close family members (siblings, parents) have had pheochromocytoma, or if you have a genetic condition like the ones we discussed earlier (Multiple endocrine neoplasia 2 syndrome, Von Hippel-Lindau (VHL) disease, Neurofibromatosis type 1 (NF1), Hereditary paraganglioma syndrome, Carney-Stratakis dyad, Carney triad), it is very important to talk to your doctor about it.

What is the chance of recovery after treatment? (Prognosis)

The outlook for pheochromocytoma is generally very good if treated. We have already said that approximately 90% of tumors can be successfully removed with surgery.

However, if left untreated, this condition can lead to serious, even life-threatening complications . For example:

• Cardiomyopathy
• Myocarditis
• Uncontrolled bleeding in the brain (Cerebral hemorrhaging)
• Fluid accumulation in the lungs (Pulmonary edema)

Some pheochromocytoma patients are also at risk of stroke or myocardial infarction.

When should I see a doctor?

• If you are diagnosed with pheochromocytoma and develop any troubling symptoms, see your doctor immediately.
• If you have symptoms of pheochromocytoma, such as high blood pressure and headaches, talk to your doctor. Although pheochromocytoma is rare, it is important to treat high blood pressure.
• If you know that one of your close relatives (siblings, parents) has a genetic condition such as `Multiple endocrine neoplasia 2 syndrome` or `Von Hippel-Lindau (VHL) disease`, you may also be at higher risk of developing pheochromocytoma, so see a doctor to talk about genetic testing.

What questions should I ask the doctor?

If you are diagnosed with pheochromocytoma, it may be helpful to ask your doctor these questions:

• Why did I develop pheochromocytoma?
• Can my children and/or relatives develop pheochromocytoma?
• What treatment options do I have?
• What are the side effects of different treatments?
• How can I manage my symptoms?

Finally, the most important things to remember (Take-Home Message)

Okay, so, although pheochromocytoma is a rare tumor, it is often benign and treatable . Also, it can run in families, so if you or someone in your family is diagnosed with this condition, it is important to get genetic testing. This can also help determine if you are at risk for other health problems.

Remember, if you have any questions about your risk of developing pheochromocytoma or about this disease, don't be afraid to talk to your doctor. They are here to help you. Stay healthy!

Pheochromocytoma , adrenal gland, catecholamines, high blood pressure, headache, sweating, tumor, endocrine system