Pheochromocytoma

What is Pheochromocytoma?

Pheochromocytomas are tumors that begin in the adrenal gland’s chromaffin cells (the layer of tissue on the inner part of the kidneys that carry out hormone production). The symptoms of these tumors mainly come from the overproduction of a type of hormones called catecholamines. When similar tumors grow from chromaffin cells that aren’t in the adrenal gland, we call them paragangliomas. Most of these tumors are harmless, but in a few cases, they can turn malignant, or cancerous.

What Causes Pheochromocytoma?

Tumors can occur randomly, or they may be passed down within families. A recent study mentions that as much as 35% of cases might be due to changes in genes that are inherited (known as germline mutations). Certain inherited syndromes are associated with a type of tumor known as pheochromocytoma. These include Von-Hippel Lindau (VHL), multiple endocrine neoplasia type 2 (MEN2), and neurofibromatosis type 1 (NF1).

Risk Factors and Frequency for Pheochromocytoma

Pheochromocytomas, which are a type of secondary hypertension, often go undiagnosed. A study that focused on autopsies found undetected pheochromocytomas in 0.05% of the cases examined. Another study focused on 4180 patients with hypertension in Brooklyn and found pheochromocytomas in 0.2% of these patients. According to this study, the average annual rate of pheochromocytoma occurrence is about 0.5 per 100,000 person-years.

Signs and Symptoms of Pheochromocytoma

Pheochromocytoma is a condition that causes high blood pressure. People with this condition often experience sudden increases in blood pressure, along with headaches, rapid heart rate, and sweating. However, some people have consistently high blood pressure that does not respond to several blood pressure medications, which may be a sign of pheochromocytoma. Certain medications and procedures can cause a severe spike in blood pressure. These include dopamine receptor blockers, tricyclic antidepressants, corticosteroids, sympathomimetic agents, and neuromuscular blocking agents, as well as surgical procedures or the use of anesthesia.

When pheochromocytoma is associated with certain genetic conditions, it can be discovered through screening procedures. However, it’s worth noting that some individuals may not have high blood pressure at the time of diagnosis. There have been instances of unusually large pheochromocytomas presenting as abdominal lumps with fewer than the usual symptoms. This can happen due to a higher ratio of connective tissue to hormone-producing cells in the tumor, or the growth of the tumor inside a pocket of connective tissue.

There are multiple genetic conditions that are associated with pheochromocytomas, including von Hippel Lindau (VHL) syndrome, multiple endocrine neoplasia type 2 (MEN2), and neurofibromatosis type 1 (NF1). All of these have standard features beyond pheochromocytomas and are inherited in a dominant pattern from parent to child.

On occasion, pheochromocytoma may not present with overt symptoms. This subclinical presentation can occur when the tumor secretes specific hormones or when secretory tumors arise outside of the adrenal gland. Dramatic spikes in blood pressure can also occur unexpectedly due to various triggers, including physical and emotional stress. As such, people with subclinical pheochromocytoma are also susceptible to heart-related risks.

During a physical examination, your doctor may note symptoms such as high blood pressure, a rapid heart rate, anxiety, excessive sweating, visible nerve bundles under the skin, light brown skin spots, a lump in the thyroid gland, light brown skin spots in the armpits, lesions on the iris, blood vessel tumors in the retina, and possibly an abdominal mass.

• High blood pressure
• Rapid heart rate
• Anxiety
• Excessive sweating
• Visible nerve bundles under the skin
• Light brown skin spots (cafe-au-lait macules)
• Thyroid mass
• Light brown skin spots in the armpits
• Lesions on the iris (Lisch nodules)
• Blood vessel tumors in the retina
• Possible abdominal mass

Testing for Pheochromocytoma

If your doctor suspects you may have a pheochromocytoma (a rare tumor that grows in a small gland in your body called the adrenal gland), they will first perform a biochemical test to check for increased amounts of certain chemicals–metanephrines and catecholamines–in your body.

These substances tend to be higher when you’re sitting compared to when you’re lying down. Because of this, it’s recommended to have the blood drawn when you’ve been lying down for at least half an hour. This practice helps to avoid false positive results. Sometimes, due to operational constraints, laboratories may collect blood samples while you’re sitting. But if they get positive results, they must repeat the tests after taking a blood sample when you’re lying down.

Your doctor may also ask you to provide a 24-hour urine sample. This test is also good at confirming the presence of a pheochromocytoma. It’s recommended that your doctor also measures a waste product called creatinine in your urine. This helps to verify that you’ve provided a complete sample.

If the biochemical tests show that you may have a pheochromocytoma, the next step is to locate the tumor. Typically, a CT scan (a type of X-ray) of the abdomen and pelvis is the first choice for this. Sometimes, if you need to avoid radiation, an MRI (which uses magnetic waves) is used instead.

Interestingly, pheochromocytomas can be related to some genetic conditions. In fact, mutations (changes) in genes can be responsible for these tumors in up to 35% of cases. Because of this, if you’ve been diagnosed with a pheochromocytoma, your doctor should consider genetic testing. This is even more important if you have these tumors on both of your adrenal glands or if you’re young.

Once they’ve confirmed a pheochromocytoma diagnosis, your doctor will examine your clinical history and family medical history carefully. Some symptoms and signs can point towards genetic conditions that often correlate with having pheochromocytomas. If these are present, targeted genetic examinations should be conducted. If you test positive, your family members might also want to get checked.

Certain tumor types are usually associated with a negative family history and are thus called ‘sporadic cases’. However, in a quarter of such cases, German research has reported characteristic genetic mutations as well.

Several genes have been identified that are linked with the development of pheochromocytomas are usually split into three categories based on how they can lead to tumors: the pseudohypoxia pathway, the kinase-signaling pathway, and cluster 3, which affects something known as the Wnt pathway.

Treatment Options for Pheochromocytoma

Pheochromocytoma is a rare medical condition that is most often cured by surgical removal. Here’s what to expect with different types of surgery:

If pheochromocytomas affect only one adrenal gland, they’re referred to as “unilateral.” Most cases that occur randomly, without a genetic link, are unilateral. For these, the recommended treatment is a minimally invasive surgery known as a laparoscopic adrenalectomy, which involves making small cuts instead of a large incision.

However, if the tumor is particularly large or thought to be invading other areas, a traditional open surgery known as an open adrenalectomy might be considered. This involves a larger incision to remove the tumor.

Sometimes, pheochromocytomas affect both adrenal glands, in which case they’re referred to as “bilateral.” This is more common in cases linked to hereditary syndromes, like multiple endocrine neoplasia type 2 (MEN2) and von Hippel-Lindau (VHL) disease. In these cases, removing both adrenal glands in a procedure called total adrenalectomy can result in a lifelong need for medication to replace the steroids produced by these glands.

To avoid this, another option might be a partial or cortical sparing adrenalectomy. This involves removing only the tumor and sparing as much of the adrenal glands as possible. This can be done via both open and laparoscopic surgery. While there may be a risk of the tumor coming back, this approach may reduce the need for lifelong replacement therapy.

In preparation for surgery, the main aim is to manage and reduce complications like uncontrolled high blood pressure, rapid heart rate, and volume expansion. Although no universally agreed-upon guidelines exist for this preparation, it’s generally agreed that medical therapy started before surgery can reduce these risks.

Initially, alpha-adrenergic receptor blockers, which are medications that block the overactivity of certain hormones, are used. One common example is phenoxybenzamine. These drugs are typically started 7 to 14 days before surgery. If necessary, the dosage is gradually increased during this period. Alternatively, doxazosin, which is an alpha-1 selective agent, can be used because it usually has fewer side effects.

A few days after starting the alpha blockers, beta blockers (such as propranolol, atenolol, or metoprolol) are added to help control a rapid heart rate. These should not be started without first using the alpha blockers, as they could cause a sudden, severe increase in blood pressure.

In some cases, calcium channel blockers, another type of blood pressure medication, may be useful in controlling blood pressure before surgery. Also, because pheochromocytoma can cause changes in fluid levels in the body, a diet high in salt may be started a few days after the alpha blockers to help balance these levels and decrease the risk of low blood pressure after surgery.

In the time around surgery, it’s critical to carefully handle the tumor to prevent a sudden release of hormones, especially in cases where the tumor is in a sac-like structure called a cyst. After the tumor’s removal, there might be a sudden drop in blood pressure that will need to be managed as well.

What else can Pheochromocytoma be?

The following health issues could be possible causes of certain symptoms:

• Hyperthyroidism (an overactive thyroid)
• Anxiety disorder
• Panic attacks
• Renal artery stenosis (a narrowing of the arteries that carry blood to the kidneys)
• Hyperaldosteronism (excessive aldosterone production)
• Migraines
• Pre-eclampsia (a complication in pregnancy)
• Cardiomyopathy (heart muscle disease)
• Postural tachycardia syndrome (POTS, a condition that affects circulation)
• Drug-induced hypertension (high blood pressure caused by medication)
• Cushing syndrome (a condition caused by high cortisol levels)
• Carcinoid (a rare type of cancer that can affect various organs)
• Acrodynia (a condition affecting children exposed to mercury)

Surgical Treatment of Pheochromocytoma

About 10% of pheochromocytomas, which are tumors that typically develop in the adrenal glands, could potentially spread to other parts of the body, making them malignant or cancerous. It is tough to distinguish malignant pheochromocytomas from benign (or non-cancerous) ones, as they do not show any particular signs that readily identify them as malignant. This determination can only be made if we find certain cells, known as chromaffin cells, in tissues outside of the adrenal gland.

Doctors often use something called a “Pheochromocytoma of the Adrenal Gland Scaled Score” or PASS score for short, to try and tell if a pheochromocytoma is benign or malignant.

Treatment options for malignant pheochromocytomas include surgery. Doctors may choose to remove the primary cancer and any detected spread of cancer if it is technically feasible. However, this may not guarantee that the cancer is entirely eradicated. The exact surgery approach will depend on where the cancer has spread and can follow either a traditional open surgery or a less invasive laparoscopic technique. Bigger tumors are often treated with open surgery because it offers a lower risk of the tumor rupturing during the procedure and allows for the removal of any detected cancer spread at the same time.

In some cases, the removal of the primary cancer and any detected spread may help alleviate symptoms caused by surges in the levels of catecholamines – hormones secreted by the adrenal gland. However, it is crucial to keep in mind that only 50% of people with malignant pheochromocytomas remain alive after five years.

What to expect with Pheochromocytoma

It’s important to understand that there is a chance of pheochromocytomas (a type of rare tumor that grows in the adrenal glands) coming back. This can happen regardless of whether the case is sporadic (occurs randomly) or familial (runs in families). One study found that the chance of recurrence was higher in familial cases, tumors in the right adrenal gland, and tumors outside of the adrenal glands.

According to a recent analysis of multiple studies, the chance of these tumors coming back after being completely removed by surgery is quite low at 3% – this is based on an average period of follow-up over 77 months (around 6 years).

The Endocrine Society (a group of experts who study hormones) recommends that patients have yearly tests to check for signs of the disease returning or spreading to other parts of the body.

Possible Complications When Diagnosed with Pheochromocytoma

The paragraph contains several possible health problems:

• Heart Attack
• Cardiogenic shock, a condition where the heart suddenly can’t pump enough blood to meet the body’s needs
• Stroke
• Kidney Failure
• Fluid buildup in the lungs (Pulmonary Edema)
• Severe Lung Condition causing shortness of breath (Acute Respiratory Distress Syndrome or ARDS)
• Irregular heart rhythm (Cardiac Arrhythmias)
• High Lactic Acid levels in blood (Lactic Acidosis)
• Eye damage due to high blood pressure (Hypertensive Retinopathy)
• Brain disease caused by high blood pressure (Hypertensive Encephalopathy)
• Seizures in children
• Excessive thirst in children (Polydipsia)
• Excessive urination in children (Polyuria)
• Brain blood vessel inflammation (Cerebral Vasculitis)
• Damage to the bowel due to not enough blood supply (Ischemic Enterocolitis)
• Damage to kidney due to not enough blood supply (Renal Infarction)
• Anxiety
• Depression

Preventing Pheochromocytoma

Understanding your condition is a key part of managing pheochromocytomas, a type of tumor that can cause your body to produce too much adrenaline. This can result in symptoms that come and go unexpectedly. These episodes can be triggered by certain medications like dopamine receptor blockers, non-selective beta-blockers, some types of antidepressants, steroids, sympathomimetic (drugs that mimic the effects of the body’s natural adrenaline), and medicines used during surgeries. The following symptoms may occur in these episodes:

• Headaches
• Sweating
• Rapid heartbeat
• Difficulty breathing
• Chest pain
• Feelings of anxiety

For all patients diagnosed with pheochromocytoma, it’s important to know about any family history of specific genetic conditions like von Hippel Lindau syndrome, multiple endocrine neoplasia type 2, or neurofibromatosis type 1. If you have a family history of these specific conditions, it would be beneficial to have your relatives undergo genetic screening.

To diagnose pheochromocytoma, doctors use several tests, including blood, urine, and imaging tests. Once a diagnosis is made, the treatment options often include taking medications to manage blood pressure and other symptoms. Depending on different elements, doctors might also consider surgery to remove the tumor.