Pheochromocytoma

What is a pheochromocytoma?

The causes often remain unclear; however, around a third of all pheochromocytomas are attributable to genetic changes. For example, pheochromocytoma occurs in the hereditary diseases Von Hippel-Lindau syndrome, multiple endocrine neoplasia type 2 (MEN 2) or neurofibromatosis type 1. The treatment of choice is surgery.

Pheochromocytoma is a tumor that in most cases develops in the adrenal medulla – usually on one side only. It is usually benign and only rarely (around ten percent) malignant. The origin of the pheochromocytoma lies in the so-called chromaffin cells. These are special glandular cells in the adrenal medulla that primarily release the stress hormones adrenaline and noradrenaline and, less frequently, the neurotransmitter dopamine. These substances belong to the group of catecholamines, which increase blood pressure. There are also pheochromocytomas, which develop from chromaffin cells outside the adrenal medulla. Medical experts call them paragangliomas.

A pheochromocytoma can cause greatly increased blood pressure if it releases large quantities of catecholamines. Those affected also experience symptoms such as headaches, sweating, dizziness or cardiac arrhythmia. However, these typical complaints only occur in 50 percent of cases. Catecholamines also help us to diagnose a pheochromocytoma. We determine their degradation products in the blood or urine.

The treatment of a pheochromocytoma consists of an operation in which the adrenal gland and tumor are removed. However, those affected must first take special antihypertensive medication for a few days. Otherwise, the tumors can release life-threatening amounts of catecholamines during anesthesia or surgery and massively increase blood pressure.

Pheochromocytoma – frequency and age

There is no precise data on the incidence of pheochromocytoma. However, it is estimated that around two in one million people are diagnosed with this tumor every year. In reality, the figures could be higher because pheochromocytoma is difficult to diagnose and often remains undetected for a long time.

In principle, the tumor can affect people of any age. There seems to be a peak in frequency between the ages of 30 and 40. The tumor also affects both sexes equally. Further data on pheochromocytoma are:

• Around 85 to 90 percent of all pheochromocytomas grow within the adrenal gland, the others are localized outside.
• In around 20 to 25 percent of cases, they develop in both adrenal glands.
• Around 75 percent of tumors occur sporadically (sporadic forms). In a third of cases, the reasons lie in a genetic predisposition (familial forms).

Pheochromocytoma: causes are often genetic

The causes of pheochromocytoma, especially in sporadic forms, are often unclear. The situation is different with familial pheochromocytomas, in which various genes are altered and involved in the development. Sometimes the tumors of the adrenal medulla are malignant and in many cases also associated with other tumors or diseases.

Some examples:

• Multiple endocrine neoplasia type 2 a/b (MEN): The RET gene is altered. The risk of the tumor being malignant is three to five percent.
• Von Hippel-Lindau syndrome: The VHL gene is affected. The risk of the tumor becoming malignant is approximately five percent.
• Neurofibromatosis type 1 (Recklinghausen’s disease): The NF1 gene is altered. The risk of the pheochromocytoma being malignant is around ten percent.
• Paraganglioma syndrome type 1: The change affects the SDHD gene – the risk of malignancy is around 23 percent.
• Paraganglioma syndrome type 2: The SDHB gene is mutated. Around 50 percent of pheochromocytomas are malignant.

Symptoms: Pheochromocytoma increases blood pressure

A pheochromocytoma can cause a wide variety of symptoms. The most important and most common symptom is high blood pressure (hypertension). It is characterized by the fact that it cannot be sufficiently reduced and adjusted to normal values even by treatment with medication. The increased blood pressure is detectable in the majority of people with pheochromocytoma. The cause is the increased release of catecholamines that increase blood pressure, such as adrenaline and noradrenaline.

For some, the blood pressure values are permanently too high (permanent hypertension). Others, on the other hand, experience frequent attacks of high blood pressure. Then the blood pressure shoots up, sometimes even to values above 300 mmHg. Such high blood pressure attacks often occur during physical exertion. They can last for five to ten minutes, then the blood pressure drops again.

A number of other symptoms can also occur:

• Headache
• Sweating, outbreaks of perspiration
• Facial pallor
• Palpitations, accelerated pulse, cardiac arrhythmia
• Dizziness
• Fatigue
• Nausea
• Weight loss
• Nervousness, restlessness
• Anxiety and panic states
• Increased blood sugar level (hyperglycemia)

Always visit us promptly if you have high blood pressure or experience other unusual symptoms.

In some cases, however, there are no symptoms and the tumor is discovered as an incidental finding during general imaging. Only hormone diagnostics then lead to a definitive diagnosis.

Pheochromocytoma: Diagnosis

The diagnosis of a pheochromocytoma is not easy for us. This means that the tumor in the adrenal medulla can remain undetected for a long time. Sometimes we also discover an unusual rise in blood pressure by chance during anesthesia, an operation or a diagnostic procedure.

The diagnosis always begins with the medical history, the anamnesis. For example, we are interested in the following questions:

• What complaints do you have and since when?
• How severe are the symptoms?
• Are there situations in which the symptoms increase, for example during physical exertion?
• Do you have any known underlying illnesses, such as high blood pressure?
• Are there any hereditary diseases in your family?
• Are you taking medication, for example for high blood pressure?

After the physical examination, we supplement the findings with the following examinations, which give us further information about the diagnosis:

• Blood or urine test: We determine the breakdown products of the two catecholamines adrenaline and noradrenaline in blood plasma or urine collected over 24 hours. Metanephrine is a metabolic product of adrenaline, normetanephrine of noradrenaline. Sometimes we also determine the amount of free catecholamines adrenaline and noradrenaline in the urine. The blood sample must be taken under special conditions (after you have been lying down for at least 15 minutes). It should also be noted that some medications can falsify the test results, such as alpha blockers, tricyclic antidepressants or MAO inhibitors.
• Ultrasound examination (sonography)
• Computed tomography (CT)
• Magnetic resonance imaging (MRI = magnetic resonance imaging)
• Positron emission tomography(PET) in combination with computed tomography (CT): Nuclear medicine specialists use low-level radioactive substances (tracers); 18F-DOPA is usually used in the diagnosis of pheochromocytoma (18F-FDG is also used in special cases). For extraadrenal tumors (paragangliomas), 68Ga-DOTATATE is also used. Both hormone-producing and non-hormone-producing tumors can be easily detected in this way.
• MIBG scintigraphy (methyliodobenzylguanidine scintigraphy or adrenal medulla scintigraphy): This is also a nuclear medicine method for detecting hormone-producing tumors and pheochromocytomas. This technology has since been largely replaced by PET.
• Genetic testing for suspected hereditary causes of pheochromocytoma – in around 25 to 40 percent of those affected, pheochromocytoma has genetic causes. We use genetic tests to try to find carriers of the altered genes within the family.

It is important to note the conditions under which the blood was taken in order to be able to interpret the results. This is where the endocrinologist’s experience is required to recognize false positive or negative results. Depending on the result, it is important to find the right imaging for the individual patient, as these differ in their informative value. At the USZ, even rare examinations are available promptly and the findings are made by nuclear medicine specialists.

Pheochromocytoma: prevention, early detection, prognosis

The causes of pheochromocytoma are unknown in many cases. Therefore, you cannot prevent the tumor in the adrenal medulla in sporadic cases. There are also no special early detection measures for pheochromocytoma. We sometimes find it by chance as part of another investigation. You should always seek medical advice if you experience symptoms such as high blood pressure (permanent or sudden). This also applies to cardiac arrhythmia, heavy sweating or headaches – especially if several symptoms occur together.

However, hereditary factors play a role in around 25 to 40 percent of people with a pheochromocytoma. Regular check-ups are advisable, for example for healthy family members with the corresponding genetic changes:

If you have a known genetic disease such as neurofibromatosis type 1, multiple endocrine neoplasia type 2 a/b, Von Hippel-Lindau syndrome or paraganglioma syndrome, you must have your disease monitored closely and regularly by an endocrinologist. In this way, a pheochromocytoma can be detected and treated at an early stage.

As pheochromocytoma is a rare disease, treatment in a specialized center is advisable. In our adrenal consultation at the USZ, you will be advised on the necessary clarifications (genetic examination) and the subsequent follow-up care (regular imaging, screening for other tumors depending on the underlying disease).

Course and prognosis of a pheochromocytoma

The course and prognosis of pheochromocytoma cannot be generally predicted. First of all, it is important to determine whether the tumor is benign (usually) or malignant (more rarely). It also plays a role whether we can detect and treat the pheochromocytoma in time.

The course and prognosis after the operation depends, among other things, on the experience and cooperation of the specialists in endocrinology, anesthesia and surgery, which, due to the rarity of pheochromocytoma, is only available in a specialized center such as the USZ.

If it can be removed by surgery, the prognosis is usually favorable. The blood pressure normalizes and the symptoms disappear. However, there is a risk that the pheochromocytoma will return (recurrence). Lifelong annual check-ups are therefore very important.

An undetected and untreated pheochromocytoma, on the other hand, can have a number of consequences. Permanently or intermittently high blood pressure can damage the cardiovascular system in the long term. The increased pressure in the blood vessels also puts other organs at risk.

The course and prognosis of a malignant pheochromocytoma can vary greatly from person to person. The tumor can be aggressive, grow quickly and spread. Others develop more slowly and behave more like a benign tumor.

As with all types of cancer, the earlier we discover the tumor, the better the prognosis. If the tumor has already metastasized to other organs, the chances of survival worsen. Five years after the diagnosis of a malignant pheochromocytoma, 35 to 60 percent of those affected are still alive.

Pheochromocytoma: treatment means surgery

Pheochromocytoma is treated during an operation. We remove the adrenal gland together with the tumor. The surgical procedure is called an “adrenalectomy”. We usually perform minimally invasive operations using keyhole surgery. This laparoscopy involves just a few small incisions and is considered to be gentle. If this is not possible or if the pheochromocytoma is malignant, open surgery via abdominal incision is used.

Seven to 14 days before the operation, you must take special medication, so-called alpha blockers, against high blood pressure. Phenoxybenzamine is a frequently used active ingredient. The drug neutralizes the effect of adrenaline and noradrenaline on the blood vessels. This prevents high blood pressure incidents during anesthesia and surgery.