pheochromocytoma

Pheochromocytoma: description

A pheochromocytoma is a tumor that originates in the majority of cases from the adrenal medulla. Less common is the so-called paraganglioma. In this form, the pheochromocytoma is located outside the adrenals (extra-adrenal), along the so-called sympathetic trunk (nerve trunk, which runs along the spine in the abdominal and thoracic region). A pheochromocytoma is a rare type of tumor disease. An estimated two to eight out of every one million people get it. Mostly, the tumor affects adults, but children can also develop a pheochromocytoma.

The adrenal glands

The two adrenals are important endocrine glands of the organism. They sit -on the rounded upper end of one of the two kidneys. Due to their function, they are divided into two parts, the adrenal cortex and the adrenal medulla.

The adrenal cortex mainly produces steroid hormones that regulate, among other things, the sugar, water and mineral balance. An important hormone here, for example, cortisol, which is involved in numerous metabolic processes.

The adrenal medulla produces the so-called catecholamines epinephrine and norepinephrine. The two hormones, which are also often referred to as stress or escape hormones in the vernacular, have a decisive influence on the autonomic nervous system. Their release enables the body to adequately respond to stress situations, such as accelerating the heartbeat, increasing blood pressure, expanding the bronchi, and slowing down gastrointestinal motions.

Pheochromocytoma: Increased hormone production

Characteristic of the pheochromocytoma is that the tumor cells increasingly produce the stress hormones epinephrine and norepinephrine, more rarely dopamine. The tumor is benign in the majority (85 percent) of the cases. The tumor usually occurs only on one side, more rarely both adrenals are affected by a pheochromocytoma.

Pheochromocytoma: symptoms

The symptoms caused by a pheochromocytoma are primarily due to the increased release of the stress hormones epinephrine and norepinephrine. The symptoms may differ individually in their nature and severity. In rarer cases, a pheochromocytoma does not produce any symptoms and is then discovered by chance.

A typical symptom of a pheochromocytoma is high blood pressure: The blood pressure suddenly rises, seizure-like (paroxysmal hypertension). He can achieve threatening values, which doctors call a blood pressure crisis or hypertensive crisis. This symptom occurs in about half of patients with a pheochromocytoma.

In some cases, the pheochromocytoma also causes a permanently elevated blood pressure, doctors then speak of persistent hypertension. This is the case in about 50 percent of affected adults and 90 percent of children with a pheochromocytoma.

In addition, the following symptoms may occur in a pheochromocytoma:

• a headache
• Palpitations or tachycardia
• sweats
• Internal restlessness, anxiety, fear or panic
• Trembling (tremor)
• Pale complexion
• weight loss
• Herzenge (angina pectoris)

Due to the high level of adrenaline caused by the pheochromocytoma, the blood sugar level rises sharply. After some time, it can develop diabetes (diabetes mellitus).

Pheochromocytoma: causes and risk factors

The cause of a pheochromocytoma is not always known. Doctors then speak of a sporadic pheochromocytoma. Such a tumor develops most often between the 40th and 50th year of life.

In addition, there are hereditary (hereditary) pheochromocytoma forms, which are caused by a defect in the genome (mutation). This usually affects people who are younger than 40 years.

A pheochromocytoma may be associated with the following hereditary diseases:

• Multiple endocrine neoplasia type 2 (MEN 2 syndrome): The gene mutation is located on chromosome 10. It often causes tumors of hormone-producing organs, especially on the thyroid (thyroid carcinoma) and the adrenal glands.
• Von Hippel-Lindau syndrome: This disease is characterized by retinal, brain and spinal cord tumors and a pheochromocytoma of the adrenal medulla.
• Neurofibromatosis type 1 (NF-1, Recklinghausen’s disease): Here, tumors form, which originate from the nerve tissue and mainly affect the skin, eyes and the brain. Tumors such as pheochromocytoma also occur frequently in this disease.

Pheochromocytoma: examinations and diagnosis

Conspicuous symptoms such as seizure-type blood pressure, panic attacks, or weight loss are suspected in the diagnosis of “pheochromocytoma.” In the first step, the doctor often measures the blood pressure. However, in practice, the excitement causes a temporary increase in blood pressure in many – even healthy – people. To be able to assess the blood pressure safely, it therefore makes sense to record it over a longer period of time, usually over 24 hours (long-term blood pressure measurement). If there is no illness, the blood pressure usually drops during the night hours. However, this effect is absent in patients with a pheochromocytoma, that is, the blood pressure remains elevated.

The adrenal medulla tumor produces excessively the catecholamines epinephrine and norepinephrine. The measurement of these stress hormones is therefore particularly important for pheochromocytoma diagnostics. However, these hormones are sometimes subject to strong fluctuations even in healthy people, such as excitement. To obtain a reliable measurement result, the doctor has in principle two options. Two chemical variants of adrenaline, normetanephrine and metanephrine are measured, either in:

• a 24-hour bulk sample in urine or
• in the blood plasma, over a period of 30 minutes.

If the content of these hormones is significantly increased, further investigations follow:

Clonidine suppression test: Clonidine is an antihypertensive drug. In healthy people, clonidine inhibits the release of adrenaline and its chemical relatives. On the other hand, if there is a pheochromocytoma, the level of stress hormones remains high.

Imaging procedures: To detect a phaeochromocytoma in the adrenal medulla, computed tomography (CT) and magnetic resonance imaging (MRI) are suitable. After pheochromocytomas that are not located in the adrenals, doctors are using special imaging techniques such as MIBG scintigraphy. The patient initially receives a weak radioactive agent, which accumulates in the tumor cells. In a subsequent X-ray examination, the areas with high accumulation can then be visualized. Nevertheless, if the methods mentioned do not produce any results, a so-called DOPA-PET (positron emission tomography) is generally carried out. The amino acid L-DOPA is a precursor of adrenaline, norepinephrine and dopamine, among others. The doctor first injects radioactively labeled DOPA into the vein of the patient. The agent accumulates in the tumor cells, which is then visible in positron emission tomography.

Genetic examination: In some cases, pheochromocytoma is associated with certain hereditary diseases such as the MEN 2 syndrome, von Hippel-Lindau syndrome and neurofibromatosis type 1. Special genetic tests can be used to detect these diseases.

Pheochromocytoma: treatment

surgery

In many cases, it is possible to treat the pheochromocytoma causally. The most important step is to surgically remove the tumor. In most cases, this is possible as part of a laparoscopic (minimally invasive) procedure. For this purpose, three small incisions are usually sufficient in the abdominal wall, over which the surgeon introduces his instruments and then removes the tumor.

However, certain situations, such as large or difficult to access tumors, sometimes require a larger abdominal incision (laparotomy) to remove the tumor from the pheochromocytoma. Patients usually receive antihypertensive medication (such as dibenzyran) seven to 14 days before the procedure to prevent blood pressure crisis during surgery.

hormone replacement

In most cases, a pheochromocytoma is only one-sided, that is, the opposite adrenal gland is healthy and continues to produce hormones in sufficient quantities. However, both adrenals may be affected. In these cases, after surgery, a lack of steroid hormones and catecholamines may occur. Then it is important to replace the missing hormones in the form of drugs.

Further therapy measures

Other treatment strategies depend on whether the pheochromocytoma is benign or malignant. Malignant tumors are characterized by their ability to form secondary tumors (metastases). In a malignant pheochromocytoma in addition to the operation, among others, the radio-iodine therapy and chemotherapy available.

Newer medications, called multityrosine kinase inhibitors, inhibit the production of stress hormones like epinephrine and norepinephrine. Scientists are currently testing these drugs in studies. A corresponding preparation is currently not permitted in Germany.

Non-operable pheochromocytoma

In rarer cases doctors can not operate the pheochromocytoma. Then, the main focus is on controlling the symptoms caused by the excess of stress hormones. For example, blood pressure crises can be avoided with the help of suitable medication (usually alpha-blockers). Alpha blockers reduce the effects of adrenaline and its chemical derivatives by blocking the docking sites of these hormones.

Pheochromocytoma: disease course and prognosis

The prognosis of a pheochromocytoma depends on several factors. If the tumor can be removed early and there are no other diseases, it is usually good and the symptoms disappear. Thus, in more than half of the patients, the blood pressure normalizes after surgery.

If the disease has been around for a long time, it can lead to secondary diseases (such as heart failure), in particular due to high blood pressure.

In about 15 percent of those affected again after the treatment forms a pheochromocytoma (recurrence). Regular check-ups are therefore important in order to be able to discover and treat this as early as possible.

In the case of a rarer malignant pheochromocytoma, as with all other cancers, it is crucial that it is detected and treated as early as possible. In principle, the chances of recovery are most favorable if no daughter tumors have yet formed. Have the evil pheochromocytoma By contrast, metastases already formed, the chances of recovery decline.