A pheochromocytoma is a rare tumor of the tissues of the adrenal gland. These glands sit at the top of each kidney and secrete catecholamine hormones, which regulate heart rate, body metabolism, and blood pressure. A tumor in or around the adrenal gland would result in excessive secretion of the two major catecholamine hormones from the adrenal gland – noradrenaline (norepinephrine) and adrenaline (epinephrine). This can disturb metabolism and can raise the blood pressure and the heart rate. If undetected or left untreated, a pheochromocytoma can lead to life-threatening hypertension (high blood pressure) or heart beat irregularities.
Majority of pheochromocytomas are found within the adrenal glands. The triangular-shaped adrenal glands are located on the superior pole of each kidney. The main part of the adrenal gland that secretes these hormones is the adrenal medulla located at the center of the gland. Sometimes, pheochromocytomas can develop away from the adrenal glands like near the base of the brain, heart, or urinary bladder. These pheochromocytomas are then called extra-adrenal pheochromocytomas.
Pheochromocytoma and Cancer
Most pheochromocytomas are benign and non-cancerous. These tumors can severely disrupt the hormone levels but cannot spread to other tissues. However, 10% of pheochromocytomas (cancerous) are malignant and therefore can spread to the bones, liver, lungs and brain. No tests can reliably distinguish a cancerous from a non-cancerous pheochromocytoma. Therefore, prompt treatment is advised to avoid potentially serious outcomes.
Pheochromocytomas are very rare and occur in about 1 in 500 hypertension patients. Pheochromocytomas can affect people of all races, genders, and age. However, people between 40 to 50 years show more susceptibility to develop a pheochromocytoma.
In healthy adrenal tissue, catecholamine (norepinephrine and epinephrine) secretion is regulated. These hormones are primarily responsible for the fight or flight response in stressful situations. However, for often unknown reasons there is an increase catecholamine secretion. Excessive secretion of catecholamines results in a pheochromocytoma. Some of the predisposing factors that may stimulate the increased secretion include the effect of pressure, certain drugs, and changes in tumor’s blood circulation. Excessive levels of catecholamines raise the blood pressure and increase the rate of heart beats.
Epinephrine and Norepinephrine
Epinephrine constitutes 85% of the hormones secreted by a normal adrenal gland. However, in patients suffering from pheochromocytomas, mainly norepinephrine is secreted. On the other hand, in genetic pheochromocytomas there are large amounts of epinephrine are secreted. This difference in the secreted hormones helps in distinguishing a genetic pheochromocytoma from a regular pheochromocytoma.
Some individuals with a pheochromocytoma may not show any symptoms. In others, very high blood pressure is the main clinical feature that may result in the following symptoms:
- Nervousness and anxiety
- Pain in upper abdomen and on the sides
- Weight loss
- Pale skin
Very high blood pressure caused by a pheochromocytoma exerts excessive force on the walls of the blood vessels and can damage the vital organs. Untreated high blood pressure may lead to complications like heart failure, stroke, kidney failure, breathing problems, seizures, vision loss, and changes in mental status (mainly confusion and hallucinations).
Sudden release of adrenaline hormones can abruptly increase the blood pressure (hypertensive crisis) to 180/110 mmHg. This can lead to life-threatening conditions, like stroke or abnormal heartbeats.
Long-term exposure to adrenal gland hormones can damage the heart muscle, cause heart failure, and can increase the risk of diabetes.
In pregnant women, an undetected pheochromocytoma can cause death. However, timely diagnosis and treatment reduces the risk significantly.
The exact causes that lead to the development of pheochromocytomas are not known.
Pheochromocytomas are associated with some genetic diseases like multiple endocrine neoplasia (MEN) 2A and 2B, von Hippel-Lindau (VHL) disease, neurofibromatosis (von Recklinghausen disease), tuberous sclerosis (epiloia, Bourneville disease) and Sturge-Weber syndrome.
Many factors, however, can lead to a state of hypertensive crisis.
- Physical or emotional distress
- Surgical anesthesia
- Pressure on the tumor (during exercising, lifting heavy weights, changing body positions, strained urination or bowel movements, and pregnancy)
- Use of drugs or stimulants (like decongestants, cocaine or amphetamines).
Middle age (40 to 50 years) and a history of high blood pressure may be associated with the development of a pheochromocytoma.
The following tests may be used to diagnose a pheochromocytoma:
- Laboratory tests: High levels of adrenaline, nor-adrenaline and their breakdown products called metanephrines can be detected in blood and urine samples.
- Stress and the use of certain drugs (tricyclic antidepressants, levodopa, buspirone, labetalol, ethanol, amphetamines, sotalol, benzodiazepines, chlorpromazine, and methyldopa) may also increase metanephrines. A thorough assessment of medical history is useful in such cases.
- Imaging: A computerized tomography (CT) scan, a positron emission tomography (PET) scan, or a magnetic resonance imaging (MRI) scan of the abdomen can detect the adrenal tumor. In some cases, neck, chest and pelvis are also scanned.
- Genetic tests: These tests can detect the changes in the genes (mutations) that may lead to pheochromocytoma.
If diagnosed early, pheochromocytomas can be cured in most of the cases.
Treatment involves controlling the high blood pressure and surgical removal of the tumor. Treatment options are as follows:
The following drugs like :
- alpha blockers (phenoxybenzamine, doxazosin, prazosin and terazosin)
- beta blockers (atenolol, metoprolol, and propranolol)
- calcium channel blockers (nicardipine, diltiazem, and amlodipine) and metyrosine are used to treat high blood pressure associated with pheochromocytomas.
Alpha blockers help in keeping the blood vessels open and relaxed. This helps in smooth flow of blood and lowers the blood pressure. However, these drugs may have side effects like headache, nausea, pounding heartbeats, and weight gain.
Beta blockers make the heart beat more slowly and with less force. They also help in keeping the blood vessels relaxed. Beta blockers may cause side effects like headache, tiredness, stomach upsets and light headedness.
Calcium channel blockers also relax and widen blood vessels. In some people, they may cause side effects like headache, constipation, fast heartbeats, and drowsiness.
Metyrosine inhibits the production of catecholamines and lowers the blood pressure. However, it may have side effects like depression, drowsiness, anxiety and diarrhea.
Upon surgical removal of adrenal glands containing pheochromocytoma, most people get relief from the symptoms, including high blood pressure. A less invasive laparoscopic surgery may be performed on certain pheochromocytomas. However, if the tumor has spread to other parts of the body, other options are needed along with medications and surgery. These options include chemotherapy, radiation, or ablation of the tumor’s blood vessels.
Alpha blockers are given before surgery to control blood pressure and to prevent a hypertensive crisis. During surgery, alpha-adrenergic antagonist drugs (like phentolamine) or beta blockers (like esmolol) are given intravenously. These rapid-acting drugs control blood pressure.
Pheochromocytoma and Pregnancy
Pheochromocytoma in pregnancy is extremely dangerous for the mother and unborn child. It also poses a major challenge to the supervising physician. Prompt treatment and proper management is essential or the condition can be life-threatening for the mother and fetus. The excessive hormone secretion in pheochromocytoma in pregnancy is mainly a result of the enlarging uterus pressing against the tumor in the adrenal gland. Pheochromocytoma in pregnancy accounts for as many as 50% of deaths for both mother and unborn child. An alpha-blocker drug (phenoxybenzamine) and surgical removal of the tumor during the first two trimesters is recommended in pregnant women.