Plasma Free Metadrenalines (Metanephrines)
When you have persistent or episodic high blood pressure and symptoms such as headaches, rapid heart rate, and sweating
A blood sample taken from a vein in your arm
Preparation for the test is important for accurate results. You should discontinue adrenaline (epinephrine) and adrenaline-like drugs for at least one week before the test, stop using paracetamol (acetaminophen) 48 hours beforehand, and fast for 8-10 hours prior to collection. It is especially important not to have any caffeine-containing food (e.g. chocolate) or drinks (e.g. energy drinks like Red Bull, Coca-Cola, coffee and tea (including decaffeinated). Tobacco (smoking cigarettes or cigars) and alcohol must also be avoided for at least 4 hours before specimen collection. Talk to your doctor about any medications you are taking, since several different drugs may interfere with the test.
The plasma free metadrenalines test measures the amount of metadrenaline and normetadrenaline in the blood. These substances are metabolites of adrenaline (epinephrine) and noradrenaline (norepinephrine). Adrenaline and noradrenaline are catecholamine hormones that help regulate the flow and pressure of blood throughout the body and play important roles in the body's response to stress.
Catecholamines are produced in the adrenal medulla – the interior portion of the adrenal glands – and secreted into the blood. Once these hormones have completed their actions, they are metabolised to inactive compounds. Noradrenaline breaks down into normetadrenaline and hydroxymethylmandelic acid (HMMA) (also called vanillylmandelic acid (VMA)), and adrenaline becomes metadrenaline and HMMA. Both of the catecholamines and their metabolites are normally found in small fluctuating quantities in the blood and urine.
A rare tumour called a phaeochromocytoma can produce large amounts of catecholamines, resulting in significantly increased concentrations of metadrenaline and normetadrenaline. About 80-85% of phaeochromocytomas form in the adrenal glands and, while a few are cancerous, most are benign – they continue to grow but usually do not spread beyond their original location.
The catecholamines produced by phaeochromocytomas can cause persistent hypertension and episodes of severe high blood pressure. This can cause symptoms such as headaches, palpitations, sweating, nausea, anxiety, and tingling in the extremities. Left untreated, the symptoms may worsen as the pheochromocytoma grows. Over time, hypertension caused by the tumour may cause kidney damage, heart disease, and raise the risk of a stroke or heart attack.
Several tests, including plasma free metadrenalines, can detect the presence of phaeochromocytomas. Although they are rare, it is important to diagnose these tumours because they cause a potentially curable form of hypertension. In most cases, the pheochromocytomas can be surgically removed, which eliminates the high blood pressure and its associated symptoms and complications.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm. Although there is some disagreement over the specifics of how the sample should be collected, it may be necessary to lie down and rest quietly for 15 to 30 minutes prior to and during sample collection. In other circumstances, you may just be seated upright with little rest time before the sample collection.
Is any test preparation needed to ensure the quality of the sample?
Preparation for the test is important for accurate results. It may be necessary to discontinue adrenaline and adrenaline-like drugs for at least one week before the test, stop using paracetamol (acetaminophen) 48 hours beforehand, and fast for 8-10 hours prior to collection. It is especially important not to have any caffeine-containing food (e.g. chocolate) or drinks (e.g. energy drinks like Red Bull, Coca-Cola, coffee and tea (including decaffeinated). Tobacco (smoking cigarettes or cigars) and alcohol must also be avoided for at least 4 hours before specimen collection. Talk to your doctor about any medications being taken as several drugs may interfere with the test. Your doctor may therefore instruct you to stop taking all medications except those that are necessary for one week prior to the test. However, do not stop taking any medications without first consulting your doctor.
How is it used?
Plasma free metadrenaline is a test used to help diagnose or rule out the presence of a phaeochromocytoma. Plasma free metadrenaline testing is more sensitive than 24-hour urine catecholamines or metadrenalines testing. However, this sensitivity brings with it a certain number of false positive results, especially when the test is requested on those in whom a phaeochromocytoma is unlikely. For this reason, plasma free metadrenalines is not recommended as a routine test for the general public. Its primary use is in symptomatic people when urine testing does not provide clear-cut results. Since both blood and urine test results may be affected by stress, caffeine, alcohol, and certain drugs, a doctor may investigate a positive result by evaluating a person's stresses, diet, and medications, alter or minimise these influences, and then repeat the tests to confirm the original findings.
Occasionally, the test may be requested on an asymptomatic person if an adrenal tumour is detected during a scan conducted for another purpose or if the person has a strong personal or family history of phaeochromocytomas. These tumours may recur, and there is a genetic link in some cases.
When is it requested?
The plasma free metadrenalines test is primarily requested when a doctor either suspects that someone has a phaeochromocytoma or wants to rule out the possibility. The doctor may request it when a person has hypertension and persistent or recurring symptoms, such as headaches, sweating, flushing, and rapid heart rate. It may also be requested when a person has hypertension that is not responding to treatment as those with a phaeochromocytoma are frequently resistant to conventional anti-hypertensive medications.
Occasionally, the test may be requested when an adrenal tumour is detected incidentally (called adrenal incidentaloma) or when someone has a family history of phaeochromocytomas. It may also be used as a monitoring tool when a person has been treated for a previous phaeochromocytoma.
What does the test result mean?
Since the plasma free metadrenalines test is very sensitive and phaeochromocytomas are rare, a doctor may see more false positives with this test than true positives. The negative predictive value of the test, however, is very good. This means that if the concentrations of metadrenaline and normetadrenaline are normal in the blood, then it is unlikely that a person has a phaeochromocytoma.
If a symptomatic or asymptomatic person has only moderately elevated metadrenalines, then a doctor may re-evaluate the person's medications, diet, and stress level to look for interfering substances. They may then re-test the person, perhaps along with 24-hour urine metadrenalines testing, to determine whether the metadrenalines are still elevated. If they are, then he may order imaging scans; if they are not, then it is unlikely that the person has a phaeochromocytoma.
If levels are elevated in someone who has had a previous phaeochromocytoma, it may be an indication that the tumour is recurring.
Is there anything else I should know?
The majority of phaeochromocytomas are found in the adrenal glands and most of the rest are found within the abdominal cavity. While the plasma free metadrenalines test can help detect and diagnose phaeochromocytomas, it cannot tell the doctor where the tumour is or whether it is benign or malignant (although most are benign).
An increased risk for developing phaeochromocytomas can be inherited. Multiple endocrine neoplasia, type 2 (MEN-2) is a condition associated with alterations in specific genes. They increase the lifetime risk that those affected will develop tumours in one or more of their endocrine glands.
Several medications may interfere with the test. Consult your doctor as to which drugs may be safely discontinued before being tested. Also, caffeine-containing food (e.g. chocolate) or drinks (e.g. energy drinks like Red Bull, Coca-Cola, coffee and tea (including decaffeinated), tobacco (smoking cigarettes or cigars) and alcohol may interfere with the test and should be avoided prior to testing.
I have more than one pheochromocytoma at once?
the amount of plasma free metadrenalines detected correspond to the size of the tumour?
No, it has more to do with the characteristics of the tumour. Even a very small tumour can produce large amounts of catecholamines.
Is it really necessary to follow the dietary restrictions and lie down before testing?
There is some disagreement over the specifics of how the sample should be collected. However, the level of catecholamines (and their metabolites in blood is affected by diet and stress levels. For test accuracy, interfering substances need to be avoided and the person's physical and emotional stress levels should be minimised.