What is being tested?
The plasma free metanephrines test measures the amount of metanephrine and normetanephrine in the blood. These substances are metabolites of adrenaline and noradrenaline. 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. They are produced in the medulla (interior) of the adrenal glands. Each person has two adrenal glands and they are small, triangular organs located on top of the kidneys. The catecholamines that the adrenal glands create, and their metabolites (metanephrine and normetanephrine), are normally found in small fluctuating quantities in both the blood and urine.
However, rare catecholamine-producing tumours can produce large amounts of hormones, resulting in significantly increased concentrations of metanephrine and normetanephrine in both the blood and urine. These tumours are rare. While a few are cancerous, most are benign – they do not spread beyond their original location - although most do continue to grow in size. Importantly the catecholamines produced by these tumours can cause persistent hypertension (high blood pressure) and/or paroxysms (intermittent 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 tumour grows and, over a period of time, the high blood pressure that the tumour causes may damage body organs such as the kidneys and heart and raise the risk of an affected patient having a stroke or heart attack.
Plasma free metanephrines and urine catecholamines can be used to detect the presence of catecholamine-producing tumours. It is important to diagnose and treat these rare tumours because they cause a potentially curable form of high blood pressure. In most cases, the tumours can be surgically removed and/or treated to significantly reduce the amount of extra hormones being produced and to reduce or eliminate their associated symptoms and complications.
How is it used?
Plasma free metanephrines is a test used to help diagnose or rule out the presence of a catecholamine-producing tumour (phaeochromocytoma or paraganglioma). This test is very good at detecting these tumours. Studies have shown that plasma testing is more sensitive than the more traditional 24-hour urine catecholamines testing. However, this sensitivity brings with it a certain number of false positive results, especially when the test is ordered on patients who do not have a high likelihood of having a phaeochromocytoma or paraganglioma. For this reason, plasma free metanephrines is not recommended as a screen for the general public. Its primary use is to screen symptomatic patients to detect and to help rule out the likely presence of a phaeochromocytoma or paraganglioma.
Since the tests results may be affected by stress, caffeine, alcohol, and certain drugs, a doctor may investigate a positive result by evaluating a patient’s stresses and intake, alter or minimise these influences, and then repeat the test to confirm the original findings.
Occasionally, the test may be ordered on an asymptomatic person if an adrenal tumour is detected during a scan that is done for another purpose or if the patient has a strong personal or family history of these tumours (as they may recur, and there is a genetic link in some cases).
When is it requested?
The plasma free metanephrines test is primarily ordered when a doctor either suspects that a patient has a catecholamine-secreting tumour or wants to rule out the possibility. The doctor may order it when a patient has persistent or recurring symptoms suggesting marked high blood pressure, such as headaches, sweating, flushing, and rapid heart rate. It may also be ordered when a patient has high blood pressure that is not responding to treatment (patients with a phaeochromocytoma are frequently resistant to conventional therapies).
Occasionally, the test may be ordered when an adrenal tumour is detected incidentally or when a patient has a family history of cathecholamine-secreting tumour. It may also be used as a monitoring tool when a patient has been treated for a previous catecholamine-secreting tumour.
What does the result mean?
A normal result means that it is unlikely the patient has a catecholamine-secreting tumour.
Since the plasma free metanephrines test is very sensitive and catecholamine-secreting tumours 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 the free metanephrines are normal in the blood, then it is very unlikely that a patient has a cathecholamine-secreting tumour.
If a symptomatic patient has large amounts of free metanephrines in their blood, then it is likely that they have a catecholamine-secreting tumour. The doctor may order imaging tests (such as an MRI scan) to help find the tumour(s). If an asymptomatic patient with a tumour that has been discovered during a scan for another reason has significantly elevated free metanephrines, then it is likely that the tumour discovered is a cathecholamine-secreting tumour.
If a symptomatic or asymptomatic patient has only moderately elevated free metanephrines, then the doctor may re-evaluate the patient’s medications, diet, and stress level to look for interfering substances. The doctor may then re-test the patient, perhaps along with 24-hour urine catecholamine testing, to determine whether the free metanephrines are still elevated. If they are, then the doctor may order imaging scans; if they are not, then it is unlikely that the patient has a phaeochromocytoma or paraganglioma.
If levels are elevated in a patient who has had a previous catecholamine-secreting tumour, then it is likely that either treatment was not fully effective or that the tumour is recurring.
Is there anything else I should know?
While the plasma free metanephrines test can help detect and diagnose cathecholamine-secreting tumours, it cannot tell the doctor where the tumour is (although the majority are found in the adrenal gland and most of the rest are found within the abdominal cavity). It also cannot tell the doctor whether or not the tumour is benign (although most are).
Common questions
Yes, especially when there is a strong family history of phaeochromocytomas. A patient may have a tumour in each adrenal gland.
No, it has more to do with the characteristics of the tumour. Even a very small tumour can produce large amounts of catecholamines.
There is some disagreement over the specifics of how the sample should be collected. However, it is known that the level of catecholamines (and their metabolites) in the blood is affected by diet and stress levels. For test accuracy, interfering substances need to be avoided and the patient’s physical and emotional stress levels should be as low as possible. This should be discussed with your doctor on an individual level.
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