Also known as: Metanephrine and normetanephrine
Name: Urine metanephrines, total and fractionated
Related tests: Plasma and urine catecholamines, Plasma free metanephrines
Why get tested?
To help diagnose or rule out a phaeochromocytoma (a tumour of the adrenal glands) or other neuroendocrine tumours
When to get tested?
If you have symptoms of persistent or episodic high blood pressure, such as severe headaches, a rapid heartbeat and sweating
Sample required?
A 24-hour urine sample
What is being tested?
This test measures the amount of metanephrines excreted in the urine over a 24-hour period. Metanephrines are inactive metabolites of the catecholamines epinephrine (adrenaline) and norepinephrine. Catecholamines are a group of similar hormones produced in the nervous system and in the medulla (central part) of the adrenal glands. The adrenal glands are small, triangular organs located on top of each kidney. The main catecholamines are dopamine, epinephrine (adrenaline) and norepinephrine (noradrenaline). These hormones are released into the bloodstream in response to physical or emotional stress. They help transmit nerve impulses in the brain, stimulate gluconeogenesis and the release of fatty acids (for energy), widen the bronchioles (small airways in the lungs) and dilate the pupils. Norepinephrine also constricts blood vessels (raising blood pressure), and epinephrine increases the heart rate and metabolism. Once they have done their job, the hormones are metabolised into inactive compounds. Dopamine becomes homovanillic acid (HVA), norepinephrine becomes normetanephrine and vanillylmandelic acid (VMA), and epinephrine becomes metanephrine and VMA. Both the hormones and their metabolites are excreted in the urine.
The urine metanephrine test measures the concentration of both metanephrine and normetanephrine. These metabolites are normally present in the urine in small, variable amounts that rise noticeably during and shortly after the body has been exposed to stress. Phaeochromocytomas (rare tumours of the adrenal gland) and other neuroendocrine tumours, however, can produce large amounts of catecholamines, leading to greatly increased concentrations of the hormones and their metabolites in both blood and urine. The catecholamines produced by phaeochromocytomas can cause chronic hypertension (high blood pressure) and/or attacks or episodes of severe hypertension. This can cause symptoms such as headaches, palpitations, sweating, nausea, anxiety and tingling in the hands and feet.
About 90% of phaeochromocytomas are located in the adrenal glands. While a small proportion are cancerous, most are benign (they do not spread beyond their original location), although most continue to grow. If left untreated, the symptoms can get worse as the tumour grows and, over time, the high blood pressure caused by the phaeochromocytoma can damage body organs such as the kidneys and heart and increase the affected person’s risk of a stroke or heart attack.
The metanephrine test can be used to help diagnose a phaeochromocytoma. Although only 800 cases a year are diagnosed in the US, according to the National Cancer Institute, it is important to diagnose and treat these rare tumours, which 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 catecholamines produced and to reduce or eliminate the associated symptoms and complications.
How is the sample collected for testing?
For a 24-hour urine collection, all urine must be kept for a 24-hour period. It is important that the sample is refrigerated during this time. Since diet, exercise and medicines can affect metanephrine values, precautions are needed to ensure that the sample reflects true metabolic disease and not interference or an aberration. For this reason you should talk to your doctor about your diet and any medicines you are taking. Foods such as coffee (even decaffeinated), tea, chocolate, vanilla, bananas, oranges and other citrus fruits should be avoided for several days before the test and during the collection. There are also some medicines that can potentially affect the test results. Talk to your doctor about the prescription and over-the-counter medicines and supplements you are taking. Wherever possible, anything known to interfere should be stopped before and during sample collection. Emotional and physical stress and vigorous exercise should be minimised before and during the collection, as they can increase catecholamine secretion.
How is it used?
When is it requested?
What does the test mean?
Is there anything else I should know?
How is it used?
The metanephrine test is mainly used to help diagnose or rule out phaeochromocytoma in patients with symptoms. It may also be requested to help monitor the effectiveness of treatment once a phaeochromocytoma has been found and removed, and to monitor for recurrence. The urine metanephrine test may be requested on its own or together with the plasma metanephrine test. Plasma and urine catecholamines may also be requested, either together with urine metanephrines or as a follow-up test. Since catecholamine secretion tends to vary over time, a 24-hour urine test for metanephrines or catecholamines can detect overproduction that is missed by a blood test. Your doctor will decide which test or combination of tests will give them the most information. In many cases urine and plasma metanephrines are preferred, as they are usually present in larger amounts than urine catecholamines and remain in the circulation even when catecholamine values return to normal.
Since these tests are affected by medicines, foods and stress, there will be a certain number of false positives. For this reason the metanephrine test is not recommended as a screening test for the population. Doctors will generally investigate a positive result by assessing the patient’s diet and stress, work to change or minimise these interferences, and then have the test repeated to confirm the initial result.
Occasionally the metanephrine test may be requested for a patient without symptoms if an adrenal or neuroendocrine tumour is found on an imaging scan done for another reason, or if the patient has a strong personal or family history of phaeochromocytoma (as there may be recurrences or, in some cases, a genetic predisposition).
When is it requested?
Urine metanephrines are requested when a doctor suspects that a patient has a phaeochromocytoma or wants to rule it out. They may be requested when a patient has persistent or recurrent high blood pressure together with other symptoms such as headaches, sweating, flushing and a rapid heartbeat. They may also be requested when a patient has high blood pressure that does not respond to treatment (patients with phaeochromocytoma are often resistant to conventional treatment).
Occasionally the test may be requested when an adrenal tumour is found incidentally or when a patient has a family history of phaeochromocytoma. It is also used for surveillance when a patient has been treated for a previous phaeochromocytoma.
What does the test mean?
Since the metanephrine test is sensitive to many outside interferences and phaeochromocytomas are rare, the doctor may see many more false positives than true positives with this test. If a patient with symptoms has a high concentration of metanephrines in the urine, further investigations are advisable. If no interfering substances or stress are identified, there is a good chance that the patient may have a phaeochromocytoma. The doctor may request plasma metanephrines and/or plasma or urine catecholamines to confirm the results. If these are also high, an imaging test (such as MRI) may be requested to locate the tumour(s). If a patient without symptoms whose tumour was found on an imaging scan done for other reasons has significantly raised metanephrines, the tumour found is probably a phaeochromocytoma.
Serious illness and stress can cause moderate to large temporary increases in metanephrine levels. Doctors must assess the patient as a whole: physical condition, emotional state, medicines and diet. Once interfering substances and illnesses have been identified and eliminated, the doctor will often have the patient repeat the test to see whether metanephrines are still raised. If they are, imaging tests may be requested; if they are not, the patient is unlikely to have a phaeochromocytoma.
If levels are raised in a patient who has previously had a phaeochromocytoma, either the treatment was not completely effective or the tumour has come back. The negative predictive value of the test, however, is relatively good. This means that if metanephrine concentrations are normal, the patient is very unlikely to have a phaeochromocytoma.
Is there anything else I should know?
While the metanephrine test helps detect and diagnose phaeochromocytoma, it cannot tell the doctor how large the tumour is (even small tumours can produce large amounts of catecholamines), where it is (although most are found in the adrenal gland and nearly all the rest within the abdominal cavity) or how many tumours are present (although there is usually only one). It cannot tell the doctor whether the tumour is benign or not (most are).
It is very important to talk to your doctor before stopping any treatment. They will work with you to identify interfering substances and determine which treatments can safely be stopped and which you need to keep taking for your own good. Some of the substances that can interfere with the metanephrine test are: paracetamol (acetaminophen), aminophylline, amphetamines, appetite suppressants, coffee, tea and other forms of caffeine, chloral hydrate, clonidine, dexamethasone, diuretics, epinephrine, ethanol (alcohol), insulin, imipramine, lithium, methyldopa (Aldomet), MAO (monoamine oxidase) inhibitors, nicotine, nitroglycerin, nose drops, propafenone (Rytmonorm), reserpine, salicylates, theophylline, tetracycline, tricyclic antidepressants and vasodilators. The effects of these medicines on the metanephrine test will vary from patient to patient and are often unpredictable.
1. Can I have tumours in both adrenal glands?
2. If I eliminate all the interfering substances mentioned, will I prevent a phaeochromocytoma?
3. Why don’t I hear much about phaeochromocytomas?
4. Will my doctor ever want to test for HVA or VMA?
5. Is a 24-hour urine collection really necessary?
1. Can I have tumours in both adrenal glands?
Yes. A single adrenal tumour will usually appear in one gland or the other, but several tumours can form. This is more likely in patients with a family history of phaeochromocytoma.
2. If I eliminate all the interfering substances mentioned, will I prevent a phaeochromocytoma?
No. They interfere with the accuracy of the result, but do not cause or worsen the tumour itself.
3. Why don’t I hear much about phaeochromocytomas?
Because they are rare. It is important to diagnose them, however, because they cause a potentially curable form of high blood pressure (which is usually controllable but cannot otherwise be eliminated).
4. Will my doctor ever want to test for HVA or VMA?
Yes, occasionally, but in most cases the metanephrine and catecholamine tests will give the doctor the information they need. HVA and VMA may be more useful in diagnosing other neuroendocrine tumours. Most phaeochromocytomas do not produce dopamine or HVA.
5. Is a 24-hour urine collection really necessary?
Yes; collecting all the urine is essential for the test to be accurate. Since catecholamines are released at different times, a single sample that was not collected could be the one with the most metanephrines.