What is being tested?

This test measures the amount of metanephrines that are excreted in the urine over a 24-hour period. Metanephrines are the inactive metabolites of the catecholamines adrenaline (epinephrine) and noradrenaline (norepinephrine). Catecholamines are a group of similar hormones produced in the nervous system and in the medulla (central portion) of the adrenal glands. The adrenal glands are small, triangular organs located on top of each kidney. These hormones are released into the bloodstream in response to physical or emotional stress. They help transmit nerve impulses in the brain, increase glucose and fatty acid release (for energy), dilate bronchioles (small air passages in the lungs), and dilate the pupils. Noradrenaline also constricts blood vessels (increasing blood pressure) and adrenaline increases heart rate and metabolism. After completing their actions, the hormones are metabolised to form inactive compounds. Dopamine becomes homovanillic acid (HVA), noradrenaline breaks down into normetanephrine and 4-hydroxy-3-methoxymandelic acid (HMMA), sometimes known as vanillylmandelic acid (VMA), and adrenaline becomes metanephrine and HMMA. Both the hormones and their metabolites are excreted in the urine.

Urine metanephrine testing measures the amount of both metanephrine and normetanephrine. These metabolites are usually present in the urine in small fluctuating amounts that increase appreciably during and shortly after the body is exposed to a stressor. Phaeochromocytomas and paragangliomas can produce large amounts of catecholamines, resulting in greatly increased concentrations of the hormones and their metabolites in both the blood and urine. The catecholamines that these tumours produce can cause persistent hypertension (high blood pressure) and/or bouts or episodes of severe hypertension. This can cause symptoms such as headaches, palpitations, sweating, nausea, anxiety, and tingling in the extremities.

Phaeochromocytomas and paragangliomas are rare. While a few of these tumours are cancerous, most are benign (they do not spread beyond their original location) although most do continue to grow larger with time. Left untreated, the symptoms may worsen as the tumour grows and, over a period of time, the hypertension that the hormones cause may damage body organs, such as the kidneys and heart, and raise the risk of an affected patient having a stroke or heart attack.

The urine metanephrine test can be used to help detect the presence of phaeochromocytomas and paragangliomas. It is important to diagnose and treat these rare tumours because they cause a potentially curable form of hypertension. In most cases, the tumours can be surgically removed and/or treated to significantly reduce the amount of catecholamine being produced and to reduce or eliminate associated symptoms and complications.

How is it used?

Urine metanephrine testing is used to help detect or rule out catecholamine-secreting tumours. It may also be ordered to help monitor the effectiveness of treatment when a catecholamine-secreting tumour is discovered and removed and also to monitor for recurrence. Urine metanephrine testing may be ordered by itself or along with a plasma metanephrine test. Plasma and urine catecholamine testing also may be ordered, either along with urine metanephrines or as follow-up tests. Since catecholamine secretion tends to fluctuate over time, a 24-hour urine test for metanephrines or catecholamines may detect excess production that is missed with the blood test. It is up to the doctor to decide which test or test combinations will give them the most information. In many cases, urine and plasma metanephrines may be preferred as they are usually present in greater quantities than catecholamines in the urine and can persist in the blood even when catecholamine levels have returned to normal.

Since these tests are affected by drugs, foods, and stresses there will be a certain number of false positives. For this reason, metanephrine testing is not recommended as a screen for the general public. Doctors will frequently investigate a positive result by evaluating a patient’s stresses and intake, work to alter or minimise these influences, and then repeat the test to confirm the original findings.

Occasionally, metanephrine testing may be ordered on an asymptomatic person if an adrenal or neuroendocrine tumour is detected during a scan that is done for another purpose or if the patient has a strong personal or family history of catecholamine-secreting tumour (as they may recur and there is a genetic link in some cases).

When is it requested?

Urine metanephrines are ordered when a doctor either suspects that a patient has a catecholamine-secreting tumour or wants to rule out the possibility. They may order it when a patient has persistent or recurring hypertension along with symptoms such as headaches, sweating, flushing, and rapid heart rate. It may also be ordered when a patient has hypertension 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 catecholamine-secreting tumours. It also may be used as a monitoring tool when a patient has been treated for a previous catecholamine-secreting tumour.

What does the result mean?

Normal urine metanephrine and normetanephrine results mean it is unlikely that the patient has a catecholamine-secreting tumour.

Because the metanephrine test is sensitive to many outside influences and phaeochromocytomas are rare, a doctor may see more false positives with this test than true positives. If a symptomatic patient has large amounts of metanephrines in his or her urine, further investigation is indicated. If there are no interfering substances or stresses identified, then there is a good possibility that he or she may have a phaeochromocytoma. The doctor may order plasma metanephrine and/or urine or plasma catecholamine testing to help confirm the findings. If these are also elevated, then imaging tests (such as an MRI) may be ordered 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 metanephrines, then it is likely that the tumour discovered is a catecholamine-secreting tumour.

Serious illnesses and stresses can cause moderate to large temporary increases in metanephrine levels. Doctors must evaluate the patient as a whole - his or her physical condition, emotional state, medications and diet. When interfering substances and/or conditions are found and resolved, the doctor will frequently re-test the patient to determine whether the 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 catecholamine-secreting tumour.

If levels are elevated in a patient who has had a previous catecholamine-secreting tumour, it is likely that either treatment was not fully effective or that the tumour is recurring. The negative predictive value of the test, however, is relatively good. This means that if the concentrations of the metanephrines are normal, then it is much less likely that the patient has a catecholamine-secreting tumour.

Is there anything else I should know?

While metanephrine testing can help detect and diagnose catecholamine-secreting tumours, it cannot tell the doctor how big the tumour is (even small tumours can produce large amounts of catecholamines), where the tumour is (although the majority are found in the adrenal gland and most of the rest are found within the abdominal cavity), or how many tumours are present (although it is usually just one). It also cannot tell the doctor whether or not the tumour(s) is benign (although most are).

It is very important to talk to your doctor before discontinuing any prescribed medications. He or she will work with you to identify interfering substances and drug treatments to determine which of them can be safely interrupted and which must be continued for your well-being. Some of the substances that can interfere with metanephrine testing include: paracetamol, aminophylline, amphetamines, appetite suppressants, coffee, tea, and other forms of caffeine, chloral hydrate, clonidine, dexamethasone, diuretics, adrenaline, ethanol (alcohol), insulin, imipramine, lithium, methyldopa (Aldomet), MAO (monoamine oxidase) inhibitors, nicotine, nitroglycerine, nose drops, reserpine, salicylates, theophylline, tetracycline, tricyclic antidepressants, and vasodilators. The effects of these drugs on metanephrine testing will be different from patient to patient and are often not predictable.

Common questions

• Can I have tumours in both of my adrenal glands?

Yes. Usually a single adrenal tumour will arise in one gland or the other, but multiple tumours can form. This is more likely in patients with a strong family history of phaeochromocytomas.

• If I avoid all of the interfering substances mentioned, could I prevent a phaeochromocytoma?

No. They interfere with accurate test results, but they do not cause or exacerbate the tumour itself.

• Why haven’t I heard about phaeochromocytomas?

Because they are rare. They are important to diagnose, however, because they are a potentially curable cause of hypertension (which is usually controllable but not curable).

• Will my doctor ever test for HVA or HMMA?

Yes, occasionally, but in most cases metanephrine and catecholamine testing give your doctor the information they need. HVA and HMMA may be more useful in the diagnosis of other neuroendocrine tumours. Most phaeochromocytomas do not produce dopamine or HVA.

• Is it really necessary to collect urine for 24 hours?

Yes, for accurate test results it is essential that all of the urine be collected. Because the catecholamines are released at varying times, the one sample not included might be the one with the most metanephrines in it.

More information

RCPA Manual: Metanephrines - urine