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Metanephrine, Free

Optimal Result: 0 - 57 pg/mL, or 0.00 - 0.34 nmol/L.

Metanephrines, namely metanephrine and normetanephrine, are metabolic byproducts derived from the catecholamines epinephrine (also known as adrenaline) and norepinephrine.

The plasma free metanephrines test gauges the levels of these substances within the bloodstream.

Catecholamines are hormones produced by the adrenal glands, which are small triangular organs situated atop the kidneys, as well as by cells within the sympathetic nervous system, where they function as neurotransmitters.

The primary catecholamines consist of dopamine, epinephrine, and norepinephrine.

These compounds are released in response to physical or emotional stress and serve various roles, such as transmitting nerve signals within the brain, enhancing the release of glucose and fatty acids for energy, expanding the bronchioles in the lungs, and dilating the pupils. Norepinephrine also constricts blood vessels, elevating blood pressure, while epinephrine increases heart rate and metabolic activity.

Following their actions, catecholamines undergo metabolism into inactive compounds.

→ Epinephrine is broken down into metanephrine and vanillylmandelic acid (VMA)

→ Norepinephrine is converted into normetanephrine and VMA.

Both the hormones and their metabolites are excreted from the body through urine.

Normally, catecholamines and their breakdown products exist in low, fluctuating quantities in the blood and urine, with substantial increases occurring primarily during and shortly after stressful situations.

However, uncommon tumors known as pheochromocytomas that originate in the adrenal glands or paragangliomas that develop outside the adrenal glands can produce excessive amounts of these hormones, leading to markedly elevated concentrations in both the blood and urine. These conditions are collectively referred to as PPGL (pheochromocytoma and paraganglioma). They can induce sustained or intermittent episodes of high blood pressure, often accompanied by severe headaches, palpitations, sweating, nausea, anxiety, and tingling in the extremities.

Pheochromocytomas and paragangliomas are rare, and while a few may be malignant, most are benign and localized. Nonetheless, if left untreated, these tumors may continue to grow, exacerbating symptoms. Over time, the hypertension resulting from excessive hormone production may damage the kidneys, contribute to heart disease, and heighten the risk of stroke or heart attack.

Although these tumors are infrequent, it is crucial to diagnose them because they represent a potentially curable form of hypertension. In most cases, surgical removal and/or treatment can effectively reduce or eliminate the overproduction of catecholamines and alleviate associated symptoms and complications.

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This test measures the substances metanephrine and normetanephrine in your blood. 

Healthcare providers disagree on the best test for diagnosing adrenal gland tumors. Some providers believe a urine test to measure catecholamines is better than this blood test because it has fewer false-positive results.

You may need this test if your healthcare provider believes that you have an adrenal gland tumor.

Symptoms include:

→ Fast heartbeat

→ Headaches

→ Sweating

→ Rise and fall in blood pressure

You also may have fever, chest pain, stomach pain, nausea, vomiting, anxiety, tremors, heat intolerance, and weight loss.

Most pheochromocytomas are not cancer.

Normal metanephrine and normetanephrine blood levels mean it is unlikely that you have a tumor that produces catecholamines. The plasma free metanephrines test is very sensitive and these tumors are rare, making it the best test for excluding PPGL.

What does it mean if your Metanephrine, Free result is too high?

High levels of metanephrine and normetanephrine when you have signs and symptoms suggest the presence of a tumor. It is recommended that patients with a positive result receive appropriate follow-up according to the test values noted and the clinical presentation. Imaging scans, such as MRI, should be done to locate the tumor.

If levels are elevated after you have been treated for one of these tumors, it may be an indication that the treatment was not fully effective or that the tumor is recurring and appropriate follow-up is needed.

Note on false positives: The test for metanephrines is very sensitive and false positives do occur. The test is affected by stress, drugs, smoking and various foods. If you have only moderately elevated metanephrines, then your healthcare provider may re-evaluate your medications, diet, and stress level to look for interfering substances or conditions. Once these are resolved, you may be tested again to determine whether the metanephrines are still elevated. Sometimes the plasma free metanephrines test will be done along with 24-hour urine metanephrines testing and/or followed by catecholamines testing or imaging procedures to help decide if a catecholamine-secreting tumor is present.

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