When should plasma metanephrines be ordered?

From the Guidelines

Plasma metanephrines should be ordered in patients with clinical suspicion for pheochromocytoma or paraganglioma, particularly those with resistant hypertension, signs and symptoms of catecholamine excess, adrenal incidentalomas, genetic syndromes associated with pheochromocytoma, or a family history of pheochromocytoma. The test measures free metanephrines (metanephrine and normetanephrine), which are metabolites of epinephrine and norepinephrine, and has a high sensitivity of approximately 96-100% making it excellent for ruling out disease 1.

Key Considerations

• Patients should fast overnight, avoid acetaminophen for 5 days prior, and remain supine for at least 30 minutes before blood collection to ensure optimal results.
• Certain medications (including tricyclic antidepressants, MAO inhibitors, sympathomimetics) can cause false positives, so these should be discontinued if possible before testing 1.
• If medication discontinuation isn't feasible, this information should be noted when interpreting results.
• Plasma metanephrines are generally preferred over 24-hour urine collections due to better patient compliance and comparable diagnostic accuracy 1.

Interpretation of Results

• If plasma metanephrines are >4 upper limit of reference range, it is consistent with disease, and imaging should be pursued to localize the lesion 1.
• If results are 2–4 upper limit of reference range, testing should be repeated in 2 months.
• If results are marginally elevated, testing should be repeated in 6 months or a clonidine suppression test should be considered to exclude false positivity 1.

Clinical Context

The diagnosis of pheochromocytoma should be entertained in a hypertensive patient with a combination of headaches, palpitations, and sweating, typically occurring in an episodic fashion, with a diagnostic specificity of 90% 1. Given the high morbidity and mortality of not treating these tumors, and the fact that one-third are inherited, it is essential to consider the diagnosis in anyone referred for resistant hypertension 1.

From the Research

When to Order Plasma Metanephrines

Plasma metanephrines should be ordered in the following situations:

• When there are signs and symptoms suggestive of catecholamine excess, regardless of whether the patient has hypertension or not 2
• In patients with newly diagnosed hypertension who also have additional signs of catecholamine excess 2
• In patients with typical paroxysmal symptoms, unusual or refractory hypertension, discovery of an adrenal incidentaloma, or a family history of pheochromocytoma or paraganglioma 3
• In patients with manifestations of hypercatecholaminemia or coexisting neoplasms 4
• When pheochromocytoma is suspected due to sustained or paroxysmal hypertension associated with headaches, sweating, or palpitations 4

Key Points to Consider

• Plasma free metanephrines and fractionated urinary metanephrines are the most sensitive chemical tests for diagnosing sporadic and familial pheochromocytomas 4
• Measurements of plasma free metanephrines provide a superior test compared to other available tests for diagnosis of pheochromocytoma 5
• A normal plasma free metanephrines test result reliably excludes all but the smallest of pheochromocytomas, making it a cost-effective test 5
• Genetic testing should be carried out in patients with pheochromocytoma, as 40% of patients have germline mutations 2, 3, 6