What does an elevated metanephrines level in urine indicate?

From the Guidelines

Elevated metanephrines in urine is a strong indicator of a potential pheochromocytoma or paraganglioma, and patients with these results should undergo further testing, such as blood tests, CT scans, MRI, or specialized nuclear medicine scans, to confirm the diagnosis, as recommended by the 2018 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1. The presence of elevated metanephrines in urine suggests excessive production of adrenaline-like hormones in the body, which may be caused by rare tumors that develop in the adrenal glands or certain nerve tissues. These tumors release excess catecholamines (adrenaline and noradrenaline), which break down into metanephrines that are then excreted in urine. Some key points to consider include:

• Common symptoms associated with these conditions include high blood pressure (often episodic), headaches, sweating, rapid heartbeat, and anxiety.
• False positives can occur due to certain medications (including some antidepressants, decongestants, and stimulants), stress, strenuous exercise before the test, or dietary factors like caffeine consumption.
• The 2007 guidelines for the management of arterial hypertension recommend measurement of plasma free metanephrines or urinary fractionated metanephrines as the diagnostic test of choice for pheochromocytoma 1.
• The 2023 CUA guideline endorsed by the AUA recommends screening for pheochromocytoma with plasma or 24-hour urinary metanephrines in patients with adrenal incidentalomas that display ≥ 10 HU on non-contrast CT or who have signs/symptoms of catecholamine excess 1. Follow-up with a healthcare provider is essential to determine the cause and appropriate treatment, which may range from monitoring to surgical removal of any identified tumors.

From the Research

Elevated Metanephrines in Urine

Elevated metanephrines in urine can be an indicator of pheochromocytoma, a rare tumor of the adrenal gland that produces excess catecholamines 2, 3, 4. The diagnosis of pheochromocytoma depends on the demonstration of catecholamine excess, which can be measured through 24-hour urinary catecholamines and metanephrines or plasma metanephrines 2.

Key Findings

• Elevated metanephrines in urine can be the only biochemical finding in some cases of pheochromocytoma 3.
• More than four times elevation of plasma fractionated metanephrines or elevated 24-hour urinary fractionated metanephrines are keys to diagnosing pheochromocytoma 4.
• Serum metanephrines determination can also be used for diagnosis, with a sensitivity of 100% and a specificity of 94% above a threshold value of 50 nmol/l in patients with normal renal function 5.

Diagnostic Approach

• The diagnosis of pheochromocytoma should first be established biochemically by measuring plasma free metanephrines and urinary fractionated metanephrines 6.
• Radiological imaging tests, such as computed tomography (CT) or magnetic resonance imaging (MRI), can be used to localize the tumor 2, 6.
• Functional imaging tests, such as scintigraphy with (123)I-metaiodobenzylguanidine (MIBG), can also be used to diagnose pheochromocytoma 6.

Treatment and Prognosis

• The treatment of choice for pheochromocytoma is laparoscopic surgery after adequate alpha adrenergic blockade 2, 6.
• Approximately 10% of tumors are malignant, and chemotherapy is used for inoperable disease 6.
• Prognosis is good except in malignant disease, in which 5-year survival is less than 50% 6.