What are the laboratory tests for the workup of pheochromocytoma (adrenal gland tumor)?

From the Guidelines

The workup for pheochromocytoma should include plasma free metanephrines or 24-hour urinary fractionated metanephrines and catecholamines as the initial biochemical tests, with plasma free metanephrines being the preferred first-line test due to its high sensitivity of approximately 96%-100%. The diagnosis of pheochromocytoma is crucial due to its high morbidity and mortality if left untreated, and the average 3-year delay in diagnosis 1. The screening test of choice for pheochromocytoma/paraganglioma is measurement of circulating catecholamine metabolites, with catechol O-methyl transferase releasing normetanephrine and metanephrine from the tumors, measured as plasma free or urinary fractionated metanephrines 1. Some key points to consider in the workup of pheochromocytoma include:

• Initial biochemical testing should include plasma free metanephrines or 24-hour urinary fractionated metanephrines and catecholamines, which are the most sensitive tests for diagnosis 1.
• If these tests are positive, confirmatory imaging should be performed, typically starting with CT or MRI of the abdomen and pelvis with contrast 1.
• For patients with known genetic syndromes or extra-adrenal disease, functional imaging such as 123I-MIBG scintigraphy, 18F-FDG PET/CT, or 68Ga-DOTATATE PET/CT may be necessary to localize the tumor 1.
• Certain medications, including tricyclic antidepressants, decongestants, and levodopa, can interfere with test results, so these should be discontinued before testing if possible 1.
• Patients should avoid caffeine, alcohol, and strenuous exercise for 24 hours before blood sampling, and blood collection should be performed after the patient has been supine and resting for at least 15-30 minutes to minimize false positives from stress-induced catecholamine release 1. The most recent and highest quality study, published in 2020, recommends the use of fractionated metanephrines in 24-hour urine or plasma-free metanephrines and methoxytyramine for the diagnosis of pheochromocytoma 1. It's also important to note that some patients may be at high risk of metastases, including those with adrenal pheochromocytoma 5 cm or any extra-adrenal paraganglioma, known SDHB germline mutation, or plasma methoxytyramine more than threefold above the upper reference limit 1.

From the Research

Laboratory Tests for Pheochromocytoma

The diagnosis of pheochromocytoma should first be established biochemically by measuring:

• Plasma free metanephrines 2, 3, 4
• Urinary fractionated metanephrines 2, 3, 5 These tests are used to detect the presence of catecholamines produced by the tumor.

Biochemical Diagnosis

The best test to establish the diagnosis of pheochromocytoma has been determined to be:

• Plasma free metanephrines, which have a high sensitivity (99%) and specificity (89%) 3
• Urinary fractionated metanephrines, which have a high sensitivity (97%) and specificity (69%) 3

Comparison of Biochemical Tests

Studies have compared the diagnostic accuracy of different biochemical tests, including:

• Plasma free metanephrines measured by a commercial immunoassay and urinary catecholamines 4
• Plasma-free metanephrines (PFM) or urinary fractionated metanephrines (UFM) 5 These studies have shown that plasma free metanephrines are a useful diagnostic test for pheochromocytoma, with a high specificity compared to urinary catecholamines.

Special Cases

There have been reports of pheochromocytoma with elevated metanephrines as the only biochemical finding 6 In such cases, the diagnosis of pheochromocytoma can be confirmed by surgical pathology, even if other biochemical tests are normal.

Radiological Imaging Tests

The radiological imaging tests of choice for pheochromocytoma are:

• Computed tomography (CT) 2
• Magnetic resonance imaging (MRI) 2 These tests are used to localize the tumor and guide surgical treatment.

Functional Imaging Tests

The first-line specific functional imaging test for pheochromocytoma is:

• Scintigraphy with (123)I-metaiodobenzylguanidine (MIBG) 2 If this test is unavailable, scintigraphy with (131)I-MIBG is the second choice. Positron emission tomography (PET) with (18)F-F-fluorodopamine (F-DA) is useful in metastatic disease.