How to diagnose pheochromocytoma?

From the Guidelines

Diagnosing pheochromocytoma requires measuring plasma free metanephrines or 24-hour urinary metanephrines and catecholamines as the initial step, due to their high sensitivity and specificity, as recommended by the American Heart Association 1. The diagnosis of pheochromocytoma is crucial due to its high morbidity and mortality if left untreated.

Key Diagnostic Steps

• Measuring plasma free metanephrines or 24-hour urinary metanephrines and catecholamines is the first step in diagnosing pheochromocytoma, with a sensitivity of 96%−100% and specificity of 89%−98% for plasma free metanephrines 1.
• If biochemical testing is positive, imaging studies such as CT scan or MRI of the abdomen and pelvis should be performed to locate the tumor, with CT having a sensitivity of about 90% 1.
• Functional imaging with 123I-MIBG scintigraphy, 18F-FDG PET, or 68Ga-DOTATATE PET may be used for tumors not visible on conventional imaging or to confirm the functional nature of suspicious masses 1.
• Genetic testing is recommended for all patients with pheochromocytoma, as about 40% have an underlying germline mutation in genes such as RET, VHL, NF1, SDHB, and SDHD 1.

Important Considerations

• Certain medications, such as tricyclic antidepressants and decongestants, can cause false-positive results and should be ruled out during the diagnostic process 1.
• Severe illness or stress can also lead to false-positive results, and therefore, should be considered when interpreting test results 1.
• The recent Endocrine Society guideline recommends starting with computed tomography, with magnetic resonance imaging as an alternative, and metaiodobenzylguanidine scanning to further evaluate suspected metastatic disease 1.
• The 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline also supports the use of 24-hour urinary fractionated metanephrines or plasma metanephrines for diagnosing pheochromocytoma 1.

From the Research

Diagnostic Tests for Pheochromocytoma

To diagnose pheochromocytoma, several biochemical tests can be used, including:

• Plasma free metanephrines: This test has been shown to have high sensitivity and specificity for diagnosing pheochromocytoma 2, 3, 4, 5
• Urinary fractionated metanephrines: This test is also effective in diagnosing pheochromocytoma, with high sensitivity and specificity 2, 6, 4, 5
• Plasma catecholamines: This test has lower sensitivity and specificity compared to plasma free metanephrines and urinary fractionated metanephrines 2
• Urinary catecholamines: This test also has lower sensitivity and specificity compared to plasma free metanephrines and urinary fractionated metanephrines 2
• Urinary vanillylmandelic acid: This test has low sensitivity and specificity for diagnosing pheochromocytoma 2

Interpretation of Test Results

When interpreting the results of these tests, it is essential to consider the following:

• Elevated plasma free metanephrines or urinary fractionated metanephrines are key to diagnosing pheochromocytoma 4
• A clonidine test may be performed if the results are equivocal 4
• Imaging tests such as CT or MRI scans may be used to confirm the diagnosis 4
• Preanalytical factors, such as drug interference, can influence metanephrine measurement and cause false positive results 5

Clinical Considerations

In clinical practice, the following considerations are important:

• Pheochromocytoma is often suspected due to hypertension or other clinical symptoms 4
• Genetic testing should be considered in patients with a family history of pheochromocytoma or other familial syndromes 4
• Preoperative preparation with α1-blockers, Calcium Channels Blockers, and/or β-Blockers is essential to minimize risks during operation and the postoperative period 4