What are the diagnostic criteria for pheochromocytoma?

From the Guidelines

Diagnosing pheochromocytoma requires a combination of clinical suspicion, biochemical testing, and imaging studies, with the initial step involving screening for excess catecholamines through plasma free metanephrines, which is the most sensitive test, as recommended by the most recent guidelines 1. The diagnostic criteria for pheochromocytoma include:

• Clinical suspicion based on signs and symptoms of catecholamine excess, such as headaches, palpitations, and sweating
• Biochemical testing, including:

• Plasma free metanephrines, which has a sensitivity of 96-100% and specificity of 89-98% 1
• Urinary fractionated metanephrines, which has a sensitivity of 86-97% and specificity of 86-95% 1

• Imaging studies, including:

• CT or MRI of the abdomen and pelvis, with CT having a sensitivity of about 90% 1
• Functional imaging with MIBG (metaiodobenzylguanidine) scintigraphy, which is specific for catecholamine-producing tumors
• PET scans, which may be helpful in cases where tumors are not visualized by conventional imaging It is essential to note that patients should avoid medications that can interfere with test results, such as tricyclic antidepressants, decongestants, and certain antihypertensives, for at least two weeks before testing. Genetic testing should be considered for all patients, especially those with a family history, bilateral tumors, or young age of onset, as approximately 40% of pheochromocytomas are associated with hereditary syndromes like MEN2, von Hippel-Lindau, or neurofibromatosis type 1 1. The diagnosis is ultimately confirmed by histopathological examination after surgical removal, which remains the definitive treatment.

From the Research

Diagnostic Criteria for Pheochromocytoma

The diagnostic criteria for pheochromocytoma involve biochemical tests to establish the presence of catecholamine production by the tumor. The following are key points to consider:

• Biochemical diagnosis should be established by measuring plasma free metanephrines and urinary fractionated metanephrines 2, 3, 4, 5, 6
• Plasma free metanephrines have been shown to have high sensitivity (99% [95% CI, 96%-100%]) and specificity (89% [95% CI, 87%-92%]) for diagnosing pheochromocytoma 3
• Urinary fractionated metanephrines also have high sensitivity (97% [95% CI, 92%-99%]) but lower specificity (69% [95% CI, 64%-72%]) compared to plasma free metanephrines 3
• Other biochemical tests, such as plasma catecholamines, urinary catecholamines, and urinary vanillylmandelic acid, may also be used but have lower sensitivity and specificity compared to plasma free metanephrines and urinary fractionated metanephrines 3, 6
• Imaging tests, such as computed tomography (CT) or magnetic resonance imaging (MRI), may be used to localize the tumor once biochemical diagnosis is established 2, 4

Biochemical Tests

The following biochemical tests may be used to diagnose pheochromocytoma:

• Plasma free metanephrines: high sensitivity and specificity, considered the best test for excluding or confirming pheochromocytoma 3, 5, 6
• Urinary fractionated metanephrines: high sensitivity but lower specificity compared to plasma free metanephrines 3, 5
• Plasma catecholamines: lower sensitivity and specificity compared to plasma free metanephrines and urinary fractionated metanephrines 3
• Urinary catecholamines: lower sensitivity and specificity compared to plasma free metanephrines and urinary fractionated metanephrines 3, 6
• Urinary vanillylmandelic acid: lower sensitivity and specificity compared to plasma free metanephrines and urinary fractionated metanephrines 3

Imaging Tests

The following imaging tests may be used to localize the tumor once biochemical diagnosis is established:

• Computed tomography (CT): considered the "gold standard" for localizing pheochromocytomas, especially for tumors located in the adrenal medulla 2, 4
• Magnetic resonance imaging (MRI): useful for localizing tumors, especially for those located in extra-adrenal chromaffin tissues (paragangliomas) 2, 4
• Scintigraphy with (123)I-metaiodobenzylguanidine (MIBG): useful for localizing tumors, especially for those that are not visible on CT or MRI 2
• Positron emission tomography (PET) with (18)F-F-fluorodopamine (F-DA): useful for localizing metastatic disease 2