From the Guidelines
The laboratory workup for pheochromocytoma should begin with biochemical testing for catecholamines and their metabolites, specifically measurement of circulating catecholamine metabolites such as plasma free or urinary fractionated metanephrines, as recommended by the most recent guidelines 1.
Initial Screening Tests
The initial screening tests for pheochromocytoma include:
- 24-hour urinary fractionated metanephrines and catecholamines
- Plasma free metanephrines, which have higher sensitivity 1 For the 24-hour urine collection, patients should avoid foods high in catecholamines (like coffee, chocolate, and bananas) for 48-72 hours before testing and discontinue interfering medications if possible (including tricyclic antidepressants, levodopa, and sympathomimetics) 1.
Confirmatory Testing
Plasma free metanephrines should be collected after the patient has been supine and resting for at least 30 minutes. If initial tests are positive, confirmatory testing may include clonidine suppression testing, which has 100% specificity and 96% sensitivity of failure to reduce plasma metanephrines by 40% 1.
Imaging Studies
Once biochemical diagnosis is established, imaging studies such as CT or MRI of the abdomen and pelvis should be performed to localize the tumor, as recommended by the recent Endocrine Society guideline 1.
Additional Testing
For patients with familial syndromes or extra-adrenal disease, additional testing may include MIBG scintigraphy or PET scanning. Genetic testing should be considered, particularly in patients with bilateral tumors, family history, or young age of onset, to evaluate for hereditary syndromes like MEN2, von Hippel-Lindau, or neurofibromatosis type 1. The most recent guideline from 2023 1 supports the use of plasma or 24-hour urinary metanephrines for screening patients with adrenal incidentalomas that display ≥ 10 HU on non-contrast CT or who have signs/symptoms of catecholamine excess.
From the Research
Laboratory Workup for Pheochromocytoma
The laboratory workup for pheochromocytoma typically involves measurements of plasma free metanephrines or urinary fractionated metanephrines.
- Plasma free metanephrines have a high diagnostic sensitivity of 98% and specificity of 92% 2
- Urinary fractionated metanephrines also have high sensitivity and specificity, with values of 97% and 69%, respectively 3
- Measurements of plasma catecholamines, urinary catecholamines, and urinary vanillylmandelic acid can also be used, but have lower sensitivity and specificity compared to plasma free metanephrines and urinary fractionated metanephrines 3
- A new radioimmunoassay (RIA) for the measurement of free metanephrines in plasma has been developed and shows good agreement with tandem mass spectrometry (LC-MS/MS) method 4
Diagnostic Tests
The following diagnostic tests can be used to diagnose pheochromocytoma:
- Plasma free metanephrines
- Urinary fractionated metanephrines
- Plasma catecholamines
- Urinary catecholamines
- Urinary vanillylmandelic acid
- Radioimmunoassay (RIA) for free metanephrines in plasma
Test Interpretation
- A positive test result indicates the presence of pheochromocytoma, but a negative result does not completely rule out the diagnosis 2, 5
- Borderline increased results should be followed up with repeat testing to either exclude or confirm diagnosis 6
- The choice of test and interpretation of results should be individualized based on patient characteristics and clinical presentation 3