From the Guidelines
The workup of pheochromocytoma begins with biochemical testing to confirm the diagnosis, typically measuring plasma free metanephrines or 24-hour urinary fractionated metanephrines and catecholamines, as recommended by the most recent guidelines 1.
Key Steps in the Workup of Pheochromocytoma
- Biochemical testing is the first step, focusing on plasma free metanephrines or 24-hour urinary fractionated metanephrines and catecholamines, due to their high sensitivity for detecting catecholamine-secreting tumors 1.
- If biochemical testing is positive, imaging studies should be performed to localize the tumor, with CT scan with contrast of the abdomen and pelvis being the first-line imaging modality, and MRI as an alternative 1.
- For patients with confirmed biochemical evidence but negative conventional imaging, functional studies such as 123I-MIBG scintigraphy or 18F-FDG PET/CT may be necessary 1.
- Genetic testing should be considered for all patients with pheochromocytoma, as up to 40% have an underlying germline mutation in susceptibility genes like RET, VHL, NF1, or SDHx 1.
Preoperative Preparation
- Prior to surgical resection, which is the definitive treatment, patients require preoperative alpha-adrenergic blockade with phenoxybenzamine (starting at 10 mg twice daily and titrating up) or doxazosin (starting at 2 mg daily) for 1-2 weeks, followed by beta-blockade (such as propranolol 20-40 mg three times daily) only after adequate alpha-blockade 1.
- Liberal salt and fluid intake should be encouraged during preoperative preparation to prevent orthostatic hypotension 1.
Importance of Comprehensive Workup
- The comprehensive approach to pheochromocytoma workup is essential because these tumors can cause life-threatening cardiovascular complications if not properly diagnosed and managed 1.
- A multidisciplinary review by endocrinologists, surgeons, and radiologists is recommended when the imaging is not consistent with a benign lesion, there is evidence of hormone hypersecretion, the tumor has grown significantly during follow-up imaging, or adrenal surgery is being considered 1.
From the Research
Diagnostic Approach
The workup of pheochromocytoma involves a combination of biochemical tests, imaging studies, and genetic screening. The following steps are recommended:
- Initial biochemical testing should include measurements of plasma free or urinary fractionated metanephrines 2, 3, 4, 5
- Consideration should be given to preanalytical factors leading to false-positive or false-negative results 5
- Computed tomography (CT) or magnetic resonance imaging (MRI) should be used for initial imaging, with CT suggested for initial imaging and MRI as a better option in patients with metastatic disease or when radiation exposure must be limited 2, 5
- Functional imaging modalities such as metaiodobenzylguanidine (MIBG) scintigraphy, positron emission tomography (PET), or single photon emission computed tomography (SPECT) can be used to assess the functionality of the tumor 2, 5
Biochemical Testing
Biochemical testing is crucial for the diagnosis of pheochromocytoma. The following tests are recommended:
- Plasma free metanephrines: highly sensitive and specific for diagnosing pheochromocytoma 3, 4, 5
- Urinary fractionated metanephrines: highly sensitive and specific for diagnosing pheochromocytoma 3, 4, 5
- Clonidine test: can be used to confirm the diagnosis if the results of plasma or urinary metanephrines are equivocal 4
Imaging Studies
Imaging studies are essential for the localization of pheochromocytoma. The following imaging modalities are recommended:
- CT: high sensitivity for detecting pheochromocytoma, but lacks specificity 2, 5
- MRI: high sensitivity for detecting pheochromocytoma, and better than CT in patients with metastatic disease or when radiation exposure must be limited 2, 5
- PET/CT/MR: offers high sensitivity and specificity for detecting pheochromocytoma and paraganglioma 6
Genetic Screening
Genetic screening is recommended for all patients with pheochromocytoma, as gene mutations are reported in 32-79% of cases 2, 5. The following genetic tests are recommended: