What is the recommended workup for a suspected pheochromocytoma?

From the Guidelines

The recommended workup for suspected pheochromocytoma begins with biochemical testing to confirm the diagnosis, specifically measuring plasma free metanephrines or 24-hour urinary fractionated metanephrines and catecholamines, as stated in the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1.

Key Considerations

• Prior to testing, patients should avoid medications that can interfere with results (such as tricyclic antidepressants, decongestants, and certain antihypertensives) for at least 2 weeks if possible.
• For the 24-hour urine collection, patients should avoid caffeine, alcohol, and strenuous exercise for 24 hours before and during collection.
• If biochemical tests are positive, imaging studies should follow, typically starting with CT or MRI of the abdomen and pelvis with contrast to locate the tumor, as recommended by the American Heart Association 1.

Additional Testing

• For patients with confirmed biochemical evidence but negative conventional imaging, functional studies like 123I-MIBG scintigraphy or 18F-FDG PET/CT may be necessary, as suggested by the Endocrine Society guideline 1.
• Genetic testing should be considered for all patients with confirmed pheochromocytoma, particularly those with bilateral tumors, family history, or young age of onset, as approximately 40% of cases are associated with hereditary syndromes 1.

Management

• This comprehensive approach is essential because pheochromocytomas can cause life-threatening hypertensive crises if undiagnosed, and proper identification allows for appropriate preoperative management with alpha-blockers (typically phenoxybenzamine starting at 10mg twice daily or doxazosin starting at 2mg daily) followed by beta-blockers if needed before surgical removal, as recommended by the European Heart Journal 1.
• Identifying a single tumour mandates surgical excision after adequate pharmacological preparation, because secreting PPGLs can cause fatal events with no warning, and administering doxazosin or terazosin, followed by a beta-blocker, usually controls BP and adrenergic crises 1.

From the Research

Biochemical Evaluation

• The workup for a suspected pheochromocytoma starts with the measurement of plasma or urine metanephrines 2
• Elevated levels of catecholamines and/or their metabolites in plasma or 24-h urine confirm the diagnosis 3
• Urinary free metanephrines are a reliable method for diagnosing pheochromocytoma and paraganglioma, with a sensitivity of 97.2% and specificity of 98.1% 4

Imaging Techniques

• Computed tomography (CT) is suggested for initial imaging, but magnetic resonance imaging (MRI) is a better option in patients with metastatic disease or when radiation exposure must be limited 5
• CT scan and/or MRI scan are used to localize the tumor once the biochemical diagnosis is made 6
• (123)I-metaiodobenzylguanidine scintigraphy is a useful imaging modality for metastatic pheochromocytomas and paragangliomas 5

Genetic Testing

• Genetic testing should be considered in all patients with pheochromocytoma to identify hereditary disorders that may be present in more than 30% of cases 3
• Patients with paraganglioma should be tested for SDHx mutations, and those with metastatic disease for SDHB mutations 5

Preoperative Preparation

• Patients with functional pheochromocytomas should undergo preoperative blockade to prevent perioperative complications 5
• Pre-treatment with α1-blockers at least 10-14 days before operation is recommended, with alternatives or adjuncts being Calcium Channels Blockers and/or β-Blockers 6
• Preparation should include a high-sodium diet and fluid intake to prevent postoperative hypotension 5