What is the workup of a pheochromocytoma?

Workup of Pheochromocytoma

The initial step in the workup of pheochromocytoma is measurement of plasma free metanephrines, which has the highest sensitivity (96-100%) and specificity (89-98%) as a single test. 1

Biochemical Testing

First-Line Tests

• Plasma free metanephrines:

  • Should be collected after patient has been lying supine for 30 minutes
  • Highest diagnostic accuracy (sensitivity 96-100%, specificity 89-98%)
  • Results >4 times upper limit of normal are highly consistent with pheochromocytoma 1

• Alternative first-line test: 24-hour urinary fractionated metanephrines

  • Sensitivity: 86-97%
  • Specificity: 86-95% 1

Second-Line Tests

• Clonidine suppression test:
  • Used for borderline elevations
  • 100% specificity and 96% sensitivity 1

Imaging Studies

• Imaging should only be pursued after biochemical evidence of pheochromocytoma 1

Anatomical Imaging

• CT scan of abdomen: First-line imaging modality 1
• MRI: Alternative imaging option, preferred for suspected pheochromocytoma due to risk of hypertensive crisis with IV contrast for CT 2

Functional Imaging

For patients with high risk of metastases (any of the following):

• Tumor size ≥5 cm
• Extra-adrenal paraganglioma
• Known SDHB germline mutation
• Plasma methoxytyramine >3x upper limit of normal 2

Options include:

• 18F-FDG PET/CT: Preferred for SDHB-related metastatic pheochromocytomas 1
• 123I-MIBG scintigraphy: Recommended for non-metastatic adrenal pheochromocytoma 1
• DOTATATE-PET: For suspected metastatic disease 2, 1
• 18F-FDOPA PET: Highest sensitivity for head and neck paragangliomas 1

Diagnostic Algorithm

1. Biochemical confirmation: Plasma free metanephrines or 24-hour urinary fractionated metanephrines
2. Anatomical localization: CT or MRI of abdomen
3. Functional imaging: If high risk for metastases or to evaluate for radionuclide therapy options
4. Genetic testing: Consider in all patients with confirmed pheochromocytoma

Special Considerations

Genetic Testing

• Approximately 25-35% of pheochromocytomas are hereditary 2, 1
• Genetic testing should be considered in all patients, especially those with:
  • Young age at diagnosis
  • Bilateral or multifocal disease
  • Extra-adrenal location
  • Family history of pheochromocytoma or related syndromes 1

Diagnostic Pitfalls

• Avoid fine needle biopsy: Contraindicated in suspected pheochromocytoma due to risk of hypertensive crisis 2
• Avoid CT with contrast before alpha-blockade due to risk of catecholamine crisis 2
• Avoid delay in diagnosis: Average delay is 3 years, which increases morbidity and mortality 1
• False positives: Certain medications, foods, and conditions can interfere with catecholamine measurements
• False negatives: Especially in patients with paroxysmal hypertension 3

Phentolamine Blocking Test

While less commonly used now, the phentolamine blocking test can be used diagnostically:

• Most reliable in patients with sustained hypertension
• A positive response is indicated by blood pressure reduction >35 mmHg systolic and >25 mmHg diastolic after phentolamine administration
• Should always be confirmed by other diagnostic procedures 3

Preoperative Management

After diagnosis but before surgery:

• Alpha-adrenergic blockade: Essential for 10-14 days before surgery
  • Options: Phenoxybenzamine (non-selective) or selective α1-blockers (doxazosin, prazosin, terazosin)
  • Target BP <130/80 mmHg supine, systolic BP >90 mmHg upright 1
• Beta-blockers: Only after adequate alpha-blockade if tachyarrhythmias develop 1
• Volume expansion: High-sodium diet and fluid intake to prevent orthostatic hypotension 1

By following this systematic approach to the workup of pheochromocytoma, clinicians can ensure accurate diagnosis and appropriate management to reduce morbidity and mortality associated with this rare but potentially life-threatening condition.