What is the diagnostic workup for pheochromocytoma?

Diagnostic Workup for Pheochromocytoma

The diagnostic workup for pheochromocytoma should begin with plasma free metanephrines as the first-line biochemical test, followed by anatomical imaging with CT or MRI if positive, and functional imaging if needed for localization of extra-adrenal disease. 1

Initial Biochemical Testing

First-Line Test

• Plasma free metanephrines (normetanephrine and metanephrine) is the preferred initial test with:
  • Highest sensitivity (99%) and good specificity (89%) 2
  • Best test for excluding or confirming pheochromocytoma 2
  • Recommended by the Endocrine Society as the first-line test 1

Second-Line Testing (if plasma test is equivocal)

• 24-hour urine collection for catecholamines and metanephrines should be performed if plasma testing shows less than fourfold elevation 3
• Urinary fractionated metanephrines have high sensitivity (97%) but lower specificity (69%) 2

Interpretation of Results

• Significant elevation: Values >4 times the upper reference limit strongly suggest pheochromocytoma 1
• Equivocal results: Values between 1-4 times the upper reference limit require further investigation 1
• False positives can occur with:
  • Medications (tricyclic antidepressants, MAO inhibitors)
  • Acute stress or illness
  • Caffeine consumption
  • Improper sample collection

Imaging Studies

Anatomical Imaging

• First-line imaging: Adrenal protocol CT or MRI after biochemical confirmation 1
• MRI is preferred over CT if pheochromocytoma is strongly suspected due to risk of hypertensive crisis with IV contrast 1
• CT sensitivity is approximately 90-95% for adrenal pheochromocytomas

Functional Imaging (if needed)

• Indicated when:

  • Initial anatomical imaging is negative despite positive biochemical testing
  • Suspicion of multifocal or metastatic disease
  • Hereditary syndromes associated with pheochromocytoma

• Options include:

  • Meta-iodobenzylguanidine (MIBG) scintigraphy: Useful for confirming catecholamine-producing tumors 3
  • FDOPA-PET: Superior for detection of pheochromocytomas in hereditary syndromes (based on small study of 25 patients) 3
  • Consider MIBG if laboratory testing is suggestive of pheochromocytoma with negative abdominal/pelvic imaging 3

Special Considerations

Genetic Testing

• Consider genetic testing in all patients with:
  • Young age at diagnosis (<50 years)
  • Bilateral, multifocal, or extra-adrenal tumors
  • Family history of pheochromocytoma or related syndromes
  • Associated clinical features of hereditary syndromes

Clinical Indicators

• Pheochromocytoma should be considered in patients with:
  • Hypertension (especially if paroxysmal or resistant to treatment)
  • Age >30 years 3
  • Pregnancy with hypertension 3
  • Paroxysmal hypertension 3
  • Hypertension-associated headache, palpitations, or sweating 3
  • Adrenal incidentaloma
  • Family history of pheochromocytoma

Follow-up Testing

• For patients diagnosed with pheochromocytoma:
  • Plasma/urine metanephrines should be measured 8 weeks post-surgery 1
  • Imaging should be performed at 3-6 months post-surgery 1
  • Annual surveillance with plasma metanephrines for long-term follow-up 3

Common Pitfalls to Avoid

• Screening asymptomatic patients: Biochemical or imaging screening in asymptomatic patients without specific risk factors is not recommended 3
• Beta-blockers before alpha-blockers: Never use beta-blockers before adequate alpha-blockade in patients with suspected pheochromocytoma 1
• Relying on a single test: While plasma free metanephrines are highly sensitive, equivocal results should prompt additional testing
• Ignoring clinical context: Test results should always be interpreted in the context of the patient's clinical presentation

By following this systematic approach to the diagnostic workup of pheochromocytoma, clinicians can ensure timely diagnosis and appropriate management of this potentially life-threatening condition.