Which populations should be prioritized for imaging in suspected pheochromocytoma and what is the initial imaging modality of choice?

Imaging and Population Prioritization for Suspected Pheochromocytoma

The initial imaging modality of choice for suspected pheochromocytoma is CT scan of the abdomen, and populations that should be prioritized include patients with genetic syndromes (SDHx, VHL, RET, NF1), those with significant biochemical evidence (metanephrines >4 times upper limit), and patients with the classic triad of headache, sweating, and palpitations. 1

Patient Populations to Prioritize for Imaging

High-Priority Populations

• Patients with genetic predisposition:

  • SDHx mutation carriers (especially SDHB with high malignancy risk)
  • VHL syndrome patients
  • MEN2 syndrome patients
  • NF1 mutation carriers
  • TMEM127 and MAX mutation carriers 1, 2

• Patients with biochemical confirmation:

  • Plasma free metanephrines >4 times upper limit of normal
  • 24-hour urinary fractionated metanephrines >4 times upper limit of normal 1, 3

• Symptomatic patients with:

  • Complete triad of headache, palpitations, and diaphoresis
  • Paroxysmal hypertension or resistant hypertension
  • Hypertension with orthostatic hypotension 1, 3

Medium-Priority Populations

• Patients with borderline elevations of metanephrines who have positive clonidine suppression test
• Patients with unexplained paroxysmal symptoms without hypertension
• Young patients (<40 years) with hypertension 1, 4

Imaging Modality Selection Algorithm

First-Line Imaging

1. CT scan of abdomen - First-line imaging modality for all suspected pheochromocytomas 1

   • High sensitivity for adrenal and abdominal lesions
   • Should only be pursued after biochemical evidence of pheochromocytoma

2. MRI - Alternative first-line imaging, particularly useful for:

   • Pregnant patients
   • Patients with contrast allergy
   • Children and young adults (to reduce radiation exposure) 1

Functional Imaging Based on Genetic Status and Tumor Location

For Patients with Unknown or Negative Genetic Testing:

• Non-metastatic adrenal pheochromocytoma: 123I-MIBG scintigraphy
• Head and neck paragangliomas: 18F-FDOPA PET
• Extra-adrenal or multifocal disease: 18F-FDG PET
• Metastatic disease: 18F-FDG PET or 18F-FDA PET (if available) 2

For Patients with Known Genetic Mutations:

• SDHx mutations: 18F-FDG PET (particularly for SDHB-related metastatic disease)
• VHL mutations: 18F-FDOPA PET
• RET mutations (MEN2): 18F-FDOPA PET
• NF1 mutations: 18F-FDG PET 2

Important Considerations

Diagnostic Approach

• Imaging should only be pursued after biochemical confirmation of pheochromocytoma 1
• For equivocal biochemical results, clonidine suppression test may be used before proceeding to imaging 1, 3

Special Situations

• Metastatic disease: 18F-FDG PET is the imaging modality of choice for SDHB-related metastatic pheochromocytomas/paragangliomas 2
• Head and neck paragangliomas: 18F-FDOPA PET has the highest sensitivity (approaching 100%) 2
• MEN2-related pheochromocytomas: Many patients don't need specific functional imaging if tumor is confined to adrenal gland with characteristic elevation of metanephrines 2

Pitfalls to Avoid

• Performing imaging before biochemical confirmation can lead to incidental findings and unnecessary procedures 1
• Using 123I-MIBG scintigraphy alone for staging hereditary and metastatic pheochromocytomas/paragangliomas can significantly underestimate disease extent 2
• Failing to consider genetic testing, as approximately 25% of pheochromocytomas are hereditary 1

By following this algorithm, clinicians can optimize the diagnostic approach to suspected pheochromocytoma, ensuring appropriate use of resources while maximizing detection of these potentially life-threatening tumors.