What is the recommended treatment for pheochromocytoma?

Recommended Treatment for Pheochromocytoma

The recommended treatment for pheochromocytoma is complete surgical resection with mandatory preoperative alpha-adrenergic blockade for 10-14 days to prevent perioperative complications. 1

Preoperative Management

Alpha-Adrenergic Blockade

1. Alpha-blockade should be initiated when:

   • Normetanephrine levels are ≥2-fold the upper reference limit
   • Patient is symptomatic 1

2. Alpha-blocker options:

   • First-line: Phenoxybenzamine (40-80 mg/day) - non-selective α-blocker 1, 2
   • Alternative: Selective α1-blockers (doxazosin, prazosin, or terazosin) 1

3. Considerations for alpha-blocker selection:

   • Phenoxybenzamine provides slightly better control of systolic blood pressure but causes more postoperative hypotension 3
   • Doxazosin has fewer side effects (less orthostatic hypotension, edema, and nasal congestion) 3
   • Higher doses of phenoxybenzamine (around 270 mg/day) may decrease intraoperative hemodynamic instability compared to lower doses (140 mg/day) 4

Additional Medications

• Beta-blockers should only be added after adequate alpha-blockade if tachycardia persists 1
• Important: Never use beta-blockers before establishing alpha-blockade as this can precipitate a hypertensive crisis 5
• Calcium channel blockers can be used as adjunct therapy for refractory hypertension 1

Management of Hypertensive Emergencies

• First-line options: Phentolamine, nitroprusside, or urapidil 1
• Alternative: Nicardipine 1
• Avoid labetalol due to potential to accelerate hypertension 1

Surgical Management

Surgical Approach

• Preferred approach for small tumors (<8 cm) without invasion: Laparoscopic adrenalectomy 1
• Recommended for larger tumors (>5-6 cm) or with invasion: Open surgery 1

Perioperative Considerations

• Complete surgical resection (R0) is the mainstay of potentially curative treatment 1
• Continuous hemodynamic monitoring is essential during surgery 6
• Be prepared for blood pressure fluctuations:
  • Hypertension during tumor manipulation
  • Hypotension after tumor removal

Management of Metastatic Disease

For patients with metastatic pheochromocytoma, treatment options include:

1. "Wait and see" approach for low tumor burden and asymptomatic cases 1
2. Radiopharmaceuticals (131I-MIBG) 1
3. Locoregional ablative procedures 1
4. Combination chemotherapy (cyclophosphamide, vincristine, dacarbazine) 1
5. For SDHx-related metastatic disease: temozolomide or tyrosine kinase inhibitors 1
6. Anti-resorptive therapies for widespread bone metastases 1

Post-Treatment Follow-up

• Plasma/urine metanephrines should be measured 8 weeks post-surgery 1
• Imaging should be performed at 3-6 months post-surgery 1
• Continue surveillance for at least 10 years, with lifelong follow-up for genetic cases 1
• Regular check-ups:
  • Every 3-4 months for 2-3 years
  • Then every 6 months
  • Annual biochemical measurements 1

Important Considerations and Pitfalls

• Never perform fine needle biopsy of suspected pheochromocytoma as it can precipitate hypertensive crisis and risk tumor seeding 1
• Never use beta-blockers before alpha-blockade as this can lead to unopposed alpha-adrenergic stimulation and severe hypertension 1, 5
• 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 1
• FDG-PET is superior to MIBG for SDHB-related tumors and should be the preferred imaging method for these cases 7, 1