What is the management and treatment of pheochromocytoma?

Management and Treatment of Pheochromocytoma

The definitive treatment for pheochromocytoma is complete surgical resection (R0 resection) following appropriate preoperative alpha-adrenergic blockade to control catecholamine excess and prevent perioperative complications. 1, 2

Diagnosis

• Measurement of plasma free metanephrines is the most sensitive and specific single test for diagnosing pheochromocytoma in clinically suspected cases 1, 2
• If plasma testing is equivocal, a 24-hour urine collection for catecholamines and metanephrines should be performed 1, 2
• Additional measurement of plasma methoxytyramine provides useful information to assess the likelihood of malignancy 1
• After positive biochemical testing, localization is performed using CT or MRI of the abdomen 1, 2
• Functional imaging, such as Meta-iodobenzylguanidine (MIBG) scintigraphy, helps detect multifocal disease 1

Preoperative Management

Alpha-Adrenergic Blockade

• Alpha-adrenergic blockade must be initiated 7-14 days before surgery to control blood pressure and prevent perioperative complications 3

• Two main options for alpha blockade:

  1. Non-selective, non-competitive alpha-blocker: Phenoxybenzamine (FDA-approved for pheochromocytoma) 4
  2. Selective alpha-1 blockers: Doxazosin, prazosin, or terazosin 3

• The PRESCRIPT trial showed phenoxybenzamine resulted in less intraoperative hemodynamic instability compared to doxazosin, though both were effective 3

• Blood pressure targets: <130/80 mmHg when supine, systolic BP >90 mmHg when upright 3

Additional Preoperative Measures

• Beta-blockers (e.g., metoprolol) should be added ONLY AFTER adequate alpha blockade to control tachycardia and arrhythmias 3, 4
• Calcium channel blockers can be used as adjuncts to alpha-blockers for refractory hypertension or as monotherapy in cases with mild hypertension 3
• Metyrosine (alpha-methylparatyrosine) may be used to inhibit catecholamine synthesis, particularly for preoperative preparation 5
• High-sodium diet and administration of 1-2 liters of saline 24 hours before surgery, along with compressive stockings, to reduce risk of orthostatic and postoperative hypotension 3

Surgical Management

• Complete surgical resection (R0) is the mainstay of potentially curative treatment 3, 1
• Laparoscopic approach is preferred for most adrenal pheochromocytomas, but an open approach is recommended for tumors >5 cm 2
• For locally advanced tumors, resection of adjacent organs may be necessary to achieve R0 resection 3
• Locoregional lymphadenectomy improves tumor staging and may lead to favorable oncologic outcomes 3
• Cytoreductive (R2) resection in malignant pheochromocytoma may improve quality of life and survival by reducing tumor burden and controlling hormonal hypersecretion 3

Intraoperative Management

• Careful anesthetic management is essential to prevent hypertensive crises and arrhythmias 6
• Intraoperative hypertension may be treated with magnesium sulfate, intravenous alpha-adrenergic antagonists, calcium antagonists, nitroprusside, or nitroglycerin 3
• Tachycardia can be treated with intravenous beta-blockers (e.g., esmolol) 3

Management of Malignant/Metastatic Disease

• Disease and symptom control are the main treatment goals for patients with inoperable pheochromocytoma 1
• Treatment options include:
  • Radiopharmaceuticals such as 131I-MIBG for patients with sufficient MIBG uptake 1
  • Metyrosine for chronic treatment of patients with malignant pheochromocytoma 5
  • Alpha-blockade for symptom control 4

Postoperative Care and Follow-up

• Monitor for postoperative hypotension, which should be treated aggressively with fluid resuscitation 3
• Monitor glucose levels as hypoglycemia may occur after reduction of catecholamine levels 3
• Biochemical testing should be performed approximately 14 days after surgery to verify complete resection 2
• Long-term follow-up includes:
  • Clinical evaluation (adrenergic symptoms and blood pressure)
  • Biochemical testing (metanephrines, normetanephrines, chromogranin A, and methoxytyramine)
  • Imaging as clinically indicated 1, 2
• Biochemical tests should be repeated every 3-4 months for 2-3 years, then every 6 months 2
• Lifetime follow-up is recommended for proven malignant disease, SDHB mutation, primary extra-adrenal disease, and cases without relevant preoperative hormonal secretion 2

Special Considerations

• Genetic testing should be considered, particularly in patients with family history, young age at diagnosis, bilateral or multifocal disease, or extra-adrenal location 1
• Risk factors for malignancy include tumor size ≥5 cm, extra-adrenal paraganglioma, SDHB germline mutation, and elevated plasma methoxytyramine 1, 2
• In pregnant patients with pheochromocytoma, alpha-blockade followed by surgical resection is recommended, with timing dependent on gestational age 3