What is the management approach for pheochromocytoma?

Management of Pheochromocytoma

The optimal management of pheochromocytoma requires alpha-adrenergic blockade for 10-14 days preoperatively followed by surgical resection, which is the definitive treatment for this potentially life-threatening condition. 1

Diagnosis

• Initial diagnosis relies on measuring metanefrinas fraccionadas in urine or free metanephrines in plasma, which have the highest sensitivity (97-98%) and specificity for pheochromocytoma 2
• After positive biochemical confirmation, localization is performed using CT or MRI of the abdomen, with MRI being preferred due to the risk of hypertensive crisis with IV contrast during CT 2
• For whole-body screening, anatomical imaging combined with PET scan (preferably with radiolabeled somatostatin analogs) is recommended 2

Preoperative Management

Pharmacological Preparation

• Alpha-adrenergic blockade must be initiated 10-14 days before surgery with gradually increasing dosages to achieve blood pressure targets of <130/80 mmHg supine and >90 mmHg systolic when standing 1
• FDA-approved medications for pheochromocytoma include:
  • Phenoxybenzamine - indicated to control episodes of hypertension and sweating in pheochromocytoma 3
  • Metyrosine - indicated for preoperative preparation, management when surgery is contraindicated, and chronic treatment of malignant pheochromocytoma 4
• Both selective α1-blockers (doxazosin, prazosin, terazosin) and non-selective blockers (phenoxybenzamine) are effective, with phenoxybenzamine potentially providing better intraoperative hemodynamic stability 1, 5
• Beta-blockers should only be added after adequate alpha blockade to control tachyarrhythmias, never before alpha blockade to avoid unopposed alpha stimulation 1
• Calcium channel blockers may be used as adjuncts to alpha-blockers for refractory hypertension 1, 6

Volume Expansion

• High-sodium diet and administration of 1-2 liters of saline 24 hours prior to surgery, along with compressive stockings, should be employed to reduce the risk of orthostatic and postoperative hypotension 1

Surgical Management

• Laparoscopic adrenalectomy is the preferred approach for most pheochromocytomas, showing better intraoperative hemodynamic stability compared to open surgery 1
• Open surgery should be considered for tumors with high suspicion of malignancy, large size (>6 cm), or local invasion 1
• For pregnant patients with pheochromocytoma diagnosed in the first 24 weeks of gestation, laparoscopic adrenalectomy after alpha-adrenergic blockade is recommended 6
• If diagnosed in the third trimester, medical management until fetal viability followed by cesarean section with tumor removal in the same session is recommended 6

Intraoperative Management

• Hypertension during surgery may be treated with magnesium sulfate, intravenous phentolamine, calcium antagonists, nitroprusside, or nitroglycerin 1
• Tachycardia can be treated with intravenous esmolol 1
• Careful monitoring and management of hemodynamic parameters is essential throughout the procedure 1, 7

Postoperative Care

• Aggressive treatment of postoperative hypotension is essential due to the sudden decrease in catecholamine levels 8
• Close monitoring of blood glucose levels is crucial as hypoglycemia commonly occurs after the reduction of catecholamine levels 8
• For patients undergoing bilateral adrenalectomy:
  • High-dose hydrocortisone (150 mg/day) should be administered during the immediate postoperative period 8
  • Maintenance therapy includes oral hydrocortisone 15-25 mg/day in divided doses and fludrocortisone (0.05-0.2 mg daily) for mineralocorticoid replacement 8

Special Considerations

Malignant Pheochromocytoma

• Cytoreductive (R2) resection may improve quality of life and survival in malignant pheochromocytoma by reducing tumor burden and controlling hormonal hypersecretion 1
• Metyrosine is indicated for chronic treatment of patients with malignant pheochromocytoma 4

Bilateral Disease

• For patients with high risk of metachronous disease, cortical-sparing techniques may be considered, but must be weighed against the risk of incomplete tumor removal 1

Pregnancy

• When pheochromocytoma is diagnosed during pregnancy, early recognition and proper treatment are crucial, as undiagnosed cases have approximately 50% maternal and fetal mortality 6
• With proper management, mortality rates can be reduced to <5% maternal and 15% fetal 6

Follow-up Protocol

• Postoperative biochemical testing should be performed 2-8 weeks after surgery to confirm complete resection 1
• Imaging should be done at 3-6 months postoperatively to verify complete tumor removal 1
• Regular monitoring of chromogranin A and metanephrines is recommended every 3-4 months for the first 2-3 years 8
• Lifelong surveillance with increased intervals is recommended for patients with malignant or hereditary pheochromocytoma 1

Common Pitfalls and Caveats

• Never initiate beta-blockers before adequate alpha blockade, as this can lead to unopposed alpha stimulation and hypertensive crisis 1
• In patients with autonomic hyperreactivity due to suspected amphetamine or cocaine intoxication with pheochromocytoma, treatment with benzodiazepines should be initiated first 6
• Labetalol has been associated with acceleration of hypertension in individual cases of pheochromocytoma and should be used with caution 6