What is the management approach for pheochromocytoma?

Management of Pheochromocytoma

Surgical resection is the only curative treatment for pheochromocytoma and must be preceded by 7-14 days of alpha-adrenergic blockade to prevent life-threatening perioperative hypertensive crises. 1, 2

Immediate Diagnostic Confirmation and Risk Mitigation

• Biochemical confirmation requires measurement of plasma free metanephrines (highest sensitivity 97-98%) or 24-hour urinary fractionated metanephrines as the diagnostic test of choice 3
• Initiate alpha-blockade within 24-48 hours of biochemical diagnosis, even before imaging is complete 1, 2
• Never perform biopsy of suspected pheochromocytoma—this is absolutely contraindicated and can precipitate fatal hypertensive crisis 1, 4

Preoperative Medical Preparation (Critical 7-14 Day Window)

Alpha-Blockade Protocol

• Phenoxybenzamine (nonselective alpha-blocker) is FDA-approved for pheochromocytoma and should be titrated gradually over 7-14 days 5, 2
• Alternative: Doxazosin (selective alpha-1 blocker) can be used with similar efficacy 2
• Target blood pressure goals: <130/80 mmHg supine AND systolic >90 mmHg standing 1, 2, 4

Sequential Addition of Other Agents

• Beta-blockers must ONLY be added AFTER adequate alpha-blockade to control reflex tachycardia—never before, as this causes unopposed alpha-stimulation and hypertensive crisis 2, 4
• Calcium channel blockers can be added as adjuncts for refractory hypertension despite adequate alpha-blockade 2

Volume Expansion (Often Overlooked)

• High-sodium diet and 1-2 liters of intravenous saline 24 hours before surgery to prevent postoperative hypotension from sudden catecholamine withdrawal 2, 4
• Compression stockings should be employed to reduce orthostatic hypotension risk 2

Common Pitfall: The literature shows some centers have operated without preoperative alpha-blockade 6, but this approach is not recommended by current guidelines and carries unnecessary risk. The zero mortality achieved with proper alpha-blockade 7 versus historical mortality rates makes preoperative preparation mandatory.

Imaging for Localization

• CT or MRI of abdomen/pelvis immediately after biochemical diagnosis to localize tumor and assess for bilateral disease, extra-adrenal paragangliomas, or metastases 1, 4
• Whole-body imaging with SSTR PET/CT (somatostatin receptor imaging) is first-line for detecting multifocal disease or metastases, particularly in hereditary syndromes 3
• 123I-MIBG scintigraphy can complement anatomic imaging when SSTR PET is unavailable 3

Surgical Approach

Technique Selection

• Laparoscopic adrenalectomy is preferred for most pheochromocytomas and is the standard of care 1, 2, 7
• Open surgery should be considered for tumors >5-6 cm, suspected malignancy, or local invasion 2, 4
• Complete R0 resection (tumor-free margins) is the only curative approach 1, 4

Intraoperative Management

• Hypertensive episodes: Treat with magnesium sulfate, phentolamine, calcium antagonists, nitroprusside, or nitroglycerin 1, 4
• Anticipate postoperative hypotension: Aggressively treat with fluid resuscitation—patients require large volumes (often several liters) in the first 24-48 hours due to changed vascular compliance and residual alpha-blockade effects 1, 8

Critical Timing Note: Hypertensive surges occur most commonly during anesthesia induction rather than tumor manipulation 7, so vigilance is required from the start of the procedure.

Postoperative Care

Immediate Monitoring (First 24-48 Hours)

• Admit to intensive care unit for close hemodynamic monitoring 9
• Monitor glucose levels closely—hypoglycemia commonly occurs after catecholamine levels drop 1, 4
• Large fluid requirements persist for approximately 36 hours (3 half-lives of phenoxybenzamine) 8

Confirmation of Cure

• Measure plasma or urine metanephrines at 2-8 weeks postoperatively to confirm complete tumor removal 1, 2, 4
• Approximately 80% of patients achieve cure of hypertension 7

Lifelong Surveillance (Mandatory for All Patients)

All patients require lifelong follow-up due to 10-15% recurrence risk, even after apparently complete resection 1, 4

Surveillance Schedule

• First 2-3 years: Clinical monitoring (blood pressure, adrenergic symptoms) and biochemical testing (plasma/urine metanephrines, chromogranin A) every 3-4 months 1, 4
• After 2-3 years: Continue same monitoring every 6 months indefinitely 1, 4
• Whole-body MRI at least every 2-3 years to detect recurrence or metastases 4

Genetic Testing (Essential Component)

• All patients with pheochromocytoma should undergo genetic testing as approximately 25-40% have hereditary disease 3, 9
• SDHD pathogenic variants require specialized management with expert interdisciplinary teams due to high rates of multifocal disease and head/neck paragangliomas 3
• Genetic results guide surveillance intensity and family screening 9

Management of Metastatic/Inoperable Disease

When complete surgical resection is not feasible:

First-Line Systemic Therapy

• Peptide receptor radionuclide therapy (PRRT) for SSTR-positive tumors with moderate-to-high tumor burden and slow-to-moderate progression 3
• 131I-MIBG therapy for MIBG-avid tumors, though PRRT is generally preferred for SDHD-related tumors 3
• Disease control rates with PRRT reach ≥80% with progression-free survival of 17-39 months 3

Second-Line Options

• Chemotherapy (CVD regimen: cyclophosphamide, vincristine, dacarbazine) for rapidly progressive disease or high visceral tumor burden 3
• Tyrosine kinase inhibitors (sunitinib) for progression after radionuclide therapy 3
• Temozolomide as alternative when other therapies fail or are contraindicated 3

Important Caveat: TKIs may worsen hypertension, requiring aggressive antihypertensive adjustment during therapy 3

Interdisciplinary Team Approach

• All management decisions should be discussed by an expert interdisciplinary tumor team familiar with pheochromocytoma to ensure optimal outcomes 3
• This is particularly critical for hereditary syndromes, metastatic disease, and complex cases 3