What is the recommended initial pre‑operative pharmacologic management for a newly diagnosed pheochromocytoma, including drug choices, dosing, and duration?

Initial Management of Pheochromocytoma

Immediate Preoperative Medical Management

Alpha-adrenergic blockade must be initiated within 24-48 hours of diagnosis and continued for 7-14 days before any surgical intervention to prevent perioperative hypertensive crises and reduce mortality. 1, 2, 3

Alpha-Blocker Selection and Dosing

• First-line agents: Phenoxybenzamine, doxazosin, prazosin, or terazosin are all acceptable options 1, 4
• Phenoxybenzamine: Non-selective, irreversible alpha-blocker; traditionally considered the gold standard 4, 5
• Doxazosin: Selective α1-blocker with controlled-release formulation; has minimal adverse reactions, high safety profile, and easier administration compared to phenoxybenzamine 5
• Dosing strategy: Gradually titrate upward over the 7-14 day preparation period to achieve target blood pressure goals 1, 2

Blood Pressure Targets

• Supine BP: <130/80 mmHg 1, 2, 3
• Standing systolic BP: >90 mmHg (to avoid excessive orthostatic hypotension) 1, 2, 3
• Monitor orthostatic vital signs closely as patients often have relative hypovolemia despite alpha-blockade 1

Sequential Addition of Other Antihypertensives

Critical sequencing rule: Never initiate beta-blockers before adequate alpha-blockade is established, as this causes unopposed alpha-adrenergic stimulation and can precipitate fatal hypertensive crisis 1, 3, 6

• Beta-blockers: Add ONLY after adequate alpha-blockade to control tachyarrhythmias or persistent tachycardia; preferably use β1-selective agents 1, 3
• Calcium channel blockers: Can be added as adjunctive therapy for refractory hypertension despite adequate alpha-blockade; amlodipine is commonly used 1, 7
• Alternative approach: Calcium channel blockers may be used as presurgical monotherapy in patients with normal-to-mildly elevated blood pressure or when severe orthostatic hypotension limits alpha-blocker use 1

Preoperative Volume Expansion (Critical Step)

• High-sodium diet throughout the preparation period 1, 3
• Intravenous saline: Administer 1-2 liters of isotonic saline over the 24 hours preceding surgery 1, 2, 3
• Rationale: Prevents postoperative hypotension caused by peripheral hypovolemia that occurs after catecholamine levels drop suddenly 1
• Compression stockings should also be employed 3

Duration of Medical Preparation

Minimum 7-14 days of alpha-blockade before surgery 1, 2, 3

• Most patients require 10-14 days to achieve adequate blockade 7, 2
• The maximum biochemical effect of catecholamine suppression occurs within 2-3 days, but hemodynamic stabilization requires the full preparation period 8

Adjunctive Preoperative Medication

Metyrosine (Tyrosine Hydroxylase Inhibitor)

• Mechanism: Inhibits the rate-limiting step in catecholamine biosynthesis, reducing endogenous catecholamine production by 35-80% 8
• Dosing: 1-4 grams per day in divided doses 8
• Effect timeline: Maximum biochemical effect within 2-3 days; catecholamine levels return to baseline 3-4 days after discontinuation 8
• Clinical benefit: Decreases frequency and severity of hypertensive attacks, headache, nausea, sweating, and tachycardia 8
• Note: While FDA-approved, metyrosine is not routinely mentioned in recent guidelines as first-line therapy but may be considered for severe cases 8

Diagnostic Workup (Concurrent with Medical Preparation)

• Imaging: Obtain CT or MRI of abdomen immediately to localize tumor and assess for bilateral disease, extra-adrenal paragangliomas, or metastases 2, 3
• Absolute contraindication: Do NOT perform biopsy of suspected pheochromocytoma—this can trigger fatal hypertensive crisis 2, 3

Intraoperative Management Preparation

Be prepared to treat intraoperative hypertensive crises with: 1, 3, 9

• Magnesium sulfate
• Phentolamine (5 mg IV for adults, 1 mg for children) 10
• Calcium antagonists
• Sodium nitroprusside
• Nitroglycerin
• Remifentanil (short-acting opioid with sympatholytic properties) 9

Postoperative Monitoring (First 48-72 Hours)

• Hypotension: Anticipate and aggressively treat with fluid resuscitation; norepinephrine may be required 2, 3, 10
• Hypoglycemia: Monitor glucose levels closely as catecholamine withdrawal causes rapid decline in counter-regulatory hormones 1, 2, 3
• Blood pressure: Wean antihypertensive medications as tolerated 3

Biochemical Confirmation of Cure

• Measure plasma or urine metanephrines at 2-8 weeks post-surgery to confirm complete tumor removal 2, 3

Common Pitfalls to Avoid

• Never use beta-blockers first: This is the most dangerous error—always establish alpha-blockade first 1, 3, 6
• Inadequate preparation duration: Rushing to surgery before 7-14 days of medical preparation increases perioperative mortality 1, 2
• Insufficient volume expansion: Failure to administer saline and high-sodium diet leads to severe postoperative hypotension 1, 3
• Performing biopsy: This is absolutely contraindicated 2, 3

Special Population: Pregnancy

• First 24 weeks gestation: Laparoscopic adrenalectomy after 10-14 days of alpha-blockade 7
• Third trimester: Medical management until fetal viability, then cesarean section with tumor removal in same session 7
• Maternal mortality: <5% with proper management vs. 50% if undiagnosed 7