What are the symptoms and treatment options for pheochromocytoma, particularly in adults between 20 and 50 years old?

Pheochromocytoma: Symptoms and Clinical Presentation

Pheochromocytoma presents with a classic triad of severe headaches, palpitations, and profuse sweating in the context of hypertension, which when occurring episodically has 90% diagnostic specificity. 1

Cardinal Symptoms

The Classic Triad (High Specificity)

• Severe headaches occur in 72-92% of patients 2
• Profuse sweating (diaphoresis) occurs in 60-70% of patients 2
• Palpitations occur in 51-73% of patients 2
• When all three symptoms occur together in an episodic fashion, diagnostic specificity reaches 90% 1
• Two or more symptoms from this triad are present in the majority of pheochromocytoma patients and are more sensitive than requiring all three 3

Hypertension Patterns

• Hypertension occurs in >90-95% of patients 4, 5, 2
• 50% have sustained (continuous) hypertension 1, 2
• 50% have paroxysmal (episodic) hypertension 1, 2
• The increased blood pressure variability itself is an independent cardiovascular risk factor beyond the elevated pressure 1
• 5% of patients remain normotensive despite active disease 5

Additional Symptoms

• Pallor is suggestive of pheochromocytoma when present 3
• Visual symptoms increase the likelihood of pheochromocytoma 3
• Flank pain is suggestive when present 3
• Unexplained orthostatic hypotension in a hypertensive patient is highly suggestive 3
• Anxiety and panic-like symptoms including cold sweats and tachycardia occur due to catecholamine surges 1

Important Negative Predictor

• Flushing suggests a NON-pheochromocytoma diagnosis 3

Pathophysiology of Symptoms

Pheochromocytomas are catecholamine-producing tumors that cause episodic or sustained release of norepinephrine and epinephrine, acting on alpha and beta-adrenergic receptors throughout the body. 1 This explains why symptoms closely resemble panic attacks and can mimic numerous other conditions. 1, 4

High-Risk Populations Requiring Screening

Mandatory Screening Indications

• Paroxysmal or resistant hypertension with any symptoms from the classic triad 1
• All patients with Multiple Endocrine Neoplasia (MEN) 2a or 2b and their first-degree relatives, even if asymptomatic and normotensive 2
• Neurofibromatosis Type 1 (NF1) patients over age 30 with hypertension, particularly if pregnant or with paroxysmal symptoms 6
• New-onset hypertension with unexplained orthostatic hypotension 3
• Hypertension plus diabetes mellitus or hypermetabolism 2
• Hypertensive crisis during anesthesia induction or radiologic procedures 2
• Incidentally discovered adrenal mass 6

Clinical Scenarios

• Resistant hypertension (not controlled on multiple medications) 6, 3
• Labile hypertension with minimal symptoms still warrants screening 3
• Hypertension-associated headache, palpitations, or sweating 6

Diagnostic Approach

Best Screening Test

Plasma free metanephrines (normetanephrine and metanephrine) is the single best screening test with 99% sensitivity and 89% specificity. 1 This test should be performed under standardized conditions (supine position with indwelling IV cannula). 6

Confirmatory Testing

• If plasma testing is equivocal (less than fourfold elevation), perform 24-hour urine collection for catecholamines and metanephrines 6, 1
• Urinary metanephrine is consistently abnormal in pheochromocytoma patients 3, 2
• Values greater than 1.5-2-fold above the upper limit of normal are highly suggestive and warrant imaging studies 3

Treatment Overview

Preoperative Medical Management (Critical First Step)

Alpha-adrenergic blockade MUST be initiated at least 7-14 days before surgery with gradually increasing dosages. 7, 8 This is non-negotiable for patient safety.

• Target blood pressure: <130/80 mmHg supine AND systolic >90 mmHg standing 7, 8
• Beta-blockers should ONLY be added AFTER adequate alpha blockade to control tachyarrhythmias 7, 1
• NEVER initiate beta-blockers before alpha blockade - this can precipitate fatal hypertensive crisis from unopposed alpha stimulation 7, 1
• Calcium channel blockers can be used as adjuncts for refractory hypertension 6, 7
• High-sodium diet and 1-2 liters of saline 24 hours prior to surgery reduces orthostatic and postoperative hypotension 7

Surgical Management (Definitive Treatment)

Laparoscopic adrenalectomy is the preferred surgical approach and is curative in 90% of cases. 6, 7, 5

• Complete surgical extirpation (R0 resection) is the only curative treatment 6, 7, 8
• Open surgery is reserved for tumors >6 cm, high suspicion of malignancy, or local invasion 7
• Tumors <5 cm can be safely removed laparoscopically 5

Special Populations

For pregnant patients diagnosed in the first 24 weeks of gestation, perform laparoscopic adrenalectomy after 10-14 days of alpha-blockade. 6, 7 If diagnosed in the third trimester, continue medical management until fetal viability, then perform cesarean section with tumor removal in the same session. 6, 7

Critical Pitfalls to Avoid

• NEVER perform fine needle biopsy of suspected pheochromocytoma - this can precipitate fatal hypertensive crisis 8
• NEVER start beta-blockers before alpha-blockade 7, 1
• Monitor for hypoglycemia after surgery due to sudden catecholamine reduction 8
• Perform biochemical testing 2-8 weeks postoperatively to confirm complete resection 8

Long-Term Surveillance

All patients require lifelong surveillance due to 10-15% recurrence risk and 10-12% malignancy rate. 6, 8

• Clinical monitoring every 3-4 months for first 2-3 years, then every 6 months 8
• Biochemical testing (plasma/urine metanephrines) every 3-4 months for 2-3 years, then every 6 months 8
• Continue surveillance for at least 10 years minimum 6