Pheochromocytoma

Pheochromocytoma is a rare tumor that develops in the chromaffin cells of the adrenal medulla, causing excessive production of catecholamines (adrenaline and noradrenaline). These tumors can trigger life-threatening hypertensive crises and, if left untreated, may lead to stroke, heart attack, or other serious complications. While 90% are benign, all pheochromocytomas require treatment due to their potential for severe cardiovascular effects.

⚠️ Hypertensive Crisis Emergency

Seek immediate emergency care for: severe headache with blood pressure >180/120, chest pain, severe anxiety or panic, profuse sweating, rapid heartbeat, or vision changes. These may indicate a pheochromocytoma crisis requiring immediate treatment.

Medical Disclaimer: This information is for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for diagnosis and treatment of any medical condition.

Understanding Pheochromocytoma

Pheochromocytomas arise from chromaffin cells, which normally produce catecholamines as part of the body's stress response. When these cells become tumorous, they produce excessive amounts of these hormones, leading to episodic or sustained symptoms.

Key Facts

  • Incidence: 2-8 cases per million people annually
  • Can occur at any age, peak 40-50 years
  • Equal distribution between genders
  • 90% are benign, 10% malignant
  • 90% arise in adrenal glands
  • 10% are bilateral
  • 10% occur in children
  • 10% are familial
  • 10% are extra-adrenal (paragangliomas)
  • 10% are malignant

The "Rule of 10s"

Historically, pheochromocytomas were described by the "rule of 10s" - though modern data shows these percentages vary:

  • 10% are bilateral
  • 10% are extra-adrenal
  • 10% are malignant
  • 10% occur in children
  • 10% are familial (now known to be up to 40%)
  • 10% are not associated with hypertension

Signs and Symptoms

Classic Triad

The classic triad occurs in about 40% of patients:

  1. Severe headaches: Pounding, throbbing
  2. Excessive sweating: Profuse, drenching
  3. Palpitations: Rapid, forceful heartbeat

Common Symptoms

  • Hypertension:
    • Sustained in 50%
    • Paroxysmal (episodic) in 45%
    • Normal blood pressure in 5%
  • Cardiovascular:
    • Chest pain
    • Shortness of breath
    • Orthostatic hypotension
    • Arrhythmias
  • Neurological:
    • Anxiety or panic attacks
    • Tremors
    • Pallor
    • Nervousness
  • Metabolic:
    • Weight loss
    • Heat intolerance
    • Hyperglycemia
  • Gastrointestinal:
    • Nausea
    • Abdominal pain
    • Constipation

Paroxysmal Attacks

Episodic symptoms may be triggered by:

  • Physical activity or position changes
  • Abdominal pressure or massage
  • Certain medications
  • Foods high in tyramine
  • Emotional stress
  • Anesthesia
  • Childbirth

Attack Characteristics

  • Duration: Few minutes to hours
  • Frequency: Daily to monthly
  • Severity: Mild to life-threatening
  • Pattern: Often unpredictable

Causes and Risk Factors

Sporadic Cases (60-70%)

  • No identifiable cause
  • Random genetic mutations
  • Usually single tumors
  • Older age at presentation

Hereditary Syndromes (30-40%)

Multiple Endocrine Neoplasia Type 2 (MEN2)

  • RET gene mutations
  • Associated with:
    • Medullary thyroid cancer
    • Parathyroid adenomas
    • Often bilateral pheochromocytomas

Von Hippel-Lindau Disease (VHL)

  • VHL gene mutations
  • Associated with:
    • Retinal angiomas
    • CNS hemangioblastomas
    • Renal cell carcinoma
    • Pancreatic tumors

Neurofibromatosis Type 1 (NF1)

  • NF1 gene mutations
  • Associated with:
    • Café-au-lait spots
    • Neurofibromas
    • 1-5% develop pheochromocytomas

Hereditary Paraganglioma-Pheochromocytoma Syndromes

  • SDH gene mutations (SDHB, SDHC, SDHD)
  • Higher risk of malignancy
  • Often extra-adrenal tumors
  • Family screening important

Diagnosis

Biochemical Testing (First Step)

Diagnosis requires biochemical evidence of catecholamine excess:

Plasma Free Metanephrines

  • Most sensitive test (97-99%)
  • Preferred initial test
  • Patient should be supine for 30 minutes
  • Avoid caffeine, acetaminophen before test
  • Results 3-4x upper normal highly suggestive

24-Hour Urine Metanephrines

  • Alternative first-line test
  • High sensitivity and specificity
  • Requires complete collection
  • Dietary restrictions may apply

Additional Tests

  • Plasma catecholamines (less sensitive)
  • Urine catecholamines
  • Chromogranin A (tumor marker)

Imaging Studies (After Biochemical Confirmation)

CT Scan

  • First-line imaging
  • 90-95% sensitivity
  • Shows adrenal masses >1cm
  • Avoid IV contrast initially

MRI

  • T2 "light bulb" bright signal
  • Better for extra-adrenal tumors
  • Safe in pregnancy
  • No radiation exposure

Functional Imaging

  • MIBG Scan:
    • I-123 MIBG scintigraphy
    • 90% sensitivity
    • Helps locate extra-adrenal tumors
  • PET Scans:
    • FDG-PET for malignant tumors
    • DOTATATE-PET increasingly used
    • Higher sensitivity than MIBG

Genetic Testing

  • Recommended for all patients
  • Up to 40% have germline mutations
  • Affects management and screening
  • Important for family members

Treatment

Preoperative Management

Critical to prevent intraoperative hypertensive crisis:

Alpha-Blockade (First Priority)

  • Phenoxybenzamine:
    • Non-selective, irreversible
    • Start 10-14 days before surgery
    • Titrate to blood pressure control
    • Target: mild orthostatic hypotension
  • Selective alpha-blockers:
    • Doxazosin, prazosin, terazosin
    • Reversible blockade
    • May be adequate for some patients

Beta-Blockade (Only After Alpha-Blockade)

  • Never give before alpha-blockade
  • Controls tachycardia and arrhythmias
  • Propranolol or atenolol commonly used
  • Start 2-3 days after alpha-blockade

Additional Medications

  • Metyrosine: Inhibits catecholamine synthesis
  • Calcium channel blockers: Additional BP control
  • Volume expansion: Liberal salt and fluids

Surgical Treatment

Approach

  • Laparoscopic adrenalectomy:
    • Preferred for tumors <6cm
    • Less morbidity
    • Shorter recovery
  • Open surgery:
    • Large tumors (>6cm)
    • Suspected malignancy
    • Paragangliomas

Perioperative Management

  • Experienced anesthesia team essential
  • Arterial line monitoring
  • Central venous access
  • Vasopressors and vasodilators available
  • Monitor for hypoglycemia post-op

Treatment of Malignant Disease

  • Surgery: Debulking when possible
  • I-131 MIBG therapy: For MIBG-avid tumors
  • Chemotherapy: CVD regimen
  • Radiation: For bone metastases
  • Targeted therapy: Sunitinib, cabozantinib
  • Peptide receptor radionuclide therapy: DOTATATE

Follow-up and Monitoring

Postoperative Monitoring

  • 2-4 weeks post-op:
    • Plasma/urine metanephrines
    • Blood pressure monitoring
    • Check for residual disease
  • Annual lifelong:
    • Biochemical testing
    • Blood pressure checks
    • Screen for recurrence

Genetic Syndrome Surveillance

  • Screen for associated tumors
  • Family member testing
  • Earlier and more frequent monitoring
  • Genetic counseling

Malignant Disease Monitoring

  • More frequent biochemical testing
  • Regular imaging (CT/MRI)
  • Functional imaging as needed
  • Monitor for metastases

Special Considerations

Pregnancy

  • High maternal and fetal mortality if undiagnosed
  • Diagnose with plasma metanephrines
  • MRI for localization (no radiation)
  • Alpha-blockade with phenoxybenzamine
  • Surgery in second trimester if possible
  • Combined C-section and tumor removal

Pediatric Considerations

  • Higher likelihood of genetic syndrome
  • More often bilateral
  • Sustained hypertension more common
  • Genetic testing mandatory
  • Lifelong surveillance needed

Crisis Management

  • IV phentolamine for hypertensive crisis
  • Avoid beta-blockers until alpha-blocked
  • Nitroprusside for severe hypertension
  • Volume resuscitation
  • ICU monitoring

Prognosis

Benign Pheochromocytoma

  • Excellent prognosis with complete resection
  • Cure rate >95%
  • Hypertension resolution in 75%
  • 5-year recurrence rate: 5-15%
  • Normal life expectancy if cured

Malignant Pheochromocytoma

  • 5-year survival: 40-70%
  • Better prognosis with:
    • Complete initial resection
    • Slow disease progression
    • Response to therapy
  • Common metastatic sites:
    • Bones
    • Liver
    • Lungs
    • Lymph nodes

Factors Affecting Outcome

  • Early diagnosis and treatment
  • Proper preoperative preparation
  • Experienced surgical team
  • Genetic syndrome presence
  • Tumor size and location
  • Malignant features