Endocrine: Pheochromocytoma

Definition

• Pheochromocytoma: Neural Crest/Chromaffin Cell Tumor of the Adrenal Medulla
  • Pheochromocytoma of the Adrenal Medulla is More Common (85%) than Extraadrenal Sites
• Paraganglioma: Extra-Adrenal Neural Crest/Chromaffin Cell Tumor
  • Most Common Extraadrenal Site: Organ of Zuckerkandl
  • Extra-Adrenal Sites Secrete Norepinephrine Not Epinephrine (Missing PNMT from Adrenal Medulla)

Genetic Associations

• MEN 2A (RET)
• MEN 2B (RET)
• Von Hippel Lindau Syndrome (VHL)
• Neurofibromatosis Type 1 (NF1)
• Many Others: Paraganglioma Syndromes, Carney Triad, etc.
• *Familial Causes are More Likely to Be Bilateral, Benign, Present at Younger Age & Have Extraadrenal Tumors

Rule of 10’s

• 10% Bilateral
• 10% Extra-Adrenal (Paraganglioma)
• 10% Malignant
• 10% Multifocal
• 10% Pediatrics
• 10% without Hypertension
• 10% Incidentally Discovered
• *Previously Believed 10% Familial, Although Recent Genetic Studies Find This to be Underestimated & Closer to 50%

Presentation

• Often Present with Symptomatic “Spells” at Varying Intervals that May be Induced by Anxiety or Exertion
• Classic Triad:
  • Headaches
  • Palpitations
  • Diaphoresis
• Episodic HTN
• Anxiety
• Tremors
• Heat Intolerance
• Chest Pain
• Feeling of Impending Doom

Diagnosis

• Screening: Plasma Metanephrines
  • Plasma is More Sensitive but Not Diagnostic
  • High Fales-Positive Rate (10%)
    • Causes of False Elevation:
      • Antidepressants & Antipsychotics
      • Cocaine & Amphetamines
      • Coffee & Tea
      • Beer & Wine
      • Some Fruits & Vegetables
      • Chocolate & Vanilla
      • α/β-Blockers
  • Can Limit False-Positives if Testing After a Period of Rest & Overnight Fast
• Diagnosis: 24-Hour Urine Metanephrines
• Do Not FNA/Biopsy – Can Induce Hypertensive Crisis

Localization

• Primary Imaging: Adrenal CT or MRI
• Metaiodobenzylguanidine (MIBG) Scan
  • Functional Imaging Excellent for Localizing Extra-Adrenal Sites
  • Frequently Unnecessary
  • General Indications:
    • Tumors Not Found on CT/MRI
    • Localizing Paragangliomas
    • Large Pheochromocytomas Concerning for Malignancy
• Other Possible Modalities:
  • PET/CT
  • Somatostatin Receptor Scintigraphy

Treatment

• Primary Treatment: Unilateral Adrenalectomy
  • *See Endocrine: Adrenalectomy
  • Bilateral Nodules: Bilateral Subtotal Cortical-Sparing Adrenalectomy
  • Unresectable: Surgical Debulking
  • Paraganglioma: Surgical Resection
• Intraoperative Management:
  • First Step: Ligate Adrenal Vein (Avoid Catecholamine Spillage with Handling)
  • Excellent Communication with Anesthesia is Critical (Especially When Ligating the Adrenal Vein – May See Rapid Hypotension)
  • Preferred Medications for Intraoperative Hypertension: Nitroprusside or Esmolol

Preoperative Management

• First Step: α-Blockade Mn
  • Unopposed α-Stimulation Can Cause Hypertensive Crisis, CVA & MI
  • Preferred Regimen: Phenoxybenzamine (Nonselective & Irreversible α-Blocker) 10 mg BID for 1-2 Weeks
    • Can Increase 10-20 mg Every 3 Days if Needed
  • Goals for Appropriate Dosing: BP < 130/80, Mildly Orthostatic & Dry Nasal Mucosa/”Stuffy Nose”
  • Alternative Regimens:
    • Selective α-Blockers (Prazosin, Doxazosin or Terazosin)
    • CCB (Nifedipine, Verapamil, Nicardipine or Amlodipine)
• Second Step: β-Blockade if Needed for Reflex Tachycardia
  • Wait to Start ≥ 2 Days After Initiation of α-Blockade
• Additional Considerations:
  • High-Salt Diet to Restore Fluid Volume
  • Metyrosine (Tyrosine Hydroxylase Inhibitor) May Be Used to Control Hypertension from Unresectable Tumors – Use Limited Due to Significant Side Effects