What is Pheochromocytoma?

Pheochromocytoma: Definition and Clinical Significance

Pheochromocytoma is a rare catecholamine-producing tumor originating from chromaffin cells of the adrenal medulla, causing potentially life-threatening hypertension and cardiovascular complications due to excess catecholamine secretion. 1

Epidemiology and Prevalence

• Rare tumors with annual incidence of 0.1 to 0.6 per 100,000 population 1
• Account for approximately 4% of adrenal incidentalomas 1
• Higher prevalence found in autopsy series
• Approximately 30% of cases are hereditary with genetic mutations 1

Pathophysiology

• Develop from neuroendocrine cells derived from neural crest stem cells 1
• Produce and secrete excess catecholamines (norepinephrine, epinephrine, dopamine)
• Located primarily in adrenal medulla (90% of cases) 1
• Extra-adrenal tumors (paragangliomas) account for 10% of cases 1

Clinical Presentation

Catecholamine excess leads to characteristic symptoms:

• Hypertension: May be sustained or paroxysmal (episodic)
• Classic triad: Headaches, palpitations, and episodic sweating 1
• Other symptoms include:
  • Pallor
  • Anxiety/apprehension
  • Tremor
  • Weight loss
  • Hyperglycemia
  • Orthostatic hypotension (in epinephrine-predominant tumors) 1

Diagnosis

Diagnosis relies on:

1. Biochemical confirmation:

   • Measurement of plasma free metanephrines (sensitivity 96-100%, specificity 89-98%) 1
   • Urinary fractionated metanephrines (sensitivity 86-97%, specificity 86-95%) 1
   • Levels typically >4 times the upper limit of normal in true pheochromocytoma

2. Imaging studies:

   • CT or MRI as initial imaging modality 1
   • MRI typically shows high signal intensity on T2-weighted images 2
   • Functional imaging with metaiodobenzylguanidine (MIBG) scintigraphy or FDOPA-PET for suspected multifocal disease 1

Genetic Considerations

• Approximately 30-35% of cases are hereditary 1
• Associated genetic syndromes include:
  • Multiple Endocrine Neoplasia type 2 (MEN2)
  • Von Hippel-Lindau syndrome (VHL)
  • Neurofibromatosis type 1 (NF1)
  • Succinate dehydrogenase (SDHx) mutations
  • TMEM127 and MAX mutations 1
• Genetic testing should be considered, particularly in:
  • Young patients
  • Bilateral tumors
  • Extra-adrenal location
  • Family history of pheochromocytoma or related syndromes

Treatment

• Surgical resection is the only curative treatment 3, 4
• Preoperative management is critical:
  • Alpha-adrenergic blockade (typically with phenoxybenzamine or doxazosin) must be initiated first
  • Beta-blockers may be added after adequate alpha blockade
  • Volume expansion is often necessary
• Laparoscopic adrenal-sparing surgery is the preferred approach when feasible 3

Prognosis and Follow-up

• Excellent prognosis with timely removal of benign tumors 5
• Approximately 10-15% of tumors are malignant, with higher rates in SDHB mutation carriers 1
• Long-term follow-up includes annual surveillance with plasma metanephrines 1
• Poor prognosis in patients with metastatic disease 5

Special Considerations

• In NF1 patients, pheochromocytoma should be considered in those with hypertension who are over 30 years of age, pregnant, or have paroxysmal symptoms 1
• Pheochromocytomas can have atypical imaging features, including cystic, hemorrhagic, or calcific changes, making diagnosis challenging 2
• Biochemical or imaging screening in asymptomatic patients without genetic predisposition is not recommended 1

Pheochromocytoma represents an important, potentially lethal condition that requires high clinical suspicion, appropriate biochemical testing, and timely surgical intervention to prevent devastating cardiovascular complications.