What are the recommended investigations and management for pheochromocytoma?

Investigations and Management of Pheochromocytoma

The recommended diagnostic approach for pheochromocytoma includes biochemical testing with plasma free metanephrines as the first-line test, followed by anatomical imaging with CT/MRI and functional imaging in selected cases, with complete surgical resection as the definitive treatment after proper preoperative alpha-blockade.

Diagnostic Workup

Biochemical Testing

• First-line test: Measurement of plasma free metanephrines - most sensitive and specific single test for detecting pheochromocytoma 1
• If plasma testing is equivocal (less than fourfold elevation), perform 24-hour urine collection for catecholamines and metanephrines 1
• Values greater than 1.5-2 times the upper limit of normal are highly suggestive of pheochromocytoma 2

Imaging Studies

1. Anatomical Imaging:

   • CT or MRI of abdomen is the first-line imaging modality 1
   • MRI is preferred in suspected pheochromocytoma due to risk of hypertensive crisis with IV contrast for CT 1

2. Functional Imaging (when indicated):

   • 123I-MIBG scintigraphy - highly specific for pheochromocytoma 1
   • FDG-PET - particularly useful for malignant pheochromocytomas 1
   • 68Ga-DOTA-SSTa PET or FDOPA-PET - helpful for detecting multifocal disease 1

When to Suspect Pheochromocytoma

• Hypertensive patients over 30 years of age
• Pregnant patients with hypertension
• Patients with paroxysmal hypertension
• Hypertension associated with headache, palpitations, or sweating 1
• Presence of two or more symptoms from the classic triad (headache, palpitations, diaphoresis) 2
• Unexplained orthostatic hypotension in hypertensive patients 2

Management

Preoperative Preparation

1. Alpha-adrenergic blockade:

   • Phenoxybenzamine is indicated for controlling episodes of hypertension and sweating 3
   • Should be initiated 10-14 days before surgery

2. Beta-blockade:

   • Only after adequate alpha-blockade is established
   • Indicated if tachycardia is excessive 3
   • Typically with propranolol 4

3. Perioperative considerations:

   • Meticulous management of hormonal, glucose, electrolytes, cardiac and fluid/blood pressure abnormalities 1
   • Close monitoring during induction of anesthesia, which is often associated with hypertensive surges 4

Surgical Management

• Complete surgical extirpation (R0 resection) is the mainstay of potentially curative approaches 1
• Laparoscopic approach is preferred for small tumors (<5-6 cm) without invasion 1
• Open approach recommended for tumors >5-6 cm or with suspected locoregional disease 1
• For extra-adrenal tumors, approach depends on location:
  • Thoracic PGLs require specialized cardiac surgical expertise
  • Pelvic PGLs require consideration of potential sexual dysfunction 1

Management of Malignant Pheochromocytoma

• Defined by presence of metastasis 1
• Treatment options include:
  • Radiopharmaceuticals (131I-MIBG) for patients with good MIBG uptake 1
  • Combination chemotherapy (cyclophosphamide, vincristine, dacarbazine - CVD) 1
  • Locoregional ablative procedures 1

Follow-up

• Biochemical testing 14 days after surgery to check for remaining disease 1
• Thereafter every 3-4 months for 2-3 years, then every 6 months 1
• For patients with confirmed malignant disease, imaging should be repeated at least every 6 months during the first year and yearly afterward 1
• Lifelong surveillance is recommended for malignant pheochromocytoma 1

Special Considerations

Genetic Testing

• Consider genetic testing as approximately 25% of pheochromocytomas are hereditary 5
• Particularly important in patients with:
  • Extra-adrenal tumors
  • Bilateral adrenal tumors
  • Family history of pheochromocytoma
  • Young age at diagnosis (<50 years)
  • Associated conditions (NF1, VHL, MEN2)

Pitfalls to Avoid

1. Diagnostic pitfalls:

   • Guided biopsies of potentially resectable adrenal tumors are potentially harmful and should be avoided 1
   • Relying solely on symptoms without biochemical confirmation
   • Failing to consider pheochromocytoma in patients with resistant hypertension

2. Management pitfalls:

   • Initiating beta-blockers before adequate alpha-blockade (can worsen hypertension)
   • Inadequate preoperative preparation leading to intraoperative hypertensive crisis
   • Insufficient follow-up duration (should be at least 10 years) 1

By following this structured approach to diagnosis and management, the morbidity and mortality associated with pheochromocytoma can be significantly reduced.