What is the recommended workup and treatment guideline for pheochromocytoma?

Workup and Management of Pheochromocytoma

The initial step in diagnosing pheochromocytoma is measurement of plasma free metanephrines, which has the highest sensitivity (96-100%) and specificity (89-98%) as a single test, followed by appropriate imaging only after biochemical confirmation. 1

Diagnostic Algorithm

Step 1: Biochemical Testing

• First-line test: Plasma free metanephrines (collected after patient has been lying supine for 30 minutes)

  • Sensitivity: 96-100%, Specificity: 89-98%
  • Results >4 times upper limit of normal are consistent with pheochromocytoma 1

• Alternative first-line test: 24-hour urinary fractionated metanephrines

  • Sensitivity: 86-97%, Specificity: 86-95% 1

• For borderline elevations: Clonidine suppression test

  • 100% specificity and 96% sensitivity 1

Step 2: Imaging (Only After Biochemical Confirmation)

• First-line imaging: CT scan of the abdomen 1
• Alternative imaging: MRI 1
• Functional imaging for suspected metastatic disease:
  • 18F-FDG PET (preferred for SDHB-related metastatic disease)
  • 18F-FDOPA PET (highest sensitivity for head and neck paragangliomas)
  • 123I-MIBG scintigraphy (recommended for non-metastatic adrenal pheochromocytoma) 1

Step 3: Genetic Testing

• Consider in all patients, especially those with:
  • Young age at diagnosis
  • Bilateral or multifocal disease
  • Extra-adrenal location
  • Family history of pheochromocytoma 1
• Common genetic mutations: SDHx, VHL, RET, NF1, TMEM127, MAX 1

Management Protocol

Preoperative Management

1. Alpha-adrenergic blockade (10-14 days before surgery):

   • Non-selective α-blocker: Phenoxybenzamine (40-80 mg/day) 2
   • Selective α1-blockers: Doxazosin, prazosin, or terazosin 1

2. Beta-blockers only after adequate alpha-blockade if tachycardia or arrhythmias develop 1

3. Volume expansion:

   • High-sodium diet
   • 1-2 liters saline infusion 24 hours before surgery
   • Compressive stockings 1

4. Blood pressure targets:

   • <130/80 mmHg in supine position
   • Systolic BP >90 mmHg in upright position 1

5. Alternative medication: Metyrosine can be used for preoperative preparation 3

Surgical Management

• Preferred approach: Laparoscopic adrenalectomy for small tumors (<8 cm) without invasion
• Open surgery for larger tumors (>5-6 cm) or with evidence of invasion 1
• Complete surgical resection (R0) is the mainstay of potentially curative treatment 1

Management of Inoperable/Malignant Disease

• Medical options:
  • Metyrosine for chronic treatment of malignant pheochromocytoma 3
  • Phenoxybenzamine to control episodes of hypertension and sweating 2
  • Radiopharmaceuticals (131I-MIBG)
  • Locoregional ablative procedures
  • Combination chemotherapy (CVD: cyclophosphamide, vincristine, dacarbazine) 1

Follow-up Protocol

• Immediate post-treatment:

  • Measure plasma or urine metanephrines by 8 weeks post-surgery
  • Imaging at 3-6 months post-surgery 1

• Long-term follow-up:

  • Continue for at least 10 years
  • Regular check-ups every 3-4 months for 2-3 years, then every 6 months
  • Annual biochemical measurements 1
  • Lifelong surveillance for patients with genetic syndromes, extra-adrenal primary disease, tumor size >5 cm, or SDHB mutations 1

Common Pitfalls and Caveats

1. Diagnostic delay: Average delay in diagnosis is 3 years, which increases morbidity and mortality 1

2. Beta-blocker risk: Never administer beta-blockers before alpha-blockade (risk of hypertensive crisis) 1

3. False positives in biochemical testing: Can occur with certain medications, foods, or stress; proper patient preparation is essential

4. Malignancy risk: Approximately 10% of pheochromocytomas are malignant, with 5-year survival less than 50% in these cases 4

5. Recurrence: Can occur decades after initial resection, necessitating long-term follow-up 5

6. Pregnancy considerations: If diagnosed in first 24 weeks, perform laparoscopic adrenalectomy after alpha-blockade; if diagnosed in third trimester, continue medical management until fetus is viable 1

By following this structured approach to diagnosis and management, clinicians can optimize outcomes for patients with pheochromocytoma and minimize associated morbidity and mortality.