Pheochromocytoma Symptoms and Treatment
The classic triad of symptoms for pheochromocytoma includes headaches, palpitations, and sweating, typically occurring in an episodic fashion, with this combination having a diagnostic specificity of 90%. 1
Clinical Presentation
Common Symptoms
- Hypertension: Present in approximately 95% of patients
- 50% have sustained hypertension
- Characterized by increased blood pressure variability
- Often resistant to conventional treatment
- Classic triad (highly specific when occurring together):
- Headaches (often severe)
- Palpitations
- Episodic sweating
- Other common symptoms:
- Anxiety/tremor
- Pallor
- Nausea
- Weakness
- Abdominal or chest pain
- Weight loss
Important Clinical Considerations
- Symptoms are often paroxysmal (occurring in episodes)
- Blood pressure variability is a hallmark feature, related to the level of norepinephrine secretion by the tumor 1
- Despite improved diagnostic techniques, there remains an average 3-year delay between initial symptoms and final diagnosis 1
- Many cases are missed altogether, with autopsy studies showing tumors contributed to 55% of deaths and were not suspected in 75% of cases 1
Diagnostic Approach
First-Line Testing
- Plasma free metanephrines (normetanephrine and metanephrine) is the best screening test with 99% sensitivity and 89% specificity 1, 2
- Plasma metanephrines ≥4 times upper limit of normal are consistent with disease 2
- Levels 2-4 times upper limit of normal require repeat testing in 2 months 2
Additional Testing
- 24-hour urine collection for catecholamines and metanephrines if plasma testing is equivocal 2
- Plasma methoxytyramine measurement can help assess malignancy risk 2
Imaging
- MRI is preferred over CT scan if pheochromocytoma is strongly suspected (to avoid risk of hypertensive crisis with IV contrast) 2
- Adrenal protocol CT or MRI should be performed to evaluate adrenal masses 2
- Functional imaging options:
- Meta-iodobenzylguanidine (MIBG) scintigraphy if conventional imaging is negative
- FDOPA-PET for hereditary syndromes
- FDG-PET for potentially malignant lesions 2
Treatment Approach
Preoperative Management
Alpha-adrenergic blockade is essential and should be started if:
Beta-blockers should only be added after adequate alpha-blockade if tachycardia persists 2, 3
- Adding beta-blockers before alpha-blockade can worsen hypertension
Duration: Alpha blockade should be maintained for 10-14 days before surgery 2
Surgical Management
- Laparoscopic adrenalectomy is recommended for small tumors (<8 cm) without invasion 2
- Open surgery is recommended for larger tumors (>5-6 cm) or with evidence of invasion 2
- Complete surgical resection (R0) is the mainstay of potentially curative treatment 2
Postoperative Surveillance
- Plasma/urine metanephrines should be measured 8 weeks post-surgery 2
- Imaging should be performed at 3-6 months post-surgery 2
- Continue surveillance for at least 10 years, with lifelong follow-up for genetic cases 2
Management of Metastatic Disease
- Radiopharmaceuticals (131I-MIBG)
- Locoregional ablative procedures
- Combination chemotherapy (cyclophosphamide, vincristine, dacarbazine)
- For SDHx-related metastatic disease: temozolomide or tyrosine kinase inhibitors 2
Genetic Considerations
- Approximately 30% of pheochromocytomas are hereditary 1
- Genetic testing should be considered in all patients, especially those with:
- Young age at diagnosis
- Bilateral or multifocal disease
- Extra-adrenal location
- Family history 2
Common Pitfalls
- Failing to consider pheochromocytoma in patients with labile hypertension
- Administering beta-blockers before adequate alpha blockade
- Performing fine needle biopsy of suspected pheochromocytoma (can precipitate hypertensive crisis)
- Missing the diagnosis, which can be fatal if untreated, especially during surgery or other stressful procedures 4
- Inadequate preoperative alpha blockade leading to intraoperative hypertensive crisis