When should pheochromocytoma be suspected in a patient?

When to Suspect Pheochromocytoma

Pheochromocytoma should be suspected in hypertensive patients with the classic triad of headaches, palpitations, and sweating, typically occurring in an episodic fashion, which carries a diagnostic specificity of 90%. 1

Clinical Presentations That Should Trigger Suspicion

High-Risk Clinical Scenarios

• Patients with resistant hypertension (prevalence of pheochromocytoma is 0.1-0.6% in general hypertensive population) 1
• Hypertension with marked blood pressure variability 1
• Hypertension crisis during procedures (surgery, anesthesia, radiological procedures with contrast)
• Patients over 30 years of age with paroxysmal hypertension 1
• Pregnant patients with unexplained hypertension 1
• Hypertension-associated headache, palpitations, or sweating 1
• Patients with NF1 (neurofibromatosis type 1) who develop hypertension 1

Classic Symptom Triad

• Episodic headaches (often described as severe or "the worst headache of my life")
• Palpitations (tachycardia)
• Diaphoresis (excessive sweating)

This classic triad, when occurring together in a hypertensive patient, has a diagnostic specificity of 90% 1

Other Common Symptoms

• Pallor
• Tremor
• Anxiety or panic attack-like symptoms
• Orthostatic hypotension
• Weight loss
• Hyperglycemia or impaired glucose tolerance
• Abdominal pain 2

High-Risk Patient Populations

Genetic Predisposition

• Patients with known genetic syndromes:
  • Neurofibromatosis type 1 (NF1)
  • Multiple endocrine neoplasia (MEN) type 2
  • Von Hippel-Lindau disease
  • Paraganglioma syndromes (SDHx mutations)

Age Considerations

• The median age of presentation in one study was 43 years (range 14-61 years) 1
• However, pheochromocytoma can occur at any age, including in children 2

Diagnostic Pitfalls and Delayed Diagnosis

Despite improved diagnostic techniques, there remains an average of 3 years between initial symptoms and final diagnosis of pheochromocytoma 1. Many cases are missed altogether, with autopsy studies showing that these tumors contributed to 55% of deaths and were not suspected in 75% of cases 1.

Common Misdiagnoses

• Anxiety or panic disorder
• Essential hypertension
• Cardiomyopathy or myocarditis 2
• Hyperthyroidism 3

Recommended Screening Approach

First-Line Testing

• Plasma free metanephrines (normetanephrine and metanephrine) is the best screening test with 99% sensitivity and 89% specificity 1, 4
• Collection should be done after the patient has been lying supine for 30 minutes 4

Alternative Testing

• 24-hour urinary fractionated metanephrines (sensitivity 86-97%, specificity 86-95%) 4
• Clonidine suppression test for borderline elevations (100% specificity, 96% sensitivity) 4

Important Notes on Testing

• Results >4 times upper limit of normal are highly consistent with pheochromocytoma 4
• Biochemical testing should precede imaging studies 4
• Avoid fine needle biopsy in suspected cases due to risk of hypertensive crisis 4

Imaging Considerations

• CT scan of the abdomen is first-line imaging after biochemical confirmation 4
• MRI is preferred in suspected pheochromocytoma due to risk of hypertensive crisis with IV contrast for CT 4
• Functional imaging (MIBG scanning or FDOPA-PET) for suspected metastatic disease 4

Key Takeaways

1. Consider pheochromocytoma in patients with episodic symptoms of headache, palpitations, and sweating, especially with hypertension
2. The diagnosis is often delayed by an average of 3 years, increasing morbidity and mortality
3. Plasma free metanephrines is the most sensitive and specific screening test
4. Early diagnosis and appropriate treatment significantly reduce mortality risk

Remember that although pheochromocytoma is rare, missing the diagnosis can be fatal, making it an important consideration in the differential diagnosis of hypertension, especially when accompanied by the characteristic symptom triad.