Why do we check urine catecholamines (catecholamine levels) in patients with syncope (fainting)?

Urine Catecholamines in Syncope Evaluation

Urine catecholamines are primarily checked in syncope evaluation to screen for pheochromocytoma and catecholaminergic polymorphic ventricular tachycardia (CPVT), both of which can cause life-threatening arrhythmias and sudden death if undiagnosed.

Role in Pheochromocytoma Detection

Pheochromocytoma is a rare but potentially lethal cause of syncope that presents with:

• Paroxysmal hypertension
• Headaches
• Palpitations
• Sweating
• Syncope during hypertensive episodes

The 2017 ACC/AHA/HRS Syncope Guidelines recommend targeted testing based on clinical suspicion rather than routine screening 1. When pheochromocytoma is suspected:

• Fractionated plasma metanephrines offer the highest sensitivity (97-100%) 2, 3
• 24-hour urinary metanephrines and catecholamines provide better specificity (98% vs 85% for plasma) 2
• Overnight urine collections may provide better diagnostic sensitivity and specificity (100% sensitivity, 98% specificity) compared to 24-hour collections 4

Role in Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)

The 2017 ACC/AHA/HRS guidelines specifically mention exercise testing to screen for CPVT in patients with exertional syncope 1. CPVT is characterized by:

• Exercise-induced ventricular arrhythmias
• Syncope during physical activity or emotional stress
• Normal resting ECG
• Family history of sudden cardiac death

For patients with suspected CPVT and syncope:

• Exercise restriction is recommended (Class I) 1
• Beta blockers without intrinsic sympathomimetic activity are first-line therapy (Class I) 1
• ICD therapy is reasonable for those with exercise/stress-induced syncope despite optimal medical therapy (Class IIa) 1

When to Consider Catecholamine Testing

Urine catecholamines should be considered when:

1. Syncope occurs with paroxysmal hypertension
2. Syncope occurs during exercise or emotional stress
3. Patient has adrenal mass with incidental finding
4. Family history of pheochromocytoma or MEN syndromes
5. Episodic symptoms of headache, sweating, and palpitations preceding syncope

Testing Approach

For suspected pheochromocytoma:

• Fractionated metanephrines (normetanephrine and metanephrine) are preferred for initial screening 5
• Avoid using total metanephrines, total catecholamines, or VMA alone due to lower sensitivity 5
• Consider timing of collection (overnight may be superior to 24-hour) 4

Common Pitfalls

1. False positives can occur due to:

   • Medications (tricyclic antidepressants, MAOIs, sympathomimetics)
   • Acute stress or illness
   • Contrast media administration 6

2. False negatives can occur with:

   • Intermittent catecholamine secretion
   • Pure epinephrine-secreting tumors (may have normal VMA) 5
   • Small or asymptomatic tumors

3. Inappropriate testing when more common causes of syncope haven't been ruled out:

   • Cardiac arrhythmias
   • Vasovagal syncope
   • Orthostatic hypotension

Integration with Broader Syncope Evaluation

Catecholamine testing should be part of a targeted approach based on clinical suspicion, not routine screening. The 2017 ACC/AHA/HRS guidelines emphasize that:

• Routine laboratory testing has low diagnostic yield 1
• Targeted testing based on history, physical exam, and ECG is reasonable (Class IIa) 1
• Exercise testing is useful for syncope occurring during exertion (Class IIa) 1

Remember that cardiac causes of syncope carry the highest mortality risk, so evaluation should prioritize ruling out arrhythmias and structural heart disease before pursuing rarer endocrine causes.