Urine Catecholamine Measurements: Clinical Applications
Primary Diagnostic Purpose
Urine catecholamine measurements are used to screen for and diagnose pheochromocytoma and paraganglioma in adults presenting with hypertension, particularly when accompanied by the classic triad of palpitations, sweating, and headaches. 1
When to Order Urine Catecholamine Testing
Screen patients with the following presentations:
- Resistant hypertension (BP >140/90 mmHg despite optimal doses of ≥3 antihypertensive medications including a diuretic), where pheochromocytoma prevalence reaches 4% 1, 2
- Paroxysmal hypertension with classic triad: headache, palpitations, and sweating ("cold sweat"), which has 90% diagnostic specificity when occurring together 1, 2
- Early-onset hypertension (<30 years of age) 2
- Significant blood pressure variability or pallor 2
- Incidentally discovered adrenal mass (adrenal incidentaloma) 3, 2
- Family history of pheochromocytoma or associated genetic syndromes (MEN2, VHL, NF1, hereditary paraganglioma syndromes) 1, 2
Specific Test Options and Performance
24-Hour Urinary Fractionated Metanephrines
- Sensitivity: 86-97% and specificity: 86-95% for pheochromocytoma diagnosis 1
- Measures normetanephrine, metanephrine, and 3-methoxytyramine 4, 5
- Preferred for pediatric patients who are continent of urine 1
- Acceptable alternative to plasma testing, particularly for low-risk patients 1
24-Hour Urinary Catecholamines
- Measures norepinephrine, epinephrine, and dopamine 4, 6
- Should be performed alongside metanephrines when plasma testing is equivocal (less than fourfold elevation) 1
- Overnight collections provide better diagnostic sensitivity (100%) and specificity (98%) compared to 24-hour collections (88% sensitivity, 82% specificity) 7
Interpretation Algorithm
Results ≥4 Times Upper Limit of Normal
- Consistent with pheochromocytoma/paraganglioma 1
- Proceed immediately to imaging (MRI preferred over CT due to hypertensive crisis risk with IV contrast) 1, 2
Results 2-4 Times Upper Limit of Normal
- Repeat testing in 2 months 1
- Consider genetic testing for hereditary syndromes, especially in younger patients 1
Marginally Elevated Results (1-2 Times Upper Limit)
- Repeat testing in 6 months 1
- Consider clonidine suppression test (100% specificity, 96% sensitivity) to exclude false positivity 1
Critical Pitfalls to Avoid
False Positive Causes
- Obesity, obstructive sleep apnea, or tricyclic antidepressant use can elevate catecholamine metabolites 1
- False positive elevations are usually <4 times the upper limit of normal 1
- Confirm that interfering medications and foods were avoided prior to testing 1
Dangerous Clinical Errors
- Never perform fine needle biopsy of suspected pheochromocytoma before biochemical exclusion—this can precipitate fatal hypertensive crisis 1, 3
- Never initiate beta-blockade alone before alpha-blockade in suspected pheochromocytoma—this causes severe hypertensive crisis due to unopposed alpha-adrenergic stimulation 1
- Avoid contrast-enhanced CT until pheochromocytoma is definitively excluded 1
Comparison with Plasma Testing
While plasma free metanephrines have higher sensitivity (96-100%) and are considered first-line by most guidelines 1, 2, urine testing remains valuable because:
- More practical for pediatric patients once continent 1
- Useful confirmatory test when plasma results are equivocal 1
- Overnight collections simplify protocol while avoiding stress and exercise effects 7
- Can help predict tumor characteristics in high-risk patients 1
Special Clinical Scenarios
Head/Neck Paragangliomas
- Up to 30% produce dopamine, indicated by increases in plasma methoxytyramine 1
- Urine methoxytyramine is not useful as it derives from renal DOPA decarboxylation, not tumor production 1