Normal Value Range for Spot/Random Urine Metanephrines
The normal reference range for spot urine metanephrines adjusted by creatinine is approximately 15-202 µg/g creatinine for metanephrine and 34-461 µg/g creatinine for normetanephrine, with slight variations by sex. 1
Gender-Specific Reference Intervals
The most recent high-quality research using LC-MS/MS methodology established the following reference ranges for spot urinary metanephrines normalized to creatinine:
For Males:
- Metanephrine: 20.2-174.0 µg/g creatinine 1
- Normetanephrine: 47.6-452.0 µg/g creatinine 1
- 3-Methoxytyramine: 20.6-398.5 µg/g creatinine 1
For Females:
- Metanephrine: 15.3-202.0 µg/g creatinine 1
- Normetanephrine: 34.4-461.0 µg/g creatinine 1
- 3-Methoxytyramine: 38.0-392.6 µg/g creatinine 1
Clinical Context and Interpretation
When screening for pheochromocytoma, values >4 times the upper limit of normal are highly specific for the diagnosis and warrant immediate imaging. 2 Values between 1-4 times the upper limit require repeat testing and potentially clonidine suppression testing. 2
Important Considerations for Accurate Results:
- Spot urine samples should be normalized to creatinine concentration to account for variations in urine concentration due to hydration status 3
- Results should be interpreted with caution when urinary creatinine is below 2 mmol/L, as these can appear falsely elevated 3
- Samples are stable at room temperature or 4°C for at least 4 days without preservatives 1
Factors That May Elevate Results:
Several conditions can cause false-positive elevations in spot urine metanephrines that are typically <4 times the upper limit of normal:
- Severe acute illness or hospitalization (67.4% of ICU patients have supranormal values without pheochromocytoma) 4
- Obesity 2
- Obstructive sleep apnea 2
- Tricyclic antidepressant use 2
Diagnostic Performance:
Spot urinary metanephrines demonstrate superior specificity compared to plasma measurements (98.7% vs 93.0% for normetanephrine), with positive likelihood ratios of 69.21 for urinary normetanephrine/creatinine versus 12.68 for plasma normetanephrine. 5 The sensitivity and specificity of spot urinary measurements are similar to 24-hour urine collections, making them a more convenient alternative. 1