Metanephrines, urine

Clinical background:

Phaeochromocytoma and functional paraganglioma are rare neuroendocrine tumours that are characterised by excessive secretion of catecholamines, occurring in approximately 0.1% of hypertensive patients. The biochemical detection of this tumour involves confirmation of excess urinary excretion of metadrenalines. Urinary fractionated metadrenalines have been shown to be a more reliable biochemical index of increased tumour production of catecholamines than urinary catecholamines.

Specimen container paediatric:

Random urine collection: white universal container [Send to laboratory immediately].

Specimen container adult:

24 urine collection: a 24 hour urine collected into a container with sand and sulphuric acid preservative.

Overnight urine collection: an overnight urine collection into a container with sand and sulphuric acid preservative.

Random urine collection: white universal container  [Send to laboratory immediately].

Minimum volume paediatric:

1 – 10 mL urine

Minimum volume adult:

1 – 10 mL urine

Special requirements:

Random samples have limited stability, send to lab immediately.

Urine metanephrines are used for the diagnosis of pheochromocytoma. 

To test for neuroblastoma – measure urine HMMA and HVA (neuroblastoma screen).

Sample stability:

Urine samples are stable at 4°C for up to 6 weeks.

For longer periods store at –15°C.

Transport requirements:

Ambient temperature

Quality assurance:

UK National External Quality Assurance Scheme (NEQAS) for Urinary Catecholamines

Interpretation:

Urine metanephrine or normetanephrine values greater than 4 times the upper reference interval are highly suggestive of the presence of phaeochromocytoma/paraganglioma. Elevated results are reported with appropriate comments.

Reference ranges:

24-hour Metanephrine (µmol/24hr):

• 0 – 9m: 0 – 0.2
• 9 – 12m: 0 – 0.5
• 1 – 2y: 0 – 0.3
• 2 – 6y: 0.1 – 0.5
• 6-10y: 0.3 – 0.7
• 10-16y: 0.2 – 1.2
• Adult (female): 0 – 1.8
• Adult (male): 0 – 2.2

24-hour Normetanephrine (µmol/24hr):

• 0 – 9m: 0.2 – 0.8
• 9 – 12m: 0.1 – 0.6
• 1 – 2y: 0.2 – 0.6
• 2 – 6y: 0.3 – 0.6
• 6-10y: 0.3 – 1.0
• 10-16y: 0.3 – 1.6
• Adult (female): 0 – 3.0
• Adult (male): 0 – 3.8

24-hour 3-methoxytyramine (µmol/24hr):

• 0 – 9m: N/A
• 9 – 12m: N/A
• 1 – 2y: N/A 
• 2 – 6y: N/A 
• 6-10y: N/A 
• 10-16y: N/A
• Adult (female): 0 – 2.8
• Adult (male): 0 – 2.8

Overnight / Random Metanephrine (­µmol/mmol creatinine):

• 0 – 9m: 0.12 – 0.41
• 9 – 12m: 0.08 – 0.37
• 1 – 2y: 0.02 – 0.30
• 2 – 6y: 0.04 – 0.29
• 6-10y: 0.07 – 0.18 
• 10-16y: 0 – 0.18
• Adult (female): 0 – 0.3
• Adult (male): 0 – 0.3

Overnight / Random Normetanephrine (µmol/mmol creatinine):

• 0 – 9m: 0.94 – 2.07
• 9 – 12m: 0.16 – 0.68
• 1 – 2y: 0.22 – 0.79
• 2 – 6y: 0.06 – 0.37
• 6 – 10y: 0.06 – 0.28
• 10 – 16y: 0 – 0.25
• Adult (female): 0 – 0.35
• Adult (male): 0 – 0.35 

Overnight / Random 3-methoxytyramine (µmol/mmol creatinine):

• 0 – 9m: N/A
• 9 – 12m: N/A
• 1 – 2y: N/A 
• 2 – 6y: N/A 
• 6-10y: N/A
• 10-16y: N/A
• Adult (female): 0 – 0.22
• Adult (male): 0 – 0.22

Factors affecting result:

Drugs can interfere analytically or pharmacodynamically with measurement of plasma or urinary metanephrines, potentially causing false positive results. Analytical interference is more likely to affect the urine metanephrine HPLC-ECD assay. The LC-MS/MS method for plasma free metanephrines is considered to be far less susceptible to analytical interference.

Many drugs are now known to increase catecholamine and metabolite concentrations, including tricyclic antideppressant’s, selective serotonin reuptake inhibitors, serotonin and noradrenaline reuptake inhibitors, α- and β- adrenergic receptor blockers, calcium channel blockers, monoamine oxidase inhibitors, Levo(L)-Dopa, methyldopa and several stimulant/sympathomimetic drugs.

Ideally patients should discontinue all medications that may affect plasma and urinary catecholamine or metanephrine concentrations prior to sampling. In practice, it is not always possible to discontinue medication before testing and it might be better to repeat testing only when initial tests are elevated.