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Metadrenalines

Pseudonyms: sometimes called metanephrines, normetadrenalines or normetanephrines; Please Note: This test is NOT 'catecholamines'.

Quantification of urine normetadrenaline and metadrenaline is used for the detection of phaeochromocytomas, which are tumours of the adrenal medulla that secrete increased amounts of catecholamines. Phaeochromocytomas are a rare but treatable cause of hypertension and due to the high prevalence of hypertension it is important to be able to identify individuals with a phaeochromocytoma for further investigation and management.

General information

Collection container: Adults - 24h urine collection. NOTE: must contain acid, collect from the lab.

Paediatrics - 24h urine collection.  NOTE must contain acid, collect from the lab.

NOTE. Requests for metadrenalines in paediatrics are rare, because the typical clinical scenario is diagnosis of neuroblastoma and the analysis required in this setting is for catecholamines (noradrenaline, dopamine, HMMA, HMA) for diagnosis and monitoring.  If in doubt, refer to the duty biochemist on 0161-701-2255.

Type and volume of sample: A carefully timed urine collection is required. A minimum volume of 5mL is required for analysis if the sample is coming from an external laboratory.

Specimen transport/special precautions: Take care as the acid is a hazardous material but is required for the stability of the metadrenalines during the 24h collection.

Laboratory information

Method principle:

High-Performance Liquid Chromatography (HPLC) with electrochemical detection (ECD) is used to measure total metadrenaline and normetadrenaline in urine after acid hydrolysis and solid phase extraction.  A commercial reagent kit is used (Chromsystems).

Biological reference ranges:

Normetadrenaline Male 0 to 5.3 μmol/24h
Female 0 to 4.3 μmol/24h
Metadrenaline (male and female) 0 to 2.0 μmol/24h

 

Turnaround times: Results should be available within 2 weeks of sample receipt.

Clinical information

Factors known to significantly affect the results:

  • Analytical

Paracetamol has been reported to interfere with at least one HPLC-ECD based method (Davidson, 2004).The majority of drugs that have been shown to analytically interfere with the measurement of metanephrines are a problem with methods based on spectrophotometric and fluorometric detection and should not interfere with electro-chemical detection. However, drugs may interfere with the Chromsystems method so it is essential that chromatograms should be interpreted with caution.

  • Physiological

In addition to analytical interference there are a number of drugs that can alter the levels of metanephrines through physiological routes. The majority appear to lead to an increased level of metanephrines so could provide false positive results and therefore should be considered when elevated excretion is detected in patient samples.The table below highlights some of the drug groups that can induce an increase in metanephrine levels. In addition it is important to remember that some clinical situations, such as CPR, may require the administration of adrenaline and/or noradrenaline which will increase levels of their metabolites soon afterwards.

- Normet Met

Tricyclic antidepressants

Amitriptyline, notriptyline, imipramine

+++ -

α-blockers (nonselective)

Phenoxybenzamine

+++ -

α-blockers (selective)

Doxazosin, terazosin, prazosin

- -

β-blockers

Atenolol, metoprolol, propranolol, lebetalol*

+ +

Monoamine oxidase inhibitors

Phenelzine, trancypromine, selegiline

+++ +++

Sympathomimetics

Ephedrine, pseudoephedrine, amphetamines, abuterol

++ ++

 

Table 1. Drug-induced increases in metanephrines

+++, substantial increase, ++, moderate increase, +, mild increase if any, -, little or no increase. *Labetalol can also cause direct analytical interference with some methods. Taken from Burtis et al. 2006.

Burtis, C.A., Ashwood, E.R. and Bruns, D.E. (2006). Tietz textbook of clinical chemistry and molecular diagnostics. Fourth Edition, Elsevier Saunders, St. Louis, Missouri, USA.

Davidson, D.F. (2004). Paracetamol-associated interference in an HPLC-CED assay for urinary free metadrenalines and catecholamines. Annals of Clinical Biochemistry 41: 316-320.

Clinical decision points:

clinical suspicion of PPGL

PPGL = pheochromocytoma and paragangliomas.

The algorithm for interpretation of results has been taken from the review by van Berkel et al (Eur J Endo 2014; 170: R109 - R119). Locally, the clonidine suppression test is not used so the follow up test to a raise urine result are plasma metadrenalines.

 

(Last reviewed 25th June 2017)