Metanephrines (urine)

Metanephrines are the 3-O-methylated metabolites of catecholamines. They are formed in chromaffin cells by the action of catechol-O-methyl transferase which produces metanephrine (MN) from adrenaline; normetanephrine (NMN) from noradrenaline; and 3-methoxytyramine (3-MT) from dopamine.

Measurement of metanephrines is used to demonstrate elevated production of catecholamines and is recommended as a first line investigation for the diagnosis of phaeochromocytoma and paraganglioma (PPGL).

PPGL are rare neuroendocrine tumours arising from adrenal chromaffin cells (phaeochromocytoma) and extra-adrenal chromaffin cells of the sympathetic paravertebral ganglia (paraganglioma). Rarely these tumours are biochemically silent but commonly they produce excessive levels of one or more catecholamines. The presence of membrane-bound catechol-O-methyl transferase in tumour cells results in the metabolism of secreted catecholamines to their respective metanephrines. This occurs in a continuous manner, independent of catecholamine release, thus providing a diagnostic advantage of metanephrines measurement over catecholamines.

Diagnosis of phaeochromocytoma depends on a high index of clinical suspicion and biochemical confirmation of excessive metanephrine secretion.

24 hour urine metanephrine measurement may be considered when signs and symptoms of catecholamine excess are present, particularly if paroxysmal. These include:

- Hypertension
- Sweating
- Anxiety
- Palpitations
- Headache

Other clinical settings where plasma metanephrine testing is indicated include:

- PPGL symptoms provoked by use of medications associated with adverse effects*
- Adrenal incidentaloma, with or without hypertension
- Hereditary predisposition or syndromic features suggesting hereditary PPGL

(MEN-2, Von Hippel-Lindau syndrome, Neurofibromatosis type-1)
- Previous history of PPGL

*dopamine D2 receptor antagonists, βadrenergic receptor blockers, sympathomimetics, opioid analgesics, norepinephrine reuptake inhibitors (including tricyclic antidepressants), serotonin reuptake inhibitors, monoamine oxidase inhibitors, corticosteroids, peptides (ACTH, glucagon), neuromuscular blocking agents.

Reference intervals will be given with the report

Random urine samples are accepted where it is difficult to provide 24 hour collections. These must be acidified on their initial receipt in the laboratory specimen reception.
Samples with pH>3.0 are unsuitable for this assay.