Metanephrine and Normetanephrine, Plasma

Diagnostic Use

Screening test for catecholamine-secreting phaeochromocytomas or paragangliomas with high sensitivity and specificity. A negative result rules out a secretory tumour with high probability.

Pheochromocytoma is a rare, though potentially lethal, tumour of chromaffin cells of the adrenal medulla that produces episodes of hypertension with palpitations, severe headaches, and sweating ("spells"). Patients with pheochromocytoma may also be asymptomatic and present with sustained hypertension or an incidentally discovered adrenal mass.

Pheochromocytomas and other tumours derived from neural crest cells (e.g., paragangliomas and neuroblastomas) secrete catecholamines (epinephrine, norepinephrine, and dopamine). Metanephrine and normetanephrine (collectively referred to as metanephrines) are the 3-methoxy metabolites of epinephrine and norepinephrine, respectively. The metanephrines are stable metabolites and are co-secreted directly with catecholamines by pheochromocytomas and other neural crest tumours. This results in sustained elevations in plasma free metanephrine levels, making them more sensitive and specific than plasma catecholamines in the identification of pheochromocytoma patients. Metanephrine and normetanephrine are both further metabolized to conjugated metanephrines and vanillylmandelic acid.

Department

Specialist Biochemistry

Delphic Registration Code

PNOR

Laboratory Handling

Phlebotomy

Please collect one full tube dedicated for this test only. If collected outside of CHL please separate and freeze plasma, before sending to CHL

Separating

Aliquot at least 1 ml , separate within 4 hours of collection - Specialist Biochemistry Freezer

Laboratory

Gross haemolysis reject, gross lipemia OK, gross icterus OK

Test Adds

Frozen 28 days

Constituent Tests

• 3-Methoxytyramine (3-MT), Plasma

Synonyms

Metanephrine and Normetanephrine
Normetadrenaline and Metadrenaline

Turnaround Time

3 weeks

Test Code

4739

Specimen Type

• Plasma

Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred if West Coast

• Lithium Heparin - Gel (Light Green Cap)

Acceptable

• Lithium Heparin - Non-gel (Green Cap)
• Lithium Heparin - Gel (Light Green Cap)

Preferred Sample Volume (ml)

5

Minimum Sample Volume (ml)

1

No of Samples Required

1

Pre-testing Requirements

Patient does NOT need to be resting/supine for a screening test, but may require to be if results are marginally raised.

Aliquot Instructions

Sample Type

• Plasma

Minimum Volume (ml)

1.0

Transport to Lab

Frozen

Interpretation

Stress and acute, severe illness are associated with a physiological increase in metanephrines.

Drugs including beta-blockers, noradrenaline reuptake inhibitors and tricyclic antidepressants may raise in vivo metanephrine levels and make interpretation difficult.

Chronic renal failure may increase plasma metanephrines up to 2-fold.

Levels up to 2.5 fold URL may be attributable to stress of any acute illness, renal impairment or interfering medications, as listed above. Consider repeat testing after fasting, avoidance of caffeine and nicotine, omission of interfering drugs or after lying supine for 30 minutes.
Testing 24-hour urine metanephrines may also be considered.

Levels > 3 fold URL have a high positive predictive value for phaeochromocytoma or paraganglioma and patients should be referred to an Endocrinologist.

Plasma 3-methoxytyramine (3-MT), a dopamine metabolite associated with SDHx mutations with more malignant potential is available on request.

References/resources:

1. Eisenhoffer, G., Lattke, P., Herberg, M. et al. 2013. Reference intervals for plasma free metanephrines with an age adjustment for normetanephrine for optimized laboratory testing of phaeochromocytoma. Ann Clin Biochem, 50(1): 62-9.
2. Lenders, W., Duh, Q., Eisenhoffer, G. et al. 2014. Diagnosis and treatment of phaeochromocytoma and paraganglioma. JCEM , 6(1):1915-42.
3. Eisenhofer, G., Huysmans, F. et al. 2005. Plasma metanephrines in renal failure. Kidney Int, 67(2): 668-77.
4. Darr, R., Pamporaki, C., Peitzsch, M. et al. 2013. Biochemical diagnosis of phaeochromocytoma using plasma-free normetanephrine,metanephrine and methoxytyramine: importance of supine sampling under fasting conditions. Clinical Endocrinology, 80(4): 478-86.

Reference Intervals

Age (years)	Normetanephrine (pmol/L)	Metanephrine (pmol/L)
0-17	<900	<500
18-29	<1100
30-59	<1200
60+	<1400

Age related reference interval introduced March 2022. Reference ranges are for non-supine (seated/ambulatory) patients.

Test Method

Resin extraction, LC-Mass Spec detection

Non-Funded Test Cost

$153.95 (Exclusive of GST)

Billing Code

4739

Contact Information

Enquiry Form

Contact Information

Enquiry Form