Diagnostic Use
This is a diagnostic test for phaeochromocytoma and paraganglioma. A negative result rules out a secretory tumour with high probability.
Interpretation
There is strong evidence to support the use of age‑based reference ranges for the interpretation of the plasma normetanephrine concentration (1). False positive and false negative tests may still occur:
- Stress and acute, severe illness associated with a physiological increase in metanephrines (2).
- Certain drugs including beta‑blockers, noradrenaline reuptake inhibitors and tricyclic antidepressants may raise in vivo metanephrine levels and make interpretation difficult (2). It is recommended these drugs be withdrawn for at least 5 half‑lives prior to testing if it is clinically appropriate.
Plasma free metanephrines are increased up to 2‑fold in chronic renal failure, but are still useful for diagnosing phaeochromocytoma in this setting (3).
Age-based normetanephrine reference interval (supine, fasted patients)
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Age (years)
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Normetanephrine (pmol/L)
|
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< 5
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< 720
|
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5 – 20
|
< 540
|
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20 – 40
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< 600
|
|
40 – 60
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< 800
|
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> 60
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< 980
|
Interpretation of plasma metanephrines in non-fasted, non-supine (seated/ambulant) patients
An audit of local laboratory results and the subsequent diagnosis of phaeochromocytoma/paraganglioma has recommended the use of the following ranges in non-fasted, non-supine patients:
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Age (years)
|
Normetanephrine (pmol/L)
|
|
< 30
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< 900
|
|
30 – 40
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< 1100
|
|
40 – 70
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< 1200
|
|
> 70
|
< 1400
|
If there is on-going clinical suspicion of phaeochromocytoma/paraganglioma in a non-fasted, non-supine patient with a result between the two reference intervals, a follow-up test is recommended. This may be:
- Retest plasma metanephrines in a fasted patient who has been precannulated and allowed to rest supine for 20 minutes before a sample is taken via the IV cannula (2). This will require referral for outpatient collection or specialist endocrine review. LabTests does not provide this service. Collecting fasted, rested, supine samples generally results in a significantly lower normetanephrine level, hence the reference ranges are lower (1,4).
- 24-hour urine metanephrines ? a 24hr collect for urine metanephrines may be arranged through the laboratory. A raised urine level increases suspicion of phaeochromocytoma/paraganglioma, however it is slightly less sensitive than the fasted, rested, supine plasma test and so a small number of cases may be missed (5).
Test Method
Liquid chromatography - tandem mass spectrometry
Limitations / Interference
Certain drugs including beta‑blockers, noradrenaline reuptake inhibitors and tricyclic antidepressants may raise in vivo metanephrine levels and make interpretation difficult (2). It is recommended these drugs be withdrawn for at least 5 half‑lives prior to testing if it is clinically appropriate.
Mild to moderate increases falsely high plasma metanephrine levels due to interference in the LabPLUS assay. Urine metanephrines are not affected by this interference.
Stress and acute, severe illness associated with a physiological increase in metanephrines (2).
References (fpr Diagnostic Use, Interpretation and Limitations/Interferences):
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.
5. Rifai, N., Horvath, R. & Wittwer, C. 2018. Tietz textbook of clinical chemistry and molecular diagnostics . St. Louis, MO: Elsevier.
Uncertainty of Measurement
Normetanephrine: 20%
Metanephrine : 16%