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Metanephrines, Fractionated, Free, LC/MS/MS, Plasma

Test code(s) 19548

This is an outdated version of this FAQ. It was effective 04/20/2012 to 12/28/2014.

The current version is available here.

Question 1. Why are there so many different tests used for the diagnosis of pheochromocytoma?  Which one is the best?  

Both plasma metanephrines and plasma catecholamines have been used for the diagnosis of pheochromocytoma. If plasma metanephrines and/or catecholamines are not available, then the next best test is urinary fractionated metanephrines and/or catecholamines.

The 24-hour urine tests for metanephrines and catecholamines remain useful screening tests for pheochromocytoma, based on data from some research groups showing good diagnostic specificity of urine testing.1 The urine specimen requires a complete 24-hour collection and an acid preservative must be added to the collection container. 

Urinary VMA is no longer used as a diagnostic test for pheochromocytoma. However, urinary VMA can be used in conjunction with urinary HVA for the diagosis of neuroblastoma.

Question 2. What are the advantages and potential disadvantages of the plasma metanephrine test over the standard urine tests for pheochromocytoma?

There are considerable data showing that the plasma metanephrines test is more sensitive than urinary metanephrines and/or catecholamines, likely because even small pheochromocytomas may continually leak metanephrines even if they are not actively secreting catecholamines. Another consideration is practicality, in that a 24-hour urinary collection can be difficult for some patients. A potential disadvantage of the plasma metanephrines test is that it requires additional patient preparation (at least 20 minutes of rest prior to blood draw, preferably in a reclining or seated position with a butterfly or indwelling blood drawing catheter in place). Also, because plasma metanephrine levels are affected by acute stress, patients in whom blood drawing generates great anxiety (e.g., children) may be more likely to have mildly elevated levels from stress alone. A normal result for plasma metanephrines is strong evidence against the diagnosis except in early pre-clinical disease.

Question 3. What is the clinical sensitivity and specificity of the plasma metanephrines test?

Sensitivity for plasma metanephrines is 96% to 99% and the specificity is 79% to 89%.1

Question 4. What is the definition and clinical significance of borderline plasma metanephrines?

Plasma metanephrine and/or normetanephrine levels ≥4-fold the upper limits of the reference ranges are strongly suggestive of a pheochromocytoma.2 Levels between 1 and 4-fold elevated are considered borderline and are significant, but not diagnostic, and may be due to medications  (see Question 6 below) or stress.

 

The standard protocol to minimize stress during sample collection stipulates that the patient should be reclining for 20 minutes with an IV inserted before withdrawing the specimen from the IV. Patient should also refrain from alcohol and tobacco for 12 hours.

Question 5. Which test(s) should be ordered to verify borderline elevated plasma metanephrines?

24-hour urine for metanephrines should be ordered. Chromogranin A levels are elevated in most patients with pheochromocytoma; however, the test is not specific and is seen in other disorders such as carcinoid.

Question 6. Which drugs can cause false-positive elevations of plasma metanephrine and/or normetanephrine?

Drugs that may cause false-positive elevations of plasma metanephrine and/or normetanephrine include: tricyclic antidepressants, alpha-blockers, beta-blockers, monoamine oxidase inhibitors, sympathomimetics, and stimulants. It is important that patients abstain from these medications preferably for 1-2 weeks prior to sample collection.

Question 7. Should plasma metanephrines be performed if the results are negative in the 24-hour urine catecholamines test?

If clinical suspicion remains high, and especially if symptoms are episodic, plasma metanephrines should be measured due to their high diagnostic sensitivity. The 24-hour urine tests are not always successful in detecting intermittently secreting tumors.

 

References

  1. Kudva YC, Sawka AM, Young WF. The laboratory diagnosis of adrenal pheochromocytoma: the Mayo Clinic Experience. J Clin Endocrinol Metab. 2003; 88: 4533-4539
  2. Algeciras-Schimnich A, Preissner CM, Young WF Jr, et al. Plasma chromogranin A or urine fractionated metanephrines follow-up testing improves the diagnostic accuracy of plasma fractionated metanephrines for pheochromocytoma. J Clin Endocrinol Metab. 2008;93:91-95.
This FAQ is provided for informational purposes only and is not intended as medical advice. A physician’s test selection and interpretation, diagnosis, and patient management decisions should be based on his/her education, clinical expertise, and assessment of the patient.

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