Patient tests with high serum catecholamines, but metanephrines are normal. Will 24 hour urine of the metanephrines still be preferred over a 24 hour urine of catecholamines to diagnose high epinephrine and possible pheochromocytoma in such a patient?
24 Hour Urine Metanephrines To Test Catecholamines
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Serum catecholamines are high. Serum metanephrines are normal.
My understanding is that pheochromocytoma is normally screened by a 24 hour urine metanephrine, not a 24 hour urine catecholamines. That may have to do with the fragility of catecholamines, and metanephrines are used as a proxy because of their greater stability. If 24 hour urine metanephrines is high, then a 24 hour urine catecholamines can be done as confirmation. That seems to be clinical practice?
In this question, it was the premise about serum metanephrines being normal that throws me off. Does it make sense for serum catecholamines to be high and serum metanephrines to be normal, and does that fact alter the diagnostic pathway for the 24 hour urine? In other words, is it possible the 24 hour urines would mirror the results of the serum tests, with 24 hour urine catecholamines being high and 24 hour urine metanephrines being normal? If you started with the 24h metanephrines you might miss the 24h catecholamines result.
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Is this an in class question? Diagnostic guidelines suggest 24 urine metanephrine AND catecholamine run concurrently as first line protocol. Serum metanephrine tests are non-specific and are only run if index of suspicion is high. Afaik serum catecholamine levels aren't routinely measured.
You are correct in that metanephrine is the more stable metabolite of epinephrine so it is more commonly found in serum/urine. Did the question discriminate between epinephrine/norepinephrine as the source of the catecholamine levels?
Question showed values for fractionated catecholamines and serum epinephrine was quite high. But I'm thinking the serum value data might be a trick and it doesn't affect the diagnostic pathway, since serum values can change dramatically one moment to the next.
Regarding 24 hour urine for both metanephrines and catecholamines both being first line, I note some studies like this one:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419007/
which contains the line: "...numerous independent studies have now confirmed that measurements of fractionated metanephrines (i.e. normetanephrine and metanephrine measured separately) in urine or plasma provide superior diagnostic sensitivity over measurement of the parent catecholamines (Table 3)15–17."
Some sources suggest that the first line diagnostic is the 24 hour urine metanephrine, and only if that is high is it confirmed with 24 hour urine catecholamines. I'm trying to gain more nuanced understanding of when that might not be the best diagnostic sequence.
Regarding 24 hour urine for both metanephrines and catecholamines both being first line, I note some studies like this one:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419007/
which contains the line: "...numerous independent studies have now confirmed that measurements of fractionated metanephrines (i.e. normetanephrine and metanephrine measured separately) in urine or plasma provide superior diagnostic sensitivity over measurement of the parent catecholamines (Table 3)15–17."
Some sources suggest that the first line diagnostic is the 24 hour urine metanephrine, and only if that is high is it confirmed with 24 hour urine catecholamines. I'm trying to gain more nuanced understanding of when that might not be the best diagnostic sequence.
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From what I seem to rmbr for the diagnosis you need serum Metanephrines and/or 24 hour urine metanephrines (or both, not necessarily).
Your case: HIGH CATECHOLAMINES and NORMAL METANEPHRINES
Catecholamines=Production
Metanephrines=Breakdown
In your patients weird scenario he has high catecholamines which means the glands are hypersecreting possibly from Flight, Fright or Fight stress responses, Pheochromocytoma, CNS Tumor, any form of Increased Cortisol or even Thyrotoxicosis. But the normal Metanephrines could possibly mean the COMT (breakdown of catecholamines) isn't funtioning properly probably because maybe the patient is on Talcapone or Entacapone (given a history of Parkinson's). Because in Parkinson patients they are usually on Levodopa (precursor for catecholamines) Carbidopa together which increases catecholamines and Entacapone (decreasing breakdown) = Together they're called Triple Therapy. Which leads me to this.
Urinary fractionated metanephrine levels are 97% sensitive and Plasma free metanephrine levels are 99% sensitive so a negative result can effectively rule out Pheochromocytoma.
If your patient definitely has Pheochromocytoma then lab tests need to be repeated and overviewed.
Maybe not enough information is provided so I can't come to a definitive conclusion unless I'm missing something, but as far as I'm concerned your patient does not have Pheochromocytoma my friend.
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This is why there is little clinical value in measuring serum catecholamine levels. From UpToDate:
"Measuring plasma fractionated metanephrines is a first-line test when there is a high index of suspicion for pheochromocytoma. Plasma fractionated metanephrines are also a good first-line test for children because obtaining a complete 24-hour urine collection is difficult.
24-hour urinary fractionated catecholamines and metanephrines should be the first test in patients with a somewhat lower index of suspicion for pheochromocytoma."
High index of suspicion is past/family hx or adrenal mass on CT with symptomatology.
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In this case, unless your pre-test risk is through the roof, he doesn't have a pheo. It's pharmaceutically/physiologically induced.
The COMT insight was interesting. So couldn't you use that premise to steer to a different conclusion? Patient may have genetic or pharmacologically-induced impairment of COMT or MAO, thereby preventing normal breakdown of catecholamines. Metanephrines measurement in serum or urine may not give a reliable diagnostic. Therefore, test both 24 hour urine metanephrines and catecholamines as a first line diagnostic.
Just making the devil's advocate argument, using your interesting observation as the starting point....
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You're welcome...Yes we can come to that possible conclusion. It is feasible to conclude that COMT gene mutations are not a theory and in fact an actuality and that in the case of pharmacologically-induced impairment also these would drive the testing towards BOTH not either/or for a more reliable diagnosis, or should I say rule out.
By the way where did you get this question from? Cause I've done thousands of questions and countless Qbanks and haven't come across this one yet. Seems to me like this was more on the lines of a Step 2 question if you ask me.
Either way hope you got your answer. Good luck.
