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  • Subject: Plasma Metanephrine testing for pheochromocytoma at the National Institutes of Health
  • Speaker: Dr. Graeme Eisenhofer of the National Institutes of Health (NIH Bethesda, MD)

[Monitor] [29 beginning users in channel Pheo Illness Private Chat:]
[tues1day – PheoGroup – Kelly5 – DeH – Huntington – DrW – AlexDude – DrRay – EdgarAl – ophelia – KarenMom – dratp – Giant – drsteinmann – TopHat – cindylou – Shepherd – UCSFvisitor – jenni – CourtGrrl – Hyde – StanfordAC – darlart – MaryPeebels – NIH – cghow – wells – Lisawick]

PheoGroup: Good evening
cghow: Hi
MaryPeebels: Welcome. PheoGroup will start discussion at 9pm EST
MaryPeebels: NIH is Dr. Graeme Eisenhofer of the National Institutes of Health. PheoGroup is our moderator, Debra Harlander. Mary Peebels is monitor.
MaryPeebels: For approximately 45 minutes, PheoGroup and NIH have the floor. If time permits, there will be open questions afterwards – Any questions to Dr. Eisenhofer must be general, not personal. He can give no medical advice.
PheoGroup: Good evening everyone
PheoGroup: I would like to thank all those who are here, and I would like to especially thank our guest, Dr. Graeme Eisenhofer
PheoGroup: Dr. Eisenhofer is a research scientist at National Institutes of Health in Bethesda MD
NIH: I'm pleased to be here
PheoGroup: The format for this chat will be as follows: we will begin with questions sent into our group for Dr. Eisenhofer
PheoGroup: We will then open the floor to questions
PheoGroup: We ask specifically that Dr. Eisenhofer be presented with general questions. He cannot give any medical advice.
PheoGroup: If you are ready Dr. Eisenhofer we can begin….
NIH: Sure
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MaryPeebels: Welcome. Please wait. PheoGroup and NIH have the floor.
PheoGroup: If a person's doctor suspects pheochromocytoma, what are the first tests that should be done to help confirm the diagnosis?
NIH: Because of the high sensitivity of the test and the low incidence of the tumor it is my opinion, biased as it may be, that plasma free metanephrines should be carried out as the first test.
NIH: If not available then the next best test is urinary FRACTIONATED METANEPHRINES
NIH: -but not urinary TOTAL metanephrines
NIH: Both tests may be combined with measurements of plasma or urinary catecholamines
NIH: next question if you wish
PheoGroup: Thank you…
PheoGroup: Can you give a brief explanation of what makes the plasma metanephrine test different from tests we now have available for pheo?
NIH: First, the free metanephrines are produced continuously within pheo tumor cells from catecholamines leaking from storage vesicles within the cell cytoplasma.
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NIH: Thus, these metabolites are produced independently of catecholamine released by tumors. This has advantages since catecholamine release can be episodic or relatively non-existent in some pheos.
NIH: Second, metanephrines commonly measured in urine are different metabolites. They are actually sulfdate conjugated, require an additional metabolic step for synthesis and are consequently produced in different parts of the body than the free metanephrines.
NIH: Third, the advantages of a plasma test over a urine test outweigh the disadvantages.
NIH: That would be about it in a nutshell.
PheoGroup: Thank you
PheoGroup: What are the statistic on the accuracy of this test?
NIH: So far out of over 150 patients that we have positively diagnosed with pheo, only two have had normal plasma concentrations of free metanephrines.
NIH: However, both of these patients did not have symptoms, both had very small tumors
NIH: Needless to say the other biochemical tests in these patients were also negative. These results indicate
NIH: To finish, these results indicate a sensitivity of 99% compared to 63% for VMA and 83% tom 85% for urinary or plasma catecholamines.
NIH: next question
PheoGroup: Are there any medications, i.e. beta blockers, that interfere with the results of 24 hour urine tests? And also are there medications that should be avoided to perform the plasma metanephrine test?
NIH: Many drugs can potentially interfere with assays of catecholamines and any other substances, but this often depends on the method and laboratory. Whether it is a problem or not depends on the level of expertise and competency of the operator running the assay.
NIH: In our lab, caffeine is a problem both directly and indirectly.
NIH: Next question
PheoGroup: What medications and substances should be avoided for the plasma metanephrine test?
NIH: Acetaminophen or any drugs containing acetaminophen can be a problem. We haven't identified any other source of interference. Clonidine or its metabolites show up in our chromatograms but they aren't a problem.
NIH: That's about it for interference with our assay.
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jhux3238: junebug here – I would like a copy of the chat
[Moderator to jhux3238] No problem. I am going to send transcripts of this chat.
PheoGroup: If a person is negative in the 24 hour catecholamine urine tests, would you still recommend the plasma metanephrine test to confirm or eliminate the diagnosis of pheo, and why?
NIH: Yes, I would particularly if the symptoms are episodic. 24 hr urine tests are not always that good at picking up intermittently secreting tumors.
NIH: Certainly I would since some of these tests, particularly 24 hr urinary fractionated metanephrines suffer from notoriously poor specificity.
NIH: That is their test results are often positive even though no pheo is present.
PheoGroup: Do you have any statistics on percentages of people with negative urine tests who test positive on the plasma metanephrine test?
NIH: In our latest series of patients with pheo 17% had negative 24 hr urinary catecholamines, 27% had negative urinary total (THAT'S TOTAL) urinary metanephrines, and 37% had negative urinary VMA. Of these we picked up all but the two I mentioned above with a positive plasma free metanephrine.
PheoGroup: Once a person has been diagnosed with pheo, and has it removed, how long after surgery should the 24 hour urine test be performed?
NIH: Here at the NIH we wait at least 3 weeks or until the patient is fully recovered from surgery.
PheoGroup: If the urine test is negative following surgery, would it be worthwhile to have the plasma metanephrine test, and if so when should it be performed and how often?
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NIH: Actually, it would be best to use the plasma test at the outset after surgery. Again at least 3 weeks or until the patient is recovered.
PheoGroup: Would yearly followup with the plasma test be sufficient, or is it necessary?
NIH: There are no clear guidelines on this. Certainly, since 10 to 15% of patients have recurrent disease or metastases there should be some follow up.. and I'll go on here.
NIH: Typically, no follow-up is done and it is the onset of new symptoms that brings a patient back for testing. I think we need better guidelines here. Certainly in familial pheo followup testing should be done at yearly or at least two yearly intervals.
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PheoGroup: If a person has a pheo removed can pathology make certain as to whether the tumor is metastatic?
NIH: to the best of my knowledge no, and this is a problem that requires more research. Typically the definition of metastatic disease is based on location and whether there are multiple tumors, but even this is problematic… and I shouldn't go into more detail than this…
PheoGroup: Can you tell us how accurate MIBG scanning is in finding pheos?
NIH: MIBG is a highly specific imaging test, that is it is good for identifying a pheo as a pheo and not some other kind of mass or tumor. MIBG is also useful in identifying or locating extra adrenal pheos and metastases. however…
NIH: the 131I-MIBG used routinely in the US is not all that sensitive compared to the 123I-MIBG used elsewhere in the world. This is definitely one area of medical care that we in the US are way behind in compared to other countries.
NIH: next question if you wish
PheoGroup: Can you explain why it is necessary to have the patient have their blood drawn for the plasma test where they live, rather than come to NIH directly?
NIH: Admitting a patient to the NIH involves a fair amount of procedural and administrative work….
NIH: If all the patients who want this blood test were to come to the NIH our clinical staff would be overwhelmed. As it is our capacity for testing outside samples is becoming strained.
NIH: I hope that answers that one.
PheoGroup: Yes, thank you! Final question….What is the future availability of this plasma test?
NIH: An important question, let me take a bit of time.
PheoGroup: Certainly
NIH: Presently NIH is moving from research to service
NIH: I have made our procedures freely available and I am assisting others to set up the method elsewhere.
NIH: Also…
NIH: Joyce Graff of the VHL Family Alliance has kindly offered to make our manual available over the internet. Hopefully this will help make the test more widely available than it currently is.
PheoGroup: Would you like to add any additional comments on this subject Dr. Eisenhofer?
NIH: I hope this assures you that we will not abandon the test until it is available elsewhere on a wider scale.
PheoGroup: We certainly appreciate it.
PheoGroup: At this time, we have only a few minutes remaining on our time that we asked Dr. Eisenhofer to spend with us
MaryPeebels: I regret we have run out of time. But I want to thank Dr. Eisenhofer for visiting and answering these important questions.
PheoGroup: We appreciate the time he has given this evening
NIH: As far as additional comments, I'd just like to applaud Mary, yourself and all the others for getting this support group together.
PheoGroup: Thank you
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MaryPeebels: Thanks. We couldn't do it without you, Dr. Eisenhofer!
PheoGroup: Your assistance has made a lot of what we do possible
PheoGroup: Please also thank Dr. Pacak for us…
NIH: NO problem and glad to offer some additional support to your group.
MaryPeebels: Thank you for being moderator of this chat, PheoGroup.
MaryPeebels: Thank to all of our visitors here in chat also.
PheoGroup: Yes, and we apologize for running out of time…. perhaps we can do this again some time in the future if Dr. Eisenhofer is willing.
MaryPeebels: I will send out transcripts of this chat. Plus it will be on a web page at our site.
MaryPeebels: Good evening, everyone. Thanks again, Dr. Eisenhofer. Hope to see you again in chat.
NIH: Talk later.
tues1day: Bye- Thanks for arranging this – the questions were GREAT!
PheoGroup: sorry we did not get to everyone!
MaryPeebels: Thank you. Goodnight and best wishes to everyone.
[Monitor] [35 logged users in channel Pheo Illness Private Chat:]
[tues1day – PheoGroup – Kelly5 – DeH – Huntington – DrW – AlexDude – DrRay – EdgarAl – ophelia – KarenMom – dratp – Giant – drsteinmann – TopHat – cindylou – Shepherd – UCSFvisitor – jenni – CourtGrrl – Hyde – StanfordAC – Skrawletta – darlart – MaryPeebels – NIH – cghow – wells – Lisawick – jhux3238 – Zeta – bshort – mklevesque – jbr – RJZ]
[/End Chat Log channel Pheo Illness Private Chat]

Dr. Graeme Eisenhofer of the National Institutes of Health (NIH Bethesda, MD)
Members of the Pheochromocytoma Support Group