The 5 pheo tests are subjected to interferences by quite a few factors. I list those factors here according to their significance. The most important message, however, is that these factors are usually not a big deal and can be rather easily figured out by an expert. Reaching a pheo diagnosis requires all things considered, rather than any evidence in isolation.
Major interferences:
1. In many diseases, catecholamines and metanephrines levels are indeed genuinely elevated, and can be rather high. About 30 such diseases are known. Obstructive sleep apnea, severe anxiety, and essential hypertension are the most common ones.
2. Any major stress, such as stroke, severe infection, and bad pain, elevate catecholamines and metanephrines levels.
3. Some drugs such as cocaine, phenoxybenzamine, tricyclic antidepressants, and monoamine oxidase inhibitors can also elevate catecholamines and metanephrines levels. Sinemet elevates dopamine levels tremendously.
Minor interferences:
Eating, standing, the stress of venipuncture, and old age. These conditions usually elevate catecholamines and metanephrines levels only slightly.
Variable interferences:
These are caused by drugs (usually beta blockers) and they are assay-dependent. The clinicians and the lab should communicate about them.
Errors:
Clerical and lab errors are also realistic possibilities. They are rare but can happen.
When I order pheo tests, I actually tell the patients initially not to worry about any interferences. If the results are normal (which is the case in most patients), the patient does not have pheo. If the results are elevated (usually in 20% of cases), I will then decide on a case-by-case basis.
This will be the last post this year. Happy holidays! I will continue posting next year.
Dr. Pheo
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Dr. Pheo
ReplyDeleteWith the Plasma Free Metanephrine test being very sensitive, it is easy to understand the possible false positives. Do you know if there is anything that will interfer with the test to produce a false negative? Like MAO inhibitors?
DJPheo,
ReplyDeleteFalse negative metanephrines are very rare. When the pheo is very small, metanephrines may be normal. Some paragangliomas are not functional thus metanephrines are normal. MAO inhibitors actually can cause false positive test results.
Dr. Pheo
Dr Pheo - I know you will be taking a well earned rest from this blog so I dont expect a reply for a while... but what happened to your non genetic malignant pheo patient? Why do so few people present with this? Does the diagnosis occur predominantly post mortem after a sudden unexplained death - as I suspect?
ReplyDeleteThanks for putting up with us all picking your brains, I'm sure you have enough to cope with in your "real" job but it's very reassuring to know you are there. Thanks again and Happy 2010 :)
Dear Jane,
ReplyDeleteThank you for the nice words!
That patient unfortunately has passed away after years of malignant pheo. Only 10% of pheos are malignant and they may take years to show. Most patients with malignant pheo are diagnosed years before death--not as you suspected.
Happy holidays to Ian and you.
Dr. Pheo
Dear Dr. Pheo can you list other major interferences with pheo tests or provide a link ?
ReplyDeleteThank you.
P.S : you have a very comprehensive and useful blog. Thks for making this effort.
Dear Sergiu,
ReplyDeleteIt is impractical to list all interferences. Some interferences may be significant in only a few patients. I am not aware of a link listing all interferences.
Dr. Pheo
Thank you, Dr. Pheo
ReplyDeleteThen I will ask a different, perhaps more useful question :
What other tumors produce hormones/molecules and have similar symptoms with pheo ?
Dear Sergiu,
ReplyDeleteOther catecholamine-secreting tumors include paraganglioma, ganglioneuroma, ganglioneuroblastoma, and neuroblastoma. About 30 other diseases can closely mimic pheo in symptoms and lab results as well. It is best for you to see a pheo expert to determine if you have a catecholamine-secreting tumor or other diseases.
Dr. Pheo
Dr. Pheo re interference,
ReplyDeletethere are many substances listed that may interfere with 24 hr urine including COFFEE, acohol and nicotine (as well as vanilla, ganglion-blockers and other less common things). Is this true - how important is it that I refrain from these things? Additionally, I read (scholarly) that, counterintuitively, coffee risks a false negative. Thoughts (none of my doctors, quite expert here in nyc - for hmo insurance, seem to know. Ordered the test for me with no caveats - just pee for 24 hrs - didn't do it yet). Does the urine jug require a preservative? Enjoy your holiday - edith.
Dear Edie,
ReplyDeleteThose can interfere with the urine tests. A better test is plasma metanephrines that has very little chemical interference. You do need acid preservatives for the urine test.
Dr. Pheo
Wow - did not expect a response so quickly - omg! Do thank you. Dr. did not inform me of any of this, but did my best on my own to get info. No preservatives in the urine sample, for sure. Just an empty jug. guess i must repeat - so the show goes on (sigh). I suppose i must pay to see subspecialist not on insurance -tired of this merry-go-round!
ReplyDeleteDr. Pheo
ReplyDeleteDo you know of any interferences that could cause false negatives as a result of taking the following medications:
Cymbalta
Synthroid
Testosterone Cyp
Benazepril
Amlodipine Besylate
Nortriptyline
Simvastatin
Pramipexole
I had many of the Pheo symptoms prior to some of these meds. My Plasma Fract. Metanephines, Normetanphrine was .99 on a <.90 scale.
Hello, I recently had a metanephrine blood test done but the result was so abnormal that it seems like it must have been an lab error? (More than a hundred thousand.) How high can levels be in a person with pheo? Wouldn't all that adrenaline going on in my body had killed me already? Strange thing is I have many of the symptoms...
ReplyDeleteDear MH,
DeleteLikely this is a cleric error in the units (switching nmol and mmol) of the report. I have seen this kind error before.
Dr. Pheo
Dr. Pheo,
ReplyDeleteLove your blog. In a recent blood test, I had slightly elevated epinephrine levels (less than two-fold upper limit) and everything else was normal (norepinephrine, Dopamine, TSH, etc). Does this sound like a Pheo?
Thanks
Dear Unknown,
ReplyDeleteUsually this slight elevation should not be a big concern. If you have a pheo in the past, or have a genetic syndrome, or have a suspicious adrenal mass, the slight elevation should not be written off.
Dr. Pheo
Thank you Dr. I have not had a pheo in the past and do not have a genetic syndrome. Could a slight rise in epinephrine be due to anxiety? I have always been afraid of going to the dr's and always experience extreme anxiety when in the office.
ReplyDeleteDear CADD,
ReplyDeleteAnxiety can do that.
Dr. Pheo
Dear Dr. Pheo,
ReplyDeleteThank you for providing this amazing service through your blog.
I am looking for some guidance in relation to some test results I have received. I hope you can help clear up some confusion I have. When my symptoms started I was a healthy 35yr old female. I have had two 24hr metanephrine test done a couple of years apart. Both times the results have been high, but not 2-3x high, and both times I have been on Clonidine 0.1mg 3-4x daily for the management of erythromelalgia and blood pressure spikes (both of which have led to the suspicion of a pheo). My concern is, since I have been on Clonidine during each test and have still had high test results, should the Clonidine have suppressed the results of the metanephrine tests? And if so, would the results have been even higher had I not been on Clonidine? I am very confused about this, and not sure if there needs to be any further investigation or not. Thank you for your time and expertise!
Ms.V
1st 24h metanephrine test:
metanephrine 215mcg/24hr rr:30-180
normetanephrine 413mcg/24hr rr:111-419
metaneph,total 628mcg/24hr rr:149-535
2nd 24hr metanephrine test:
metanephrines 181mcg/24hr rr:36-190
normetanephrine 552mcg/24hr rr:35-482
metaneph, total 733mcg/24hr rr:115-695
Dear Anonymous,
DeleteIs it safe to hold clonidine for a few days, then I would suggest measuring plasma metanephrines after that.
Dr. Pheo
Dr. Pheo,
ReplyDeleteI have a 9 year old little girl who is suspected of having a pheo. Her metenephrine is 100. (Normal is <57.)Also atch is 123 with >53 being normal.My question is how likely is it that the stress of the blood draw could have brought it up that high? Does this sound like a Pheo?
Thanks,
Amy
Dear Amy,
DeleteI am sorry but I don't know much about children's pheo.
Dr. Pheo
What is your approach if patient is on SNRI and has elevated urinary and plasma metanephrines. She can not get off SNRI even for a day.
ReplyDeleteDear EndoNY,
DeleteThe effects of SNRI on metanephrines tests are very minor. The extent of metanephrines elevation should be correlated with severity of clinical symptoms. Borderline elevation is usually false positive.
Dr. Pheo