Thursday, February 6, 2014

Tis the season to be false positive

If the interpretation of pheo marker results is already complicated, our current season adds one more variable for us to consider.

A seasonable paper on seasonal variations of pheo marker levels was just published. The researchers charted pheo blood marker levels in each month of the entire year in people without pheo. They found that the normetanephrine levels were about 20% higher in wintertime than in summertime. The normetanephrine levels did not vary between seasons in patients with pheo. As you probably have guessed, the study was done in the Netherlands and Germany (one city in each country) where there are big temperature differences between winter and summer. Actually, during the same wintertime, the normetanephrine levels are a little higher in the colder city. To prove that the cold temperature causes elevation of normetanephrine levels, the researchers warmed the forearms where blood was drawn and found the levels dropped.

The 20% higher blood normetanephrine levels in wintertime do not sound too much but can make a result from high normal to borderline abnormal. We already know that anxiety, stress, sleep apnea, hypertension, older age, and some medications are associated with higher normetanephrine levels. All these factors, including wintertime, need to be weighed before a decision is made about the lab results. As I have reiterated many times before, the pheo diagnosis should not be based on a single lab test but should be based on the totality of the patient’s condition. Clinical presentation, lab results, and imaging characteristics are all important.

It would be interesting to do the same study in a tropical area like Hawaii. We would predict that the blood normetanephrine levels in people without pheo remain similar throughout the year.

The new wintertime confounding factor in pheo test result interpretation reminds us once again that a test result is influenced by many factors. Simply calling a test result positive or negative will result in misdiangosis. 


Dr. Pheo

37 comments:

  1. Hello Dr. Pheo,
    This is very interesting - thank you for sharing the information. (I would be more than happy to volunteer for the Hawaii study)
    I wonder if this has anything to do with the "high altitude" part of this? Is that true, that people with SDHB should not live in high altitudes?
    I was reading an earlier post on corticosteroid and pheo, especially when you discussed the difference between the adrenal medulla and cortex. Would a pheo ever form in the cortex? How about a Pheo and an adeneoma in the cortex? Could anyone ever have two types of adrenal tumors at the same time, causing confusion in diagnosis?
    Sorry for all the questions.
    It's great to read all the information you have...we appreciate it.
    Best,
    Frances

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    1. Dear Francis,

      Thanks. It is probably different from the high altitude issue which is more about low oxygen. I don't know whether there are already data on high altitude and more frequent pheo in people with SDHB.

      Pheo is mostly from the medulla. There are tumors with mixed features and there are people with two tumors, one from the cortex, the other from the medulla. These are rare though.

      Dr. Pheo

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    2. Thank you, Dr. Pheo.

      I had bi-lateral pheo's removed in December. It was found that in my right adrenal there were Adenoma's in my cortex in addition to the small pheo. (My pheo's were very, very small.)
      I am just very confused about all this. I am very concerned about how this SDHB mutation is causing so much heartache in my family. I hope for some new discoveries; it's the children I worry about most.
      Thank you so much for all your kind help.
      Frances

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  3. Dear Jen,

    The likelihood of pheo is not high. The best next step will be the clonidine suppression test to give additional information.

    Dr. Pheo

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  4. Thank you SO much! Love to hear this, and that IS what my doctor is doing next for me. I'm keeping fingers crossed for continued good news, and appreciate your input. Have a great day.

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  5. Hi! I have a few year history of having a 1.1 cm adenoma on one of my adrenal glands. I was CT scanned because of symptoms such as whacky blood pressure, flushing, palpitations and excessive urination. My blood pressure is mostly normal, but when a "spell" hits out of the blue, like yesterday, it shot up to 164/95, which is high for me. Past testing from a couple of years ago showed normal levels of catecholamines. The real question I have is, at night when I roll over to my left side(I half sit up as I roll over), it will 80% of the time bring on palpitations and my heat flush. I absolutely cannot stand any pressure on my abdomen, such as tight clothes or even sitting at a 90 degree position. Could a growth on an adrenal be fairly quiet until pressure is put on it, and then it release cats that then cause symptoms? Thanks!

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    1. Dear Anonymous,

      A small pheo, when agitated, can cause problems. Whether your small adrenal tumor is a pheo is best tested by plasma metanephrines.

      Dr. Pheo

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  6. Hi Dr Pheo, could you help me this this please:
    Thanks in advance

    1) Left Adrenal
    2) 42
    3) No
    4) Single
    5) hashimotos

    Jesse

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  7. I was wondering if pheos use iodine to make catecholamines? I used to get panicky if I had iodine in my daily diet(iodized salt), so switched to uniodized and felt better. I still consumed iodine foods, such as shrimp.Years later I had my thyroid removed, and I decided to try iodized salt again. Within 2 weeks I was having my panicky, adrenaline feeling again. I know when I've had CT scans with contrast to check on the adrenal nodule I have, about 10-14 days later I have high blood pressure, tachycardia, and panicky for a few days. It took me a couple of CT scans to see the pattern. So, my question is, without a thyroid, what in the body uses iodine to increase (apparently) catecholamines? Can possible pheo nodules do that?

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    Replies
    1. Dear Anonymous,

      I actually have not heard anything about the link between iodine use and catecholamine synthesis or release.

      Dr. Pheo

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    2. Thanks so much. That then rules out the adrenals using the iodine.

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  8. I had a left laparoscopic adrenalectomy for a pheo 7 years ago. Also had a complete thyroidectomy for papillary carcinoma later that same year. I was diagnosed with stage 2B small cell carcinoma of the cervix in Sept 2013. I was treated with chemotherapy and radiation. The initial workup that was done in Sept revealed a small renal mass that was concerning to my oncologist, who referred me to a urologist for further evaluation. He ordered plasma free metanephrines- the normetanephrine value came back at 3.90 (normal <.90) and metanephrine value was <.20 (normal <.50). I had been having some what felt like "mini" pheo episodes (very brief episodes of back & chest pain associated with headache & hypertension; sweating spells). He put me on dibenzaline and I had a partial nephrectomy on March 4. The pathology report for the 2 specimens that were sent showed both were extra- adrenal paragangliomas in perinephretic fat and in gerota's fat, one incompletely excised. The kidney margin was free of tumor. I have a follow up CT and appt with him in 4 months, and I see my oncologist in April. I was told that 97% of these tumors are benign. Should I feel ok with this information?

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    1. Dear Cathy,

      Was it the left or the right kidney that was partially removed? The side actually matters.

      Dr. Pheo

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    2. Left-same side.

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    3. Then they are likely recurrence of the old pheo rather than new paragangliomas. Either way, I wonder why the second tumor cannot be completely taken out. You may ask your doctor that. You should also do an MIBG scan at the same time of the CT.

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    4. Would you please explain why left or right kidney makes a difference? Is there an impact on outcome? Malignancy?

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    5. If a pheo is found on the opposite side where the first pheo resided, then this is bilateral pheo which is often due to genetic mutations. Prognosis is usually favorable. If a pheo is found again at the same side, then it is likely recurrence which suggests an aggressive course. It not malignant per se but malignant pheo often presents as recurrence initially.

      Dr. Pheo

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  9. Thanks for your reply. My oncologist sent me for a PET. The report stated "no concerning hypermetabolic lesion appreciated." My endocrinologist also ordered repeat plasma free metanephrines (normetanephrine 1.30-nmol/L- slightly elevated from the ref range of <.90) and a chromogranin a (263 ng/ml, ref range <.93). Not on any GI meds but my BUN and creatinine have been slightly elevated since I began treatment for the small cell cervical cancer. I've continued to have mild pheo-like attacks. Should I be concerned with these test results or just relax for now?

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    1. Dear Cathy,

      The imaging and test results show that the tumor bulk is greatly reduced by the surgery but whether all tumor cells are gone is not guaranteed. Your symptoms are unlikely related to pheo. I would continue to monitor your plasma metanephrines probably every 6 months or so.

      Dr. Pheo

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  10. Can you tell me the hospital in the US that you would recommend for biomarker tests and gists determination in my daughter that is positive for sdhb and having severe stomach issues and headaches, abdominal xray that show impaction, and a brother with a large pheo removed 2 years ago in adrenal gland. We have already been to NIH and received no help.

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    1. I am sorry that I don't know the answer. I would have thought that NIH would be the best place.

      Dr. Pheo

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  11. Hi I have read the post and am thankfull I found it. My dr did a 24 hr test and it came back normetanephrine 242-marker range 82 -500....normetanephr 847 markers 110- 1050...dr say because of my symthoms and urine test they suspect pheo.what shouls I do.

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    1. My symthoms are constipation cheat pain with heart rate going up .blurry vision.abdomnial pains especially on right lower side. These feeling hit me out the blue. And have made me depressed and anxious

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    2. Dear Anonymous,

      If the urine metanephrine and normetanephrine levels are both normal (as they appear to be), pheo is ruled out. You should then search for other causes of your symptoms.

      Dr. Pheo

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  12. The dr says my normetanephrine should only be 500..

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    1. Please be reminded that my opinions here are just for your information. You should always follow your own doctor's recommendations.

      Dr. Pheo

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    2. My dr says he doesn't know about pheo.he just did the test because of my symthoms...and he doent undersyand how one came high and the one in 3 weeks low.

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  13. What can cause normetanephire to be up about 300 .....

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  14. 36 year old female history of anxiety, severe migraines, autonomic dysfunction (pots syndrome) , axially freckling no other outer criteria for neurofibro-1 possibly segmental. Awaiting metanephrine plasma result...my question is can a person go years undiagnoised? Can postpartum cardiomyopathy actually be pheo complications and is a blood pressure increase of normal reading of 90/60 to 120/85 during my eposides actually consider a increase?

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    1. Dear Anonymous,

      These are both possible. The metanephrines test will help to see if pheo is indeed the unifying diagnosis.

      Dr. Pheo

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    2. Thank you for the response. Still awaiting results very nervously. I finally figured out how to go through your older topics and came across the Specialist list is there a updated version?

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    3. Dear Anonymous,

      There are new specialists I would like to add. I just have not had enough time to verify their publications yet.

      Dr. Pheo

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  15. Anonymous said...

    Dr. Pheo, I had a 4.0 cm tumor removed in May of 2014 due to a pheo tumor on my left adrenal gland. I do NOT have high blood pressure now that the tumor is removed, but I do have severe headaches that never end. I also have had genetic testing and have found to have a 5-MTHFTHR gene with a TT. My family physician says it was inherited from my mother's side of the family, but both my mother and father each had the TT gene and passed it on to me. Please, can you help me with the never-ending headaches I suffer from. I can hardly stand the pain.





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    1. Dear Anonymous,

      I am not aware of a link between pheo and MTHFR polymorphism. I suggest ruling out recurrence of pheo. I really do not know much about headache per se.

      Dr. Pheo

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