Friday, January 1, 2010

“Adrenal medulla hyperplasia”

Recently I saw an elderly patient with episodic hypertension. The pheo markers were mildly elevated at times but normal at others. Before I saw the patient, abdominal and pelvic CT had already been done and some thickening of left adrenal gland was noted. No tumors were identified. MIBG scan had also been done, and there was a slight uptake in the left adrenal area. A few of those involved in the patient’s care believed that she/he had pheo. The patient also firmly accepted the pheo diagnosis after reading about pheo. Once again, I was the pain-in-the-neck doctor and told the patient that it was very unlikely that she/he had pheo. Then someone brought up the issue of “adrenal medulla hyperplasia” and wondered if it was not pheo, it might be “adrenal medulla hyperplasia”. I have followed the literature on this alleged condition for a while and would like to share my thoughts here with you.

Adrenal medulla, the inner part of adrenal gland where pheo is derived from, is part of the sympathetic nervous system (the “fight-and-flight” system). The exact role of adrenal medulla in blood pressure control is still not so clear. For example, most patients with bilateral adrenalectomy do not have low blood pressure. In the earlier part of last century, adrenalectomy was used to treat hypertension with mixed results. The adrenal medulla has a very small mass of less than 1 gram. The adrenal medulla of some patients indeed becomes bigger with more cells (“hyperplasia”). In patients with multiple endocrine neoplasia type 2 (MEN2), adrenal medulla hyperplasia occurs before pheo develops. In patients with long-standing hypertension, the adrenal gland tends to be bigger and both cortex and medulla are bigger.

In the literature, there are a handful of reports claiming adrenal medulla hyperplasia can cause symptoms very similar to that of pheo. In these reports, usually the patients have labile hypertension and pheo is suspected. The pheo markers are either normal or mildly elevated. The adrenal glands are either normal or mildly enlarged but clearly without a tumor on CT or MRI. MIBG scan typically is borderline positive. These reports then claim the patients immediately get better after unilateral or bilateral adrenalectomy. The pathology exam of course shows adrenal medulla hyperplasia.

Based on my own experience, my discussion with other experts on pheo, and review of literature, I simply think there are no adequate evidence and no need to consider the so-called adrenal medulla hyperplasia as a disease in clinical practice. My reasoning is as follows:

1. Adrenal medulla hyperplasia is either a pre-tumor lesion or a secondary change caused by hypertension rather than causing hypertension.
2. Nowadays most patients with labile hypertension can be satisfactorily controlled by medications.
3. There are no universal criteria accepted by pathologists to diagnose adrenal medulla hyperplasia.
4. Most patients with “adrenal medulla hyperplasia” do not have labile hypertension.
5. The diagnosis of “adrenal medulla hyperplasia” is often a hindsight after pheo is not found in the adrenal.
6. Most patients continue to experience the same symptoms after adrenalectomy.

As medicine is ever-developing, I can imagine that adrenal medulla hyperplasia may indeed cause symptoms in a small number of patients. The problem is that many patients will undergo unnecessary and ineffective adrenalectomy if we allow “adrenal medulla hyperplasia” to be in the differential diagnosis of hypertension. The proponents of “adrenal medulla hyperplasia” need to establish a clear set of diagnostic criteria to identify the few patients who might benefit from adrenalectomy.

Dr. Pheo

75 comments:

  1. Hi Dr. Pheo, Happy New Year.

    If you may remember, under your Pheo Testing in the Real World section, I posted my husband's lab results.

    The endocrinologist insisted this was a pheo, and wanted him on phenoxybenzamine. He would not run a CT, as he insists it could trigger a pheo and did not believe the NIH that it wouldn't. After much "discussion" it was decided that a referral elsewhere was in order.

    A history (sort of accurate) and the metanephrine values only (not catecholamines) were sent to an expert. His response was that there was no indication whatsoever of a pheo.

    What he said was that it was a false positive caused by medications he was on primarily cyclobenzaprine CR 30mg daily. He is also on opioids for his pain condition, and the expert said that contributed to a false positive as well. He said that the plasma free metanephrines test was useless when slightly elevated.

    So he was not able to be evaluated in person by that expert. By the tone of the letter, the expert was not impressed by the endocrinologist.

    So... okaaay... we just want to be certain, as our physicians do keep thinking the symptoms match.

    We are trying to figure out the following, to see if we should still be re-testing him, or consider the pheo 100% ruled out.

    Do the catecholamine values matter at all (the expert did not see them)?

    Is cyclobenzaprine + opioids sufficient to cause that elevation? (I'm guessing yes here)

    We found it interesting (but unsure if it matters) that the urine has high metanephrine, but very low epinephrine. Is that significant in any way?

    He has now switched from cyclobenzaprine to skelaxin. But as we have discovered, none of our doctors know the effects of the medications upon this test. So if we were to re-test, how could we figure out which, if any, meds needed to be discontinued?

    Finally, and this is just "dog with a bone" syndrome - we, and the primary doctor, have been valiently trying to figure out how opoids could cause a false positive. As opoids are CNS depressants, we would have thought that, if anything, they'd lower catecholamines and metanephrines. If you would care to contribute to my education here, I would be grateful.

    Our primary is very cooperative, and will be happy to re-run the tests if we wish. But it would be most pointless to keep running them, if he remains on interfering medications - and no one knows how to interpret that. The primary wants to be really sure this isn't a pheo.

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  2. Dear T,

    I suggest that everybody look at the big picture here rather than the technical details (which may never be clarified). The big question is how likely your husband has pheo. It sounds like an expert does not believe he has pheo. The probablility of pheo is rather low here (research has shown when two physicians do not agree on whether there is pheo, most times it is not pheo). Other causes of his symptoms should be sought after.

    If you want to be really sure, a clonidine suppression test may help.

    Dr. Pheo

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  3. Thank you - I do understand it is unlikely.

    We just would have felt more confident, had the expert been given an accurate medication list, and all of the labs, or we had actually talked to him. But, apparently none if that is going to happen. Hopefully they will find some diagnosis.

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  4. Dr. Pheo,

    Links between birth control Yaz and pheo have been popping up. Do you have any information? My daughter has the SDHB mutation and is taking Yaz, and what I've read tonite is a little scary. But all I can find is message board posts, and nothing from the medical profession.

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  5. Dear Pam,

    Thank you for asking. I did a bit of an investigation on the association between Yazmin and pheochromocytoma. The only info was that the Yazmin drug insert described without details that rats treated with Yazmin have more pheo.

    Before more is known, I think it would be prudent not to use Yazmin especially since she has SDHB mutations. There are many other brands of OCPs.

    Dr. Pheo

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  6. Another question: To treat a cervical lymph node paraganglioma that is growing fast (within a month affecting swallowing and trachea), could radiation help shrink the tumor before surgery? I thought that radiation didn't affect PGL, especially those in head/neck. Patient has dozens of tumors throughout body, is on Sutent, but this one is causing problems. What's your opinion on treatment with radiation?

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  7. Dear Pam,

    I will first see if the lymph node can be safely resected by surgery.

    Dr. Pheo

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  8. Hi,

    My name is Annie Smith and I am the assistant editor of Medicalschool.org. I am contacting you today in hopes of developing a relationship with your website; we have seen your site and think your content is great. Medicalschool.org is a purely informational site dedicated to the general Public and Medical Professionals.

    I hope you show some interest in building relationship, please contact me at annie.medicalschool.org@gmail.com.

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  9. Dear Annie,

    Can you tell me first what "building relationship" entails? The Dr. Pheo's blog is a public service website and anybody can link or cite this blog so long as due credit is given. Please note that I personally conceive and type every word on the blog myself therefore the content should be considered both informative and creative. I have the copyright for blog contents.

    Dr. Pheo

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  10. Dr. Pheo -

    I want your advice. I live in MS. One of my friends gets these really bad headaches multiple times a week, often multiple times a day. They subside and come back. I witnessed one today and I have been trying to research it, and I think pheochromocytoma may be what he has. I saw on Dr. Oz on tv where this lady had it and went to the dr and they couldn't find anything. Well, it has been going on with him for several years, and he has been to 3 different doctors and has even checked into the hospital. They tell him they can't find anything. His symptoms include high blood pressure plus he gets these attacks of headaches, anxiety, sweating, nausea, dizziness, etc. that is associated with the disease. Can you recommend any doctors or type of doctors for him to see? With it being a rare disease and our location, I think maybe he hasn't seen the right doctor.

    Any advice, insight, or help you can give would be greatly appreciated!

    Thanks!

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  11. Dear Jessica,

    Although other diseases can also cause your friend's symptoms, I agree it is wise to check if he has pheo. To do that, he can simply ask any of his doctors to order a test called "plasma metanephrines" and see what the results are. If the results are normal, it is unlikely he has pheo. If the results are abnormally high, he will then need to see an endocrinologist for further diagnosis.

    The following is a real story. A patient of mine had typical symptoms of pheo but none of his doctors realized that. The patient checked on the internet and suggested to his doctors to order a test for pheo. Again, none of the doctors would do that. He eventually begged a doctor friend (not his own doctor) to order a test which indeed showed pheo. Then he found me on the internet. I confirmed the diagnosis and a surgeon resected the pheo.

    I am not saying your friend must have pheo. It is just that his symptoms are suggestive enough so that pheo should be tested.

    Dr. Pheo

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  12. Dr Pheo -

    That is great! Thanks a bunch! I will let him know. If pheo is not what it is, what else could it be? He has seen 3 different doctors and stayed in the hospital for 2 days running tests, MRI's and all. Everybody has told him nothing is wrong, but that is obviously not true.

    Thanks again for all of your help!

    Jessica

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  13. Dear Jessica,

    Almost all causes of hypertension can present with fluctuations of blood pressure. If he does not have pheo, he needs to be seen by a knowledgeable and open-minded physician to identify other causes.

    Dr. Pheo

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  14. Dear Dr. Pheo,
    I took Yaz for 3 1/2 months last year and suddenly had high blood pressure and hot flashes/night sweats and severe headaches after I stopped the medication. Now six months later, my blood pressure is all over the place and I have Orthostatic Hypertension, which I can't find much information about. I don't have diabetes. I just took the 24 hour urine test and am waiting for results.

    Have you ever heard of anyone having Orthostatic Hypertension with pheochromocytoma?
    My blood pressure is 160/100 to 139/90 while sitting up, and 100/68 to 120/75 while lying down.

    I'm not menopausal or perimenopausal.

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  15. Dear Maria,

    Orthostatic hypertension can be associated with pheo but it is not diagnostic of pheo. The 24-hr urine metanephrines will give more accurate information.

    Dr. Pheo

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  16. Dr. Pheo,

    I am writing for your thoughts on my current situation.

    I am 24/m, physically fit, and not on any medications. In November, I saw my doc for a LONG overdue physical and my blood pressure was 170/100. Since then , I've noted that my BP is always 140/80+ and sometimes spikes very high. Records from my previous physical (18 yrs old) noted BP of 120/70. No family history of high BP except for my Grandma.

    Over the last year, I've had the first four migraines of my life. Also significant, I saw a holistic DR/chiropractor at age 20 and unprompted, he said that my "adrenal gland was shutting down." There was no further investigation.

    My Dr. initially thought the high BP could be White Coat Hypertension but wanted to rule out a pheo. We then did a 24 hr urine test for metanephrines (and normets) and the levels came back elevated - but not diagnostic-level. He then tested plasma metanephrines and those were also elevated. Based on these results, he performed a CT scan of my torso, which came back normal.

    Due to the normal CT, he retested the plasma and urinary metanephrines and the levels came back higher than they were in the first set of tests. Based on the second set of results, an MIBG scan was taken. I just received the results of the MIBG and the four hour study was normal. However, based on the images taken at 24 hours, the radiologist's findings were, "Intense activity seen in the region of the adrenal glands bilaterally, somewhat more prominent in the right than on the left. There is a mild reduction in activity in the superior portion of the liver as compared to the inferior peripheral uptake." The radiologists impression was, "Intense activity in the adredal glands bilaterally, somewhat more active on the right than on the left. These may represent medullary hyperplasia versus bilateral adenomas."

    I've now been referred to an endocrinologist but my primary doctor is stumped by the MIBG results.

    Does it seem likely to you that I have a pheo, or pheos bilaterally? Or medullary hyperplasia? Any help or advice you could give would be helpful.

    Your blog has been SO helpful over the last few months. Thank you very much.

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  17. Sorry I forgot to add that it was an I-123 MIBG scan.

    Also, here are the metanephrine test results. Unfortunately, I don't have the reference levels - only reference I was given was "high."

    24hr U Normetanephrine - 1471
    24hr U Metanephrine - 873
    24hr U Volume - 6200
    Plasma Normetanephrine - 184
    Plasma Metanephrine - 79

    Thanks again.

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  18. Dear Evan,

    I have to ask you for more information.

    1. The normal reference ranges of the urine and plasma metanephrines are actually very important. They are shown on all lab reports. It will be great if you can find them. If you cannot, let me know the name of the lab that measured them.

    2. Did the CT scan include the pelvis as well?

    Let me know the answers to the two questions. I will then share my thoughts with you.

    Dr. Pheo

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  19. The tests were done through Quest Diagnostics. The Quest website has normal reference levels but since my results were provided without measurment units, I don't know how to interpret them.

    The CT scan included the pelvis as well.

    Thanks!

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  20. Dear Evan,

    With the information you provided, I think you have a fair chance of having small pheo(s). I suggest that you do a clonidine suppression test. Do you have any family history of endocrine tumors?

    Dr. Pheo

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  21. Great - I'll make sure the clonidine suppression test is done. There is no history of endocrine tumors in my family.

    Thank you for your help!

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  22. Hello Dr. Pheo,
    My identical twin, Eileen, died on December 1, 2008 from complications for a functioning extra-adrenal pheochromocytoma (her spine was collapsing from metastasies to her spine, she was operated on on November 15th. Such a sad, sad story. But such a brave, brave fighter.
    My nephew, my brothers son, was just diagnosed with Carny Triad and has had 2 pheo's removed so far. My granson was diagnosed with a stage 3 neuroblastoma at 11 months old. He is now 16 months old and doing well after surgery at Sloan Kettering. Because of my family history, my doctor orderd the 24 hour urine and a Plasma Free test. My urine is ok but my Plasma free Normetanephrine is 651 (with a range of 0-145; my Metanephrine is 93 (with a range of 0-62. I have contacted my sisters oncologist and they are going to see my nephew to start a familial men1 or 2 study. Do you think my numbers are of concern? Thank you so much, I am sweating, panicing and flushed like you can't believe. My bp is 159/80 with Diovan.

    Thank you for any insight,
    Frances

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  23. Dear Frances,

    Your abnormal metanephrines are very concerning. You should treat them very seriously.

    Does your nephew have Carney Triad or a dyad of paraganglioma and GIST? Based on the history you provide, the most likely mutations may be in the SDH genes rather than MEN2. MEN1 does not cause paraganglioma.

    Dr. Pheo

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  24. Dear Dr. Pheo,

    Thank you for your prompt reply. It certainly gives me some peace of mind. The surgeons at Robert Wood Johnson in NJ gave my nephew the diagnosis of Carney Trid. He has another lesion in his lung. We are in the begining stage of genetic testing.

    Thank you VERY much,
    Frances

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  25. Dr Pheo,

    You were really helpful when my 80-yr-old mother had a pheo removed last year. Now her BP is back up high again (her doctor has increased her medication) and today the doctor ordered her another 24-hr urine test. She is terrified that she now has another pheo. Does this happen so quickly? she had the magnetic tests last year and nothing showed up except the one on her adrenal gland.
    thanks!

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  26. This comment has been removed by the author.

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  27. Hi, it's Frances again. About my post on my blood plasma levels; the oncologist who took care of my sister asked that I send over the results of my urine/blood work and told me not to worry - that the urine is more reliable and the blood plasma could have been affected by my stress level that day. (I have already made an appointment with an endochronologist) I am confused. Could stress affect the limits that much?

    Thank you,
    Frances

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  28. Dear Frances,

    In a person like you who has clear pheo family history, any increase of pheo markers is alarming and should be addressed. At the minimum, the plasma metanephrines should be repeated.

    It sounds like that your nephew does have Carney triad, which is very usuaual as Carney triad is sporadic and not inherited.

    Dr. Pheo

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  29. Dear flufffluff,

    Hypertension can be caused by many reasons. I won't jump to pheo recurrence just for hypertension. Let's first see what the pheo marker results are. It is unusual to have pheo recurrence or metastasis in such a short period of time.

    Dr. Pheo

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  30. Dear Dr. Pheo,

    Thank you once again. That is what I was thinking. Peace.

    Best regards,
    Frances

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  31. Hello Dr. Pheo,

    This might be the strangest question and/or statement made to you regarding pheo's. (I am going to the endo. dr. on Friday) My leg muscles are so weak; I can hardly walk without extreme fatigue. It just seems such a strange thing to happen.

    I am 51 and I have put on weight due to the difficult family circumstances and due to the fact that I have a bad injury to my left knee (due to a fall on pavement) I am waiting for a knee replacement that my doctor insists on waiting a while to do because of my age.

    I'm sorry to write to you again with such a strange thing but it is so bothersome I thought it best to ask. Thank you for all your prompt and informative answers to my questions. Wish me luck on Friday.

    Frances

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  32. Hi Dr. Pheo,

    Please disregard my previous weird post about the leg weakness. It is such a long shot; I thought there might be a connection with the levels of Normetanephrine and/or Metanephrine and muscle weakness.

    My nephew, who has the Carney Triad Syndrome, sent me this message:

    "I finally got resutls from the genetic testing and I apparently have a mutation in the SDHB gene, which apparently puts me at risk for the pheos, but we figured that already".

    Is this something my family should be checked for or is there another gene we should be looking for?

    Thanks
    Frances

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  33. Dear Frances,

    The leg weakness is beyond my expertise.

    SDHB mutation can explain the familial pheo in your family. It is unlikely that another mutation also exists in your family. Does your nephew have pulmonary chondroma or paraganglioma in the chest? It is actually an important question. The SDHB mutation is associated with paragangliom and GIST, but not usually with pulmonary chondroma.

    Dr. Pheo

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  34. Hi Dr. Pheo,

    I believe Sean has pulmonary chondra.

    What does that mean?

    Frances

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  35. Dear Frances,

    If he does have pulmonary chondroma, his disease will be unusual and of academic interests. Most patients with classical Carney triad are female and do not have family history, and the genetic causes of their disease are not known yet. SDHB mutation is known to cause familial paraganglioma and GIST, the so-called Carney-Stratakis syndrome".

    Dr. Pheo

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  36. Hi Dr. Pheo,

    Thank you again for your informative reply. I will forward the information to Sean. Do you think my twin sister, Eileen, most probably had this gene? Her pheo was the very bad type. I am not seeing an endocrinologist until next month and am still suffering very bad sweats and anxiety. It may be the stress of family affairs but it is quite bothersome. If you like, I will keep you informed of the family “gene” status.

    Frances

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  37. Dear Frances,

    Your twin sister likely has this mutation, as well as you. Please update me on the testing results when they are available.

    Dr. Pheo

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  38. Dear Dr. Pheo,

    Very interesting. I will surely keep you posted.

    Thanks again for your prompt response.

    Frances

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  39. Dear Dr. Pheo,

    Do you think that my grandson's neuroblastoma has anything to do with this gene?

    Frances

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  40. Dear Frances,

    It is possible. Familial neuroblastoma is rare. If you also have the SDHB mutation, he probably needs to be tested of the same mutation.

    Dr. Pheo

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  41. Dear Dr. Pheo,

    I am scheduled to enter a study at the NIH on April 20th. When I gave Kathryn my medication list she stated that these medications can interfere with the blood test. I am taking:

    Diovan HCT- 320mg/12.5mg
    Amlodipine (Norasc) 10 mg
    Clonazepam 0.5 - 1 or 2 x a day
    Sertraline (Zoloft) 50mg per day.
    Baby asprin (MI in 2004)

    I feel foolish not stating this before and I thought the only kind of anti depressant's that affected the results were the older types. Do you think these medications could raise my levels that much?

    Thank you
    Frances

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  42. Dear Frances,

    It is hard to say. My own experience is that these medications are usually no problems for most patients. Again, with your family history, any elevation of pheo markers is serious enough.

    Please read my Dec 3 post for more info on interference.

    Dr. Pheo

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  43. Dr. Pheo,

    Thank you and I will read it. You have been very helpful.

    Sorry to be a pest, I'm just confused.

    Frances

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  44. Dear Dr. Pheo,

    I read your post on interactions with the plasma blood test; it was very informative. My twin sister, Eileen, got severe high blood pressure as soon as she got pregnant at 21. It was never controled. the pheo was not diagnosed until 25 years later, after much pain and suffering (Eileen going through it and me watching). Eileen never had a headache, never. I thought I would add this so that maybe doctors will think "outside the box", so to speak, in terms of symptoms to be mindful of. I don't know it this helps anyone but I hope it does.

    Thank you for your infomation and reply's to my questions. I'll let you know what happens at the NIH.

    Frances

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  45. What is involved in doing a Clonidine suppression test? I have one scheduled for 4/16/10 at 9:30 AM at GBMC in Baltimore. Any preparations?? Just curious! Thanks for your response.

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  46. Please see my new posting. You should contact GBMC for detailed instructions.

    Dr. Pheo

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  47. Dear Dr. Pheo,

    As usual, an excellent explaination of the GBMC test. And many thanks for all the helpful blogs.
    Waiting for the visit to NIH is the hardest part. I stand corrected; the worst part is waiting to see the results of my grandson's testing that were done at CHOP. I am thanking God, and you, for modern technology during these trying times.

    Frances
    Frances

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  48. Dear Dr. Pheo,

    We just got word that my grandson (with the neuroblastoma) has the mutation of the SDHB gene. I am stunned. The doctors at Childrens Hospital in PA are certain that this is what caused the neuroblastoma. I believe this means that I have it as well as my daughter.

    Thank you so much for all your excellent information on all of this. I would have been more stressed out without your help. Sorry to have been such a pest about all this.
    Any recomondiations?

    Frances

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  49. Dear Frances,

    With all things considered, I agree that you and your daughter most likely have the same mutation. As this is a significant issue, it would be ideal that you and all your children be tested for the same mutation.

    Your abnormal pheo markers are now even more significant and I believe you should do abdominal and pelvic imaging and MIBG scan.

    Dr. Pheo

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  50. Dear Dr. Pheo,

    I am leaving for the NIH on Sunday for testing on Monday and Tuesday. I'll let you know of any new happenings. Thank you so very much.

    Frances

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  51. Dear Dr. Pheo,

    My visit at the NIH went very well. Dr. Pacak wants me to come back for the full evaluation. I believe he has the same thoughts on the pheo marker tests as you.

    Thank you again for your excellent blog. I'll keep you updated.

    Frances

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  52. Hi Dr. Pheo,

    My plasma levels were normal at the NIH. Very strange. Of course, everything is strange with my family and this thing right now. I am very relieved. The rest of my family is more on board now with getting tested. My nephew will be getting in touch with the NIH and will go after the school year finishes. As you know, his is a very unusual case and they are very eager to get working on it. Thank you so much for letting me pick your brain and you giving me such clear answers.

    Frances

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  53. Dear Frances,

    If we assume that you are a carrier, you should do abdominal CT or MRI anyway for a baseline screening. Some pheo/para in patients with SDHB mutations do not secrete a lot of catecholamines or metanephrines.

    Dr. Pheo

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  54. Dear Dr. Pheo,

    Thank you, I will. I believe the NIH will be following up with me. At least my family is more on board with me on this now and my nephew will be contacting them shortly. My daughter (I only have one child) has had her other son tested and will contact the NIH also. She is understandably upset at all this. Seeing her son go through what he did would make any mother scared. She's a trooper, though. She was also a big help with helping me with my sister, Eileen. Unless someone has dealt the the dire consequences of a delayed diagnosis, they could never really understand. I will spare you the details but I assure you it is, well, heartbreaking.

    I hope you realize what a great thing you do with this blog. You have saved me from much unnecessary heartache and helped me start healing.

    I will fill you in on any new SDHB gene news of interst.

    Thank you
    Frances

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  55. Dear Dr. Pheo,

    My other grandson has the SDHB gene mutation. My results are not back from NIH yet. I am thinking that both me and my daughter are positive also. My niece (my twin sisters' daughter) is planing to start a family soon. She has been in contact with a genetic counselor who, quite frankly, frightened her. Do you belive this gene mutation is a reason to forgo motherhood? I realise this is a question you may not feel you can answer. I guess my question is this: With my family history, how worried should we be for future generations?

    (I lost another sister at 43 to breast cancer which was actualy found in her pituatary gland first)

    Many Thanks,
    Frances

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  56. Dear Frances,

    I do get asked by patients quite often about this issue. Ultimately it will be personal decision. As the chance of having the mutation is 50% but the disease manifests itself variably, most people choose to take the risk and have children.

    Prenatal diagnosis of the mutation is possible but I am not aware of any commercial tests. I will write a piece on prenatal diagnosis and why it is not done routinely.

    I suggest that she talk to another counselor who is well versed on familial endocrine tumors.

    Dr. Pheo

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  57. Dear Dr. Pheo,

    Thanks for your reply. I guess we should be thankful that there are so many scans and tests to check for these tumors. I would think that most people go ahead with thier families and try to keep on top of it. Does this gene keep getting passed down? How long do you think it was in my family? It's so strange, really.
    When I went with Eileen to Yale to see about entering into a clinical trial with a Dr. Modlin from South Africa, Eileen steped out of the room. Dr. Modlin asked me if I knew where most of these tumors were found. I really didn't know what he was getting at so I just replied that I thought they were usually found in the head. He said, "No, No - I don't mean in the body; these tumors are usually found in asylums at autopsy. Shook me up for quite a while, I must say. Thank God this kind of thing doesn't happen much anymore, I would guess - and I thank God that I stuck it out with Eileen, because many people started to wonder about her.
    Thanks again for your excellent answers and the service you do with your blog.
    God Bless,
    Frances

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  58. Dear Frances,

    As the SDH mutations cause pheo/para usually after the carriers already have had children, the mutations pass through each generation. It is hard to estimate how long it has been in your family but probably for a long time.

    Dr. Pheo

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  59. Dear Dr. Pheo,

    Thank you. I think this has been in the family a long time also.

    One more thing: My throid fuctions are normal but I do have thyroid antibodies, which Dr. Neary from the NIH thought might be due to Hypothyroidism. There are two nodules on each side of my gland. I understand that this is common but was wondering if it could contribute to my weakness and weight gain. Could all this have to do with depression, also?

    Thank God this is my biggest health problem at the present time but I am eager to get back to "normal" and am more than a little frustrated with myself.

    As always, thank you so much for the pethora of information you have shared with me.

    God Bless,
    Frances

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  61. Dear Dr. Pheo,

    Upon furhter thought, I thought it best to add that during the ultrasound of my thyroid at the NIH, the tech doing the scan steped out of the room stating that he had to have his doctor do the scan. When the doctor came into the room he asked me if I had pain in the thyroid area. When I replied, no; he asked me if I was sure. He then explained the various scenarios about thyroid cancer and the difficulty in selecting just a couple of nodules to biopsy and said he would recommend follow-up. (I don't think I have cancer, by the way)
    I did a little reading on a couple of thyroid conditions and am now anxious that I will have to wait another 4 months to see an endocronologist here (on the Jersey Shore) and don't feel comfortable taking supplements without further evaluation. I should add that my mother and three other sisters took or take synthroid (?) for underactive thyroids. My oldest sister actually just had her thyroid removed because it was so enlarged.
    To be honest, I just don't know which end is up right now. I will tell you that I was fired from my job when Eileen was falling and, well, the other effects of her spine collapsing. I had to take her to the hospital and try to help her which I guess was not good for business. I tried to take my vacation time but was fired before I could do that. I am still unemployed and am in danger of losing my home. Helping my daughter with my grandson with the neuroblastoma has put me further in "the hole". I tell you this to put some kind of perspective on my stress levels at this time. This is after many years of trying to help Eileen. I am feeling kind of whipped.
    I am also in constant pain as I am waiting for a knee replacement after a bad fall in 2004. Since I am 52, the doctor wants to wait 6 months to a year to do the replacement. So, I don't want to over react to anything, but maybe you can see my frustration level. Whew...sorry about sharing too much of my story but I am kind of lost and need a bit of help. I was always healthy and active but have now put on over 20 pounds (puffy face and all) and can't excercise much with the knee like it is.
    Have you ever recomended taking supplements like selenium or iodine? I doubt it, but I was wondering if there is something I could do in the meantime.

    Sorry about being a pest again.
    Thanks,
    Frances

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  62. Dear Frances,

    Since your thyroid function is normal at present, I do not recommend selenium or iodine supplements. The thyroid antibody means you have a higher chance of having low thyroid function but does not mean you must have it.

    The thyroid nodules are a topic by themselves. Basically if they are all smaller than 1 cm in diameter and do not appear suspicious on ultrasound, you can just monitor them. Otherwise a needle biopsy is generally recommended.

    Obviously you have been through so much. Hopefully things will be better.

    Dr. Pheo

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  64. Dear Dr. Pheo,

    Thanks. I needed to hear that.

    Things will improve; I'm sure of it.

    God Bless,
    Frances

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  65. Dear Dr Pheo,

    I am a 46 y.o. male with labile BP (anywhere from 110/70 to 180/120), refractory to antihypertensive medication. I sweat excessively & have a fast pulse (sometimes 120 bpm at rest). I also sometimes experience palpitations when turning to my right side in bed.

    My plasma normetadrenaline was 1260 pmol/L (normal <900) in one test, prompting an MIBG scan.

    The I-123 MIBG scan showed "intense focal activity in the left adrenal gland, highly suspicious for a pheo".

    However, a CT scan showed "mild thickening of the medial limb of left adrenal but no obvious focal lesion" and an MRI showed "mildly nodular left adrenal with no evidence of discrete macronodule".

    My subsequent plasma normetadrenalines were normal twice, as were 24-hour urine catecholamines.

    May I please ask for your opinion?

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  66. Hi Dr. Pheo,

    I just wanted to update you. My daughter and two grandsons are at the NIH. My daughter is being screened and, as the two little one's have already had thier scans, the doctors are just meeting with them. My grandson, Xander, the little one who is doing well after the neuroblastoma is of special interest to the doctors there. We had the slides of the cancer sent to the NIH and they are working with them now. With all the cancer, along with the SDHB gene, I am hoping that out of our grief may come hope for others. It has been such a rough road but I am begining to see the light again.

    I can't thank you enough for all the wonderful advise and just letting me vent a little. You are a brilliant doctor and have helped change my views about a lot of things.

    Things ARE getting better.

    God Bless,
    Frances

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  67. Dear Frances,

    Thank you for letting me know. I wish you all the best.

    Dr. Pheo

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  68. Dear Dr. Pheo,

    I just wanted to update you.

    The doctors at the NIH that I met with called me to advise me of some things of interst to them. They seem very interested in the mutation that my grandson has. I guess the mutation he has is something they have been searching for. We discussed my twin sister, Eileen, also. Since only one biopsy was able to be done of her primary tumor in 1991 (the tumor was unresectable; it was right at the point where the aeorta and abdominal aeorta meet, wraped arount her inferior vena cava, mesinteric artery and renal vessels). I took a chance and called the hospital. They did have the slides still and sent them to the NIH. They also had another biopsy that was done on the cancer in/on her spine) and a biopsy of a brest tumor(that wasn't diagnosed as breast cancer). The doctor seemed pleased with being able to get these.

    So, maybe after all this grief, some good investigations and discoveries will be made to be of help to others. Let's hope!!!

    Frances

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  70. Dear Dr.

    I'm a 29yrs old patient, Suddenly i got hypertension before 1.5 yr, alllab tests gave me good results (kidney function, liver functione, electrolytes, lipid profile,...) Physician asked me to make, renin, aldestrone and catecholeamines. I got normal renin and aldestrone but elevated catecholeamines (normal range max value is 100 but mine was 164) in 24hrs urine collection.
    Dr. started to give me carvidilol 25mg but i kept getting high blood pressure of around 150/110, short breathining, high heart rate, flushes,sweating, and extraordinary headach.
    I made MIBG and they told me suspecious lesions, ultrasound gave normar result.
    I made adrenalina, nor adrenaline, catecholeamines and VMA in urine, Adrenaline(Normal 20, i got 25), Noradrenaline(Normal 70, i got 125), VMA(Normal 16, i got 36) and catecholeamines (Normal 100, i got 143)
    Abdom CT scan gave a prominent left adrenal gland with hyperplasia. PET CT and Octereotide scans gave normal results.
    Now i take 50mg carvidilol and 12mg cardura daily.
    Dr. Made clonidine suppression test for me, noradrenaline got reduced from 1025 (normal max=600) to 524...fractionated catecholeamines get reduced to 528 My Dr. Still see all these results equivocal.
    I repeated Noradrenaline, adrenaline and metanephrines in urin again, Noradrenaline(normal max=70, I got 126), adrenaline (normal max=20, I got 25), and metanephrines (normal max=1000, I got 1205).
    Is it pheo?
    What do you advice? Any other more tests needed? I'm suspecious from 1yr and I want to get ur guidance pls.
    Is it essential hypertension? I think no family history. Also I've an Identical twin sister, she doesn't have HTN, is it possible she may get the same problem?
    Waiting to hear from you very soon
    Regards...

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  71. Hi Dr. Pheo,

    I am a 38 year old male with asthma being my only real complaint. Five weeks ago I was at home when I felt my body become very quite followed immediately with a sensation of losing blood and going into shock. I took my blood pressure and it was 97/57 (has been pretty normal my whole life) and thought I had some sort of internal bleeding going on, and almost immediately after that thought my heart felt almost a "pop" and then started beating super-fast. I started to walk to the hospital, but after 10 minutes or so I started to feel normal and thought that if I wasn't dead yet, that it would be alright in a day or two. I could feel my heart beating for the next week, and it seemed out of place, hesitant, followed by double and triple beats from time-to-time. I almost fainted about a week later while standing in a lineup, and my body seemed to recover by again throwing the heart into overdrive and felt like I was in a marathon. Later that same night, my heart started beating like crazy again, and I went to the hospital.

    At the hospital my beats per minute was 150 and bp of 147/97 and was immediately looked at by a bunch of super-concerned people. They took a general set of blood samples and asked me a bunch of questions. A couple of hours later the results came back and everything was pretty much right down the center in terms of results. Ativan and metoprolol seemed to get me back down to a regular state. I was referred to a cardiologist and discharged without any explanation other than Sinus Tachycardia NOS. A few days later the same thing happened and I went in to talk to my GP, who said it sounded like anxiety. I have also been having severe night sweats over the past year and that seemed to catch her attention, and then sent me for some blood tests to check for ptuitary and parathyroid issues, along with a fasting glucose test. The glucose result was a bit above reference but she didn't think it was anything to worry about, and wanted to wait to see what the cardiologist said. I went and saw the cardiologist after wearing a Holter monitor and he remarked that he thought my cardiovascular system was fine, but there was a competing pacemaker to my sinus node pacemaker and that he thought it was secondary to something else. My blood pressure in his office was 160/ 100 with a heart rate of about 110 bpm which he seemed quite concerned about. He called my other doctor and came back with a prescription for diltiziem and a referral for a fractionated catecholamine test. By this time I had noticed that I was no longer using my inhaler for asthma, where as prior to these 'episodes' I was using it 1-4 times daily which he thought was strange and when he listened to my lungs he said they were like an 18 year olds. He could also see that I was 'on something' because my speech was really rapid. I did the urine test the next day, but felt exhausted from the day before and had no episode during the urine test. I got the results back and my normetanephrines are slightly elevated (2.67umol/d - ref is 0.48-2.42) and the same with my norepinephrine results (507 umol/d - ref is 89-470). All other results were within range (metanephrine, epinephren and dopamine). I do have regular flushing that is noticeable as well.

    Are there any more tests I should be suggesting as I feel like the doctors are baffled, the cardiologist doesn't want to really look into it (he told me that as a specialist that it isn't in his wheelhouse to see this through and I should be consulting with my GP, but she seems stumped)? Any advice would be greatly appreciated.

    Thanks,

    -Unknown (for reasons)

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  72. Pheochromocytoma Or Conn Syndrome or Androgenital syndrome with feminization character
    Dear Dr Pheo I have to tell you form start that I'm a GP looking after the below person and don't know how to help him further The pateint is an educated immigrant from Africa who lectures at a University here in melbourne He has been hypertensive for years . and was found to be very hypertensive witth hypertophy heart during immigration Medicals in south Africa . He narrated long history of palpitation . blurry of vission tightness of chest and worsening symptosm after drinking coffee or coca cola . He was found to be hypokalemia and hypertensive and had a try of spirolactone which help with the symptoms and K+ has been corrected since Plasma aldosterone was rasied and he has been using Betaloc 200mg daily for the palpitation andf tachycardia He did developed gyneacomastia . it has been ongoing before spirolactone since puperty but became more pronounced abfter spuirolactone and Had mastectomy apprantly lately he will just have blurry of vission and sweaty and was suspected to be having phaechromocytoma . he had 24 urine cathecolamine wihich was elaveyd and plasma metanephrine level was elvated too He had MRI which didn't show any adrenal pathology upon CT scan he had 2 years earlier which was normal too He had MIBG ytest whichshows a ctivities on the Left adrernal galnd in keeping with pheachronmocytoma My question is could someone have both pheochromocytoma and conn syndrome together . what about his feminization [preserntation too No doubt this man Had adrenal issue . without a tumour seen on MRi . can surgery still be done using the MIBG result

    View profile for Remi »

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    1. Dear Remi,

      Pheo and Conn can co-exist. This patient unlikely has pheo unless his pheo markers are markedly elevated. CAH due to 17 alpha-hydroxylase deficiency is a concern. I am against left adrenalectomy which unlikely cures him.

      Dr. Pheo

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