Tuesday, November 23, 2010

Corticosteroid and pheo

This interesting topic is suggested by a reader. The relationship between corticosteroid and pheo is multifold and involves several fundamental physiological issues.

Firs of all, the close proximity of the adrenal cortex and adrenal medulla is an intriguing phenomenon. The adrenal glands are small organs. An adrenal gland actually is further divided into two organs, the cortex (secreting corticosteroid) and medulla (where pheo is derived from), each with related but different functions. Why is the adrenal medulla wrapped around by the cortex? Why isn't the medulla located inside other organs, say, the spleen or liver, or a free-standing organ like a ganglion? I can only think of two other organs, pituitary and pancreas, which are also further divided into two organs. In the case of pituitary, anterior and posterior; pancreas, exocrine and endocrine. The question is still unsettled. Existing evidence suggests that the corticosteroid secreted by the adrenal cortex is important in maintaining the medulla what it is. If one takes the cells from the medulla and puts them in culture, those cells automatically differentiate into neuronal cells. If one adds high concentrations of corticosteroid into the culture, the medulla cells will remain neuroendocrine cells and do not differentiate into neuronal cells. As the medulla cells are derived from the neurocrest during embryonic development, it is hypothesized that the migrating neurocrest cells encounter adrenal cortex cells (which provide high concentrations of corticosteroid) and really like them and stay with them. Thus the story of adrenal cortex and adrenal medulla.

Second, corticosteroid stimulates catecholamine production and release from cultured adrenal medulla cells. Corticosteroid increases catecholamine production by upregulating the key enzymes for catecholamine production. The mechanisms for which corticosteroid stimulates catecholamine release are not clear and may not be straightforward.

Third, corticosteroid prepares the target tissues of catecholamines to be responsive to catecholamines. That is why patients with adrenal insufficiency often have low blood pressure even when they have high catecholamine levels.

Lastly, there have been a number of case reports on pheo crisis induced by corticosteroid use. The pheo crisis usually starts a few hours after corticosteroid use. There may be hemorrhage within the pheo. In patients with known pheo or an adrenal tumor of unclear nature, corticosteroid should be avoided if possible. When corticosteroid is used, patients should be closely monitored. In my own experience, pheo crisis by corticosteroid is rare and not a predictable event.

On a separate note, I have been very busy recently. To readers who are used to my quick responses, I may appear to become sloppy. I apologize. I am still following this blog closely but not as frequently as before. Please rest assured that I will respond to your questions, just not as timely.

Have a great Thanksgiving!

Dr. Pheo

63 comments:

  1. That is what happened to me when I was given a very low dose of Prednisone and HC, my blood pressure went very high. My Endo stopped the treatment ( I was given the Pred then HC to try to cure my severe fatigue) for adrenal insufficiency. Biochemically a Pheo is not the diagnosis, however, now I've noticed a mass / lump (not well defined) on my upper right side abdomen. Dr. Pheo, can an Adrenal tumor be palpated?

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  2. Dear Skipper,

    One can usually palpate only a large adrenal tumor (8-10 cm).

    Dr. Pheo

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  3. Thanks Dr. My Endo is suggesting I get an ultrasound of the liver and gallbladder. If I have a swelling / mass in the location described above, would a scan of the kidney / adrenal gland be wise too? Also, the mass is not well defined more like a swelling.

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  4. Dear Skipper,

    The ultrasound of the liver and gallbladder probably will be sufficient. It is important that you tell the technician where exactly it feels like a lump.

    Dr. Pheo

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  5. Dr Pheo. can an Adrenal tumor secrete more hormones when smaller in size, but slow down the amount of hormones as the tumor grows larger?

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  6. Dear Skipper,

    It is actually the other way round. Larger tumors secrete more hormones.

    Dr. Pheo

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  7. Hi Dr.Pheo!!!

    I can't say thank you enough. I have been to see Dr.Pacak at the NIH, and I have to say they saved my life. I am currently under the care of him, and right now my hormone levels are elevated, just a bit. But, we will be watching and waiting to see what happens with my adrenal gland tumor.

    During my visit to the NIH, I got the opportunity to meet all kinds of people, just like me. I also got connected to the PheoParaTroopers.com website and I am now co-chairing the newsletter, which is coming out 1/1/11.

    I hope you and your readers will take a minute and look at the website, also sign up for the newsletter. The purpose of the PheoParaTroopers is to connect patients with this disease with others that have it. We are also trying to bring awareness, and raise funds to help with research. But, the most important thing we are trying to do is to let people know they are not alone and we have to fight this thing "together."

    One thing we are doing on the newsletter is we are going to float around "Pheo Phacts" and "Para Phacts" they will be spread throughout the newsletter to make it more fun, as fun as you can get with tumors. Do you have any “cool” facts that could be included in the newsletter? I already have a “Pheo Phact” The youngest patient with a Pheo was 2 years old, she had VHL. The oldest was 81 with a unsuspected bladder Pheo. I would love to hear anything you find an interesting “phact.”

    This newsletter and the PheoParaTroopers is a organization founded by patients for patients. However, one of our goals for the newsletter is to include articles written by medical professionals. Would you being willing to be a contributor for a future newsletter? If you have any questions, please feel free to contact me.

    Thank you,
    Heather

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  8. Dear Heather,

    Thanks for the update. For the "Phacts", we actually diagnosed and operated on an 82-year-old female patient with adrenal pheo this year. I will check my collections and let you know.

    I will be delighted to contribute to your newsletter.

    Dr. Pheo

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  9. Dr. Pheo, I had read somewhere if the adrenal tumor is large sometimes they don't secrete hormones into circulation but remain within the tumor itself, any truth to that theory?

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  10. just checking before I type alot...

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  11. Okay, that went through.

    I would like an opinion. A person has a 1 cm. nodule on their adrenal gland, found when looking for the reason to lightheadedness with standing and incr. heart rate and b/p also while upright. This has gone on for 4 years. The recent TTT showed avg. HR of 115-130, and an avg. b/p at 170/110, with systolic spikes at 200. Very heat intolerant. Standing and sitting up straight bring all this on. Resting cats. are at 80%tile of normal. Have not had standing norepi. measured, but assume really high. COULD this be a pheo that activates positionally? Symptoms are very life-limiting. Have lost 30 lbs. in 2010, by eating less, but not due to any activity, as can't tolerate it. Now am having trouble with higher fasting blood sugars, normally fight low blood sugar. Any words of wisdom?

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  12. Dear Skipper,

    It only happens to cystic pheo. Larger solid pheos do produce more catecholamines.

    Dr. Pheo

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  13. Dear sue,

    Please tell me the person's age and sex.

    The person should measure plasma metanephrines to test for pheo. My clinical suspicion is not high.

    Dr. Pheo

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  14. Female, age 50. Plasma normets. at 126 pg/ml.

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  15. Dear sue,

    If the normal range is less than 148 and metanephrine is also normal, the person is very unlikely to have pheo.

    Dr. Pheo

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  16. I was hoping you could give some insight on my sister's tumor. She was scheduled to have surgery in 3 weeks. She has a glomus jugulare tumor located by the 7th and 8th nerves. It is large, 3.5X3.5X2. All was going well until they realized that her dopamine is high, blood level 153. Since she has low blood pressure they are concerned that they can't give her a blocker since it would lower her blood pressure further. Now surgery is put on hold. Do you have any words of insight regarding this? She is having facial episodes and has limited her activity.

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  17. They have identified this tumor as a paraganglioma. She has the SDHB gene mutation.

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  18. Dear Team Burns,

    If this is a tumor that only secretes dopamine but not epinephrine or norepinephrine, preoperative alpha blockade is not necessary and may even be dangerous. Her blood pressure may be higher after tumor resection.

    Dr. Pheo

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  19. Thanks. From my reading, she can go ahead with surgery, but it is risky.
    And article in the Singapore med journal (http://smj.sma.org.sg/5105/5105cr3.pdf) suggested metyrosine could be used as it inhibits tyrosine hydrolase but has no alpha blocking effects. Thanks for your quick response

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  20. Dr Pheo, can a cystic pheo cause symptoms like high blood pressure, fast heart beat and dizziness/ balance problems?

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  21. Dear Skipper,

    A cystic pheo can cause pheo symptoms. Sometimes it is more subclinical.

    Dr. Pheo

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  22. Full abdomen ultrasound normal, yet there's a lump on my upper right side no one can explain. I'm done searching, coming to grips with the fact that I will feel ill the rest of my days. 10 years of chronic diarrhea, 7 years of dizziness / balance problems, depression, low cortisol, high blood pressure, low testosterone without a diagnosis??

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  23. Dr. I've already had an MRI of the Pituitary gland, twice I believe. Wouldn't this rule out trouble with the Pit gland?

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  24. Dear Skipper,

    That suggests it is unlikely that you have a pituitary problem. In rare cases, the pituitary does not function well but appears normal on MRI.

    Dr. Pheo

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  25. Hi I have recently had flu and from day 2until about day 6 or 7 I had nearly constant episodes of racing heart sweating and nausea just like when I have my other attacks only lasting alot longer,can this happen when you have a pheo ?

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  26. If CT imaging of the adrenals is inconclusive (one adrenal slighlty larger than the other - no mass), will a clonidine suppression test exclude the adrenals as the source of moderately elevated normetanephrines. And would the test also exclude paraganglioma?

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  27. Hi what would be the best scan to ask for to see if I do infant have a pheo as I have had the 24 hour urine test that came back normal but I am convinced that after 5 years of suffering and various other tests I just need to completely rule a pheo out before I can move on to sort this all out. Manu thanks for your time.

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  28. If the clonidine suppression test excludes pheo, it also excludes functional para.

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  29. If the urine test results are normal but you have pheo symptoms, the best way is to have blood metanephrines tested. If the blood metanephrines are also normal, it is unlikely that you have pheo and I don't recommend imaging in that case.

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  30. I am in the uk and my local path lab do not do that blood test yet although they say they are working on it,so I was going to pay for a scan just to know once and for all. I do have a appointment coming up with a new neurologist but somehow just feel in my mind I need a scan as so far I have only had brain and spine MRI and lumber punctures done.

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  31. Hi, it's me again. With confirmed multiple bone mets (SDHB mutation), the last 2 weeks have brought severe back pain, with an MRI yesterday. The oncologist says 2 of the spinal tumors appear to be causing the trouble and suggests radiation. What do you think?

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  32. Celina,

    Regarding the plasma free metanephrine test. If you haven't already, you might try contacting some of the members at AMEND. Amend.org.uk. Since there are members from the UK, they know the ins and out the UK healthcare system and maybe able to suggest how to get the blood test done even if your local surgeon doesn't have access to it.

    Regards

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  33. Celina,

    I do not recommend imaging before the blood or urine test results are suggestive of pheo.

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  34. Pam,

    Radiation is a good therapy for bone metastasis. If your pheo produces catecholamines, you need to watch for pheo crisis.

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  35. Why do you not recommend imaging first as surely thats a definitive way of telling you if there is a pheo or not.

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  36. Dear Dr. Pheo,

    I am a 34 year old male who suddenly started experiencing PVCs and increased anxiety/irritability/rage. My doctor wanted to rule out pheochromocytoma. Below are my test results over the last few months in the order they were performed:

    Catecholamine and Metanephrine 24 Hour Urine:
    Metanephrine (152-1775): 1784 nmol/d
    Normetanephrine (273-3548): 1381 nmol/d
    All catecholamines within normal limits.

    Catecholamine and Metanephrine Plasma:
    Metanephrine (0.0-0.49): 0.78 nmol/L
    Normetanephrine (0.0-0.89): 0.37 nmol/L
    All catecholamines within normal limits.

    MIBG Scan:
    Small focus of increased uptake in the upper abdomen just to the left of the midline best seen on SPECT and 3D images.

    MRI:
    Unremarkable MRI of the adrenal glands with no adrenal mass seen.

    A second Catecholamine and Metanephrine 24 Hour Urine:
    Metanephrine (152-1775): 1529 nmol/d
    Normetanephrine (273-3548): 1331 nmol/d
    All catecholamines within normal limits.

    Since the MRI was negative and the last urine tests were negative, a pheo was ruled out. In your opinion, is there still any reason to suspect pheochromocytoma? For the MIBG, what would cause increased uptake in that particular area?

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  37. Celina,

    Imaging is an awkward and expensive way of ruling out pheo. It can not diagnose pheo. It will also find things incidentally that are hard to interpret.

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  38. Frey,

    It is unlikely that your PVCs are caused by a pheo. You might still have a very small pheo. The mildly elevated metanephrines should not be discarded. Most false positive results are from normetanephrines. It is very rare for the metanephrines to be false positive.

    The significance of the MIBG results is not very clear. Unilateral uptake in normal young men is not rare. The intensity of the signal is important here. If the signal is very strong, a small pheo is more likely.

    In summary, I would still follow your plasma metanephrines over time. If they become normal, then forget the pheo. If they are persistently elevated, a small pheo is more possible.

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  39. Dr. Pheo

    A recent medical case report about localizing a tumor for a pregnant woman raised some questions. Obviously the doctors took the whole issue of radiation seriously when they did the PET-CT. Was the need to localize that important in the treatment and dx of the patient... other than for the surgeon? They discuss recommendations for when to do the surgery, but in the absence of information it sounds like the tumor needs to be removed before the birth of the child. Is the delaying of surgery with a patient an equally viable option as long as the mother's blood pressure is medically controlled and a C-section is performed near term?


    South Med J. 2010;103(12):1238-1242.

    http://www.medscape.com/viewarticle/733883_sidebar1

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  40. DJPheo,

    Very interesting question. I will discuss this in detail in this month's post.

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  41. I appreciate your response. I will make sure to ask my doctor for another plasma metanephrine test. At the time of the original test I had been off Metoprolol for only four days prior. My body reacted very poorly to the medication. Could that have contributed to the slightly elevated plasma metanephrines?

    My doctor suggested I try Lexapro. If Lexapro helps, is that more evidence I do not have a very small pheo? Do SSRIs or other antidepressants mask the symptoms of a pheo, or would they have no effect at all, if one was present? Do SSRIs influence the results of the plasma metanephrine test?

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  42. Frey,

    It is hard to say. The best way is to do follow-up testing.

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  43. Dear Dr. Pheo,

    I am a 53-year-old woman who began experiencing symptoms that were highly suggestive of a pheo when I was between 24-25 years old. I recently discovered I am a 4th generation McCoy (the McC kindred) with a family history of VHL.

    I understand you are the pheo doctor, but please bear with me. I have had three urinary cortisols in the past that were elevated (more than 10 X normal range), but all were discounted as either lab errors or anxiety. An ob/gyn at that time did a preliminary CT of my adrenals which was negative.

    No one really got around to investigating the possibility of a pheo until a couple of years ago. At that time my urinary norepinephrine was only mildly elevated, so anxiety was the diagnosis. I have a history of hypotension, polyuria, nocturia, hyponatremia, hypokalemia, hypomagnesemia, hypocalcemia, vitamin D deficiency. . . . I've been very seriously ill. My working diagnosis is currently Bartter's Syndrome, but my nephrologist recently told me my K and magnesium are now within normal limits with oral supplements.

    I am now seeing someone who happens to be on your short list of recommended endocrinologists. After almost 3 decades of being ill, someone finally referred me to an endocrinologist. The endo recently ordered catecholamines and my Dopamine came back elevated at 35 pg/mL:

    Catecholamines, Fractionated, Plasma
    Plasma Dopamine 35 (H) 0 - 20 pg/mL
    Plasma Epinephrine 16 10 - 200 pg/mLFin
    Plasma Norepinephrine 474 80 - 520 pg/mL

    Metanephrines, Free, Plasma
    Normetanephrine, Free 0.70 - <0.90 nmol/L
    Metanephrine, Free 0.32 - <0.50 nmol/LFin

    Can a pheo be ruled out with a mildly elevated dopamine level? Is this significant at all?

    My urine volume is astronomical, but not consistently so, I have episodes or "attacks" of it with normal fluid intake. I am not a psychogenic drinker and I am not doing anything to cause my abnormal labs. I have very low energy, fatigue, pain and have a very poor QOL.

    24-hour Urine Volume:
    Volume 4,300 mL (800 to 2000 ml/day)

    After decades of feeling very unwell, my serum cortisol is now low, as is my ACTH.

    Aldosterone 7.0 (7-30)
    Cortisol 1.0 (4.0-11)
    ACTH-ICMA <5.0 (5-37)

    2007
    Aldosterone: Less than 4
    Cortisol: 6.6
    ACTH: 5.2

    Do you have idea what in the world may be happening to me? I just discovered that my GP forgot to forward the ACTH and Cortisol labs to my endo when she referred me .

    Thank you very much for any comments you may have.

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  44. Dear Blue,

    I have read about the Hatfield and McCoy feud. Do you know if you are a carrier of VHL?

    The slightly elevated dopamine probably is not significant but it would be nice to repeat it in a few months.

    The low cortisol and ACTH suggests secondary adrenal insufficiency. Your endocrinologist should be able to sort it out for you.

    Dr. Pheo

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  45. Thank you very much Dr. Pheo. I have not had genetic testing to see if I am a carrier of VHL.

    Good to hear the one-time elevated dopamine is probably insignificant.

    My estradiol, testosterone and IGF-1 are also low. Are these also suggestive of secondary adrenal insufficiency or hypopituitarism?

    My endo doesn't have all of my labs, but I'm sure he'll be able to sort it all out once he receives them. Unfortunately, I don't return to see him until late July.

    I apologize for dumb questions, endocrinology is relatively new to me.

    Thank you for sharing your knowledge with us,
    Blue

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  46. Dear Blue,

    Secondary adrenal insufficiency and hypopituitarism are concerns. Again your endocrinologist should be able to make the diagnosis.

    Dr. Pheo

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  47. Hello Dr.
    My daugther is 7. Almost 3 years since she changes dramatrically. Weigth gain not food realated please belive me, hot intolerance, buffalo hump, acanthosis nigricas in neck, axilas, hair in her upper lip and vagina not to dark but is there, 24H urine sometimes high some normal, urine volume always low??? low ferritin, iron, B-12, gut problems, constipation, moon face, sleep problems, high level of anxiety, worries, 2MRI normals, 1 adrenal CT show something very small what that mean??? I do not know Dr, want to wait one year maybe possible cyclical Cushing's, now I am worry of possible problems in her kidneys she has pain every time that she pees... How her body can wait a year with out any help. Thanks.

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  48. Dear evi,

    I am not a pediatric doctor so my suggestions may not mean much.

    Your daughter unlikely has Cushing's. She most likely has insulin resistance and/or ovarian overactivity. She should see a pediatric endocrinologist for definitive diagnosis. Your daughter's condition is not very rare and a pediatric specialist should figure it out.

    Dr. Pheo

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  49. Thanks Dr. Appreciatte your comment! God Bless you!

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  50. I would like to share with you that we just get the report of my daugther visit in Maryland, they told us not 100% conclusive cushing's but it could be ciclycal maybe. The findings:
    Brain MRI: pituitary slightly small no lession. Mild volume loss.
    US Pelvis: uterus infantile, the ovaries were not visualized;presumably they are in infantile size.
    CT scan adrenals: slight nodularity in the left adrenal. Nothing in the rigth adrenal
    Bone age 10-11 she was 6years 11 months when the scan.
    They told to wait a year, but she still having pains and behavior troubles, any advice. I understand that you are not a pediatrician but if you hav any comment please help us.

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  51. Dear evi,

    My opinion remains the same. Insulin resistance is more likely. I really do not know much besides that.

    Dr. Pheo

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  52. Where would one go to get an NP59 scan for adrenal Cushing's?

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  53. I don't know. The production of radiolabeled NP59 has been discontinued in US. Rumors have it that a Canadian facility is still making it. The alternative is adrenal venous sampling.

    Dr. Pheo

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  54. Hi! I've just found your blog! I'm in that awkward diagnostic phase of whatever I have at the minute! I'm a 21y F and It's all about the paroxysmal tachy (up to 190) and HT (160 systolic) with presyncope and cold flushes! What a bugger! Question though, my BP is normally around 100 systolic - is it possible to have an elevated catecholamine level with a low baseline BP? I think not, but they're making me do the urine test regardless - eurgh! I hope it's just cardiac and the BP is 'stress of the moment' but I am SO not an anxious soul - can't wait for this to all be over!!!!

    Thanks for writing this blog - it's good to know other people have similar symptoms!
    Fi

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  55. Dear Fi,

    As catecholamine release can be episodic, a person with pheo can have normal baseline blood pressure. Let's wait to see what the test results are. If they are normal, then pheo is ruled out.

    Dr. Pheo

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  56. I have all symptoms of a classic Pheo, but no high blood pressure!
    I have a cyst 20cm - they can not locate its origin.
    I have done 24hr urine testing but they actually won't tell me my results only that cortisol was 129.
    I'm experiencing stress panic attacks (never ever had a panic attack or anxiety in my life - only started getting them 4 months ok prior to the discovery)
    They are saying it all came but that it wasn't a pheo but I have read that if you don't have an episode during or prior to testing it won't show up.... is that right?

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  57. Dear Lisa,

    If the urine test measures metanephrines (not catecholamines), it does not matter if you have an episode or not at the time of urine collection.

    Dr. Pheo

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  58. Do steroids increase plasma metanephrines?

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    1. Dear Unknown,

      They may occasioanlly do.

      Dr. Pheo

      Delete
  59. Why is it, every endo I have seen has denied that pheo crisis caused by steroids is a thing? Don't endos read this material? I just saw a new one today and once again, he tells me I can take steroids and he doesn't believe I have a pheo -- even though I've ended up in ICU three times now for "mysterious septic shock." Well, actually only two times because the third time an endo diagnosed the pheo. My medical group insists one of their doctors rediagnose me and I've run into nothing but problems for over a year now. I have a very small pheo (2 cm or less) and I think there is something wrong with it. Possibly it has hemorrhaged at one time or it leaks or something. Until someone pulls the damn thing out, I'll never know. Maybe they'll find it at autopsy but it would suck to get diagnosed that way!

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