The 4th International
Symposium on Pheochromocytoma (“ISP 2014”) was held in Kyoto, Japan, September
17-20. I just returned from the meeting. This time, I was too tired to write a
meeting report during the meeting but I did take extensive notes.
Public transportation was
amazing there. The meeting organizers provided detailed instructions on using
public transportation which I took seriously. Upon landing at Osaka airport, I
bought an IC card with a little Hello-Kitty on the face. The IC card apparently
was for foreign travelers only (they wrote down my passport number and name).
The card could be used on trains and subways and in some shops. It gave
discount price for round trip between the airport and the Kyoto train station.
Very handy! I could have returned the card and got some refund but I kept it as
a souvenir because I liked it so much. A high-speed rail (JR “Haruka”) took me
from the Osaka airport in 75 minutes to the Kyoto station. Then a 5-minute walk
took me to the meeting venue.
The meeting was wonderful. I
attended every single lecture and discussion except for those on the last day.
I also presented a poster. The meeting featured many Japanese speakers who
shared their experience on pheo. It turned out that the diagnosis and treatment
of pheo in Japan were a little different from those in US and Europe. I was
surprised to know that metanephrines testing was not available in Japan but
some Japanese doctors were developing the assay there. Interestingly Japanese
surgeons had to send in 20 videos of their laparoscopy operations to be
certified. The first-time pass rate was only about 40%!
The following is a list of major
new things I learned from the meeting:
1. Two more new genes were
added to the list of pheo-predisposing genes. I will write about them after the
papers are published. So now a total of 17 genes are known to be associated
with pheo.
2. A new syndrome,
paraganglioma-somatostatinoma-polycythemia was established. The syndrome is
caused by activating mutations in the gene HIF2alpha in some but not all cells
of the body. I was fortunate enough to have an extensive discussion with one of
the lead authors of the paper to understand how they went through the thinking
process. This syndrome is particularly interesting to me as I also have
interests in somatostatinoma and other pancreatic or duodenal neuroendocrine
tumors.
3. Prediction of malignancy
may be possible now. A famous Japanese pathologist literally used the Obama’s “Yes
we can” in describing the scheme that will tell a malignant pheo from a benign
one. This scheme was discussed 3 years ago at the previous meeting but was met
with more skepticism than support. This year, the same scheme seemed to have
garnered more support than skepticism. I, among others, would like to see how
the scheme would pan out in the hands a practicing pathologist.
4. Whole-genome sequencing
seemed to very popular now. A few famous researchers were sold on the
whole-genome sequencing idea. Quite a few others and I viewed the whole-genome
sequencing with guarded optimism. I don’t see much value of whole-genome
sequencing in routine clinical care.
5. A plenary session speaker
described the status quo and predicted future directions of pheo and pheo
research. This speaker thought that routine pheo diagnosis and treatment should
be pretty straightforward if a doctor knew the right stuff. Future research
should address the treatment of malignant pheo and the role of genetic testing
in the care of patients with pheo. I agreed with the speaker full-heartedly.
Dr. Pheo
Thank you for the great update, Dr. Pheo.
ReplyDeleteDr. Pheo, I am one of many patients with POTS (postural orthostatic tachycardia syndrome) to have been tested for pheochromocytoma. None of us has ever heard of a POTS patient who turned out to have pheo, and I have a hypothesis on why that is. Pheo patients may have postural blood pressure rise, but they don't have the predictable 30+ point postural rise in heart rate. Am I right? It would be so incredibly helpful if doctors could distinguish clinically between pheo and hypertensive POTS. With hypertensive POTS, sky-high blood pressure rises on standing are often seen, and yet we may not have organ damage. I can get BP's of 230/80, for example, and I'm fine except for POTS. So: Have you had pheo patients with predictable, long term, postural heart rate rises of 30 points or more? Another way to ask the question is this: Do pheo patients ever undergo tilt table testing? If so, how do they tend to respond on tilt? Thank you!
ReplyDeleteThis is a very interesting question. I actually don't know the answer. In contemporary clinical practice, only a small number of pheo patients have orthostatic tachycardia. Because pheo diagnosis is easier to make (just blood or urine test) than POTS diagnosis, pheo is usually ruled out first so that tilt table test is seldom done.
DeleteDr.Pheo
Dr. Pheo, great blog. There is so little info about pheo's, I have found the archives very informative. I am another person who has found themselves getting "spells" of feeling ill (pounding/fast heart rate, high blood pressure spikes, sweaty/clammy feeling, headache, nausea and stomach discomfort, tingly hands and feet) that last 15-45 min. During these "spells" I feel compelled to lie down immediately. Anyhow, I had a blood test and a 24 hr urine test. I am waiting on the rests of the urine test, but I just got the results back on the blood work, and JOY! My Normetanephrine, Free is 0.20 nmol/L with a range of <0.90. (That means no tumor right :) ?) My metanephrine, free is <0.20 nmol/L with a range of <0.50 nmol/L. Here is where my question comes in (sorry for being long winded). Is it great that my metanephrine is below detectable levels, or does that indicate something is wrong? The creatinine from the 24 hr urine did come back already and it was 0.8, but the range was 1.0-2.0. I don't know if both of those being low have anything to do with each other, and if these have anything to do with Pheo. If no, I am sorry for bothering you :P! THANKS!
ReplyDeleteDear LeeLeeBot,
ReplyDeleteThe plasma metanephrine can be below the detection limit in some people. The implication of that is not very clear. The urine creatinine is mostly a reflection of your muscle mass. If you are not muscular, urine creatinine can be a bit low.
Dr. Pheo
Hi Dr.Pheo,if i have negative SDHB mutation ,does it mean i dont have malignant para? thanks
ReplyDeleteDear nina,
DeleteMalignant pheo or para is defined by its behavior. Although paras with SDHB mutations tend to be malignant, paras without SDHB mutations are not guaranteed to be benign.
Dr. Pheo
Dear Dr. Pheo,
ReplyDeleteCould you help clarify something? There are many people on our facebook support page that think you need to be in an "episode" for a urine and/or blood test for pheo. Is this correct?
As always, thank you for your kind help.
Best,
Frances
Dear Francis,
DeleteIf metanephrines are used (as recommended), the difference between levels during and outside an attack is not big. So a random plasma metanephrines test is sufficient in the vast majority of patients.
Dr. Pheo
This comment has been removed by the author.
DeleteHELP! Many months ago I was under pretty extreme emotional stress due to family and work issues...i started having extremely strong panic attacks. Rapid heart rate, high bp, and the adrenaline shakes afterward. Once, I did once have about 8 in a row...each attack stronger than the last, which landed me in the er. These lasted for weeks and got worse...two trips to the er and multiple doctor visits. I've lost 15 pounds in 2 moths and my appetite has been little to nothing. I was only able to sleep 2-3 hours per night intermittently for a few weeks to a month. Doctor prescribed benzos and of course helped a lot, but have only taken as needed. I went to an endocrinologist that did bloodwork for cortisol metanephrines cga and testosterone. All came back normal except cortisol and cga. Cortisol was only slightly elevated by one or two points... 11.5 with top end of scale being 10. Cga was done at labcorp which is the 0-5. Mine came back as 13 which scared the hell out of me considering much lower numbers I've seen from others that have either pheo or some other neuroendocrine tumor or carcinoid. My didigestion has felt horrible for the past two months..almost like im not getting enough nutrition from food...low stomach acid or sonething...almost like I can't "feel" my stomach be hungry or rumble like normal when empty. My grandmother does have pernicious anemia...so looking into that as a cause as well. I have always been anxiety prone...Sweaty hands and feet...panic attacks when I was younger after car accident ( have been in 15...yes, 15) after those, any stressor seemed to bring on a strong adrenaline response....even telling stories where something scared me or almost killed me would give me slight adrenaline shakes....i had an abdominal ct with dual contrast done a few days ago and adrenals looked normal and no evidence of tumors anywhere else ( I know they can be in other parts of the body). I did have strong anxiety with adrenal shakes in doctors office right before blood test talking about everything that has been going. So now I'm of course worried about my super high cga level....could the anxiety and adrenaline release before blood test raised my numbers? Doing the dethamexisone suppression test and 24 hour 5 hiaa test in the next few days....I've researched to the end of the internet regarding long term stress on cga levels....but everything just says..."stress can elevate cga levels"...but no percentages or any other diagnostic information is given. Thanks for your time -jared
ReplyDeleteI should mention symptoms...no flushing...sometimes heart beats hard...anxiety, sometimes slight dizziness and trouble concentrating and remembering...especially during timespecially feeling anxious.
ReplyDeleteDear jared,
DeleteStress is not a major cause of CGA elevattion. You should check gastrin levels. I assume you were not taking anti-acid medications at the time of CGA testing and had normal kidney function. If gastrin levels are also elevated, then you might have atrophic gastritis (which inrease both CGA and gastrin).
Dr. Pheo
I will talk to endo about it...my creatinine is is ally a little above normal, as I have wores out most of my adult life (32) now. My question is...chromogranins are released via the adrenals at the same time as adrenaline....if I had a strong adrenaline release before blood test, could it elevate my cga? Typically excess adrenaline is metabolized pretty quick by the body, yes?
ReplyDeleteIs it know how long cga "stays" in the blood from time or release? Thanks for ththe time and help
ReplyDeleteApologies for adding these little sides comments...basically I'm trying to figure out if my andregenic attack prior to bloodwork, and many more attacks das before blood work could elevted my cga...i don't take ppi but have been taking magnesium supplements bc it helps to calm my nerves. Could that have any effect on stomach acid?
ReplyDeleteDear Jared,
ReplyDeleteSorry for the late response. I have been away from the blog due to the holidays. Pheo is a real concern. Let's see the test results. Magnesium does not affect CGA levels. Do you have the gastrin levels and other test results now?
Dr. Pheo
I do not hve any other tests done... 5hiaa was normal. Just had a cystoscopy with stent removal today so will be doing dexamethasone suppression in a few days per my endo. Do gastrin levels come from bloodwork, and what exactly do theyes convey? Thanks again. -jred
ReplyDeleteDear Jared,
DeleteHigh gastrin levels would support that the high CGA levels are due to reduced stomach acid production (versus from a tumor).
Dr. Pheo
Dr. Pheo, I appreciate your blog. I had a right adrenalectomy two weeks ago to excise a 3.3cm confirmed pheo which was overproducing metanephrines for about 5 years. My recovery has gone well enough, but now I have been noticing a steady, daily decline in energy levels with increasing fatigue. Can you advise on the success rate for the remaining "good" adrenal to compensate and the typical timeline for this to occur and for patients to feel themselves again? Is there anything that can help the prognosis and speed the process (vitamins, diet, etc.)? Are follow-up tests warranted? Thank you for your blog.
ReplyDeleteDear David,
DeleteThe majority of people do well with one adrenal gland and the remaining gland starts working extra immediately after removal of the other. A few people, either due to the intrinsic problem of the remaining gland, or because the other gland may produce abnormally large amount of cortisol, can have permanent or temporary adrenal insufficiency. The best way is to do an "ACTH stimulation test".
Dr. Pheo
Thank you for the quick reply. As a follow-up, I do feel my remaining adrenal gland has not started "working extra immediately," but I also doubt I am in adrenal insufficiency. I feel fatigued and out of sorts, spacey. Of course, my numerous other pheo symptoms are gone, so it's been a fair trade. I understand in Cushings cases, there is often a ramp-up period before the remaining gland is fully operational, sometimes taking up to a year. Can a pheo produce both metanephrines AND cortisol, causing this depressed cortisol output in the opposite gland to happen? I believe my pre-op cortisol levels were in the normal range, but the actual output of each adrenal was never tested (AVS). I remain hopeful that things will resolve on their own.
ReplyDeleteDear David,
DeleteSome pheos have mixed features of pheo and adrenal cortical adenoma. Other pheos may produce ACTH. In both cases, the remaining adrenal gland may not function properly immediately.
Dr. Pheo
Yes, BP is now blessedly normal (but I have noticed my heart rate is now 10-20 points higher than pre-adrenalectomy when I was a solid 60 BPM). I do feel that my body is slowly adapting to my single adrenal state. I am staying patient and I very much appreciate your comments. No need to reply.
DeleteHi,
ReplyDeleteMy 80 year old Mum had a suspected Pheo, but got her negative urine results back today. She was tested for adrenalin, noradrenalin and Dopamine.
A nodule on her Adrenal Gland was found 3 years ago on a scan for something else - she was told it is nothing.
It is only recently when she was having extremely high BP that I mentioned it to the doctor.
He put her on a beta blocker - it was only when I said that could be dangerous that he took her off of it.
I would like to know if taking that could affect the urine test? She took it on the same day.
He has also said that he is just putting her symptoms down to BP, and not investigating any further.
She has had spells of sky high BP, very low BP, shaking, flushing, urinating often and worsening eczema (don't know if the eczema is relevant)
So I have written to the doctor saying that we are not happy, and would like to be referred to a Endocronologist or a Cardiologist.
Any advice you have would be greatly appreciated.
Samantha (we are in the UK)
Dear Samantha,
DeleteSince the urine test of catecholamines returned negative results, the likelihood of pheo is low. Primary hyperaldosteronism should be tested. Other causes of blood pressure fluctuation should also be considered.
Dr. Pheo
Hello, Thank you for your reply. So would you say to see an Endocronologist?I am trying to get our doctor to refer my Mum. Someone mentioned carcinoma to me - do you think that is a possibility/
ReplyDeleteThanks again, samantha
Dear Samantha,
DeleteI still recommend seeing an endocrinologist. Primary hyperaldosteronism and Cushing's syndrome should be tested. If the tumor does not change in 3 years, carcinoma is less likely. The characteristics on imaging are also important to guess if it is a carcinoma (cancer).
Dr. Pheo
Dear Dr. Pheo,
DeleteI am now eight weeks post-adrenalectomy and improving. However, the spacey feelings, fatigue, and other vague symptoms discussed in the thread above continue. At six weeks my doctor did extensive blood work which was largely normal except for notably high ACTH (55 with a reference range of 0 to 46, taken at 8AM while laying and napping); cortisol taken at the same time was normal at 17.2 (in a range of 5-25); and red blood cells were just barely below the normal low threshold. The only other notes are low-normal calcium and low-normal platelets, with everything else well within range.
My symptoms seem stress-related, as they flare in (even mildly) tense situations, like a presentation at work or a slightly intense conversation with a family member. The reaction can last a couple days before I return to normal. The fatigue is more persistent. The only physical symptoms are a transient weakness or numbness in my legs which started immediately after the operation (worse upon rising in the morning), occasional palpitations, and notable exercise intolerance with elongated recovery (I was very fit pre-op and my muscles do not feel the same responsiveness to excercise as before). Oddly, I am losing weight while gaining around the waist.
My question is whether you find the ACTH indicative of anything, or if the otherwise normal blood chemistry and vague symptoms can be considered normal for my recovery status. Yes, I am grateful to be rid of the more dramatic and debilitating symptoms I suffered with the pheo! I remain hopeful that things will improve with time...although work and home life can be challenging in the process with such a fragile stress response. I'm wondering if there is anything that I should ask my doctor about that would support my progress.
Thank you!
Dear David,
DeleteThe mildly elevated ACTH levels probably reflect that you are in stress at the time of testing. Is your blood pressure normal? Some people can have low blood pressure in the first few months after pheo removal. I suggest that you drink enough fluid, have good rest, and exercise judiciously. I am hopeful that you will get better over time.
Dr. Pheo
Hi
ReplyDeleteThank you again for your time.
Her doctor has arranged for her to see her Lymphoma consultant next week. She was diagnosed with that 3 years ago which is when the nodule on the gland was found. She was told it was benign and not Lymphoma related. So not sure why we are going there. So i presume it isn't a Carcinoma either -I just thought she could have a Carcinoma somewhere else causing the symptoms.
I have now noticed that she breathes rapidly (she is unaware) and she now gets a hot face as well as flushed, when her BP goes up.
She had the high and low BP a year ago for about a month, has had elevated BP twice over the past two years when she had to go to hospital, and she also had sudden unexplained severe fatigue for approx two months two years ago, they gave her low steroids, and when she slowly came off of them she passed out, and had other symptoms.
I will ask the consultant next week to refer to an Endo or maybe a NET?
Thank you, and sorry to keep emailing, just feel very frustrated.
Samantha
ps On last thing, and then I will definitely leave you alone! When my Mum drinks alcohol and has had an anti histamine, she flushes bright red - will just alcohol, most of the time not, and sometimes a slight flush. I don't know if this indicates anything? I was reading up on Serotonin syndrome, and anti hystamines etc and just wondered.
ReplyDeleteThank you, Samantha
Dear Samantha,
DeleteFor adrenal tumor and hypertension, an endocrinologist is probably better. Anti-histamines are used to treat flushing (and itchiness) caused by stomach carcinoid (which can secrete histamine). Alcohol can cause flushing by itself. I don't know the implications of alcohol and anti-histamine together.
Dr. Pheo
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