I wrote 2 years
ago on the seasonal variations of plasma normetanephrine levels in patients
without pheo. In early 2014, a paper reported that the normetanephrine levels are
20% higher in wintertime than in summertime in the Netherlands and Germany, and
a second study showed that normetanephrine levels are 40% higher in wintertime
than in summertime in Los Angeles, USA. As the Netherlands and Germany have
temperate climate and Los Angeles has Mediterranean climate, higher
normetanephrine levels in wintertime seem to be pretty universal. At that time,
I suggested a similar study in a tropical area like Hawaii with minimal
temperature differences throughout the year. One would predict that the plasma
normetanephrine levels in people without pheo remain unchanged throughout the
year in Hawaii.
A third study is
indeed done, although not in Hawaii, and published recently. It is done in the
West of Ireland. Ireland has a temperate oceanic climate. The average
summertime and wintertime temperatures are 14.3 and 5.8 °C respectively in the
West of Ireland. The temperature difference of 8.4 °C in the West of Ireland is
very similar to that in Los Angeles (8.6 °C), although it is generally much cooler
in the West of Ireland (average Los Angeles summertime and wintertime
temperatures are 23.2 and 14.6 °C respectively). The seasonal temperature
differences are much smaller in the West of Ireland and Los Angeles than those
in the Netherlands and Germany (17 °C). Unlike in Los Angeles, there is,
however, no difference in the plasma normetanephrine levels between the
summertime and wintertime in the West of Ireland.
There could be
multiple potential explanations of the different result obtained from the third
study. An obvious issue is that all three studies are retrospective ones which
can lead to certain biases. The most important lesson, however, is that medical
studies need to be reproduced in different settings. We cannot assume that results
from a previous study should be readily applied to another setting.
Dr. Pheo
Hi Dr Pheo.
ReplyDeleteVery interesting seasonal info. Thanks for this great blog. Forgive me, my question is off topic from the article above. My 3cm Pheo was lap. removed along with left adrenal in 2008. I am 39yrs old now. In preparation for an annual follow up and pheo retest appointment with a new Endo I began browsing research on recurrence and also reviewed my medical records from time of my initial diagnosis and surgery. I had two questions that my Endo wasn't able to answer or maybe I didn't ask clearly. Anyway, I read in one study that concluded recurrence was higher in patients that had elevated norepinephrine compared to low/normal epinephrine at initial Pheo. My initial labs showed normal epinephrine and nearly 5 fold elevation in norepinephrine. The authors categorized these patients at higher risk of recurrence and recommended more frequent re-testing (annually vs biennial) Have you heard of this high risk factor for recurrence? Why does low epinephrine cause higher risk for recurrence?
Second question. I had always assumed I had a sporadic pheo, not familial. The Endo today informed me that my record showed no genetic testing so we don't in fact know. Should patients get a genetic test? Endo said she would inquire through my insurance as this is usually the reason it is not done. Is it recommended that I should know? Doesn't it help determine how closely/frequently one should be watched for recurrence? As of now I am being tested at least yearly. Would having had a familial pheo change that frequency?
Thanks
J
Dear J,
ReplyDeleteThese two questions are pretty complicated. The biochemical profile of a pheo can be norepinephrine-predominant or epinephrine-predominant. The norepinephrine-predominant pheos are generally considered less mature than epinephrine-predominant pheos. The biochemical profile is just one of the many factors that may influence recurrence. I would not worry too much because your pheo is norepinephrine-predominant (like most pheos).
To know what mutation you have helps with screening your children and predict your future clinical course. Because you have a unilateral pheo in the adrenal gland, the chance to find a genetic mutation is not high but possible. Whether a mutation is found, you still need to be followed more or less the same for pheo recurrence per se.
Dr. Pheo
Thanks for the insight. The article that stated low epinephrine secreting pheos were associated with higher chance of recurrence was "Tumor recurrence and hypertension persistence after successful pheo operation, Pierre-Francois Plouin, Giles Chatellier et al. It is from 1997 I think. Are there newer studies that the opposite my be true, that low epinephrine secretions are linked with lower recurrence rate? Thanks again for your insight.
DeleteJ
Dear J,
DeleteI am not aware of other studies that address this issue directly.
Dr. Pheo
Also meant to meniton that I was 30 when diagnosed with initial Pheo. Is age at diagnosis also a risk factor? I had severe panic attacks requiring hospitalization at 10yrs old that didn't respond to medications. Now Doctors believe I likely had the pheo as a child as well. Are these factors that help determine if I should push for genetic testing?
ReplyDeleteJ
Dear J,
DeleteThe younger the age of diagnosis, the more likely is there a genetic predisposition, hence higher chance of recurrence.
Ideally you should get a genetic test. The practical question is which genes to test first. There is a whole series of studies and opinions on the algorithm of genetic testing. You should talk to you doctor about it.
Dr. Pheo
This comment has been removed by the author.
ReplyDeleteHello Dr. Pheo,
ReplyDeleteThanks for creating and managing this blog - it has been very useful to me for background over the last few years. I am a 48-year old male and have recurrent pheocromocytoma of the right adrenal gland and my Endocrinologist is strongly recommending I pursue MIBG I-131 radioisotope therapy. This doctor is part of a major teaching hospital. This is my plan of record and it is scheduled for next month. I have since gotten a second opinion from another major teaching hospital in my area and they recommend external beam radiation due to the fact that there is only a single site of metastases. I will provide some additional background on my case, but I was looking to get your input on the effectiveness of these two approaches and questions I should ask the doctors? Should I consider any other approaches?
(I will do my post as three separate posts - when I tried to do it as one big one it gets deleted)
Continued - part 2 of 3
ReplyDeleteMy pheo was diagnosed in 2005 after I had been experiencing periodic very high blood pressures (225/125) and severe headaches. It was found on CT first and then subsequently confirmed via 24-hour urine tests. I had a laparascopic right adrenalectomy in May 2005 and was symptom-free for the next 5 or so years. We monitored tumor markers via blood and 24-hour urine collection for the next 3 years, after which I just monitored my blood pressure to watch for any recurrence. In 2012 I had a classic pheo headache and then re-engaged with my local (non-teaching hospital) Endocrinologist where tumor markers and an MIBG scan indicated the disease had come back with tumors in the right adrenal bed. A Feb 2013 laparoscropic surgery in that area was unsuccessful in bringing down the tumor markers by much and my blood pressure remained high periodically. At this point, I engaged with a teaching hospital Endocrinologist, where both an MIBG and PET scan were done, again showing residual tumor in the right adrenal bed. A subsequent Feb 2014 laparatomy removed tissues from the right adrenal bed, right kidney, and liver and was initially very successful. Following this third surgury, two months post-op for instance my plasma normetanephrine was 164 pg/ml, where pre-surgery it had been 1679 pg/ml. I required no blood pressure medicine and BPs were on the order of 135/85. Unfortunately since this time the plasma normetanephrine, norepinephrine, and chromogranin A all slowly inched back up to their pre-surgery levels, where they had all been near-normal two months post-op. We had to slowly add in and ramp-up on Nifedipine ER to control the BP and I am currently on the max dose of 60 mg 2x/day with my non-stressed BPs still in the 135/85 realm, but with moderate stress it can easily jump to 160/100. My teaching hospital Endocrinologist has always been encouraged because I just have local seeding in the right adrenal bed and no distant metastases. Per MIBG and MRI the tumors don't appear to have grown much over the last two years, where the current info is from a Dec 2015 MRI and showed right adrenal bed nodules measuring 1.8 x 1.2 cm, 0.9 cm, 2.2 x 1.4 cm, and 1.8 cm. There is a similar lesion adjacent to the liver that only measures about 2 mm, but is thought to be another implant. An April 2016 MIBG scan shows "intense" uptake in the right adrenal bed. Also extensive genetic testing has been negative.
Continued - part 3 of 3
ReplyDeleteAny help deciding between the two treatment options I mentioned above would be very much appreciated. Also, would it make any sense for me to get a formal opinion from you? In spite of this pheocromocytoma, I am a very fit and active person, still working full time, with a young family of 3 kids and I want to make the best next treatment decision possible. I would be willing to fly and see you if you thought there was something valuable you could add.
Thanks in advance,
Golf Guy
Dear Golf Guy,
DeleteIt is a unique situation and there are no obvious right or wrong answers. I personally favor MIBG radiotherapy. Pheo is usually not sensitive to external beam radiation. Another alternative is monitoring while controlling the blood pressure by medications. You don't have to see me directly. You can see any of the pheo specialists I listed in an early post on this blog.
Dr. Pheo
I think my brother may have an eye paraganglioma. He has a growth in the upper outer white part of his eye. It is not melanoma of the eye. It has grown. His top number blood pressure is 207. He has SDHB gene mutation with family history of tumors. Could you recommend someone he can visit. His doctors are stumped. He lives in Pittsburgh PA. I would guess his catecholemines are not elevated since this would be the first step. Any advice would be greatly appreciated. I now this would be very rare, but that would fit my family history.
ReplyDeleteFamily history meaning 1 caratoid artery tumor, 1 glomus jungular tumor, 1 glomus timpanticum tumor. Thanks for your concern for all of us. We appreciate it.
ReplyDeleteDear Team Burns,
ReplyDeleteI am not aware of eye lesion as part of SDHB mutation syndrome. I actually searched the literature but did not find info pertaining to this topic.
Dr. Pheo
Thanks for your input. We will keep trying to figure this out. Have a great summer.
ReplyDeleteJust fyi, here is where my initial thought came from. http://www.aocoohns.org/wp-content/uploads/2012/04/Benjamin.pdf
ReplyDeleteIt is just hard since no pheo is showing up anywhere else. So I guess the wait and watch attitutde is all he can do right now.
Great blog!
ReplyDeleteThis comment has been removed by the author.
ReplyDeleteI was diagnosed with breast cancer in 2013 (right side) while undergoing many scans including a CT scan it showed a 3cm mass on my left adrenal gland. Nothing was said about it at the time. I have had another diagnosis of breast cancer (left breast) and this time they mentioned the adrenal mass but it not measures 2.6 x 2cm so looks like it has got smaller? The only thing I can think of is it may have shrunk as I have had chemotherapy? I have been told by my breast surgeon I need to see an endocrinologist. I have all the symptoms of pheochromocytoma but have been told over the years it was an autonomic condition called PoTS. I have really struggled with day to day life because of it. Though I have not lost weight, I have gained some, also I do not suffer from high blood pressure, it is usually on the low side. Any thoughts would be gratefully appreciated, as I am concerned.
ReplyDeleteDear Marion3,
DeleteIt is a good idea to test for pheo. It is also important to make sure the adrenal mass is not a metastatic lesion from breast cancer.
Dr. Pheo