In the olden days, there were a few dynamic tests to diagnose pheo. In those days, none of the biochemical tests and imaging methods that we take for granted today was available. If you and I feel frustrated now over diagnosing a pheo, imagine how people felt then!
The glucagon stimulation test was one of the dynamic tests invented in those days. Glucagon is a hormone produced by the alpha cells in the pancreatic islets (insulin is by the beta cells in the same islets). Glucagon has many functions. The main one is to increase blood glucose levels (that’s why it is used to treat hypoglycemia). It also stimulates the heart and increases blood pressure. At the beginning, increase of blood pressure after glucagon was used to diagnose pheo; later, the test changed to increase of norepinephrine after glucagon.
The glucagon stimulation test began to fade away after better tests for pheo were discovered. It is seldom used in the last 20 years. Whether it has any unique value in modern-day medicine, however, is never satisfactorily answered. I have been asked by my own patients about the glucagon stimulation test and some patients wonder if the test can uncover a hidden pheo. A recent study systemically examined the body’s response to glucagon and largely settled the question.
This study shows that norepinephrine increases dramatically after glucagon in only about ¼ to ½ of pheo patients. In the other ½ to ¾ of pheo patients, the increase in norepinephrine levels is too small to have any diagnostic value. In other words, it is not sensitive enough. In the subgroup of patients who have borderline metanephrine results and need further testing, the performance of glucagon stimulation test is similar.
The glucagon stimulation test is not without risks. A few patients had hypertensive crisis. One patient developed visual problems that eventually recovered in a few months.
This study, along with a few others, clearly demonstrates that the glucagon stimulation test has no place in diagnosing pheo in modern medicine. We should not use it any more for the purpose of diagnosing pheo.
Dr. Pheo
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Your article brought back memories.
ReplyDeleteGST was used (1984) more than once on our son (aged 10) at Children's Medical Center in Dallas to diagnose pheo. CMC had never had a pheo case before. The scans could not pick up the tumor location. We found an MRI that had just opened on Records Crossing that was the first one in Dallas at the time. It found the location of the pheo, wrapped around his aorta. Then my family helped raise money for CMC to get one.
The 8 hour operation was performed by Ted Vottler, the doctor who had just separated the first (Siamese, I believe but need to check) twins. It was a success by the grace of God, Dr.Ted and our son's incredible strength and desire to fight to be well! He battled over 23 years.
I liked reading your post, thank you.
Hi Dr. Pheo,
ReplyDeleteIs this the article you are referring to?
http://jcem.endojournals.org/cgi/content/abstract/95/1/238
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2009-1850
This Article
Endocrine Oncology
The Journal of Clinical Endocrinology & Metabolism Vol. 95, No. 1 238-245
Copyright © 2010 by The Endocrine Society
Low Sensitivity of Glucagon Provocative Testing for Diagnosis of Pheochromocytoma
Jacques W. M. Lenders, Karel Pacak, Thanh-Truc Huynh, Yehonatan Sharabi, Massimo Mannelli, Gennady Bratslavsky, David S. Goldstein, Stefan R. Bornstein and Graeme Eisenhofer
http://jcem.endojournals.org/cgi/content/abstract/95/1/238
Dear Casey,
ReplyDeleteThank you for sharing your family's experience.
Dr. pheo
Dear tues1day,
ReplyDeleteYes, it is the article.
Dr. Pheo
After 3 cycles of CVD chemo, my PET scan came back with much reduced tumor activity, although my norepinephrines were higher than the month before. The PET scan also showed new activity on the left ovary. An ultrasound shows something, like a cyst or tumor. Can paraganglioma involve ovaries?
ReplyDeleteDear Pam,
ReplyDeleteIt is possible that paraganglioma metastasizes to the ovary.
Dr. Pheo
Hello again Dr Pheo
ReplyDeleteThere seem to be a multitude of hormones that pheos exacerbate: commonly referred to as Cats & Mets (in the UK).
Could you post some details on here with regard to what hormones are commonly elevated in pheos and what the normal range would be? - (or a link) as I am struggling to find what "normal" is?
thanks Jane
Dear Jane,
ReplyDeleteA pheo can produce norepinephrine, epinephrine, and dopamine. Norepinephrine is converted to normetanephrine, epinephrine to metanephrine, and dopamine to methoxytyramine. The most common ones are norepinephrine and normetanephrine. The normal reference ranges vary between labs. You can get them from the labs' website.
Dr. Pheo
Hi Dr. Pheo: What do you think of this? In October 2009, I had dozens of paraganglioma, and my epinephrine levels were 4795 (80-520). After starting CVD chemo, with PET scan showing great improvement, my epinephrine levels are actually rising (currenty 5368). I've had 5 cycles of chemo, and am not on any BP meds. My oncologist doesn't have any ideas. Do you think there is anything we need to do differently?
ReplyDeleteDear Pam,
ReplyDeleteThis is a rather complicated situation. The most important question is how you feel. The other question is whether your weight is stable. I am afraid that you may have volume depletion (meaning that the salt and water in your blood are less than normal). It may be prudent to take phenoxybenzamine or other BP medications and increase fluid intake at the same time, if your heart function is normal. Of course it is important that you be evaluated by a pheo expert and receive specific opinions.
Dr. Pheo
Dear Dr Pheo,
ReplyDeleteYou were really helpful when my 80-year-old mother had a pheo removed last year. Although the surgery was successful, her BP seems to be rising again now, and the doctor has ordered her another 24-hour urine test. She is very upset and wonders if she can have another pheo - the magnetic tests she had last year before surgery did not show up any other problematic areas. Is recurrence likely?
thanks!
Please ignore that query as I just found your answer - I had thought the posting didn't work but obviously it did! Thanks
ReplyDeleteDr. Pheo,
ReplyDeleteI had a 24hr Urine test done and my dopamine levels were elevated 4x's over the high end of normal for the laboratory. What level would be of concern with someone with pheo's?
Thanks, Stacey
Dear Stacey,
ReplyDeleteThe urine dopamine is mostly produced by the kidney therefore not a great way of testing dopamine. If there is a concern, you can test plasma catecholamines (including dopamine) and methoxytyramine.
Dr. Pheo
Actually, I'm trying to determine when a doctor would feel further testing is needed. I have already been diagnosed with multiple head and neck paragangliomas. My PFM test came out clear and I was not tested further until I complained of symptoms then the 24 Hour Urine test was ordered in which only the dopamine was elevated. Would you feel further testing is necessary?
ReplyDeleteThanks, Stacey
It is important to compare the current results with previous ones. If previous urine dopamine was always normal, then I suggest measuring plasma catecholamines and methoxytyramine. Since you do have para, any abnormal test results should be treated seriously. Further testing would be prudent.
ReplyDeleteDr. Pheo
I received my results from my latest MRI and it shows a new paraganglioma in the neck region. This makes a total of five. The oncologist told me they are benign but the radiology reports all say that they suspect metastic disease and the endocrinologist I've been seeing labeled them as stage IV meaning they are unresectable. I'm confused, what is the difference between benign, metastatic and malignant pheos/paras?
ReplyDeleteThanks,
Stacey
Dear Stacey,
ReplyDeleteThere are two issues here: benign/malignant, and resectability. Most neck paragangliomas are benign. Only when they appear in unusual organs (such as liver or bone), are they considered malignant. We actually do not use the staging for head and neck tumors. Some paragangliomas are wrapped around major blood vessels so that resection is very difficult. These tumors are unresectable but still benign.
Dr. Pheo
In response to your questions to my earlier post on March 9, I feel pretty good, considering the CVD chemo takes a week to recover from, and the next 2 weeks I tire easily, but over all feel pretty normal. As for my weight, last year I had the cervical fusion/throat issue and had a stomach tube for 4+months and lost 40 pounds (from 190 to 150 - I'm 5'10"). Now I fluctuate between 150 and 160, losing the week of chemo and gaining after that. I asked my nurse about the volume depletion, and I am tested for that before each chemo infusion. The levels are slightly lower in the range given, and stay about same. Fluid intake is difficult for me since the skin graft to the back of my throat. I can only take small sips, and have to plug my nose so the liquid doesn't come out of my nose. I'm missing about half of my soft palate. And now, 2 weeks after chemo, my BP is going up (130/100) and my heart rate, too (120 after lying in bed before sleep). So I just started taking Lisinopril, and it has brought my BP down (110/80) and heart rate a little (90). My oncologist might have me start on phenoxy if my heart rate stays up. Do you know of a pheo expert in San Diego, CA? And do you have any suggestions with this information about me?
ReplyDeleteThank you so much for taking time to do this blog. We are all so very grateful. I have a .jpg of my last 2 scans, but I don't know how to post it so you can see it. You can look at my blog and see it: LifeWithPheo.blogspot.com
Dear Pam,
ReplyDeleteI read the images on your post and some of your articles. Your spirit sets a great example to everyone.
I think chemo is good for you but you do need medications to counter the effects of catecholamines. Lisinopril itself is not enough. How is your heart function? What is the QTc on your ECG? Do you have constipation, nausea, and vomiting?
I suggest that you start with phenoxybenzamine and then add a beta blocker if needed. Catecholamines not only raise blood pressure. The heart, stomach, and intestine are also affected by catecholamines. Blood sugar levels may also be elevated.
I don't know a card-carrying pheo expert in San Diego. If you are strong enough to drive to Los Angeles, there is one expert listed on my list (Dr. Yu).
Dr. Pheo
This comment has been removed by the author.
ReplyDeletehi dr pheo, just found your blog and it is
ReplyDeletereally informative. I like that you actually respond to peoples questions. I have suspected a pheo for over a year now. my PCP (who I've left) didnt know me from adam and the first word she blurted out was "pheo" I have suffered with tacycardia for years, BP swings, BG swings, hot flashes, night sweats, thyroid issues, joint and muscle pain, wide fluctuations in appetite and bowel habits, severe insomnia, GERD, back pain, anger, rage and cynisism towards everyone and everything etc.
my doctors see me as the picture of health on paper and as I am sure many pheo pts do in the early stages they have sent me down the mental health route after doing minimal testing. I had a 24 hr urinary VMA which was 5.4 (normal is zero to 7) in 08/09 and also in 08/09 I had a plasma fractionated catecholamines everything was fine except dopamine which came back at 58 pg/mL (normal =0-20. somehow, that part got totally ignored. is there a reason every endo ive seen has overlooked this dopamine level, and should it have not been ignored and persued further? is there any particular reason they all would blatently ignore this result? are any meds known to increase dopamine levels? I am on a lot of meds maybe that is why they didnt see concern in it?
this issue of a pheo struck my interest again, when today I had a glucagon stim test (not for pheo specifically, but for markedly low IGF-1 levels) and then I read this was an old test once used commonly for pheo dx. about an hour after the glucagon injection I got really sick and flushed/overheated and sweaty for about 2 hours. The nurse said pts dont usually get that sick. she watched me clearly suffering and didnt offer anything for my nausea. they never took my BP, but I have a HRM on my watch and at times it reached 120 while sitting in the chair, and that was after taking 10mg of my morning beta blocker, propranolol, I'm glad I took it, I prob would have been even more miserable had I forgotten.
is 58 a high enough dopamine level for a pheo to be present? what are the levels like for dopamine pheos? is this worth persuing? there was also question of a 6- 8mm pit tumor at one time, but I can no longer have MRI's due to an implanted medical device, so they cant really track it, and a CT scan doesnt do a justice.
thanks dr. pheo, (nice to have found an expert on such an underdiagnosed/quite rare condition!)
-Carlie
Dear Carlie,
ReplyDeleteThe dopamine of 58 is abnormal but its clinical significance is not high. Dopamine-secreting pheos usually do not cause specific symptoms. I suggest that you repeat the plasma catecholamines. Your experience during the glucagon stimulation test was not common but probably does not by itself suggest pheo. The normal VMA makes pheo very unlikely.
Dr. Pheo
Dr. Pheo,
ReplyDeleteMy husband has been sick since April. Abdominal pain, heart palpitations, flushing, severe night sweats, tingling and burning extremities, nausea, extreme fatigue. He is 67 and was diagnosed 3 years ago with interstitial lung disease. currently on 8 litres O2. we first thought his symptoms were associated with the lung disease and call the pulmonologist who said no. So we contacted our Gastroenterologist and they have been treating him for IBS. He is not getting any better, in fact the meds they had him on made his pain worse. They ordered a ct and said nothing wrong. 3 weeks ago he got so sick and in so much pain we went to ER. They ran a ct and shows tumors on both adrenals and we should consider pheo. Back to the primary who referred to endocrinologist who said no but ordered blood test and 24 hour urine. Blood am cortisol low 1.6 on a range of 4.3-22.4.... Urine -Normetanephrine High 1.42 on a range of 0-0.89 ... Metanephrin normal 0.29 on range of 0-0.49...Norepinephrine slightly elevated 50 on range of 0-45 and VMA normal. My question is can this be pheo or what? Should we request additional testing and if so for what. This has been going on far too long and we are at a loss. He was taking Percocet for pain and has since went to tramadol 4 times a day and not getting full relief.
Dear Anonymous,
DeleteHe unlikely has pheo. The low morning cortisol levels are concerning for adrenal insufficiency. His endocrinologist should figure out whether he has adrenal insufficiency and treat him if needed.
Dr. Pheo
thank you
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