After chatting with the organizers, I realized that the primary reason to have the meeting in Disney Paris was financial—similar hotels in downtown Paris would cost twice as much. In addition, there is a grand chateau nearby that is undeniably French.
On 9/16, the lectures were mostly on progress in basic and clinical research. Regarding basic research, it seems rather clear that there are two “clusters” in pheo pathogenesis. The clusters concept is not entirely new (I wrote on the clusters before) but now the molecular details are worked out to a large extent. The scheme of pheo pathogenesis is a labyrinth of interconnected molecules. As I also do basic research myself, I am sometimes sarcastic about this kind of scheme. If everything affects everything else, how do we break the pathways? We need to figure out what the “driver” molecule is. But is there such a driver?
Some researchers reported the results of experimental targeted therapy in cell models, animal models, and in patients. The animal models are particularly intriguing and are real breakthroughs.
This meeting is very heavy on characterizing patients with SDH mutations and their individual mutations. The European countries are leading this effort. I have always wondered if SDH mutations are more common in Europe. In this meeting, I saw again some small countries reporting hundreds of patients with SDH mutations. I myself have not seen many patients in the US with clear familial paraganglioma syndromes. An alternative explanation is the difference in health care system. I cannot tell you how many patients I no longer follow due to their change of insurance plan. The national insurance system in Europe is a blessing to patients with rare and complicated diseases like pheo.
During the meeting, especially around 3 am when I was suddenly awake and trying unsuccessfully to go back to sleep, I reflected on the big picture of pheo patient care and where we should direct our research resource. I will elaborate my thoughts in later posts.
Dr. Pheo
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As a patient, it is so wonderful to be able to hear a report about events like this. Thank you so much!!
ReplyDeleteVal
Thanks for sharing Dr. Pheo. Btw, if you ever send patients to get CVD, you can feel free to share with them my CVD blog. I have chronicled my first twelve cycles (and counting) so that patients can better kow what to expect. I personally would have liked to have this before I started in January.
ReplyDeletehttp://kidcvd.blogspot.com/
This is very intriguing to read. From a patient active in multiple support groups, all I ever see is SDH mutations, but with everyone spread out around the US, I can understand why doctors don't see this mutation as much (although SDHAF2 has shown no one that I can find, yet.) Even the newsletter group I work with, it seems the first question we asked each other was which SDH are you? The pheo para troopers are in the middle of working on an international database for pheo patients. I cannot wait to see what the results of this data base will be. I think the information we learn from it will surprise us all.
ReplyDeleteThank you so much for updating us on the meeting in France. I wish I could have gone, but funding it so hard to come by these days.
It doesn't look like there is a way to private message you, but I have a hypothetical question:
ReplyDeleteSuppose there is a patient who has lost 40 lbs over the last nine months. This person has the unique ability to make herself flush by applying pressure on a specific spot in her upper right abdomen and she otherwise flushes regularly. She has high blood pressure which is not well controlled by medications. Assume also that her normetanephrine level was measured at .88 nmol/L and her metanephrine was .22 nmol/L. Her hypothetical doctors don't have a clue as to what is causing her symptoms. Suppose she plans to visit another general endocrinologist next week. What tests should such an endocrinologist order next?
Thanks.
Dear s,
ReplyDeleteI would measure chromogranin A, serotonin, urine 5-HIAA to rule out carcinoid syndrome. I would also assess whether the patient is perimenopausal. The endocrinologist may order additional tests based on clinical findings.
Dr. Pheo
Thanks. If all those are normal, but the patient is sick, what then?
ReplyDeleteSorry to have posed the question as a hypothetical, it must have seemed weird. I didn't realize you would answer direct questions.
This is a very frustrating situation.
Dear s,
ReplyDeleteIt is better to wait until the workup is complete. Also please read my earlier posts on coping.
Dr. Pheo
I'm sorry, I didn't make myself clear. I've had all those tests you mentioned and they were normal. The only test approaching abnormal was the normetanephrine @.88 nmol/L, which the endocrinologist said would be much higher if there was a tumor.
ReplyDeleteI've also seen a gastroenterologist and a rheumatologist but they couldn't identify the problem either.
On Monday the 3rd I have an appointment with a different endocrinologist who is no more specialized than the last, but I'm going to keep the appointment with the hope that he'll come up with something so that I can avoid travel to get help.
Are there any tests outside the repertoire of a typical general endocrinologist that could help?
I genuinely appreciate your help, thank you.
If you are uncomfortable naming specific tests, would you please direct me to a site that lists them?
ReplyDeleteDear s,
ReplyDeleteIt is unlikely that you have pheo or carcinoid syndrome. I am not sure if there is a website listing other tests for your condition. The best strategy is to work with a physician you trust.
Dr. Pheo
With a weight loss rate of a couple pounds a month the cause will be discovered one way or another, but the search has defeated me.
ReplyDeleteDear Dr. Pheo:
ReplyDeleteI had a follow-up urine metanephrines test after a positive result on the metanephrine fraction of a plasma test (see my earlier post 8/26/2011). There are conflicting results on the different tests.
.
1. May 2010 Two positive 24 hr catecholamine results (during spells) epi 35 mcg/24hr on lst test; epi 38 mcg/24 hr on 2nd test.
2. August 2011 Plasma free metanephrine fraction elevated @ 146 pg/mL (Lab Corp non- fasting, seated position with venipuncture). (normetanephrine normal @90 pg/mL)
I just received the follow up 24hr Urine Fractionated Metanephrines test results (Mayo Lab): metanephrine: 159 mcg/24 hr (reference range 44-261 normotensive) normetanephrine: 269 mcg/24 hr(reference range148-560 normotensive). An earlier 24 hr test in July 2010 (Lab Corp) had negative results of metanephrine 223 mcg/24hr; normetanephrine 189 mcg/24 hr). I am a 72 year old male.
I don’t know what to make of the discrepancy between the two recent tests: the elevated plasma metanephrine result and the negative Mayo 24 hr urine metanephrine result. From reading your past posts I take it that a false positive metanephrine result is rare. As I mentioned earlier, all my kidney function tests have been normal.
Nor do I know what to make of the conflict between the two positive urine epi results and the two negative urine metanephrine results. I take it that an epi > 35mcg is highly specific and that a metanephrine result of 159 mcg is highly sensitive. It appears, therefore, that the catecholamine tests confirm the diagnosis and the metanephrine tests exclude a pheo.
Does it make a difference that the urine metanephrine test was not done during a “spell”? The Mayo site says that for this test ideally the collection should begin at the onset of a spell. However, in their 2007 book Pacak, Lenders, and Eisenhofer say that there is “absolutely no need” to time the collection to coincide with paroxysmal attacks when measurements involve the metanephrines.
In light of the conflicting results, how is the probability of a pheo assessed? I have to undergo an EGD (using fentanyl) and am apprehensive about doing so given these results.
Thank you.
Dear jhardy,
ReplyDeleteThe elevation of plasma metanephrine levels is concerning. It suggested that you may have a very small pheo. The next step is clonidine suppression test.
The EGD should be relatively safe if you worry about hypertensive crisis.
Dr. Pheo
Hi Dr. Pheo,
ReplyDeleteI haven't written in awhile, and am sad I have to now. After 2 years of no treatment and dozens of tumors in bone and soft tissue, this patient's blood pressure has gone up for the first time in 2 years (150/105). Dr. ordered CVD chemo (again - went through 7 cycles 2 years ago with good response) and 120 mg of Cardizem. Cats have been 2-3x normal last 2 years, and recently shot up to 4700 (high normal: 500). Been fighting these things for 6 years. Now that they are acting up again, is there anything out there that I could try? Current docs have no experience with pheo, but are open to whatever I tell them should be done. Any suggestions?
Dear Pam,
ReplyDeleteI am sorry to learn that the pheo acts up again. I would suggest a few things:
1. Make sure blood pressure and symptoms are controlled by medications.
2. CVD chemo is a good option.
3. MIBG radiotherapy is not very available and can be expensive but works very well in some people. You may want to look into that.
4. There are a few trials on metastatic pheo going on. You can contact the trial doctors to see if you are eligible.
Dr. Pheo
Hi Dr. Pheo,
ReplyDeleteI wish I had time to read all your previous posts because the answer to my question may be there somewhere. However, I feel this sense of urgency to forgo the reading and get on with the question(s). My son has MEN2B. Diagnosed 1990 at age 7. He has metastatic MTC. Adrenals have been monitored regularly. He has a tumour on one adrenal that has been growing slowly for a number of years. Last MRI or MIBG indicated a more significant increase in the size of the tumour and it's now 6cm. There's also a tiny tumour in the other adrenal. He recently did a 24 hour urine collection and results showed that one of the indicators was quite elevated this time (don't know the name or numbers, but can get this). He displays no symptoms...no anxiety, no headaches, no high bp, etc. He sometimes experiences night sweats. It's through his oncologist that these recent results were discovered and she immediately referred him to a surgeon. His endocrinologist hasn't even seen the reports yet. He saw the surgeon today and the guy gave him a terrible fright. He says that the adrenal has to come out asap or he could die. Is this true? We always assumed he had to be symptomatic. Do we have time to get a second opinion? What information should we be gathering? Thanks for your consideration.
Dear Ellen,
ReplyDeleteThe surgeon is right. Your son needs to start pre-operative preparation now. The surgery is not urgent but should be done soon after he is prepared. Pre-operative preparation is important even though he has no symptoms. It is a good idea to see the endocrinologist before the surgery and you do have time.
Dr. Pheo
Hello again Dr. Pheo,
DeleteMy son had his left adrenal taken out in December. Surgery went well. The only problem he experienced was a hard, distended stomach which settled down after time. In Febr. went to family doctor with severe stomach pains, distended stomach again. X-ray indicated gas build up. Bowel obstruction suspected. Admitted to hospital. Scans showed no obstruction. Four days on IV drip settled things. Still has a lot of stomach issues and suppressed appetite. Saw new endo/oncologist (thankfully, one you recommend on this site). Subsequently, MIBG scan, 24 hour urine collection done. Urine elevated and right adrenal and part of liver lit up on scan. Surgery to remove right adrenal and part of liver has been recommended.
Could you explain what is going on? We always thought that the pheos in MEN were benign. Are the stomach issues related to pheo? He also has chronic diarrhea b/c of MTC. MTC mets to lungs, liver, spine, groin. This is so complicated. He feels sick all the time, no energy and I am sick with worry. Can you suggest anything?
Thank you.
Ellen (in Canada)
Dear Ellen,
DeleteMedullary thyroid cancer (which metastasized to the liver in your son's case) can also attract MIBG. So the liver uptake is not necessarily pheo metastasis.
I recommend endoscope examination of his digestive tract. People with MEN2B often have mucosal neuromas in the digestive tract. Even without neuromas, poor motility is common. Ruling out a neuroma is important.
Dr. Pheo
Dear Dr. Pheo,
ReplyDeleteI want to thank you for all of your work in this area. I am from a family with a positive sdhb mutation. We look forward to your insight on the summer conference you attended. I hope you have a peace filled holiday.
I am not a candidate for MIBG. How do I find the trials?
ReplyDeleteI am posting this for a friend:
ReplyDeleteDear Dr:
Dec. 2011: Plasma Metanephrines (Free) ARUP lab:
Metanephrine Value: .20 Range 0.00-.49 nmol/L
Normetanephrine: Value: 1.02 Range 0.00-.89 nmol/L
Lab Comment: The majority of patients with a pheochromocytoma have a plasma normetanephrine concentration in excess of 2.2 nmol/L and/or a metanephrine concentration in excess of 1.1 nmol/L. The presence of increased concentrations of the analytes serves as a confirmation for the diagnosis of the tumor.
How to interpret the last sentence relative to my values?
Primary Dr. ordered the 24hr urine test at the same time the Plasma test was ordered. I have not yet provided the urine sample. Do you think it is necessary to provide the Urine sample?
I've had + Antithyroid Peroxidase for yrs with normal TSH. All Drs. previously ignored the pos. TPO. Current Dr. ran the Antithyroid test 2x's in 3 mos.:
Sept. 2011(Penn Medicine Lab): Antithyroid Peroxidase AB value: 39 IU/ml Range: <20
December, 2011(ARUP Lab?): 35 IU/ml, range: <20. Lab Comment: EQUIVOCAL: 20-50 IU/ml An equivocal result may indicate autoimmune thryoid disease. However, the clinical significance of the result may dependent on the patient's thyroid function.
Sept. 2011: Positive ANA titer 1:320, Nucleolar Pattern Penn Medicine Lab. All other labs Neg: (ANA Centromere, Anti SM/RNP, DNA Ab (DS), Sjogren's, RF, Sedrate 5). Referred to Rheum., not yet made an appt. - terrified.
LAB Comment: "Relative to the reference range established in this lab, this ANA titer is only weakly (???) positive The significance of the result should be interpreted in light of other clinical findings."
Sept. TSH 1.33, Range 27-4.20. Sept. tests I believe were thru Penn Medicine Lab. Dec.: ARUP, appears no TSH was done.
Upon receiving Metanephrines results, Dr. ordered Thyroid Ultrasound and Thryoglobulin test. Not yet scheduled appts - terrified.
Worried by results and direction my Dr. is taking especially regarding Thyroid Ultrasound. Research indicates he's looking for thyroid cancer? In your experience and opinion is the +Plasma Normetanephrine of concern for Pheo? Mayo ranges for Plasma are close to ARUP's. Have read the following which concerns me:
"The 95% reference range for a normal population is used in laboratories for determining the upper limit of normal for 24-h urinary metanephrines and catecholamines. However, the levels of metanephrines and catecholamines found in patients with spells or poorly controlled hypertension, but without pheochromocytoma, are frequently above the upper limit determined in normal value studies. To provide an acceptable level of specificity of testing, the diagnostic cut-offs for pheochromocytoma used at Mayo Clinic are approximately 2-fold higher than those for the normal population reference range. Thus, individuals with only MILDLY ELEVATED or borderline elevations of urinary total metanephrines or catecholamines are NOT inappropriately labeled as potentially having a pheochromocytoma. The altered cut-offs used at Mayo Clinic thus result in a higher level of specificity than reported by other investigators (12). Therefore, when clinicians receive a report of 24-h urinary total metanephrine results from Mayo Medical Laboratory, if a level of 1.3 mg/24 h or more is noted, the suspicion for pheochromocytoma should be high. When clinicians review the results of 24-h urinary fractionated catecholamines, the upper limits of the reference ranges shown should be approximately doubled in interpreting a positive test." Ref: http://jcem.endojournals.org/content/88/10/4533.full
The ANA/pattern frightening, pointing to systemic Scleroderma. Equally frightening +Normetanephrine. Are +ANA Nucleolar pattern, + Normetanephrines and +Antithyroid Peroxidase in any way connected?
Thank you sincerely for your time.
Hi Dr. Pheo! I am in the process of working with my dr to possibly diagnose a pheo. He wanted to do a CT & MIBG. I really can't afford the MIBG ($8,000 - and insurance won't pay a dime!!!) Will the CT be sufficient? The reason a pheo is suspected is I am a 28/female - hypertension (highest has been 166/114) tach (highest on record has been 170) severe weight loss (I am underweight now at 124) and metanepherine level at METANEPHRINE 24 HR TV: High 3000 mL out of range: 600-2000, also frequent heart palpitations, and what seem to be "adrenaline" rushes and horrible anxiety feelings.
ReplyDeleteThis came out of the blue. I am an active person who has trained all year for a half marathon so I consider myself physically fit. I've learned a lot reading your blog and I think you are doing a great thing! Do you have any comments/suggestions?
Dear Heather,
ReplyDeleteYou gave the urine volume but what are the metanephrine levels? If the metanephrines are significantly elevated, you can do CT of abdmoen, pelvis, and chest. MIBG scan is not necessarily needed. Usually CT of abdomen is sufficient but since you are young, extra-adrenal pheo needs to be ruled out.
Dr. Pheo
Dear Pam,
ReplyDeleteCheck the clinicaltrial.gov website and search with key word pheo or para.
Regarding your friend:
The metanephrine levels do NOT strongly suggest pheo. I don't know why the doctor check thyroid ultrasound and TG. Potentially the doctor looks for a thyroid cancer associated with pheo but that cancer is called MTC and calcitonin is the marker. I am not too concerned of anti-TPO and ANA as these are very common in females.
Dr. Pheo
METANEPHRINE 24 HR UR: 132 mcg/24 hr 52-341
ReplyDeleteFinal 12/09/2011 015
NORMETANEPHRINE 24HR UR: 189 mcg/24 hr 88-444
Final 12/09/2011 015
METANEPHRINE TOTAL: 321 mcg/24 hr 140-785
Final 12/09/2011 015
Test performed at Warde Medical Laboratory,
Ann Arbor, MI 48108
Medical Director: David F. Keren, M.D.
METANEPHRINE 24 HR TV: High 3000 mL 600-2000
Final 12/09/2011 015
24 HR URINE CREAT: 1.1 g/24 hr 0.8-1.8
Final 12/09/2011 015
I'm so glad I found you because it looks like the "high" value was misinterpreted by my dr if you are saying that is only the urine volume!
ReplyDeleteDear Heather,
ReplyDeleteIt does appear that the urine metanephrines are all normal. Pheo is very unlikely.
Dr. Pheo
Dear Dr. Pheo:
ReplyDeleteCan the clonidine suppression test be used to distinguish false positive from true positive results of elevated plasma metanephrine or is the test limited to cases of elevated plasma normetanephrine (or norepinephrine) ?
In his 2003 article in J Clin Endocrinol Metab, Eisenhofer seems to indicate that the test cannot be used to distinguish false positive results of plasma metanephrine and that “Clonidine-induced changes of epinephrine also offer limited help” .
Dear jhardy,
ReplyDeleteFirst of all, metanephrine or epinephrine levels are seldom elevated in isolation. Second, metanephrine levels are seldom falsely elevated if normetanephrine levels are normal. Third, the most frequently falsely elevated pheo marker is normetanephrine or norepinephrine.
Epinephrine or metanephrine levels are indeed suppressed by clonidine as well.
In practice, I treat elevated metanephrine levels in isolation as highly suggestive of pheo.
Dr. Pheo
Dr. Pheo:
ReplyDeleteThis is more related to one of your older posts, and I apologize for putting it here.
Symptoms similar to hyperthyroidism with in range TSH, T4 etc. Normotensive 24 yo male.
Pulled 5-HT, Nor/Metanephrines, and CgA. The first two were within range but the CgA was 6 nmol/mL. I also have high NE in a catecholamine battery, but that might be related to the blood draw itself.
This is likely an artifact. If I presented these results to an endo, what would be their likely course of action?
I guess my endpoint would be a diagnosis or imaging of the adrenals (unhelpful if the sympathetic overstimulation is central).
Dear sdf,
ReplyDeleteI actually prefer that you put the question under the newest post because it is easier for me to find your question.
It is very unlikely that you have pheo. An experienced endocrinologist would stop worrying about pheo here and look for alternative causes of your symptoms. If the CGA was from Labcorp, it was slightly elevated but the most common cause of CGA increase is due to anti-acid treatment. If you worry about the elevated norepinephrine, a clonidine suppression test can be done but it adds little. I would not do any imaging now.
Dr. Pheo