Two papers on risks of familial pheo appear in the May, 2009 issue of the Journal of Clinical Endocrinology and Metabolism. One Paper describes experience in about 500 Italian patients, the other over 200 Spanish patients. The paper on Italian patients is particularly informative. With the three large studies now available (the original landmark study in 2002 published in the New England Journal of Medicine and these two new papers), I feel it is time to quantify the probability of having familial pheo. I have prepared a calculator of risks for familial pheo. The calculator is based on the 3 above large studies. The calculator has only five input variables:
1) Primary location of your pheo/paraganglioma
2) Age at diagnosis
3) Family history of pheo or paraganglioma (Yes/No)
4) Single or multiple pheo/paraganglioma (Single/Multiple)
5) Do you have any of the following diseases in addition to pheo/paraganglioma (Yes/No): medullary thyroid cancer, hyperparathyrodism, hirschsprung's disease, mucosa neuroma, hemangioblastoma, renal cell carcinoma, pancreatic neuroendocrine tumor, and skin neurofibroma?
As this is a blog format, I can not post the calculator on line. If you tell me the answer to the 5 variables, I will tell you your risk of having a familial pheo. The calculator has its intrinsic limitations and perhaps even errors; and the results are only as good as the accuracy of the 5 variables. Also I can not tell you the chances of any particular mutated genes.
Of course, the calculator only gives you an estimate of risk and only your doctor and you shall decide whether to do genetic testing. You should use the results of the calculator responsibly and at your own risk; I can not be held liable for any adverse consequences.
Dr. Pheo
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I have about 7 paraganglioma tumors, and am scheduled for a non-tumor related surgery. The internal meds doc assigned to me by the hospital in my previous non-tumor surgeries has prescribed Atenolol for my pre-op prep. I notice in the paperwork accompanying the Rx that it lists pheo tumors in the "beware" paragraphs. In the 3 surgeries I've had in the last 2 months, there were no BP issues, but the literature has me concerned. What's your take on Atenolol for pre-op blockade for surgery not tumor related?
ReplyDeleteDo you still have any paragangliomas left in your body now? And are these paragangliomas functional (producing catecholamines)? If you do and they produce catecholamines, you should be alpha-blocked first, then you can use beta blockers.
ReplyDeleteAny surgery will have the risk of pheo crisis. I suggest that you let the doctor know your paraganglioma status. The pheo crisis is rather unpredictable. You may be OK for 3 operations, but you may have a crisis on the 4th (or not).
Dr. Pheo
I'm curious, so I'll bite. ^.^ Here are my five variables.
ReplyDelete1.) My paraganglioma was found on my heart. Between the Aorta, and attached to the pulmonary artery.
2.)I was 16 when we first found out I had a pheo/para. (Took nine years to find though.)
3.) No family history that's known.
4.)Single paraganglioma.
5.)No I don't have any of the listed. I had a GIST removed from my stomach when I was 18 though. Doctors have said I now have Carney Triad because 2 of the 3 have been present.
Thank you to be the first again.
ReplyDeleteYou actually have a high likelihood of having Carney Triad. As Carney Triad is not genetic and is very very rare, I did not put it as part of question 5.
To just illustrate how the formula works, let's imagine for a moment that you do not have GIST. Then the chance that you have a familial form of pheo is 13.8%. If the paragangliom is active in producing catecholamine, then the chance increase to 43%.
Dr. Pheo
Dr. Pheo
It's amazing (if I didn't have GIST) on how it jumps to 43% when it's active. Mine was very active, lol every heart beat pumped more out so it was like someone poking a pheo all the time. It made life...interesting.
ReplyDeleteThanks for the hypothetical calculation. ^.^
Also, I know GIST isn't your area of work, but I'd like to read your opinion. I've only had one GIST removed, it's been 7 years since then and I haven't had anymore found (yet) but a doctor told me to remove my entire stomach so it won't spread...if you were in my shoes what would you do?
Try this:
ReplyDelete1) right adrenal encapsulated
2) Age 27 345 days
3) No history... however high blood pressure ran in the family and several deaths due to CVA age late 40's. (1930s and early 1960s)
4) Single
5) No known at the time of diagnosis. History of slightly elevated CT since. Grandparent died age 89 complications from RCC, but not RCC itself.
Final diagnosis: RET Mutation, but one which no one had documented before. 10 years ago.
Dear Foxy,
ReplyDeleteRegarding your para and GIST, I suggest that you discuss with your doctor whether you have Carney-Stratakis syndrome (para + GIST, with family history). In this syndrome, SDHB, SDHC, or SDHD has mutations. This syndrome used to be considered as a subtype of Carney Triad but now is a stand-alone syndrome.
For treatment of stomach GIST, it will be a personal decision. Total gastrectomy prevent future GIST but your quality of life will be affected. You will have an ~50% chance of recurrence with the risk of metastasis without total gastrectomy. If I were you (and had good health coverage), I would do regular follow-up. Maybe I would be lucky to fall into the 50% without recurrence. Of course, ultimately you have to make your decision.
Dr. Pheo
Dear DJPheo,
ReplyDeleteMy formula says the chance that you have familial pheo is 24%. Of course it is just a chance to guide genetic testing.
With your grandparent having RCC, I almost think that VHL is likely. Your case illustrates well the tricky guessing of mutations. Interestingly, the first recorded case of pheo (in 1886) was initially thought to be due to VHL based on clinical info but turned out to be due to a RET mutation.
Dr. Pheo
Hi, re. Ian
ReplyDelete1. Left adrenal gland
2. 38
3. No, parents & older sibling still alive & well, grandparents lived to 75+
4. Multiple lung pheos
5. No
52% for Ian.
ReplyDeleteDr. Pheo
My genetic risk?
ReplyDelete1) first Pheo: Right Adrenal. Second--unlocated as of yet
2) 29 years old
3) NO, but Father has polycystic kidneys
4) Single but now recurrent
5) No
What are the theories or model on how pheos develop? I know somewhat about the genes that cause a gain of function and others that result in a loss of function by some specific protein. But I'm more interested in the genesis from the first cell to a mass producing excess catecholamines.
ReplyDeleteMy own assumption is that many people visualize pheos developing as a hyperplasia of cells where at some tipping point there is an overabundance of cells that start wrecking havoc on the body. All cells involved are mature catecholamine producing cells.
But I also suspect there are also more complex cancer models where pheos develop out of primative chromaffin cells or hyjacked chromaffin cells. What then is experienced is similiar to what goes on in early embryonic development with the cells expressing different hormones, proteins/polypeptides, and then start to express catecholamines. ie.. masses may develop and be relatively "harmless", be called "silent", producing other hormones or protein/polypeptides that may or may not be having subtle (or not so subtle) effects on the body, and one day wakes up to start producing catecholamines on a consistent basis? Hence the PFM tests may not pick up catecholamines because the pheo in the making hasn't matured to the point of catecholamine production.
Dear Abeja,
ReplyDelete52%.
Dr. Pheo
Dear DJPheo,
ReplyDeleteYou certainly have in-depth knowledge on pheochromocytoma pathogenesis and on tumorigenesis in general. All the scenarios you describe can be true for pheochromocytoma pathogenesis.
The pathogenesis of tumor/cancer including pheochromocytoma is not well understood as a whole. Even in patients with MEN2 or VHL, not every one has pheo. There must be multiple pathways working together to generate a tumor, and each pheo may take a unique path (likely different from each other) to get there. We need more research to learn how tumor forms.
Dr. Pheo
This comment has been removed by the author.
ReplyDeletePlease calculate/comment:
ReplyDeleteLeft Adrenal
Age 50 (symptomatic for 1 year prior to dx)
No family hx of pheo/paraganglioma, but many with CA (father- renal & pituitary, pgm- renal, uncle-lung, aunt- brain, sister- thyroid (unknown type) An uncle also has AAA and aortic arch aneurysms and marfanoid features. Lots of htn in family as well.
Single encapsulated pheo
I have had thyroid cancer (papillary), and have hyperparathyroidism. Endocrine MD unsure now whether it is primary or secondary or mixed. I have multiple pearly skin lesions on arms and legs, but haven't had them examined. Cysts identified on left kidney on MRI.
Thanks...
52% - Interesting - all Ian's genetic tests were negative. We think he was symptomatic for approx 3 yrs prior to diagnosis of a large (10cm+ pheo, 500g in weight)
ReplyDeleteDear Cldorsey,
ReplyDeleteYou have a unique family and personal history. Renal cell carcinoma and renal cyst are features of von Hipple Lindau disease. Marfanoid features are part of MEN2B while hyperparathyroidism is a feature of MEN2A. I suggest testing VHL and RET mutations first.
Most likely you have unknown inherited mutations that predispose you to tumor formation. You are in the gray zone as far as my calculator is concerned.
Dr. Pheo
Dear Dr. Pheo,
ReplyDeleteI had my pheo removed in May of 2009 and nothing about genetic testing was ever mentioned at that time. They found the pheo as an incidental finding during an MRI for a shoulder injury I had. I am very grateful that they found it at all b/c I had no symptoms. In fact, my blood pressure was normal. I went through a lot of testing just b/c the doctors didn't believe it could possibly be a pheo without symptoms. However, after a final MIBG scan (and obviously multiple tests of elevated hormones continuing to increase) they went ahead with the surgery in Orlando, FL. I was very blessed that everything went well overall and my hormones levels have returned to normal at this time. I am concerned that the tumor could eventually grow on the other adrenal gland b/c they said to keep in mind that it could be bilateral in the future. I can only assume to do a 24 hr urine test yearly to keep a watch on this...any other suggestions?
I have recently found info about genetic testing and I'm trying to research more into if this is something I should do for my own knowledge and my family. At this time I do not have children, but would love to in the future. So any info on if you think genetic testing is beneficial would be appreciated. I now live in Georgia and would need to find out where they do this time of testing in time. For the time being, if you are still posting about the calculater mentioned above, here is my info...
1. right adrenal gland
2. 28 years old
3. no known family history
4. single
5. none of the listed diseases, but was diagnosed with juvenile diabetes at 14, insulin dependent
I appreciate your help/knowledge!
Dear Megan,
ReplyDeleteYour current risk of having a mutation is 14-24%. The risk will be higher if you have another one in the future. Testing for genetic pheo is a bit complicated and you should ask your doctors about it.
If you do yearly testing, you should be able to detect a pheo in time. Knowing your genetic risk will be helpful to screen for your children, though.
Dr. Pheo
Fairly straight-forward so far, but then my Pheo hasn't been removed yet, so there may be more info to come. Thanks in advance!
ReplyDelete1) Left Adrenal
2) 38
3) No
4) Single
5) No
Dear Electronic,
ReplyDeleteIt is about 14%.
Dr. Pheo
Thanks in advance
ReplyDelete1) Left Adrenal
2) 42
3) No
4) Single
5) hashimotos
Jesse
Dear Jesse,
Delete9%.
Dr. Pheo
Dear Dr. Pheo,
ReplyDeleteMy mother was recently diagnosed with uterine cancer and genetic testing confirmed Lynch Syndrome with mutations in MLH1 and MSH2. Genetic testing on me also shows the same mutations.
Typical of a mother being more concerned with her child's health than her own, she asked her oncologist and genetic counselor about any association between this syndrome and pheochromocytoma in addition to the typical associated cancer risks.
Both indicated that any link between endocrine tumors and LS is a bit controversial with little supportive data.
Previously, I had 2 urine and 3 plasma tests a couple years ago and all were slightly elevated suggestive of pheo, but certainly not diagnostic.
After a sleep apnea test was negative, I am convinced my continued symptoms are likely stress, but my mother feels adamant that I should ask my doctors for imaging studies in lieu of the classic colonoscopies I'll need performed regularly.
I feel like I've wasted enough of everyone's time and money just getting to the suggestive-of-pheo phase, I'm not sure I feel it's worth it to continue the hunt for answers when I probably just need more meditation.
Have you had any experience with a connection between Lynch Syndrome and pheos? Would this extremely rare (if even possible) connection be worth exploring in your opinion when symptoms persist?
Thanks for your time.
Dear Mr. Smith,
ReplyDeleteI have never seen a patient with Lynch syndrome and pheo. I don't think you are more susceptible to pheo than the average person.
Dr. Pheo