Some Symptoms Of Hyperadrenergic Pots.

[jangle]

I have cold sweaty palms anxiety disorders and mild symptoms all my life that became severe over the course of a few months (really accelerated over a period of a few weeks.)

I don't have postural hypertension, but my bp elevates under stress, my serum epinephrine levels were normal in the sitting position. I also don't urinate from standing up. Additionally my ttt said I had abnormal adrenergic function.

I have no access to specialized care that would be able to determine my subtype. I don't think Levine does this, I was just wondering from people who do know their subtype what they think and is it possible to have a pots that shares some components of hyperadrenergic pots but isn't?

[issie]

Jangle,

The noriepi levels are checked in a lying down position and also a standing position after rest. So, not thinking you've had yours checked properly and it might not be telling you your whole picture. I had this test done, but, I also have high bp's. I know that Rama does not have high NE levels but his presentation is hyper response - but, he also tends to have higher bp's. But, his finding was of autoimmune origin. So, I think it would be possible for there to be a sort of hyper response. Although, anyone with tacky will tell you that it feels like this hyper response. I can't compare my high NE surges with someone who has the regular tacky because I'm not sure it would be possible to distinguish between the two. I know mine are very intense and I can get them with body movement, posture change and I also have pallor at times - severe naseau and dizziness. I'm not however, a fainter - one very good thing. You can see the color drain from my face when these "spells" take over - I have a fainty, death like look about me. My husband can see it coming on and knows when I'm about to have an issue and sure enough then comes the tacky eposiode and the severe POTS symptoms that go along with the surge. I get them many times a day - some more severe than others. I just make sure that I get seated and try to get my feet up when it happens. At least I have some warning. Along with these "spells" comes a very uncomfortable anxiety type panic, gotta get out of here, please help me handle this, I'm out of control in my body and mind type of feeling. So, that's how my high NE level swings affect me. I used to think I was having panic attacks - but, now realize it is not that - it's been POTS most all my life. Stress will however, make it a whole lot worse.

I don't know if that helped or not.

Issie

[ramakentesh]

I think its impossible to tell from symptoms. Blood pooling in hands and feet might suggest otherwise but im not really sure how you can tell. Every research group has a different take on it and I read different thoughts from docs here every day. its supposed to be 10% of patients yet nearly everyone on this site has been told they are hyper or have a hyper presentation.

[POTLUCK]

was just posting on this in ( not sure if I should repost or link to say the same. I did both but let me know the correct form. ) as I am very interested in which type and how you tell if you can't have your "flow" type tested.

In Topic: How Do You Know If U R Hyper Vs Hypo Pots

Yesterday, 04:00 PM

I am interested in whether I have Hyperadrenergic POTS as Dr. Stewart in "Primer on the Autonomic Nervous System" edited by Italo Biaggioni, David W. Robertson, Geoffrey Burnstock, Phillip A. Low, Julian F.R. Patonstates that "Low flow" POTS is similar to the "Hyperadrenergic" POTS originally proposed by Streeten. His research indicates that "low flow" POTS has reduced nitric oxide and that "regular flow" and "high flow" POTS have increased nitric oxide. Thus, if I have Low Flow POTS then treatments that increase nitric oxide such as Losartan ( via blocking Angiotensin 2 type 1 receptors ) and Vitamin C, among many other possibilities might help me. If I have one of the other types of POTS they might make me worse. Now Dr. Stewart himself writes that " these categories comprise fuzzy sets " however, if I wait till they figure it out I will not be well for a long time and I am sure many people on this site also see it as taking a best guess with their doctor.

Using this same reference I would note that Low Flow patients frequently have increased Angiotensin 2, have a higher HR, including resting than the other two types. ( one of his studies showed 85-90 average supine ), "generalized pallor, cool skin, and other findings suggesting circulatory insufficiency" "There is a marked female gender preference" ( I am male but that is not an exclusion. ) " 'There is also an inverse relationship with body mass index" " These patients often have increased upright concentrations of NE"

In http://www.stars-us....roof%20copy.pdf Dr. Blair Grubbs 2011 article refering to 29 Hyperadrenergic patients he notes "

Patients were diagnosed as having the hyperadrenergic form based on an increase in their systolic blood pressure of >10mmHg during the HUTT (2) with concomitant tachycardia or their serum catecholamine levels (serum norepinephnrine level

600 pg/mL) upon standing.

My cardio said my blood pressure was increased 10 on tilt but it really stays about the same on average and bounces alot. I would not say I have general Pallor but definately have cold hands and feet and Raynoud's syndrome. I have a BMI of 23, and Type 2 diabetes which decreases NO. I have a high lying HR ( 85-105 ) and standing bounces to 156 and as low as lying but always goes over 130 off meds. High dose ( 140mg ) propranolol does not completely lower HR. I am waiting on Free Catecholamines sitting and standing, Angiotensin 2 Renin, and Aldosterone. ( They were unfortunately done back on high dose B-blocker. ) I think I have low flow, hyperadrenergic, POTS but am not certain by any means.

[ramakentesh]

Suggested etiological mechanisms for Hyper POTS:

Beta 2 receptor desensivity - cause or consequence of POTS?

Elevated ang II which may - decreased neuronal NO and cause sympathetic excess, vasomotor nerve failure and increased periperhal resistance/low blood volume

- decrease ANG ii receptor vasoconstriction in the stomach leading to compensatory sympathetic excess and vasoconstriction

NET deficiency - with moderate postural hypertension and perhaps peripheral vasoconstriction, beta 1 stimulation of sinus node and central decreased sympath activity - still considered conjectural

Low NO state - conjectural

Idiopathic hypovolumia - high dopamine? Abnormal salt handling?

Neuropathic POTS - compensatory denervation hypersensitivity?

Endothelial disfunction - maniifests as leaky capillories in stomach circulation - being investigated.

Beta 1 receptor autoantibodies - waiting for dr Grubb to publish

Alpha receptor hypersensitibity - waiting for Dr Grubb to publish

[issie]

Thanks for the breakdown Rama.

Potluck,

I do have the pallor - that's one of my first things to happen right before an attack and then the symptoms start. I'm guessing that I'm low flow and do seem to fit allot of the symptoms for it. I also seem to have NET dysfuction and do have high NE with standing. Also have the high bp's. - Just looking over Rama's list from the things I do know - seems about right for me.

Issie

[POTLUCK]

Ramakentesh,

It seems like their are alot of possibilities. I guess that is why I like the flow divisions that Dr. Stewart is using. Their is not a lot of overlap in the flow categories if you look at the charts. Now that in no way implies that the etiolgy is the same, but it might help point a direction towards treatment. Also, it seems like more than one type of treatment might be applicable.

As an example in one person if an autoimmune response of the body was being mounted against the ACE2 in a given person, and that resulted in increased Angiotensin II and that resulted in decreased nitric oxide and that resulted in increased microvascular resistance and that resulted in a sympathetic increase to provide enough blood to the brain, and that resulted in an increase HR and BP there might be several ways you could treat.

B-blocker might slow the HR. ARB might increase nitric oxide, decrease peripheral resistance, and thereby decrease sympathetic activity ( if it is a compensatory action in that case ) and lower the heart rate. Yet the best way might be to block the immune system or response that is attacking the ACE2, via something like Rituximab, as they recently had success with CFS patients with. ( I do not know if they are using it with POTS )

There are obviously a lot of possibilities, for types and etiology but it seems to me that narrowing down the type certainly helps in choosing treatments.

I think there are likely to be many etiologies to the same damaged sytem with common pathways. But if I wanted to fix the spillway to a ****** up lake I would want to know if the problem was the water level was rising or falling as a start to figuring out what the spillway problem was.

[ramakentesh]

Dr Stewart and Medow find patients with Low flow states without increased ang II. They just havent published work on them yet. I guess they would suggest that all forms of low flow states - increased orthostatic BP and increased MSNA - would respond to intravenous vitamin C or other antioxidants.

Rituximab would be very interesting in many forms of POTS. There could be autoantibodies to beta 1, beta 2, NET or perhaps ace 2 or ang II receptors. Those as well as the a3 nicotinic receptor already published by Mayo.

[issie]

I've looked up info on Rextiuximab before and also wonder why - if they know we have autoimmune issues - why don't they stop our autoimmune system from attacking us and quell that issue and then see what else needs to be taken care of. I've discussed this with another person here on the site - pretty recently via PM's. I would love to find something to stop my autoimmune attacks!!!

Issie

[POTLUCK]

Ramakentesh,

You seem to have an amazing amount of knowledge on these things.

The problem with stewarts work that is published is that he is only showing a local response due to microdialysis injections, and not what happens when you affect the whole system. I still appreciate that he is doing the research. He seems to be currently giving Losartin to patients that test as low flow to see what happens but that study goes till 2014. I figure I will just try it now. ( 25 BID today - no clear benefit or worsening yet.) I am also taking vitamin C 500 BID.

You mentioned " all forms of low flow states - increased orthostatic BP and increased MSNA" I am thinking my system may have been in balance on the collection of meds started for TLE 20 years ago and the Diabetes may have decrease nitric oxide and changed the balance. Many of the drugs I was given 20 years ago VPA, Selegiline increase NO, and propranolol was of course blocking the highs of the HR.

link to Rituximab story, with full article at bottom link here... http://thoughtsaboutme.com/2011/10/20/norwegian-rituxan-study-published/

[issie]

Thanks for the link. I sent it to my sis who has CFS really bad. Wonder what the long term effects of that med is?

Issie

[ramakentesh]

many patients are already on Losartan and similar meds with good results. diabetes could decrease NO, could increase assymetric dimethylarginine but diabetic retinal damage is associated with increased NO rather than decreased. Also elevated glucose levels could result in neuropathic damage.

[L4UR3N]

I think the problem is that there are no universally accepted diagnostic criteria to distinguish between the two types. One study defines Hyperadrenergic POTS as standing NE above 600pg/ml, while another one defines it as above 1000, and sometimes over 2000 pg/ml. Both agree that postural hypertension must be present though.

I was diagnosed with Hyper POTS simply because I am hypertensive when I stand. My standing NE levels were above 600 pg/ml, but not anywhere near the 2000 pg/ml mentioned in some literature. I did have positive urinary methylhistamines, which seems to go along with some types of Hyper POTS. My dopamine however has never been seriously elevated--actually it's right where it should be. I do have venous pooling which I think may be the cause of my hypertension. Both my BP and pulse normalize with a NS bolus. Salt loading has unfortunately never worked well for me, and no doctor has prescribed florinef due to my hypertension (though I would really like to try it given the paradoxical reaction to NS).

I dont think that you need specialized care to get some tests that may prove valuable to you. Take some articles to your family doctor and ask for the tests that you need. You should have plasma (not urinary) NE levels lying, sitting and standing. They can measure the rest of your catecholamines at the same time. If those levels are elevated your doctor will most likely want to run some other tests on you just to exclude some other causes. If they are not elevated, and neither is your blood pressure, then you may have your answer

[issie]

Rissy, whats a NS bolus?

Issie

[L4UR3N]

Normal saline bolus

[issie]

Thanks!

Issie

[POTLUCK]

Rama,

Yes, nerve damage due to the Diabetes could be the entire problem in my case and that is of course a good thought. However, I developed the dizziness in Dec 2009 right when I was diagnosed with the Diabetes ( and my sugars were not bad -mostly under 150 ) As the dizziness got worse so did the diabetes. ( cause effect or neither ? ) but when the sugars went high ( 300's for peaks ) I got them down in a couple months, so not much time for nerve damage. ( Also eyes, kidney, peripheral nerve testing for touch etc. are all good. ) I use Actos, though doubt it does much just continue it for now not to rock the boat but endo also feels a trial without it later is a good idea. What keeps the sugars down is low carb diet. Jenny Ruhl's approach. http://www.phlaunt.com/diabetes/index.php

As I have learned more about NO I have found reference to diabetes decreasing NO but insulin increasing it. The low carb diet does not stimulate the insulin ( part of the idea for the diabetes ) but this may mean less insulin to increase NO.

Low NO could even be worsening the DM http://www.nfb.org/Images/nfb/Publications/vod/vod212/vodspr0613.htm

http://diabetes.diabetesjournals.org/content/55/1/102.abstract

In this article they use BH4 to increase NO and decrease DM 2 effects.

http://www.springerlink.com/content/6lyab59mpa6qg3nm/

This is another interesting article suggesting a stabilizing effect directly on the SA node of NO

http://george-eby-research.com/html/taurine-l-arginine-arrhythmias.pdf

I thought I had one on NO decrease and the eye in DM but maybe not, as I can't find it. Since we were talking about NO and the sun a day or two ago, I will throw this one in I just came across. Hope no one minds too many links.

http://eurheartj.oxfordjournals.org/content/early/2010/03/09/eurheartj.ehq069.full

[POTLUCK]

Diabetic Retinopathy and increased nitric oxide ( very interesting.) I do not know how you remember these things. I could not find my article (argh) so I googled the subject.

I found this article suggesting increased NO as you said

http://www.molvis.org/molvis/v15/a242/

but I found this suggesting this may not be the case. ( This article gets a bit complicated for me. )

http://diabetes.diabetesjournals.org/content/47/6/945.short It seems to be suggesting that as iNOS was upregulated baseline NO went down.

This kind of interaction ( i.e. complicated ) between iNOS, eNOS, and nNOS may have a great deal to do with the different affects in POTS and in related areas such as CFS and mast cell disorders. nNOS is a neurotransmitter, particularly important in the hypothalmus, yet Dr. Stewart's research states specifically it was the nNOS and not the eNOS that was affected in low flow POTS. Reference...

http://www.nymc.edu/fhp/centers/syncope/nNOS%20in%20low%20flow%20POTS.htm

[jangle]

Potluck I myself am going to be starting losartan soon. Keep in mind there is an inverse correlation between angiotensin ii and NO bioavailability. To say there is reduced nos is also to say there is a regional angiotensin ii elevated concentration.

[POTLUCK]

http://www.nymc.edu/fhp/centers/syncope/he%20Metabolism%20of%20Ang-II%20by%20angiotensin%20converting%20enzyme-II%20(ACE-II)%20is%20defective%20in%20Low%20Flow%20POTS%20causing%20a%20reduction%20of%20the%20vasodilator%20Ang-(1-7).htm

See picture- it is complex but I like the picture explanation. Angiotensin II appears to have an affect via both receptor types and its breakdown product. Or there may be a problem in some cases with the breakdown via ACE2 ( by antibodies? ) or by a polymorphism for the Angiotensin 2 type 1 receptor itself such as this correlation in MVP http://www.ahjonline.com/article/S0002-8703(00)70015-9/abstract or the connection with Ang 2 type 1 in Marfans

http://www.nejm.org/doi/full/10.1056/NEJMc081528

The above article on Diabetic retinopathy seemed to suggest that as iNOS was upregulated baseline NO went down. So it is not clear to me that what happens locally will have the same effect on the whole system.

"To say there is reduced nos is also to say there is a regional angiotensin ii elevated concentration" may depend if it affecting the type 1 or 2 receptor if I am not confused ( which I may be )

http://www.ncbi.nlm.nih.gov/pubmed/18182246

http://www.ncbi.nlm.nih.gov/pubmed/10691781

http://www.ncbi.nlm.nih.gov/pubmed/9218502

However with all that confusion added my idea is IF I have the low flow POTS the losartan may increase NO levels and decrease peripheral resistance. I do not know if I have the low flow type.

When are you starting it. I heard your running was helping. I always feel good while running which I suspect is NO and the faster HR, but the last time I ran my HR was elevated for hours afterwards. I have never had syncope so upright exercise is a possibility for me.

[L4UR3N]

Yes, nerve damage due to the Diabetes could be the entire problem in my case and that is of course a good thought. However, I developed the dizziness in Dec 2009 right when I was diagnosed with the Diabetes ( and my sugars were not bad -mostly under 150 ) As the dizziness got worse so did the diabetes. ( cause effect or neither ? ) but when the sugars went high ( 300's for peaks ) I got them down in a couple months, so not much time for nerve damage. ( Also eyes, kidney, peripheral nerve testing for touch etc. are all good. )

There is actually a link between prediabetes and peripheral neuropathy. Any sugar above 100 is considered abnormal, so having sugars above 100 for a prolonged period of time can definitely cause nerve damage. My neurologist is actually doing a lot of research in this area and found great success with specific lifestyle modifications. You can read about it here:

http://www.umm.edu/n...pathy/inmed.htm (a link to the clinical trials)

http://care.diabetesjournals.org/content/29/6/1294.full (what his results are showing)

http://jn.nutrition....m%20T.%20Cefalu (Also his findings on Chromium Picolinate, diabetes and endothelial function ------ Very interesing!!!!!

[L4UR3N]

oops I think this was the link I meant to post on chromium and endothelial function LOL (though the other one is good too!)

http://www.prnewswir...s-55696562.html

[issie]

I'm too tired tonight to read all this - but, will tomorrow. But, just wanted to comment on the chromium. I have been insulin resistant for about 25 years now. When it was discovered my doctor told me to start taking GTF (glucose tolerance factor) chromium. I've avoided going into diabetes by using that. I started out with 3 a day and then 2 and now 1. I will sometimes take two if I eat a splurge that day. I space it out and don't take them all at once. With diabetes on both sides of my family - I genetically am pre-disposed to it. But, seem to be doing okay with just this supplement. Even as a very young child I have severe hypoglycemia - levels down into the 30's - I didn't get the insulin resistant DX until my 20's and started on the chromium then. I do have a few ups and downs - but, stay pretty level most of the time.

Issie

[jangle]

Potluck, I have two different states of symptoms. The unstressed continuous state and the elevated anxiety/over stimulated/ stressed state which simulates presyncope severely. Running has helped the unstressed symptoms as well as mitigate the stressed symptoms but thusfar it hasn't had as significant effects on the stressed symptoms.

http://www.ncbi.nlm.nih.gov/m/pubmed/10783146/

This article explains how I believe elevated angiotensin ii is creating a hyperexcitable/anxious state by increasing the activity of neurons in the region of the brain responsible for anxiety.

I begin the losartan tomorrow.

[POTLUCK]

Jangle,

Good luck with the Losartan I read the abstract of the above, and will read the full article later. What do you mean by "simulates presyncope severely." I just learned you cannot click on someones profile or you lose what you have written, as I clicked your profile to see if you had anything that would explain the phrase, and had to rewrite everything above as it was gone when I clcked back.

Rissy2D-Thank you for the articles, and yes any elevated sugars can be harmful, although Jenny Ruhl presents a tremendous amount of literature showing damage begins above 140 & 150. Other than a few months my HgA1c is consistently below 6.0, so I am only suggesting less chance of nerve damage, not that it is ruled out.