POTS, mast cells & Vanderbilt

[Questus]

Got information from someone who was just back from a research study for 8 days at Vanderbilt, and one of the primary dysautonomia doctors there told her their theory on pots and mast cells. I did some research and found the exact same summation here. Pretty amazing. Mast cells cause hyper POTS?

Found this in as an excerpt from a very comprehensive site called stoppotsvirginia.blogspot.com

Here is the technical theory published by the researchers at Vanderbilt:
"Mast cells are localized in close proximity to blood vessels and peripheral nerves and are therefore strategically positioned to modulate sympathetic activity, vascular tone, and angiogenesis.20 Histamine is a powerful vasodilator that could explain the cutaneous vasodilatation responsible for flushing. With regard to the pathophysiology underlying the association between POTS and MCA, we propose a positive feedback loop by which MCA, with the subsequent release of vasoactive mediators, may contribute to vasodilation, reflex sympathetic activation, central volume contraction, norepinephrine release, and orthostatic intolerance (Figure 4). Conversely, our results indicate that exercise can lead to MCA, presumably through sympathetic activation."

 

[Questus]

The excerpt is from this Vandy paper. Speaking of hyperadrenergic POTS.

http://hyper.ahajournals.org/content/45/3/385.full

 

[ramakentesh]

I think you'll find this etiological theory only applies to a small subset of hyper patients. Vanderbilt have recently identified a larger subset with elevated angiotensin II and other researchers with epigenetic modification of the NET gene.

 

[Seven7]

So how do you know the type of POTs? And does it affect the treatment approach??? Anybody had good results at Vanderbilt?

 

[Questus]

I think you'll find this etiological theory only applies to a small subset of hyper patients. Vanderbilt have recently identified a larger subset with elevated angiotensin II and other researchers with epigenetic modification of the NET gene.

Raj, this same information was given this week to a patient at Vandy during an eight day study. As for the 'small subset of hyper patients'...I can only speak to mine. My standing NE is over 1400. Yes, extreme. I don't want to speak for the person who had the experience at Vandy, except to say she and I have a similar presentation. And we both have orthostatic hypotension. Go figure.

Saw my cardiologist this week and got a script for Mestinon. (Based in large part for your enthusiasm for it.) Am now suspecting I should have gone with Methyldopa due to it's ability to reduce NE.

Point blank, do you have hyper pots or not? Not to put you on the spot, but you've had strong opinions and have stated Mestinon has been great for you. Will you please share your standing NE test results pertaining to hyper pots. Are you hyper or not?

Have followed your posts on another forum, so am asking this sincerely. Please share the type of pots you have.

Thank you,
Questus

 

[ramakentesh]

With very high NE levels do you mean orthostatic HYPERtension? The three postulated etiologies for POTS caused by sympathetic excess (that is elevated NE levels, usually postural hypertension and most importantly elevated postural MSNA firing rate) are Low Flow (low blood volume, low aldosterone, impaired ang II receptor function and elevated plasma ang II), NET deficiency (usually acquired, rarely genetic) and MAST cell activation.

In MCAD the patienst have signs of Hyper POTS but with episodes of profound hypotension to the point of severe syncope and other symptoms. It is considered quite rare.

More recently some EDS patients claim and associate between EDS and MCAD but this isnt really supported by much peer-reviewed research.

 

[ramakentesh]

The problem with questions like 'do i have hyper pots or not' is that they dont take into account that each research group and facility have their own opinion on whether HYPER pots is a relevant delineation, each have differing opinions or are working on different leads as to the primary etiologies of POTS and the delineation and most acknowledge the delineations are 'fuzzy' in that one group also shows signs of another and there are no fixed rules about what medication works for which group.
Mestinon can improve sympathetic activity but it can also just improve baroreflex sensitivity which is out in the groups of POTS you might call Hyper.
it is probably not really possible to compare subjective symptoms with another patient and assume the same etiologies apply and that the same medications will help.
lastly very high NE might indicate NET deficiency.

 

[taniaaust1]

Got information from someone who was just back from a research study for 8 days at Vanderbilt, and one of the primary dysautonomia doctors there told her their theory on pots and mast cells. I did some research and found the exact same summation here. Pretty amazing. Mast cells cause hyper POTS?

This stuff has been known for quite a while now and one of few strong reasons I strongly believe I also have a mast cell disorder on top of everything else I have going wrong. I have hyperadrenalic POTS on top of the low blood volume kind. Ive self diagnosed myself with this form of POTS as I often get extremely high noradrenaline (so high that the labs didnt believe what they were seeing with 3 of my test results.. I kept being made to get the tests redone..over and over and over).

I also have orthostatic hypertension.. spikes of up to 170/136 (my BP is very low when laying thou). (and I have an uncle with systemic mastocytosis). Ive also once had what is called a darier sign (found in mastocytosis) of cause the doctors at that time didnt know what it was and at that point of time, I didnt know either. (doctor blamed my rash blistering on the sun when I hadnt even been out in it..it blistered on touch). Ive also had that skin writing disease thing at times (another sign of mast cell disorder). Im over 90% postive with these things that I must have mast cell disorder.

Im currently on Clonidine which lowers noradrenaline. Unfortunately thou that hasnt helped my POTS as such (I think my blood volume needs to be further boosted as the florinef and medical compression stockings does certainly help me, doesnt do enough) but the Clonidine has helped my huge adrenaline spikes I get.


I wish I could find a doctor who understood the mast cell disorder stuff. I saw a stupid professor in autonomic disorders at the main city hospital who just told me that its impossible to have both POTS and orthostatic hypertension.. but I do have both. She just dismissed me and even ignored the info i took in with me on all this.

 

[ramakentesh]

You can indeed have postural hypertension and POTS. Infact it occurs in a subset. its interesting though because usually there is still either reduced central sympathetic outflow despite peripheral vasoconstriction meaning dizziness and pooling in the stomach/head or there is impaired cerebral autoregulation also causing dizziness.
main observation doctors have made is that often the delineations are fuzzy - some have characteristics that confuse their delineation.

Again extremely high NE levels would be more suggestive of either NET deficiency or perhaps low flow POTS. In MCAD POTS while there is increases sympathetic drive at normal times there are also episodes of orthostatic hypotension and fainting.

A very current document that gives a pretty clear idea of the current thoughts on the delineations of POTS etiology can be found here:
http://10thintcatsymp.org/presentations/tue/10AM_NAUTILUS_9.11_RAJ.S.pdf

 

[Questus]

Rama, thank you for the PM, I appreciate it.

Please let me answer here, as I can only type for so long.

First let me say I've been very fortunate to have been seeing an expert in dysautonomia. He's treated many cases of pots, ist, and ncs. He's also a cardio surgeon. He's done every test in the book on me. Very, very comprehensive.

I know many people have not had a good experience with getting pots treatment, but my experience has been outstanding. Was first dx by Dr. Nancy K. and from her I went to the cardiologist I'm speaking of.

The catecholamine test is a critical aspect in determining if you do or do not have hyper pots. All experts agree, Vandy, Mayo and Grubb, that a standing norepinephrine level of over 600 is positive for hyperadrenergic pots. A standing NE of over 1000 indicates a strong possibility of MCA.

My standing NE is over 1400, and I have extreme MCA, and am in the process of being tested at M D Anderson for Systemic Mastocytosis,

Dr. Grubb published a paper stated the symptoms of MCA in pots patients. 100% of patients with MCA have facial flushing.

So I have no need to go to Vandy or anywhere else, I've had literally every test in the book done for dysautonomia done by the cardiologist I see. Am very fortunate to have found him.

Hyper pots is rare. Only 10% of pots patients are hyper.

And yes my BP is hypo, not hyper. My BP does jump around when standing but is low while sitting and laying down.

I know of another hyper patient with a very high NE who is also hypo. So it's not as common but it happens.

The first 2 bb's I took caused by BP to go to 80/40 and 70's/50. Clonodine was a disaster. Clonodine is perhaps the most widely used drug for hyperpots yet for me it caused extreme episodes of tachy while laying down and sitting.

I'm trying mestonin(sp)? next, but I've read some posts suggest it's not recommended for hyperpots, but my doctor felt it was worth trying.

The one drug that is being used a lot is Methyldopa for hyper pots. That would be my next attempt.

The cardiologist just gave me a script for cardio rehab, and one for saline infusions 3 times a week.

I'd recommend seeing an expert in dysautonomia before diagnosing yourself. I understand that people are having difficulty finding experts, but it's worth it.

The article I posted in my first post is still the one Vandy is sharing with patients who have hyper pots.

Is there something wrong with the front page of Dinet, I'm unable to 'load' it?

Best...

 

[Rooney]

I do have obvious facial flushing when I get up from a nap in the afternoon, 1-1.5 hour. Too groggy in the morning to notice then. What do you think this means?
I have OI, but not quite POTS per Dr. Peterson.

 

[ahimsa]

Questus, thanks for sharing all that information!

I wish I had such expert information for my own situation. My testing was done so long ago. My first tilt table test was in 1995 and my second one was in 2003 (that was done for disability insurance benefits - no new data was discovered). They measured my heart (pulse and EKG) and my blood pressure but that's it. NO blood tests at all. It's obvious that a lot more has been learned since then!

Maybe one day I'll have the energy, motivation and money to pursue more testing on my own condition. For now, I have to stick with just reading about it.

It is definitely hard to figure out detailed information about OI treatment by just looking at symptoms. I see people mixing up POTS vs. NMH (and maybe now those category names are out of date? They used to be correct....) to say nothing of different types of POTS. It makes it hard for patients to figure out which treatment should be tried. And then, as you said, even within categories there is so much patient variation.

Is there something wrong with the front page of Dinet, I'm unable to 'load' it?

I don't know which links you tried but here are two links that work for me:

http://dinet.org/ (main page)

http://forums.dinet.org/ (forums)

 

[Questus]

Ahimsa,

Classic case of cognitive dysfunction. ugg.

I meant to say the front page of Phoenix Rising. When I go to http://phoenixrising.me/ I get 2 seconds of the 'news' and the page goes blank.

Thank you for your help. I remember you helped out a long, long time ago when I had another case of overwhelming brain fog.

Txs again!

 

[ramakentesh]

Rama, thank you for the PM, I appreciate it.

Please let me answer here, as I can only type for so long.

First let me say I've been very fortunate to have been seeing an expert in dysautonomia. He's treated many cases of pots, ist, and ncs. He's also a cardio surgeon. He's done every test in the book on me. Very, very comprehensive.

I know many people have not had a good experience with getting pots treatment, but my experience has been outstanding. Was first dx by Dr. Nancy K. and from her I went to the cardiologist I'm speaking of.

The catecholamine test is a critical aspect in determining if you do or do not have hyper pots. All experts agree, Vandy, Mayo and Grubb, that a standing norepinephrine level of over 600 is positive for hyperadrenergic pots. A standing NE of over 1000 indicates a strong possibility of MCA.

My standing NE is over 1400, and I have extreme MCA, and am in the process of being tested at M D Anderson for Systemic Mastocytosis,

Dr. Grubb published a paper stated the symptoms of MCA in pots patients. 100% of patients with MCA have facial flushing.

So I have no need to go to Vandy or anywhere else, I've had literally every test in the book done for dysautonomia done by the cardiologist I see. Am very fortunate to have found him.

Hyper pots is rare. Only 10% of pots patients are hyper.

And yes my BP is hypo, not hyper. My BP does jump around when standing but is low while sitting and laying down.

I know of another hyper patient with a very high NE who is also hypo. So it's not as common but it happens.

The first 2 bb's I took caused by BP to go to 80/40 and 70's/50. Clonodine was a disaster. Clonodine is perhaps the most widely used drug for hyperpots yet for me it caused extreme episodes of tachy while laying down and sitting.

I'm trying mestonin(sp)? next, but I've read some posts suggest it's not recommended for hyperpots, but my doctor felt it was worth trying.

The one drug that is being used a lot is Methyldopa for hyper pots. That would be my next attempt.

The cardiologist just gave me a script for cardio rehab, and one for saline infusions 3 times a week.

I'd recommend seeing an expert in dysautonomia before diagnosing yourself. I understand that people are having difficulty finding experts, but it's worth it.

The article I posted in my first post is still the one Vandy is sharing with patients who have hyper pots.

Is there something wrong with the front page of Dinet, I'm unable to 'load' it?

Best...

Hi Questis - some of the articles I believe you are referring to are outdated. Not all experts in POTS agree that the delineation of POTS in hyper and non hyper has any etiological significance. Infact one major research group that you have not referred to above does not delineate.

This article from Vanderbilt demonstrated that QSART sudomotor abnormalities were found in the same percentage of POTS patients with 'hyper' POTS as in 'non hyper POTS' meaning that the arbitrary delineation of POTS based purely on NE levels may be a misnomer:
http://www.ncbi.nlm.nih.gov/pubmed/20035362

What this study means is that the HYPER delineation based on NE levels may be meaningless and that the same percentage of both have neuropathic features meaning it may have no etiological consequence.

Secondly Blair Grubb suggests hyper POTS only accounts for 10% of POTs patients yet other researchers suggest a large proportion of POTs patients have elevated MSNA. Certainly your suggestion that this delineation is fixed and not up for change as research evolves is incorrect - nothing in POTS research is fixed since there is a LOT that has yet to be explained via etiological proposed mechanisms.

Blair Grubb does state in a youtube video that in his clinical experience MCAD disorder is VERY rare even among his '10% of Hyper patients'. i think I believe he said 1% of that 10%. The rest he attributes to NET defiency although Dr Grubb while being a fantastic doctor is not involved in active research.

The best way to assess whether sympathetic outflow is excessive is MSNA nerve firing rate. Not all research facilities have access to this test. But you will find in time that this statement will be proven accurate.

i think what often happens is that people will read one article or a few articles by one or two research groups and then assume that that represents the current quickly evolving medical consensus.. The understanding of POTS etiology is in the VERY early stages and in the last few years there have been some VERY signifant inroads made in relation to ang II POTS and the epigenetics of some POTS patients.

Perhaps it might be better to review more recent documents?

As an example low flow POTS is a type of HYPER pots where NE levels can be elevated but may be normal with sensitivbity to NE perhaps upregulated. Also some neuropathic POTS patients exhibit HYPER symptoms such as elevated standin blood pressure and very high NE levels. Low Flow POTS may have signs of extreme sympathetic overactivity yet exhibit normal NE in the context of profound increases in MSNA as an example.

lastly I have never heard of elevated levels of NE being used to diagnose MCAD.

 

[ramakentesh]

So I guess all that the experts agree on is that its still unclear. But the main article on MCAD as first described by Vanderbilt as an association with POTs described patients with postural hypertension, not postural hypotension and did not report excessive NE levels.

 

[ramakentesh]

MCAD may just be a consequence of existing sympathetic overactivity anyway.

 

[Questus]

Rama...Am quoting you, (Hi Questis - some of the articles I believe you are referring to are outdated. Not all experts in POTS agree that the delineation of POTS in hyper and non hyper has any etiological significance. Infact one major research group that you have not referred to above does not delineate.)

This is getting tedious friend. You're suggesting my articles are out of date? Here's a brand new article from Mayo.

And it states: (Quoting)

Hyperadrenergic POTS

Between 30% and 60% of patients with POTS have evidence of increased central sympathetic drive, as reflected by standing plasma NE levels of 600 pg/mL or more (to convert to pmol/L, multiply by 5.911); fluctuating blood pressure or hypertensive response during HUT; and episodes of tachycardia, hypertension, and hyperhidrosis.2, 7, 20 In these patients, the episodes can be triggered not only by orthostatic stress but also by emotional stimuli and physical activity. This subgroup of patients may correspond to the so-called low-volume POTS characterized by supine vasoconstriction, supine tachycardia, pale and cold skin, and increased supine muscle sympathetic nerve activity.16 These patients have been categorized into a primary or central hyperadrenergic subgroup with plasma NE levels often between 1000 and 2000 pg/mL that compromises approximately 5% to 10% of cases and a heterogeneous group of secondary hyperadrenergic POTS.21 Loss-of-function sequence variation of the norepinephrine transporter (NET) and reduced clearance of synaptic NE were found in a case of hyperadrenergic POTS.22 However, increased NE levels more commonly reflect pharmacological NET blockade by drugs such as tricyclic antidepressants, selective NET inhibitors, and amphetaminelike drugs such as methylphenidate. Secondary hyperadrenergic POTS has also been associated with mast cell activation disorders.23 In patients with hyperadrenergic POTS, the possibility of hyperthyroidism or a catecholamine-secreting tumor, such as pheochromocytoma, should be considered. Laboratory studies should include determination of plasma and urinary metanephrine levels, and if they are elevated, imaging studies to detect pheochromocytoma may be necessary.24
Here's the link to the article. http://www.mayoclinicproceedings.org/article/S0025-6196(12)00896-8/fulltext

I've got very current articles that say the same thing from Vandy and Dr. Grubb. Have you had your standing norepinephrine levels checked. If they are over 600 you have hyper pots. If they are over 1000, you have a in a unique subset of hyper pots with probable mca.

Am having a problem posting on PR. My posts become scrambled on the front end and I can't reread them.

Also, I'm unable to read the front page of PR...Can only read the forums. Can anyone help me with this?

Also, on this subject of hyper pots with mca. I'm the one who posted the video of Dr. Grubb speaking with the African American teen who has mca. This is a rare combination and one I share. Lucky me. Not so much.

Am very, very concerned for all patients suffering with dysautonomia! We all have different symptoms and it's difficult for all.

Yes, there are different reasons for sympathetic excess and yet many of those reasons don't even apply to dysautonomia patients. It's a complicated topic.

Tania, hope you've had some luck getting saline scripts? We all have different needs and we all respond differently.
Just started a micro dose of Mestonin(sp) today and am hoping it works. BB's caused my BP to go 80/40 and 70's/50's. Clonodine should have been the perfect answer 'on paper' for me but it was a disaster for me. So am hoping Mestonin(sp) works for me. If not Methyldopia is my next try.

Looking forward to starting cardio rehab, (have become aware that insurance may discriminate against dysautonomia regarding cardio rehab...something to be aware of, but I think mine will cover it based on my query.)

Wishing everyone here the best,
Quest

 

[Seven7]

Looking forward to starting cardio rehab, (have become aware that insurance may discriminate against dysautonomia regarding cardio rehab...something to be aware of, but I think mine will cover it based on my query.)
Wishing everyone here the best,
Quest

How do you do Cardio Rehab?

 

[voner]

Questus,

thx for posting this info. It certainly does seem complex and confusing and ever-changing....

I live in an area with out any Doctors That understand dysautonomia. Do you have any idea what specific type of blood test should be requested to test your standing Norepinephrine levels? Seems any doctor could make this request at least to get that NE number back and have an idea better of what's going on.

 

[Questus]

If you've been dx with pots, you should at least have your doctor order catecholamine testing. This test will include Norepinephrine, Epinephrine, and Dopamine levels.

Back to my post above, and the new 2012 article by Mayo...All experts, (Mayo, Vandy and Grubb agree) A NE (norepinephrine) value of a minimum of 600 is indicative of hyperadrenergic pots. A NE value between 1000 and 2000 is indicative of hyper pots AND mca.

This is a test that can be ordered and done anywhere in the country. Print the Mayo article above out and share with the doctor treating you. There are also a lot of articles by Vandy and Grubb saying the same. Am always 'armed' with copies of these articles and I find the best doctors want to read them.

'How do you do Cardio rehab?' Please Google dysautonomia and cardio rehab, and you'll find lots of data.

Am overactive sympathetic pathway can occur with hypotension and hypertension in a pots 'arena'. It would be much more clear cut if it only occurred with one or the other. An overactive sympathetic pathway is can also a factor with MCA, but that is another element all together, and MCA can be found in many other disease processes, as can an overactive sympathetic pathway.

Ugg..So dysautonomia is complicated. If your NE, (that's norepinephrine) is under 600, Congrats! You have a 'garden variety' of pots, and your prognosis is better! woohoo. Hyper pots is 'forever'...It does not 'go away.' So be very happy if you can take a bb and function with it.

Rama, I'm interested in hearing more about your extensive experience with Mestinon. So far I've been able to take 30 mg, broken into 4 parts for 2 days with no problems, and feel like I feel a little more energy. Any thoughts on your first experiences with it?

Again, am not able to read anything other than the PR forums. The 'front page' news goes 'out' on me. Any ideas?

Best, Questus

(Once again my post is scrambled into straight lines of with no type, and I can't reread what I've written. So will post with good intentions.)