Hyperadrenergic Pots Research

[StacyRN]

I was told that someone on this forum mentioned that we were relying on outdated research regarding Hyperadrenergic POTS. I was told he said that any good POTS expert would not rely on plasma norepinephrine levels alone for a Hyper. POTS diagnosis. I am wondering where he got his information, and if he has any links to research articles that explain what he is saying. I'm very interested in finding out! Thanks

[firewatcher]

Honestly, all the research is "breaking," so anything more than a year or two old is outdated. I was diagnosed as having Hyper-POTS by Vandy in November of 2008 and they never drew a norepinephrine level on me. My dx was based on the results of my ANS tests alone. I did the standing test and was not put on a TTT. My results were "robust" enough for a dx without the TTT, but I was also not a study patient; I was an outpatient appointment.

A high norepinephrine level can indicate a hyperadrenergic response, but I have been told by POTS docs that not all Hyper-POTS will have elevated norepi. Sometimes the reaction to a normal norepi level can be extreme.

[StacyRN]

I was in an inpatient POTS study at Vanderbilt for 2 weeks in April 2010. I did have all the catecholamine levels done, supine, sitting, standing; and the urine ones also... extensive testing every day! I also had plasma catecholamines at Stanford in 2009. The first ones were: supine 604 pg/ml, standing 1231. At Vanderbilt they were: supine 300s, standing 1459. I was told this makes me in the 10% of those with Primary Hyperadrenergic POTS. This is within the past 2 years... I was also negative for the NET defect. I am also not helped by florinef, compression stockings, or salt. I do not have aldosterone: renin ratio problems. I do not have decreased cardiac output. Midodrine sends my sympathetic nervous system out of control, as does SSRIs and the usual drugs given to PD type POTS patients.

Yet clonidine and propranolol help me and are well-tolerated, and those are the drugs that typically help only Hyperadrenergic POTS.

I'm just wondering what the research is behind the person who said that no expert would diagnose H. POTS by norepi levels alone... because I have never heard of any other way to diagnose it, and would like to know where he got his information! Whoever you are, please respond, I'm interested in hearing what you have to say! Thanks

[firewatcher]

StacyRN,

Ramakentesh was the one who mentioned the "outdated" research. He is a proponent of Dr. Julian Stewart's work. Dr. Stewart has a different classification of POTS, based on blood flow. I think there is also a researcher in Australia who is far less "known," but has similar findings.(?) Google Low Flow POTS and you'll get more info. Hyperadrenergic POTS fits into that category.

[StacyRN]

StacyRN,

Ramakentesh was the one who mentioned the "outdated" research. He is a proponent of Dr. Julian Stewart's work. Dr. Stewart has a different classification of POTS, based on blood flow. I think there is also a researcher in Australia who is far less "known," but has similar findings.(?) Google Low Flow POTS and you'll get more info. Hyperadrenergic POTS fits into that category.

Thanks so much! Appreciate the info

[issie]

How did they check you for the NET deficiency? I was told that there were not any test to determine this. I think that is one of my issues. I too have higher noriepi levels, and all the symptoms of a hyperPOTS. I have to wait until next week for the exact firm diagnosis. I haven't tried cloninidine but on the doc's notes - he's considering trying that next. What does it do for you? I couldn't use propranalol because I couldn't take the afternoon dose because my bp bottoms out when I try to sleep. Making it go lower in the night wasn't possible and it therefore, caused me to have rebound hypertension even worse than it was before. My bp runs real high and real low. It swings all over the place. It's not an easy form of POTS - whatever you want to call it.

Issie

[StacyRN]

Hi Issie!

When I was at Vanderbilt for the study, they checked all my catecholamine levels many times, and also my DHPG level. If you have a higher than normal norpinephrine-to-DHPG ratio, then you could have the NET defect. Norepinephrine is released from the nerve cell, and some of it goes into the bloodstream (about 20%, I believe), while 80% of it is taken back up by the norepinephrine transporter, back into the cell, and converted to DHPG, and the DHPG is released into the bloodstream. (I hope I got that right, I have it in a book, but too tired to go find it right now!) Anyway, if the DHPG levels are low, it means that the norepinephrine transporter (NET) isn't taking up most of the norepi and converting it into DHPG. So that would mean the NET wasn't working right, and letting too much norepi into the bloodstream.

My DHPG levels were normal, and my norepi:DHPG ratio was within normal limits, therefore Vanderbilt said I was negative for the NET defect.

I hope I made sense! Someone else said that they had a saliva test to check for the NET defect! But I haven't heard of that and wouldn't know how it works, unless they can measure DHPG through the saliva...?

I take clonidine, 0.1 mg 3 times during the day, and then 0.2 mg at bedtime (or I will wake up in the night with the jitters and restlessness!) I also take propranolol 20 mg, 4 times a day. And klonipin and Ambien at night also, or I can't sleep! Somehow it doesn't kill me, you'd think it would!! I never get low bp though. I have always had low-normal bp, and I get an increase when I stand up and a very narrow pulse pressure, 15-20 mmHg! But it doesn't get dangerously low. My hr when I'm asleep and resting is 55-60, which is normal for the meds I take, but I never feel in danger... I'm more likely to wake up from my Hyper POTS and be restless and nervous, even on all those meds.

Thanks for writing, Issie, I really appreciate it! Hope my explanation of NET defect helped!

Stacy

[StacyRN]

Hi Issie!

When I was at Vanderbilt for the study, they checked all my catecholamine levels many times, and also my DHPG level. If you have a higher than normal norpinephrine-to-DHPG ratio, then you could have the NET defect. Norepinephrine is released from the nerve cell, and some of it goes into the bloodstream (about 20%, I believe), while 80% of it is taken back up by the norepinephrine transporter, back into the cell, and converted to DHPG, and the DHPG is released into the bloodstream. (I hope I got that right, I have it in a book, but too tired to go find it right now!) Anyway, if the DHPG levels are low, it means that the norepinephrine transporter (NET) isn't taking up most of the norepi and converting it into DHPG. So that would mean the NET wasn't working right, and letting too much norepi into the bloodstream.

My DHPG levels were normal, and my norepi:DHPG ratio was within normal limits, therefore Vanderbilt said I was negative for the NET defect.

I hope I made sense! Someone else said that they had a saliva test to check for the NET defect! But I haven't heard of that and wouldn't know how it works, unless they can measure DHPG through the saliva...?

I take clonidine, 0.1 mg 3 times during the day, and then 0.2 mg at bedtime (or I will wake up in the night with the jitters and restlessness!) I also take propranolol 20 mg, 4 times a day. And klonipin and Ambien at night also, or I can't sleep! Somehow it doesn't kill me, you'd think it would!! I never get low bp though. I have always had low-normal bp, and I get an increase when I stand up and a very narrow pulse pressure, 15-20 mmHg! But it doesn't get dangerously low. My hr when I'm asleep and resting is 55-60, which is normal for the meds I take, but I never feel in danger... I'm more likely to wake up from my Hyper POTS and be restless and nervous, even on all those meds.

Thanks for writing, Issie, I really appreciate it! Hope my explanation of NET defect helped!

Stacy

Or, let me put it this way, my DHPG levels were proportionate to my norepi levels, meaning both were high proportionately. Whew!

[StacyRN]

Actually, Hyper POTS fits more into the Normal Flow POTS category, not the Low Flow... I'm not sure I'm completely a fan of Dr. Stewart's definitions... in fact, instead of them being more advanced, they seem a little more behind the times, at least what I've read today, than the other researchers. Maybe Ram...(I can never remember that name! sorry!) can give me some specific articles that he likes, because the ones I found weren't that convincing to me... Please do, I am open, not closed-minded! But I'm also a critical thinker, and I research a lot...

Thanks!

Stacy

[issie]

Stacey,

Rama is very knowledgeable when it comes to the technical issues of POTS. Especially if your talking about angiotension and the different forms of POTS. He has a brilliant mind and can usually remember what he has read. Maybe he'll respond to you and give you his back up references. He always seems to know what he's talking about. I will look forward to following you and your conversations - I enjoy the deeper things in connection to the POTS mystery.

Issie

You could always PM him, but then we wouldn't be able to follow the thread and I'd like to be a fly on the wall.

[Birdlady]

I always wonder if I have 2 problems cancelling each other out at times. Perhaps I have something that is both lowering and raising my BP, so it just sort of stays in the middle. I know that probably sounds crazy, but I often wonder about it.

I met the >600 NE standing criteria for Cleveland Clinic, but at Vanderbilt University you have to be >1000. I definitely don't meet that. I DO have the hyperPOTS feelings though and I tend to do better on beta blockers and have no improvements on what normally helps the PD POTS types (salt, midodrine was AWFUL!, florinef)

I know this was brought up in another thread, but we also have to remember that our beta adrenergic receptors may be tuned differently too. Someone with a NE of 450 might have more HyperPOTS symptoms than someone with a 700 if the receptors are more sensitive. I don't think the number alone tells us anything. Beta adrenergic receptors change sensitivities according to our thyroid function (some studies are conflicting in this though). Those with hypothyroid tend to have higher levels of catecholamines. It is paradoxical.

During my tilt I had the classical HyperPOTS symptoms (sweating, anxious, got very hot, butterflies in my stomach), but yet my BP did not climb high. It stayed very normal until the end, but I was due for my hydrcortisone dose.

[HopeSprings]

Dr. Stewart is the Dr. who sent me for laying and standing catecholamine (sp?) blood test in 2007. From there, Vanderbilt was interested in these results because of the high standing norepi. I think they were doing a study on it? I forget how I ended up with them on this. Anyway, they sent me a DNA collection kit - and I sent them a vial of saliva (nice). They tested it for the NET defiency thing, but it was negative.

[StacyRN]

I always wonder if I have 2 problems cancelling each other out at times. Perhaps I have something that is both lowering and raising my BP, so it just sort of stays in the middle. I know that probably sounds crazy, but I often wonder about it.

I met the >600 NE standing criteria for Cleveland Clinic, but at Vanderbilt University you have to be >1000. I definitely don't meet that. I DO have the hyperPOTS feelings though and I tend to do better on beta blockers and have no improvements on what normally helps the PD POTS types (salt, midodrine was AWFUL!, florinef)

I know this was brought up in another thread, but we also have to remember that our beta adrenergic receptors may be tuned differently too. Someone with a NE of 450 might have more HyperPOTS symptoms than someone with a 700 if the receptors are more sensitive. I don't think the number alone tells us anything. Beta adrenergic receptors change sensitivities according to our thyroid function (some studies are conflicting in this though). Those with hypothyroid tend to have higher levels of catecholamines. It is paradoxical.

During my tilt I had the classical HyperPOTS symptoms (sweating, anxious, got very hot, butterflies in my stomach), but yet my BP did not climb high. It stayed very normal until the end, but I was due for my hydrcortisone dose.

You sure sound Hyper POTSy, with your reactions to the meds, etc. I hadn't thought about that our adrenergic receptors might be tuned differently...? Any good articles on that? Have to look it up, thanks! Yes, I'm HOPING Rama responds, because I want to know what research he has... I also have thyroid disease, and didn't know the link between that and higher norepi levels! And about the bp not climbing, it is normal in POTS for it to drop a little, stay the same, or climb a little... usually my systolic doesn't go up a lot, but my diastolic does, narrowing the pulse pressure. But the bp doesn't skyrocket on the TTT usually, although mine did with midodrine! And with SSRIs! Please, let Rama find this thread and give me some articles... his research studies are only done on 15-39 year olds, and I'm almost 51, so don't know how they apply to me... Thanks for this, though, Dana

[sue1234]

Stacy, I have found this 2-year old post from Rama that talks about NET and lists many links. It gets very technical, and definitely not anything my brain can decipher in the morning time!

I have been wanting to post some interesting information I have found regarding the possible common genetic links to alot of our issues. I don't understand the significance of it, but it is VERY interesting. I'll try and post sometime soon about it.