ramakentesh

A doc once suggested that in net deficiency vasoconstrictors would stop the body relying on sympathetic synapses and NE to vasoconstrict, stopping the body from squirting out all the NE because of faulty transporter.

All interesting posts.

I do well on volume expanding meds but many don't despite the suggestion that most hyper should.

the original proband (patient) with net deficiency reports hypertensive responses to similar stimulus.

What happens to me is that my blood pressure goes up in response to things that should make it go down whereas licorice, florinef and midodrine decrease it and my dizziness.

Not to mention neuropathy with denervation supersensitivity - with massive NE levels - one of whom on this site responded to SNRIs.

A patient on facebook reports daily NE levels in excess of 5,400! This simply couldnt be NET deficiency without also some sort of upregulation of NE synthesis - its just an incredibly high NE level! Which makes one think of Mayo's idea of a primary central problem where the brain is just telling the body to produce and release too much NE and perhaps dopamine. How you'd treat that I have no idea. But id probably start with considering alpha 2 agonists or SNRIs which could suppress sympathetic outflow via brain stem alpha 2 receptor stimulation.

Hope my ramblings are helfpul - for once im not typing on an annoying phone.

A great doctor - treatment wise you couldnt get better.

Did you ever recognize having a tick bite or do you think you got it some other way? Reason I'm asking is the possibility of Lyme always sticks in my brain because when I was very young my parents took a tick off of my head, but it was not embedded in my skin or anything and it was not a "deer tick". Also that was quite a long time ago before I became very symptomatic but I do wonder about Lyme, although the testing would be too expensive for me currently I think

Odds of getting lyme from a tick are slim at best. I am a wildlife photographer (mostly hobby) and spend tons of time in close proximity with deer and other wildlife. I usually end up with a couple tics per year. I get lyme tests and have always been negative. Ether I am the luckiest person in the world, or this whole lyme thing is rare and just gets hyped up

Its an interesting area. Largely considered by medical establishment in America to be a dodgy diagnosis. My friend who is a physics grad was writing a blog debunking IGENEX for false positives but was concerned about litigation. its even more interesting in Australia where no recognised govt authority has identified Lyme or Lyme-related ticks in Australia yet patients groups are now claiming Lyme disease has caused a variety of health complaints - often POTS and other things and also report benefit from Lyme treatments.

Ofcourse it is possible that chronic antibiotic treatment causes immuno stimulation or suppression and some how calms down an autoimmune response. No idea really. I am personally pretty sceptical mainly because it doesnt for my mind explain the male v female balance in conditions like POTS or the sudden onset after stressor but I cant argue with people that tell me how dramatically better they feel after Lyme treatment - credible people that I doubt would succumb to placebo effect.

its all very confusing - like how EDS causes POTS - why is it often again an acute onset later in life after a stressor in some? that doesnt make sense if it is as we are told a genetic disorder causing abnornalities in collagen synthesis that compromise the elasticity of veins. If that was its primary cause you would presume that selective venous constrictors would 'cure' EDS POTS - but many have hyper symptoms with prominent tachycardia - or at leas they tell me they do

its possible - often the body tries to use adrenalin to re-regulate faulty circulatory control - no idea if its actually possible to wear the gland out and I tend to agree with what Carrie said.

Wow your diagnosis list continues. Ill have to hassle you and L about this diagnosis.

Yes I am very interested in the autoantibodies against Peripherin mainly because other researchers implicated these and similar autoantibodies in small fiber neuropathy.

I wasnt aware Mayo were trying to patent this assay. They were also patenting a treatment modality that increases potassium ion channel activity at sympathetic synapses to presumably improve vasoconstriction.

Thanks for the info.

Off the top of my head I believe it was this study that mentioned the possibility of a role for anti peripherin activity in small fiber neuropathy:

http://www.ncbi.nlm.nih.gov/pubmed/23478869

Sorry to hear about your experience.

I developed pots at 26 and it disappeared for years then came back much worse at 32 after a bad stomach infection.

people on forums who report sudden onsers and random fluctuations tend to improve.

A lot of the symptoms you describe - while I don't personally experience - are frequently reported on this sight. I wonder if feelings of anxiety and panic are related to sympathetic activation and pots?

I hope so as antipsychotics are scary. I am surprised they have been prescribed for panic disorder or anxiety. How would depressed central dopamine help those?

I'm confused. Are you being told your symptoms are psychogenic or related to POTS? Antipsychotic medications are insanely powerful. Do you have psychotic symptoms?

I couldn't imagine dealing with mental illness on top of POTS. I really feel for you.

Its confusing and compounded by unhelpful docs.

Dr Grubb said in a recent email that he thought hyper should be delineated into NET deficiency, receptor hypersensitivity and beta 1 receptor activating auto antibodies. Although three recent studies suggested Net deficiency dud not result in a hyperagtenergic state so its confusing.

Vanderbilt and Dr Stewart would probably say there are other potential causes as well including hypovolumia/low flow POTS, abnormalities in cerebral auto regulation and compensatory sympathetic activation.

Mayo said they thought the hyperadrenergic state was compensatory or an epiphenonema in their study entitled 'The mayo clinic experience' then changed that more recently to suggest they current believe a 'central hyperadrenergic' phenotype in some hyper patients which they have told one patient on Facebook that is a very hard situation to treat.

Norepinephrine is synthesized from dopamine so many people with a very high NE level will also have a high dopamine level--the pathway is rev'ed up. eg in response to hypovolemia or vasodilatation, etc. MIne are also both elevated.

Yes I guess this is true but it is odd that its in serum just floating around.

Norepinephrine shouldn't really be floating around in serum - it should be staying within sympathetic synapses and then being reuptaken into presynaptic vesicles to be reused in the synapse of the sympathetic system. NE is not synthesized in serum, its converted from dopamine precursors neuronally (within the axon and stored within the axon in vesicles). Dopamine can be present in serum but it is very odd to have a neurotransmitter floating around in serum activating random beta receptors.

Increased Norepinephrine synthesis would in theory result in reduced stores of precursors although it doesn't seem to in POTS weirdly. But I don't think its as simple as there just being elevated synthesis of morepinephrine and dopamine because there doesn't seem evidence of this.

Dr Grubb is a fan of the norepinephrine transporter theory which could explain both elevated serum norepinephrine and dopamine. But there may also be receptor super sensitivity, problems with the alpha 2 receptor negative feedback loop that stops too much noreponephrine release and the low flow high anti II crowd which causes release if norepinephrine.

This may be a chicken or egg argument-- I have a confirmed diagnosis of hypovolemia--however, does that cause my POTS/NMH symptoms? or is it that my POTS/NMH causes my body to lose too much fluid and I become dehydrated/hypovolemic. I don't think the medical answers are in yet on this one. There is some research about some patients "salt wasting" (urinating out more salt that most people)--but this isn't a consistent finding in all patients with hypovolemia as far as I know.

the prevailing thought in NHM and neuropathic pots it might be a combination of sluggish kidney responses, plasma volume being extracted after leaking out of micro circulation and maybe even dopamine effects but its still murky.

Always good to read a positive story.

sorry if my responses were abrupt - typing on mobile phone while standing on busy train.

I was dxd hyperpots at Mayo and also hypovolemic via sodium and eventually blood volume testing. I don't know a lot about it, but my doctor explained that the hypovolemia causes a drop in bp so my body dumps a bunch of NE to raise it, which causes a kind of rebound hypertension and the high bp and high NE levels. Thus, I have to first salt and fluid load to build blood volume so I'm less likely to get the hyper episodes; the beta blocker then lowers the heartrate (and sometimes the bp too much). I will go from 90/60 flat to 140/90 within a couple of minutes, so I experience both ends of the bp spectrum. I also had abnormal QSART results and neuropathic issues.

I have hyper pots but clonidine causes rebound hypertension in me because my bp gets too low. Perhaps this distinction is not useful, as I think Rama has suggested (sorry...I don't always understand everything you say ); I'm thinking one day we may find they have subgroups based on cause, rather than manifestations of the syndrome (as "hyper" pots sometimes seems to be).

I don't really find this classification helpful; in fact, sometimes I resent it because they want to apply a one-size fits all treatment to hyper patients (ie you shouldn't salt load because you've got high NE...yet many of us do).

I was dxd hyperpots at Mayo and also hypovolemic via sodium and eventually blood volume testing. I don't know a lot about it, but my doctor explained that the hypovolemia causes a drop in bp so my body dumps a bunch of NE to raise it, which causes a kind of rebound hypertension and the high bp and high NE levels. Thus, I have to first salt and fluid load to build blood volume so I'm less likely to get the hyper episodes; the beta blocker then lowers the heartrate (and sometimes the bp too much). I will go from 90/60 flat to 140/90 within a couple of minutes, so I experience both ends of the bp spectrum. I also had abnormal QSART results and neuropathic issues.

I have hyper pots but clonidine causes rebound hypertension in me because my bp gets too low. Perhaps this distinction is not useful, as I think Rama has suggested (sorry...I don't always understand everything you say ); I'm thinking one day we may find they have subgroups based on cause, rather than manifestations of the syndrome (as "hyper" pots sometimes seems to be).

I don't really find this classification helpful; in fact, sometimes I resent it because they want to apply a one-size fits all treatment to hyper patients (ie you shouldn't salt load because you've got high NE...yet many of us do).

Exactly. And I dont understand myself sometimes.

Older work by Blair Grubb suggests all hyper have NET deficiency but Vanderbilt, Dr Stewart and mayo have many 'hyper' with QSART abnormalities or neuropathic features and low flow pots is also a variant of 'hyper'.

Exercise helps me when I'm not terrible. It makes me worse when acute.

Midodrine would help. Its a good study by a leader in the field.

Blair Grubb suggests otherwise, but nit the other research groups.

The term hyperadrenergic just means elevated sympathetic activity, norepinephrine or postural hypertension. It doesn't automatically suggest an etiology or delineate you from other pots patients.

All forms of pots can be hyperadrenergic.

The patients I know with the worst hyper symptoms and the highest NE levels all had QSART abnormalities suggesting an underlying neuropathic basis.

And one of those responded to an SNRI suggesting net deficiency was not the underlying problem.

The Norepinephrine transporter is responsible for the uptake of between 20% to 40% peripheral dopamine and dopamine in some central locations so that may be why if you have net deficiency.

Dopamine peripherally activates d1 receptors in the kidney that force sodium loss and volume loss.

Thus tachycardia from NE stuck in thin cardiac sympathetic synapse, NE leaking out of synapse and either cause alpha 2 suppression of further NE release or bleeding synapse vesicles dry in venous splanchnic sympathetic synapses and increased peripheral dopamine lowering blood volume via kidney.

A recipe for disaster.

Low blood volume goes hand in hand with all hyper pots. essential hypertension have elevated volume, sustained high BP, kidney vasoconstriction, increased cerebral volume. The opposite occurs in POTS so sodium and volume expansion are essential.