High Dopamine?

[Carrie]

Anybody else have high dopamine? I just got back the most recent catecholamines blood test results.

Epinephrine was in range but low

Dopamine was very high, out of range

Norepinephrine was just below 600, so almost hyperadrenergic but not quite at the cutoff

I've never looked into dopamine before. Going to spend some time searching it tonight, but if anyone else has this or knows of any good articles I'd love to hear about it!

Thanks.

[Joann]

My tests last year had high norepinephrine and high dopamine, normal epinephrine. Not sure what they are now. Doctors haven't officially said hyper pots, but I think that is what it is leading too. I am on the wait list for Dr. Grubb's office and I think I will finally get some answers.

I will be interested to see what you find out.

[kitt]

Carrie,

I also have very high dopamine. More than double the norm.

You'll find a lot of information regarding serotonin and dopamine. When one is high the other is low in equal proportion. I have a good article 'somewhere' that explains it. Both should be like a 'half a glass of milk' when either dopamine or serotonin is high the other is in equal proportion low.

My norepinephrine is very high though, over 1400. Think you can feel comfortable that you're not in a hyperadrenergic state.

Best,

K

[Guest Alex]

Carrie,

you might want to look at something called Dopamine Beta-Hydroxylase Deficiency aka Norepinephrine deficiency

the thing is though with this your dopamine levels should be extremely high, while the plasma epi and norepi levels should be minimal (even absent):

http://www.ncbi.nlm.nih.gov/books/NBK1474/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1459119/

http://ajpregu.physiology.org/content/286/1/R108.full.pdf+html

http://ajpheart.physiology.org/content/293/1/H684.full.pdf+html

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1031834/pdf/jnnpsyc00530-0030.pdf

general info on catecholamines:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046107/

Hope you'll find some useful info

Alex

[Carrie]

Thanks.

Interestingly, I was tested at Dr. Grubb's office and their lab's upright NE reference range is 520, not 600.

I know somewhat about DBH, but the strange thing is some of us have high DA with high NE instead of low NE. ?

[kitt]

High DBH...

vity (51).

Remarkably, baseline plasma DBH activity in healthy indi- viduals varies more than 100-fold. Individual variation in DBH activity is primarily genetically determined. Among the poly- morphisms found in the DBH gene that affect either enzyme levels or function (3, 4), the 1021C3 T polymorphism in the promoter region accounts for up to 52% of variation in plasma DBH activity (5).

Because of individual variability in DBH, associations be- tween DBH activity and various diseases have been elusive (25).

Elusive...Indeed.

Most of the literature about dopamine and illness concerns LOW dopamine, not high. The best articles I've found correlate high dopamine with low serotonin.

Dr Grubb is now saying that an NE of 520 is indicative of a hyperadrenergic state? This is contrary to everything I've read thus far. Vandy, Mayo and Dr. Grubb all seem to agree that 600 is the 'bottom line'.

I've not seen anything in any literature referring to Dr. Grubb and hyper pots and an NE of 520. Carrie, do you have a link to this?

Mayo has recently divided hyperadrenergic pots patient into two subsets. Those with an NE of 600 to 999, and those with an NE of 1000-2000.

I'd be interesting though in reading anything you can share that suggests Dr. Grubb has a different opinion.

Thanks for sharing Carrie.

[Carrie]

Hi Kitt,

Sorry for not being clear in the earlier message! No, I didn't talk specifically to Dr. Grubb to see if he'd changed his ideas on hyperPOTS. It is the reference range listed on the lab paperwork that says 520. I don't have a scan of it right now though.

So probably the cutoff for hyperPOTS is still 600, but for some reason the hospital lab lists the "normal" range from 80-520 on the lab results page (even though other labs list the "normal" range as 700+.)

Also, the lab paperwork used the same reference ranges for both supine and upright. Weird.

[Guest Alex]

Here is an article published by Dr Grubb listing the criteria for hyperPOTS

http://www.ncbi.nlm.nih.gov/pubmed/21947988 (you can access the full length article if you go to the blue/white box in the upper right corner of the screen)

Clinical presentation and management of patients with hyperadrenergic postural orthostatic tachycardia syndrome. A single center experience.

Kanjwal K, Saeed B, Karabin B, Kanjwal Y, Grubb BP.

Source

Department of Medicine,University of Toledo Medical Center, Toledo, OH, USA.

Abstract

BACKGROUND:

We present our single center experience of 27 patients of hyperadrenergic postural orthostatic tachycardia syndrome (POTS).

METHODS:

In a retrospective analysis, we reviewed the charts of 300 POTS patients being followed at our autonomic center from 2003 to 2010, and found 27 patients eligible for inclusion in this study. POTS was defined as symptoms of orthostatic intolerance (of greater than six months' duration) accompanied by a heart rate increase of at least 30 bpm (or a rate that exceeds 120 bpm) that occurs in the first 10 min of upright posture or head up tilt test (HUTT) occurring in the absence of other chronic debilitating disorders. Patients were diagnosed as having the hyperadrenergic form based on an increase in their systolic blood pressure of ≥ 10 mm Hg during the HUTT (2) with concomitant tachycardia or their serum catecholamine levels (serum norepinephnrine level ≥ 600 pg/mL) upon standing.

RESULTS:

Twenty seven patients, aged 39 ± 11 years, 24, (89%) of them female and 22 (82%) Caucasian were included in this study. Most of these patients were refractory to most of the first and second line treatments, and all were on multiple combinations of medications.

CONCLUSIONS:

Hyperadrenergic POTS should be identified and differentiated from neuropathic POTS. These patients are usually difficult to treat and there are no standardized treatment protocols known at this time for patients with hyperadrenergic POTS.

Alex

[kitt]

Hi Kitt,

Sorry for not being clear in the earlier message! No, I didn't talk specifically to Dr. Grubb to see if he'd changed his ideas on hyperPOTS. It is the reference range listed on the lab paperwork that says 520. I don't have a scan of it right now though.

So probably the cutoff for hyperPOTS is still 600, but for some reason the hospital lab lists the "normal" range from 80-520 on the lab results page (even though other labs list the "normal" range as 700+.)

Also, the lab paperwork used the same reference ranges for both supine and upright. Weird.

Carrie,

When did you last see Dr. Grubb? It's odd about the NE reference ranges being the same standing and supine. Doesn't make sense in terms of dysautonomia.

As to your initial post, I still think you're safe to conclude you're not in a hyperadrenergic state. You may want to have catecholamine testing redone at some point, but all experts including Mayo, Vandy and Grubb have determined that 600 is the bottom line for hyperadrenergic pots.

Many with an NE in the 600's have been dx. as 'borderline' hyper pots by Mayo. Interesting.

Any research you find regarding a high dopamine level would be interesting. The only articles I found regarding HIGH dopamine and pots suggest a low serotonin level as I mentioned. I've researched extensively and other than articles referencing low dopamine levels, I didn't find anything significant. Please share what you find regarding HIGH dopamine.

Carrie, how high is your dopamine? Can you share the number and the reference range? Mine was more than double the norm on quest labs.

Am wondering if only a psychiatrist who specializes in pharmacology would know how to approach balancing these two neurotransmitters, (dopamine and serotonin). Can't imagine what other kind of doctor could sort this out?

Best,

K

[Guest Alex]

Am wondering if only a psychiatrist who specializes in pharmacology would know how to approach balancing these two neurotransmitters, (dopamine and serotonin). Can't imagine what other kind of doctor could sort this out?

Best,

K

How about a neuroendocrinologist Kitt?

Alex

[Psalm 23]

My dopamine level was also elevated at 56 but the focus seemed mostly to be on my NE level which was 2922 so nothing was really said about the dopamine level being elevated. Something I want to ask about next time I go to Mayo because I have since wondered about the significance of an elevated dopamine level. I did notice on the Dinet Mechanisms of Pots page a paragraph about a hyperdopaminergic state and some references.

Janet

[badhbt]

My dopamine level was high also. It was 41, the range was 0-20. My epinephrine was low and NE level was high.

[kitt]

My dopamine level was also elevated at 56 but the focus seemed mostly to be on my NE level which was 2922 so nothing was really said about the dopamine level being elevated. Something I want to ask about next time I go to Mayo because I have since wondered about the significance of an elevated dopamine level. I did notice on the Dinet Mechanisms of Pots page a paragraph about a hyperdopaminergic state and some references.

Janet

Janet,

Thanks for sharing your catecholamine levels. What meds do you take for hyper pots?

Are you able to sleep with an NE level that high?

Think the dopamine level being so high is something that is considered an 'incidental finding'....Unlike a very low dopamine level.

Mine is very high too, and no doctor has given it much significance.

Have the script and 'stuff' to do a 24 hour urine catecholamine test with an endocrinologist, but haven't gotten around to doing it yet. Will take the dopamine level up with her.

Am more concerned about serotonin levels. When dopamine is high serotonin is low and vice versa, but don't think it's something a doctor will necessarily 'treat'.

From my paste above it states "Remarkably, baseline plasma DBH activity in healthy indi- viduals varies more than 100-fold. Individual variation in DBH activity is primarily genetically determined."

A 100-fold variation in dopamine is huge, so I'm guessing that may be why it's not looked at too seriously.

Although from the posts here it seems to be common with both pots patients and hyper pots patients.

Janet, can you provide a link to (pasting from your post):

Dinet Mechanisms of Pots page a paragraph about a hyperdopaminergic state and some references.

Best,

K

[Guest Alex]

http://www.ncbi.nlm.nih.gov/pubmed/3881951?dopt=Abstract

another article of possible interest?!

Orthostatic hypotension: a posture-induced hyperdopaminergic state.

Kuchel O, Buu NT, Hamet P, Larochelle P, Gutkowska J, Schiffrin EL, Bourque M, Genest J.

Abstract

To explore the role of dopaminergic mechanisms in orthostatic hypotension we compared the postural responses of 20 such patients to those of a control group by radioenzymatic determination of free and sulfated catecholamines and related indices. Patients with orthostatic hypotension, unlike control subjects, experienced an increase in total plasma dopamine (DA) (free + sulfate) in response to upright posture (p less than 0.01). Of the 20 patients with orthostatic hypotension, 16 were normo- or hyperadrenergic with normal basal and posture-responsive or hyperresponsive plasma free and total norepinephrine (NE). The other 4 were hypoadrenergic with low basal and posture-unresponsive NE. Hypoadrenergic patients had, in the upright position, no increase in pulse rate and more severe hypotension, less diuresis and natriuresis, lower urinary free and total DA, lower total NE excretion, and higher plasma and urinary total DA:total NE ratio than normo- or hyperadrenergic patients or control subjects. Normo- or hyperadrenergic patients had higher PRA and plasma aldosterone in the upright position than hypoadrenergic patients or control subjects (all p less than 0.05). We suggest that an excessive increase in free DA occurs in response to upright posture, perhaps representing a compensatory reaction of the remaining autonomic nervous system to an excessive fall in blood pressure. The free dopamine may be biologically active but it is so rapidly sulfoconjugated that it can be detected only as DA sulfate. These findings, combined with reports of orthostatic hypotension precipitated by administration of dopaminomimetic drugs and relieved by administration of dopaminergic antagonists, are consistent with the interpretation that excessive DA release may perpetuate, by its vasodilating and natriuretic action, the orthostatic hypotension.

Alex

[Guest Alex]

and one more

http://jpet.aspetjournals.org/content/305/3/800.full.pdf+html

Sources and Significance of Plasma Levels of Catechols and Their Metabolites in Humans

[Psalm 23]

Kitt. The pots meds I take are clonidine 0.1mg bid, mestinon 60 mg tid, and propranalol 5 mg bid.The clonidine 0.1mg was meant to be a starting dose but after upping it to 0.15mg and not tolerating it I had to go back to 0.1mg and at that point the small propranalol dose was added in. Based on my high NE levels ( supine was also high at I236) I would be classified as a hyperpots patient but I'm reluctant to refer to myself as such because I left Mayo as a hyper response patient so I am not really sure what I am. I seem to have a mixture of both hyperpots and neuropathic features. I have been developing many new and worsening problems in the last year so I plan on a return Mayo trip and will hopefully gain better understanding of my situation and any new recommendations for treatment.

In regards to sleep that was not helped by any of the pots meds. Prior to Mayo I had been sleeping fairly well by taking elevil 10 mg at bedtime (it had originally been ordered for sleep and pain ) but was told elevil worsened pots symptoms so I needed to discontinue it. I was advised to try meletonin for sleep but it did nothing for me. The only thing that finally helped with sleep was neurontin which was prescribed for pain. It wasn't until I had reached a dose of 2400mg a day that I realized I was able to sleep for stretches of 6-8 hours at a time. Prior to that I seemed to wake up every 2 hours. Something I'm sure you are very familiar with. So horrible. I am extremely noise sensitive so I have found wearing ear plugs and running a fan helps with sleep.

Thank you so much for the dopamine information. I guess I kind of figured if it were a significant finding it would have been brought to my attention.

The dopamine information source I made mention of is part of dysautonomia network's web site. If you look under potsplace and mechanisms of pots you will find it listed there. I'm not sure about a specific link though.

What medications or things in general have helped with your condition ?

Thank you

Janet

[kitt]

Janet, Thanks much for sharing.

From what I've been told Mayo has told many people that they have a 'hyperadrenergic response' and are in a

'hyperadrenergic state' These are pots patients who've been to Mayo pots patients presenting with extreme hyperadrenergic pots... (NE over 1000) so am still confused about that.

Mayo has recently published a paper that is very clear about pots DX and classifies pots patients in two subgroups. Those with an NE level of 600-999 and those with an NE of 1000 to 2000. They've not acknowledged hyper pots patients with NE levels over 2000. (Am not suggesting people who have been treated at Mayo don't present with an NE higher than 2000, but Mayo has not acknowledged that subset in their peer reviewed publications...(Please correct me with a link if I'm mistaken.)

Janet, back to you.

Good to know neurontin helped you with sleep. I have more neurontin scripts than I can even count. It was prescribed to me many times for pain to due another issue, and I filled the scripts but I only took it a few times. Am sensitive to meds, so try to keep meds at a mimimum... BUT if it helps with sleep, I'll definitely talk with the doctor who prescribes it! Thanks for mentioning it. 2400mg a day sounds like a lot to me. Do you have side effects?

Clonodine caused extreme episodes of tachycardia for me when I was sitting and supine. (Odd, I know.) So I switched to Methyldopa, which is VERY helpful with sleep, but it does allow me to sleep but not until the wee hours of the night. A huge improvement though. Prior to Methyldopa, I was only sleeping for an hour or two at at a time during the night.

I'm interested in hearing about your neurotin dosage and your sleep issues.

Am surprised 10mg of Elavil was discouraged? It's such a low dose. I also was prescribed that, but like most scripts, I also discontinued it (with my doctors knowledge), but if it helps with sleep...I'm IN.

Thanks again for sharing Janet.

Best,

K

[ramakentesh]

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.

[ramakentesh]

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.

[ramakentesh]

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

[kitt]

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

How does Dr. Grubb suggest otherwise?

[NMPotsie]

Kitt just as an FYI I was on 1800 mg/day of gaba (neurontin) for my back pain and the doc said the dosage could go much higher, so 2400 probably isn't excessive.

It did help me sleep but caused horrible emotional side effects--random bouts of crying, depression, apathy, etc. (I am not, nor have I ever been, an emotional person...this was totally out of character for me). These are commonly known side effects of the drug by doctors, but they aren't ever up front about it. It also lowers your seizure threshold, so you can't dabble in it...you have to get on and off slowly and over time or you risk seizures.

Lyrica is very similar to gaba chemically, but works better for some people as far as the side effects go. I was prescribed this but never took it (along with Zoloft, to counter the emotional side effects of the drugs...I just decided no more drugs and opted for surgery).

Not saying it doesn't work perfectly fine for some people...just giving you my experience so that you can watch for those side effects if you choose to try it.

[ramakentesh]

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'.

[kitt]

Kitt just as an FYI I was on 1800 mg/day of gaba (neurontin) for my back pain and the doc said the dosage could go much higher, so 2400 probably isn't excessive.

It did help me sleep but caused horrible emotional side effects--random bouts of crying, depression, apathy, etc. (I am not, nor have I ever been, an emotional person...this was totally out of character for me). These are commonly known side effects of the drug by doctors, but they aren't ever up front about it. It also lowers your seizure threshold, so you can't dabble in it...you have to get on and off slowly and over time or you risk seizures.

Lyrica is very similar to gaba chemically, but works better for some people as far as the side effects go. I was prescribed this but never took it (along with Zoloft, to counter the emotional side effects of the drugs...I just decided no more drugs and opted for surgery).

Not saying it doesn't work perfectly fine for some people...just giving you my experience so that you can watch for those side effects if you choose to try it.

NM Potsie,

Good to know!

I see the doc who prescribed it to me Thursday, so this is timely for me.

Thank you and Janet both for the timing.

My recollection though is that neurotin even at low dose, (400 mg?) seemed to have a 'dumbing' effect on me. It's been a while since I took it, but that was my initial memory. I admit I did not give it a good chance. It just seemed to have a very strong impact though, and I immediately thought..."No, I don't want to take this."

But it was prescribed for a type of pain that I don't associate with hyper pots. CFS pain or neuro pain.

The side effects you had are disturbing.

Janet, did you experience anything like that?

I'm really for as few drugs as possible, but when it comes to reducing sympathetic activity and sleep...I'll try!

Best,

K

"

[HyperPOTS8]

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.