3-Iodothyronamine ( T1AM ) administered to rodents induce a hypometabolic state

[sb4]

@Iritu1021 The M3 receptor is in part responsible for vascular contractions (OI, low blood flow, pounding heart), gland excretions saliva/gastric/sweat (dry mouth/gastroparesis/no sweat response), and gut motility (gastroparesis). These are all my worse symptoms.

I did antibodies test with results of very low antibodies for 5 of 7 receptors. The other 2 where just outside the at risk range. One of these was M3. Now it could well be that it isn't causing any problem in me, however why is it so much higher that the other 5 very low adrenergic and muscarinic receptors? Why does it correlate so well with my symptoms? I think this is worth pursuing in me.

So T1AM is an antagonist to the M3 receptor right? Would doing very low dose T3 balance out some of this effect do you think?

When I was taking T3/T4 combo I noticed that I would get intermittent ptosis (droopy eyelids) which looked a lot like mild myasthenia gravis

Have you considered trying Mestinon? Some POTS patients have had good success with it and it's also used for myasthenia gravis.

 

[Iritu1021]

@sb4 , what you're describing sounds almost identical to what I had back in 2015. I know the "heart pounding low flow POTS feeling"( It's completely different than hyperadrenergic high flow POTS I got when I tried to use TSH suppression method with high doses of thyroid).

In my experience low dose T3 does help with what you've described. I don't know which drugs you're taking now or have taken in the past that might have messed up your receptor settings - can you think of anything that triggered these symptoms?

One alternative explanation to your M3 antibodies being higher than others could be that you simply have way too many M3 receptors in your body. Perhaps it's some adaptive response to the lack of norepinephrine and T3 since M3 also plays a part in vasoconstriction. Have you tried to raise your acetylcholine levels or have you experimented with any M3 agonsits or antagonists?

 

[Iritu1021]

Forgot to mention - I haven't tried Mestinon but I've tried galantamine which inhibits acetylcholinesterase. It seemed to have helped a little bit but didn't feel like the real answer, and certainly nowhere close to the "global effect" I had from T3. Maybe I didn't stay on it long enough or maybe mestinon would be different.

Overall, I feel like I migrated back toward fibromyalgia type clinical picture which is where I had been for years before I crashed myself into POTS back in 2014.
I don't have droopy eyelids anymore, it was only when I was on T3/T4 combo, my eyes look pretty big now so I'm pretty sure that it was somehow related to the thyroid. I think T4 always made me feel worse, maybe because it raises T1AM.

The two unexplained issues that bother me now periodically is a) throat pain/tightness - which I suspect might be related to some nerve pressure from thyroid enlargement since my TSH has gone up and b) a weird TMJ/cheek area muscle tightness and neck spasms in the neck of my back area. The latter I have not been able to pin down at all yet but I remember I got very bad TMJ from high doses of T3. In the evenings (probably because T3 level drops) I get muscle spasms.

I also got extreme muscle pain all over when I stopped taking T3, it was like "rigor mortis" feeling. It seems like almost every major symptoms on dysautonomic spectrum that I experienced in my life was made either better or worse by manipulating my thyroid axis.

p.s. I use the term "dysautonomic" very broadly, not just in reference to my POTS

 

[Iritu1021]

found an article that discusses the strong association between autoimmune thyroiditis and myasthenia gravis

"In fact, autoimmune thyroiditis seems to be the most associated pathology to MG".

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5508005/

 

[Iritu1021]

thyronamines act as specific dopamine and norepinephrine reuptake inhibitors
they inhibit the transport of monamines into synaptic vesicles

May be the link to:
low NET (norepinephrine transporter) in POTS
hyperadrenergic state
serotonin intolerance

Thyronamines inhibit plasma membrane and vesicular monoamine transport.
Snead AN1, Santos MS, Seal RP, Miyakawa M, Edwards RH, Scanlan TS.
Author information

Abstract
Thyroid hormone has long been known to have important transcriptional regulatory activities. Recently, however, the presence of endogenous derivatives of thyroid hormone, thyronamines, has been reported in various mammalian tissues. These derivatives have potent in vitro activity with a class of orphan G-protein-coupled receptors, the trace amine-associated receptors, and profound in vivo effects when administered to mice. We report here a novel neuromodulatory role for thyronamines. In synaptosomal preparations and heterologous expression systems, thyronamines act as specific dopamine and norepinephrine reuptake inhibitors. Thyronamines also inhibit the transport of monoamines into synaptic vesicles. These observations expand the nontranscriptional role of thyroid hormone derivatives and may help to explain the pharmacological effects of thyronamines in vivo.

 

[frozenborderline]

have any of you run your thyroid values thru spina software which checks a number of indexes?

my results had one parameter out of range, which indicated that i had some kind of rare thyroid resistance that would need to be treated with triac


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899439/

http://spina.sourceforge.net/

i still may try small t3 doses because i'm so desperate

 

[pattismith]

Hi guys,

V rarely do I post personal anecdotal stuff but it may fit in here, certainly on the other thyroid thread by @pattismith I think.

I'm severe borderline v severe some days now (totally bedridden, worse on my borderline days etc) but back when I was moderate, I tried a dose of Armour Thyroid.

It was one of those, ‘what the heck’ moments and I knew t3’s role in metabolism but my extensive thyroid labs, including rt3 and concurrently ratio was good. My t3 was infact upper range.

Anyway, within an hour or 2 of taking half a grain of Armour Thyroid, (4.5mcg t3, 19mcg t4) the huge lactic acid feeling in my arms and legs went away, felt ‘light’ (in retrospect just normal) and I went from 30-60% health in those 2 hours. It was incredible. Literally like a switch.

Lasted 2 days. Never could replicate again at all kinds of different dosages, straight t3 etc.

I have pondered so so much about this, what I have come up with ties in with Julia Newtons research and t3 and AMPK:

Newton: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122982

T3 AMPK- https://www.ncbi.nlm.nih.gov/m/pubmed/18703632/

(Basicallly that it temporarily normalised some or all of the issues mentioned in Julia Newtons study).

It may be a total crock and doesn’t seem to fit with Chris Armstrong’s theory I don’t think. But it makes some sense to me.


B

Ben, I had a look at these articles, it is said that T3 can activate AMPK by phosphorylation (non genomic action) in 6 hours, so it is unlikely the way T3 can give quick improvement to us.
I think non genomic action on cell's Ca content/flux might be quicker, but I have to do more research on it.

 

[sb4]

One alternative explanation to your M3 antibodies being higher than others could be that you simply have way too many M3 receptors in your body. Perhaps it's some adaptive response to the lack of norepinephrine and T3 since M3 also plays a part in vasoconstriction. Have you tried to raise your acetylcholine levels or have you experimented with any M3 agonsits or antagonists?

That's interesting, I hadn't thought of that. The problem I have though, is that I feel my sympathetic tone is way higher than parasympathetic. I never feel relaxed, dry mouth, gastroparesis, insomnia. It's entirely possible that some parasympathetic receptors or higher but more sympathetic ones are higher. What about the idea that a small / moderate amount of acetylcholine is relaxing, yet a large amount is stimulating. Then, if I did have more M3 and thus more antibodies, yet I was stimulating it hard due to poor nor/epinephrine uptake, then could this also mean that the overstimulated M3 would produce opposite effects. The dry mouth, etc???

In my experience low dose T3 does help with what you've described. I don't know which drugs you're taking now or have taken in the past that might have messed up your receptor settings - can you think of anything that triggered these symptoms?

Well my symptoms where triggered after tonsilitus 7yrs ago. My symptoms have been more or less the same since the start however got drastically worse over the years. So whilest it's certainatly possible that I did something to worsen my M3 receptors (Huperzine A, methylfolate) I think the source of the problem was the virus I got that kicked all of this off.

what you're describing sounds almost identical to what I had back in 2015. I know the "heart pounding low flow POTS feeling"( It's completely different than hyperadrenergic high flow POTS I got when I tried to use TSH suppression method with high doses of thyroid).

Interesting, I do intend to try very small doses of T3 at some point, maybe in a few months time, however I do not have slow release version so will have to dose every couple of hrs I think.

 

[Iritu1021]

have any of you run your thyroid values thru spina software which checks a number of indexes?

my results had one parameter out of range, which indicated that i had some kind of rare thyroid resistance that would need to be treated with triac


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899439/

http://spina.sourceforge.net/

i still may try small t3 doses because i'm so desperate

That's very interesing! I definitely want to try and and play with that software, thanks for recommending it! How would you even get triac, it doesn't look like it is approved anywhere? Do you think maybe Wilson's method would work for you?

 

[Iritu1021]

That's interesting, I hadn't thought of that. The problem I have though, is that I feel my sympathetic tone is way higher than parasympathetic. I never feel relaxed, dry mouth, gastroparesis, insomnia. It's entirely possible that some parasympathetic receptors or higher but more sympathetic ones are higher. What about the idea that a small / moderate amount of acetylcholine is relaxing, yet a large amount is stimulating. Then, if I did have more M3 and thus more antibodies, yet I was stimulating it hard due to poor nor/epinephrine uptake, then could this also mean that the overstimulated M3 would produce opposite effects. The dry mouth, etc???



Well my symptoms where triggered after tonsilitus 7yrs ago. My symptoms have been more or less the same since the start however got drastically worse over the years. So whilest it's certainatly possible that I did something to worsen my M3 receptors (Huperzine A, methylfolate) I think the source of the problem was the virus I got that kicked all of this off.



Interesting, I do intend to try very small doses of T3 at some point, maybe in a few months time, however I do not have slow release version so will have to dose every couple of hrs I think.

I can't say that I fully understand the how sympathetic and parasympathetic systems "play catch up" with each other but I do remember having very dry mouth and constant sense of overstimulation at that time, and this muffled feeling of my heart pounding whenever I stood up.

The one and only helpful doctor I've me was a "rogue" family practitioner whom I saw in the very beginning for adrenal fatigue (she said she went into "grassroots" alternative medicine after finally figuring out her own thyroid issues). She prescribed me separate capsules of 1 mcg slow release T3 and also low dose T4 and cortisol (needs to be prepared at compounding pharmacy with methacel filler). I quickly figured out that T3 capsules were making me feel better while T4 capsule were making me worse, so I only took T3. Looking back I don't know why I kept taking cortisol back then because it was making me worse too. I was just really sold out back then on my adrenal issues because my cortisol was low (which was probably an adaptive response). I could probably get even better if I wasn't messing with my adrenals back then. Still, I could have a pretty good run on 1 mcg until late afternoon when it would start to wear off.

Unfortunately, I still wanted an official diagnosis, not something bogus like "adrenal fatigue" - so I traveled to another city to see a POTS specialist, got convinced that I had Ehlers-Danlos, got put on a lot of drugs that were wrong for me and it all went downhill from there. Looking back now, if I just stayed on T3 only (without cortisol) and if knew back then how to dose it better, my story probably could have developed very differently.

The other thing that might be causing CNS overstimulation is bacterial toxin production. Have you done Genova's Organix and GI Effects? I remember that after taking midodrine, I had some Clostridium species toxin in my blood (cause stuff starts growing when there is no good blood flow). I took metronidazole and my nervous system felt much better after that. I'm now starting to believe that the gut microbiome plays a very big role in all of this, since it seems that this is where T1AM is produced. Perhaps, T1AM is not really our "human" hormone, just something that the bugs use to manipulate our metabolism for their own gain.

 

[Iritu1021]

@debored13 ... so I ran two sets of numbers on SPINA - my labs
when I first got sick and wasn't yet on any thyroid (all normal). But my latest set of labs shows TTSI twice the normal! As I understand that means that I have too much TSH stimulating immunoglobulin (or maybe some neurologic settings that cause that)... Did all my thyroid manipulation cause me to develop some sort of pseudo-Grave's picture that now offsets my intracellular hypothyroidism?? That may sound crazy but is it possible that this may be the same reason why IVIG helps some people - because it has TSH stimulating antibodies in it??

one other thing I noticed that I only had anti-TPO antibodies in the past but now I also always have anti-thyroglobulin antibodies...

 

[frozenborderline]

That's very interesing! I definitely want to try and and play with that software, thanks for recommending it! How would you even get triac, it doesn't look like it is approved anywhere? Do you think maybe Wilson's method would work for you?

i have seen it available on some websites/online pharmacies. I guess if it comes in blister packs i wouldn't worry about the source as much

 

[frozenborderline]

@debored13 ... so I ran two sets of numbers on SPINA - my labs
when I first got sick and wasn't yet on any thyroid (all normal). But my latest set of labs shows TTSI twice the normal! As I understand that means that I have too much TSH stimulating immunoglobulin (or maybe some neurologic settings that cause that)... Did all my thyroid manipulation cause me to develop some sort of pseudo-Grave's picture that now offsets my intracellular hypothyroidism?? That may sound crazy but is it possible that this may be the same reason why IVIG helps some people - because it has TSH stimulating antibodies in it??

one other thing I noticed that I only had anti-TPO antibodies in the past but now I also always have anti-thyroglobulin antibodies...

i'm sorry, I can't really answer these questions in full as I am very very tired recently, it was just a software i wanted to introduce to people. it has been tested, here's one of the studies:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899439/

you can find more studies for triac too and if you look around under the right name you can find it available on chemical/steroid/pharmacy websites

 

[pattismith]

@debored13 ... so I ran two sets of numbers on SPINA - my labs
when I first got sick and wasn't yet on any thyroid (all normal). But my latest set of labs shows TTSI twice the normal! As I understand that means that I have too much TSH stimulating immunoglobulin (or maybe some neurologic settings that cause that)... Did all my thyroid manipulation cause me to develop some sort of pseudo-Grave's picture that now offsets my intracellular hypothyroidism?? That may sound crazy but is it possible that this may be the same reason why IVIG helps some people - because it has TSH stimulating antibodies in it??

one other thing I noticed that I only had anti-TPO antibodies in the past but now I also always have anti-thyroglobulin antibodies...

it doesn't seem to be that TTSI has anything to do with "TSH Stimulating Immunoglobuline",
it is "Thyrotroph Thyroid hormon Resistance Index also called TT4RI"

Iritu, would you give me the study that states Low Dose Lithium can activate D1 ?

 

[Iritu1021]

@pattismith I never said lithium activates D1. I only know that it can activate D2 (the main dio in the CNS) based on the rodent study I linked earlier.

http://press.endocrine.org/doi/10.1210/endo.141.3.7358

Fourteen days of administration of two different dosages of lithium had opposing effects on 5′D-II activities (Fig. 5, right). The 0.15% lithium diet reduced 5′D-II activity in the cortex, whereas the 0.3% lithium diet enhanced it. T4 levels were significantly elevated after the low dose and significantly reduced after the high dose. Likewise, the serum concentrations of T4and T3 were enhanced after the 0.15% diet and lowered after the 0.3% diet (Table 1). The activities of 5D-III were, however, significantly reduced after administration of both dosages.

It is also possible that lithium inhibits both T3 and T1AM synthesis, therefore if you take T3+lithium, you end up with net gain minus T1AM effect.

I'm more convinced by what I observed personally than from what I've read.

The dose of lithium I took before my TSH levels began to go up was pretty high (I worked up to 20 mg of lithium orotate per day in divided doses). I would not be able to tolerate that dose without some thyroid onboard. I tried lithium before and while it calmed me it always worsened my CFS and gave me "leaden paralysis".

Initially, I took it with low dose levothyroxine, not T3. After a month on that regimen my T4 was borderline high (1.7) - very strange given how low the dose I was taking - but strangely my TSH also went up for the first time. There was a disconnect in the feedback mechanism which I could (Unfortunately, I got those through primary care doctor who failed to order T3. I began to have more energy and motivation and better sensory perception but it gave me severe psychological anxiety and palpitations so I stopped. Before lithium I could not tolerate T4 at all, it made me feel dreadful, so this was still a significant change.

I remember that when I combined lithium and T3 it had a very powerful amplification effect on T3. I pretty much had to discontinue T3 right away.

The other explanation is that lithium has direct effect on modulating TRH release (described here):
https://www.ncbi.nlm.nih.gov/pubmed/12401339
https://www.nature.com/articles/1380514.pdf?origin=ppub

Also, both lithium and carbamazepine decrease deoidonase 3.
https://www.ncbi.nlm.nih.gov/pubmed/8981386

I did look at that SPINA and while I misunderstood initially what TTSI stands for, I'm still trying to figure out why do did my body raised my TSH so much at the same time when it simultaneously more than doubled my thyroid resistance. I'm no longer taking lithium on a regular basis but the TSH trend continues. That makes me think that I'm actually hyperthyroid right now and the markedly increased resistance is a protective mechanism.

The other possible explanation I can think of right now is that there was some hypothalamic level response when I went on lithium because it caused functional iodine deficiency (lithium replace iodine). When I first got off lithium my T3 was naturally at 3.5 which never happened before. I had too much anxiety on that level. I suspect my ideal fT3 is 3.2. Very narrow range. Anything below that affects my mood, energy brain function. Anything above that gives fibromyalgia, anxiety and POTS.

I'm going to test myself for TSH receptor antibodies just to rule the concurrent processes going on that might be making thyroid regulation so tricky. If there are no antibodies then I will lean toward hypothalamic or genomic changes.

By the way I did find cases online about IVIG raising thyroid antibodies in patients, and one woman who had pre-existing Graves but was hypothyroid before IVIG wrote that it caused her to develop hyperthyroidism again.

 

[Iritu1021]

i'm sorry, I can't really answer these questions in full as I am very very tired recently, it was just a software i wanted to introduce to people. it has been tested, here's one of the studies:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899439/

you can find more studies for triac too and if you look around under the right name you can find it available on chemical/steroid/pharmacy websites

Thank you, I appreciate you sharing this and I hope you feel better soon. Hang in there!

 

[Iritu1021]

I came across another potential way to upregulate cellular D2 - bile acids

https://www.ncbi.nlm.nih.gov/pubmed/16400329

 

[pattismith]

I came across another potential way to upregulate cellular D2 - bile acids

https://www.ncbi.nlm.nih.gov/pubmed/16400329

this is amazing! Can we take BA as a supplement?

 

[Iritu1021]

this is amazing! Can we take BA as a supplement?

Oh yeah, definitely. Ox bile is something naturopaths prescribe quite often for hypothyroid patients as "digestive aid". Here in the US you can find it pretty easily in health stores and online.
I actually happened to have an unopened bottle from Seeking Health - I bought it over a year ago thinking I might give it a try and then forgot all about it.

 

[frozenborderline]

Oh yeah, definitely. Ox bile is something naturopaths prescribe quite often for hypothyroid patients as "digestive aid". Here in the US you can find it pretty easily in health stores and online.
I actually happened to have an unopened bottle from Seeking Health - I bought it over a year ago thinking I might give it a try and then forgot all about it.

I'm curious about this because I feel like even my nutrient absorption is compromised by poor digestion and it's tricky to supplement thyroid without being able to eat and digest a bunch, since increasing thyroid hormones requires increasing calories