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T1AM decreases thyroid production without effect on HPT

Discussion in 'Thyroid Dysfunction' started by Iritu1021, Jul 13, 2018.

  1. Iritu1021

    Iritu1021 Breaking Through The Fog

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    Over the last few months, there were several of us who have failed miserably on high dose T3 or NDT, made quite remarkable improvement after working ourselves up slowly to full replacement doses of T4 (which also required some initial adjustment period). At least one person I know of even had elevated rT3 and still did better on T4 than on T3 which goes completely against the grain of current alternative thyroid theories. We have already talked plenty about how TSH is essentially useless when it comes to determining response to the thyroid.

    I've written quite a bit about T1AM before both on this forum and on my website but this is a new article that really reaffirms my interest in this - because it tells you that overproduction of T1AM (likely related to gut microflora) can impair thyroid synthesis without effect on hypothalamic-pituitary-thyroid axis. It also affects intracellular calcium which could explain many of the common CFS symptoms.

    I really hope someone studies this hormone more in CFS population. I'm posting the complete abstract of the article below. The reason why T3 didn't work for us the way it works for regular hypothyroid patients could be that while it is more effective, it is also more likely to upregulate T1AM (that's a speculation on my part, there could be many other reasons of course, such as CNS preference for T4).

    3-Iodothyronamine Decreases Expression of Genes Involved in Iodide Metabolism in Mouse Thyroids and Inhibits Iodide Uptake in PCCL3 Thyrocytes.
    Schanze N1,2, Jacobi SF2,3, Rijntjes E1, Mergler S4, Del Olmo M1, Hoefig CS1,2, Khajavi N3, Lehmphul I1, Biebermann H3, Mittag J2,5, Köhrle J1.
    Author information

    Abstract
    BACKGROUND:
    3-Iodothyronamine (3-T1AM) is an endogenous decarboxylated thyroid hormone (TH) metabolite. Pharmacological doses of 3-T1AM decrease heart rate, body temperature, and metabolic rate in rodents-effects that are contrary to classic TH excess. Furthermore, a single dose of 3-T1AM was shown to suppress the hypothalamic-pituitary-thyroid (HPT) axis in rats. It was hypothesized that 3-T1AM might play a role in the fine-tuning of TH action and might have a direct regulatory effect on the thyroid gland.

    METHODS:
    This study tested whether repeated 3-T1AM treatment interfered with thyroid function and the HPT axis in mice. Therefore, male C57BL/6 mice were intraperitoneally injected with 5 mg/kg of 3-T1AM or vehicle daily for seven days. Additionally, the effects of 3-T1AM on the differentiated rat thyrocyte cell line PCCL3 were analyzed.

    RESULTS:
    Repeated administration of 3-T1AM decreased thyroidal mRNA content of the sodium iodide symporter (Nis), thyroglobulin, and pendrin in mice. No interference with the HPT axis was observed, as determined by unaltered pituitary mRNA levels of triiodothyronine-responsive genes, including thyrotropin subunit β. Furthermore, 3-T1AM treatment did not change transcript levels of hepatic triiodothyronine-responsive genes, such as deiodinase 1. In line with this, serum TH concentrations were not changed after the treatment period of seven days. In concordance with the in vivo findings, 3-T1AM decreased the thyrotropin-dependent expression of Nis and functional iodide uptake in PCCL3 cells in vitro. Additionally, uptake and metabolism of 3-T1AM by PCCL3 cells was observed, as well as 3-T1AM-dependent changes in intracellular Ca2+ concentration that might be involved in mediating the reported effects.

    CONCLUSIONS:
    In conclusion, 3-T1AM application decreased expression of selected TH synthesis genes by acting directly on the thyroid gland, and it might therefore affect TH synthesis without involvement of the HPT axis.

    @BadBadBear, @drob31, @debored13, @pattismith, @Hip
     
    Last edited: Jul 13, 2018
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  2. Judee

    Judee Senior Member

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    Wisconsin
    Do you have a guideline or a PR thread I could read regarding slowly increasing the T4? I would like to see if this will help me.

    I think my body felt intuitively that the T3 as the NDT was affecting me badly but my environmental doctor of 11 years would not let me wean off of it so I was getting all these weird side affects.

    He really wasn't listening to me and since I haven't been back to him in a couple of years, I finally weaned off of it on my own last year.

    I used to get something I called "spiral down." Whenever I would roll onto my right side in bed, I would suddenly feel tingly all over, the little bit of strength I had felt like it was "spiraling down" a drain and I would feel like I was going to pass out. For the longest time I could only sleep on my left side because of this.

    Since I stopped the NDT that "spiral down" has almost completely disappeared. Plus, I don't get hypoglycemic episodes everyday like I was before. I still get them but only about once every 1-3 weeks.
     
  3. Iritu1021

    Iritu1021 Breaking Through The Fog

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    I started T4 at 6.25 mcg and basically just increased as I was able to tolerate it to 1.7 mcg/kg of body weight. (Some sources say you have to use the ideal body weight rather than actual weight, but in psychiatry and thyroid cancer they use doses that are even higher than 1.7 mcg/kg).

    In the beginning I would get a slightly unpleasant feeling when I would first take it. I think it's harder to get started on it if you don't have high TSH or if neurotransmitters or other things in the body that are off. Once my body would adjust to the new levels, then I would raise again.

    When you get to higher doses (>25 mcg), it's probably wise to wait at least 2 weeks, or ideally 4 weeks since T4 has a long half life (7 days) and builds up in the system slowly. It seems that it's different for different people - some tolerate it better in the morning, some at night, some in divided doses throughout the day.
     
  4. drob31

    drob31 Senior Member

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    Maybe I can chime in here...

    The more hypothyroid I am, the more of a tendency toward hypoglycemia I get. Especially post prandial hypoglycemia. This has dissipated greatly since I started t4.

    Infact I can eat a relatively large meal and have energy afterwards, which would assuredly crashed me before. I know there is a complex interplay here, but I had low glucagon which can be caused by being hypothyroid, and my theory is that my glucagon is being increased now (although I need new bloodwork to confirm).
     
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  5. Nine lives

    Nine lives

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    When I was first diagnosed with hypothyroid my savvy MD had me do a mixture of T4 and NDT (but still too much I think). For T4 only Tirosint worked. Just because I wanted to save money 3 years ago, I ditched the Tirosint (under my poor plan it is pretty expensive). I did equivalent in NDT. T3 shot up and I had heart palpitations, my SHBG was in very high hundreds so that contributed to feeling awful. In the end I dropped my NDT dose radically just to help get SHBG down.

    Read Blanchard book a few months ago, and am back on Tirosint. I feel like I am on less of a rollercoaster. Time will tell. Glad that there are others who feel the same way!
     
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  6. Iritu1021

    Iritu1021 Breaking Through The Fog

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    @Nine lives When you say "only Tirosint worked", do you mean other brands didn't work or generic T4? I'm taking Levoxyl, which Blanchard used in his practice. Do you think Tirosint is better than Levoxyl?
     
  7. Nine lives

    Nine lives

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    I am intolerant to most medications. I cannot remember the brand of T4 I tried but I came out with a lot of skin rashes - possibly a reaction to the filler. Then I tried compounded T4/T3 - possibly as a slow release compounded formulation. This simply did not get into my system. I felt severely hypo and even blood tests showed rock bottom values. With Tirosint - no rashes and it seemed to get into my system

    I was interested by Blanchard's recommendation of the 50 mcg Levoxyl being the best tolerated. I may have to try this one day when money gets tight. It is possible that when I tried T4 before - it was Synthyroid (I no longer have the notes).

    Are you taking any T3 at all? I am taking a quarter grain once a day AM sublingually.

    I am sure there will be more adjustments. I enjoyed Blanchard's comment that thyroid dose should change seasonally. I have struggled to get my doctors to do this.
     
  8. Iritu1021

    Iritu1021 Breaking Through The Fog

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    How did you learn about Blanchard's book? I feel like literally nobody knows about it.

    I'm not taking any T3 as for some reason it always seems to backfire and make me more tired and spacey a few days later. I know that @drob31 has the same problem.
    What dose of T4 are you on? I worked my way up to 125 mcg now with low dose Prozac to improve T4 to T3 conversion. I might try adding T3 again, maybe I wasn't on enough T4 earlier but I feel like T3 just messes up my deiodinase settings.

    What's interesting is that when I tried Prozac before I went to T4 it made me feel really bad and gave me blurry vision, with T4 I can tolerate it without much problem even at a higher dose than last time. My metabolism has clearly changed.
     
    Last edited: Jul 17, 2018 at 7:38 PM
  9. Nine lives

    Nine lives

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    Not sure where I stumbled across it, but it was a find. I love doctors who think outside the box.

    I am on 75mcg Tirosint. I will do some blood work in a month or two. I really don't want to suppress TSH totally (but that would probably be down to NDT). That was another Blanchard takeaway for me. I am aiming for free T4 above 1.4 ng/dl. I feel I could increase the dose a bit but would like to look at bloodwork first.

    I will definitely increase in the fall even if things look good now.
     
  10. Iritu1021

    Iritu1021 Breaking Through The Fog

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  11. drob31

    drob31 Senior Member

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    I just got a script for 1 mcg SRT3 yesterday, so I will be experimenting with that. Possibly breaking it in half and testing it.
     
  12. Iritu1021

    Iritu1021 Breaking Through The Fog

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    I have an update too - on 5 mg of fluoxetine (Prozac) my T3 went from 3.2 to 3.5 and now my TSH is slightly suppressed for the first time. I think I will back track on my T4 dose now. Low TRH might be causing my neurotransmitters to fall even lower.

    Also, my ionized calcium is borderline low. I ordered calcitonin test too, it's still pending.
     
  13. drob31

    drob31 Senior Member

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    It's odd, when I spoke to my doc yesterday he says he takes t3 because he's on prozac. He seemed to think prozac lowers t3, instead of increasing it (via conversion).
     
  14. drob31

    drob31 Senior Member

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    Also, unless I'm mistaking, there's flouride in prozac?
     
  15. Iritu1021

    Iritu1021 Breaking Through The Fog

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    Here's the study that shows that at least when it comes to the rat brain, fluoxetine increases activity of Type II deiodinase, which is the major deiodinase in CNS.

    https://www.ncbi.nlm.nih.gov/pubmed/8173980

    Blanchard believed that in cases of hypothyroid depression, most people experience initial improvement due to increased conversion from SSRI but if it's not matched by increased T4 production, people will eventually become more hypothyroid over time and the SSRI stops working for them.

    I don't know if it's true for all SSRIs or just fluoxetine. I also observed increase in T3 conversion from atomoxetine. I suspect that stimulants have the same effect.

    In psychiatry they do it backwards - they first start the patient on antidepressant, then add either T4 or T3 for augmentation. But as CFS patients we can't get away with that so we need to do it in reverse order. There was no way I could tolerate Prozac before T4.
     
  16. Iritu1021

    Iritu1021 Breaking Through The Fog

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    You need to give me a study that shows there is a fluoride in there beyond negligible amount that one would find in many other places too. And even if that were true - which I highly doubt - given that I'm on a full replacement dose of thyroid, fluoride is of little concern to me at this point.

    I could feel increase in T3 within the first hour of taking Prozac. It certainly was not related to antidepressant effect which takes weeks to manifest.
     
  17. drob31

    drob31 Senior Member

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    Ok, just looking at it from all angles.

    Did you feel better when it increased?
     
  18. Iritu1021

    Iritu1021 Breaking Through The Fog

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    Yes, I immediately felt more mental energy and greater clarity. But also have some side effects from serotonin, which seem to be subsiding now as the receptors adjust.

    I suspect that whatever viral infection is causing my thyroid problems also affects my parathyroid glands since they are so close together. I think that's probably what's causing my muscle spasms.
     
  19. drob31

    drob31 Senior Member

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    I have muscle spasms as well, usually in my calves, but i always thought it was "adrenal" related. Also thought it was maybe due to caffeine.
     
  20. drob31

    drob31 Senior Member

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    So I seem to do much better with t4 at night before bed, and not in the morning.

    I feel better on thyrodin 12.5 mg tabs as opposed to 100 mcg tabs or thyroxin 50 mcg or 100 mcg.

    so 8 12.5 mg pills feels the best when taken at night. Splitting up the dose does not seem to work as well, as I had a bad result from taking it in the morning.
     

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