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Higher prevalence of ‘low T3 syndrome’ in patients with CFS: A case-control study

Discussion in 'Latest ME/CFS Research' started by Ema, Mar 2, 2018.

  1. Hip

    Hip Senior Member

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    If low thyroid hormone receptor activation were playing a role in my fatigue levels, surely taking supplemental T3 at around 25 mcg daily would greatly improve my fatigue. I did perhaps feel slightly more energized when taking T3, but the effect was not strong enough for me to definitely conclude that T3 made energy improvements.

    I probably should try T3 again some time, as it was a few years ago that I lasted tried it.



    That's interesting, so you are saying that T3 would displace any RT3 bound to the thyroid hormone receptor, because of T3's higher receptor affinity.

    I am trying to figure out where I got this idea that RT3 antagonizes the effects of T3, if there is no actual evidence for it. I guess I probably read it on some alternative medicine website or something.
     
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  2. Ema

    Ema Senior Member

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    http://www.tiredthyroid.com/rt3.html
     
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  3. Hip

    Hip Senior Member

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    That's a useful article. This page linked to from the above article says:
    But in those two study references [8] and [9], it mentions nothing about RT3 blocking thyroid receptors as its mechanism of action.
     
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  4. CFS_for_19_years

    CFS_for_19_years Hoarder of biscuits

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    My brain is too numb at the moment to delve into much detail, but when I googled "RT3 blocking thyroid receptors" it led me to https://www.nahypothyroidism.org/deiodinases/ which had several references (184-189). So whether RT3 blocking T3 is a myth or not, I'll let the rest of you decide:

    I think googling "RT3 blocking thyroid receptors" will lead to more published papers, and not some hearsay on web blogs.
     
  5. pattismith

    pattismith Senior Member

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    thanks CFS, let's see what we can learn from it!
    This study just tells that rT3 is far less active than T3 to produce ATP, and that acidosis lower T3 ability to produce ATP..(Nothing about rT3 blocking T3)

    Adverse effects of reverse triiodothyronine on cellular metabolism as assessed by 1H and 31P NMR spectroscopy.
    Okamoto R1, Leibfritz D.

    Abstract
    Effects of 3,3',5'-triiodothyronine (rT3) in connection with 3,3',5-triiodothyronine (T3) on 3T3 cells were studied in vitro by means of 1H and 31P NMR spectroscopy. In the cells incubated with 5 nM T3 for 3 h at pH 7.4, the ATP/ADP ratio was elevated from 6.9 to 8.4, whereas it was reduced to 6.1 in cells incubated with rT3. When the cells were incubated at pH 6.7, the ATP/ADP ratio was reduced to 6.6 and 5.2 at 1 and 2 h, respectively. In the presence of 5 nM of T3, however, the ratio was maintained above the control level. A 1-h preincubation with rT3 dramatically augmented the reductions caused by elevated acidity. These reductions were completely reversed when the cells were incubated with T3.
     
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  6. pattismith

    pattismith Senior Member

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    I followed some links you gave CFS, but couldn't find any evidence for rT3 blocking T3...

    the TH resistance theory says you can raise T3 intake until you reach effectiveness, as long as you don't experience the hyperthyroid effects. 25 mcg is considered a low dose.

    Dr Lowe who performed studied on Fibromyalgic patients published some works:

    "Effective T3 dosages were supraphysiologic, and ranged from 93.75-to-150 meg. Available patients had maintained improvement at 2-month follow-up. Tests showed no clinically significant cardiac, osseous, muscle, or hepatic adverse effects."

    He did some other studies with up to 4 months follow up, with no adverse effect.
     
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  7. mermaid

    mermaid Senior Member

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    I was interested in your reply Patti as this has been my experience, although as far as I know I do not have Low T3 Syndrome. I am diagnosed with autoimmune hypothyroidism/Hashimoto's some 10 years before I also acquired the ME/CFS label (over 20 years ago now). I was put on the standard Thyroxine/T4 treatment which I took for 17 years. I did seem improved for the first few years, although having looked at my medical record since, I can see that my TSH was quite stubborn in falling and my dose was not increased as it probably should have been.

    After a few years my health began to fail though it took a long time to get to a bad level and I put it all down to the menopause for years! I gained a lot of weight and I had a lot of immune issues - mostly sore throats and viruses. This went on for years and even when I got the ME/CFS diagnosis no one explored the thyroid link or even checked my FT3 until I finally asked, and even then I had to pay for it! (ie we don't pay for our other thyroid checks in the UK).

    To cut a long story short, I persuaded an Endo to give me T3 to take, but as you say above, I felt worse on T4/T3 which seemed to puzzle them. Fairly quickly I persuaded the Endo to give me T3 only which I took for 5 years and slowly my health improved over this time, and my weight dropped slowly, and by 2016 I felt the best I had done for years. My energy though not perfect was much better.

    Late 2016 and 2017, the Endos (different ones) descended on me, and persuaded me that T3 had caused my osteoporosis (I think I have told this part of the story before) and that I should try a T4/T3 mix again. I agreed, even though I tried NDT in early 2017 and I felt dreadful on it - very hypo even though I was taking enough. Still, I thought, it's worth a try to see what happens and as they are hot on removing T3 from patients here now, I thought I would comply.

    Within 2 weeks of introducing the smallest dose of T4 (25mcg) I began to have frequent viruses again, and had 2 in July and 2 in August. They shifted the T4 up to 50mcg, while reducing the T3 down and I continued to get viruses - until they increased to 75mcg in Oct when I had 4 migraines in a week (I do get migraine but not that much!).

    I then wrote to them and told them I wasn't going to continue and have slowly reduced the T4 until I am now on only 12.5 mcg per day. The viruses have reduced again to almost nothing and the migraine are at my normal level. I even had some immunoglobulin tests done before I began and about 2 months in and you can see that my IgG dropped out of range.

    Of course the Endos do not accept any of it, and have discharged me back to the GP who I went to see recently. I was afraid that she too would not agree to my T3 use but she is refreshingly supportive even though she doesn't understand much about the thyroid and she allows me to dictate how much I use. At the moment it's 45mcg which is 10mcg less than I was on previously so I will see how I go with the tiny bit of T4, which I may stop altogether, although I have heard it's good to have a small amount of T4 for the brain.
     
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  8. pattismith

    pattismith Senior Member

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    I was intrigued about T3 failing to help me some years ago and now working on me.

    The main difference between my first T3 trial and my current one is that I had several heavy antibiotic treatments over a year, to fight intracellular infections and others. (I have Ig G against Mycoplasma Pneumo, Chlam Pneumo and Yersinia Enterolitica, and joints problems).

    So whereas these treatments got me worse by disrupting my ion channels and neuro-muscular transmission on one hand, they also actively fighted my intracellular bacteria, and made me sensitive to T3 again.

    Of course, it is only assumptions, but it fits with the Thyroid Hormons Resistance some docs have theorized to explain CFS/ME as an intracellular hypothyroid state triggered by infections

    http://forums.phoenixrising.me/inde...tracellular-hypothyroidism.57031/#post-947057
     
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  9. pattismith

    pattismith Senior Member

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    Do you have good B12 level in blood?

    vitamine b12 is very important for osteoporosis (and often overlooked) and also K2
     
  10. mermaid

    mermaid Senior Member

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    @pattismith
    Yes, I made sure that my B12 in blood was optimised many years ago (about 8) when I began to find ways to treat the ME/CFS issues and it's never showed low in testing - quite the opposite. I even injected it at one point but it didn't change symptoms. I wasn't taking K2 until about 18 months ago, but do so now.
     
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  11. pattismith

    pattismith Senior Member

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    Low T3 Syndrome is associated with low T1AM and high 3.5.T2 (here)

    If only a subset of CFS/ME is concerned by this syndrome, resistance to thyroid hormons is suspected for others.

    This resistance could be well explained by increased T1AM, because this TH has the anility to block T3!

    http://forums.phoenixrising.me/inde...o-rodents-induce-a-hypometabolic-state.57289/

    I wonder if this thyroid resistance could be the exact contrary of the Low T3 Syndrome but with similar clinical outcome.
    In that case, 3.5.T2 would be low and this would lead to a tendancy for cholesterol to rise under a fat rich diet.

    In Low T3 Syndrome, high 3.5.T2 would tend to protect cholesterol to rise under a high fat diet.
    (this is my case as I have low cholesterol and Low T3 Syndrome)

    http://forums.phoenixrising.me/inde...tivates-mitochondria.51881/page-4#post-961301

    @Iritu1021
    @Wishful
     
  12. pattismith

    pattismith Senior Member

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    From my readings, Low T3 Syndrome could be improved by up-regulating D1 and down-regulating D3.

    T3 can upregulate D1, but upregulating Growth Hormon could be interesting as it can do both up D1 and down D3...


    11 Ways to Boost Human Growth Hormone (HGH) Naturally
     
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  13. pattismith

    pattismith Senior Member

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    The full article is now available and access free:

    https://www.frontiersin.org/articles/10.3389/fendo.2018.00097/full

    from the introduction:

    "Taken together, dysfunctional central housekeeping involving interactions between both the HPA and hypothalamus–pituitary–thyroid (HPT) axes and the sympathetic/adrenal medulla, rather than single-hormone-axis disturbances, might play a key role in the development of CFS symptoms"

    edit:

    "When combined, controls and CFS patients with low FT3 (<4.4 pmol/L) were also found to more often exhibit low hsCRP (<1 mg/L) in the whole group"

    editbis:

    The low limit value they took for fT3 is 4.4 pmol/l, with the high limit 6.7.

    on a UK site, (british thyroid fundation), the normal ranges are 3.5 - 7.8 pmol/L

    On Mayoclinic 2.8-4.4 pg/mL, which means 4.3 - 6.77 pmol/l

    on a Belgium site, it is 3.5 – 6.5 pmol/L

    on my french lab, it is 2.88 - 4.88 (I am 2.9)

    on a medical french web site, it is 3 - 8.5 pmol /l

    Why so much differences?...

     
    Last edited: Mar 25, 2018
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  14. pamojja

    pamojja Senior Member

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    'Usually' lab reference ranges are calculated by each lab individually, for example considering all samples taken, and subtracting the lowest and highest 2.5%. The remaining 95% in the middle considered 'normal'. Ignoring the fact that lab test are more usually taken only once one's health isn't optimal. As years pass and more data comes in, these reference values change accordingly, and are of course different for each lab since each is testing a specific population.

    The functional medicine approach, on the other hand, uses 'optimal' values. And since there have been studies finding at which ranges the thyroid is functioning optimally, they go by them. Usually the upper half of 'normal' for fT3 and fT4 compared to the regular lab-method described above.

    For example a lab 15 kms from here has 2.5-4.2 pg/ml for fT3, an other one just across the street 2.0-4.4 pm/ml.
     
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  15. CFS_for_19_years

    CFS_for_19_years Hoarder of biscuits

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    The difference is attributed to 1) slight differences in the population that was tested, and 2) different types of assays. One lab may use a kit from one clinical test vendor, and another may use their own reagents. I've been employed in establishing normative data for several clinical tests.

    Also, keep in mind that not all test ranges fit into a bell-shaped curve. For example, this is how the distribution of TSH is graphed:
    [​IMG]
    The most common value is between 1.0 and 1.5. Anything above 2.5 should be considered abnormal.

    I'm going to use TSH as an example. I think other thyroid tests would have some of the same features.

    For TSH assays, test vendors include Siemens Centaur, Architect, Roche and Immulite. For one study to establish age-specific ranges, the four TSH assays showed good agreement at low-normal TSH concentrations (<2 mU/l), but at concentrations of 4·0 mU/l, there were intermethod differences of approximately 1 mU/l.

    See https://www.medscape.com/viewarticle/773055_1
    Age-specific TSH Reference Ranges Have Minimal Impact on the Diagnosis of Thyroid Dysfunction
    Here's another example for hematology reference ranges:
    The Reference Intervals for the Haematological Parameters in Healthy Adult Population of Chennai, Southern India
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3552202/
     
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  16. Ema

    Ema Senior Member

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    Super interesting!

    How do you know if it fits into a bell curve or not? Is there some way to look it up?
     
  17. CFS_for_19_years

    CFS_for_19_years Hoarder of biscuits

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    You need to search on Google for each individual test. For instance, if you want to know if the distribution curve for testosterone is normal or not, the following phrase on Google will give you some results that will say it is skewed to the left:
    testosterone "distribution curve"
    Here's one of the results:

    https://www.researchgate.net/figure...ked-skewing-to-the-left-of-the_fig1_280590804

    I spent a long time looking for a distribution curve for free T3 and here is what I found:
    http://labmed.ucsf.edu/labmanual/db/resource/proc-Axsym-Free_T3.pdf
    The scatter graph on Page 6 is harder to eyeball and interpret for normal distribution since it is turned 90 degrees from a usual distribution curve. There are statistical values for skewness and kurtosis that will define if a distribution is normal or not.
    The normal range for healthy individuals was calculated from the 1,275 specimens and was found to be 1.45 to 3.48 pg/mL (central 95%). Mean is 2.46 pg/mL.


    On Page 7 they compared their free T3 assay to two other diagnostic kits. A correlation coefficient of 1.0 is perfect and theirs were 0.948 and 0.959. I interpret that to mean if you tested all three kits using the same blood sample you could see a variation of 4 - 5%.

    I assume your units are pmol/L. Your 2.88 - 4.88 pmol/L is equivalent to 1.87 - 3.18 pg/mL, which is close to the range of 1.45 to 3.48 pg/mL used for the assay above.

    Enough nerdiness. :nerd:
     
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  18. pattismith

    pattismith Senior Member

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    What looks strange to me in this study is that they found 16 patient with Low fT3 (under 4.4 pmol/l), but not any patient with rT3 above the reference ranges....

    This is the main reason why I wonder if the reference ranges they use for fT3 are really acurate...
     
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  19. anni66

    anni66 mum to ME daughter

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  20. Sing

    Sing Senior Member

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    Do you have any links to these studies on Fibromyalgic patients by Dr. Lowe? I also wonder if he was only prescribing them T3, rather than a combination of T4 and T3 which might stymie the usefulness of the T3.
     
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