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thyroid hormons and virus

Discussion in 'Other Health News and Research' started by pattismith, Jan 22, 2018.

  1. pattismith

    pattismith Senior Member

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    A Cohort Historical Analysis of the Relationship between Thyroid Hormone Malady and Alpha-Human Herpesvirus Activation
    2014
    Abstract
    Background
    A number of physiological factors have been suggested to participate in the alpha- Human Herpesvirus (αHHV) reactivation, such as hormonal aberration. Thyroid hormone (TH) was shown to play a suppressive role in Herpes Simplex Virus Type-1 (HSV-1) gene expression and replication in cell culture and animal models. We hypothesize that reactivation of αHHV in humans may be due to, at least in part, by TH status.

    Methods
    Prior to implementing a full-scale population-based prospective inquiry into this hypothesis, a pilot study using a medical claims data base and a case-controlled, retrospective cohort investigation was conducted to develop a hypothetical link between TH complication and αHHV reactivation. Using diagnostic codes for treating thyroid disorders and αHHV infections as proxies for biologic/clinic outcomes, we queried a large, comprehensive hospital data base to construct two patient cohorts: Cohort 1 was comprised of patients receiving TH diagnoses over a twelve-year period, and Cohort 2 was composed of patients not receiving TH diagnoses during this period. Diagnoses of αHHV were recorded for each cohort and the difference in the frequency was examined for statistical significance. Demographic analyses such as age, gender, etc were also performed.

    Results
    Using 2×2 contingency table analyses and Statistical Analysis Software (SAS), an Odds Ratio (OR) of 2.83 was observed for the total population of 21 years old and above with a chi-square of 61.55 and p < 0.001, confirming that a severe significant difference was found between these two cohorts. This result suggested that patients with αHHV diagnosis have higher chances to have TH disorders. Additional investigation revealed that female were at higher/significant probability to have both TH and αHHV diagnosis, indicating a link of αHHV reactivation to a complex hormonal profile difference between genders. Our observation indicated that female patients of 21 years of age and above exhibited a very high incidence (OR of 3.40, p < 0.001) compared to the male groups (OR of 1.91, p < 0.05), indicating the possibility that hormonal alteration in females maybe transient but robust and can lead to αHHV reactivation more often than the males.

    Conclusion
    These results indicated that TH dysfunction may have implication in αHHV pathogenesis and females exhibited much higher probability to suffer αHHV reactivation due to TH disruption. Although the results from this pilot study have limitations and require additional controlled clinical examination such as more detailed patient records, lab data, therapeutic outcome, etc, it provides a tool to assess the effects of hormone imbalance on virus reactivation by retrospective analyses using existing large scale data base.


    Influence
    of Thyroid Hormone Disruption on the Incidence of Shingles
    2015
    SUMMARY

    The reactivation of dormant alpha-Human Herpes Virus (αHHV) has been attributed to various causes often referred to as stressors. However, no clinical study investigating the relationship between stressors and reactivation exists in humans at this time. Herpes Simplex Virus Type-1 (HSV-1), an important αHHV, was shown to have its gene expression and replication regulated by Thyroid hormone (TH) using molecular biology approaches. Varicella Zoster Virus (VZV) is categorized in αHHV superfamily and shares similar homology with HSV-1. We hypothesize that a history of TH imbalance may be associated with the incidence of shingles (VZV reactivation). This current pilot study, based on a hospital medical claim database, was conducted as a retrospective case-controlled investigation to determine if a putative link between TH imbalance and incidence of shingles is present. An OR of 2.95 with a Chi-square of 51.74 was calculated for the total population diagnosed with TH disruption and shingles. Further analyses indicated that African American males exhibited much higher chance of simultaneous diagnoses. These results showed that a TH imbalance history may affect VZV reactivation at different incidence rates in different races and age groups.

    New insights on thyroid hormone mediated regulation of herpesvirus infections
    2017
    Abstract

    Thyroid hormone (T3) has been suggested to participate in the regulation of herpesvirus replication during reactivation. Clinical observations and in vivo experiments suggest that T3 are involved in the suppression of herpes virus replication. In vitro, differentiated LNCaP cells, a human neuron-like cells, further resisted HSV-1 replication upon addition of T3. Previous studies indicate that T3 controlled the expression of several key viral genes via its nuclear receptors in differentiated LNCaP cells. Additional observation showed that differentiated LNCaP cells have active PI3K signaling and inhibitor LY294002 can reverse T3-mediated repression of viral replication. Active PI3K signaling has been linked to HSV-1 latency in neurons. The hypothesis is that, in addition to repressing viral gene transcription at the nuclear level, T3 may influence PI3K signaling to control HSV-1 replication in human neuron-like cells. We review the genomic and non-genomic regulatory roles of T3 by examining the phosphoinositide 3-kinase (PI3K) pathway gene expression profile changes in differentiated LNCaP cells under the influence of hormone.
    The results indicated that 15 genes were down-regulated and 22 genes were up-regulated in T3-treated differentiated LNCaP cells in comparison to undifferentiated state. Of all these genes, casein kinase 2 (CK2), a key component to enhance PI3K signaling pathway, was significantly increased upon T3 treatment only while the cells were differentiated. Further studies revealed that CK2 inhibitors tetrabrominated cinnamic acid (TBCA) and 4, 5, 6, 7-tetrabromo-2H-benzotriazole (TBB) both reversed the T3-mediated repression of viral replication. Together these observations suggested a new approach to understanding the roles of T3 in the complicated regulation of HSV-1 replication during latency and reactivation.
     
  2. pattismith

    pattismith Senior Member

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    @BadBadBear sent to me this amazing article about direct virus effect on thryoid.(herpesvirus, parvovirus, enterovirus, etc);

    There is a small part about auto-antibodies against T3 and T4 that could explain some thyroid disoders observed with atypical thyroid panels:


    Viruses and thyroiditis: an update

    II-B-3b/Epstein Barr Virus (EBV)

    EBV infection is known to be involved in tumoral diseases such as lymphoma but also in autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus [98].
    Antibodies against EBV viral capsid antigen (IgG-VCA) and antibodies against early antigen (IgG-EA-D/DR) have been more often found in thyroiditis than in controls [99].

    What is unusual is that EBV may induce anti-T3 antibodies.

    Acute EBV infection with severe primary hypothyroidism was described in a 16-year old female patient. She had high low FT4 and low FT3 but discordant elevated total T3.
    Later, 34 patients with EBV infection were tested for thyroid hormone levels. Five patients with acute EBV and one with previous infection had total T3 values above the mean which was due to anti-T3 antibodies

    I found a laboratory page about dosage of T3 auto-antibody


    Clinical Background :

    Patients with autoimmune thyroid diseases, including autoimmune (Hashimoto) thyroiditis and Graves disease, may rarely develop antibodies to T3 (triiodothyronine) and/or T4 (thyroxine).
    T3 antibodies interfere with T3 assay measurement by com- peting with the anti-T3 immuno- globulins used in the T3 assay.
    When a patient has a serum T3 concentrati\on that is discordant with other test results, eg, elevated serum T3 in the presence of a detectable serum TSH concentration, then it may be appropriate to determine if anti-T3 antibodies are present

    The problem seems to exist in dogs too:

    What is the purpose of measuring T3 autoantibodies and T4 autoantibodies?

    In dogs, antibodies which cross-react with T4 and/or T3 are markers for lymphocytic thyroiditis.

    These antibodies are generated against T4 and T3 containing epitopes on the thyroglobulin molecule, i.e., they are subsets of TgAA.
    Positive values indicate thyroid gland pathology, and also tell us about the validity of the thyroid hormone results.

    T3AA and T4AA are present in around 35% and 14% of hypothyroid dogs respectively.


    In the Endocrine Diagnostic Section at Michigan State University, T3 antibodies cause a false decrease in TT3 and a false increase in FT3 results.
    T4 antibodies falsely increase TT4 and may increase FT4 results in the standard thyroid profiles.

    In a hypothyroid dog with T4AA, T4 may be falsely elevated into the normal range and the true diagnosis masked.
    To obtain an accurate measure of T4 status in a T4AA positive animal, submit a sample for free T4 by equilibrium dialysis (FT4d) which is not affected by antibody. FT4d is included in Premium Thyroid Profiles. Although these antibodies have a large effect in the laboratory test tube, the clinical impression is that they do not interfere significantly with the availability of thyroid hormone in a thyroxine-treated hypothyroid dog.

    @Iritu1021
    @marinho33
     
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  3. Iritu1021

    Iritu1021 Breaking Through The Fog

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    Huh. Very interesting. T3/T4 antibodies have been on my radar lately but I haven't yet looked into the subject too closely. But this is a little concerning - does that mean that we can we drive the antibodies up by taking more T3?

    The way I'm reading it right now they don't consider them clinically significant, only an interference with measurement? Is that your interpretation too? (Of course it doesn't really mean they are right).
     
    Last edited: Mar 24, 2018
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  4. BadBadBear

    BadBadBear Senior Member

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    Rocky Mountains
    Thank you so much for posting this for me, @pattismith

    There is another interesting study that high T3 autoantibodies induces T cell increase, I will post a link when I find it again.☺ .So we start to see a syndrome of low T3, increased immune system activity.
     
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  5. pattismith

    pattismith Senior Member

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    yes, the problem of anti-T3AA (or T4) will interfer with T3and T4 measurement. This mean it could mask hypothyroidism or subclinical hypothyroidism.
    So I think if TSH is elevated or borderline high with high T3 or high T4, these AA must be ruled out, especially if the patient has already other AA like Anti-TPO, anti Tg or anti TR...

    I too wonder if antiT3AA will block T3 effect, and if T3 treatment is indicated, I don't know more about it.
     
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  6. Iritu1021

    Iritu1021 Breaking Through The Fog

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    So what you're saying someone might have a false high T3/T4 due to antibody interference while actually being hypothyroid?

    But I wonder if all the antibody upregulation is what creates a dependence on taking thyroid once you go down that path... At least I feel like that's what happened in me and I have a lot of other thyroid antibodies. I'm now waiting for anti-TSH Ab test. I haven't seen anti-T3 or anti-T4 on the lab websites I use, I don't know how I would go about getting that done or what would I do about a positive test result...
     
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  7. pattismith

    pattismith Senior Member

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    Do you have both anti-TPO and anti-TG AA?


    "Extremely high or low levels of the FT3 or FT4, particularly in euthyroid patients without clinical features, are highly indicative of the presence of autoantibodies against T3 or T4.
    This situation is observed in 40 cases out of 100 000 tests.
    In 70 % of these cases, the anti-TPO a anti-TG are simultaneously increased. It is possible that concentrations of T3 and T4 autoantibodies are higher, but are not detected because of the bound antigen.
    30 % of anti-TG positive patients also show anti-T3 antibodies, but their levels are only detected after the splitting of immunocomplexes."

    in this interesting case study:


    "The mechanism of genesis of anti-T4 or T3 antibodies is far from clear, although they are nearly confined to autoimmune thyroid diseases,3,8,1114,18) and regarded as a kind of autoantibodies.
    Most of these antibodies are reported to cross-react with thyroglobulin,4,10,18) and it is also reported experimental animals can produce anti-thyroid hormone antibodies when immunized with thyroglobulin under appropriate condition, suggesting that immunogen of antithyroid hormone antibody would be thyroglobulin and this antibody to thyroglobulin would cross-react with thyroid hormones.18)
    This assumption is consistent with the findings that most of the patients with these antibodies have high titer of antithyroglobulin antibody as 1:6402 and 1 ;12802 in our cases.
    Clinical significance of these anti-thyroid hormone antibodies seems mainly to consist in disturbance of radioimmunoassay for thyroid hormones, but Karlsson et al.7) reported a case of hypothyroidism due to anti-T3 antibody. In our first case, the administration of prednisolone and Cytoxan brought about diminution of goiter size and decrease in TSH levels with improvement of lupus symptoms.
    This suggests the possibility that the anti-T4 antibody having cross-reactivity with T3 would have induced hypothyroidism in our first case. But we could not exclude the possibility that the decrease in TSH might be due to the improvement of autoimmune thyroiditis because the patient had high titer of antimicrosomal antibody besides antithyroglobulin antibody, and we did not prove that histology of her thyroid was normal with biopsy."

    I also found a french article, it says that these AA are a sub-group of the anti-thyroglobulin AA and that they don't have any clinical effect (they only interfer with lab values).
     
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  8. Gondwanaland

    Gondwanaland Senior Member

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    I have just made some association of ideas, which is very rudimentary, and wanted to get some insight from you folks who seems to have a far better understanding of things than I do.

    This antiviral has been talked about in another thread,
    Gemcitabine, a broad-spectrum antiviral drug, suppresses enterovirus infections through innate immunity induced by the inhibition of pyrimidine biosynthesis and nucleotide depletion.

    Ever since starting T3 replacement my serum uric acid went up.

    Now I wonder if T3 inhibits pyrimidine biosynthesis? Or at least creates a purine surplus?

    Could this be the machanism by which it suppresses viruses?

    I frequently get flu symptoms when I need to change my hormone replacement, and there is a special balance between thyroid and estrogen.

    Also I wonder where intolerance to progesterone replacement fits in.

    Now for the most interesting part:

    Molybdenum is the cofactor of Xanthine Oxidase, enzyme that produces uric acid.

    I don't tolerate Moly supplementation, but need it badly, and the one food that gives me a noticeable Moly dose is chickpeas. When I don't eat chickpeas at dinner, I get horrible chills all night long. Additionally, I think Moly has a role in Melatonin synthesis.

    Antoher reason why I need high uric acid is becauuse it is a powerful anti-oxidant, which I need for die-off byproducts (?)

    I think there is an intesection of Xanthine oxidase with energy generation (proteolysis), so I think Moly might compete with Iodine.

    @picante @Lolinda

    >>> ETA
    So somehow now that I taking a lower dose of T3 there seems to be an increased need for uric acid.

    If I cook my chickpeas with onions (to divert Moly to be used by Sulfite oxidase), it isn't as effective for sleep/Melatonin production and well-being.

    Also I have read about Inosine is taken as a immunostimulant? Inosine is a direct precursor of purines and uric acid.
     
    Last edited: Mar 25, 2018
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  9. Iritu1021

    Iritu1021 Breaking Through The Fog

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    I used to have only anti-TPO which have gone down but anti-TG then appeared in low levels. I thought it might had something to do with increased thyroglobulin levels in blood due to altered iodine metabolism.
     
  10. Iritu1021

    Iritu1021 Breaking Through The Fog

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    I don't know the exact mechanism but you might need to think through if you're on the right dose of thyroid.
    http://www.clinexprheumatol.org/article.asp?a=1194
    "Our findings confirm the data in the literature concerning the high prevalence of hyperuricemia and gout in hypothyroidism. It shows that hyperthyroidism can cause a significant increase in serum uric acid, as well, although lower than the hyperuricemia due to thyroid hormone deficiency."
     
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  11. Gondwanaland

    Gondwanaland Senior Member

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    I read somewhere that vit D lowers anti-TPO, it should be related with insulin sensitivity
    (?)
     
  12. Gondwanaland

    Gondwanaland Senior Member

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    Yes, I am aware of that, but everytime I tried to up or lower my replacement dosage I got increased uricemia :confused:
    Next week I will draw blood again to see how it is going now with lower T3 replacement.
     
  13. Gondwanaland

    Gondwanaland Senior Member

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    Actually Ithink that my increased need for Moly is because it is needed for the sulfation of fat-soluble vitamins. My Vit D-25OH is steadily declining while the Vit D-1,25OH is raising.
     
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  14. Iritu1021

    Iritu1021 Breaking Through The Fog

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    Then your next question should be what's driving the increased sulfation?
     
  15. Iritu1021

    Iritu1021 Breaking Through The Fog

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    Personally, I could never get the dose right just through dosing. I think thyroid hormones only works well for people with primary thyroid dysfunction or maybe primary + peripheral if they augment with cortisol. For people like us who have all three - primary, secondary and tertiary (peripheral), especially in severe form, it seems to be a nearly impossible task.

    It appears - based on my own experience, that we usually end up with some tissues being hyper, others hypo, some times of the day/month high, others times of the day/month low - for me, personally, it was a complete mess and constant struggle for several years before I really gave up on even trying. This is why pattismith and I are both trying to figure out some potential options of combining low doses of T3 with peripheral augmentation strategies (other than cortisol) and this is what SPINA can be potentially useful for - in figuring out which and how many processes are going on in someone at the same time.

    Keep in mind that every time you start and stop thyroid, your deiodinase settings completly change. In normal people, hypothalamus can handle these changes but in us it can't, we have to go through a difficult adjustment process until (and if) genetic adaptations kick in.
     
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