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CFS/ME and intracellular hypothyroidism

frozenborderline

Senior Member
Messages
4,405
But what does a high TTSI actually mean clinically? Yes it's suggested, by, as far as I can tell, only one group of people, that it suggests resistance to thyroid hormones, probably genetically based, but that's all google will tell me.

If I inform my NHS GP that a calculation based on my "normal" thyroid panel says I have a high TTSI and this means I am thyroid hormone resistant she will probably just give me the "look" and say my numbers are in range, that I don't have any thyroid issues, so why am I wasting money on private testing.

So.......how to get around this, and is it clinically significant enough to be worth the effort?
Clinically it seems fairly straightforward, which doesn't mean it will be in practice. If the papers i've read are right, high TTSI is a sign of thyroid hormone resistance, which can and should be treated with triac: https://en.wikipedia.org/wiki/Tiratricol . Now, I doubt your average GP is caught up with the research enough to look at your spina results and do this. This means you may have to take matters into your own hands. I'm going to do more research into the availability of this chemical and whether or not there are reliable brands/sources I can get my hands on that would not be contaminated or have a COA.
 

clive powney

Senior Member
Messages
206
Location
coventry
I just ran my thyroid panel results from a few years ago through the SPINA software (before I was on any thyroid replacement therapy) and all of my values were in range - apart from my TTSI which was 296 - way out of range.
After this panel I tried :-
T4 - any dose of which above a very small amount increases my symptoms of tiredness and I end up sleeping on and off all day with no refreshment. I have tried t4 on about 4 occasions now with exactly the same result. About 2 -3 days in, I end up comatosed and it takes a while for this to improve
NDT - no real change in symptoms
T3 - been using this for over 2 years now with a marked positive effect gone from a score of 4/10 to around 7/10. This is now sustained and I rarely need a sleep during the day and am generally reasonably happy , but still nowhere near my pre-illness capabilities.This did take a while to improve though - think it was (from research) the time to clear t4 from my system - around 2 months
I do take around 80mcg spread over the day which is far more than my endo wants me to but because of the improvement in my symptoms he is happy for me to continue
.Any thoughts anyone???
 

clive powney

Senior Member
Messages
206
Location
coventry
Additionally - I just ran my wife's panel from may 2014 through the software and she was also out of range on the TTSI - 319.
She has very similar symptoms to me apart from excessive sleepiness and does not see any improvement particularly on T4.
She hasn't tried T3 yet as she is not as experimental as I am!
 

clive powney

Senior Member
Messages
206
Location
coventry
just found this link :-
https://clinicaltrials.gov/ct2/show/NCT02060474
Not that we have the syndrome, but potentially where there has been something happen to us to upset the balance of our hormones, possibly a similar syndrome could develop with different symptoms if developed in later life. Looking at my wifes panel :
free t4 13.8 (12-20) low end pmol/l
free t3 5.7 (3.4 - 6) high end pmol/l
total t4 80.6 (77-150) low end nmol/l
tsh 4.15 (1 - 4) slightly raised mIU/L
t4:t3 2.4 (2.5 - 4.0) low
on these figures she was not diagnosed as hypothyroid, but it is interesting that very low normal end t4 levels have produced a high end free t3 - perhaps what this theory is based on?
my results (same units):-
free t4 12.6 (12-20) low end
free t3 4.33 (3.4 - 6) mid range
total t4 61.1 (77-150) low
tsh 4.2 slightly raised
t4:t3 2.9 low end
 
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pattismith

Senior Member
Messages
3,957

High TTSI associated to normal thyroid panel is probably a more subtile type of TH resistance than the one endocrinos are used to diagnose, with usually out of range TH and genetic mutations into TH nuclear receptors or into TH transporters.
This tool (SPINA) is only for research purpose for now, see here a special thread devoted to it, but it certainly gives us much informations.

We can just speculate as why some CFS/ME patients have TH resistance, maybe a consequence of their immune system reaction to an infectious trigger?

Nobody has tried Triact in this indication to my knowledge, so it's impossible to say if it is safe and even useful...

If T3 is working for you, it is a great news, but keep in mind that if your thyroid resistance decreases with time, you may become more sensitive to T3 and you will be able to lower the dosage.
@BadBadBear was able to lower her T3 intake when she started her new treatment Mestinon + Famvir here
 
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clive powney

Senior Member
Messages
206
Location
coventry
@pattismith the second link is the same as the first one.
It is interesting your comment on TH resistance maybe a consequence of immune reaction after an infectious trigger, as both my wife and I developed symptoms within a few months of each other and whilst they are not the same there is a lot of similarity between us. T3 is the ONLY thing that has worked for me and given me a life, albeit not where I want to be. I have been CFS/ME diagnosed for 14 years and my wife with fibromyalgia for 10 + years.
 

frozenborderline

Senior Member
Messages
4,405
High TTSI associated to normal thyroid panel is probably a more subtile type of TH resistance than the one endocrinos are used to diagnose, with usually out of range TH and genetic mutations into TH nuclear receptors or into TH transporters.
This tool (SPINA) is only for research purpose for now, see here a special thread devoted to it, but it certainly gives us much informations.

We can just speculate as why some CFS/ME patients have TH resistance, maybe a consequence of their immune system reaction to an infectious trigger?

Nobody has tried Triact in this indication to my knowledge, so it's impossible to say if it is safe and even useful...

If T3 is working for you, it is a great news, but keep in mind that if your thyroid resistance decreases with time, you may become more sensitive to T3 and you will be able to lower the dosage.
@BadBadBear was able to lower her T3 intake when she started her new treatment Mestinon + Famvir here
TRIAC has been used to treat thyroid hormone resistance, nobody on this board has tried it though.
 

CFS_for_19_years

Hoarder of biscuits
Messages
2,396
Location
USA
What is TRIAC, @debored13 ? TIA ☺
I'll take a shot at answering.

TRIAC is 3,5,3'-Triiodothyroacetic Acid or simply triiodothyroacetic acid. See:

Tiratricol
https://en.wikipedia.org/wiki/Tiratricol
Tiratricol (also known as TRIAC or triiodothyroacetic acid) is a thyroid hormone analogue. Triiodothyroacetic acid is also a physiologic thyroid hormone that is present in the normal organism in low concentrations.

Triiodothyroacetic acid has unique potential for therapy of resistance to thyroid hormone
https://www.ncbi.nlm.nih.gov/pubmed/7608251
 

pattismith

Senior Member
Messages
3,957
in this paper, I found some TTSI ( = TT4RI) values of patients with thyroid resistance from a mutation in the THRB gene :


Homozygous Thyroid Hormone Receptor β-Gene Mutations in Resistance to Thyroid Hormone: Three New Cases and Review of the Literature

Conclusion:
We report three new subjects, from two families, in whom RTH was associated with homozygous mutations in the THRB gene. They represent an important addition to the single known patient homozygous for a mutant TRβ. The clinical and laboratory abnormalities indicate a strong dominant-negative effect and are in agreement with data obtained from mice expressing a mutant Thrb in both alleles. This report strengthens the concept that the mutated TRβ interferes with the function of the TRα1 in humans.

The syndrome of resistance to thyroid hormone (RTH) is caused by decreased tissue responsiveness to thyroid hormone (TH) (1, 2). The biochemical hallmark of RTH is abnormally elevated serum free TH levels together with nonsuppressed TSH secretion. The clinical presentation is highly variable, ranging from isolated biochemical abnormalities to a mixture of hypo-hyperthyroid signs and symptoms (13). The cause is mostly mutations in TH receptor β (THRB) gene (1, 2).

With the exception of a single family with recessively inherited RTH due to a deletion of the THRB gene (4), inheritance of RTH is autosomal dominant (1). Clinical and biochemical manifestations are attributed to the interference of mutant TRβ with the function of the normal receptor, a phenomenon termed “dominant-negative effect” (DNE) (5).

.....



We used the thyrotroph T4 resistance index (TT4RI), the product of FT4I and TSH (17), to estimate the relative resistance of the hypothalamo-pituitary axis to TH (calculated using data from Table 3).
This allows the inclusion of individuals on l-T4 replacement. In increasing order of resistance, subjects without WT TRβ from the five families ranked as follows: G<F<Mozv<S<Mbyd, with scores of 920, 4,920, 10,456, 140,290, and 239,120 (normal, 136 ± 73), respectively.
It is of interest that heterozygous relatives ranked in almost similar order F<G<Mozv<S<Mbyd, with scores of 129, 200, 293, 330, and 830, respectively. Note that the TT4RI of heterozygotes of families G and F are well within the normal range.
 

pattismith

Senior Member
Messages
3,957
Hi pattismith - I have added in the units

Your wife has high TTSI (318), yours is high also (294).

I wish some searcher will study this thyroid resistance in CFS patients. It seems an important recurrent finding.

upload_2018-3-19_13-25-3.png


upload_2018-3-19_13-23-20.png
 

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clive powney

Senior Member
Messages
206
Location
coventry
is there any way we could get a whole load of people on here to run their numbers through this ? I suspect that the majority of people here would have had a thyroid panel done sometime recently.
It is also interesting that it suggests that I need to take t3 or triac (optimally) and the on ly thing that has had a beneficial effect on me is T3
 

pattismith

Senior Member
Messages
3,957
is there any way we could get a whole load of people on here to run their numbers through this ? I suspect that the majority of people here would have had a thyroid panel done sometime recently.
It is also interesting that it suggests that I need to take t3 or triac (optimally) and the on ly thing that has had a beneficial effect on me is T3
I opened a thread here to get more CFS/ME patients tested, but it got not much success for now :):

http://forums.phoenixrising.me/inde...ion-deiodinases-activity-th-resistance.58209/
 

pattismith

Senior Member
Messages
3,957
"The existence of acquired partial thyroid hormone resistance has been postulated [241, 242], but this condition may be rare or underrecognised.

In NTIS, however, disruption of thyroid hormone signalling by cytokines, metabolites, toxins or drugs may contribute substantially to the clinical phenotype of affected patients [242].

Possible mechanisms of acquired thyroid hormone resistance include impairments of transmembrane transport [15, 16, 243], deiodination [19, 227, 228, 244], entry into nucleus [245, 246], receptor binding [243, 247253], and nongenomic effects of iodothyronines [28, 254264].

Similar effects may ensue from exposure to endocrine disruptors [265] like phthalates [266268], brominated flame retardants [266, 267, 269], perfluorinated compound [266, 267, 270], polychlorinated biphenyls [271276], bisphenol A [254, 266269, 274], or bisphenol F [277].

Some environmental toxins may also act as thyroid hormone agonists, as demonstrated for certain polychlorinated biphenyls [278, 279]."

Dietrich 2012
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544290/
 

pattismith

Senior Member
Messages
3,957
just found this link :-
https://clinicaltrials.gov/ct2/show/NCT02060474
Not that we have the syndrome, but potentially where there has been something happen to us to upset the balance of our hormones, possibly a similar syndrome could develop with different symptoms if developed in later life. Looking at my wifes panel :
free t4 13.8 (12-20) low end pmol/l
free t3 5.7 (3.4 - 6) high end pmol/l
total t4 80.6 (77-150) low end nmol/l
tsh 4.15 (1 - 4) slightly raised mIU/L
t4:t3 2.4 (2.5 - 4.0) low
on these figures she was not diagnosed as hypothyroid, but it is interesting that very low normal end t4 levels have produced a high end free t3 - perhaps what this theory is based on?
my results (same units):-
free t4 12.6 (12-20) low end
free t3 4.33 (3.4 - 6) mid range
total t4 61.1 (77-150) low
tsh 4.2 slightly raised
t4:t3 2.9 low end

Clive, I wonder if anti-T3 auto-antibodies could explain your values; Do you have a test for your anti-TPO and anti-thyroglobulin antibodies?
 

tiredowl

Senior Member
Messages
170
Location
Norway
Clinically it seems fairly straightforward, which doesn't mean it will be in practice. If the papers i've read are right, high TTSI is a sign of thyroid hormone resistance, which can and should be treated with triac: https://en.wikipedia.org/wiki/Tiratricol . Now, I doubt your average GP is caught up with the research enough to look at your spina results and do this. This means you may have to take matters into your own hands. I'm going to do more research into the availability of this chemical and whether or not there are reliable brands/sources I can get my hands on that would not be contaminated or have a COA.

Did you find a source for where to get this supplement/drug ?
Looks like it is not available anywhere but in France for some reason...