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

Ema

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Chronic fatigue syndrome (CFS) is a heterogeneous disease with unknown cause(s). CFS symptoms resemble a hypothyroid state, possibly secondary to chronic (low-grade) (metabolic) inflammation.

We studied 98 CFS patients (21-69 years, 21 males) and 99 age- and sex-matched controls (19-65 years, 23 males).

We measured parameters of thyroid function, (metabolic) inflammation, gut wall integrity and nutrients influencing thyroid function and/or inflammation.

Most remarkably, CFS patients exhibited similar TSH, but lower FT3 (difference of medians 0.1%), TT4 (11.9%), TT3 (12.5%), %TT3 (4.7%), SPINA-GD (14.4%), SPINA-GT (14.9%), 24-hour urinary iodine (27.6%) and higher %rT3 (13.3%). FT3 below the reference range, consistent with the 'low T3 syndrome', was found in 16/98 CFS patients vs. 7/99 controls (OR 2.56; 95% CI=1.00 - 6.54). Most observations persisted in two sensitivity analyses with more stringent cut-off values for BMI, hsCRP and WBC. We found possible evidence of (chronic) low-grade metabolic inflammation (ferritin and HDL-C). FT3, TT3, TT4 and rT3 correlated positively with hsCRP in CFS patients and all subjects. TT3 and TT4 were positively related to hsCRP in controls. Low circulating T3 and the apparent shift from T3 to rT3 may reflect more severely depressed tissue T3 levels.

The present findings might be in line with recent metabolomic studies pointing at a hypometabolic state. They resemble a mild form of 'non thyroidal illness syndrome' and 'low T3 syndrome' experienced by a subgroup of hypothyroid patients receiving T4 monotherapy. Our study needs confirmation and extension by others. If confirmed, trials with e.g. T3 and iodide supplements might be indicated.
https://www.frontiersin.org/articles/10.3389/fendo.2018.00097/abstract
 

pattismith

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I would like to thank these scientists, they give me some hope!

Begoña Ruiz-Núñez1, 2*, Rabab Tarasse1, Emar Vogelaar3, Janneke Dijck-Brouwer1 and Frits Muskiet1
  • 1Laboratory Medicine, University Medical Center Groningen, Netherlands
  • 2Healthy Institute, Spain
  • 3European Laboratory of Nutriënts (ELN), Netherlands
 

pattismith

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"They resemble a mild form of 'non thyroidal illness syndrome' and 'low T3 syndrome' experienced by a subgroup of hypothyroid patients receiving T4 monotherapy."

I don't understand this sentence so I am waiting for the full article to be available...
 

Ema

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"They resemble a mild form of 'non thyroidal illness syndrome' and 'low T3 syndrome' experienced by a subgroup of hypothyroid patients receiving T4 monotherapy."

I don't understand this sentence so I am waiting for the full article to be available...
I think it means that the illness is a brain problem, not an actual problem with the thyroid gland. Meaning the body has turned down thyroid production, rather than the thyroid is unable to produce a normal amount of hormone. https://chriskresser.com/low-t3-syndrome-i-its-not-about-the-thyroid/
 

pattismith

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I think it means that the illness is a brain problem, not an actual problem with the thyroid gland. Meaning the body has turned down thyroid production, rather than the thyroid is unable to produce a normal amount of hormone. https://chriskresser.com/low-t3-syndrome-i-its-not-about-the-thyroid/
what you are trying to explain is the meaning of the Euthyroid Sick Syndrome/Non Thyroidal Illness/Low T3 Syndrome.

But what I don't understand in this sentence is specifically how they can talk about Low T3 Syndrome for hypothyroid patients under T4 monotherapy!
LowT3 Syndrome is only known in euthyroid patients by definition.
If you talk about hypothyroid patient under T4 therapy with low T3, you will talk about a "low T3 State", which is not the same issue.

I am waiting for the publication to clarify this.
 

Hip

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So just for ease of reading, here are the average thyroid hormone parameters of ME/CFS patients measured in the study, with the percentage figures indicating how much they were lower or higher than in healthy controls:
Thyroid parameters of ME/CFS patients compared to healthy controls

TSH = normal

Total T4 = lower by 12%

Free T3 = lower by 0.1%
Total T3 = lower by 13%
Percentage T3 = lower by 5%

Percentage reverse T3 higher by 13%

Sum activity of peripheral deiodinases (SPINA-GD) = lower by 14%
Calculated secretory capacity of the thyroid gland (SPINA-GT) = lower by 15%

Iodine in urine = lower by 28%

T3 is the thyroid hormone with most of the active effects (T3 is 3 to 5 times more active than T4). And it is only the free form of the hormone that is physiologically active.

So the fact that free T3 is not much different to normal in ME/CFS (it's only lowered by 0.1%) suggests that T3 levels are not the issue.

However, since the percentage reverse T3 is higher by 13% in ME/CFS, and reverse T3 acts to counter the effects of T3, possibly this might have detrimental effects.

But I am not sure what is meant by percentage reverse T3; that's not an absolute measure of reverse T3 levels, but represents the ratio of reverse T3 in comparison to some other (unspecified) thyroid parameter.
 
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pattismith

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Are they talking about fT3/rT3 ratio?

However, since the percentage reverse T3 is higher by 13% in ME/CFS, and reverse T3 acts to counter the effects of T3, possibly this might have detrimental effects.
Do you have scientific evidences that reverse T3 acts to counter T3?

I have read that rT3 is inactive and has very low affinity for T3 receptors so I wonder if rT3 really has the ability to interfer.
 

Hip

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Do you have scientific evidences that reverse T3 acts to counter T3?
I have read that reverse T3 binds to the same thyroid hormone receptors as T3 and T4, and because reverse T3 is more-or-less inactive at these receptors, and because it blocks T3 and T4 from binding to and activating the receptor, the effect of reverse T3 is to lower thyroid hormone receptor activation.

But you are suggesting this is not scientifically proven, and is more of a hypothesis or assumption? I did a quick Google search, and could not find any scientific source that confirmed the above, so perhaps you are right, and this is only an assumption about the function of reverse T3.



Are they talking about fT3/rT3 ratio?
It could be. They talk about the importance of the free T3 / reverse T3 ratio here, so that seems to be a standard ratio in thyroid endocrinology.
 

pattismith

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I do have the low T3 syndrome, and I have read lots of scientific papers about it and found not any evidence of rT3 interfering with T3 activity, so I assume it is only an hypothesis, although quite a reasonable one.

So the fact that free T3 is not much different to normal in ME/CFS (it's only lowered by 0.1%) suggests that T3 levels are not the issue.
0.1% lower is only a mean average drop of fT3, it does not mean much. It just mean that fT3 levels in CFS groups are probably very diverse, and that only a subgroup have low fT3. This is confirmed by the following sentence:

"FT3 below the reference range, consistent with the 'low T3 syndrome', was found in 16/98 CFS patients vs. 7/99 controls "

So 16.3% of CFS patients of this group had fT3 below the normal range and were considered affected by the Low T3 syndrome.

16.3% is not the majority of CFS patients, but it is all the same a rather important subgroup of patients, so I think it is important to screen it from the begining when the disease just starts.

The fT3/rT3 ratio may be more acurate to do the screening.
 

Hip

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So 16.3% of CFS patients of this group had fT3 below the normal range and were considered affected by the Low T3 syndrome.

16.3% is not the majority of CFS patients, but it is all the same a rather important subgroup of patients, so I think it is important to screen it from the begining when the disease just starts.
Yes, it's a good idea to screen for thyroid hormone abnormalities.

I came out normal on the UK NHS thyroid function test, which I believe only measures TSH and T4 (it says here that T3 tests are not routinely done in the NHS, because T3 levels can often remain normal, even if you have a significantly underactive thyroid).

And just to be double sure, I also experimented with taking supplemental T3, at up to 25 mcg daily, but noticed no benefit.
 

sb4

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I do intent to try T3 at some point in the future but I will be using caution as I suspect things could get a lot worse if your body has reduced thyroid function for a reason. If you have deficiencies of any B vitamin really, or Mg, or poor PDH function, I can see T3 making things much worse. If you start very low and slow you maybe able to overcome this though.
 

Hip

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I do intent to try T3 at some point in the future but I will be using caution as I suspect things could get a lot worse if your body has reduced thyroid function for a reason.
Body-builders sometimes use T3 for several months in a row to increase metabolism and burn off fat. I have not heard of any stories where this has led to permanent changes in thyroid hormone levels.
 

pattismith

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@Hip ,
i think I have the Low T3 Syndrome from the start of my illness (35 years ago), even though fT3 has always been in the low/normal range. I only discovered it when I saw my fT3 was going lower and lower with time, and when I tested my rT3 which was very high.

My fT3/rT3 ratio is 3.8, whereas it is considered normal if above 8, and optimal at around 17.

the fact you didn't react to your T3 trial doesn't say much. Did you had adverse effect from it?
if not, it could be meaningful: it could be consistent with a thryroid hormon resistance (again it's only an hypothesis which is equivallent to the intracellular hypothyroidism theory).

I have already done a T3 trial some years ago, and got no improvement from it.
And now I relieve most of my symptoms for 9 hours with only 6.25 mcg in the morning, so there is an other mistery to solve...

I also have reduced immunity and Herpes virus problems, and T3 has shown it's ability to fight the herpesvirus (at less HSV1 and alphaHHV):

http://forums.phoenixrising.me/index.php?threads/thyroid-hormons-and-virus.57307/


I do intent to try T3 at some point in the future but I will be using caution as I suspect things could get a lot worse if your body has reduced thyroid function for a reason. If you have deficiencies of any B vitamin really, or Mg, or poor PDH function, I can see T3 making things much worse. If you start very low and slow you maybe able to overcome this though.
First thing to do is to closely monitor the effect of T3 on your body (temperature, heart rate and blood pressure) in order to control if T3 has some effect on you.
Second thing is to listen to your body, I think most of us have learnt to do so unfortunately.
 
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Ema

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what you are trying to explain is the meaning of the Euthyroid Sick Syndrome/Non Thyroidal Illness/Low T3 Syndrome.

But what I don't understand in this sentence is specifically how they can talk about Low T3 Syndrome for hypothyroid patients under T4 monotherapy!
LowT3 Syndrome is only known in euthyroid patients by definition.
If you talk about hypothyroid patient under T4 therapy with low T3, you will talk about a "low T3 State", which is not the same issue.

I am waiting for the publication to clarify this.
I think you just did. :)

Euthyroid just means "having a normally functioning thyroid gland". You can have a normally functioning thyroid gland and still have too little thyroid hormone. I don't think the two are mutually exclusive. This article, for example, seems to use the terms interchangeably.
 
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sb4

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Body-builders sometimes use T3 for several months in a row to increase metabolism and burn off fat. I have not heard of any stories where this has led to permanent changes in thyroid hormone levels.
I am sure they do but am not sure how this is relevant to what I was saying. Body builders will most likely not have mineral deficiencies / antibody problems to deal with. If you have CFS, there is a decent chance you have, so you could run the risk of amplifying these problem. So probably best to start low and slow.
 

Ema

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Body-builders sometimes use T3 for several months in a row to increase metabolism and burn off fat. I have not heard of any stories where this has led to permanent changes in thyroid hormone levels.
I don't think it would lead to permanent damage, but it could lead to increased negative symptoms if the low T3 state is adaptive in some not-yet understood way. That was my experience with a full replacement dose of T3. It felt like I was beating a dead horse.

T3 has a much greater affinity, something like 3x, I think, for that receptor than rT3, so I don't really see how it could ever "clog" up the receptors, no matter the level. If that was possible, Graves' disease would never be an issue, because the rT3 would be protective against that state. But that's not the way it works.
 

pattismith

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I think you just did. :)

Euthyroid just means "having a normally functioning thyroid gland". You can have a normally functioning thyroid gland and still have too little thyroid hormone. I don't think the two are mutually exclusive. This article, for example, seems to use the terms interchangeably.
yes you are right, but I still think the two problems should be separated (euthyroid Low T3 and hypothyroid with T4 monotherapy and Low T3) until more studies are able to say if the pathogenesis pathways are the same or not.:thumbsup:

I'm still impatient to read the full paper to see how they screened and selected the cohort, and if they included hypothyroid patients under therapy in it.
 

nanonug

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I think the most important conclusion from this study is, as they point out, that "the present findings might be in line with recent metabolomic studies pointing at a hypometabolic state," lending additional credence to the previous studies pointing in the same direction. The increase in rT3 is consistent with a biological response to physiological stressors, much like increased expression of pyruvate dehydrogenase kinase.

In the last 15 years or so, I've used thyroid glandulars quite often, but never got much out of it. In addition, several years ago, when I was in a pretty bad state, I had to discontinue the thyroid glandular because it made me feel much worse.

Looking at a study from 1998 entitled "3,5,3'-triiodothyronine induces mitochondrial permeability transition mediated by reactive oxygen species and membrane protein thiol oxidation", the following conclusion catches my eye: "Our results lead to the conclusion that T3 induces a situation of oxidative stress in isolated liver mitochondria." If oxidative stress is a problem, then supplementing with thyroid hormone might not be a good idea. Doesn't Dr. Cheney also say that supplementing with thyroid is bad for people with SEID?
 

pattismith

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I

In the last 15 years or so, I've used thyroid glandulars quite often, but never got much out of it. In addition, several years ago, when I was in a pretty bad state, I had to discontinue the thyroid glandular because it made me feel much worse.
using T4 or T4 + T3 if you have Low T3 syndrome could make you feel very bad (you didn't say how was your thyroid panel so I ignore if you were already aware of your real thyroid status when you did your trial).
I have the Low T3 Syndrome and was very bad as soon as I was taking any T4, either alone or with T3.
I had not any hyperthyroid effect from it, but it was worsening my condition.
@BadBadBear has the same Low T3 Syndrome and experienced the same with any T4.

So a bad experience with T3+T4 hormons does not mean you couldn't benefit from T3 alone.
 

nanonug

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So a bad experience with T3+T4 hormons does not mean you couldn't benefit from T3 alone.
That's a good point, considering I was taking a glandular with all the porcine Ts.

The whole shebang (TSH, T4, T3, FT4, FT3, RT3, T3 Uptake) were all within the "normal" range but there was "upside potential" for improvement. The glandular I was taking only mildly increased thyroid and kept things within normal as well but still caused problems at my worse. Considering T3 leads to increases in oxidative stress, and assuming that oxidative stress is a problem in SEID, which I do, any increase in T3 is potentially bad. Of course we are all different and it doesn't surprise me that your situation is different as well.