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Hashimoto’s/Hypothyroidism and Low Testosterone?

Anyone dealt with this combo as far as contributing to chronic fatigue? I reached out to my thyroid dr last week regarding an over all crappy low energy feeling,  heat intolerance ect.  I’ve been increasing my compounded T3 almost monthly to no avail.  She added the testosterone tests to my up coming labs this month for next months visit and noted my symptoms sounded like low T.  Also with noting I have been mold detoxing for a year now with cholestrymine and the past few months have been using infrared sauna treatments.  This combination has me a little depleted to she and I both agreed.  What does everyone think?
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649848 tn?1534633700
flyingfool... do you have a link to something that discusses T4 converting to an enzyme that might prevent cancer?  I've looked and all I can find in relation to enzymes and T4 is what we all pretty much know - that T4 is converted by the deiodinase enzymes to T3.  There are 3 enzymes - D1, D2 and D3.  D1 converts T4 to T3 to cells throughout the body; D2 converts T4 to T3 in the pituitary; and D3 converts T4 to rT3, which is exact opposite of T3 and is inactive.  
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T4 itself is a hormone, enzymes are proteins, so T4 wouldn't be converted to an enzyme, but from what I can find, it looks like it can be converted into an anti-cancer derivative called Tetrac.


"The principal secretory product of the thyroid gland, L-thyroxine (T4), is anti-apoptotic at physiological concentrations in a number of cancer cell lines. The hormone also decreases cellular abundance and activation of proteolytic caspases and of BAX and causes increased expression of X-linked inhibitor of apoptosis (XIAP). The anti-apoptotic effects of thyroid hormone largely are initiated at a cell surface thyroid hormone receptor on the extracellular domain of integrin αvβ3 that is amply expressed and activated in cancer cells." ... "By a variety of mechanisms, thyroid hormone (T4) is an endogenous anti-apoptotic factor that may oppose chemotherapy-induced apoptosis in αvβ3-expressing cancer cells. It is possible to decrease this anti-apoptotic activity pharmacologically by reducing circulating levels of T4 or by blocking effects of T4 that are initiated at αvβ3."  

Above is from the abstract.  A short, lay version:  T4 is anti-apoptotic (stops programmed cell death), and in cancer cell lines in vitro (in a dish in the lab), it blocks apoptosis (which is programmed cell death), by binding to a receptor on the outside of the cell.  You want cancer cells to die, and blocking apoptosis helps cancer cells survive.  If there is too much T4 around, chemotherapies that target and kill cancer cells may be less effective.  The authors go on to block the receptor on the outside of cells that T4 binds to with a T4 derivative (Tetrac) that binds to the same receptor, but does not block apoptosis, and when T4 can't bind because Tetrac is bound, apoptosis proceeds and the cancer cells die (which is good, you want cancer cells to die when you put drugs used as chemotherapy on them).  

As far as I can tell, T4 is the problem, causing anti-apoptosis or a pathway preventing programmed cell death.  I was curious to see what role the  T4-derivative (Tetraiodothyroacetic acid (tetrac)) plays in normal cell life, is it a hormone found in all humans?  (see below)

Here's some more of what I can find on Tetrac (which may be the T4 derivative mentioned in flyingfool's answer):

"Tetraiodothyroacetic acid (tetrac) has emerged as an antagonist of integrin αvβ3 (Bergh et al., 2005) that is being investigated as a therapeutic agent for tumors (Yalcin et al., 2010a; Yalcin et al., 2009; Yalcin et al., 2010b). The awareness of the antagonism by tetrac of the thyroid hormone receptor on integrin αvβ3, as well as tetrac’s associated anti-angiogenic properties, emerged from the discovery of the pro-angiogenic properties of T4 and T3 (Mousa et al., 2006). It has been determined that integrin αvβ3 contains a cell surface receptor site for thyroid hormone that is responsible for the pro-angiogenic effects of of T4 (Bergh et al., 2005). Tetrac is a deamination product of T4 that was shown initially to block the pro-angiogenic effect of thyroid hormone by blocking thyroid hormone binding to its cell surface receptor, integrin αvβ3 (Bergh et al., 2005). Tetrac has no thyromimetic activity at the hormone receptor site (Davis et al., 2004), but has pleiotropic effects on survival pathway gene expression in cancer cells (Glinskii et al., 2009; Yalcin et al., 2010b). Tetrac has also been shown to block the pro-angiogenic actions of VEGF and FGF-2 (Mousa et al., 2008) and platelet-derived growth factor (PDGF) (SA Mousa and PJ Davis: personal communication) on cultured human dermal microvascular endothelial cells, as well as the chick chorioallantoic membrane and mouse matrigel models of angiogenesis. This anti-angiogenic effect of tetrac on multiple pro-angiogenic molecules further increases its attractiveness as a therapeutic agent."

Lay summary: Researchers are investigating the use of Tetrac as an anti-angiogenic agent.  Angiogenesis is the formation of new blood cells, when this happens in tumors, it can fuel tumor growth and blocking blood cell formation can help kill or stop tumor growth.  Both T4 and T3 have pro-angiogenic effects.  This paper was specifically looking at Tetrac as a therapeutic to stop proliferative diabetic retinopathy, but presumably tetrac can block angiogenesis in other pathologies like cancer.  (there are a ton of papers, I'm not going to keep googling.)

So far, I've found lots of papers showing the T4 derivate Tetrac is both anti-apoptotic (allows cancer cells to die!) and anti-angiogenic (prevents new blood vessels from forming!), both are anti-cancer activities.

Most of these studies look at Tetrac as an anti-cancer agent by adding it to cells in vitro, but once I googled "thyroxine and tetrac" to find out if there is an enzyme that converts them, I found that it is found endogenously (normally) in humans at low concentrations.

This review looks at thyroid hormone derivatives (there are many):


"Tetrac, the physiological T4 metabolite found in human serum in low nanomolar concentrations [82, 112, 113, 114], has recently received major attention as a powerful ligand of the cell membrane THM receptor ανβ3 integrin [115] and as a precursor for deiodination to Triac [116]."

Was that a slightly too deep dive into Tetrac?  Probably.  Looks like tetrac is anti-cancer (anti-angiogenesis and pro-apoptosis) and that too much T4 promotes cancer growth (anti-apoptotic and pro-angiogenesis), at least in some in vitro and mouse models.  (Maybe human studies too, I did not do an exhaustive search.)

Avatar universal
That is the largest dose of T3 I have ever heard someoe report taking!

As I I suspected you have very low Free T4.  You are BELOW the range.

With such a large dose of T3 I would expected to have much higher level of FT3. You are at only 42% of the range.  Which would be a sure sign to me that you have an absorption problem.

My wife seems to have some issues with absorption also.  She has to take of almost ANY medicine she takes she has to take a significantly larger dose than the "average" person to achieve anything close to the same result.  The problem comes when Dr's get freaked out by the dose and do not want to Rx a dose that is outside the normal maximum dosages. Even if the patient is not responding. Which tends to leave my wife under-medicated which really sucks!

Your reverse T3 going below range is not really surprising.  As the ONLY way reverse T3 is manufactured is by the conversion of T4 into T3.  And because you have so much T3, the body is not converting much or any T4 into T3 since it is not needed.

T3 is used up in HOURS. So if you are taking the full 80mcg at once in the morning. It is no surprise you "crash" in the afternoon.  You can try cutting the pill in half and taking the first half in the morning, and the 2nd half about 1 to 3PM. If you take it too late you may have trouble falling asleep.

The blood level of T3 peaks about 4 HOURS after taking it. By 8 hrs most of it is gone.  So taking the 2nd dose starts ramping up in the blood as the morning dose is wearing off.  This should help you not crash in the afternoon.

Still a T3 only protocol with such a huge dose is rare.  and frankly I don't personally believe that is a good approach.

I have read that T4 breaks down into an enzyme I can't remember the name of. And its role is in part to help protect against cancer.  This enzyme is the ONLY way that the body gets or makes this specific enzyme. So having "enough" T4 in the blood I believe is important.  With such a large dose of T3 you are taking. You probably have very low T4 and thus no reserves to back up on. T4 is the inactive version but can convert to T3 if the body needs it.  But that assumes again there is T4 available for conversion.  Just another reason why I am not a big fan of T3 only. Except for a short time to "clear" out a Reverse T3 condition.  and is usually the only way we see T3 only protocol given.

heat intolerance is more  symptom of Hyper and with a large dose of T3 it may make you Hyper, if only for a few hours about 4 hours after taking it when the blood level of T3 is near or at its peak.  Splitting the dose would probably eliminate that issue, or at least minimize it some.

Fatigue is a low testosterone symptom.  I can't recall being hot is a symptom of low testosterone.  I have borderline low testosterone myself.  Not low enough YET, to consider going on T replacement.  That is a huge commitment and it is VERY tricky to get the cascade of hormone reactions that occur.  From my research, it is more complicated for hormone management in men than in women believe it or not.  So I am not in any hurry to get on testosterone replacement until I absolutely feel I have to in order to function "normally".
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The T3 is a sustained release capsule
Avatar universal
I wonder if the dosage is actually mg of an NDT. Which would be just under one grain of something like Armour.

If it is 80 mcg of T3 only that is the largest dose I have ever heard of.

T3 only is usually only used temporarily for those people who have a reverse T3 problem.  You state that your Reverse T3 is below range.  With extremely low RT3 and a huge dose of T3 only (assuming that is what you are taking) should result in a sky high Free T3 level and would imagine hyper symptoms.  Which you state you have HEAT intolerance, an indication of Hyper.  Have you checked your resting heart rate?  Do you have any other symptoms?
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Straight off of the bottle label- T3 Liothyronine 80 mcg.  No other hyper symptoms.  Mostly fatigue ( afternoon especially) , brain fog,  difficulty focusing.  My question is basically could Low T be a culprit?   When they checked it last year Free Testosterone was in the lower third of the range and SHBG was high.  Heat intolerance is a symptom of low T.
649848 tn?1534633700
I'm not real familiar with cholestrymine, so I did a little research... Sequestering agents, such as cholestrymine have a tendency to bind to medications as well as to the toxin(s) you're trying to eliminate.  The timing of taking your thyroid medication and the cholestrymine should be at least several hours apart in order to prevent your thyroid medication from being eliminated from your body or malabsorbed.  

That said, I also found this:  "The theory that all mycotoxins can be bound out of the body is long outdated. The latest research dictates not all mycotoxins can be bound, some must be dissolved, while other must be deactivated, this is a constantly evolving science

No scientific evidence is available that supports that the clinical use of Cholestyramine actually effectively binds any mycotoxins out of the body. The historical evidence supports the use of Cholestyramine as an effort to rid the human body of mycotoxins may provide no more than a placebo effect in most patients as used by certain doctors."  

I haven't had a chance to look into the effect of adding infrared sauna.

What dose of thyroid hormone medication(s) are you taking and what are your actual thyroid hormone levels?  Your doctor should be ordering tests for Free T4 and Free T3, along with TSH every time you're changing dosages of medication.  It would be helpful if you could post your actual results, along with reference ranges.  
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Free T3 3.1 (2.3-4.2)
Free T4  0.5 (0.8-1.8)
TSH 0.04 (.40-4.5)
Reverse T3 dropped below reference range
80 mcg compounded T3

These were done  7/20.  I see the Dr every 4 months.  They’re really good about going up 5mcg if it doesn’t seem effective.  I usually give it a couple months before asking to increase dosage.
It appears that your medication could be bound by the cholestrymine, but I have questions about your thyroid dosage...

80 mcg compounded T3...does that mean your compounded medication contains "only" T3?  Typically, if one is on a compounded medication, there's both T4 and T3.  If there's both, what is the amount of each?  T3 is more potent than T4, so, typically, there's less T3 than T4, but not always.  

If your compounded medication contains only T3, why is that?  It's pretty rare for someone to be on a T3 only medication.  If it's T3 only, why is it compounded and not synthetic T3, such as Cytomel or its generic counterpart, Liothyronine?

You said:  "They’re really good about going up 5mcg if it doesn’t seem effective."  Again, is this only T3 or are is there T4 involved as well?  80 mcg of T3 is a huge dose.

Sorry to ask so many questions - just need to clarify everything.
It’s  sustained release T3 only from a compounding pharmacy.  I doubt the binder is affecting T3 much since there were taken several hours apart (Evening) and symptoms haven’t really changed since taking a break from cholestrymine.
We've had a few people on compounded sustained release T3 and most find that it doesn't work very well.   I'm not sure how you take it, but it really should be taken in 2 doses 12 hrs apart, but most doctors prescribe it all to be taken at once.  

Have you tried a different type of T3 medication, such as regular release T3 or a synthetic (cytomel/Liothyronine) and/or considered adding some T4 to it?  
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