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Thyroid UK
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Total t4/t3 vs Free t4/t3

I know the difference between total and free tests (that total measures all levels, even those bound to proteins) so does that mean t4/t3 that is bound to proteins are unavailable to do anything? I thought t4 binds to certain proteins in order to absorb into the cell and then conversion to t3 takes place within the cell? The more I read the more confused I get. Just when I think I've got it :-(

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This is how I see things:

Most of the T4 and T3 in the blood is bound to proteins. While bound they appear to have no activity.

Some of the small amount unbound T4 and T3, will be actively transported into cells. (Indeed, it is a bit more complex because the T4 and T3 also need to be actively transported across the blood-brain barrier as well!)

Some T4 gets converted to T3 and used within individual cells. E.g hair follicles.

Some T4 gets converted to T3 and then released back into the bloodstream. E.g. liver and skeletal muscle.

I am not at all surprised you are getting confused. Doesn't everyone?

As I see it, the binding of thyroid hormones has the following effects:

It provides a way of transporting thyroid hormone round the body safely - not affecting the body it passes through.

It provides a way of storing quite a lot of thyroid hormone ready to be used wherever it is needed.

It helps to keep the levels of free thyroid hormones fairly steady.



An interesting question NJ, and one that's been on my mind since trialling an increased proportion of T3 in recent weeks.

Pardon my usual length, but it's an opportunity to link some thought and maybe draw some tentative conclusions regarding medical practice. To maybe even suggest a new direction for thyroid medical practice.

What i seem to be seeing Rod (even in the case of T3 which has such a short half life, and which delivers a fairly rapid response to dose changes) is that there seems to be a noticeable buffering effect.

As in even though T3 delivers fairly rapid responses to changes in dosage, that there is noticeably a building up of T3 reserves in the body. (presumably the bound hormone)

The T3 felt very 'peaky' and cyclical at first - perhaps because the lower quantity of T3 in the blood was almost immediately being used and perhaps rising and falling. It by now (about three weeks later) feels much more stable. As though enough of a buffer/reserve has built up so that what the body needs is always available.

This seems to tie in with the Miller School study linked by Shambles tiny.cc/iza2uw - which seems basically to say that T3 has its own independent system of buffering and control.

That while TRH and TSH are involved in the regulation of blood levels of T4 (i.e. control of the production of the precursor hormone by the thyroid) that they do not regulate the levels of plasma (blood levels) T3 - which they say is the key indicator of proper replacement.

Plasma T3 levels it seems are regulated by entirely separate means - which don't seem to be well understood. They found that inactivating an enzyme in the pituitary in specially bred mice that produced major changes in TRH, TSH and T4 did not affect T3 levels in the plasma/blood.

Pardon if all this sounds a bit obscure, but it seems like it all points towards a system where T4 (but not T3) is produced and buffered/stored/bound in response to TSH.

This buffered T4 is 'freed' - that is made available for production of T3 (conversion) etc by means i'm not familiar with (enzyme reactions etc ?) - but which it seems may be compromised in the many of us that suffer from secondary hypothyroidism.

This T3 it seems (correct me if i have it wrong) is in turn also buffered (bound with protein in the blood), and released as needed under a separate and entirely independent system of control (the finding of the above study) to deliver the plasma T3 levels required for well being.

To your point NJ. It IS horribly complex. More to the point it's very clear that TSH is not a good indicator that biologically correct levels of T3 are available where it's needed. About the best that can be said for it is that if TSH levels are OK then T4 levels may be OK - AND if that and all of the above long string of downstream systems are in 100% perfect working order we should be making available the correct quantities of plasma T3 and be well. i.e. not be hypo

We're in the end though expected to take this on trust. Worse still it's common for the medics to ignore hypo symptoms that positively and obviously suggest that we have downstream problems and most definitely are not OK...

What seems to be becoming clear is that there's an almost entirely separate system in the body that controls the buffering, activation and use of T3 - and that it's how well this is performing that determines whether or not we are hypothyroid.

The T4 system is relevant only inasmuch as it ensures a supply of the precursor hormone - but even then some of us cannot use this.

The worrying part (as recently commented by my endo) is that it seems the test methods are not available for clinical testing to determine what's happening in the T3 system.

This if true seems to point towards some potentially fairly basic conclusions - but ones with major implications for current medical/thyroid practice:

1. T4/TSH is only a reliable (?) diagnostic tool for primary hypothyroidism. i.e. problems where the thyroid is not making hormone.

2. Plasma T3 (not sure whether that's free or bound or both) is the best available 'scientific' indicator that a person is euthyroid or properly replaced. (that's not a guarantee of wellness though - because it seems that toxins and other problems can compromise our ability to use T3 effectively at the cellular level)

3. It's clinical usefulness must however be compromised by the fact that the T3 system causes plasma T3 levels to cycle significantly over the day/night cycle under the control of what sounds like multiple variables.

4. There's additionally lots of experience that suggests that we're individually quite highly variable in terms of the blood levels of hormone we need to feel well.

5. This all surely points to a scenario where:

(a) Medicine must embrace the use of T3 (where T4 is not working) in thyroid replacement.

(b) This in absence of effective other means via symptom led methods of diagnosis and optimisation of dosage in the context of co-operative doctor/patient relationships.

Thoughts anybody?




Medical Practice with regard to the total Thyroid Hormone System needs to be urgently reviewed.

The medical profession is so lobotomised, it ignores anything that cannot be described in terms of the Thyrotropin (TSH) and Free Thyroxine (FT4) 'Normal Ranges', which are regularly misapplied.

As recognised above, the TSH/FT4 Normal Ranges can only be relied upon for the positive act of diagnosing Primary Hypothyroidism.(hyperthyroidism) by virtue of the Normal Range limits being exceeded.

Given the proven inter-individuality of patients' FT4 Set-Points / Working Points; TSH & FT4 values within the 'Normal Ranges do not necessarily indicate that patients are healthy.

The simple fact of the matter is that it is unbound free fraction of T3 our FT3 which is important to our health and well-being.

I would add that our brains are on a different circuit to the rest of the body, and only T4/FT4 can cross the blood brain barrier. To be converted within the brain to T3/FT3. This can lead to L-T4 monotherapy causing an improvement in general feelings of well-being etc, whilst the rest of the body is deficient in FT3. (Low T3 Syndrome & Reverse T3 Dominance spring to mind) and both TSH & FT4 reflect 'Normal' blood serum concentrations

I must stress that low FT3 causes damage to the heart:. The mean value of the reference range for Dilated Cardiomyopathy [DCMP] is 4.0 pmol/l (In fact the UK FT3 'Normal Range' of 3.55-->5.44 pmol/l sits over the upper limit of the Danger Zone for DCMP, which is 5.4 pmol/l). I do not believe in coincidences?

Low FT3 initiates damage to the cellular structure of the heart and induces a vicious circle where low FT3 causes more damage to the heart and the thyroid system responds to protect the heart by reducing available FT3.

Yes the Medical Practices pursued in response to FT3 insufficiency require an urgent review.




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