Going by standard laboratory test range guidelines is often NOT going to tell you whether you are correctly treated.
I have frequently heard the view expressed that there are ideal levels of Free T4 and Free T3 (and even Reverse T3). I completely disagree with this.
T3 is the potent, biologically active thyroid hormone. A single molecule of T3 active in the cell is at least ten times more potent in making the cell work than T4. Recent studies suggest that T3 may be over fifteen times more potent than T4.
T3 also binds extremely easily to the thyroid receptors in the cell nuclei. A thyroid receptor is a bit like a lock and the thyroid hormone is a bit like a key. There are multiple thyroid hormone receptors in the cell nucleus of each cell and in the many mitochondria in each cell (which makes the energy needed for the cell).
Thyroid hormone is mostly bound to protein but some is ‘free’ which means it is unbound. When thyroid hormones are unbound/free, they are able to pass into the cell membrane and then into the cell. We feel well when enough FT3 has bound to the thyroid receptors within the cells on both the cell nuclei and mitochondria.
Free T3 (FT3) operates genomically at the cell nucleus, which means that it has the effect of making some genes ‘go to work’ and begin their process of making proteins. The way it does this is through something called ‘gene transcription’, but that is beyond the scope of this blog post. Just think about it as the T3 affecting the cell nucleus in the most profound way it can, in order to make the cell metabolism run faster and more effectively.
FT4 does not operate genomically at all and its effect is much weaker on the cells – not 3-4 times weaker as sometimes is stated but at least 10 times weaker than FT3. FT4 also binds to receptors on the cell wall and can act non-genomically there.
FT4 also enters the cells and can be converted there to FT3 or rT3.
Reverse T3 (rT3 is a ‘T3 blocker’), i.e. it reduces the number of D2 deiodinase enzymes somewhat and thus lowers T4 to T3 conversion levels in those people with T4 in their body (from the thyroid gland or from thyroid medication containing T4). RT3 is converted from T4 by D3 deiodinase enzymes. High levels of D3 deiodinases are known to hinder the T3 hormone from binding to receptors in the cell nuclei.
So, high rT3 can be a marker that T3 is blocked.
RT3 is necessary, as it provides a means of clearing excess FT4 and for lowering metabolism when needed. RT3 slows metabolic rate by lowering T4 to T3 conversion. When rT3 is being produced at high levels in someone with a lot of T4, this means the T4 is being converted to rT3 and not to FT3, and so this is a marker that metabolism may be being slowed down.
FT3, and to a far lesser extent FT4, speed metabolic rate up.
RT3 is not a poison and it does not directly block T3 or stop T3 binding to the thyroid receptors – this is very misunderstood by a lot of thyroid patients and some doctors. In fact, for most people, rT3 is very necessary.
However, some thyroid patients have very sensitive metabolisms and have a hard time coping with high rT3. Some thyroid patients even struggle to cope with T4 (perhaps due to the rT3 that inevitably comes with it).
So, rT3 cannot bind to the nuclear receptors but can bind to the receptors in the cell wall. High rT3 levels will also cause fewer D2 and D1 deiodinase enzymes to be produced – so less conversion from T4 to T3.
RT3 tends to lower the conversion to T3 but does not stop T3 binding to the thyroid receptors at the cell nuclei.
However, as rT3 rises, as a result of poorer conversion to T3, the D2 and D1 conversion enzyme levels fall, and the D3 enzyme rises. D3 deiodinase actually does stop T3 from accessing the cell nuclei.
Consequently, rT3 does have some minor negative effects and can be viewed as marker that metabolism may be slowing. The real blocker of T3 is the D3 deiodinases and they may well be high if rT3 is very high.
If the amount of rT3 is too high for the person, this may indicate slowing metabolism. If rT3 is excessively high, the individual thyroid patient may simply not have enough useful FT3 effect at the cell nucleus, i.e. it might be blocked due to the D3 enzyme. Most likely though T3 levels will have fallen due to the effect on having lower D2 and D1 deiodinase enzymes.
FT4 has to be converted to enough FT3 to be of any use. If it is converted to too much rT3, there will be less FT3 and that won’t be good.
However, there are no hard and fast rules over how high is considered too high for rT3. There are rules about what the ideal levels are for FT3 or FT4 either. Nor is there a good or bad FT3/rT3 ratio. Good judgement has to be used, looking at patient response to treatment.
Every individual thyroid patient needs his or her levels to be where they need to be for them. Just having thyroid laboratory test results within the reference range is no guarantee that the person is well!
A healthy person will have good intracellular actions of FT3, rT3 and FT4, for them as an individual. But we cannot measure these with any existing laboratory test.
Someone who has lost thyroid tissue will have lost part of their ability to convert well from T4 to T3. If someone has one or both of the gene defects that affect T4 to T3 conversion (DIO1 or DIO2 gene defects), they will also potentially have worse T4 to T3 conversion.
Other problems may also exist for the individual that makes their thyroid hormones less effective than they were when they were healthy, and that also contribute to issues within the cells.
- We cannot measure the levels of the thyroid hormones within the cells. A thyroid blood test is just a measure of what is in the bloodstream.
- We cannot see the exact intracellular conversion rate and what level of FT4, FT3 and rT3 exists within the cells.
- We cannot see how well the hormones are transported into the cells, nor how well they bind to the receptors.
- This critical information is invisible to thyroid laboratory testing, or any other form of testing (other than dissection, and personally I am not up for that particular measurement of my hormones!).
We know from patient experience that:
- Some people just cannot get well with T4 therapy (Synthroid, Levothyroxine).
- Some people cannot even get well with NDT or T4/T3 – but more do well with this than with T4 alone.
- Some people need T3-Only and almost no rT3 and FT4 in order to recover. This is not just about getting a high enough FT3. It is about the eradication of the FT4 and all the rT3.
In my own case, if I add any T4 to my working T3 dosage, my symptoms begin to come back (even if I increase the T3 dosage). I need a FT3 a few points over the top of the reference range to feel well. But I also need FT4 near zero and near zero rT3 and near zero TSH. I am not in the slightest bit hyperthyroid or thyrotoxic. Generalisations about a good FT4 and FT3 level can be misleading at times – for some people.
Consequently, for a few people FT4 also seems to be a hindrance. Whether this is due to the FT4 itself, or the rT3 it can create, I do not know for sure. I suspect that in my case, when I add any T4, I make more D3 enzymes that block the ability to get enough T3 to the cell nuclei. I also think any rT3 hinders my own system. But this is my own speculation on seeing the behaviour of my own system over twenty years.
For some it is better to shift the balance towards more FT3 and far less rT3 and less FT4.
Hungry for sherbet lemons analogy
The analogy I have used on forums is based in a shop selling sweets/candy for children. It is not a perfect analogy – but it gets the point across.
Imagine there are three groups of kids.
The group that YOU are in is really keen to buy some sherbet lemons in the sweet shop. The sherbet lemons represent successful binding with cell receptors.
A neighbouring, but friendly group, also wants to buy some sherbet lemons.
However, the bullies from the next town have turned up, and they want to buy some also.
The three groups are all there in the sweet shop.
You have to have enough presence in the sweet shop with all of your mates in your group, to have a chance of getting the attention of the 4 people serving behind the counter.
The bullies (if they turn up in numbers) will just elbow you and jostle you and your mates out of the way – these are like rT3. You hope that you do not have too many of them there.
The neighbouring friendly group are OK, but they have the ability to get in the way, and some might get converted into members of the bullies gang.
If you really need to get those sherbet lemons for all of your mates, you really do not want many of the neighbouring friendly kids turning up, as they can interfere and possibly even join the rival gang – they are like FT4.
Your group (the FT3 kids) really need to be dominating in numbers, if you are really hungry for sweets and want to buy a lot.
The takeaway is that we each need enough T3, for us as individuals, in order to feel well
Healthy people with perfectly normal thyroid hormone function can tolerate the normal levels of the other hormones. It is Ok to have some bullies (rT3), and a good number of neighbouring friendly kids (FT4), even if they convert to a few more bullies. This is because the normal kids (FT3) are not so desperate for sherbet lemons (getting and being active at the receptors in the cells).
The trick is working out what each thyroid patient is, and if the are a ‘desperate for sherbet lemons kid’ or not?
All thyroid patients are different and these differences can be quite significant. We are all unique and need unique solutions that suit us all as individuals.
So, doctors and endocrinologists treating thyroid patients, need a full toolkit of all the different thyroid therapies in order to choose the right solution for the individual.
Doctors and endocrinologists also need to stop thinking of thyroid patients as all being the same and needing to just have their lab test results somewhere in the reference range – this does not respect the individual nature of every thyroid patient!
All the thyroid treatments: T4, NDT, T4/T3 and T3-Only need to be available for use if required.
(Updated in November 2019)