Thyroid Patients Need Enough T3 Thyroid Hormone to Resolve Their Hypothyroidism Symptoms

Going by standard laboratory test range guidelines is often NOT going to tell you whether you are correctly treated. This is especially true if all your doctor is testing is only TSH, or even TSH and FT4. If either of these is true, you need to learn more and learn fast.

I frequently hear thyroid patients tell me that their doctor believes that they are properly treated with thyroid medication because they have TSH, FT4 and FT3 results that are within the laboratory reference ranges. I utterly disagree with this view and the patients that contact me and tell me this often have terrible ongoing symptoms of hypothyroidism.

This situation gets even worse if the doctor concerned is only judging treatment based on TSH and FT4 levels!

I also disagree with the view that there are ideal levels of Free T4 and Free T3 (and even Reverse T3) that can be applied to all thyroid patients.

T3 is the potent, biologically active thyroid hormone. A single molecule of T3 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 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 nucleus of each cell and in the many mitochondria, which make 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 through the membranes into the cells. Only Free T3 (FT3) binds to the nuclear thyroid receptors, but Free T4 (FT4) can be converted into FT3 within the cells. However, some people do not convert enough FT4 into FT3. We feel well when enough FT3 is available to both the cell nuclei and mitochondria.

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 T3 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 our cells work in the way they are intended to do.

This is why it is so imperative that FT3 is actually tested and focused on during treatment in order to see it improve to a level that helps the patient with their symptoms.

FT4 does not operate genomically at all. FT4 can bind to receptors on the cell wall and acts non-genomically there. 

FT4 also enters the cells and can be converted there to either FT3 or Reverse T3 (rT3).

RT3 can be seen as a T3 ‘blocker’ or ‘hinderer’, i.e. the process that converts FT4 in rT3 can reduce the number of D2 deiodinase enzymes 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, hence high rT3 levels can be seen as a hindrance to T3 or as a partial blocker. This is especially true if the individual is still experiencing less than optimal FT3 levels and/or hypothyroidism symptoms.

So, high rT3 can be a marker that T3 action within the cells is being hindered by high levels of D3 deiodinase enzymes.

RT3 is necessary, as it provides a means of clearing excess FT4 and 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. High rT3 does not automatically mean the person will be hypothyroid though. The entire situation with an individual would need to be assessed with rT3 being only a part of the data used.

FT3, and to a significantly 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 necessary if they have a lot of FT4 that needs to be cleared by the body – it is a means of removing excess FT4. However, rT3 in itself is absolutely not necessary for the body to function well. Neither is FT4 in many cases. However, rT3 is needed if there is too much FT4 that needs clearance. To clarify this further, some people do just fine and dandy if they have only T3 and absolutely no FT4 or rT3 in their systems – I am one of these people and I know many others like me. The point is that some people process T4 well enough into enough FT3 that having some rT3 is not an issue.

However, some thyroid patients have very sensitive metabolisms and have a hard time coping if rT3 is very high. Some thyroid patients even struggle to cope with T4.

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.

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 hinder T3 from accessing the cell nuclei.

Consequently, rT3 can be viewed as one 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. Although low FT3 levels would be the most obvious marker of slow metabolism.  

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 would not be good. 

However, there are no hard and fast rules over how high is considered too high for rT3. There are no 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 the patient’s response to treatment, i.e. their clinical presentation and the way thyroid lab results change as treatment is altered.

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 levels of FT3, rT3 and FT4, for them as an individual.

Someone who has lost thyroid tissue will have lost part of their ability to convert as well as they used to 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 these problems can also contribute to issues within the cells.

To Summarise:

• We cannot measure the levels of 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.
  
• The above information is invisible to thyroid laboratory testing, or any other form of testing currently available.

We know from patient experience that:

1. Some people just cannot get well with T4 therapy (Synthroid, Levothyroxine).
   
2. Some people cannot even get well with NDT or T4/T3 – but more do well with this than with T4 alone.
   
3. A few 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 having far less (or no) FT4 and 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 an FT3 at or just above 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. For some, it is better to shift the balance towards more FT3 and far less rT3 and less FT4.

It ought to be incredibly clear from the above that FT3 absolutely has to be tested when checking thyroid laboratory tests. In an ideal situation, rT3 would be tested also. The full thyroid panel with TSH, FT4, FT3 and rT3 really does provide useful insights as well as the clinical presentation of the patient as treatment is adjusted.

Hungry for sherbet lemons analogy

The analogy I have used on forums is based on 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 too 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 they 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 just to have their lab test results somewhere in the reference range. This does not respect the individual nature of every thyroid patient. It is very sad that in many cases, thyroid patients are being deprived of having sufficient T3 to enable a high enough FT3 level in order for them to feel well again. This even happens as a general practice in some countries that have strict limits on how much T3 can be given to any patient, regardless of how low their FT3 is or how poorly they feel. All of these restrictions based on flawed assumptions need to be changed.

The bottom line is that all the thyroid treatments: T4, NDT, T4/T3 and T3-Only need to be available for use if required.

Best wishes,

Paul

(Updated in October 2022)