The content of this article is extremely relevant to those thyroid patients who plan on introducing some T3 into their treatment.
Working with so many thyroid patients over the past fifteen years has made me very aware of some of the pitfalls that can happen when someone introduces T3 doses. This is especially true when they already have T4 present in their system. The T4 may be there because they have some remaining thyroid function. However, it is more usually because they are already on some T4 medication but remain with many symptoms of hypothyroidism. They may also have low in the range FT3 and possibly high rT3. So, the patient or their physician or practitioner decide to introduce some T3. I am also assuming that these patients have tested other hormones and nutrients before adding in any T3. This basic testing is outlined in all my books, and it includes things like cortisol, iron, B12 etc.
When T3 is first being introduced, it is best to start with one or two doses of 5 mcg. If I am providing advice, then if the thyroid laboratory test results appear to suggest extremely poor conversion from FT4 to FT3, then I often encourage the patient to reduce the T4 content of their treatment at the same time as adding T3. Some very nervous patients, sometimes want to begin with smaller doses than 5 mcg.
Whatever the starting T3 dose sizes are, the range of response to them can be quite varied by patient:
- Of course, in some cases, even small introductory doses of T3, do immediately benefit the thyroid patient. For many, this benefit can continue and the T3 dosage may be slowly titrated until an effective T3 dosage is achieved.
- In some cases, there may be some immediate benefit of adding the T3. Even small doses like 5 mcg might achieve this and it might continue. Note: this is not the most common result in my experience.
- The thyroid patient may experience some immediate benefit which lasts for a few days. This can often be followed by a relapse to their previous symptoms. The patient may have felt elated with the response but is then deflated that it is not going to work. This type of response can even occur with T3 doses of 10 mcg or more, i.e., there is improvement but after some days this improvement vanishes.
- For some thyroid patients, small T3 doses like 5 mcg or 2.5 mcg may elicit no response at all in the symptoms or signs of the person.
- The last scenario is that, when the small doses of T3 are introduced, the thyroid patient’s health further deteriorates. Even T3 doses of 5 mcg, 2.5 mcg or less, can cause this in some patients.
Existing symptoms can worsen. New hypothyroid symptoms can appear. These thyroid patients often erroneously conclude that they are in some way allergic to T3, or will never be able to tolerate T3.
I have now introduced the type of response that can come when someone starts using T3 in small doses and why larger doses are often needed. Note: I understood the reason behind this issue, before I even wrote my Recovering with T3 book, which was released in 2011.
Here are a couple of extracts directly from Recovering with T3.
The first extract is from Chapter 14 in Recovering with T3 and it concerns the Lessons that I Learned on Divided Doses of T3:
“LESSON #7: WAVES OF T3
For each divided dose of T3, I discovered that there was definitely a ‘threshold level’ that had to be exceeded before any real benefit was experienced from the hormone. As I increased the dose beyond this threshold level, the effects were greater. If I exceeded the threshold too much, then I experienced symptoms of tissue over-stimulation. In the early years, my threshold level tended to be lower as the day progressed, this was due to some remaining issues with hypocortisolism, which eventually disappeared. So, later in the day I required lower doses of T3 to achieve the same effect. I often use a specific analogy to describe to other people how T3 appears to behave:
‘Imagine a sandy beach, which is sheltered from the sea by large rocks. Only a wave that is large and powerful enough, is capable of striking the rocks and sending a spray of seawater over them, to drench the sand beyond.’
Each T3 divided dose is like a wave, the intra-cellular targets of T3 are akin to the beach and the rocks represent all the possible bio-chemical barriers that the T3 has to overcome. I do not believe that this is just some idle analogy. This is definitely how T3 replacement appears to feel and work within my own body.”
The second extract is from later in the same chapter of Recovering with T3:
“I have also discovered that the contents of an individual T3 dose needs to be delivered at once. If I attempt to take 4 quarters of a single T3 divided dose spread over two hours then it is not effective at all. Lots of small doses of T3 do not work well. This fits well with the wave analogy above – you need a big enough ‘wave’ to be effective.”
So, I have been aware of the potential for issues when introducing T3 and for using small doses of T3 for a very long time. In fact, this knowledge has really assisted me to help thyroid patients achieve safe and effective T3 or T3/T4 dosing strategies.
How the regulation of T4 to T3 conversion underlies the problems with introducing T3, and the use of small T3 doses
Thyroid patients who have some remaining thyroid function, or those already using T4 medication, will have some T4 in their systems. The conversion of FT4 to FT3 is not done at a fixed rate. The conversion rate is variable and regulated. It can vary from patient to patient, and it can vary throughout the day, even for the individual.
Conversion from FT4 to FT3 is performed by the D1 and D2 deiodinase enzymes. Conversion from FT4 to rT3 is performed by the D3 deiodinase enzymes. When the number of D1 or D2 enzymes increase, FT4 to FT3 conversion rate gets higher and FT3 rises. When the number of D1 or D2 enzymes decrease, FT4 to FT3 conversion rate lowers and FT3 can fall.
Similarly, the number of D3 deiodinase enzymes are regulated. When higher numbers of D3 exist, FT4 to rT3 conversion increases. With lower numbers of D3 enzymes, the FT4 to rT3 conversion rate lowers.
The cells in our body respond to the current situation and can regulate the conversion of FT4 to FT3 and FT4 to rT3. The clearance of thyroid hormones is also under regulation.
TSH is used by some of our cell types to regulate conversion from FT4 to FT3, and FT4 to rT3. The level of FT3 is also used by our cells to regulate conversion. So, a lowering of TSH, or an increase in FT3 will cause lower conversion from FT4 to FT3. Increasing TSH, or lowering FT3, will cause higher conversion from FT4 to FT3. A similar thing occurs with FT4 to rT3.
I explain the above in more detail in this blog post:
https://paulrobinsonthyroid.com/more-t4-t3-thyroid-medication-might-not-always-raise-patients-ft3-levels-in-thyroid-hormone-treatment/ – so please refer to this blog post for more technical details, including research references at the end, that back up the information on FT4 to FT3 conversion being variable and regulated.
Having introduced the mechanism involved, let me now explain what can happen when small T3 doses are used.
Doses that are as small as 2.5 mcg, or 5 mcg, can be especially problematic. When someone takes a T3 dose, not all of it will be absorbed from the small intestine to the bloodstream. Not all of this absorbed T3 will become Free T3 (FT3). Moreover, not all of the absorbed FT3 will make it to the cells and to the cell nuclei.
Therefore, very small doses of T3, will not provide very much extra FT3 to the cell nuclei. With tiny doses of 5 mcg or 2.5 mcg of T3, or less, you often do not know what the effect will be on the regulation of conversion rate of FT4 to FT3; whether it will result in more, the same or lower FT3 after the small T3 dose has been taken.
In some cases, a thyroid patient who may already feel very ill, might take a small T3 dose of 2.5 mcg or 5 mcg and the nett result may be that they end up with lower FT3 within hours of taking it.
I know of patients who were extremely hypothyroid to begin with, that felt even worse after the small dose was taken. Even 2.5 mcg doses of T3 can do this to some.
Now, whilst a very small number of thyroid patients actually seem to have genuine issues tolerating T3, most of the patients who react badly to small T3 doses, have actually simply become more hypothyroid. Elevated heart rate can also be caused due to the strain of lower FT3 on the heart – which can make the patient think that they are hyperthyroid!
In the vast majority of cases, the poor responses are related to the lowering of the existing FT4 to FT3 conversion rate due to taking the T3 dose. The T3 dose has been far too small to raise FT3 very much but the conversion rate has been down-regulated and the end result is worse FT4 to FT3 conversion than it was before taking the T3 dose.
What are the typical reactions of the patient who has tried taking small doses of T3 and had a poor response?
It is easier to deal with those patients who have some immediate improvement with introductory T3 doses. Even if this improvement vanishes within days, they may read my books, or talk to me and realise that this is actually an encouraging sign that T3 may well work for them. These patients will have seen the glimmer of hope that this is going to be the way forward for them. Reading my books will have explained how to proceed next – which is often to lower any T4 medication further and slowly increase the T3 dosage.
However, if the response of the patient is very bad indeed, the patient is, of course, reluctant to explore the use of T3 again. Some patients can become more hypothyroid after taking small doses of T3. As FT3 levels fall, various symptoms can occur. If you review the range of symptoms associated with hypothyroidism that I describe in this blog post:
https://paulrobinsonthyroid.com/symptoms-of-hypothyroidism/ , then almost any of these might be induced. However, with lower FT3 levels, the cardiovascular system can be under more strain and this can raise heart rate. So, an elevated heart rate after a small T3 dose can appear to be the polar opposite of being more hypothyroid. The patient can think they are having a hyper or allergic response to the T3.
Some patients may continue to use very tiny T3 doses, because these do not seem to make their symptoms worse. I know of people who just end up using small doses such as 1 or 2 mcg of T3, just because they feel that this is all they can cope with. These patients may simply think that they are not able to tolerate T3, or they are allergic to it. Once they have this view, it can be very difficult to shift it.
What solutions are usually effective when a thyroid patient has experienced difficulty with small doses of T3?
For those who initially experienced some benefit which then quickly disappeared, a lot depends on whether they have read my work. These patients are unlikely to meet any doctors, endocrinologists or other practitioners who would explain that this is actually a good sign to them. As I have explained above (see the first blog post referenced), and in my books, the solution for these people is usually to reduce their T4 medication a LOT, combined with slowly titrating the T3 dosage up. My Recovering with T3 book protocol can be used to manage the T3 dosing safely and effectively. Once the T4 medication is not high enough to convert to a lot of rT3, and the T4 medication cannot have a big impact on lowering FT3 levels through worse conversion, the T3 dosage can be raised enough to provide good FT3 levels. When FT3 is high enough from the T3 medication, then any lowering of FT4 to FT3 conversion will no longer make significant impact. The patient can get well.
However, for the thyroid patients who have been struggling to use anything other than the tiniest of doses without side effects, things can be far more difficult. The solution for these people is likely to be not only a reduction in the amount of T4 medication being used, but also an increase in the T3 doses to be used. Of course, when someone has had a bad response to 2.5 or 5 mcg of T3, the prospect of raising the T3 dose size usually makes them think that the response will be even worse. So it is a difficult, but necessary, step to take.
The T4 medication would need to be reduced. This would be especially important if the FT4 was already high and/or rT3 was high. I would not want the FT4 to FT3 conversion to deteriorate significantly when more T3 was added. I also would not want FT4 to convert to more rT3. However, the patient may be too nervous to reduce the T4 medication, given that they are already feeling hypothyroid.
Larger doses of T3 would need to be used. The small doses, like 2.5 mcg or 5 mcg or even smaller ones, often fail their purpose. However, larger doses can work really well. The reason for this is that with people whose regulation of conversion rate is poised at a point ready to deteriorate, it is important to have them take enough T3 to compensate for this. In this way, FT3 is at least maintained, and may actually be increased. Only by increasing FT3 for these people who have low FT3, and remain with thyroid symptoms on T4 medication, can symptoms be alleviated.
Even 7.5 mcg doses of T3 may actually be too small for some people. The threshold at which the T3 dose size becomes such that it actually adds extra FT3 will vary by person, and is dependent on how much T4 the person is on and how badly it is converting to FT3. The over-riding point is this. It should not be assumed that, because small doses are a problem, larger ones will not work. This is a mistake that many patients and doctors make. In fact, many doctors just end the trial of T3 because of a poor response to small doses of T3.
The two-pronged attack of increasing the T3 dose size, and reducing the T4 medication, is usually quite effective in this situation. It may be the only course of action that is actually going to work, if the patient is to recover.
However, any mention of this planned approach by myself, or in my books, or articles, can be extremely difficult for the thyroid patient. After all, they have only experienced poor results when adding T3 doses like 2.5 mcg or 5 mcg or even less. They have several hurdles to overcome:
- Firstly, there is the psychological issue to get over. These people believe they are intolerant or allergic in some way to T3. This is, of course, nonsense as T3 is a natural hormone and unless there is some filler or binder in the tablet, there is not going to be any allergy. In the majority of cases, the poor response occurs regardless of the brand of T3 and can even occur with compounded T3 with almost no extraneous compounds in it. This response may have even prompted the patient’s doctor to begin suggesting that they have chronic fatigue syndrome or ME.
- Secondly, the patient may not understand the mechanism that is at work. I have now explained it here. Without an understanding of the mechanism at work, the patient will not understand why adding a small T3 dose has caused nothing but problems for them. If I am speaking to a thyroid patient, then I can explain it, and suggest one of my books or articles. But other than that, it is difficult to see how someone would take the necessary next steps, if they had not read my work, or talked to me.
- Thirdly, even when I have explained the actual reason why the patient can feel much worse after taking a small, or tiny, T3 dose, and I have outlined what the steps should be to move forward, they often remain too nervous to take those steps, as all their experience so far has been of having a poor response. They may still be frightened that larger doses will cause even worse symptoms. However, in the majority of cases, the opposite is true. Larger doses of T3 are actually the solution, when combined with less T4 medication.
Note: there are a few patients that seem to have a poor response to any form of standard T3, or even NDT. Sometimes, it is extremely difficult to ascertain why this is. One example is if mitochondrial disease is present. With mitochondrial problems the cells do not make enough adenosine triphosphate (ATP). ATP is cellular energy, needed by the cell nuclei. Taking T3 in the presence of low ATP can cause a range of bad reactions. For other patients, the problems may be due to a very fast clearance rate of T3. For these people, small doses of T3 may be cleared quickly leaving them hypothyroid, yet larger doses make them feel hyperthyroid. When patients do find that any form of standard T3 is far too difficult to use, and no root cause has been found, then trialling slow release T3 might be an option. However, this article is relevant to the vast majority who have had a poor response to small doses of T3.
Wrapping up
I have explained the types of symptoms and reactions that people can get when they first introduce T3, or add in small T3 doses. I have explained the mechanism behind this and why it can be so confusing if you do not understand how the regulation of the deiodinase enzymes works. This article, together with the blog post referenced at the start, explain the mechanism in enough detail for correct thyroid medication treatment to be applied.
I have also explained the particular issues with very small T3 doses and how these can make symptoms far worse, introduce new symptoms, or even appear to be causing hyperthyroid responses.
I finally cover the solutions that need to be applied to actually deal with the situation and introduce T3, without too many issues and with improvement to signs and symptoms. However, I also explain the particular issues faced by those patients who have experienced a bad response when using small doses of T3, or introducing T3.
Note: there can be extremely rare situations when someone has a bad response to any form of T3. One example is if mitochondrial disease is present. However, this article is relevant to the vast majority who have had a poor response to small doses of T3.
I am hoping that this article helps some of the thyroid patients who may experience these problems with small doses of T3, or a physician or practitioner who is trying to assist them. These issues do not occur for everyone but some thyroid patients do experience them and I know that it often causes them to stop using the T3. However, once the thyroid system is understood in a little more depth, then what appear to be incomprehensible responses, can actually become clear. After that, providing a better thyroid treatment is much easier.
