Effect of Thyroid Stimulating Hormone (TSH) on Conversion of T4 to T3

This post is really relevant to many thyroid patients who are trying to feel healthier by adding T4 or T3 medication to their T4 or NDT medication.

It also applies to those who simply begin any thyroid hormone treatment or make an increase in the dosage of it.

Why do so many thyroid patients feel slightly better for a few days or a week after an increase in thyroid medication  (T4 or T3), and then they feel just as bad as they did before?

The answer to this question may well be linked to the effect of TSH on the conversion of Free T4 (FT4) to Free T3 (FT3).

The tissues in our body produce deiodinase enzymes that are critical in the conversion of FT4 to FT3. 

D2 and D1 deiodinase enzymes convert FT4 to FT3.

D3 deiodinase enzymes convert FT4 to Reverse T3 (rT3).

Although rT3 itself only has a minor effect in reducing the level of D2 enzymes, it is a marker for problems. This is because when rT3 is high, there is likely to be a higher level of D3 enzymes. D3 enzymes prevent T3 from binding with receptors in the cell nuclei, i.e. they block the effect of T3.

Consequently, rT3 can be seen as a ‘T3 blocker’, but it is really the D3 enzymes that are doing this. 

The more D2 and D1 deiodinase enzymes there are, the better the conversion rate from FT4 to FT3, i.e. higher FT3. The fewer D2 and D1 dieodinase enzymes there are the lower the conversion, i.e. lower FT3.

The thyroid gland is also the biggest converter of T4 to T3 in the body. The thyroid gland produces less of its own T4 and T3 when TSH goes lower. The thyroid produces more T4 and T3 when TSH is higher.

Importantly, the thyroid also makes fewer D2 and D1 deiodinase enzymes when TSH is lower, and more enzymes when TSH is higher. 

So, the conversion rate of T4 to T3 within the thyroid gland is lower with lower TSH. The conversion rate of T4 to T3 within the thyroid gland is higher with higher TSH. 

Researchers call the process of adjusting the level of deiodinase enzymes up-regulation (making more) or down-regulation (making fewer).

What are the Implications?

What happens if a patient adds more T4 medication?

After an increase in T4 medication, the effect will usually be that the level of TSH over the next few days will tend to be lower. This effect may take several days to occur after an increase. It may only be small change in TSH, but it is likely to be significant.

Until this change in TSH occurs, the patient will have more FT4 now as a result of the increase in T4 medication. This increase in FT4 should produce more FT3. It ought to result in an improvement in well being of the thyroid patient.

However, the lowering of TSH that inevitably occurs due to the higher level of thyroid hormones, will tend to induce a reduction in the rate of conversion of FT4 to FT3.

Consequently, after a few days, or a week or so, of feeling better, the poor thyroid patient is right back where they started and feeling poorly again. Do you recognise that pattern?

This entire thesis does not apply to those patients that respond well to T4 medication, as these patients convert FT4 very well and can cope well with FT4 in their bodies.

However, for those that do not do well with T4 medication, this should go a long way to explain this phenomenon.

What happens if a patient adds some T3 medication?

Well, the same thing occurs when a little T3 medication is added alongside T4 medication.

When a thyroid patient begins to add T3 to T4 medication, the first thing that happens is that free T3 levels increase. Lo and behold!  FT3 levels rise and the thyroid patient feels better!

This is not a surprise.  This improvement can last for 3 days, 5 days or even a little longer. It rarely LASTS beyond this.

Thyroid patients often expect the improvement they feel when they add T3 to their T4 medication to LAST.  It is a top up of T3 after all …… why shouldn’t it last?

Well, the reason it never lasts is due to the control system that is in place.

The lowering of TSH that comes with the increase in FT3 level, lowers the conversion rate of FT4 to FT3.

Consequently, for those patients who rely on some T4 medication (or some natural thyroid medication or some T4  from their own thyroid gland), adding T3 medication can create an initial great result. However, this is often followed after some time by lower conversion of FT4 to FT3.

The net result is often a good improvement of symptoms followed by FT3 dropping to a level that is just as low as it was to begin with. You add T3 hormone and FT3 increases, and later you are then back to where you started. Is this a familiar pattern?

This is a frequent occurrence. It seems to occur in the majority of cases of thyroid patients who add some T3 medication to their existing T4 medication.

This mechanism is important to be aware of, and can make all the difference in getting thyroid hormone dosage correct for the person.

Excluding other common problems may be helpful. Running the full iron panel is a good idea. Having the cortisol saliva test and 8:00am morning cortisol blood test is also sensible. Testing other nutrients that might be low like B12, vitamin D etc. may also be required.

However, if adding some T3, results in a clear improvement that then disappears, one has to suspect the above mechanism is operating.

What can be done to improve things?

Do not get disheartened. You already have your clue that you need higher FT3!

Slowly increasing the T3 content of thyroid medication, using 2-4 divided doses, can frequently resolve the problems. The T3 content may sometimes be T3 or NDT (depending on which is most appropriate).

It may also be very necessary to reduce the amount of T4 based medication that you are taking and increase the T3 medication. This can switch the balance to more T3, without having the same suppressive effect on TSH.

In addition, when TSH is fully suppressed the mechanism ceases to operate (TSH cannot get lower) and further additions of T3 begin to actually add FT3.

Note: research has now shown that a suppressed TSH when on thyroid treatment is acceptable. It does not mean the person is hyperthyroid or thyrotoxic. A suppressed TSH in a thyroid patient under treatment with thyroid medication, is an entirely different situation to a patient who is not on thyroid medication.

My latest book The Thyroid Patient’s Manual covers both the mechanism described here and the research explaining that a suppressed TSH is not a concern when a thyroid patient is taking thyroid medication.

Sometimes the rT3 level of the patient is too high, and bigger reductions of T4 are needed.

It is a balancing act, but being aware of how the system works is critical. Being aware of how the mechanism works is a real help when trying to add T3 to T4 meds.

Knowledge is power! In this case it helps to set expectations, and helps patients and doctors to understand the response and what the next steps might be.

Some more things to consider

In addition to the above, brown adipose tissue (in some of our fatty tissue), also has TSH receptors, and will similarly use deiodinase enzyme up-regulation and down-regulation. So, TSH will affect conversion rate of FT4 to FT3 there also.

According to thyroid researchers, is it likely that there are other tissues with extracellular TSH receptors. The cells of the heart, fat, and bone are thought to have TSH receptors, and it is likely that more locations will be discovered over time.

There are some really interesting research studies that support this. Some easily found examples of research are:

  • “Effect of thyrotropin on conversion of T4 to T3 in perfused rat liver”
    Ikeda, K., Takeuchi, T., Ito, Y., Murakami, I., Mokuda, O., Tominaga, M., Mashiba, H.
    Life Sciences, Volume 38, Issue 20:1801-1806, 1986
    http://www.ncbi.nlm.nih.gov/pubmed/3010024

  • “Effect of TSH on conversion of T4 to T3 in perfused rat kidney”
    Ikeda, T., Honda M., Murakami, I., Kuno, S., Mokuda, O., Tokumori, Y., Tominaga, M., Mashiba, H.
    Metabolism, Volume 34, Issue 11:1057-1060, 1985.
    http://www.ncbi.nlm.nih.gov/pubmed/4058310
I mention the mechanism of TSH affecting T4 to T3 conversion and the above research my book Recovering with T3. I have also employed this understanding for many years when supporting thyroid patients.

Note: These research references are based on isolated, perfused rats’ livers and kidneys. This means that the increase in FT4 to FT3 conversion that was measured within these tissues, when TSH was injected into them, proved that conversion rate adjusted in these tissues as a result of TSH adjusting. Liver and kidney tissues are not supposed to have TSH receptors within them, so more research in this area is required.

The implications of this research fits very well with observed responses to increases of T4 medication in those patients that are not responding well to it.

I hope this information may be very helpful with thyroid patients are having their medication levels adjusted..

Best wishes,

Paul

(Updated in February 2019)

Paul Robinson

Paul Robinson is a British author and thyroid patient advocate. The focus of his books and work is on helping patients recover from hypothyroidism. Paul has accumulated a wealth of knowledge on thyroid and adrenal dysfunction and their treatment. His three books cover all of this.

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