New paper showing TSH is controlled by both T4 and T3

We've a new paper out, in which we measure the contribution of T4 and T3 in controlling TSH levels. T4 is slightly stronger in this than T3 but not by much. Also we've a first estimate of how much on average the thyroid directly contributes to T3 production overall. The first answer seems to be around 1/4 of the total production. That is, the body provides the other 3/4 by T4-T3 conversion. Therefore in patients with no thyroid the body has to work extra hard to produce the missing T3, needing more T4 to achieve it (even if the body can which for some people it can't) and therefore suppressing TSH even down to undetectable levels in some cases. Ergo, the "healthy" TSH level is inappropriate as a diagnostic for patients on T4 with little or no working thyroid.

Title -Dual control of pituitary thyroid stimulating hormone secretion by thyroxine and triiodothyronine in athyreotic patients

 Journal- Therapeutic advances in endocrinology and metabolism 8(6):83-95 · July 2017

DOI: 10.1177/2042018817716401

21 Replies

An HTML page of the whole paper can be found here :

A PDF of the whole paper can be found here :

Thanks for links humanbean.

Thank you diogenes and humanbean (for the links). Much food for thought for Hashi patients who have thyroids that are kicked to pieces and those who have had thyroidectomies. Bedtime reading to be read very slooooowly :D

I can't remember the context but I read an article recently where the author(s) stated confidently that T3 had no impact on TSH. I had never heard that theory before so was astonished.

Diogenes, has the idea that T3 has no impact on TSH been a widespread one?

I take T3 only. The more T3 I take the lower my TSH is and the less T4 I produce. But if levels of T4 were the only determinant of TSH then mine should be sky-high because I have so little T4. So I'm surprised that anyone could have thought that T3 didn't affect TSH.

Have I got the wrong end of the stick somewhere?

If some authors made such a confident statement then they'd better abandon it - I don't know of any quantitative statement about T4 and T3's relative effects on TSH made before this with any degree of certainty. I'd say that T3's effect on TSH was known but not to what extent.

Most of what I've read (and I've read more on thyroid than most humans) seems to be along the lines of 3-4 mcg of T4 having the same effect on TSH suppression as 1 mcg of T3. So T3 suppresses TSH at 3-4 times the rate of T4.

This is roughly right. Our recent paper shows that on the average the FT4 content of serum contributes about 55% of TSH suppression and FT3 about 40%. Since FT3 is only about 1/3 of FT4 in amount on average, then the molecular effect is 3 x 40/55 or about 2.3 (FT3/FT4).


What factor would you use for T3 then? For example, let's say someone's TSH was exactly where they wanted it on T4-only meds. If they were adding T3 meds to their regimen, and attempting to calculate how much T4 to remove to keep the TSH roughly identical, should they use a factor of 1 mcg of T3 having the same effect on TSH as 3 mcg of T4?

You can't calculate in that precise way. People are different as to how efficiently their bodies convert T4 to T3 in the absence of a working thyroid. They are also independently different as to how sensitive their cells are to T3. We know this because in health some people live well on half the FT3 that others need. So you can never say exactly how much T3 would be produced per second say from a given dose of T4. Nor can you relate TSH to this because again people's pituitarys differ in their sensitivity to T3 and T4. I'm afraid the whole thing boils down to personal trial and error. There are too many variables all with influences on each other.

The only thing that has ever managed to suppress my TSH completely is T3, either taken as synthetic T3 or NDT...and it does not take much T3 to achieve that, either.

Have you sent that to the ITT campaign? 😀

No, but it would be more effective if an independent person sent it.

Thank you Diogenes for this research paper. Perhaps useful to take to show a stubborn and ignorant endocrinologist!

Thank you diogenes Downloaded Kitti1 😊

Thanks, Diogenes, I will be very happy to present this to my endo at my next consultation if she persists in trying to persuade me that my TSH should be less suppressed.

That's really helpful, thank you!!!!!

Thank you for passing this on Diogenes

Helloh there. This seems to be answering my condition of why my TSH level is below range. However, my GP has referred me to the Endocrinologist but appointment is in October. I explained to my doctor that I had put back my 25mcg of thyroxine, he didn't comment. So, I am waiting for that appointment now.

Thanks for the information.

This is really good information. It leaves me with the question on what the dose of Armor thyroid should be for me. My TSH is .0035 and the range is .9 to 1.6. My T4 is mid range and my T3 is slightly high at 6.4. The range is 2.4 to 5.9. I'm on 90 MG of Armor. I feel a bit achy and a bit low energy. I was on 180MG and felt nervous and irritable and I even gained weight! Should I just pay attention to T3? If so, is it okay to be slightly high? Or should I take more T4 to help the T3 out? Thanks in advance!

My usual reply is, if you aren't feeling well on present medication, then gently (GENTLY) experiment with juggling T4 and T3 to see what transpires. FT3 is the important thing to control and perhaps you could gently lower the T3 a little and add a little T4. If you get FT3 in the high normal range and FT4 mid normal then that could be a useful endpoint. But experience must triumph over numbers.

Thank you humanbean for posting the link, and thank you diogenes for the paper and all the rigorous research you're doing. It's so good to have you rooting for us throidies.

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