TRH Regulates TSH Bioactivity

[jimh111]

TSH has various isoforms, different molecules that differ in bioactivity. This is one reason why TSH is an inperfect marker for thyroid status, a TSH assay tells you how much TSH there is but not how active it is. Bioactvity is measured by exposing thyroid tissue to TSH and measuring activity. I'm not a biochemist so I've chickened out of the technical details.

A few recent posts have been on the topic of the 'axis', how TRH feedforward and fT3, fT4 feedback regulate TSH and thyroid hormone status.

There are a number of studies that show that TRH regulates TSH bioactivity, here are a couple:

pubmed.ncbi.nlm.nih.gov/308...

joe.bioscientifica.com/view...

Thus, TRH stimulates TSH secretion and increases the bioactivity of the TSH. I feel this is important because if patients secrete less TSH than might be expected for their fT3, fT4 levels then it is likely that this TSH has reduced bioactivity.

As an example I tried coming off thyroid hormone about a year ago. Whilst on 50 mcg L-T4 I had the following TFT results: -

TSH 2.73 (0.27 - 4.2) fT3 2.7 (3.1 - 6.8) fT4 9.7 (12.0 - 22.0)

Clearly I was hypothyroid and my TSH was too low for my fT3, fT4 levels. I've no reason to believe my thyroid is not healthy. Thus, a TSH of 2.73 should be enough to stimulate normal thyroid secretion with normal fT3, fT4 levels. This suggests my TSH has low bioactivity.

Furthermore, way back in 1999, before I'd been on high dose L-T3 for many years my results were:-

TSH 1.0 (0.4 - 5.5) fT3 4.9 (3.5 - 6.5) fT4 13.3 (9.0 - 20.0)

In this case a lot less TSH (1.0 v 2.73) was able to stimulate much more secretion, a further indication that my current TSH has reduced bioactivity.

I think it is important to remember that the assay only tells you how much TSH there is, it doesn't tell you how good it is.

[Lalatoot]

Really interesting and useful. Thanks Jimmy. Thanks too for the simple version that we can understand

[Gingernut44]

Thanks for posting - there in lies the problem when GPs and some Endos insist that TSH is the only test required!!

[TSH110]

Thank you for the post. It’s very interesting information. I had no idea there were different forms of TSH or that it can vary in bio activity.

[TaraJR]

linda96 you may like to read this post.

[dtate2016]

Thank you so much for the research. We have been indoctrinated so long by so many that TSH is the all and end-all. There are many who have had a clue (but only a clue), that this just was not so. Now the science and the voices for markers other than TSH are increasingly louder. We are going to win this battle against auto immunity, etc.! And when we do, I have a intuitive notion that it is NOT going to be that complicated.

[jimh111 in reply to dtate2016]

I'm not against using TSH provided we use it intelligently. For example, measuring TSH in newborns has saved countless thousands from cretinism but when TSH doesn't reflect the clinical presentation we must ask why. Ultimately it is the clinical response to thyroid hormone that is definitive. Sometimes the hypothalamic pituitary thyroid axis fails and in these cases TSH is of no use for diagnosis or monitoring therapy.