New Insights into Thyroid Hormone Action

You are hypothyroid but that's easy, just take a little pill every day...

188,813 papers on PubMed that refer to "thyroid", and we still have researchers talking about "shed new light" and "novel insights" because they fully accept that there is much yet to be found out.

Pharmacol Ther. 2017 Feb 4. pii: S0163-7258(17)30026-8. doi: 10.1016/j.pharmthera.2017.02.012. [Epub ahead of print]

New Insights into Thyroid Hormone Action.

Mendoza A1, Hollenberg AN2.

Author information

1Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.

2Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. Electronic address:


Thyroid hormones (TH) are endocrine messengers essential for normal development and function of virtually every vertebrate. The hypothalamic-pituitary-thyroid axis is exquisitely modulated to maintain nearly constant TH (T4 and T3) concentrations in circulation. However peripheral tissues and the CNS control the intracellular availability of TH, suggesting that circulating concentrations of TH are not fully representative of what each cell type sees. Indeed, recent work in the field has identified that TH transporters, deiodinases and thyroid hormone receptor coregulators can strongly control tissue-specific sensitivity to a set amount of TH. Furthermore, the mechanism by which the thyroid hormone receptors regulate target gene expression can vary by gene, tissue and cellular context. This review will highlight novel insights into the machinery that controls the cellular response to TH, which include unique signaling cascades. These findings shed new light into the pathophysiology of human diseases caused by abnormal TH signaling.

Copyright © 2017. Published by Elsevier Inc.

PMID: 28174093

DOI: 10.1016/j.pharmthera.2017.02.012

Sadly, the full paper is behind a high paywall.

23 Replies

  • I'm assuming the HPT axis is only "exquisitely modulated to maintain constant TH" in "normal" (hate that word) healthy individuals which I'm not ;-)

    Another good paper to show GP'S why they shouldn't panic over my suppressed tsh. It's a long road but I'm aiming for a referral to new endo and a trial reduction of levo with some t3 added in. So far got couple weeks wait to see new gp. In meantime I'm doing ok but no longer working or exercising (or doing much housework!) so that's not good for health either.

    Thanks for all your papers you post, I find them helpful reading.

  • Fine if you have a thyroid but if you dont what use is the TSH test that most doctors use?

  • Glynisrose,

    TSH responds to the levels of T4 and T3 in your system. It doesn't matter whether the thyroid gland is there or not.

  • Quite agreed, Clutter.

    I don't think the paper is advocating targetting TSH.

    They (authors of the paper) actually recognise that the processes that transport thyroid hormone from the bloodstream and everything that happens thereafter is of the utmost importance. Having acceptable thyorid hormone levels in the blood seems a necessary precursor to everything else. If the rest of the processes don't work proeprly, though, then it isn't enough.

  • Exquisite = "beautiful and delicate". However I assume they are using it with the secondary meaning of "highly sensitive and discriminating".

  • I hate that word "exquisite", probably because I've come across it in books in the phrase "exquisite torture".

  • I'm glad you said that. I too find it an odd choice for the same reason.

    The other definition is "intensely felt" but I was hesitant to suggest that torture was on my mind.

    I'm recovering from another bout of vertigo and I have to watch what I say: the self-censoring tends to go a bit!

  • Glad use of that word was noticed!

    Funny how they love the "exquisite" sensitivity of the TSH test, as well.

    Does anyone remember Masochism Tango by Tom Lehrer?

  • I've never heard of it before, but it was worth listening to! :)

  • I know the Vatican Rag and Poisoning Pigeons in the Park, but will have to look that one up.

  • I did wonder if people would be curious about my choice of reading material. But I don't read weird books, so I have no idea where I've come across the phrase, I just know that I have! :D

  • What are "weird" books? ;)

  • The only "weird" books I've read are SF&F, but I don't think that's what you meant. ;)

  • SF&F isn't weird. I read those! :)

  • I did wonder if you meant fifty shades of Grey hb 😊

  • Thanks for posting helvella - if I understand the synopsis right it means that blood levels of thyroid hormones are not a good indicator of hormone levels in the cells.

    I have been pondering on this recently, because on paper (according to my latest blood tests) I should be practically hyperactive and although I am feeling better and my symptoms have improved, they have not improved to the extent one might expect.

    My T3 is 6.5 in a range with a max. of 6.8 yet my weight remains fairly static and my temperature has not changed and my blood pressure is still on the low side.

    There must be an explanation somewhere.

  • But those aren't symptoms of anything, do you have other symptoms?

  • Well we disagree mistydog. As I said feeling better as most symptoms have lessened, but still feel that my metabolism is slow evidenced by slow pulse, low blood pressure and low temperature. Still not lost much weight. Sorry if those symptoms don't suit your idea of hypothyroidism!

  • Obviously you don't feel well, but are those things making you feel unwell? I am just trying to help?

  • It's more than that with my now high in range T3, I would have expected these indicators to have moved to a more optimal level i.e. show clearly that the meds are working.

    I read this book today 'Impaired Thyroid Hormone sensitivity' and wondered whether this explains it. I possibly need high dose T3......

    Just trying to understand and get answers. Thank you for your interest 😊

  • Hope you can get some.

  • Have you seen this:

    (Or is that what you were referring to?)

  • I hadn't seen that. Thanks for posting helvella The book I was referring to jwas written by one of the members on here and is a more accessible version of the technical info in the link you provided.

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