Fetal exposure to high maternal thyroid hormone (TH) levels causes central resistance to TH in adult humans and mice

Yet another reason that we each need to be considered and treated as the individuals we are - with all the variations that implies.

J Clin Endocrinol Metab. 2017 Jun 6. doi: 10.1210/jc.2017-00019. [Epub ahead of print]

Fetal exposure to high maternal thyroid hormone (TH) levels causes central resistance to TH in adult humans and mice.

Srichomkwun P1, Anselmo J2, Liao XH1, Hönes GS3, Moeller LC3, Alonso-Sampedro M1, Weiss RE4, Dumitrescu AM1, Refetoff S1,5.

Author information

1 Departments of Medicine.

2 Department of Endocrinology and Nutrition, Hospital Divino Espírito Santo, 9500-370 Ponta Delgada, Azores-Portugal.

3 Department of Endocrinology and Metabolism, University Hospital Essen, University of Duisburg, Essen 45122, Germany.

4 Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.

5 Pediatrics and Committee on Genetics, The University of Chicago, Chicago, IL, 60637, USA.

Abstract

Context:

Fetuses exposed to the high thyroid hormone (TH) levels of mothers with resistance to thyroid hormone beta (RTHβ), due to mutations in the THRB gene, have low birth weight and suppressed TSH.

Objective:

Determine if such exposure to high TH levels in embryonic life has a long-term effect into adulthood.

Design:

Observations in humans with a parallel design on animals to obtain a preliminary information regarding mechanism.

Setting:

University research centers.

Patients or other participants:

Humans and mice with no RTHβ exposed during intrauterine life to high maternal TH levels from mothers who were, nevertheless, euthyroid due to RTHβ. Xοʋτρολσwere humans and mice of the same genotype but born to fathers with RTHβ αʋδμοτηερσwithout RTHβ and thus, with normal serum TH levels.

Interventions:

TSH responses to stimulation with thyrotropin-releasing hormone (TRH) during adult life in humans and male mice before and after treatment with triiodothyronine (T3). Measurements of gene expression in anterior pituitaries, hypothalami and cerebral cortices of the mice.

Results:

Adult humans and mice without RTHβ, exposed to high maternal TH in utero, showed persistent central resistance to TH as evidenced by reduced responses of serum TSH to TRH when treated with T3. In mice, anterior pituitary TSHβ and deiodinase 3 (D3) mRNAs, but not hypothalamic and cerebral cortex D3 were increased.

Conclusions:

Adult humans and mice without RTHβ exposed in-utero to high maternal TH levels, have persistent central resistance to TH. This is likely mediated by the increased expression of D3 in the anterior pituitary, enhancing local T3 degradation.

PMID: 28586435

DOI: 10.1210/jc.2017-00019

ncbi.nlm.nih.gov/pubmed/285...

Full paper behind paywall here:

academic.oup.com/jcem/artic...

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6 Replies

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  • Ha - ummm just to check as the way it's written is a little confusing for me and I'm not entirely sure about RTHβ - total guess but is this a mutation? The context seems to indicate otherwise but the conclusion reads as if they are saying those without RTHβ (as in normal) who are exposed to high maternal thyroid levels show indications of having issues with central resistance into adulthood??? Is this the same as pituitary resistance and would be indicated by high T4/T3 levels but no suppression of TSH?????? Can't access the full thing to see if detail helps make sense of it.

    Sorry I find it really difficult to add new words/medical phrases into my head but am interested as I'm sure my little one's having some sort of weird thyroid issue and my T3 levels were a little high throughout pregnancy and reading up a little more so wanted to understand it properly in case it's relevant which I don't think I am quite, kinda scratching my head a little tbh lol :-D

  • The writing is not good!

    For someone who says they find the words difficult, you don't betray that. You are spot on - as I understand.

    It would almost certainly help to have the full paper available.

  • I thought it might be written badly - or hoping lol! I understand things okay if written well and put into context but since I lost all my vocab and had to relearn, I have difficulty with slotting in new not often used words or terms into my brain/memory and haven't looked into RTHβ or central anything yet so things like this with all new words and lack of anything else, really stump me sometimes lol.

    Hmm that is interesting, I had a choice between high T3 levels or a high tsh so had to make the best decision I could at the time but this could fit her issues - better than simply hypo anyway. I'm going to try and get her tested somehow as am certain something is going on and has only had tsh looked at so far, so at least if her results come back weird like that and not obviously hypo, it might make sense to me now lol!

    Thanks for the post :-)

  • I have been wondering if central resistance might be part of this thread's issues:

    healthunlocked.com/thyroidu...

  • Gosh, yes would fit as you would expect tsh to be much lower with those levels. I remember not answering that one as couldn't work it out for myself neither to add anything possibly useful lol! I'm assuming not much you can do about it apart from treat for hyper?

  • Yes - because there is no known way of changing the sensitivity of the pituitary to thyroid hormone.