Mutation of Thyroid Receptor alpha 1

Mutation of Thyroid Receptor alpha 1

Have you got:

o... low (F)T4,

o... high T3,

o... low rT3 (not that you would know because it is never tested),

o... normal TSH serum levels,

in combination with growth retardation, delayed bone development and constipation?

This paper (only the abstract is available to us mortals) might be of profound interest.

Published online before print April 30, 2013, doi: 10.1210/jc.2013-1050

The Journal of Clinical Endocrinology & Metabolism April 30, 2013 jc.2013-1050

Clinical phenotype of a new type of thyroid hormone resistance caused by a mutation of the TRa1 receptor; consequences of LT4 treatment

Alies A. van Mullem, Dionisios Chrysis, Alexandra Eythimiadou, Elizabeth Chroni, Agathocles Tsatsoulis, Yolanda B. de Rijke, W. Edward Visser, Theo J. Visser and Robin P. Peeters

Abstract

Context Recently, the first patients with inactivating mutations in TRa1 have been identified. They have low (F)T4, high T3, low rT3 and normal TSH serum levels, in combination with growth retardation, delayed bone development and constipation.

Objective The aim of the current study was to report the effects of levothyroxine (LT4) treatment on the clinical phenotype of two patients (father and daughter) with a heterozygous inactivating mutation in TRa1.

Setting and Participants Both patients were treated with LT4 for the last 5 years. To evaluate the effect of LT4 treatment, LT4 was withdrawn for 35 days and subsequently re-initiated. Data were collected from medical records, by re-analysis of serum collected over the last 6 years, and by a detailed clinical evaluation.

Results Treatment with LT4 resulted in a suppression of serum TSH, normalization of serum (F)T4 and rT3, whereas T3 levels remained elevated in both patients. In addition, there was a normalization of the dyslipidemia, as well as a response in serum IGF1, SHBG and creatine kinase in the index patient. All these parameters returned to pre-treatment values when LT4 was briefly stopped. LT4 also resulted in an improvement of certain clinical features, such as constipation and nerve conductance. However, cognitive and fine motor skill defects remained.

Conclusion This study reports the consequences of LT4 treatment over a prolonged period of time in two of the first patients with a heterozygous mutation in TRa1. LT4 therapy leads to an improvement of certain but not all features of the clinical phenotype.

jcem.endojournals.org/conte...

Rod

Image is Structure of the THRA protein.

10 Replies

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  • Thanks...some day some time all these studies will come together and be heeded and acted on.. Your research much appreciated.

  • What really strikes me about this is the phrase LT4 therapy leads to an improvement of certain but not all features of the clinical phenotype.

    This is, surely exactly what a proportion of people have been saying, well, forever. Levo helps with xxx but I still suffer yyy. Liothyronine helps with zzz but still get aaa....

    One day...

    Rod

  • By some strange default when antidepressants are no longer lucrative or an accepted/acceptable option..maybe then. Got half an ear on Glastonbury will read again tomorrow.

  • Yet another variant of thyroid dysfunction. The more we learn, the more stupid appears the comment most patients have heard from their doctors: "The thyroid is very simple, and all you need is a little pill"

    No, doctor, it is NOT simple. And a little pill just won't do.

    Thanks for this, Rod.

    Marie XX

  • Thanks Rod,

    Good bit of research :) The lengths we have to go to prove something patients and certain docs have been saying for years!! Shame they don't apply the adage 'the proof is in the pudding' cos if they did they would have to open their door much wider than levothyroxine....

    maybe....one day.....when they don't feel they have to keep protecting the arguments for the current status quo.....lol

  • Thank you very much for this Rod. It partly answers my question some time ago. The list of blood test results does not mention the Free T3 level. I would be interested to know this.

    Best wishes and many thanks for all your work.

    Jenny

  • As I understand, Free T3 and Total T3 do tend to go together quite well. But if anything affects the capacity of the binding proteins in the blood that can cause Total T3 changes.

    You could always email the authors? They might not respond, but they might.

    Rod

  • Hi guys

    Essentially if you are a patient you can request it, the inof is on this page:

    endojournals.org/site/misc/...

    You need this info for requesting it: Clinical phenotype of a new type of thyroid hormone resistance caused by a mutation of the TRa1 receptor; consequences of LT4 treatment

    JCEM (J Clin Endocrinol Metab. 2013 Apr 30)

    pages 2013-1050

    Afraid I can't access it at my research institue and they will know from my IP address that I am at a research charity.

    Cheers,

    Nora

  • I thought the paper was on-line only until publication date?

    Will do a patient access request anyway. :-)

    (Still waiting for the last two I asked for - now what papers were they... ?)

    Rod

  • Many thanks for this.

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