Successful every-other-day liothyronine therapy for severe resistance to thyroid hormone beta with a novel THRB mutation; case report

We see so few papers on resistance to thyroid hormone, it seems appropriate to post when one does arrive.

I have no explanation whatsoever for every-other-day liothyronine therapy being potentially worth trying. But it does make me think of the fact that Dr Lowe went down the one-dose-a-day route - very much against the little-and-often approach often suggested.

BMC Endocr Disord. 2016 Jan 12;16(1):1. doi: 10.1186/s12902-015-0081-7.

Successful every-other-day liothyronine therapy for severe resistance to thyroid hormone beta with a novel THRB mutation; case report.

Maruo Y1, Mori A2, Morioka Y3, Sawai C4, Mimura Y5, Matui K6, Takeuchi Y7.

Author information

1 Department of Pediatrics, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, 520-2192, Japan. maruo@belle.shiga-med.ac.jp.

2 Department of Pediatrics, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, 520-2192, Japan. asamim@belle.shiga-med.ac.jp.

3 Department of Pediatrics, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, 520-2192, Japan. yori708@belle.shiga-med.ac.jp.

4 Department of Pediatrics, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, 520-2192, Japan. csawai@belle.shiga-med.ac.jp.

5 Department of Pediatrics, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, 520-2192, Japan. osawa@belle.shiga-med.ac.jp.

6 Department of Pediatrics, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, 520-2192, Japan. matsui@belle.shiga-med.ac.jp.

7 Department of Pediatrics, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, 520-2192, Japan. takeuchi@belle.shiga-med.ac.jp.

Abstract

BACKGROUND:

Resistance to thyroid hormone beta (RTHβ) is a rare and usually dominantly inherited syndrome caused by mutations of the thyroid hormone receptor β gene (THRB). In severe cases, it is rarely challenging to control manifestations using daily therapeutic replacement of thyroid hormone.

CASE PRESENTATION:

The present case study concerns an 8-year-old Japanese girl with a severe phenotype of RTH (TSH, fT3, and fT4 were 34.0 mU/L, >25.0 pg/mL and, >8.0 ng/dL, respectively), caused by a novel heterozygous frameshift mutation in exon 10 of the thyroid hormone receptor beta gene (THRB), c.1347-1357 del actcttccccc : p.E449DfsX11. RTH was detected at the neonatal screening program. At 4 years of age, the patient continued to suffer from mental retardation, hyperactivity, insomnia, and reduced resting energy expenditure (REE), despite daily thyroxine (L-T4) therapy. Every-other-day high-dose liothyronine (L-T3) therapy improved her symptoms and increased her REE, without thyrotoxicosis.

CONCLUSION:

In a case of severe RTH, every-other-day L-T3 administration enhanced REE and psychomotor development, without promoting symptoms of thyrotoxicosis. Every-other-day L-T3 administration may be an effective strategy for the treatment of severe RTH.

PMID: 26754848 [PubMed - in process]

ncbi.nlm.nih.gov/pubmed/267...

7 Replies

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  • Helvella, this does intrigue me! I have allergic reaction to thyroxine so eventually was put on lyiothyronine t3. Now, I feel so much better if I take just one dose first thing in the morning than taking 2 doses as recommended. Coincidence, not sure of course. A lot of people will not believe I could be allergic t4 and I get questioned about it all the time. I realise that the article says RESISTANCE and therefore perhaps doesn't improve symptoms on t4.

    Thank you for the article, it makes me feel less of a freak!

  • Mabsie,

    I have read about cases and it has happened to myself where T4 intolerance is reduced with the addition of T3.

    It seems once the receptors readily accommodate the T3, the T4 synethsis is enabled allowing conversion and further T3.

    How or why this happens I don't know and am not suggesting you change your meds.

    Flower

  • Thanks Flower. After the very severe allergic reaction I had to t4 I'd be reluctant to try again. I had an anaphylactic reaction. Fortunately it was done under control in hospital. X

  • Helvella.

    I haven't heard of the gene mutation this poor little girl has.

    I understand most THR seen is down to RT3 and therefore rectifiable but to have intolerance down to unchangable genetics must be a nightmare.

    I don't understand why the first test results are all in differing measurements ? . .

    How do you interpret the FT3 to TT3 ?

    Interesting that inspite of having this unfortunate genetic makeup she was able to initially benefit from the supplementation of T4 before a dramatic decline ? Sound familiar ?

    I hope her CCG don't withdraw her meds as I hear they don't always take genetic variations into consideration ... ( Lol .. I know, really poor joke.)

    At least this report has a happy ending.

    Flower

  • Most likely every other day T3 treatment is due to poorer T3 clearance and turnover. Thus once a day would be too much and maybe difficult to titrate.

  • Amazing she doesn't have heart palpitations on such a large dose.

  • I think it's because the cells don't take in T3 well and binding of T3 in the cells may be poor - thus what would be a fatal T3 level to normal people isn't for this patient.

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