Evidence map›Paper›PMID 41159509›Full record

ArticleEuropean thyroid journal2025

Extreme resistance to thyroid hormone caused by a novel mosaic thyroid hormone receptor beta mutation.

Ferdy S van Geest, Wenjun Liao, Paul G Voorhoeve, Willemijn G Leen, Nitash Zwaveling-Soonawala, V Krishna Chatterjee, Sjoerd A A Van den Berg, Frederik A Verburg, Marcel E Meima, Erica L T van den Akker and 1 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in European thyroid journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Ferdy S van GeestAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.ORCID https://orcid.org/0000-0002-6960-5775
Wenjun LiaoAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Paul G VoorhoeveDepartment of Pediatrics, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
Willemijn G LeenDepartment of Neurology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
Nitash Zwaveling-SoonawalaDepartment of Pediatric Endocrinology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.ORCID https://orcid.org/0000-0003-0318-5541
V Krishna ChatterjeeWellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK.ORCID https://orcid.org/0000-0002-2654-8854
Sjoerd A A Van den BergAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Frederik A VerburgDepartment of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Marcel E MeimaAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.ORCID https://orcid.org/0000-0002-5392-0519
Erica L T van den AkkerDivision of Endocrinology, Department of Pediatrics, Erasmus MC-Sophia Children's Hospital, University Medical Center, Rotterdam, The Netherlands.
W Edward VisserAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.ORCID https://orcid.org/0000-0002-5248-863X

Funding

Wellcome TrustWellcome Trust 210755/Z/18/Z
6 · The paper itself

Abstract

Background: Patients with resistance to thyroid hormone β (RTHβ) show elevated thyroid hormone concentrations with non-suppressed thyroid-stimulating hormone (TSH) concentrations and large phenotypic variability. Triac therapy has been successfully applied in some patients. Mosaic mutations causing mild RTHβ have been reported three times so far. Patient: We present a case of severe RTHβ caused by a mosaic frameshift mutation in the thyroid hormone receptor β (p.R438Lfs445X). Methimazole and Triac combination therapy was commenced at the age of 8 years, resulting in a substantial decrease in free T4 concentrations and an increase in TSH concentrations (follow-up duration of >18 months). His extreme agitation, motor restlessness, weight, and some motor and communication skills improved. The mutation was fully unresponsive to stimulation with T3 in in vitro and ex vivo analyses. Conclusion: The p.R438Lfs445X mutation leads to a severe phenotype of RTHβ. Mosaicism might underlie a subset of patients with the clinical phenotype of RTHβ. Combined methimazole/Triac therapy had beneficial effects on several thyrotoxic features.

Indexed as

Frameshift MutationMosaicismThyroid Hormone Receptors betaThyroid Hormone Resistance SyndromeAntithyroid AgentsChildHumansMaleMethimazoleThyrotropinTriiodothyronineAntithyroid AgentsMethimazoleThyroid Hormone Receptors betaThyrotropinTriiodothyroninemosaicismresistance to thyroid hormone beta syndromethyroid hormone analogthyroid hormone receptor betaTriac

Identifiers

PMID41159509
PMCPMC12608061

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.