Evidence map›Paper›PMID 37286550›Full record

ArticleNature communications2023

Resistance to thyroid hormone induced tachycardia in RTHα syndrome.

Riccardo Dore, Laura Watson, Stefanie Hollidge, Christin Krause, Sarah Christine Sentis, Rebecca Oelkrug, Cathleen Geißler, Kornelia Johann, Mehdi Pedaran, Greta Lyons and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
–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

14 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

24 authors.

Riccardo DoreInstitute for Endocrinology and Diabetes, Center of Brain Behavior & Metabolism, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.ORCID 0000-0001-5988-9885
Laura WatsonNational Institute Health and Care Research Cambridge Clinical Research Facility, Addenbrooke's Hospital, Cambridge, UK.
Stefanie HollidgeMRC Epidemiology Unit and Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Christin KrauseInstitute for Human Genetics, Department of Epigenetics & Metabolism, Center of Brain Behavior & Metabolism, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
Sarah Christine SentisInstitute for Endocrinology and Diabetes, Center of Brain Behavior & Metabolism, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
Rebecca OelkrugInstitute for Endocrinology and Diabetes, Center of Brain Behavior & Metabolism, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
Cathleen GeißlerInstitute for Endocrinology and Diabetes, Center of Brain Behavior & Metabolism, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
Kornelia JohannInstitute for Endocrinology and Diabetes, Center of Brain Behavior & Metabolism, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.ORCID 0000-0002-5089-7237
Mehdi PedaranInstitute for Endocrinology and Diabetes, Center of Brain Behavior & Metabolism, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
Greta LyonsWellcome-MRC Institute of Metabolic Science, Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Nuria Lopez-AlcantaraInstitute for Endocrinology and Diabetes, Center of Brain Behavior & Metabolism, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
Julia ReschInstitute for Endocrinology and Diabetes, Center of Brain Behavior & Metabolism, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
Friedhelm SaykInternal Medicine I, Universitätsklinikum Schleswig-Holstein, Ratzeburger Allee 160, 23562, Lübeck, Germany.
Karl Alexander IwenInstitute for Endocrinology and Diabetes, Center of Brain Behavior & Metabolism, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
Andre FrankeInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.ORCID 0000-0003-1530-5811
Teide Jens BoysenInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.
Jeffrey W DalleyDepartment of Psychology, University of Cambridge, Cambridge, CB2 3EB, UK.ORCID 0000-0002-2282-3660
Kristina LorenzInstitute of Pharmacology and Toxicology, University of Würzburg, Versbacher Straße 9, 97078, Wuerzburg, Germany.
Carla MoranWellcome-MRC Institute of Metabolic Science, Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Kirsten L RennieMRC Epidemiology Unit and Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Anders ArnerDepartment of Clinical Sciences, Lund University, c/o Igelösa Life Science AB, Igelösa 373, 225 94, Lund, Sweden.
Henriette KirchnerInstitute for Human Genetics, Department of Epigenetics & Metabolism, Center of Brain Behavior & Metabolism, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
Krishna ChatterjeeWellcome-MRC Institute of Metabolic Science, Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.ORCID 0000-0002-2654-8854
Jens MittagInstitute for Endocrinology and Diabetes, Center of Brain Behavior & Metabolism, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany. jens.mittag@uni-luebeck.de.ORCID 0000-0001-7778-5158

Funding

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

Abstract

Mutations in thyroid hormone receptor α1 (TRα1) cause Resistance to Thyroid Hormone α (RTHα), a disorder characterized by hypothyroidism in TRα1-expressing tissues including the heart. Surprisingly, we report that treatment of RTHα patients with thyroxine to overcome tissue hormone resistance does not elevate their heart rate. Cardiac telemetry in male, TRα1 mutant, mice indicates that such persistent bradycardia is caused by an intrinsic cardiac defect and not due to altered autonomic control. Transcriptomic analyses show preserved, thyroid hormone (T3)-dependent upregulation of pacemaker channels (Hcn2, Hcn4), but irreversibly reduced expression of several ion channel genes controlling heart rate. Exposure of TRα1 mutant male mice to higher maternal T3 concentrations in utero, restores altered expression and DNA methylation of ion channels, including Ryr2. Our findings indicate that target genes other than Hcn2 and Hcn4 mediate T3-induced tachycardia and suggest that treatment of RTHα patients with thyroxine in high dosage without concomitant tachycardia, is possible.

Indexed as

Thyroid Hormone Resistance SyndromeThyroxineAnimalsHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsMaleMiceMutationTachycardiaThyroid Hormone Receptors alphaThyroid HormonesHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsThyroid Hormone Receptors alphaThyroid HormonesThyroxine

Identifiers

PMID37286550
PMCPMC10247713

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Registered trials

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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.