ArticleThe Journal of clinical endocrinology and metabolism2014
Mutations of the thyroid hormone transporter MCT8 cause prenatal brain damage and persistent hypomyelination.
Article in The Journal of clinical endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.
- Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document.Thyroid : official journal of the American Thyroid Association · 2021Guideline
- Multiscale characterization and distribution of the thyroid hormone transporter MCT8 in the adult and aged human brain.Acta neuropathologica communications · 2026Article
- Reduced thyroid hormone transport in a human placental model with inhibited MCT8.European thyroid journal · 2026Article
- T3 enhances neuronal activity in an induced pluripotent stem cell derived model of early human brain development.European thyroid journal · 2026Article
- Thyroid hormones and metabolic flexibility: tissue-specific control of energy homeostasis.Frontiers in physiology · 2026Review
- Neuron-specific expression of murine thyroid hormone transporters Mct8 and Oatp1c1 is dispensable for hippocampus-dependent neuronal functions.Frontiers in endocrinology · 2026Article
- Magnesium L-Threonate Reduces Hippocampal Amyloid-β Load without Cognitive Improvement in a PTU-induced Hypothyroidism Model in Young Rats.Molecular neurobiology · 2025Article
- Thyroid hormone promotes fetal neurogenesis.JCI insight · 2025Article
- Maternal thyroid hormone is required to develop the hindbrain vasculature in zebrafish.Communications biology · 2025Article
- Nuclear hormone receptors control fundamental processes of human fetal neurodevelopment: Basis for endocrine disruption assessment.Environment international · 2025Article
- Sciatic nerve analysis in thyroid hormone transporters Mct8 and Oatp1c1 knockout mice.European thyroid journal · 2025Article
- Toward a treatment for thyroid hormone transporter MCT8 deficiency - achievements and challenges.European thyroid journal · 2024Review
- Combined Levothyroxine and Propylthiouracil Treatment in Children with Monocarboxylate Transporter 8 Deficiency: A Multicenter Case Series of 12 Patients.Thyroid : official journal of the American Thyroid Association · 2024Article
- Brain development and bioenergetic changes.Neurobiology of disease · 2024Review
- Mapping Thyroid Hormone Action in the Human Brain.Thyroid : official journal of the American Thyroid Association · 2024Review
- Insights on the role of thyroid hormone transport in neurosensory organs and implication for the Allan-Herndon-Dudley syndrome.European thyroid journal · 2024Review
- Impaired T3 uptake and action in MCT8-deficient cerebral organoids underlie Allan-Herndon-Dudley syndrome.JCI insight · 2024Article
- Optimized Mass Spectrometry Detection of Thyroid Hormones and Polar Metabolites in Rodent Cerebrospinal Fluid.Metabolites · 2024Article
- New approach methods to assess developmental and adult neurotoxicity for regulatory use: a PARC work package 5 project.Frontiers in toxicology · 2024Article
- Neurovascular unit disruption and blood-brain barrier leakage in MCT8 deficiency.Fluids and barriers of the CNS · 2023Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 8 institutions in 5 countries.
Funding
Abstract
contextMutations in the MCT8 (SLC16A2) gene, encoding a specific thyroid hormone transporter, cause an X-linked disease with profound psychomotor retardation, neurological impairment, and abnormal serum thyroid hormone levels. The nature of the central nervous system damage is unknown.
objectiveThe objective of the study was to define the neuropathology of the syndrome by analyzing brain tissue sections from MCT8-deficient subjects.
designWe analyzed brain sections from a 30th gestational week male fetus and an 11-year-old boy and as controls, brain tissue from a 30th and 28th gestational week male and female fetuses, respectively, and a 10-year-old girl and a 12-year-old boy.
methodsStaining with hematoxylin-eosin and immunostaining for myelin basic protein, 70-kDa neurofilament, parvalbumin, calbindin-D28k, and synaptophysin were performed. Thyroid hormone determinations and quantitative PCR for deiodinases were also performed.
resultsThe MCT8-deficient fetus showed a delay in cortical and cerebellar development and myelination, loss of parvalbumin expression, abnormal calbindin-D28k content, impaired axonal maturation, and diminished biochemical differentiation of Purkinje cells. The 11-year-old boy showed altered cerebellar structure, deficient myelination, deficient synaptophysin and parvalbumin expression, and abnormal calbindin-D28k expression. The MCT8-deficient fetal cerebral cortex showed 50% reduction of thyroid hormones and increased type 2 deiodinase and decreased type 3 deiodinase mRNAs.
conclusionsThe following conclusions were reached: 1) brain damage in MCT8 deficiency is diffuse, without evidence of focal lesions, and present from fetal stages despite apparent normality at birth; 2) deficient hypomyelination persists up to 11 years of age; and 3) the findings are compatible with the deficient action of thyroid hormones in the developing brain caused by impaired transport to the target neural cells.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.