Resistance to Thyroid Hormone Beta: A Focused Review

Παππά, Θεοδώρα; Refetoff, Samuel

doi:10.3389/fendo.2021.656551

Cited by 61 publications

(71 citation statements)

References 71 publications

(81 reference statements)

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“…Generally, a higher female predominance has been observed in cases with thyroid dysgenesis [ 11 ]. On the other hand, equal occurrences of RTH have been reported between the sexes [ 15 ]. Meanwhile, five out of the six reported cases of RTH with thyroid dysgenesis were female [ 6 , 7 , [12] , [13] , [14] ].…”

Section: Discussionmentioning

confidence: 99%

Resistance to thyroid hormone in a child with thyroid agenesis: A case report with review of the literature

Hasan¹,

Mohammed²,

Ahmed³

et al. 2022

Annals of Medicine &Amp; Surgery

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Section: Discussionmentioning

confidence: 99%

Resistance to thyroid hormone in a child with thyroid agenesis: A case report with review of the literature

Hasan¹,

Mohammed²,

Ahmed³

et al. 2022

Annals of Medicine &Amp; Surgery

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“…The clinical phenotype of resistance to thyroid hormones due to THRB mutations (52) frequently includes varying degrees of intellectual disability and hyperactivity (53)(54)(55).…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome profiling of thyroid hormone effectors in the human fetal neocortex: expression of SLCO1C1, DIO2, and THRB in specific cell types

Díez

Morte

Bernal

2021

Thyroid

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Background: Thyroid hormones are crucial for brain development, acting through the thyroid hormone nuclear receptors (TR) α1 and β to control gene expression. T3, the receptor-ligand, is transported into the brain from the blood by the monocarboxylate transporter 8 (MCT8). Another source of brain T3 is from the local deiodination of T4 by type 2 deiodinase (DIO2). While these mechanisms are very similar in mice and humans, important species-specific differences confound our understanding of disease using mouse models. To fill this knowledge gap on thyroid hormone action in the human fetal brain, we analyzed the expression of transporters, DIO2, and TRs, which we call thyroid hormone effectors, at single-cell resolution. Methods:We analyzed publicly available single-cell transcriptome datasets of isolated cerebral cortex neural cells from three different studies, with expression data from 393 to almost 40,000 cells. We generated Uniform Manifold Approximation and Projection scatterplots and cell clusters to identify differentially expressed genes between clusters, and correlated their gene signatures with the expression of thyroid effectors. Results:The radial glia, mainly the outer radial glia, and astrocytes coexpress SLCO1C1 and DIO2, indicating close cooperation between the T4 transporter OATP1C1 and DIO2 in local T3 formation. Strikingly, THRB was mainly present in two classes of interneurons: a majority expressing CALB2/calretinin, from the caudal ganglionic eminence, and in somatostatin-expressing interneurons from the medial ganglionic eminence. By contrast, many cell types express SLC16A2 and THRA.Conclusions: SLCO1C1 and DIO2 coexpression in the outer radial glia, the universal stem cell of the cerebral cortex, highlights the likely importance of brain-generated T3 in neurogenesis. The unique expression of THRB in discrete subsets of interneurons is a novel finding whose pathophysiological meaning deserves further investigation.

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“…They are mostly presented with symptoms and signs of mild hypothyroidism and sometimes with local effects (i.e., symptoms and signs of increased intracranial pressure). Besides the clinical presentation of hypothyroidism, thyroid hormone resistance syndromes can also present as mental health problems ( 49 , 58 , 59 ). LT4-dose tapering is more complex in patients with secondary and tertiary hypothyroidism as the fT4 levels, which is the basis of how the quality of LT4 dosing is assessed, are less flexible ( 49 , 60 ).…”

Section: Thyroid Diseases and Conditions Associated With Lt4 Usementioning

confidence: 99%

Levothyroxine Treatment and the Risk of Cardiac Arrhythmias – Focus on the Patient Submitted to Thyroid Surgery

et al. 2021

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Levothyroxine (LT4) is used to treat frequently encountered endocrinopathies such as thyroid diseases. It is regularly used in clinical (overt) hypothyroidism cases and subclinical (latent) hypothyroidism cases in the last decade. Suppressive LT4 therapy is also part of the medical regimen used to manage thyroid malignancies after a thyroidectomy. LT4 treatment possesses dual effects: substituting new-onset thyroid hormone deficiency and suppressing the local and distant malignancy spreading in cancer. It is the practice to administer LT4 in less-than-high suppressive doses for growth control of thyroid nodules and goiter, even in patients with preserved thyroid function. Despite its approved safety for clinical use, LT4 can sometimes induce side-effects, more often recorded with patients under treatment with LT4 suppressive doses than in unintentionally LT4-overdosed patients. Cardiac arrhythmias and the deterioration of osteoporosis are the most frequently documented side-effects of LT4 therapy. It also lowers the threshold for the onset or aggravation of cardiac arrhythmias for patients with pre-existing heart diseases. To improve the quality of life in LT4-substituted patients, clinicians often prescribe higher doses of LT4 to reach low normal TSH levels to achieve cellular euthyroidism. In such circumstances, the risk of cardiac arrhythmias, particularly atrial fibrillation, increases, and the combined use of LT4 and triiodothyronine further complicates such risk. This review summarizes the relevant available data related to LT4 suppressive treatment and the associated risk of cardiac arrhythmia.

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Resistance to Thyroid Hormone Beta: A Focused Review

Cited by 61 publications

References 71 publications

Resistance to thyroid hormone in a child with thyroid agenesis: A case report with review of the literature

Resistance to thyroid hormone in a child with thyroid agenesis: A case report with review of the literature

Single-cell transcriptome profiling of thyroid hormone effectors in the human fetal neocortex: expression of SLCO1C1, DIO2, and THRB in specific cell types

Levothyroxine Treatment and the Risk of Cardiac Arrhythmias – Focus on the Patient Submitted to Thyroid Surgery

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