Genetic disorders of thyroid development, hormone biosynthesis and signalling.


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Authors
Moran, Carla 
Schoenmakers, Nadia  ORCID logo  https://orcid.org/0000-0002-0847-2884
Visser, W Edward 
Schoenmakers, Erik 
Agostini, Maura 
Abstract

Development and differentiation of the thyroid gland is directed by expression of specific transcription factors in the thyroid follicular cell which mediates hormone biosynthesis. Membrane transporters are rate-limiting for cellular entry of thyroid hormones (TH) (T4 and T3) into some tissues, with selenocysteine-containing, deiodinase enzymes (DIO1 and DIO2) converting T4 to the biologically active hormone T3. TH regulate expression of target genes via hormone-inducible nuclear receptors (TRα and TRβ) to exert their physiological effects. Primary congenital hypothyroidism (CH) due to thyroid dysgenesis may be mediated by defects in thyroid transcription factors or impaired thyroid stimulating hormone receptor function. Dyshormonogenic CH is usually due to mutations in genes mediating thyroidal iodide transport, organification or iodotyrosine synthesis and recycling. Disorders of TH signalling encompass conditions due to defects in membrane TH transporters, impaired hormone metabolism due to deficiency of deiodinases and syndromes of Resistance to thyroid hormone due to pathogenic variants in either TRα or TRβ. Here, we review the genetic basis, pathogenesis and clinical features of congenital, dysgenetic or dyshormonogenic hypothyroidism and disorders of TH transport, metabolism and action.

Description

Funder: Sherman Foundation


Funder: NIHR Cambridge Biomedical Centre

Keywords
congenital hypothyroidism, thyroid dysgenesis, thyroid hormone receptors, thyroid hormone resistance, thyroid hormones, Humans, Hypothyroidism, Iodide Peroxidase, Signal Transduction, Thyroid Hormones, Transcription Factors
Journal Title
Clin Endocrinol (Oxf)
Conference Name
Journal ISSN
0300-0664
1365-2265
Volume Title
Publisher
Wiley
Sponsorship
Wellcome Trust (095564/Z/11/Z)
Wellcome Trust (210755/Z/18/Z)
Wellcome Trust (219496/Z/19/Z)