The Thyroid and Its Regulation by the TSHR: Evolution, Development, and Congenital Defects

  • Heiko KrudeEmail author
  • Heike Biebermann


The most frequent inborn endocrine disorder is congenital hypothyroidism (CH) with a prevalence of 1 in 3000 newborns. In most cases a morphological defect of the thyroid gland occurs, and in these cases of “thyroid dysgenesis,” a defect in the different steps of thyroid organogenesis that resembles the phylogenetic development of the thyroid can be expected. However, so far, in this larger group of patients suffering from thyroid dysgenesis, a defect is only rarely found in transcription factor genes known from thyroid organogenesis and phylogenesis, e.g., in NKX and PAX genes. In addition some patients with defects of thyroid development were found to have a TSH receptor (TSHR) gene mutation. Together only 5% of thyroid dysgenesis can be explained today by genetic defects, suggesting epigenetic or other molecular causes, and only in 10% of patients a normally located thyroid gland is detected. In this smaller group of patients, genetic defects in candidate genes for thyroid hormone synthesis are frequently found. From the 1880s treatment in CH was started, first with thyroid extracts, later after installation of newborn screening programs for CH with LT4. In this chapter we will summarize the actual knowledge about the development of the thyroid gland in terms of their evolutionary origin as well in their ontogenetic maturation and to use this precognition as a basis for an understanding of the pathogenesis of congenital hypothyroidism with a specific emphasis on function and dysfunction of the TSHR.


Thyroid development Thyroid evolution TSH receptor TSH receptor mutation Congenital hypothyroidism 


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© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute for Experimental Paediatric Endocrinology, Charite University-Medicine-BerlinBerlinGermany

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