An outline of inherited disorders of the thyroid hormone generating system

Thyroid. 2003 Aug;13(8):771-801. doi: 10.1089/105072503768499671.


To date, various genetic defects impairing the biosynthesis of thyroid hormone have been identified. These congenital heterogeneous disorders result from mutations of genes involved in many steps of thyroid hormone synthesis, storage, secretion, delivery, or utilization. In contrast to thyroid dyshormonogenesis, the elucidation of the underlying etiology of most cases of thyroid dysgenesis is much less understood. It is suggested that genetic factors might play a role in some cases of thyroid dysgenesis and the best candidate genes involved are those encoding transcription factors known to play a role in the embryonic development of the thyroid gland. Moreover, discordance for thyroid dysgenesis is the rule for monozygotic twins as recently reported and this may result from epigenetic phenomena, early somatic mutations, or postzygotic events. In the final part of this review the molecular defects involved in proteins that transport thyroid hormone in the circulation are described: thyroxine-binding globulin (TBG), transtiretin and albumin, that may be associated with altered thyroid function tests and other pathologic conditions such as amyloidotic polyneuropathy.

Publication types

  • Review

MeSH terms

  • Animals
  • Genetic Diseases, Inborn / classification*
  • Humans
  • Hypothalamo-Hypophyseal System / physiology
  • Prevalence
  • Thyroid Diseases / classification
  • Thyroid Diseases / epidemiology
  • Thyroid Diseases / genetics*
  • Thyroid Gland / physiology
  • Thyroid Hormones / physiology*


  • Thyroid Hormones