Molecular basis of resistance to thyroid hormone

Trends Endocrinol Metab. 2003 Sep;14(7):327-33. doi: 10.1016/s1043-2760(03)00114-0.


Resistance to thyroid hormone (RTH) is a syndrome in which patients have raised serum thyroid hormone (TH) levels and raised or inappropriately normal thyrotropin (TSH) levels. In general, patients exhibit TH resistance in the pituitary and peripheral tissues. Novel techniques and genetically engineered mouse model systems have increased our understanding of thyroid hormone receptor (TR) action, and shed new light on the underlying molecular mechanisms for RTH. In particular, we are learning how mutant TRs from RTH patients can block wild-type TR function, with consequent effects in various tissues and cells. This dominant-negative activity has important implications for other hormone-resistant conditions and in hormone-sensitive tumors. This article examines the molecular basis of RTH.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Genes, Dominant
  • Humans
  • Mutation / genetics
  • Receptors, Thyroid Hormone / genetics
  • Receptors, Thyroid Hormone / physiology
  • Thyroid Hormone Resistance Syndrome / genetics*
  • Thyroid Hormone Resistance Syndrome / physiopathology


  • Receptors, Thyroid Hormone