Update in thyroidology

Abstract

The human and mouse genome databases have provided powerful tools to probe many unanswered questions in thyroidology. Mechanistic knowledge regarding thyroid development, thyroid gland regulation by hypothalamic-pituitary function, thyroid hormone transport and action, thyroid autoimmunity and genetics, and thyroid oncogenesis have expanded enormously using molecular genetics. This basic information is providing the foundation for new clinical approaches to the diagnosis and therapy of thyroid disorders. For example, old dogma regarding the transport of thyroid hormones into cells being mediated by passive diffusion is being discarded as knowledge of new small molecule transporters has been discovered and related to human disease. The genetic basis for autoimmune thyroid disease is being unraveled by discovery of genetic variations associated with risk for autoimmune disease and important molecules in the disorder's pathogenesis. The translation of basic molecular genetic knowledge into clinical care is no better illustrated than in thyroid cancer, in which genetic mutations in molecules of the MAPK pathway have been shown to account for more than 70% of papillary thyroid cancers. Furthermore, certain mutations may predict clinical outcomes, such as cancer recurrence. The new molecular understanding of thyroid cancer causation is now opening a new therapeutic frontier as drugs are developed that modulate the MAPK pathway.