[Mutations in the thyrotropin receptor gene in the pathogenesis of toxic thyroid adenomas, toxic goiter nodules and autosomal dominant hyperthyroidism]

Abstract

In iodine deficiency regions such as Germany, more than 50% of toxic thyroid adenomas and some toxic goiter nodules harbor activating mutations in the TSH receptor or Gs-alpha gene. These mutations cause cellular hyperfunction and hyperthyroidism but are not sufficient to generate thyroid adenomas and nodules. In the pathogenesis of these tumors, other primary and secondary molecular mechanism are operative, including overexpression of growth factors, their receptors and of signaling proteins. Expression of some of these growth factors is regulated by TSH-dependent pathways. However, iodine deficiency and its effect on thyroid growth remains the most important pathogenetic factor for these diseases. Therefore, toxic adenomas as well as the majority of nonfunctioning and eufunctioning thyroid nodules and adenomas are relatively rare in regions with high iodide intake of the population.