Abstract

Thyroid nodules are present in up to 30% of the German population. The causative role of iodine deficiency which is still endemic in this country has long been established. Recent progress has shed some light on the pathogenesis of nodular thyroid disease which still remains less well understood than goitrogenesis. Most thyroid nodules appear to be of clonal origin. Functional abnormalities have been related to alterations within the TSH signaling cascade, particularly mutations in the TSH receptor and stimulating G-protein-alpha-subunit. Proliferation which is dissociable from thyroid function has been linked to genetic differences of the thyroid cells themselves and growth factors being partly overexpressed by thyroid nodules. Data regarding the correlation of the molecular characteristics to the clinical behavior and growth potential have not yet been elucidated. On the other hand, there are only a few clinical studies that have addressed the long-term natural history of thyroid nodules. From these studies at least it appears that thyroid nodules tend to grow slowly and their increase in size may even by modern ultrasonography technique become apparent only after several years. Those in vitro and in vivo observations have important implications for the planning of therapeutical trials. Studies have focused so far mainly on short term effects of different therapeutic regimens such as iodine or levothyroxine. However, pathophysiological considerations and clinical observation would encourage studies over more prolonged periods of time.

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