Abstract

Proliferative thyroid diseases are more prevalent in females than in males. Upon the onset of puberty the incidence of thyroid cancer is only increasing in females and declining again after menopause. Estrogen is a potent growth factor both for benign and malignant thyroid cells which may explain the sex difference in the prevalence of thyroid nodules and thyroid cancer. It exerts its growth-promoting effect through the classical genomic and a non-genomic pathway, mediated via a membrane-bound estrogen receptor. This receptor is linked to the tyrosine kinase signaling ways MAPK and PI3K. In papillary thyroid carcinomas these pathways may be activated either by a chromosomal rearrangement of the tyrosine receptor kinase TRK-A, by Ret/PTC genes or by a B-RAF mutation and in addition, in females stimulated by high levels of estrogen. Furthermore, estrogen is involved in the regulation of angiogenesis and metastasis which are critical for the outcome of thyroid cancer. In contrast to other carcinomas, however, detailed knowledge on this regulation is still missing in thyroid cancer.