MOLECULAR ASPECTS OF THE PATHOGENESIS OF NODULAR GOITERS, THYROID-NODULES AND ADENOMAS

One of the most significant results of recent molecular thyroid resear ch on the pathogenesis of nodular goiters may be the finding that not only thyroid adenomas but also many thyroid nodules are clonal in orig in and thus are true benign tumors. Both clonal and polyclonal nodules may coexist within the same nodular goiter. Since clonal nodules may secondarily acquire a heterogeneous phenotype, they can become morphol ogically indistinguishable from polyclonal lesions. The molecular mech anisms that generate thyroid nodules and adenomas are still poorly und erstood. Certainly, the recent detection of activating mutations in th e TSH receptor and the Gs-alpha gene in a subset of toxic thyroid aden omas and nodules may explain the generation of hyperfunction in these tumors, but there is strong evidence that these mutations are not the unique and primary cause of tumor formation. In this respect the conce pt of natural occurring heterogeneity of thyroid growth and function c an provide a plausible explanation for the early stages of nodular tra nsformation: If a thyrocyte has a high intrinsic growth potential or i f it is affected by overexpression of a protooncogene or a growth fact or or hit by an oncogene or other molecular events, the cell will outg row and form a tumor. The inborn qualities of proliferating cells or t he sequence of various genetic alterations in proliferating cells or t he sequence of various genetic alterations in proliferating cells will in turn determine the phenotype and function of the tumor.