Molecular aspects of the pathogenesis of nodular goiters, thyroid nodules and adenomas.
One of the most significant results of recent molecular thyroid research on the pathogenesis of nodular goiters may be the finding that not only thyroid adenomas but also many thyroid nodules are clonal in origin 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 morphologically indistinguishable from polyclonal lesions. The molecular mechanisms that generate thyroid nodules and adenomas are still poorly understood. Certainly, the recent detection of activating mutations in the TSH receptor and the Gs alpha gene in a subset of toxic thyroid adenomas 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 concept of natural occurring heterogeneity of thyroid growth and function can provide a plausible explanation for the early stages of nodular transformation: If a thyrocyte has a high intrinsic growth potential or if it is affected by overexpression of a protooncogene or a growth factor or hit by an oncogene or other molecular events, the cell will outgrow and form a tumor. The inborn qualities of proliferating cells or the sequence of various genetic alterations in proliferating cells will in turn determine the phenotype and function of the tumor.
Derwahl
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University Clinic of Internal Medicine Bergmannsheil, Bochum, Germany.
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D002999:Clone Cells / Q000473:pathology; D019204:GTP-Binding Proteins / Q000235:genetics; D006044:Goiter, Nodular / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation; D009857:Oncogenes; D011989:Receptors, Thyrotropin / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D016606:Thyroid Nodule / Q000235:genetics* / Q000473:pathology
D011989:Receptors, Thyrotropin; D019204:GTP-Binding Proteins