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First published online on December 22, 2004
Endocrine Reviews, doi:10.1210/er.2004-0005
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Endocrine Reviews 26 (4): 504-524
Copyright © 2005 by The Endocrine Society

Molecular Pathogenesis of Euthyroid and Toxic Multinodular Goiter

Knut Krohn, Dagmar Führer, Yvonne Bayer, Markus Eszlinger, Volker Brauer, Susanne Neumann and Ralf Paschke

III. Medical Department (K.K., D.F., Y.B., M.E., V.B., S.N., R.P.), and Interdisciplinary Center for Clinical Research Leipzig (K.K), University of Leipzig, D-04103 Leipzig, Germany

Correspondence: Address all correspondence and requests for reprints to: Professor Ralf Paschke, Universität Leipzig, Zentrum für Innere Medizin, Medizinische Klinik und Poliklinik III, Ph.-Rosenthal-Strasse 27, 04103 Leipzig, Germany. E-mail: pasr{at}medizin.uni-leipzig.de

The purpose of this review is to summarize current knowledge of the etiology of euthyroid and toxic multinodular goiter (MNG) with respect to the epidemiology, clinical characteristics, and molecular pathology.

In reconstructing the line of events from early thyroid hyperplasia to MNG we will argue the predominant neoplastic character of nodular structures, the nature of known somatic mutations, and the importance of mutagenesis. Furthermore, we outline direct and indirect consequences of these somatic mutations for thyroid pathophysiology and summarize information concerning a possible genetic background of euthyroid goiter.

Finally, we discuss uncertainties and open questions in differential diagnosis and therapy of euthyroid and toxic MNG.




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