title: The New Molecular Landscape of Cushing's Disease.
abstract: Cushing's disease (CD) is caused by corticotropin-secreting pituitary adenomas and results in substantial morbidity and mortality. Its molecular basis has remained poorly understood until the past few years, when several proteins and genes [such as testicular orphan nuclear receptor 4 (TR4) and heat shock protein 90 (HSP90)] were found to play key roles in the disease. Most recently, mutations in the gene of ubiquitin-specific peptidase 8 (USP8) increasing its deubiquination activity were discovered in a high percentage of corticotroph adenomas. Here, we will discuss emerging insights in the molecular alterations that finally result in CD. The therapeutic potential of these findings needs to be carefully evaluated in the near future, hopefully resulting in new treatment options for this devastating disorder.
authors.affiliation: Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.
authors.forename: Silviu
authors.initials: S
authors.lastname: Sbiera
authors.affiliation: Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Deutschbein
authors.affiliation: Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Weigand
authors.affiliation: Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Reincke
authors.affiliation: Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany. Electronic address: fassnacht_m@ukw.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Fassnacht
authors.affiliation: Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.
authors.forename: Bruno
authors.initials: B
authors.lastname: Allolio
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D000818:Animals; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D047748:Pituitary ACTH Hypersecretion / Q000235:genetics / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D066246:ErbB Receptors
keywords: 14-3-3 proteins; Cushing's disease; epidermal growth factor receptor; gene expression; pituitary; ubiquitin-specific peptidase 8