ROSIGLITAZONE TREATMENT IN PATIENTS WITH CUSHINGS DISEASEROSIGLITAZONE TREAT

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. SPECIFIC AIMS Specific Aim: PPAR-? ligands are a useful and safe medical therapy for Adrenocorticotrophic Hormone (ACTH)-secreting pituitary tumors (Cushing s disease). As ACTH-secreting pituitary tumors exhibit abundant peroxisome proliferator activated receptor-gamma (PPAR-?) expression and the PPAR-? ligand rosiglitazone exerts potent anti-hormonal and anti-proliferative effects in in vitro and in vivo corticotroph tumor models, the effects of rosiglitazone on pituitary tumor growth, and pituitary tumor ACTH and adrenal steroid hormone secretion will be tested. The potential role of the PPAR-? ligand rosiglitazone in treating Cushing s disease will be examined in a Phase II clinical trial involving 15 patients with ACTH-secreting pituitary tumors (Cushing s Disease), who are newly diagnosed. The study will examine: (1) effects of rosiglitazone treatment on abrogating hypercortisolism, and (2) effects of rosiglitazone treatment on abrogating pituitary corticotroph growth. Additionally the effects, if any, of rosiglitazone treatment on abrogating plasma ACTH levels and inflammatory markers (C-reactive protein, IL-6, serum sialic acid, soluble intracellular and vascular adhesion molecules (sICAM-1, and sVCAM-1), and amyloid A) will be examined.