Novel therapeutic approaches in Cushing's disease: PPar-gamma agonists

The rationale for the treatment of Cushing's disease is to normalize serum cortisol and ACTH levels, while preserving the anterior pituitary function. The treatment of choice for Cushing's disease is surgery. However, in some circumstances the patients can need further treatment modalities including reoperation, radiotherapy and medical therapy. The medical therapy for Cushing's disease is preferred in order to decrease the excessive cortisol levels prior to surgery, to decrease the complications or to control hypercortisolaemia while awaiting the full effect of radiotherapy or of the treatment of metastatic disease. Between the two groups of drugs-steroidogenesis inhibitors and centrally acting drugs-steroidogenesis inhibitors, particularly metyrapone and ketoconazole, are the preferred agents. Centrally acting drugs may be superior to steroidogenesis inhibitors in the treatment of Cushing's disease by decreasing the adrenocorticothrophic hormone (ACTH) levels and inhibiting the tumor growth. In this review we are aimed to evaluate the possible use of peroxisome proliferator-activated receptor-gamma agonists as centrally acting drugs in the treatment of Cushing's disease.