title: Cushing's syndrome: an update on current pharmacotherapy and future directions.
abstract: BACKGROUND
  Endogenous Cushing's syndrome (CS) is characterized by chronic overproduction of cortisol and is associated with increased mortality and morbidity. It can be caused by a pituitary adenoma, ectopic adrenocorticotropic hormone (ACTH) production or primary adrenal disease. Successful tumor-directed surgery is the keystone treatment. When surgery is unsuccessful, contraindicated or in case of acute disease, pharmacotherapy is indicated to treat hypercortisolism.
  
  
  METHODS
  In this review, pharmacotherapeutic options for CS will be covered discussing the different possible targets, that is: i) inhibition of ACTH secretion; ii) suppression of steroidogenesis; and iii) blockade of cortisol effects at tissue level. Preclinical and clinical studies will be discussed considering mono- and combination therapy, taking into account efficacy, toxicity and mechanism of action. Per CS entity, future directions of pharmacotherapies will be addressed.
  
  
  CONCLUSIONS
  The number of medical treatment options for CS has increased in the past years. In contrast to decades ago, prospective trials are now being performed focusing on pituitary-directed drugs like pasireotide, the glucocorticoid receptor blocker mifepristone and 'new generation' steroid synthesis inhibitors. Future studies will focus on tumor-shrinking effects of neuromodulatory drugs, the optimal order and combination of pharmacotherapy, long-term efficacy and safety and new targets for medical treatment of CS.
authors.affiliation: Erasmus Medical Center, Department of Internal Medicine, Division of Endocrinology , Dr. Molewaterplein 50, 3015GE Rotterdam , The Netherlands +31 10 7040704 ; +31 10 7044862 ; r.feelders@erasmusmc.nl.
authors.forename: Sara G
authors.initials: SG
authors.lastname: Creemers
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Hofland
authors.forename: Steven W J
authors.initials: SW
authors.lastname: Lamberts
authors.forename: Richard A
authors.initials: RA
authors.lastname: Feelders
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D003480:Cushing Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D010902:Pituitary Gland / Q000187:drug effects / Q000503:physiopathology
chemical_list: D000324:Adrenocorticotropic Hormone
keywords: ACTH; Cushing’s syndrome; cortisol; management; pharmacotherapy