title: Currently used and investigational drugs for Cushing´s disease.
abstract: Cushing's disease (CD) is caused by a corticotroph adenoma of the pituitary gland that secretes excess adrenocorticotropic hormone (ACTH) causing increased morbidity and mortality. Surgery is the treatment of choice, but is not always successful. Alternatives include radiotherapy, adrenal surgery, and pharmaceutical therapy. The latter is increasingly gaining momentum due to the recent development of compounds that reduce hypercortisolaemia or its symptoms, acting through different mechanisms. Areas covered: In this article, the authors provide a complete overview of the treatment options for Cushing´s disease, including adrenal-directed, tumor-targeted, and peripheral therapies that are currently used or in development, and discuss their potential advantages and limitations. Expert opinion: Considering the lack of long-term remission in up to half of the patients after surgery, and the delayed response to radiotherapy along with potential side effects, there is a strong need for an effective pharmaceutical treatment. Pasireotide, mifepristone, ketoconazole and metyrapone have been approved by regulatory authorities but their use remains limited due to considerable costs and side effects. Research in this field has focused recently on the improvement of pre-existing drugs and the development of safe new ones. However, few approaches aim at targeting the source of the disease, the ACTH-secreting adenoma.
authors.affiliation: a Clinical Neuroendocrinology , Max Planck Institute of Psychiatry , Munich , Germany.|b Endocrinology Division, Department of Medicine , University-Hospital of Padua , Padua , Italy.
authors.forename: Denis
authors.initials: D
authors.lastname: Ciato
authors.affiliation: c Endocrinology Division , Carlos G. Durand Hospital , Buenos Aires , Argentina.
authors.forename: Aizhar G
authors.initials: AG
authors.lastname: Mumbach
authors.affiliation: a Clinical Neuroendocrinology , Max Planck Institute of Psychiatry , Munich , Germany.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Paez-Pereda
authors.affiliation: a Clinical Neuroendocrinology , Max Planck Institute of Psychiatry , Munich , Germany.
authors.forename: Günter K
authors.initials: GK
authors.lastname: Stalla
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000150:complications; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D015195:Drug Design; D015507:Drugs, Investigational / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D058990:Molecular Targeted Therapy; D047748:Pituitary ACTH Hypersecretion / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology
chemical_list: D015507:Drugs, Investigational; D000324:Adrenocorticotropic Hormone
keywords: ACTH; Cushing’s disease; dopamine agonists; retinoic acid; somatostatin analogues