Cushing's syndrome: an update on current pharmacotherapy and future directions. (August 2015)

• Record Type: Journal Article
• Authors: Creemers, Sara G; Hofland, Leo J; Lamberts, Steven WJ; Feelders, Richard A
• Is Part Of: Expert opinion on pharmacotherapy. Volume 16:Number 12(2015)
• Page Start: 1829
• Page End: 1844
• Publication Date: 2015-08
• Subjects: Chemotherapy -- Periodicals; 615.5805
• DOI: 10.1517/14656566.2015.1061995
• Languages: English
• ISSNs: 1465-6566

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold> <italic>Introduction:</italic> </bold> 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.</p> <p> <bold> <italic>Areas covered:</italic> </bold> 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.</p> <p> <bold> <italic>Expert opinion:</italic> </bold> 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.</p> </abstract>