Medical Treatment of Cushings Syndrome: Adrenal-Blocking Drugs and Ketaconazole

Cushing’s syndrome is associated with serious morbidity and increased mortality. Irrespective of its cause, i.e. a pituitary adenoma, ectopic ACTH production or an adrenal neoplasia, Cushing’s syndrome is primarily treated surgically. However, when surgery is unsuccessful or contraindicated, medical therapy is needed to treat hypercortisolism. The spectrum of available drugs includes adrenal-blocking agents, neuromodulatory drugs and glucocorticoid receptor antagonists. Adrenal blocking drugs suppress adrenal cortisol production via inhibition of steroidogenic enzymes. Ketoconazole and metyrapone are most frequently used for this purpose, but chronic treatment with these drugs can be limited by side effects like hepatotoxicity (ketoconazole) and increased androgen and mineralocorticoid production (metyrapone). Etomidate can be used to rapidly reverse cortisol excess in patients with acute complications of (severe) hypercortisolism like psychosis. In Cushing’s disease, combination therapy with drugs that target the corticotropic adenoma, i.e. the universal somatostatin analogue pasireotide and/or the dopamine agonist cabergoline, and low-dose ketoconazole seems a rational approach to achieve biochemical control. Copyright © 2010 S. Karger AG, Basel Published online: September 10, 2010 Richard A. Feelders Department of Internal Medicine, Erasmus Medical Center Rotterdam ’s Gravendijkwal 230 NL–3015 CE Rotterdam (The Netherlands) Tel. +31 10 704 0704, Fax +31 10 703 3726, E-Mail r.feelders @ erasmusmc.nl © 2010 S. Karger AG, Basel 0028–3835/10/0925–0111$26.00/0 Accessible online at: www.karger.com/nen D ow nl oa de d by : 54 .7 0. 40 .1 1 11 /1 9/ 20 17 1 0: 02 :3 7 A M