title: Ketoconazole therapy: an efficacious alternative to achieve eucortisolism in patients with Cushing's syndrome.
abstract: Cushing's syndrome (CS) is a serious condition requiring drug management in diverse clinical settings. Fifty four patients (44 females, 10 males) with CS, aged 14-63, received ketoconazole (KTZ) prior to surgery (n= 27), as complementary therapy after surgery and/or radiotherapy (n= 16), or as primary treatment (n= 11). It was given at a 600 (500 - 600) mg/day (median - Cl195) maintenance dose for periods ranging from 15 days to 13 years. Clinical signs, hepatic enzymes and urinary free cortisol (UFC) were evaluated before and during KTZ treatment. UFC normalised or decreased to subnormal values in 85% of the patients, in 5 to 150 days after starting treatment; although failing to normalise, UFC decreased to 12-48% of pre-treatment values in the remaining patients. Clinical signs improved throughout. Side effects were adrenal insufficiency (18.5%), reversible hepatic toxicity (11%), allergic skin rash (5.5%) and gastric intolerance (3.7%); in 11% of patients, an "escape phenomenon" was observed. Twenty-four out of the total (44.4%) were treated for prolonged periods, from one up to 13 years. In conclusion, this study confirms that KTZ is an effective and generally well tolerated treatment for CS particularly: a) shortly before surgery, b) because of persistent hypercortisolism after surgery or awaiting the results of radiotherapy, c) as a reasonable option in patients with CS of unknown aetiology and, d) as long-term therapy in any case of unsolved hypercortisolism after failure of current treatments.
authors.affiliation: División Endocrinología, Hospital de Clínicas José de San Martin, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
authors.forename: Daniel
authors.initials: D
authors.lastname: Moncet
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Morando
authors.forename: Fabian
authors.initials: F
authors.lastname: Pitoia
authors.forename: Silvia B
authors.initials: SB
authors.lastname: Katz
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rossi
authors.forename: Oscar D
authors.initials: OD
authors.lastname: Bruno
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000704:Analysis of Variance; D003480:Cushing Syndrome / Q000188:drug therapy* / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007654:Ketoconazole / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004791:Enzyme Inhibitors; D000324:Adrenocorticotropic Hormone; D007654:Ketoconazole