Ketoconazole revisited: a preoperative or postoperative treatment in Cushing's disease

F Castinetti, I Morange, P Jaquet, B Conte-Devolx, T Brue
2008 European Journal of Endocrinology  
ContextAlthough transsphenoidal surgery remains the first-line treatment in Cushing's disease (CD), recurrence is observed in about 20% of cases. Adjunctive treatments each have specific drawbacks. Despite its inhibitory effects on steroidogenesis, the antifungal drug ketoconazole was only evaluated in series with few patients and/or short-term follow-up.ObjectiveAnalysis of long-term hormonal effects and tolerance of ketoconazole in CD.DesignA total of 38 patients were retrospectively studied
more » ... ith a mean follow-up of 23 months (6–72).SettingAll patients were treated at the same Department of Endocrinology in Marseille, France.PatientsThe 38 patients with CD, of whom 17 had previous transsphenoidal surgery.InterventionKetoconazole was begun at 200–400 mg/day and titrated up to 1200 mg/day until biochemical remission.Main outcome measuresPatients were considered controlled if 24-h urinary free cortisol was normalized.ResultsFive patients stopped ketoconazole during the first week because of clinical or biological intolerance. On an intention to treat basis, 45% of the patients were controlled as were 51% of those treated long term. Initial hormonal levels were not statistically different between patients controlled or uncontrolled. Ketoconazole was similarly efficacious as a primary or postoperative treatment. Among 15 patients without visible adenoma at initial evaluation, subsequent follow-up allowed identification of the lesion in five cases. No adrenal insufficiency was observed. Adverse effects were rare in patients treated long term.ConclusionsKetoconazole is a safe and efficacious treatment in CD, particularly in patients for whom surgery is contraindicated, or delayed because of the absence of image of adenoma on magnetic resonance imaging.
doi:10.1530/eje-07-0514 pmid:18166822 fatcat:c3aduy67ofd5dk4tyhdrqlfvym