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

2008; Oxford University Press; Volume: 158; Issue: 1 Linguagem: Inglês

10.1530/eje-07-0514

1479-683X

Frédéric Castinetti, Isabelle Morange, P Jaquet, B. Conte‐Devolx, Thierry Brue,

Growth Hormone and Insulin-like Growth Factors

Although 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.Analysis of long-term hormonal effects and tolerance of ketoconazole in CD.A total of 38 patients were retrospectively studied with a mean follow-up of 23 months (6-72).All patients were treated at the same Department of Endocrinology in Marseille, France.The 38 patients with CD, of whom 17 had previous transsphenoidal surgery.Ketoconazole was begun at 200-400 mg/day and titrated up to 1200 mg/day until biochemical remission.Patients were considered controlled if 24-h urinary free cortisol was normalized.Five 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.Ketoconazole 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.