1. Ketoconazole revisited: a preoperative or postoperative treatment in Cushing's disease
- Author
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P. Jaquet, I. Morange, Bernard Conte-Devolx, Frederic Castinetti, Thierry Brue, Interactions cellulaires neuroendocriniennes (ICN), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Male ,Time Factors ,Hydrocortisone ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Antifungal drug ,MESH: Magnetic Resonance Imaging ,Cushing syndrome ,0302 clinical medicine ,Endocrinology ,MESH: Carboplatin ,MESH: Germ-Line Mutation ,MESH: Neoplasms ,MESH: Collagen Type XI ,MESH: Treatment Outcome ,MESH: Aged ,MESH: DNA Repair ,MESH: Middle Aged ,MESH: Follow-Up Studies ,General Medicine ,Middle Aged ,Magnetic Resonance Imaging ,MESH: Hydrocortisone ,MESH: Drug Resistance, Neoplasm ,3. Good health ,MESH: Ovarian Neoplasms ,Ketoconazole ,Treatment Outcome ,MESH: Enzyme Inhibitors ,030220 oncology & carcinogenesis ,Female ,France ,MESH: Pancreatic Neoplasms ,medicine.drug ,Adult ,MESH: Preoperative Care ,medicine.medical_specialty ,MESH: Cell Line, Tumor ,Adolescent ,030209 endocrinology & metabolism ,MESH: Drug Administration Schedule ,MESH: Postoperative Care ,Drug Administration Schedule ,03 medical and health sciences ,Internal medicine ,Preoperative Care ,medicine ,Adrenal insufficiency ,Humans ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,Pituitary ACTH Hypersecretion ,Adverse effect ,Aged ,Retrospective Studies ,Postoperative Care ,MESH: Adolescent ,Transsphenoidal surgery ,MESH: Humans ,Intention-to-treat analysis ,business.industry ,MESH: Pituitary ACTH Hypersecretion ,MESH: Time Factors ,MESH: Adult ,MESH: Retrospective Studies ,Cushing's disease ,medicine.disease ,MESH: Male ,Surgery ,MESH: France ,MESH: Ketoconazole ,MESH: Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,business ,MESH: Female ,MESH: Genes, BRCA1 ,MESH: Genes, BRCA2 ,Follow-Up Studies - Abstract
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 with 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.
- Published
- 2008