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Ketoconazole in Cushing's disease: is it worth a try?
Castinetti, Frederic; Guignat, Laurence; Giraud, Pauline; Muller, Marie; Kamenicky, Peter; Drui, Delphine; Caron, Philippe; Luca, Fiorina; Donadille, Bruno; Vantyghem, Marie Christine; Bihan, Helene; Delemer, Brigitte; Raverot, Gerald; Motte, Emmanuelle; Philippon, Melanie; Morange, Isabelle; Conte-Devolx, Bernard; Quinquis, Laurent; Martinie, Monique; Vezzosi, Delphine; Le Bras, Maelle; Baudry, Camille; Christin-Maitre, Sophie; Goichot, Bernard; Chanson, Philippe; Young, Jacques; Chabre, Olivier; Tabarin, Antoine; Bertherat, Jerome; Brue, Thierry.
Afiliação
  • Castinetti F; Aix Marseille Université, Hopital de la Timone (F.C., M.P., I.M., B.C.-D., T.B.), Service d'Endocrinologie, 13005, Marseille, France; Hôpital Cochin Service d'Endocrinologie et Maladies Métaboliques (L.G., L.Q., C.B., J.B.), 75014, Paris, France; Centre Hospitalier Universitaire (CHU) de Bordeaux Hôpital du Haut Lévêque Service d'Endocrinologie-Diabétologie et Maladies Métaboliques (P.G., A.T.), 33600 Pessac, France; CHU de Grenoble Hôpital Albert Michallon Service d'Endocrinologie-Diabétologie-
J Clin Endocrinol Metab ; 99(5): 1623-30, 2014 May.
Article em En | MEDLINE | ID: mdl-24471573
BACKGROUND: The use of ketoconazole has been recently questioned after warnings from the European Medicine Agencies and the Food and Drug Administration due to potential hepatotoxicity. However, ketoconazole is frequently used as a drug to lower circulating cortisol levels. Several pharmacological agents have recently been approved for the treatment of Cushing's disease (CD) despite limited efficacy or significant side effects. Ketoconazole has been used worldwide for more than 30 years in CD, but in the absence of a large-scale study, its efficacy and tolerance are still under debate. PATIENTS AND METHODS: We conducted a French retrospective multicenter study reviewing data from patients treated by ketoconazole as a single agent for CD, with the aim of clarifying efficacy and tolerance to better determine the benefit/risk balance. RESULTS: Data from 200 patients were included in this study. At the last follow-up, 49.3% of patients had normal urinary free cortisol (UFC) levels, 25.6% had at least a 50% decrease, and 25.4% had unchanged UFC levels. The median final dose of ketoconazole was 600 mg/d. Forty patients (20%) received ketoconazole as a presurgical treatment; 40% to 50% of these patients showed improvement of hypertension, hypokalemia, and diabetes, and 48.7% had normal UFC before surgery. Overall, 41 patients (20.5%) stopped the treatment due to poor tolerance. Mild (<5N, inferior to 5-fold normal values) and major (>5N, superior to 5-fold normal values) increases in liver enzymes were observed in 13.5% and 2.5% of patients, respectively. No fatal hepatitis was observed. CONCLUSIONS: Ketoconazole is an effective drug with acceptable side effects. It should be used under close liver enzyme monitoring. Hepatotoxicity is usually mild and resolves after drug withdrawal.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hipersecreção Hipofisária de ACTH / Inibidores de 14-alfa Desmetilase / Cetoconazol Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Adolescent / Adult / Aged / Aged80 / Child / Female / Humans / Male / Middle aged Idioma: En Revista: J Clin Endocrinol Metab Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hipersecreção Hipofisária de ACTH / Inibidores de 14-alfa Desmetilase / Cetoconazol Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Adolescent / Adult / Aged / Aged80 / Child / Female / Humans / Male / Middle aged Idioma: En Revista: J Clin Endocrinol Metab Ano de publicação: 2014 Tipo de documento: Article