The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Ketoconazole in Cushing's Disease: Is It Worth a Try?
Abstract
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.
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“Mean UFC is routinely used in clinical practice and research to monitor disease control and treatment response in patients with CS treated with medical therapy (129-137).”
From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [129]
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“In clinical trials, the efficacy of steroidogenesis inhibitors and pituitary-directed therapies in patients with CS was primarily evaluated by the normalization of cortisol secretion per UFC (129-137).”
From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [129]
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In the citing paper
“The restoration of cortisol circadian rhythm following medical therapy has not been investigated or established for most medications used to treat CS, and it is not routinely measured to determine treatment response (129-137).”
From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [129]
Experimental — accuracy not yet measuredIn the citing paper
“At doses of to mg daily, this steroidogenesis inhibitor has been shown to improve glucose metabolism in patients with CS and in those with type DM (-).”
From Glucose Metabolism Abnormalities in Cushing Syndrome: From Molecular Basis to Clinical Management (2017) · cites this paper as [284]
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Citations
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Metadata
- Authors
- Castinetti, F., Guignat, L., Giraud, P., Muller, M., Kamenicky, P., Drui, D., Caron, P., Luca, F., Donadille, B., Vantyghem, M. C., Bihan, H., Delemer, B., Raverot, G., Motte, E., Philippon, M., Morange, I., Conte-Devolx, B., Quinquis, L., Martinie, M., Vezzosi, D., Le Bras, M., Baudry, C., Christin-Maitre, S., Goichot, B., Chanson, P., Young, J., Chabre, O., Tabarin, A., Bertherat, J., & Brue, T.
- Affiliations
- 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 (FR)
- Centre Hospitalier Universitaire de Bordeaux (FR)
- Hôpital Albert Michallon (FR)
- Université Paris-Sud Service d'Endocrinologie et Maladies de la Reproduction (P.K., P.Ch., J.Y.), 94270, Le Kremlin Bicetre, France
- Centre Hospitalier Universitaire de Nantes (FR)
- Hôpital Larrey (FR)
- Hôpital d'Hautepierre (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Hôpital Avicenne (FR)
- Centre Hospitalier Universitaire de Reims (FR)
- Hôpital Neuro-cardiologique Fédération d'Endocrinologie du Pôle Est (G.R.), 39500 Bron, France
- Hôpital de Bicêtre Endocrinologie Pédiatrique (E.M.), 94270, Le Kremlin Bicetre, France
- Aix-Marseille Université (FR)
- CHU de Nantes Hôpital G & R Laënnec St-Herblain Endocrinologie, Maladies Métaboliques et Nutrition (D.D., M.L.B.), 44093, Nantes, France
- Assistance Publique-Hôpitaux de Paris, Hôpital St-Antoine Service d'Endocrinologie-Diabétologie et Médecine de la Reproduction (B.Do., S.C.-M.), 75012, Paris, France
- Université Paris-Sud (FR)
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2014-05-01
- Volume
- 99
- Issue
- 5
- Pages
- 1623-1630
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2125518985
- Semantic Scholar
- 06bf42858cb6de53f9f93e22f528a6e524a20a4a
- Cited by
- 285
- References
- 42
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 23 · 2023: 20 · 2022: 32 · 2021: 23 · 2020: 21 · 2019: 28 · 2018: 31 · 2017: 21 · 2016: 23 · 2015: 23 · 2014: 11
- FWCI
- 20.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- ketoconazole, Cushing's disease, hepatotoxicity, liver enzyme monitoring, urinary free cortisol, drug efficacy, drug tolerance, presurgical treatment, hypertension, hypokalemia, diabetes mellitus
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Female, Humans, Hydrocortisone, Ketoconazole, Male, Middle Aged, Retrospective Studies, Treatment Outcome, Pituitary ACTH Hypersecretion, 14-alpha Demethylase Inhibitors
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