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Ketoconazole treatment in Cushing’s syndrome: experience in 34 patients
Abstract
OBJECTIVE: Ketoconazole treatment of Cushing's syndrome has been reported in single cases and a few small groups of 5-8 patients. We report our experience in 34 patients. DESIGN: Clinical study, with pretreatment and post-treatment evaluations. PATIENTS: Out of 67 patients with Cushing's syndrome admitted during the last 6 years, 34 (28 females/six males; age range 14-67 years) received ketoconazole as a palliative treatment due to severe clinical conditions or management of the disease while awaiting results of definitive therapy. MEASUREMENTS: Urinary cortisol, plasma cortisol and ACTH, and routine chemistry were measured every week for 4 weeks, and then once a month. RESULTS: Comparing the last values (mean +/- SEM) during treatment with baseline, urinary cortisol decreased from 1296 +/- 176 to 270 +/- 69 nmol/d (n = 34; P less than 0.001); plasma cortisol decreased from 672 +/- 31 to 549 +/- 35 nmol/l (n = 34; P less than 0.001). For patients with pituitary-dependent Cushing's syndrome, urinary cortisol decreased from 1073 +/- 126 to 200 +/- 21 nmol/d (n = 28; P less than 0.001) while plasma ACTH changed from 12.5 +/- 1.3 to 11.3 +/- 0.8 pmol/l (n = 26; not significant). Twelve patients were treated for more than 6 months, and those with pituitary-dependent disease all received pituitary radiation therapy, except the two who eventually escaped pharmacological control. One additional patient with adrenal carcinoma and one with ectopic ACTH syndrome showed lack of control of urinary cortisol levels. Ketoconazole was withdrawn within the first week in two patients for allergic reaction and acute liver toxicity. Other side-effects included: asymptomatic liver function abnormalities in three patients; gastrointestinal symptoms in four; worsening of gynaecomastia in one. Rapid clinical improvement was observed together with the normalization of urinary cortisol levels, with regression of symptoms such as diabetes mellitus, hypertension, hypokalaemia, and restoration of well being. CONCLUSIONS: These data confirm that ketoconazole is valuable in the management of hypercortisolism, provided that patients are closely watched to exclude those who may develop liver toxicity and to prevent the occurrence of adrenal insufficiency.
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“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 [279]
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Palliative Care and Endocrine Diseases
Rao, P. D., & Kumar, K. (2024) · Springer eBooks · doi:10.1007/978-3-031-48991-4_112
Medical therapies for Cushing’s syndrome
Pivonello, R., Paola, N. D., Simeoli, C., & Colao, A. (2026) · Elsevier eBooks · doi:10.1016/b978-0-323-96100-4.00001-6
Speck, C. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-44037-3.00007-5
Pituitary Tumors, ACTH-Secreting
Putignano, P., Giraldi, F. P., & Cavagnini, F. (2004) · Elsevier eBooks · doi:10.1016/b0-12-475570-4/00013-5
Metadata
- Authors
- Sonino, N., Boscaro, M., Paoletta, A., Mantero, F., & Zillotto, D.
- Affiliations
- University of Padua (IT)
- University of Catania (IT)
- Corresponding author
- Sonino, Nicoletta
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 1991-10
- Volume
- 35
- Issue
- 4
- Pages
- 347-352
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W1966571242
- Cited by
- 201
- References
- 20
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 7 · 2020: 5 · 2019: 9 · 2018: 7 · 2017: 5 · 2016: 5 · 2015: 10 · 2014: 10 · 2013: 9 · 2012: 12
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (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 syndrome, hypercortisolism, pituitary-dependent Cushing's disease, adrenocortical carcinoma, ectopic ACTH syndrome, urinary cortisol, plasma cortisol, ACTH, hepatotoxicity, adverse drug reactions, palliative care, diabetes mellitus, hypertension, hypokalemia, gynecomastia
- MeSH terms
- Adolescent, Adult, Aged, Cushing Syndrome, Drug Administration Schedule, Female, Humans, Hydrocortisone, Ketoconazole, Male, Middle Aged, Chemical and Drug Induced Liver Injury
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