A reappraisal of the medical therapy with steroidogenesis inhibitors in C ushing's syndrome
Open accessAbstract
OBJECTIVE: To evaluate the outcome of preoperative therapy with ketoconazole (KTZ) and/or metyrapone (MTP) in previously untreated patients with Cushing's syndrome (CS). DESIGN AND PATIENTS: Sixty-two patients with CS (85% ACTH dependent), treated with steroidogenesis inhibitors prior to surgery between 1983 and 2010, were retrospectively studied. T(0) and t(1) defined baseline and end of preoperative medical treatment. RESULTS: Outcomes were based upon clinical and biochemical (normal UFC) control of hypercortisolism at t(1) : group CO (controlled) included 20 patients (32%) with eucortisolism and significant clinical improvement; group NC (not controlled) 30 (48%) with persistent hypercortisolism and no control of symptoms; and group PC (partially controlled) 12 patients (19%) who despite eucortisolism had no real clinical improvement. Median duration of treatment was 4 months (range: 1-30·7), and median cumulative dose of KTZ and MTP was 57 g (range: 3·6-240) and 120 g (range: 7·5-1215). CO patients were treated more with KTZ alone than the other groups (P < 0·05). MTP alone was administered more in PC than in CO patients (P < 0·01). No clinical differences were observed between groups at baseline. Systolic blood pressure at t(1) was higher in PC than in NC patients (P < 0·05). Hypertension persisted more in PC patients than in the other groups (P < 0·05) after a median postsurgery follow-up of 108 months (range: 4-276). CONCLUSIONS: Preoperative administration of KTZ, MTP or both normalized UFC in 52% of patients with CS, but concomitant clinical improvement did not always follow. Larger, multicentre studies are needed to individualize preoperative medical treatment and improve outcome in patients with CS.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
At doses of 200 to 1200 mg daily, ketoconazole has been shown to improve glucose metabolism in patients with Cushing syndrome and in those with type 2 diabetes.
“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 [283]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Chobanian, A. V., Bakris, G. L., Black, H. R., Cushman, W. C., Green, L. A., Izzo, J. L., Jones, D. W., Materson, B. J., Oparil, S., Wright, J. T., et al. (2003) · Hypertension · doi:10.1161/01.hyp.0000107251.49515.c2 · Cited by 13,271 · see citing works
Detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III)
Grundy, S. M., Becker, D. M., Clark, L. T., Cooper, R., Denke, M. A., Howard, J. L., Hunninghake, D. B., Illingworth, D. R., Luepker, R. V., McBride, P. E., et al. (2002) · Civil War Book Review · Cited by 12,198 · see citing works
Standards of medical care in diabetes 2010
American Diabetes Association (2010) · Diabetes Care · doi:10.2337/dc10-s011 · Cited by 3,470 · see citing works
Newell-Price, J. D. C., BERTAGNA, X. Y., Grossman, A. B., & Nieman, L. K. (2006) · The Lancet · doi:10.1016/s0140-6736(06)68699-6 · Cited by 1,220 · see citing works
Treatment of adrenocorticotropin-dependent Cushing’s syndrome: a consensus statement
Biller, B. M. K., Grossman, A. B., Stewart, P. M., Melmed, S., Bertagna, X., Bertherat, J., Buchfelder, M., Colao, A., Hermus, A. R., Hofland, L. J., et al. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2734 · Cited by 853 · see citing works
Colao, A., Pivonello, R., Spiezia, S., Faggiano, A., Ferone, D., Filippella, M., Marzullo, P., Cerbone, G., Siciliani, M., & Lombardi, G. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.8.5896 · Cited by 448 · see citing works
Verhelst, J. A., Trainer, P. J., Howlett, T. A., Perry, L., Rees, L. H., Grossman, A. B., Wass, J. A. H., & Sesser, G. M. (1991) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1991.tb03517.x · Cited by 308 · see citing works
Pasireotide alone or with cabergoline and ketoconazole in Cushing's disease.
Feelders, R., de Bruin, C., Pereira, A., Romijn, J., Netea-Maier, R., Hermus, A., Zelissen, P., van Heerebeek, R. E. A., de Jong, F. D., van der Lely, A. J., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmc1000094 · Cited by 251 · see citing works
Incidence of Venous Thromboembolism in Patients with Cushing's Syndrome: A Multicenter Cohort Study
Stuijver, D. J. F., van Zaane, B., Feelders, R. A., Debeij, J., Cannegieter, S. C., Hermus, A. R., van den Berg, G., Pereira, A. M., de Herder, W. W., Wagenmakers, M. A. E. M., et al. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1661 · Cited by 208 · see citing works
Ketoconazole treatment in Cushing’s syndrome: experience in 34 patients
Sonino, N., Boscaro, M., Paoletta, A., Mantero, F., & Zillotto, D. (1991) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1991.tb03547.x · Cited by 201 · see citing works
Ketoconazole revisited: a preoperative or postoperative treatment in Cushing’s disease
Castinetti, F., Morange, I., Jaquet, P., Conte-Devolx, B., & Brue, T. (2008) · European Journal of Endocrinology · doi:10.1530/eje-07-0514 · Cited by 175 · see citing works
Use of Ketoconazole in the Treatment of Cushing’s Syndrome
Loli, P., Berselli, M. E., & Tagliaferri, M. (1986) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-63-6-1365 · Cited by 153 · see citing works
Therapy of Cushing's syndrome with steroid biosynthesis inhibitors
Engelhardt, D., & Weber, M. M. (1994) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(94)90267-4 · Cited by 133 · see citing works
Monaghan, P. J., Owen, L. J., Trainer, P. J., Brabant, G., Keevil, B. G., & Darby, D. (2011) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1258/acb.2011.011014 · Cited by 111 · see citing works
Medical Treatment of Cushing’s Syndrome: Adrenal-Blocking Drugs and Ketaconazole
Feelders, R. A., Hofland, L. J., & de Herder, W. W. (2010) · Neuroendocrinology · doi:10.1159/000314292 · Cited by 94 · see citing works
Use of ketoconazole in the treatment of Cushing's disease and ectopic ACTH syndrome
Tabarin, A., Navarranne, A., Guerin, J. B., Corcuff, J., Parneix, M., & Roger, P. (1991) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1991.tb01737.x · Cited by 83 · see citing works
CLINICAL EXPERIENCE WITH KETOCONAZOLE AS A THERAPY FOR PATIENTS WITH CUSHING'S SYNDROME
McCance, D. R., Hadden, D. R., Kennedy, L., Sheridan, B., & Atkinson, A. B. (1987) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1987.tb01189.x · Cited by 77 · see citing works
Metyrapone Is Useful Only as Adjunctive Therapy in Cushing's Disease
Orth, D. N. (1978) · Annals of Internal Medicine · doi:10.7326/0003-4819-89-1-128 · Cited by 64 · see citing works
Adipokines and Cardiovascular Risk in Cushing’s Syndrome
Valassi, E., Biller, B. M. K., Klibanski, A., & Misra, M. (2011) · Neuroendocrinology · doi:10.1159/000330416 · Cited by 53 · see citing works
Self-citationBOSCARO, M., SONINO, N., RAMPAZZO, A., & MANTERO, F. (1987) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1987.tb01174.x · Cited by 43 · see citing works
Prolonged remission in florid Cushing’s syndrome following metyrapone treatment
BEARDWELL, C. G., ADAMSON, A. R., & SHALET, S. M. (1981) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1981.tb00638.x · Cited by 34 · see citing works
Pharmacological management of Cushing's syndrome: an update
Dang, C. N., & Trainer, P. J. (2007) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302007000800020 · Cited by 31 · see citing works
KETOCONAZOLE AND PLASMA AND URINE STEROID LEVELS IN CUSHING'S DISEASE
Mortimer, R. H., Cannell, G. R., Thew, C. M., et al. (1991) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.1991.tb01492.x · Cited by 23 · see citing works
[Short term effects of ketoconazole in Cushing's syndrome].
Cerdas, S., BILLAUD, L., Guilhaume, B., Laudat, M. H., BERTAGNA, X. Y., & LUTON, J. P. (1989) · PubMed · Cited by 15 · see citing works
Arterial hypertension as a complication of prolonged ketoconazole treatment
Leal‐Cerro, A., García‐Luna, P. P., Villar, J. R., Miranda, M. L., Pereira, J. L. S., Gómez-Pan, A., & Astorga, R. (1989) · Journal of Hypertension · doi:10.1097/00004872-198900076-00102 · Cited by 14 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Feelders, R.A., de Bruin, C., Pereira, A.M. et al. (2010) Stepwise medical treatment of Cushing's disease with pasireo- tide mono-or combination therapy with cabergoline and low- dose ketoconazole. New England Journal of Medicine, 362, 1846-1848.
Cited by
Sorted by citations
Treatment of Cushing's syndrome: an Endocrine Society clinical practice guideline
Nieman, L. K., Biller, B. M. K., Findling, J. W., Murad, M. H., Newell-Price, J., Savage, M. O., & Tabarin, A. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-1818 · Cited by 1,270 · see citing works
Ketoconazole in Cushing's disease: is it worth a try?
Castinetti, F., Guignat, L., Giraud, P., Muller, M., Kamenicky, P., Drui, D., Caron, P., Luca, F., Donadille, B., Vantyghem, M. C., et al. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-3628 · Cited by 285 · see citing works
Daniel, E., Aylwin, S., Mustafa, O., Ball, S., Munir, A., Boelaert, K., Chortis, V., Cuthbertson, D. J., Daousi, C., Rajeev, S. P., et al. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-2616 · Cited by 231 · see citing works
Efficiency and tolerance of mitotane in Cushing's disease in 76 patients from a single center
Baudry, C., Coste, J., Bou Khalil, R., Silvera, S., Guignat, L., Guibourdenche, J., Abbas, H., Legmann, P., Bertagna, X., & Bertherat, J. (2012) · European Journal of Endocrinology · doi:10.1530/eje-12-0358 · Cited by 187 · see citing works
Glucose Metabolism Abnormalities in Cushing Syndrome: From Molecular Basis to Clinical Management
Scaroni, C., Zilio, M., Foti, M., & Boscaro, M. (2017) · Endocrine Reviews · doi:10.1210/er.2016-1105 · Cited by 140 · see citing works
Fleseriu, M., & Castinetti, F. (2016) · Pituitary · doi:10.1007/s11102-016-0742-1 · Cited by 87 · see citing works
Baroni, M. G., Giorgino, F., Pezzino, V., Scaroni, C., & Avogaro, A. (2016) · Journal of Endocrinological Investigation · doi:10.1007/s40618-015-0404-6 · Cited by 41 · see citing works
- Authors
- Valassi, E., Crespo, I., Gich, I., Rodríguez, J., & Webb, S. M.
- Affiliations
- Universitat Autònoma de Barcelona (ES)
- Hospital de Sant Pau (ES)
- Department of Biochemistry Hospital Sant Pau Barcelona Spain
- Corresponding author
- Valassi, Elena
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2012-10-05
- Volume
- 77
- Issue
- 5
- Pages
- 735-742
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W2093986817
- Cited by
- 91
- References
- 26
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 7 · 2023: 9 · 2022: 7 · 2021: 5 · 2020: 6 · 2019: 6 · 2018: 8 · 2017: 5 · 2016: 8 · 2015: 12 · 2014: 5 · 2013: 5 · 2012: 4
- FWCI
- 6.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- 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
- Cushing's syndrome, steroidogenesis inhibitors, ketoconazole, metyrapone, preoperative medical therapy, ACTH-dependent Cushing's syndrome, hypercortisolism, urinary free cortisol, hypertension, surgical outcomes
- MeSH terms
- Adolescent, Adult, Aged, Antimetabolites, Child, Cushing Syndrome, Female, Humans, Ketoconazole, Male, Metyrapone, Middle Aged, Retrospective Studies, Young Adult, Preoperative Period
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
