Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2023 May 8:14:1145775.
doi: 10.3389/fendo.2023.1145775. eCollection 2023.

Ketoconazole as second-line treatment for Cushing's disease after transsphenoidal surgery: systematic review and meta-analysis

Camila Viecceli  1 , Ana Carolina Viana Mattos  1 , Vânia Naomi Hirakata  1 , Sheila Piccoli Garcia  1 , Ticiana da Costa Rodrigues  1   2   3 , Mauro Antônio Czepielewski  1   2   3
Affiliations
Meta-Analysis

Ketoconazole as second-line treatment for Cushing's disease after transsphenoidal surgery: systematic review and meta-analysis

Camila Viecceli et al. Front Endocrinol (Lausanne). .

Abstract

Introduction: The first-line treatment for Cushing's disease is transsphenoidal surgery for pituitary tumor resection. Ketoconazole has been used as a second-line drug despite limited data on its safety and efficacy for this purpose. The objective of this meta-analysis was to analyze hypercortisolism control in patients who used ketoconazole as a second-line treatment after transsphenoidal surgery, in addition to other clinical and laboratory criteria that could be related to therapeutic response.

Methods: We searched for articles that evaluated ketoconazole use in Cushing's disease after transsphenoidal surgery. The search strategies were applied to MEDLINE, EMBASE, and SciELO. Independent reviewers assessed study eligibility and quality and extracted data on hypercortisolism control and related variables such as therapeutic dose, time, and urinary cortisol levels.

Results: After applying the exclusion criteria, 10 articles (one prospective and nine retrospective studies, totaling 270 patients) were included for complete data analysis. We found no publication bias regarding reported biochemical control or no biochemical control (p = 0.06 and p = 0.42 respectively). Of 270 patients, biochemical control of hypercortisolism occurred in 151 (63%, 95% CI 50-74%) and no biochemical control occurred in 61 (20%, 95% CI 10-35%). According to the meta-regression, neither the final dose, treatment duration, nor initial serum cortisol levels were associated with biochemical control of hypercortisolism.

Conclusion: Ketoconazole can be considered a safe and efficacious option for Cushing's disease treatment after pituitary surgery.

Systematic review registration: https://www.crd.york.ac.uk/prospero/#searchadvanced, (CRD42022308041).

Keywords: Cushing’s disease; ketoconazole; meta-analysis; systematic review; treatment.

PubMed Disclaimer

Conflict of interest statement

TCR received a CNPQ research grant. MAC worked on clinical research for Crinetics and on the advisory board for Novo Nordisk. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram: Identification and selection of articles for the meta-analysis.
Figure 2
Figure 2
Funnel Plot of hypercortisolism remission with Ketoconazole.
Figure 3
Figure 3
Funnel Plot of hypercortisolism non-remission with ketoconazole.
Figure 4
Figure 4
Forest plot of hypercortisolism remission with Ketoconazole.
Figure 5
Figure 5
Forest plot of hypercortisolism non-remission with ketoconazole.
See this image and copyright information in PMC

References

    1. Fleseriu M, Castinetti F. Updates on the role of adrenal steroidogenesis inhibitors in cushing’s syndrome: a focus on novel therapies. Pituitary (2016). 643–53. doi: 10.1007/s11102-016-0742-1 - DOI - PMC - PubMed
    1. Fleseriu M, Auchus R, Bancos I, Ben-Shlomo A, Bertherat J, Biermasz NR, et al. . Consensus on diagnosis and management of cushing’s disease: a guideline update. Lancet Diabetes Endocrinol (2021) 9(12):847–75. doi: 10.1016/S2213-8587(21)00235-7 - DOI - PMC - PubMed
    1. Nieman LK, Biller BMK, Findling JW, Newell-Price J, Savage MO, Stewart PM, et al. . The diagnosis of cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab (2008) 93(5):1526–40. doi: 10.1210/jc.2008-0125 - DOI - PMC - PubMed
    1. Nieman LK, Biller BMK, Findling JW, Murad MH, Newell-Price J, Savage MO, et al. . Treatment of cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab (2015) 100(8):2807–31. doi: 10.1210/jc.2015-1818 - DOI - PMC - PubMed
    1. Clayton RN, Raskauskiene D, Reulen RC, Jones PW. Mortality and morbidity in cushing’s disease over 50 years in Stoke-on-Trent, UK: audit and meta-analysis of literature. J Clin Endocrinol Metab (2011). 632–42. doi: 10.1210/jc.2010-1942 - DOI - PubMed

Publication types