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Updates on the role of adrenal steroidogenesis inhibitors in Cushing’s syndrome: a focus on novel therapies

PURPOSE: Endogenous Cushing’s syndrome (CS) is a rare disease that results from exposure to high levels of cortisol; Cushing’s disease (CD) is the most frequent form of CS. Patients with CS suffer from a variety of comorbidities that increase the risk of mortality. Surgical resection of the disease-...

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Autores principales: Fleseriu, Maria, Castinetti, Frederic
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5080363/
https://www.ncbi.nlm.nih.gov/pubmed/27600150
http://dx.doi.org/10.1007/s11102-016-0742-1
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author Fleseriu, Maria
Castinetti, Frederic
author_facet Fleseriu, Maria
Castinetti, Frederic
author_sort Fleseriu, Maria
collection PubMed
description PURPOSE: Endogenous Cushing’s syndrome (CS) is a rare disease that results from exposure to high levels of cortisol; Cushing’s disease (CD) is the most frequent form of CS. Patients with CS suffer from a variety of comorbidities that increase the risk of mortality. Surgical resection of the disease-causing lesion is generally the first-line treatment of CS. However, some patients may not be eligible for surgery due to comorbidities, and approximately 25 % of patients, especially those with CD, have recurrent disease. For these patients, adrenal steroidogenesis inhibitors may control cortisol elevation and subsequent symptomatology. CS is rare overall, and clinical studies of adrenal steroidogenesis inhibitors are often small and, in many cases, data are limited regarding the efficacy and safety of these treatments. Our aim was to better characterize the profiles of efficacy and safety of currently available adrenal steroidogenesis inhibitors, including drugs currently in development. METHODS: We performed a systematic review of the literature regarding adrenal steroidogenesis inhibitors, focusing on novel drugs. RESULTS: Currently available adrenal steroidogenesis inhibitors, including ketoconazole, metyrapone, etomidate, and mitotane, have variable efficacy and significant side effects, and none are approved by the US Food and Drug Administration for CS. Therefore, there is a clear need for novel, prospectively studied agents that have greater efficacy and a low rate of adverse side effects. Efficacy and safety data of current and emerging adrenal steroidogenesis inhibitors, including osilodrostat (LCI699) and levoketoconazole (COR-003), show promising results that will have to be confirmed in larger-scale phase 3 studies (currently ongoing). CONCLUSIONS: The management of CS, and particularly CD, remains challenging. Adrenal steroidogenesis inhibitors can be of major interest to control the hypercortisolism at any time point, either before or after surgery, as discussed in this review.
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spelling pubmed-50803632016-11-07 Updates on the role of adrenal steroidogenesis inhibitors in Cushing’s syndrome: a focus on novel therapies Fleseriu, Maria Castinetti, Frederic Pituitary Article PURPOSE: Endogenous Cushing’s syndrome (CS) is a rare disease that results from exposure to high levels of cortisol; Cushing’s disease (CD) is the most frequent form of CS. Patients with CS suffer from a variety of comorbidities that increase the risk of mortality. Surgical resection of the disease-causing lesion is generally the first-line treatment of CS. However, some patients may not be eligible for surgery due to comorbidities, and approximately 25 % of patients, especially those with CD, have recurrent disease. For these patients, adrenal steroidogenesis inhibitors may control cortisol elevation and subsequent symptomatology. CS is rare overall, and clinical studies of adrenal steroidogenesis inhibitors are often small and, in many cases, data are limited regarding the efficacy and safety of these treatments. Our aim was to better characterize the profiles of efficacy and safety of currently available adrenal steroidogenesis inhibitors, including drugs currently in development. METHODS: We performed a systematic review of the literature regarding adrenal steroidogenesis inhibitors, focusing on novel drugs. RESULTS: Currently available adrenal steroidogenesis inhibitors, including ketoconazole, metyrapone, etomidate, and mitotane, have variable efficacy and significant side effects, and none are approved by the US Food and Drug Administration for CS. Therefore, there is a clear need for novel, prospectively studied agents that have greater efficacy and a low rate of adverse side effects. Efficacy and safety data of current and emerging adrenal steroidogenesis inhibitors, including osilodrostat (LCI699) and levoketoconazole (COR-003), show promising results that will have to be confirmed in larger-scale phase 3 studies (currently ongoing). CONCLUSIONS: The management of CS, and particularly CD, remains challenging. Adrenal steroidogenesis inhibitors can be of major interest to control the hypercortisolism at any time point, either before or after surgery, as discussed in this review. Springer US 2016-09-06 2016 /pmc/articles/PMC5080363/ /pubmed/27600150 http://dx.doi.org/10.1007/s11102-016-0742-1 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Article
Fleseriu, Maria
Castinetti, Frederic
Updates on the role of adrenal steroidogenesis inhibitors in Cushing’s syndrome: a focus on novel therapies
title Updates on the role of adrenal steroidogenesis inhibitors in Cushing’s syndrome: a focus on novel therapies
title_full Updates on the role of adrenal steroidogenesis inhibitors in Cushing’s syndrome: a focus on novel therapies
title_fullStr Updates on the role of adrenal steroidogenesis inhibitors in Cushing’s syndrome: a focus on novel therapies
title_full_unstemmed Updates on the role of adrenal steroidogenesis inhibitors in Cushing’s syndrome: a focus on novel therapies
title_short Updates on the role of adrenal steroidogenesis inhibitors in Cushing’s syndrome: a focus on novel therapies
title_sort updates on the role of adrenal steroidogenesis inhibitors in cushing’s syndrome: a focus on novel therapies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5080363/
https://www.ncbi.nlm.nih.gov/pubmed/27600150
http://dx.doi.org/10.1007/s11102-016-0742-1
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