Management and Medical Therapy of Mild Hypercortisolism

Mild hypercortisolism (mHC) is defined as an excessive cortisol secretion, without the classical manifestations of clinically overt Cushing’s syndrome. This condition increases the risk of bone fragility, neuropsychological alterations, hypertension, diabetes, cardiovascular events and mortality. At...

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Autores principales:	Vittoria Favero, Arianna Cremaschi, Alberto Falchetti, Agostino Gaudio, Luigi Gennari, Alfredo Scillitani, Fabio Vescini, Valentina Morelli, Carmen Aresta, Iacopo Chiodini
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	hypercortisolism adrenal steroidogenesis glucocorticoid receptor 11 betahydroxysteroid dehydrogenase somatostatin dopamine Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/f066ee1f63764208949ae38c0e3798e1
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spelling	oai:doaj.org-article:f066ee1f63764208949ae38c0e3798e12021-11-11T16:58:47ZManagement and Medical Therapy of Mild Hypercortisolism10.3390/ijms2221115211422-00671661-6596https://doaj.org/article/f066ee1f63764208949ae38c0e3798e12021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11521https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Mild hypercortisolism (mHC) is defined as an excessive cortisol secretion, without the classical manifestations of clinically overt Cushing’s syndrome. This condition increases the risk of bone fragility, neuropsychological alterations, hypertension, diabetes, cardiovascular events and mortality. At variance with Cushing’s syndrome, mHC is not rare, with it estimated to be present in up to 2% of individuals older than 60 years, with higher prevalence (up to 10%) in individuals with uncontrolled hypertension and/or diabetes or with unexplainable bone fragility. Measuring cortisol after a 1 mg overnight dexamethasone suppression test is the first-line test for searching for mHC, and the degree of cortisol suppression is associated with the presence of cortisol-related consequences and mortality. Among the additional tests used for diagnosing mHC in doubtful cases, the basal morning plasma adrenocorticotroph hormone, 24-h urinary free cortisol and/or late-night salivary cortisol could be measured, particularly in patients with possible cortisol-related complications, such as hypertension and diabetes. Surgery is considered as a possible therapeutic option in patients with munilateral adrenal incidentalomas and mHC since it improves diabetes and hypertension and reduces the fracture risk. In patients with mHC and bilateral adrenal adenomas, in whom surgery would lead to persistent hypocortisolism, and in patients refusing surgery or in whom surgery is not feasible, medical therapy is needed. Currently, promising though scarce data have been provided on the possible use of pituitary-directed agents, such as the multi-ligand somatostatin analog pasireotide or the dopamine agonist cabergoline for the—nowadays—rare patients with pituitary mHC. In the more frequently adrenal mHC, encouraging data are available for metyrapone, a steroidogenesis inhibitor acting mainly against the adrenal 11-βhydroxylase, while data on osilodrostat and levoketoconazole, other new steroidogenesis inhibitors, are still needed in patients with mHC. Finally, on the basis of promising data with mifepristone, a non-selective glucocorticoid receptor antagonist, in patients with mild cortisol hypersecretion, a randomized placebo-controlled study is ongoing for assessing the efficacy and safety of relacorilant, a selective glucocorticoid receptor antagonist, for patients with mild adrenal hypercortisolism and diabetes mellitus/impaired glucose tolerance and/or uncontrolled systolic hypertension.Vittoria FaveroArianna CremaschiAlberto FalchettiAgostino GaudioLuigi GennariAlfredo ScillitaniFabio VesciniValentina MorelliCarmen ArestaIacopo ChiodiniMDPI AGarticlehypercortisolismadrenal steroidogenesisglucocorticoid receptor11 betahydroxysteroid dehydrogenasesomatostatindopamineBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11521, p 11521 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hypercortisolism adrenal steroidogenesis glucocorticoid receptor 11 betahydroxysteroid dehydrogenase somatostatin dopamine Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	hypercortisolism adrenal steroidogenesis glucocorticoid receptor 11 betahydroxysteroid dehydrogenase somatostatin dopamine Biology (General) QH301-705.5 Chemistry QD1-999 Vittoria Favero Arianna Cremaschi Alberto Falchetti Agostino Gaudio Luigi Gennari Alfredo Scillitani Fabio Vescini Valentina Morelli Carmen Aresta Iacopo Chiodini Management and Medical Therapy of Mild Hypercortisolism
description	Mild hypercortisolism (mHC) is defined as an excessive cortisol secretion, without the classical manifestations of clinically overt Cushing’s syndrome. This condition increases the risk of bone fragility, neuropsychological alterations, hypertension, diabetes, cardiovascular events and mortality. At variance with Cushing’s syndrome, mHC is not rare, with it estimated to be present in up to 2% of individuals older than 60 years, with higher prevalence (up to 10%) in individuals with uncontrolled hypertension and/or diabetes or with unexplainable bone fragility. Measuring cortisol after a 1 mg overnight dexamethasone suppression test is the first-line test for searching for mHC, and the degree of cortisol suppression is associated with the presence of cortisol-related consequences and mortality. Among the additional tests used for diagnosing mHC in doubtful cases, the basal morning plasma adrenocorticotroph hormone, 24-h urinary free cortisol and/or late-night salivary cortisol could be measured, particularly in patients with possible cortisol-related complications, such as hypertension and diabetes. Surgery is considered as a possible therapeutic option in patients with munilateral adrenal incidentalomas and mHC since it improves diabetes and hypertension and reduces the fracture risk. In patients with mHC and bilateral adrenal adenomas, in whom surgery would lead to persistent hypocortisolism, and in patients refusing surgery or in whom surgery is not feasible, medical therapy is needed. Currently, promising though scarce data have been provided on the possible use of pituitary-directed agents, such as the multi-ligand somatostatin analog pasireotide or the dopamine agonist cabergoline for the—nowadays—rare patients with pituitary mHC. In the more frequently adrenal mHC, encouraging data are available for metyrapone, a steroidogenesis inhibitor acting mainly against the adrenal 11-βhydroxylase, while data on osilodrostat and levoketoconazole, other new steroidogenesis inhibitors, are still needed in patients with mHC. Finally, on the basis of promising data with mifepristone, a non-selective glucocorticoid receptor antagonist, in patients with mild cortisol hypersecretion, a randomized placebo-controlled study is ongoing for assessing the efficacy and safety of relacorilant, a selective glucocorticoid receptor antagonist, for patients with mild adrenal hypercortisolism and diabetes mellitus/impaired glucose tolerance and/or uncontrolled systolic hypertension.
format	article
author	Vittoria Favero Arianna Cremaschi Alberto Falchetti Agostino Gaudio Luigi Gennari Alfredo Scillitani Fabio Vescini Valentina Morelli Carmen Aresta Iacopo Chiodini
author_facet	Vittoria Favero Arianna Cremaschi Alberto Falchetti Agostino Gaudio Luigi Gennari Alfredo Scillitani Fabio Vescini Valentina Morelli Carmen Aresta Iacopo Chiodini
author_sort	Vittoria Favero
title	Management and Medical Therapy of Mild Hypercortisolism
title_short	Management and Medical Therapy of Mild Hypercortisolism
title_full	Management and Medical Therapy of Mild Hypercortisolism
title_fullStr	Management and Medical Therapy of Mild Hypercortisolism
title_full_unstemmed	Management and Medical Therapy of Mild Hypercortisolism
title_sort	management and medical therapy of mild hypercortisolism
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f066ee1f63764208949ae38c0e3798e1
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Management and Medical Therapy of Mild Hypercortisolism

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