Cardiovascular and metabolic risk factors in patients with subclinical Cushing

Petramala, Luigi; Olmati, Federica; Concistrè, Antonio; Russo, Ralph P.; Mezzadri, Martina; Soldini, Maurizio; Vincentis, Giuseppe De; Iannucci, Gino; Toma, Giorgio De; Letizia, Claudio

doi:10.1007/s12020-020-02297-2

Cited by 27 publications

(27 citation statements)

References 46 publications

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“…Indeed, for exogenous glucocorticoid administration, pharmacokinetics may importantly influence the level of glucocorticoid excess, especially for low-dose systemic treatments, or in case of local administrations. For endogenous Cushing's syndrome, increased morbidity and mortality related to mild autonomous cortisol excess is well demonstrated on population level (9,10), but 6 cannot be estimated properly on an individual level using classical hormone assays. For patients with adrenal insufficiency, titration of glucocorticoid supplementation relies mainly on clinical assessment.…”

Section: Introductionmentioning

confidence: 99%

Identification of glucocorticoid-related molecular signature by whole blood methylome analysis

Armignacco

Jouinot

Bouys

et al. 2022

European Journal of Endocrinology

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Objective: Cushing’s syndrome represents a state of excessive glucocorticoids related to glucocorticoid treatments or to endogenous hypercortisolism. Cushing’s syndrome is associated with high morbidity, with significant inter-individual variability. Likewise, adrenal insufficiency is a life-threatening condition of cortisol deprivation. Currently, hormone assays contribute to identify Cushing’s syndrome or adrenal insufficiency. However, no biomarker directly quantifies the biological glucocorticoid action. The aim of this study was to identify such markers. Design: We evaluated whole blood DNA methylome in 94 samples obtained from patients with different glucocorticoid states (Cushing’s syndrome, eucortisolism, adrenal insufficiency). We used an independent cohort of 91 samples for validation. Methods: Leukocyte DNA was obtained from whole blood samples. Methylome was determined using the Illumina methylation chip array (~850000 CpG sites). Both unsupervised (Principal Component Analysis) and supervised (Limma) methods were used to explore methylome profiles. A Lasso-penalized regression was used to select optimal discriminating features. Results: Whole blood methylation profile was able to discriminate samples by their glucocorticoid status: glucocorticoid excess was associated with DNA hypomethylation, recovering within months after Cushing’s syndrome correction. In Cushing’s syndrome, an enrichment in hypomethylated CpG sites was observed in the region of FKBP5 gene locus. A methylation predictor of glucocorticoid excess was built on a training cohort and validated on two independent cohorts. Potential CpG sites associated with the risk for specific complications, such as glucocorticoid-related hypertension or osteoporosis, were identified, needing now to be confirmed on independent cohorts. Conclusions: Whole blood DNA methylome is dynamically impacted by glucocorticoids. This biomarker could contribute to better assess glucocorticoid action beyond hormone assays.

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Section: Introductionmentioning

confidence: 99%

Identification of glucocorticoid-related molecular signature by whole blood methylome analysis

Armignacco

Jouinot

Bouys

et al. 2022

European Journal of Endocrinology

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“…Some researchers also noticed an improvement in AH [106][107][108][109][110], body weight and BMI [107][108][109][110]. Petramala et al also demonstrated a reduction in the number of used antihypertensive drugs after surgery [48].…”

Section: Treatmentmentioning

confidence: 95%

“…Patients affected with subclinical Cushing's syndrome are at higher risk of CVE and AH [7,33,[44][45][46][47][48][49]. Moreover, patients with mACS are also at risk of new CVE described as coronary heart disease and ischemic or haemorrhagic stroke with further persistence of cortisol secretion [33].…”

Section: Cardiovascular Diseases and Arterial Hypertension (Ah)mentioning

confidence: 99%

Comorbidities in Mild Autonomous Cortisol Secretion – A Clinical Review of Literature

Czapla-Iskrzycka

Świątkowska−Stodulska

Sworczak

2022

Exp Clin Endocrinol Diabetes

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Mild autonomous cortisol secretion (mACS) is a state of cortisol excess usually associated with existence of adrenal incidentaloma. Because of the lack of symptoms of the disease, the biochemical evaluation is the most important to determine a diagnosis. However, scientific societies have different diagnostic criteria for mACS, which makes the treatment of this disease and using results of original papers in daily practice more difficult. Chronic hypercortisolemic state, even if mild, may lead to diseases that are mostly connected with overt Cushing’s syndrome. Some of them can cause a higher mortality of patients with mACS and those problems need to be addressed. In this review we describe the comorbidities associated with mACS: cardiovascular disorders, arterial hypertension, diabetes mellitus, insulin resistance, dyslipidemia, obesity, metabolic syndrome, non-alcoholic fatty liver disease, vertebral fractures and osteoporosis. The point of this paper is to characterise them and determine if and how these conditions should be managed. Two databases – PubMed and Web of Science were searched. Even though the evidence are scarce, this is an attempt to lead clinicians through the problems associated with this enigmatic condition.

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“…L'ipertensione è una delle alterazioni più frequenti nella SAC (prevalenza media del 70% circa), seguita dalle alterazioni del metabolismo glucidico (circa il 30% dei pazienti). Studi trasversali e retrospettivi a lungo termine hanno messo in evidenza anche un incremento della prevalenza e dell'incidenza di eventi cardiovascolari, come infarto, ictus e morte da cause cardiovascolari nei pazienti con SAC non trattati, rispetto ai soggetti con masse surrenaliche non secernenti (Tabella 1) [10][11][12][13][14][15][16][17].…”

Section: Secrezione Autonoma DI Cortisolounclassified

Il rischio cardiovascolare nel paziente con lesione surrenalica

Tucci

Dalmazi

2022

L'Endocrinologo

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SommarioIl riscontro di lesioni surrenaliche è in crescente aumento nella pratica clinica. Le lesioni surrenaliche secernenti (aldosterone, cortisolo o catecolamine) si associano a un elevato rischio di comorbidità ed eventi cardiovascolari rispetto alle lesioni non secernenti e alla popolazione generale, con quadri clinici sostanzialmente diversi in accordo al tipo di secrezione ormonale. Questa rassegna riassume le principali problematiche cardiovascolari nelle lesioni surrenaliche benigne.

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Cardiovascular and metabolic risk factors in patients with subclinical Cushing

Cited by 27 publications

References 46 publications

Identification of glucocorticoid-related molecular signature by whole blood methylome analysis

Identification of glucocorticoid-related molecular signature by whole blood methylome analysis

Comorbidities in Mild Autonomous Cortisol Secretion – A Clinical Review of Literature

Il rischio cardiovascolare nel paziente con lesione surrenalica

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