Body Composition After Endogenous (Cushing's Syndrome) and Exogenous (Rheumatoid Arthritis) Exposure to Glucocorticoids

Resmini, Eugenia; Csaba, Farkas; Murillo, Barrios; Barahona, María José; Santos, Alicia; Martínez-Momblán, Ma Antonia; Roig, Olga; Ybarra, Juan; Geli, C.; Webb, SM

doi:10.1055/s-0030-1255032

Cited by 21 publications

(26 citation statements)

References 19 publications

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“…total body fat and trunk fat is higher in endogenous than exogenous CS (107). Recently, it has been shown that patients with CS due to primary pigmented nodular adrenal disease have a typically milder obese phenotype than other forms of CS, even when their cortisol levels are comparable and their CS is not atypical or cyclical (108).…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

Metabolic comorbidities in Cushing's syndrome

Ferraú

Korbonits

2015

European Journal of Endocrinology

149

121

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Cushing's syndrome (CS) patients have increased mortality primarily due to cardiovascular events induced by glucocorticoid (GC) excess-related severe metabolic changes. Glucose metabolism abnormalities are common in CS due to increased gluconeogenesis, disruption of insulin signalling with reduced glucose uptake and disposal of glucose and altered insulin secretion, consequent to the combination of GCs effects on liver, muscle, adipose tissue and pancreas. Dyslipidaemia is a frequent feature in CS as a result of GC-induced increased lipolysis, lipid mobilisation, liponeogenesis and adipogenesis. Protein metabolism is severely affected by GC excess via complex direct and indirect stimulation of protein breakdown and inhibition of protein synthesis, which can lead to muscle loss. CS patients show changes in body composition, with fat redistribution resulting in accumulation of central adipose tissue. Metabolic changes, altered adipokine release, GC-induced heart and vasculature abnormalities, hypertension and atherosclerosis contribute to the increased cardiovascular morbidity and mortality. In paediatric CS patients, the interplay between GC and the GH/IGF1 axis affects growth and body composition, while in adults it further contributes to the metabolic derangement. GC excess has a myriad of deleterious effects and here we attempt to summarise the metabolic comorbidities related to CS and their management in the perspective of reducing the cardiovascular risk and mortality overall.

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Section: European Journal Of Endocrinologymentioning

confidence: 99%

Metabolic comorbidities in Cushing's syndrome

Ferraú

Korbonits

2015

European Journal of Endocrinology

149

121

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“…Excess exposure to cortisol results in the development of insulin resistance, visceral fat formation, and reduction in lean body mass, and predisposes individuals to diabetes mellitus, premature coronary artery disease, and osteoporosis (Faggiano et al 2003; Kelly et al 1998; Pearce et al 1998; Resmini et al 2010; Tauchmanova et al 2002). Excess cortisol exposure also disrupts cognition and mood as well as other neural processes by inducing dendritic remodeling, suppressing neurogenesis, and causing atrophy of the hippocampus (Sapolsky et al 1990).…”

Section: Introductionmentioning

confidence: 99%

A measure of glucocorticoid load provided by DNA methylation of Fkbp5 in mice

et al. 2011

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Rationale Given the contribution of cortisol dysregulation to neuropsychiatric and metabolic disorders, it is important to be able to accurately compute glucocorticoid burden, a measure of allostatic load. One major problem in calculating cortisol burden is that existing measures reflect cortisol exposure over a short duration and have not been proven to reliably quantify cortisol burden over weeks or months. Method We treated two cohorts of mice with corticosterone in the drinking water and determined the relationship between serial plasma corticosterone levels drawn over 4 weeks and the whole-blood DNA methylation (DNAm) changes in a specific glucocorticoid-sensitive gene, Fkbp5, determined at the end of the treatment period. Results We observed that the percent reduction in DNAm in the intron 1 region of Fkbp5 determined from a single blood draw strongly reflected average glucocorticoid burden generated weekly during the prior month of glucocorticoid exposure. There were also strong correlations in DNAm with glucocorticoid-induced end organ changes in spleen weight and visceral fat. We tested a subset of these animals for anxiety-like behavior in the elevated plus maze and found that DNAm in the blood also has predictive value in determining the behavioral consequences of glucocorticoid exposure. Conclusion A whole-blood assessment of Fkbp5 gene methylation is a biomarker that integrates 4 weeks of glucocorticoid exposure and may be a useful measure in states of excess exposure. It will be important to determine if Fkbp5 DNAm changes can also be a biomarker of glucocorticoid burden during chronic social stress.

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“…Oral glucose tolerance test, 24-hour ambulatory blood pressure monitoring, echocardiography, electrocardiogram, and carotid ultrasound have been proposed in the followup to establish the cardiovascular risk in cured CS [31,141]. A combination of treatments directed both against hypercortisolism and aimed at controlling cardiovascular risk factors seems appropriate to reduce cardiovascular events in these patients [1,2,59].…”

Section: Discussionmentioning

confidence: 99%

Persistent Comorbidities in Cushing’s Syndrome after Endocrine Cure

Resmini

2014

Advances in Endocrinology

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It was assumed that resolution of hypercortisolism in Cushing syndrome (CS) was followed by normalization of morbidity; however, in the last decade evidence is accumulating that patients with cured CS still have increased morbidity and mortality after the biochemical control of hypercortisolism. Patients with CS have an increased cardiovascular and metabolic risk and persistent accumulation of central fat, with an unfavorable adipokine profile, not only during the active phase of the disease but also long after biochemical remission. Clinical management should be particularly careful in identifying global cardiovascular risk, as a primary goal during the followup of these patients, aimed at improving global vascular morbidity. Moreover bone mass is reduced not only due to the endogenous hypercortisolism but also due to duration and dose of exogenous glucocorticoid (GC) replacement therapy after surgery. Thus, therapy in operated patients with inhibition of the hypothalamic-pituitary-adrenal axis should be reduced to the lowest dose and duration possible. Specific treatments should be considered in patients with decreased bone mass, aimed at reducing the increased fracture incidence. Finally, cognitive and health related quality of life impairments, described in active disease, are still abnormal after endocrine cure. Thus, residual morbidity persists in cured CS, suggesting irreversibility of GC-induced phenomena, typical of chronic hypercortisolism.

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Body Composition After Endogenous (Cushing's Syndrome) and Exogenous (Rheumatoid Arthritis) Exposure to Glucocorticoids

Cited by 21 publications

References 19 publications

Metabolic comorbidities in Cushing's syndrome

Metabolic comorbidities in Cushing's syndrome

A measure of glucocorticoid load provided by DNA methylation of Fkbp5 in mice

Persistent Comorbidities in Cushing’s Syndrome after Endocrine Cure

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