Protein metabolism in glucocorticoid excess: study in Cushing's syndrome and the effect of treatment

Burt, Morton G.; Gibney, James

doi:10.1152/ajpendo.00524.2006

Cited by 33 publications

(20 citation statements)

References 57 publications

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“…Our results also indicate that the central obesity associated with long-term hypercortisolism in CS is not completely reversible after treatment. Previous studies on the reversibility of reduced LBM and skeletal muscle mass have demonstrated either unchanged (4,8,9,10) or reduced LBM after treatment (7,11). In our study, after adjustment for various confounders, no difference in skeletal muscle mass was observed between patients and controls.…”

Section: Discussioncontrasting

confidence: 58%

“…The study also demonstrates that ongoing GC replacement and a common polymorphism in the GC receptor gene are associated with adverse skeletal health in patients with CS in long-term remission. Adipose tissue mass decreases after treatment for CS (4,7,8,9,10), but whether complete normalisation occurs at long-term follow-up is not fully explored. One previous cross-sectional study found an increased total and abdominal fat mass in patients with CS after a mean time of 11 years in remission in comparison with age-, gender-and BMI-matched controls (11).…”

Section: Discussionmentioning

confidence: 99%

“…The median (interquartile rage) time in remission was 13 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) years. Nineteen (38%) patients were receiving GC replacement therapy: ten after bilateral adrenalectomy, seven due to pituitary insufficiency after transsphenoidal pituitary surgery and/or radiotherapy and two after unilateral adrenalectomy.…”

Section: Hormonal Statusmentioning

confidence: 99%

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Body composition and bone mineral density in women with Cushing's syndrome in remission and the association with common genetic variants influencing glucocorticoid sensitivity

Ragnarsson

Glad

Bergthorsdottir

et al. 2015

European Journal of Endocrinology

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Objective: Adverse body compositional features and low bone mineral density (BMD) are the characteristic of patients with active Cushing's syndrome (CS). The aim of this study was to evaluate body composition and BMD in women with CS in long-term remission and the influence of polymorphisms in genes affecting glucocorticoid (GC) sensitivity on these end-points. Design, patients and methods: This was a cross-sectional, case-controlled study, including 50 women previously treated for CS and 50 age and gender-matched controls. Median (interquartile range) remission time was 13 (5-19) years. Body composition and BMD were measured with dual-energy X-ray absorptiometry. Five polymorphisms in four genes associated with GC sensitivity were analysed using TaqMan or Sequenom single-nucleotide polymorphism genotyping. Results: Patients with CS in remission had increased abdominal fat mass (P!0.01), whereas BMD was not significantly different at any site between patients and controls. In patients, the NR3C1 Bcl1 polymorphism was associated with reduced total (P!0.05) and femur neck BMD (P!0.05). The polymorphism rs1045642 in the ABCB1 gene was associated with increased abdominal fat mass (P!0.05) and decreased appendicular skeletal muscle mass (P!0.05). GC replacement was associated with reduced total BMD (P!0.01), BMD at lumbar spine (P!0.05) and increased abdominal fat (P!0.01). Conclusion: Ongoing GC replacement therapy together with polymorphisms in two genes related with GC sensitivity is associated with abdominal obesity and adverse skeletal health in patients with CS in long-term remission.

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Section: Discussioncontrasting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Hormonal Statusmentioning

confidence: 99%

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Body composition and bone mineral density in women with Cushing's syndrome in remission and the association with common genetic variants influencing glucocorticoid sensitivity

Ragnarsson

Glad

Bergthorsdottir

et al. 2015

European Journal of Endocrinology

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“…However, long-term GC use is often associated with side effects including weight gain, impaired glucose homoeostasis, osteoporosis and muscle and skin atrophy (1). GCs induce protein catabolism by increasing irreversible oxidative loss of protein, resulting in skin thinning and muscle atrophy and weakness (2,3). To date, no specific treatment is available to prevent or reverse GC-induced protein wasting.…”

Section: Introductionmentioning

confidence: 99%

Effect of short-term GH and testosterone administration on body composition and glucose homoeostasis in men receiving chronic glucocorticoid therapy

Ragnarsson

Burt

Johannsson

2013

European Journal of Endocrinology

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Objective: Long-term pharmacological glucocorticoid (GC) therapy leads to skeletal muscle atrophy and weakness. The objective of this study was to investigate whether short-term treatment with GH and testosterone (T) can increase lean mass without major impairment of glucose homoeostasis in patients on GC therapy. Design, materials and methods: This was a prospective, open-label, randomised, crossover study. Twelve men (age 74G6 years) on chronic GC treatment participated. The effects of 2 weeks' treatment with GH, testosterone and the combination of both on lean body mass (LBM), appendicular skeletal muscle mass (ASMM), extracellular water (ECW), body cell mass (BCM) and plasma glucose concentrations were investigated. Results: LBM increased significantly after GH (D1.7G1.4 kg; PZ0.007) and GHCtestosterone (D2.4G1.1 kg; PZ0.003), but not testosterone alone. ASMM increased after all three treatment periods; by 1.0G0.8 kg after GH (PZ0.005), 1.7G0.4 kg after GHCtestosterone (PZ0.002) and 0.8G1.0 kg after testosterone (PZ0.018). The increase in ASMM was larger with combined treatment than either GH or testosterone alone (P!0.05). ECW increased significantly after GHC testosterone by 1.5G2.6 l (PZ0.038) but not after GH or testosterone alone. BCM increased slightly after single and combined treatments, but the changes were not significant. Fasting glucose increased significantly after GH (D0.4G0.4 mmol/l, PZ0.006) while both fasting (D0.2G0.3 mmol/l, PZ0.045) and post glucose-load (D1.8G2.3 mmol/l, PZ0.023) plasma glucose concentrations increased after GHCtestosterone. Conclusions: GH and testosterone induce favourable and additive body compositional changes in men on chronic, low-dose GC treatment. In the doses used, combination therapy increases fasting and postprandial glucose concentration.

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“…Patients with Cushing's syndrome and high levels of corticosteroid production have significantly reduced lean body mass (13). Because corticosteroids are known to result in significant changes in body composition and protein metabolism, we aimed to examine the effects of high-dose corticosteroid therapy on whole body protein metabolism in children with newly diagnosed Crohn disease.…”

mentioning

confidence: 99%

Corticosteroids Increase Protein Breakdown and Loss in Newly Diagnosed Pediatric Crohn Disease

2011

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Children with Crohn disease have altered growth and body composition. Previous studies have demonstrated decreased protein breakdown after either corticosteroid or anti-TNF-␣ therapy. The aim of this study was to evaluate whole body protein metabolism during corticosteroid therapy in children with newly diagnosed Crohn disease. Children with suspected Crohn disease and children with abdominal symptoms not consistent with Crohn disease underwent outpatient metabolic assessment. Patients diagnosed with Crohn disease and prescribed corticosteroid therapy returned in 2 wk for repeat metabolic assessment. Using the stable isotopes [d5] phenylalanine, [1-13 C] leucine, and [ 15 N 2 ] urea, protein kinetics were determined in the fasting state. Thirty-one children (18 controls and 13 newly diagnosed with Crohn disease) completed the study. There were no significant differences in protein breakdown or loss between patients with Crohn disease at diagnosis and controls. After corticosteroid therapy in patients with Crohn disease, the rates of appearance of phenylalanine (32%) and leucine (26%) increased significantly, reflecting increased protein breakdown, and the rate of appearance of urea also increased significantly (273%), reflecting increased protein loss. Whole body protein breakdown and loss increased significantly after 2 wk of corticosteroid therapy in children with newly diagnosed Crohn disease, which may have profound effects on body composition. (Pediatr Res 70: 484-488, 2011) C hildren with Crohn disease suffer from growth impairment before diagnosis, and despite therapy, continue to have growth difficulties which may persist to altered adult growth outcomes. At diagnosis, these children suffer from not only linear growth impairment but also deficits in lean body mass (1) and bone mineral density (2). These deficits may result from altered nutritional intake, malabsorption, and inflammation. A prospective observational study demonstrated increases in BMI and fat mass in the 2 y after diagnosis of pediatric Crohn disease; however, no significant change in lean body mass and persistent deficits in bone mineral content were observed (2). Emerging evidence suggests gender differences in body composition may exist in pediatric patients with Crohn disease. Females with Crohn disease may have more persistent lean body mass deficits than males (3). Current therapeutic strategies may not be resulting in significant and important improvements in lean body mass in these patients.Both malnutrition and inflammation may be observed in pediatric patients with Crohn disease, and they may have opposing effects on substrate metabolism. In patients with chronic malnutrition, there are marked reductions in whole body protein turnover (4), including protein synthesis and breakdown, and in urea excretion, a marker of protein loss (5). In these patients, adaptations to reduction in protein intake result in minimization of protein loss. However, inflammation leads to increased whole body protein metabolism. Injection of T...

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Protein metabolism in glucocorticoid excess: study in Cushing's syndrome and the effect of treatment

Cited by 33 publications

References 57 publications

Body composition and bone mineral density in women with Cushing's syndrome in remission and the association with common genetic variants influencing glucocorticoid sensitivity

Body composition and bone mineral density in women with Cushing's syndrome in remission and the association with common genetic variants influencing glucocorticoid sensitivity

Effect of short-term GH and testosterone administration on body composition and glucose homoeostasis in men receiving chronic glucocorticoid therapy

Corticosteroids Increase Protein Breakdown and Loss in Newly Diagnosed Pediatric Crohn Disease

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