Changes in body composition and adipose tissue distribution after treatment of women with Cushing's syndrome

Lönn, Lars; Kvist, Henry; Ernest, Ingrid; Sjöström, Lars

doi:10.1016/0026-0495(94)90010-8

Cited by 87 publications

(61 citation statements)

References 16 publications

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“…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: Discussionmentioning

confidence: 99%

Section: Hormonal Statusmentioning

confidence: 99%

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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“…Understanding the changes in fat distribution seen in men and women with Cushing's syndrome may improve our understanding of the mechanisms of the development of visceral fat distribution and the metabolic syndrome. It may also contribute to diagnostic and prognostic information in patients with Cushing's syndrome, and be useful in assessing follow-up (21).…”

Section: Discussionmentioning

confidence: 99%

Computed tomography assessment of fat distribution in male and female patients with Cushing's syndrome

Rockall

Sohaib

Evans

et al. 2003

European Journal of Endocrinology

107

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Objective: Our aims were to describe the abdominal fat distribution in male patients with Cushing's syndrome (CS) on computerised tomography (CT), to compare our findings with non-cushingoid patients, to validate previous reports of increased visceral fat in female patients with CS and to identify any correlations between fat distribution and biochemical findings. Design: Retrospective and observational. Patients: Appropriate CT scans were identified in 31 patients (seven male) with active CS. Measurements: Total, visceral and subcutaneous fat areas were obtained. The percentage of visceral fat and the visceral to subcutaneous fat ratio (V:S ratio) were calculated. Biochemical data were recorded. Control data of fat distribution were obtained from the literature. Results: There was a significant increase in the V:S ratio in male patients with CS when compared with non-cushingoid controls (1.175^0.59 vs 0.77^0.39, 95% confidence interval (CI) 0.0817 -0.728). There was a significant increase in the V:S ratio in female patients with CS (0.845^0.53 vs 0.38^0.19, 95% CI 0.269 -0.661). There was no difference in the V:S ratio between male and female patients with CS (1.175^0.59 vs 0.845^0.53, 95% CI 20.144 -0.804). No significant correlations between fat distribution and glucose levels, circulating cortisol, ACTH or lipids were found. Conclusions: Our data demonstrate an increase in visceral fat distribution in both male and female patients with CS, with the abolition of the normal male to female difference in visceral fat. Increased visceral fat may increase the risk of the metabolic syndrome in this group of patients.

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“…Cortisol augments directly or indirectly the total mass of adipose tissue and redistributes it from peripheral to central depots (13). Glucocorticoids also regulate multiple processes in the adipose tissue.…”

Section: Cushing's Syndrome and Metabolic Syndrome: High Circulating mentioning

confidence: 99%

Adipose tissue expression of 11beta-Hydroxysteroid dehydrogenase type 1 in cushing's syndrome and in obesity

Espíndola-Antunes

Kater

2007

Arq Bras Endocrinol Metab

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Glucocorticoids have a major role in determining adipose tissue metabolism and distribution. 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) is a NADPHdependent enzyme highly expressed in the liver and adipose tissue. In most intact cells and tissues it functions as a reductase (to convert inactive cortisone to active cortisol). It has been hypothesized that tissue-specific deregulation of cortisol metabolism may be involved in the complex pathophysiology of the metabolic syndrome (MS) and obesity. Transgenic mice overexpressing 11βHSD1 in adipose tissue develop obesity with all features of the MS, whereas 11βHSD1-knockout mice are protected from both. The bulk of evidences points to an overexpression and increased activity of 11βHSD1 also in human adipose tissue. However, 11βHSD1 seems to adjust local cortisol concentrations independently of its plasma levels. In Cushing's syndrome, 11βHSD1 is downregulated and may not be responsible for the abdominal fat depots; it also undergoes downregulation in response to weight loss in human obesity. The nonselective 11βHSD1 inhibitor carbenoxolone improves insulin sensitivity in humans, and selective inhibitors enhance insulin action in diabetic mice liver, thereby lowering blood glucose. Thus, 11βHSD1 is now emerging as a modulator of energy partitioning and a promising pharmacological target to treat the MS and diabetes. Os glicocorticóides (GC) têm papel importante na determinação do metabolismo e da distribuição do tecido adiposo. A 11β-hidroxisteróide desidrogenase tipo 1 (11βHSD1) é uma enzima dependente de NADPH, altamente expressa nos tecidos hepático e adiposo. Em muitas células e tecidos intactos, ela funciona como redutase (convertendo cortisona em cortisol). Postula-se que uma desregulação tecido-específica do cortisol estaria envolvida na complexa fisiopatologia da síndrome metabólica (SM) e obesidade. Ratos que superexpressam 11βHSD1 no tecido adiposo desenvolvem obesidade e todas as características da SM, enquanto ratos knockout para 11βHSD1 são protegidos. Evidências apontam para uma super-expressão e aumento da atividade 11βHSD1 também no tecido adiposo humano. Entretanto, a 11βHSD1 parece ajustar a concentração local de cortisol independente da sua concentração séri-ca. Na síndrome de Cushing, a expressão da 11βHSD1 é regulada para baixo, não devendo ser a causa dos depósitos de gordura visceral; em obesos, há também regulação para baixo em resposta à perda de peso. A carbenoxolona, um inibidor não seletivo da 11βHSD1, melhora a sensibilidade insulínica em humanos e inibidores seletivos aumentam a sensibilidade insulínica hepática e melhoram o controle glicêmico em ratos diabéticos. Assim, a 11βHSD1 está emergindo como um modulador da compartimentalização de energia e um alvo farmacológico promissor para o tratamento da SM e do diabetes.

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Changes in body composition and adipose tissue distribution after treatment of women with Cushing's syndrome

Cited by 87 publications

References 16 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

Computed tomography assessment of fat distribution in male and female patients with Cushing's syndrome

Adipose tissue expression of 11beta-Hydroxysteroid dehydrogenase type 1 in cushing's syndrome and in obesity

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