title: Metabolic comorbidities in Cushing's syndrome.
abstract: 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.
authors.affiliation: Centre for Endocrinology William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferraù
authors.affiliation: Centre for Endocrinology William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK m.korbonits@qmul.ac.uk.
authors.forename: Márta
authors.initials: M
authors.lastname: Korbonits
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D050218:Body Fat Distribution; D015897:Comorbidity; D003480:Cushing Syndrome / Q000453:epidemiology / Q000378:metabolism*; D050171:Dyslipidemias / Q000453:epidemiology / Q000378:metabolism*; D005938:Glucocorticoids / Q000378:metabolism*; D005943:Gluconeogenesis / Q000502:physiology; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000453:epidemiology / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology; D056128:Obesity, Abdominal / Q000453:epidemiology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D005938:Glucocorticoids; D007328:Insulin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I