Adipokines and Cardiovascular Risk in Cushing’s Syndrome

Valassi, Elena; Biller, Beverly M. K.; Klibanski, Anne; Misra, Madhusmita

doi:10.1159/000330416

Cited by 50 publications

(50 citation statements)

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“…In human medicine, hyperleptinemia in patients with Cushing's syndrome is related to a higher prevalence of cardiovascular diseases11 and it has been suggested that hyperleptinemia has proinflammatory, prothrombotic, and pro‐oxidant effects 33. The present findings suggest that the development and progression of complications related to HAC are probably associated with hyperleptinemia, although future longitudinal studies in dogs with HAC are required to support or refute this.…”

Section: Discussionmentioning

confidence: 53%

“…Inflammatory cytokines were detected in several overweight dogs with PDH, although we did not examine the source of these cytokines so it is not clear if they were produced by adipose tissue (as is possible34), or whether there was infectious disease (to which dogs with HAC are prone). In human medicine, it has also been suggested that chronic hypercortisolemia in patients with Cushing's syndrome affects serum TNF‐α and IL‐6 levels, thereby contributing to the persistence of a low‐grade inflammatory state 11. However, further studies will be necessary to clarify the relationships between hyperleptinemia or inflammatory cytokines and the well‐known complications in dogs with HAC.…”

Section: Discussionmentioning

confidence: 99%

“…In dogs, it has been suggested that increased visceral adiposity and the dysregulation of adipokines are associated with endocrine disorders, including diabetes mellitus (DM) and hypothyroidism 9, 10. In human medicine, several studies have reported that patients with Cushing's syndrome had a higher prevalence of DM, hypertension, and cardiovascular diseases caused by adipokine dysregulation 11, 12, 13. In dogs, it is well known that the chronic hypercortisolemia caused by HAC is associated with complications, such as visceral obesity with insulin resistance, glucose intolerance, hypertension, cardiovascular disease, thromboembolism, and increased susceptibility to infection 14, 15, 16, 17.…”

mentioning

confidence: 99%

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Serum Adipokine Concentrations in Dogs with Naturally Occurring Pituitary‐Dependent Hyperadrenocorticism

Cho

Paek

Kang

et al. 2013

Veterinary Internal Medicne

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BackgroundAn excess of intra‐abdominal fat is observed frequently in dogs with hyperadrenocorticism (HAC). Adipokine dysregulation is a possible cause of complications related to visceral obesity, but little information is available on adipokine in dogs with naturally occurring HAC.ObjectivesTo examine the differences in the circulating adipokines concentrations in overweight dogs with and without pituitary‐dependent HAC (PDH).AnimalsThirty healthy dogs and 15 client‐owned dogs with PDH.MethodsCase–controlled observational study, which enrolled 15 overweight dogs diagnosed with PDH and 30 otherwise healthy dogs of similar body condition score. Nine of 15 dogs with PDH were treated with low‐dose trilostane twice daily and reassessed after treatment.ResultsThe serum leptin (P < .0001) and insulin (P < .0001) concentrations were significantly higher in the PDH group (leptin, 22.8 ± 8.8 [mean ± SD]; insulin, 9.1 ± 6.1) than the healthy group (leptin, 4.9 ± 3.7; insulin, 1.9 ± 0.9). However, there were no significant differences in the adiponectin, resistin, tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, IL‐10, and IL‐18 levels between the 2 groups. In the PDH group, the serum cortisol concentrations had a linear association with the leptin concentrations, and there were significant decreases in the leptin (P = .0039) and insulin (P = .0039) levels after trilostane treatment. However, the leptin and insulin levels remained higher after trilostane treatment than in healthy control dogs with similar body condition score.Conclusions and Clinical ImportanceHypercortisolemia in dogs with PDH might upregulate the circulating leptin levels. However, a large population‐based study will be necessary to determine whether the upregulation of leptin is involved directly with the complications caused by HAC.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Serum Adipokine Concentrations in Dogs with Naturally Occurring Pituitary‐Dependent Hyperadrenocorticism

Cho

Paek

Kang

et al. 2013

Veterinary Internal Medicne

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“…This suggests that obesity is crucial when considering adiponectin levels in CS patients (113). Conflicting data have been reported about adiponectin levels before and after resolution of CS (104,114,115).…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

Metabolic comorbidities in Cushing's syndrome

Ferraú

Korbonits

2015

European Journal of Endocrinology

144

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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“…It would be tempting to enter data on the glucocorticoid-induced leptin resistance [42,43] and on the elevation of leptin level in patients with Cushing's syndrome [44,45], confirmed by the experiments in vitro [46], but no association was found between leptin levels and BFD patterns [47].…”

Section: Discussionmentioning

confidence: 99%

Anthropometric correlates of morning plasma cortisol level and hormonal and biochemical response to fasting in obese premenopausal women

Melnikov¹,

Kim²

2017

Integr Obesity Diabetes

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Numerous studies have established associations between hormonal parameters and body shape but they focused on the patterns of body fat distribution and, mainly, abdominal fat deposition. Based on the anthropometric features of patients with Cushing's syndrome, we hypothesized that there are somatometric predictors, other than waist-to-hip ratio, of increased cortisol production. To test this hypothesis and to identify the indicators of endocrine and metabolic responsiveness to shortterm fasting, we searched associations among 37 anthropometric traits and metabolic and hormonal parameters. An observational repeated measures study was performed on 64 moderately obese women using the partial correlation analysis. Blood glucose, serum lipids and urea concentrations, morning plasma cortisol, serum triiodthyronine (T3), thyroxin levels, and insulin activity (IRI) were examined before and after 4-and 7-day total fasting. The morning plasma cortisol level (RIA) showed the strongest correlation, independent of total fatness, with chest-hip circumference ratio (CHR) (r=0.48, p<0.005), whereas no significant association could be found with waist-hip ratio (WHR). IRI level correlated directly with WHR (r=0.47, p<0.001). The 4-day fasting significantly raised cortisol levels (+23%), free fatty acids (FFAs) (+79%), and triglyceride (TGs) (+34%) concentrations, and lowered IRI (-43%), T3 (-33%) and glucose (-27%) levels. The cortisol response to 4-day fasting tended to relate with age (r=0.25) and age-independently correlated with body height (r=-0.30) and WHR (r=-0.27). Both basal levels and fast changes in glucose and TGs concentrations correlated with age (glucose, r=0.38; TGs, r=0.24; d-glucose, r=-0.32; d-TG, r=-0.24). The relative weight loss after the 27-day weight-loss program increased with increasing basal FFAs and thyroxin levels. In conclusion, CHR was found to be a powerful predictor for morning plasma cortisol level. The relation established seems to reflect the differential sensitivity of the upper and lower body subcutaneous adipocytes to the metabolic stimuli of the hormone and/or other factors associated with glucocorticoids.level. In addition to this primary objective, there were two aims: (1) to describe anthropometric correlates for the response of endocrine variables and the patterns of protein, glucose, and lipid metabolism to short-term fasting, and (2) to verify hormonal, metabolic and somatometric predictors for the weight reduction during weight-loss program (WLP). Taking into account the sex-dependence of cortisol metabolism in obesity [18] we performed this research on obese women who were usually being investigated from the standpoint under study. Subjects and methods SubjectsThe study was undertaken on 64 Russian fertile women living in Novosibirsk city and referred to the endocrine division of the academic clinic for treatment of obesity by a WLP. The patients' free and informed consent to participate in the study was obtained. No women had signs of hirsutism, other endocrine disorders, ...

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Adipokines and Cardiovascular Risk in Cushing’s Syndrome

Cited by 50 publications

References 378 publications

Serum Adipokine Concentrations in Dogs with Naturally Occurring Pituitary‐Dependent Hyperadrenocorticism

Serum Adipokine Concentrations in Dogs with Naturally Occurring Pituitary‐Dependent Hyperadrenocorticism

Metabolic comorbidities in Cushing's syndrome

Anthropometric correlates of morning plasma cortisol level and hormonal and biochemical response to fasting in obese premenopausal women

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