Cardiovascular consequences of cortisol excess (original) (raw)
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Cushing, Cortisol, and Cardiovascular Disease
Hypertension, 2000
Cushing's syndrome of glucocorticoid excess is named after the eminent Boston neurosurgeon Harvey W. Cushing (1869Cushing ( -1939. The recognition that glucocorticoid excess produces hypertension led to examination of the role of cortisol in essential hypertension, but it is only over the last decade that evidence has emerged to support the concept. Despite the widespread assumption that cortisol raises blood pressure as a consequence of renal sodium retention, there are few data consistent with the notion. Although it has a plethora of actions on brain, heart and blood vessels, kidney, and body fluid compartments, precisely how cortisol elevates blood pressure is unclear. Candidate mechanisms currently being examined include inhibition of the vasodilator nitric oxide system and increases in vasoconstrictor erythropoietin concentration.
Cardiovascular Risk In Cushing's Syndrome
Pituitary, 2004
Chronic cortisol hypersecretion causes central obesity, hypertension, insulin resistance, dyslipidemia, protrombotic state, manifestations which form a metabolic syndrome in all patients with Cushing's syndrome. These associated abnormalities determine an increased cardiovascular risk not only during the active phase of the disease but also long after the "biomedical remission". Clinical management of these patients should be particularly careful in identifying global cardiovascular risk. Considering that remission from hypercortisolism is often difficult to achieve care and control of all cardiovascular risk factors should be one of the primary goals during the follow up of these patients. Extending the indications of the recent consensus on Cushing's syndrome, we suggest to carry out an OGTT to avoid underestimation of diabetes mellitus, an echocardiography and Doppler ultrasonography of the epiaortic vessels in all patients at diagnosis and during follow-up.
Cushing's syndrome is associated with increased mortality, mainly due to cardiovascular complications, which are sustained by the common development of systemic arterial hypertension and metabolic syndrome, which partially persist after the disease remission. Cardiovascular diseases and hypertension associated with endogenous hypercortisolism reveal underexplored peculiarities. The use of exogenous corticosteroids also impacts on hypertension and cardiovascular system, especially after prolonged treatment. The mechanisms involved in the development of hypertension differ, whether glucocorticoid excess is acute or chronic, and the source endogenous or exogenous, introducing inconsistencies among published studies. The pleiotropic effects of glucocorticoids and the overlap of the several regulatory mechanisms controlling blood pressure suggest that a rigorous comparison of invivo and in-vitro studies is necessary to draw reliable conclusions. This review, developed during the first 'Altogether to Beat Cushing's syndrome' workshop held in Capri in 2012, evaluates the most important peculiarities of hypertension associated with CS, with a particular focus on its pathophysiology. A critical appraisal of most significant animal and human studies is compared with a systematic review of the few available clinical trials. A special attention is dedicated to the description of the clinical features and cardiovascular damage secondary to glucocorticoid excess. On the basis of the consensus reached during the workshop, a pathophysiology-oriented therapeutic algorithm has been developed and it could serve as a first attempt to rationalize the treatment of hypertension in Cushing's syndrome.
Effect of hypercortisolism control on high blood pressure in Cushing's syndrome
Medicina, 2007
Many hypertensive patients affected by endogenous Cushing's syndrome (CS) persist with high blood pressure (HBP) despite good control of cortisol excess. We assessed the effect of preoperative ketoconazole administration and of definitive treatment of CS on arterial hypertension and analysed the factors involved in the persistence of hypertension. We assessed retrospectively 71 patients with CS and HBP (60 women, 11 men; 50 pituitary, 21 adrenal) successfully treated by surgery and/or radiotherapy; 19 of them received ketoconazole (KNZ) before surgery. After treatment, patients were divided into those with persistent high blood pressure (PHBP) and those with normal blood pressure (NBP). As possible predictive factors for PHBP we analysed age, duration and family history of HBP, pre-treatment 24 hour urinary free cortisol (24h-UFC) and body mass index (BMI). HBP normalized in 53 out of 71 patients (74.6%), regardless of the origin of Cushing's syndrome. PHBP patients were old...
Pathophysiology of Dyslipidemia in Cushing’s Syndrome
Neuroendocrinology, 2010
fat where lipolysis is activated, resulting in the release of free fatty acids into the circulation. The increase of free fatty acids may enhance the accumulation of hepatic lipids reducing glucose uptake and activating various serine kinases which results in decreased insulin signaling. Moreover, mice with a liver-specific disruption of the glucocorticoid receptor had diminished hepatic triglycerides levels. In humans, a high prevalence (up to 20%) of hepatic steatosis was also reported in patients with Cushing's syndrome. Genetic variations in the glucocorticoid receptors may also affect the activity of cortisol, lipid metabolism and cardiovascular risk.
Cushing 'S Syndrome: Pathophysiology And Management
2018
Introduction: Cushing's syndrome a state of high blood cortisol level due to various reasons. The syndrome has much comorbidity like hypertension, heart diseases, pathological fractures, diabetes mellitus, and coagulopathy. the diagnosis is largely clinical based on history and examination, and treatment depends upon the cause. Aim of the work: In this study, our aim was to understand the pathophysiology behind Cushing's syndrome and its various causes. We will also discuss the diagnoses and ways of management. Methodology: we conducted this review using a comprehensive search of MEDLINE, PubMed and EMBASE from January 1994 to March 2017. The following search terms were used: Cushing's syndrome, Cushing's disease, adrenocorticotrophic hormone, high blood steroid levels, pathological fractures, diagnosis of Cushing's, management of Cushing's. Conclusion: Cushing's syndrome is the result of any long-term pathology that leads to high levels of circulating cortisol in the bloodstream. Up to 80% of patients with Cushing's syndrome can have hypertension which will lead to significant increase in both morbidity and mortality if left untreated. Asides from blood pressure control, surgical resection remains the most ideal treatment modality in the treatment of most causes of Cushing's syndrome.
The Journal of Clinical Endocrinology & Metabolism, 2002
Subclinical Cushing's syndrome (SCS) is increasingly being reported in incidentally discovered adrenal adenomas; its hallmark is mild autonomous cortisol hyperproduction without specific clinical signs of cortisol excess. Increased prevalence of hypertension, obesity, and impaired glucose tolerance have been described in SCS, but there is no specific study of the risk factors for cardiovascular diseases. In this crosssectional study we assessed the cardiovascular profile in 28 consecutive SCS patients (19 women and 9 men; aged 56 ؎ 10.6 yr) compared with 100 controls matched for age, gender, and body mass index. Systolic (P < 0.001) and diastolic (P < 0.005) blood pressures were higher in patients, as were fasting glucose, insulin, total cholesterol, triglycerides (all P < 0.001), and fibrinogen (P < 0.05). Moreover, the insulin resistance index was increased in patients as was the waist to hip ratio and mean carotid artery intima-media thickness (all P < 0.001). Of the patients, 60.7% had arterial hypertension, 71.4% had lipid abnormalities, 28.6% had impaired glucose tolerance, 35.7% type 2 diabetes mellitus, and 53.6% had abnormalities in hemostatic parameters. Atherosclerotic plaques were more frequent in patients (P < 0.0001). Only 4 (14.3%) patients did not have multiple risk factors for cardiovascular events. Six (21.3%) had clinical evidence of cardiovascular disease; another 11 (39.3%) had cardiovascular abnormalities as revealed by ultrasound scanning of carotid arteries and/or electrocardiogram records. These results strongly suggest that an increased cardiovascular risk profile, similar to that described in overt Cushing's syndrome, is present is SCS subjects. This finding supports the concept that chronic mild endogenous cortisol excess may have important systemic effects on the human body. (J Clin Endocrinol Metab 87: 4872-4878, 2002)
Epidemiology and mortality of Cushing’s syndrome
Best Practice & Research Clinical Endocrinology & Metabolism, 2021
Endogenous Cushing's syndrome (CS) is a rare endocrine disorder characterised by excess cortisol secretion due to either ACTH-dependent conditions [commonly an ACTH-producing pituitary adenoma (Cushing's disease)] or ACTH-independent causes (with most common aetiology being a benign adrenal adenoma). Overall, the annual incidence of CS ranges between 1.8-3.2 cases per million population. Mortality in active CS is elevated compared to the general population, and a number of studies support the view that survival is also compromised even after apparent successful treatment. The main cause of death is cardiovascular disease highlighting the negative impact of cortisol excess on cardiovascular risk factors. Early diagnosis and prompt treatment of the cortisol excess, as well as vigilant monitoring and stringent control of cardiovascular risk factors are key elements for the long-term prognosis of these patients.
Undetectable urinary free cortisol concentrations in a case of Cushing's disease
European Journal of Endocrinology, 1999
Measurement of the 24-h urinary free cortisol is a valuable screening test of endogenous hypercortisolism and, although false positive results may occur in a few situations, for example endogenous depression, false negative results are unusual. We report a case of a 48-year-old lady with pituitarydependent Cushing's disease, whose 24-h urinary free cortisol excretion was consistently undetectable in association with increased plasma and salivary cortisol concentrations and reduced dexamethasone suppressibility. The patient had chronic renal impairment (creatinine clearance 21 ml/min) as a consequence of hypertension, despite only modestly increased urea and creatinine concentrations. Urinary free cortisol measurements must be interpreted with caution in patients with renal impairment.