Role of radiosurgery in the treatment of Cushing's disease

Patients with Cushing's syndrome have increased morbidity and mortality from cardiovascular causes, most commonly myocardial infarction and stroke, but also aneurysms and pulmonary emboli. 1,2 These are also common causes of death in the general population in developed countries and are age-dependent. It has been estimated that untreated Cushing's syndrome patients have a four-to five-fold higher mortality rate than the general population, with only 50% of patients surviving 5 years from diagnosis. 3 The 5-year survival rate was improved to 86% after bilateral adrenalectomy. 4 The major risk factors for this mortality in the general population are diabetes (DM2), hypertension, smoking, dyslipidaemia, abdominal obesity/metabolic syndrome, and male gender. These same risk factors pertain in all forms of glucocorticoid excess. Here, I focus on endogenous Cushing's syndrome and pertinent to this is that the majority of patients (70%-80%) have adrenocorticotrophic hormone (ACTH)-dependent pituitary Cushing's disease and are frequently women (75% of cases) of premenopausal age, typically between 30 and 55 years old at diagnosis. This sex and age-group has a low incidence of cardiovascular disease in the general population. Furthermore, Cushing's syndrome patients are exposed to excess glucocorticoid for approximately 3-4 years before diagnosis and effective treatment, thereby increasing the likelihood of early development of cardiovascular risk factors.Even more concerning is the fact that, even after 'cure' of the Cushing's syndrome, the risk factors may not fully normalise with adequate amelioration of glucocorticoid excess.

“…This article is part of an update series on the diagnosis and treatment of Cushing's syndrome. [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52]…”

Section: Overall Conclusionmentioning

confidence: 99%

Cardiovascular complications of Cushings syndrome: Impact on morbidity and mortality

Clayton

2022

“…This article is part of an update series on the diagnosis and treatment of Cushing's syndrome. [113][114][115][116][117][118][119][120][121][122][123][124][125][126][127][128][129]…”

Section: Discussionmentioning

confidence: 99%

Glucose and lipid metabolism abnormalities in Cushing's syndrome

Salehidoost

Korbonits

2022

Prolonged excess of glucocorticoids (GCs) has adverse systemic effects leading to significant morbidities and an increase in mortality. Metabolic alterations associated with the high level of the GCs are key risk factors for the poor outcome. These include GCs causing excess gluconeogenesis via upregulation of key enzymes in the liver, a reduction of insulin sensitivity in skeletal muscle, liver and adipose tissue by inhibiting the insulin receptor signalling pathway, and inhibition of insulin secretion in beta cells leading to dysregulated glucose metabolism. In addition, chronic GC exposure leads to an increase in visceral adipose tissue, as well as an increase in lipolysis resulting in higher circulating free fatty acid levels and in ectopic fat deposition.Remission of hypercortisolism improves these metabolic changes, but very often does not result in full resolution of the abnormalities. Therefore, long-term monitoring of metabolic variables is needed even after the resolution of the excess GC levels.

“…This article is part of an update series on the diagnosis and treatment of Cushing's syndrome. [61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77] AUTHOR CONTRIBUTIONS Alies Juliëtte Dekkers: Writingoriginal draft. Jorge Miguel Miguel Amaya: Writingreview and editing.…”

Section: Current Status and Future Perspectivesmentioning

confidence: 99%

Long‐term effects of glucocorticoid excess on the brain

Dekkers

Amaya

Meulen

et al. 2022

The metabolic and cardiovascular clinical manifestations in patients with Cushing's syndrome (CS) are generally well known. However, recent studies have broadened the perspective of the effects of hypercortisolism, showing that both endogenous and exogenous glucocorticoid excess alter brain functioning on several time scales. Consequently, cognitive deficits and neuropsychological symptoms are highly prevalent during both active CS and CS in remission, as well as during glucocorticoid treatment. In this review, we discuss the effects of endogenous hypercortisolism and exogenously induced glucocorticoid excess on the brain, as well as the prevalence of cognitive and neuropsychological deficits and their course after biochemical remission. Furthermore, we propose possible mechanisms that may underly neuronal changes, based on experimental models and in vitro studies. Finally, we offer recommendations for future studies.