Hypothalamic–pituitary–adrenal axis recovery after treatment of Cushing's syndrome

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. [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

“…This article is part of an update series on the diagnosis and treatment of Cushing's syndrome. [47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63]…”

Section: Inter-gender Differences In the Distribution Of Symptomsmentioning

confidence: 99%

Clinical presentation and etiology of Cushing's syndrome: Data from ERCUSYN

Valassi

2022

This review presents the data on clinical presentation at diagnosis in 1564 patients included in the European Registry on Cushing's syndrome (ERCUSYN), of whom 1045 (67%) had pituitary‐dependent Cushing's syndrome (CS) (PIT‐CS), 385 (25%) had adrenal dependent CS (ADR‐CS) and 89 (5%) had ectopic adrenocorticotropic hormone syndrome (ECT‐CS). The most frequent symptoms in the overall series were weight gain (83%), hypertension (79%), skin alterations (76%) and myopathy (70%). Diabetes mellitus was present in 32% and depression in 35% of patients. Skin alterations, menstrual irregularities and reduced libido were more prevalent in PIT‐CS patients compared to ADR‐CS patients, whereas patients with ECT‐CS more frequently had diabetes mellitus, myopathy, hirsutism and vertebral fractures compared to the other etiologies, consistent with a more severe clinical scenario. Reduced libido and bone fractures were more prevalent in men compared to women. Quality of life was poor at diagnosis, irrespective of the etiology of CS, and also associated with the presence of depression at baseline. A delay of 2 years between the onset of symptoms and diagnosis was also observed, with a high number of specialists consulted, who often missed the correct diagnosis. To develop strategies aimed at shortening the time elapsed to diagnosis, it is important to rapidly start treatment and reduce the burden of the disease on patient psychophysical health and longevity.

“…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.