Cushing’s disease: the burden of illness

Abstract

Cushing's syndrome is caused by prolonged exposure to elevated cortisol levels. The most common form of endogenous Cushing's syndrome is Cushing's disease, which results from an adrenocorticotropic hormone-secreting pituitary tumour. Cushing's disease is associated with increased mortality, mostly attributable to cardiovascular complications, and a host of comorbidities such as metabolic and skeletal disorders, infections and neuropsychiatric disturbances. As a consequence, Cushing's disease substantially impairs health-related quality of life. It is crucial that the condition is diagnosed as early as possible, and that rapid and effective treatment is initiated in order to limit long-term morbidity and mortality. The initial treatment of choice for Cushing's disease is selective transsphenoidal pituitary surgery; however, the risk of recurrence after initial surgery is high and remains so for many decades after surgery. A particular concern is the growing body of evidence indicating that the negative physical and psychosocial sequelae of chronic hypercortisolism may persist in patients with Cushing's disease even after long-term surgical 'cure'. Current treatment options for post-surgical patients with persistent or recurrent Cushing's disease include second surgery, radiotherapy, bilateral adrenalectomy and medical therapy; however, each approach has its limitations and there is an unmet need for more efficacious treatments. The current review provides an overview of the burden of illness of Cushing's disease, underscoring the need for prompt diagnosis and effective treatment, as well as highlighting the need for better therapies.

Translational evidence of prothrombotic and inflammatory endothelial damage in Cushing syndrome after remission

“…As expected, ACS presented various cardiometabolic comorbidities, while both ACS and RCS presented, as compared to matched CTR, increased inflammatory parameters such as hs‐CRP, fibrinogen and an increased WHR . Interestingly, platelet number was increased only in ACS, while in RCS, platelet number correlated with sVCAM‐1.…”

“…Several studies have demonstrated that remission of CS is associated with a significant improvement of metabolic parameters, although recovery is incomplete in the vast majority of cases, maintaining an increased cardiovascular risk . The mechanisms implicated are unclear and might involve vascular and circulatory factors due to the nonphysiological adrenal replacement therapy, another hormonal deficiency (growth or sexual hormones) and the persistence of increased visceral adipose tissue with deleterious cytokine secretion, maintaining an inflammatory and prothrombotic state and metabolic syndrome‐like features …”

“…Sustained evidence from clinical observational studies clustered in the two recent reviews by Colao et al and di Minno et al indicates that some clinical features of CS might remain resistant to change after correction of cortisol excess . Increased cardiovascular risk persists in patients with CS even 5 years after its successful remission, due to the maintenance of increased waist/hip ratio, diastolic blood pressure, total/HDL cholesterol ratio and plasma inflammatory markers, as compared with controls matched for body mass index (BMI) and age .…”

A role for activity‐dependent epigenetics in the development and treatment of major depressive disorder

“…37 Interestingly, psychiatrically healthy adults receiving GC replacement therapy, and patients with elevated circulating cortisol in Cushing's syndrome, demonstrate altered methylation of NR3C1 38 and FKBP5. 32 In the case of Cushing's syndrome, patients also often display chronic psychiatric symptoms, 39 which may be as a result of the extended exposure to circulating cortisol in adulthood.…”

Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and Its Molecular Link to Patient Osteoporosis

“…Nearly one third of patients required an additional second-line treatment, including second surgery, radiotherapy, bilateral adrenalectomy and medical therapy. However, each approach has its limitations [10]. Therefore, it is critical to understand molecular mechanisms of CD and elucidate intrapituitary hormone networks.…”