MANAGEMENT OF ENDOCRINE DISEASE: The burden of Cushing's disease: clinical and health-related quality of life aspects

Abstract

Objective: Cushing's disease (CD) is a rare endocrine disorder characterized by excess secretion of ACTH due to a pituitary adenoma. Current treatment options are limited and may pose additional risks. A literature review was conducted to assess the holistic burden of CD. Design: Studies published in English were evaluated to address questions regarding the epidemiology of CD, time to diagnosis, health-related quality of life (HRQoL), treatment outcomes, mortality, prevalence of comorbidities at diagnosis, and reversibility of comorbidities following the treatment. Methods: A two-stage literature search was performed in Medline, EMBASE, and Science Citation Index, using keywords related to the epidemiology, treatment, and outcomes of CD: i) articles published from 2000 to 2012 were identified and ii) an additional hand search (all years) was conducted on the basis of bibliography of identified articles. Results: At the time of diagnosis, 58-85% of patients have hypertension, 32-41% are obese, 20-47% have diabetes mellitus, 50-81% have major depression, 31-50% have osteoporosis, and 38-71% have dyslipidemia. Remission rates following transsphenoidal surgery (TSS) are high when performed by expert pituitary surgeons (rates of 65-90%), but the potential for relapse remains (rates of 5-36%). Although some complications can be partially reversed, time to reversal can take years. The HRQoL of patients with CD also remains severely compromised after remission. Conclusions: These findings highlight the significant burden associated with CD. As current treatment options may not fully reverse the burden of chronic hypercortisolism, there is a need for both improved diagnostic tools to reduce the time to diagnosis and effective therapy, particularly a targeted medical therapy.

THERAPY OF ENDOCRINE DISEASE: Outcomes in patients with Cushing's disease undergoing transsphenoidal surgery: systematic review assessing criteria used to define remission and recurrence

“…However, these maximum rates of remission can be considered to be overestimations of the true outcomes of Cushing's disease after initial microscopic TSS, because the potential for relapse remains high. In this review, the reported rates of recurrence ranged from 5.0 to 47.4%; similarly, rates of 5-36% were also reported in a recent publication (61). The wide range of rates of remission and recurrence observed highlight the fact that statistics for treatment outcomes are dependent on the criteria used to define those outcomes.…”

Routine screening for Cushing's syndrome is not required in patients presenting with hirsutism

“…Hypercortisolemia-associated morbidities, particularly increased cardiovascular risk, may persist in a substantial number of CS patients despite normalization of hypercortisolemia (3,4). Increased mortality and morbidities like hypertension, hyperglycemia, increased fat mass, hypercoagulability, decreased bone mineral density and quality, psychopathologies, and cognitive impairment significantly improve after successful treatment of CS, but even after long-term remission, these morbidities and mortality may not be completely reversible (5). Therefore, early diagnosis and treatment is important before the presentation of overt cardiovascular, metabolic, and psychiatric disorders.…”

Budget impact of pasireotide for the treatment of Cushing’s disease, a rare endocrine disorder associated with considerable comorbidities

“…(pituitary adenoma) [1][2][3][4][5] . Patients with CD experience a remarkably broad spectrum and high prevalence of comorbidities associated with chronic hypercortisolism, and diagnosis of CD is challenging in part because of the many disparate manifestations of the disease 2 .…”

“…The many comorbidities associated with CD include ischemic heart disease, obesity, hypertension, impairment of glucose tolerance, dyslipidemia, and thrombotic diathesis 3,[12][13][14] , which together increase cardiovascular risk. Other comorbidities found among CD patients include infections (urinary tract infections and pneumonia), psychopathologies (anxiety, depression, and cognitive deficit), as well as skeletal problems (fractures and osteoporosis) 3,[12][13][14] .…”

“…The many comorbidities associated with CD include ischemic heart disease, obesity, hypertension, impairment of glucose tolerance, dyslipidemia, and thrombotic diathesis 3,[12][13][14] , which together increase cardiovascular risk. Other comorbidities found among CD patients include infections (urinary tract infections and pneumonia), psychopathologies (anxiety, depression, and cognitive deficit), as well as skeletal problems (fractures and osteoporosis) 3,[12][13][14] . Patients most often complain of fatigue/weakness (85%), changes in physical appearance (63%), emotional instability (61%), cognitive impairment (49%), depression (32%), and sleeping difficulties (12%); 80% report interference with family life and relations with their partner and 56% with school/work performance 15 .…”