Cardiovascular risk in patients with Cushing’s disease – an interdisciplinary problem

Cushing’s disease is a chronic endogenous hypercortisolaemia associated with overproduction of adrenocorticotropic hormone by a pituitary adenoma, leading to multiple systemic complications that significantly increase morbidity and mortality, as well as reduce the quality of life as a result of prolonged tissue exposure to excess cortisol. Hypercortisolaemia in Cushing’s disease is associated with significant functional and constitutional disorders of the entire body. The consequences of chronic hypercortisolaemia include haemodynamic disorders associated with excessive vascular contraction and increased blood pressure, obesity, carbohydrate metabolism disorders, dyslipidaemia, and coagulopathies, which may contribute to significant cardiovascular remodelling. Cardiovascular disorders have a particular impact on long-term prognosis and quality of life in Cushing’s disease. If left untreated, Cushing’s disease significantly increases the cardiovascular risk and limits the treatment options for secondary organ complications. Cardiovascular mortality (myocardial infarction, heart failure, stroke) is several times higher in patients with Cushing’s disease than in the general population. Early diagnosis of the corticotropic pituitary tumour, as well as a thorough morphological and functional cardiovascular assessment seem essential in risk stratification. Normalisation of cortisol levels after combined neurosurgical and/or pharmacological treatment reduces mortality and the risk of cardiovascular and respiratory complications. The aim of this study is to present the complexity of clinical problems in patients with Cushing’s disease, who are in a particular need of interdisciplinary care.

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Bilateral adrenalectomy in Cushing's disease: Altered long-term quality of life compared to other treatment options

Annales d Endocrinologie ◽

10.1016/j.ando.2018.01.002 ◽

2019 ◽

Vol 80 (1) ◽

pp. 32-37 ◽

Cited By ~ 9

Author(s):

Pauline Sarkis ◽

Muriel Rabilloud ◽

Jean-Christophe Lifante ◽

Anna Siamand ◽

Emmanuel Jouanneau ◽

...

Keyword(s):

Quality Of Life ◽

Cushing’S Disease ◽

Treatment Options ◽

Bilateral Adrenalectomy ◽

Cushing's Disease

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

Acta Endocrinologica ◽

10.1530/eje-11-1095 ◽

2012 ◽

Vol 167 (3) ◽

pp. 311-326 ◽

Cited By ~ 134

Author(s):

R A Feelders ◽

S J Pulgar ◽

A Kempel ◽

A M Pereira

Keyword(s):

Quality Of Life ◽

Cushing’S Disease ◽

Treatment Options ◽

Current Treatment ◽

Cushing's Disease ◽

Health Related Quality ◽

Time To Diagnosis ◽

Related Quality ◽

Health Related

ObjectiveCushing'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.DesignStudies 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.MethodsA 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.ResultsAt 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.ConclusionsThese 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.

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Perioperative Quality of Life in Cushing’s Disease

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2016.295 ◽

2016 ◽

Vol 44 (1) ◽

pp. 69-77 ◽

Cited By ~ 2

Author(s):

Vincent Chen Ye ◽

Ryojo Akagami

Keyword(s):

Quality Of Life ◽

Cushing’S Disease ◽

Short Form ◽

Retrospective Chart Review ◽

Pituitary Tumour ◽

Cushing's Disease ◽

Complication Rates ◽

Canadian Population ◽

Sf 36

AbstractBackground: Our study evaluated the perioperative quality of life (QoL) in Cushing’s disease (CD) patients, along with correlations between patient variables and cure rate. Methods: The 36-item Short-Form Health Survey (SF)-36 questionnaire was used to assess perioperative QoL. Patients completed one survey preoperatively and two surveys postoperatively. Retrospective chart review was conducted to collect SF-36 data as well as examine variables including: age, hospital stay, size of tumour, pathological diagnosis, timing of cure, and complication rates. Statistical analysis was conducted on the scores reported by the SF-36, and were compared with the normal Canadian population values, and to a sample of QoL from nonfunctioning pituitary tumour patients. This project was approved by University of British Columbia Research Ethics Board #H15-01572. Results: In general, CD patients have relatively poor QoL that does improve as expected when cured, but not quite to normal levels. Factors associated with cure included presence of macroadenoma, confirmatory pathology, and patient age. Postoperative timing of cure appears to affect the durability of cure, with an immediate cure having a higher durability rate than delayed cure. Most recurrences occurred within 10 months postoperatively. Conclusions: This review of the perioperative QoL in CD helps to illustrate how QoL changes throughout the treatment process, how QoL compares to normal Canadian population levels, and how QoL compares to patients with nonfunctioning pituitary adenomas. As treatment outcome has such a high impact on QoL, the variables identified in this study will help to better inform patients about the treatment course.

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The development of the Tuebingen Cushing’s disease quality of life inventory (Tuebingen CD-25). Part II: normative data from 1784 healthy people

Clinical Endocrinology ◽

10.1111/j.1365-2265.2011.04280.x ◽

2012 ◽

Vol 76 (6) ◽

pp. 861-867 ◽

Cited By ~ 18

Author(s):

Monika Milian ◽

Philipp Teufel ◽

Juergen Honegger ◽

Baptist Gallwitz ◽

Guenter Schnauder ◽

...

Keyword(s):

Quality Of Life ◽

Cushing’S Disease ◽

Normative Data ◽

Healthy People ◽

Cushing's Disease ◽

Quality Of Life Inventory ◽

Life Inventory

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Abstract #1040637: Effect of Osilodrostat on Clinical signs, Physical Features and Health-related Quality of Life (HRQoL) by Degree of mUFC Control in Patients with Cushing’s Disease (CD): Results from the LINC3 Study

Endocrine Practice ◽

10.1016/j.eprac.2021.04.744 ◽

2021 ◽

Vol 27 (6) ◽

pp. S130-S131

Author(s):

Rosario Pivonello ◽

Maria Fleseriu ◽

John Newell-Price ◽

Akira Shimatsu ◽

Richard A. Feelders ◽

...

Keyword(s):

Quality Of Life ◽

Cushing’S Disease ◽

Clinical Signs ◽

Cushing's Disease ◽

Health Related Quality ◽

Related Quality ◽

Health Related ◽

Physical Features

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Treatment effectiveness of pasireotide on health-related quality of life in patients with Cushing's disease

Acta Endocrinologica ◽

10.1530/eje-13-1013 ◽

2014 ◽

Vol 171 (1) ◽

pp. 89-98 ◽

Cited By ~ 14

Author(s):

Susan M Webb ◽

John E Ware ◽

Anna Forsythe ◽

Min Yang ◽

Xavier Badia ◽

...

Keyword(s):

Quality Of Life ◽

Cushing’S Disease ◽

Treatment Effectiveness ◽

Clinical Signs ◽

Signs And Symptoms ◽

Cushing's Disease ◽

Health Related Quality ◽

Related Quality ◽

Health Related

ObjectiveCushing's disease (CD) can significantly impair patients' health-related quality of life (HRQOL). This study investigated the treatment effectiveness of pasireotide on HRQOL of CD patients, and assessed the relationships between HRQOL and urinary free cortisol (UFC) and CD-related signs and symptoms.DesignIn this phase III, randomized, double-blind study, patients with UFC ≥1.5×upper limit of normal (ULN) received s.c. pasireotide 600 or 900 μg twice daily. The trial primary endpoint was UFC at or below ULN at month 6 without dose titration. Open-label treatment continued through month 12. HRQOL was measured using the Cushing's Quality of Life Questionnaire (CushingQoL) instrument at baseline and follow-up visits until month 12 during which clinical signs and features of CD, and the Beck Depression Inventory II (BDI-II), were also collected.MethodsPearson's/Spearman's correlations between changes in CushingQoL and changes in clinical signs and symptoms were assessed. Changes in CushingQoL and the proportion of patients achieving a clinically meaningful improvement in CushingQoL were also compared among patients stratified by mean UFC (mUFC) control status (controlled, partially controlled, and uncontrolled) at month 6. Analyses were also conducted at month 12, with multivariable adjustment for baseline characteristics and CushingQoL.ResultsChange in CushingQoL was significantly correlated with changes in mUFC (r=−0.40), BMI (r=−0.39), weight (r=−0.41), and BDI-II (r=−0.54) at month 12 but not at month 6. The percentage of CushingQoL responders at month 12 based on month 6 mUFC control status were as follows: 63, 58.8, and 37.9% in the controlled, partially controlled, and uncontrolled groups respectively. Adjusted CushingQoL scores at month 12 were 58.3 for controlled patients (Δ=11.5 vs uncontrolled,P=0.012) and 54.5 for partially controlled patients (Δ=7.7 vs uncontrolled,P=0.170).ConclusionsPasireotide treatment can result in a meaningful HRQOL improvement among those who complete a 12-month treatment period, most often among patients achieving biochemical control.

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