Cushing Syndrome
Conditions
Keywords
Circadian Rhythm, Quality of Life
Brief summary
The purpose of this study is to prospectively study patients with Cushing's syndrome before and after treatment, with a special emphasis on physical function, quality of life, and circadian rhythms. The hypotheses are: * Cushing's syndrome negatively impacts health-related quality of life (HRQoL) and physical functioning * Cushing's syndrome is associated with altered circadian rhythms at the whole body level and in peripheral target tissues. * These complications partially reverse following disease control.
Interventions
OTHERno intervention, as this is an observational study
no intervention
Sponsors
Aarhus University Hospital
University of Aarhus
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* New (≤ 2 months) diagnosis of Cushing's syndrome (CS) of endogenous etiology: * ACTH-dependent CS * ACTH-independent CS * Age \>18 years * Written informed consent
Exclusion criteria
* Active cancer * Iatrogenic or malignant cause of CS such as adrenocortical carcinoma * Chronic heart failure (New York Heart Association class IV) * Chronic kidney disease Chronic Kidney Disease stage ≥3 (eGFR \>30 ml/min) * Liver disease in the form of cirrhosis * Deemed unable to complete the study safely by investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in CushingQoL-score | Baseline, 3 months after and 1 year after treatment | Questionnaire filled out by patients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in waist circumference | Baseline, 3 months after and 1 year | waist circumference is recorded with measuring tape. |
| Change in 24 hour urinary steroid metabolome | Baseline, 3 months after and 1 year | Steroid metabolome |
| Change in 24 hour urinary adreneric metabolites | Baseline, 3 months after and 1 year | Adrenergic metabolites |
| Change in Hospital Anxiety and Depression Scale (HADS) score | Baseline, 3 months after and 1 year after treatment | Questionnaire filled out by patients |
| Change in Single item Sleep Quality Scale (SQS) score | Baseline, 3 months after and 1 year | Questionnaire filled out by patients |
| Change in arterial stiffness and endothelial function. | Baseline, 3 months after and 1 year | Arterial stiffness is assessed as Carotid-femoral PWV (cfPWV), measured using the SphygmoCor device (version 9; AtCor Medical |
| Change in endothelial function. | Baseline, 3 months after and 1 year | Endothelial function will be assessed by the EndoPAT® device (Itamar Medical) |
| Change in blood pressure | Baseline, 3 months after and 1 year | Blood pressure, both standard office readings and as AOBP (Automated Office Blood Pressure) |
| Change in Insulin resistance | Baseline, 3 months after and 1 year | Assessed through fasting blood levels of insulin and glucose (Homeostasis Model Assessment, HOMA) |
| Change in Hba1C | Baseline, 3 months after and 1 year | Assessed as glycated hemoglobin A1C levels measured at three time points |
| Change in Messenger RNA expression of core clock genes in blood leukocytes and biopsies of skeletal muscle and adipose tissue. | Baseline, 3 months after and 1 year | Messenger RNA expression of core clock genes such as BMAL1, CLOCK, PER1-3, CRY1-2, REV-ERBα -β and -γ, RORA-C will be determined. For comparison, housekeeping genes such as Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), β2 microglobulin (B2M) and β-actin (ACTB) will be used. All will be expressed as -fold change from baseline expression levels |
| Change in body composition | Baseline, 3 months after and 1 year | Dual X-ray absorptiometry (DXA), is used to measure whole body lean body mass, and fat mass in gram |
| Change in Bone Mineral Density | Baseline, 3 months after and 1 year | Dual X-ray absorptiometry (DXA), bone mineral density (BMD) of the lumbar spine and femoral neck. |
| Change in Vertebral Fracture Assessment | Baseline, 3 months after and 1 year | Dual X-ray absorptiometry (DXA), is used to assess vertebral fractures (VFA). |
| Change in weight | Baseline, 3 months after and 1 year | Change in weight in kilograms |
| Change in BMI | Baseline, 3 months after and 1 year | Height and weight are combined to express body mass index (BMI, kg/m2) |
| Change in hip circumference | Baseline, 3 months after and 1 year | Hip circumference is recorded with measuring tape. |
| Change in Timed up and go (TUG)-test | Baseline, 3 months after and 1 year | The TUG Test combines measures of physical performance and coordination. The TUG test measures the time to stand up, walk 3 m in a straight line, and immediately return to the chair. The result is expressed as the fastest time in seconds |
| Change in Short Physical Performance Battery (SPPB) and chair rising test - score | Baseline, 3 months after and 1 year | The short physical performance battery (SPPB) is a group of bed-side measures that combines the results of walking speed, chair stand and balance tests. The result is expressed as a collective score from 0-12 |
| Change in Handgrip strength | Baseline, 3 months after and 1 year | Handgrip strength is measured using a hand dynamometer with the participant seated |
| Change in total physical activity | Baseline, 3 months after and 1 year | Measured with an Actigraph tri-axial accelerometer on the non-dominant wrist. Expressed as Counts/day |
| Change in Sedentary time | Baseline, 3 months after and 1 year | Measured with an Actigraph tri-axial accelerometer on the non-dominant wrist. Expressed as hours/day |
| Change in total sleep time | Baseline, 3 months after and 1 year | Measured with an Actigraph tri-axial accelerometer on the non-dominant wrist. Expressed as hours/day |
| Change in IPAQ-S7S | Baseline, 3 months after and 1 year | The questionnaire records types and intensity of physical activity and consists of seven open items |
| FACS of blood leukocytes | Baseline, 3 months after and 1 year | Flow assisted cell sorting (FACS) will be performed on blood leukocytes followed by real time quantitative polymerase chain reaction on distinct cells or in single cell suspension from relevant tissue. |
| Change in 24 hour urinary free cortisol | Baseline, 3 months after and 1 year | free cortisol |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in cytokines levels in blood | Baseline, 3 months after and 1 year | Such as Interleukin 6 Interleukin 10 Tumor necrosis factor alfa Transforming growth factor alfa Measured with cytokine luminex |
| Participant records: Number of infections, prescriptions for antibiotics | Baseline, 3 months after and 1 year | Assessed via electronic patient records |
| Change in metabolic and cardiovascular markers in blood | Baseline, 3 months after and 1 year | Such as plasma levels of Adiponectin, Leptin, Free fatty acids, cholesterol |
| Change in coagulation and inflammation markers in blood | Baseline, 3 months after and 1 year | Such as ADAM17 (Tumor necrosis factor-α-converting enzyme - TACE) Soluble CD16 (Human Low affinity immunoglobulin gamma Fc region receptor III-A) Fibrinogen vWF D-dimer Plasminogen, plasminogen activator inhibitor 1 Plasmin inhibitor |
Countries
Denmark
Contacts
Primary ContactSimon Bøggild Hansen, MD
Backup ContactJens Otto Lunde Jørgensen, Professor
Outcome results
None listed