Adrenalectomy Versus Follow-up in Patients With Subclinical Cushings Syndrome (AUSC)

Tracking Information
First Submitted Date ICMJE	November 18, 2010
First Posted Date ICMJE	November 23, 2010
Last Update Posted Date	January 16, 2018
Study Start Date ICMJE	June 2011
Estimated Primary Completion Date	December 2020 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: January 8, 2018)	Improvement of blood pressure [ Time Frame: At two years after intervention ]; Blood pressure as assessed by 24 hours measurement is considered to be improved if at least one of the following outcomes has occurred, and is sustained, during 2 years of follow-up: Normalization of hypertension without medical treatment; Unchanged or decreased blood pressure in patients with hypertension if the number or dose of the patient's antihypertensive drug (s) has been reduced; Unchanged normal blood pressure in patients who were normotensive at the time of randomization.
Original Primary Outcome Measures ICMJE; (submitted: November 22, 2010)	Normalization of hypertension [ Time Frame: At two years after intervention ]; Normalization of hypertension according to classification of the World Health Organization (WHO) assessed by 24 hours blood pressure measurement.
Change History	Complete list of historical versions of study NCT01246739 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: January 8, 2018)	Normalization of diabetes mellitus [ Time Frame: At two years after intervention ]Normalization of diabetes mellitus according to the criteria of the WHO and assessed by oral glucose tolerance test; Decreased body mass index (BMI) to < 30 [ Time Frame: At two years post intervention ]Standard assessment of BMI; Bone density [ Time Frame: At two years post intervention ]Bone density assessed with dual energy x-ray absorptiometry (DEXA) at the lumbar spine and hip; Blood lipids [ Time Frame: At two years post intervention ]Triglyceride and cholesterol changes of whole serum and of the lipoprotein classes; low-density-lipoprotein (LDL), very-low-density-lipoprotein (VLDL) and high-density-lipoprotein (HDL); Cardiac function [ Time Frame: At two years post intervention ]Cardiac function assessed by echocardiography; left ventricular ejection fraction (EF), left ventricular end-diastolic diameter (LVDD), left ventricular mass index (LVMI), ratio between mitral peak velocity flow of the early filling wave and the atrial wave (E/A ratio); Cognitive function [ Time Frame: At two years after intervention ]Mini Mental State Examination (MMSE) for cognitive function; Quality of Life [ Time Frame: At two years after intervention ]Quality of Life assessed by the generic instrument short form 36 (SF-36).; Atherosclerosis [ Time Frame: At two years after intervention ]Carotid ultrasound/duplex scans with evaluation of intimal thickness and plaques. Blood pressure measurement for ankle index; Adrenal cortical insufficiency [ Time Frame: At two years after intervention ]Rate of patients with postoperative adrenal cortical insufficiency in patients operated due to subclinical Cushings syndrome
Original Secondary Outcome Measures ICMJE; (submitted: November 22, 2010)	Normalization of diabetes mellitus [ Time Frame: At two years after intervention ]Normalization of diabetes mellitus according to the criteria of the WHO and assessed by oral glucose tolerance test; Decreased body mass index (BMI) to < 30 [ Time Frame: At two years post intervention ]Standard assessment of BMI; Bone density [ Time Frame: At two years post intervention ]Bone density assessed with dual energy x-ray absorptiometry (DEXA) at the lumbar spine and hip; Blood lipids [ Time Frame: At two years post intervention ]Triglyceride and cholesterol changes of whole serum and of the lipoprotein classes; low-density-lipoprotein (LDL), very-low-density-lipoprotein (VLDL) and high-density-lipoprotein (HDL); Cardiac function [ Time Frame: At two years post intervention ]Cardiac function assessed by echocardiography; left ventricular ejection fraction (EF), left ventricular end-diastolic diameter (LVDD), left ventricular mass index (LVMI), ratio between mitral peak velocity flow of the early filling wave and the atrial wave (E/A ratio); Cognitive function [ Time Frame: At two years after intervention ]Mini Mental State Examination (MMSE) for cognitive function; Quality of Life [ Time Frame: At two years after intervention ]Quality of Life assessed by the generic instrument short form 36 (SF-36).; Atherosclerosis [ Time Frame: At one and two years after intervention ]Carotid ultrasound/duplex scans with evaluation of intimal thickness and plaques. Blood pressure measurement for ankle index
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Adrenalectomy Versus Follow-up in Patients With Subclinical Cushings Syndrome
Official Title ICMJE	Adrenalectomy Versus Follow-up in Patients With Mild Hypercortisolism: a Prospective Randomized Controlled Trial
Brief Summary	Incidental findings of adrenal tumours,"incidentalomas", occur in 1-5 % in the general population and 10-25 % of these patients will exhibit biochemical mild hypercortisolism. Although the patients do not have clinical signs of classical Cushing's syndrome, they have an increased risk for hypertension, dyslipidemia, diabetes mellitus, osteoporosis and obesity. The hypothesis of the study is, that surgery of the adrenal adenoma responsible for the increased secretion of cortisol, will in part cure or ameliorate the metabolic syndrome.
Detailed Description	Adrenal incidentalomas, adrenal tumours detected without symptoms and signs of hormonal hypersecretion or malignancy, are common. Depending on modality (MRI, CT. Ultrasonography) adrenal tumours occur in approximately 1-5% of the population. In about 10% of patients, the tumours are bilateral. At autopsy studies adrenal tumours occur in 1% of patients under the age of 30, but in approximately 7% of patients older than 70 years. Investigation of the adrenal tumours focus on to exclude malignancy (which is uncommon), and an increased secretion of hormones (adrenaline, aldosterone, cortisol), so-called functional tumours. However, most often adrenal incidentalomas are non-functional. The most common functional disorder is increased secretion of cortisol, and then usually without clinical stigmata, known as subclinical Cushing's syndrome (or mild hypercortisolism). Clinical stigmata, Cushing's syndrome, is empirically associated with elevated levels of urinary cortisol. Subclinical Cushing's syndrome occurs in 10-25% of patients with adrenal incidentalomas. The incidence has been estimated at 0.8 / 1,000 inhabitants, making it a common disease. Diagnosis is based to detect an autonomous release of cortisol from the adrenal gland (a disorder of the so-called hypothalamic-pituitary-adrenal axis). Fundamental to the diagnosis is that the secretion of cortisol is not inhibited <50 nmol / L at 8.00, after an overnight test with 1 mg of oral dexamethasone. In addition, at least one of the following criteria for disturbance of the hypothalamic-pituitary-adrenal axis is suggested to be present: attenuated or abolished circadian rhythm of cortisol; ACTH in the low normal range or supressed; DHEAS low or supressed (age dependent) Numerous studies have shown that high blood pressure, diabetes, impaired glucose tolerance, and unfavourable lipid profile, is common in patients with subclinical Cushing's syndrome, and basically do not differ from patients with overt Cushing's syndrome. At follow-up of patients with adrenal incidentalomas, some patients exhibit intermittent mild hypersecretion of cortisol, others develop overt Cushing's syndrome (unusual) and still some patients with initially normal hypothalamic-pituitary-adrenal axis, develop a subclinical Cushing's syndrome. The aim of this study is to investigate if adrenalectomy for subclinical Cushing's syndrome (mild hypercortisolism without clinical signs), result in an improvement in cardiovascular risk factors, cardiac function, and arteriosclerosis compared to follow-up
Study Type ICMJE	Interventional
Study Phase	Not Applicable
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Adrenal Tumour With Mild Hypercortisolism
Intervention ICMJE	Procedure: Adrenalectomy; Adrenalectomy (open or laparoscopic)
Study Arms	No Intervention: Follow-up Patients who are diagnosed with biochemically mild hypercortisolism (so-called subclinical Cushing´s syndrome), who are followed only.; Experimental: Surgery Patients diagnosed with adrenal tumour and with biochemically mild hypercortisolism (so-called subclinical Cushing´s syndrome), operated with adrenalectomy Intervention: Procedure: Adrenalectomy
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Recruiting
Estimated Enrollment ICMJE; (submitted: November 22, 2010)	60
Original Estimated Enrollment ICMJE	Same as current
Estimated Study Completion Date	December 2022
Estimated Primary Completion Date	December 2020 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Adrenal tumour with biochemical mild hypercortisolism defined as pathological dexamethasone suppression test (cortisol > 50 nmol/L at 8.00 am after 1 mg dexamethasone at 10 pm, plus one of the following criteria Low or suppressed adrenocorticotropic hormone (ACTH) Low or suppressed dehydroepiandrosterone (DHEA) No or pathological circadian rhythm of cortisol Exclusion Criteria: Increased levels of 24 hours urinary excretion of cortisol; Pregnancy or lactation; Inability to understand information or to comply with scheduled follow-up; Mild hypercortisolism with bilateral adrenal tumours, without a gradient (lateralization on venous sampling)
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact: Anders OJ Bergenfelz, MD, PhD +4646172086 anders.bergenfelz@med.lu.se Contact: Erik Nordenström, MD, PhD +4646172305 erik.nordenstrom@skane.se
Listed Location Countries ICMJE	Denmark, Norway, Sweden
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01246739
Other Study ID Numbers ICMJE	2010/297
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Region Skane
Study Sponsor ICMJE	Region Skane
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Anders OJ Bergenfelz, MD, PhD Department of Surgery, Skåne University Hospital, Lund, Sweden
PRS Account	Region Skane
Verification Date	January 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP