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

Primary Purpose

Adrenal Tumour With Mild Hypercortisolism

Status
Active
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Adrenalectomy
Sponsored by
Region Skane
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adrenal Tumour With Mild Hypercortisolism focused on measuring mild hypercortisolism, adrenal tumour, surgical procedures, elective, indication

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Århus University Hospital
  • Haukeland University Hospital
  • Sahlgrenska University Hospital
  • Skåne University Hospital-Lund, Department of Surgery

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Follow-up

Surgery

Arm Description

Patients who are diagnosed with biochemically mild hypercortisolism (so-called subclinical Cushing´s syndrome), who are followed only.

Patients diagnosed with adrenal tumour and with biochemically mild hypercortisolism (so-called subclinical Cushing´s syndrome), operated with adrenalectomy

Outcomes

Primary Outcome Measures

Improvement of blood pressure as assessed by 24 hours blood pressure measurement
Blood pressure 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.

Secondary Outcome Measures

Normalization of diabetes mellitus
Normalization of diabetes mellitus according to the criteria of the World Health Organization and assessed by oral glucose tolerance test
Decreased body mass index (BMI) to < 30
Standard assessment of BMI
Bone density
Bone density assessed with dual energy x-ray absorptiometry (DEXA) at the lumbar spine and hip
Blood lipids
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
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
Mini Mental State Examination (MMSE) for cognitive function
Quality of Life assessed by SF 36
Quality of Life assessed by the generic instrument short form 36 (SF-36).
Atherosclerosis
Carotid ultrasound/duplex scans with evaluation of intimal thickness and plaques. Blood pressure measurement for ankle index
Adrenal cortical insufficiency
Rate of patients with postoperative adrenal cortical insufficiency in patients operated due to subclinical Cushings syndrome

Full Information

First Posted
November 18, 2010
Last Updated
March 30, 2023
Sponsor
Region Skane
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1. Study Identification

Unique Protocol Identification Number
NCT01246739
Brief Title
Adrenalectomy Versus Follow-up in Patients With Subclinical Cushings Syndrome
Acronym
AUSC
Official Title
Adrenalectomy Versus Follow-up in Patients With Mild Hypercortisolism: a Prospective Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 2011 (undefined)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Region Skane

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adrenal Tumour With Mild Hypercortisolism
Keywords
mild hypercortisolism, adrenal tumour, surgical procedures, elective, indication

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Follow-up
Arm Type
No Intervention
Arm Description
Patients who are diagnosed with biochemically mild hypercortisolism (so-called subclinical Cushing´s syndrome), who are followed only.
Arm Title
Surgery
Arm Type
Experimental
Arm Description
Patients diagnosed with adrenal tumour and with biochemically mild hypercortisolism (so-called subclinical Cushing´s syndrome), operated with adrenalectomy
Intervention Type
Procedure
Intervention Name(s)
Adrenalectomy
Intervention Description
Adrenalectomy (open or laparoscopic)
Primary Outcome Measure Information:
Title
Improvement of blood pressure as assessed by 24 hours blood pressure measurement
Description
Blood pressure 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.
Time Frame
At two years after intervention
Secondary Outcome Measure Information:
Title
Normalization of diabetes mellitus
Description
Normalization of diabetes mellitus according to the criteria of the World Health Organization and assessed by oral glucose tolerance test
Time Frame
At two years after intervention
Title
Decreased body mass index (BMI) to < 30
Description
Standard assessment of BMI
Time Frame
At two years post intervention
Title
Bone density
Description
Bone density assessed with dual energy x-ray absorptiometry (DEXA) at the lumbar spine and hip
Time Frame
At two years post intervention
Title
Blood lipids
Description
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)
Time Frame
At two years post intervention
Title
Cardiac function
Description
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)
Time Frame
At two years post intervention
Title
Cognitive function
Description
Mini Mental State Examination (MMSE) for cognitive function
Time Frame
At two years after intervention
Title
Quality of Life assessed by SF 36
Description
Quality of Life assessed by the generic instrument short form 36 (SF-36).
Time Frame
At two years after intervention
Title
Atherosclerosis
Description
Carotid ultrasound/duplex scans with evaluation of intimal thickness and plaques. Blood pressure measurement for ankle index
Time Frame
At two years after intervention
Title
Adrenal cortical insufficiency
Description
Rate of patients with postoperative adrenal cortical insufficiency in patients operated due to subclinical Cushings syndrome
Time Frame
At two years after intervention

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anders OJ Bergenfelz, MD, PhD
Organizational Affiliation
Department of Surgery, Skåne University Hospital, Lund, Sweden
Official's Role
Principal Investigator
Facility Information:
Facility Name
Århus University Hospital
City
Århus
ZIP/Postal Code
8000
Country
Denmark
Facility Name
Haukeland University Hospital
City
Bergen
ZIP/Postal Code
5021
Country
Norway
Facility Name
Sahlgrenska University Hospital
City
Gothenburg
ZIP/Postal Code
41345
Country
Sweden
Facility Name
Skåne University Hospital-Lund, Department of Surgery
City
Lund
ZIP/Postal Code
22185
Country
Sweden

12. IPD Sharing Statement

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Adrenalectomy Versus Follow-up in Patients With Subclinical Cushings Syndrome

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