Adrenal Tumour With Mild HypercortisolismAUSCNCT01246739
Adrenalectomy Versus Follow-up in Patients With Subclinical Cushings Syndrome
A study testing Adrenalectomy in people with Adrenal Tumour With Mild Hypercortisolism, run by Region Skane at 4 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adrenal Tumour With Mild Hypercortisolism
- What is being tested?
- Adrenalectomy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 4 sitesin 3 countries
- Study dates
- Jun 2011to Feb 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
Sweden2 sites
Sahlgrenska University Hospital
Gothenburg, 41345
Skåne University Hospital-Lund, Department of Surgery
Lund, 22185
About this study
Official title: Adrenalectomy Versus Follow-up in Patients With Mild Hypercortisolism: a Prospective Randomized Controlled Trial
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.
Read the 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
- Being tested
- Adrenalectomy
- Keywords
- mild hypercortisolism, adrenal tumour, surgical procedures, elective, indication
- Medical subject headings
- Adrenal Gland Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdrenalectomyProcedure or surgery
Adrenalectomy (open or laparoscopic)
| Study group | Role | What they receive |
|---|---|---|
| Follow-up | No intervention | Patients who are diagnosed with biochemically mild hypercortisolism (so-called subclinical Cushing´s syndrome), who are followed only. |
| Surgery | Experimental | Patients diagnosed with adrenal tumour and with biochemically mild hypercortisolism (so-called subclinical Cushing´s syndrome), operated with adrenalectomy Receives: Procedure: Adrenalectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At two years after intervention
Secondary outcomes (9)
Normalization of diabetes mellitus
Normalization of diabetes mellitus according to the criteria of the World Health Organization and assessed by oral glucose tolerance test
Measured: At two years after intervention
Decreased body mass index (BMI) to < 30
Standard assessment of BMI
Measured: At two years post intervention
Bone density
Bone density assessed with dual energy x-ray absorptiometry (DEXA) at the lumbar spine and hip
Measured: At two years post intervention
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)
Measured: At two years post intervention
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)
Measured: At two years post intervention
Cognitive function
Mini Mental State Examination (MMSE) for cognitive function
Measured: At two years after intervention
Quality of Life assessed by SF 36
Quality of Life assessed by the generic instrument short form 36 (SF-36).
Measured: At two years after intervention
Atherosclerosis
Carotid ultrasound/duplex scans with evaluation of intimal thickness and plaques.
Blood pressure measurement for ankle index
Measured: At two years after intervention
Adrenal cortical insufficiency
Rate of patients with postoperative adrenal cortical insufficiency in patients operated due to subclinical Cushings syndrome
Measured: At two years after intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2010 (estimated)
- Study startJun 2011
- Primary completionFeb 2024
- Study completionFeb 2024
Why it stopped: Slow recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adrenal Tumour With Mild HypercortisolismStudies of the same condition, open and under way.
- More trials run by Region SkaneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Region Skane
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anders OJ Bergenfelz, MD, PhD, Principal investigator, Department of Surgery, Skåne University Hospital, Lund, Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01246739
- Sponsor's protocol ID
- 2010/297
- Acronym
- AUSC
- Status last verified
- Mar 2024
- First submitted
- 18 Nov 2010
- Last updated
- 10 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
Publications
Ueland GA, Ragnarsson O, Heie A, Kjellbom A, Lindgren O, Muth A, Palazzo F, Poulsen PL, Rolighed L, Thordarson HB, Wernig F, Bergenfelz A. Randomized trial studying metabolic outcomes and quality of life after adrenalectomy versus conservative management for mild autonomous cortisol secretion. Endocr Connect. 2025 Jul 19;14(7):e250361. doi: 10.1530/EC-25-0361. Print 2025 Jul 1.
PubMed 40600855
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adrenalectomy Versus Follow-up in Patients With Mild Hypercortisolism: a Prospective Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT01246739
- Acronym / sponsor ID
- AUSC / 2010/297
- Keywords
- mild hypercortisolism, adrenal tumour, surgical procedures, elective, indication
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow recruitment
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Region SkaneUniversity, hospital or other
- Study start
- Jun 2011
- Primary completion
- Feb 2024 (actual)
- Study completion
- Feb 2024 (actual)
- First posted
- 23 Nov 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Follow-up | No intervention | –Patients who are diagnosed with biochemically mild hypercortisolism (so-called subclinical Cushing´s syndrome), who are followed only. |
| Surgery | Experimental | Procedure: AdrenalectomyPatients diagnosed with adrenal tumour and with biochemically mild hypercortisolism (so-called subclinical Cushing´s syndrome), operated with adrenalectomy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AdrenalectomyAdrenalectomy (open or laparoscopic) | Procedure or surgery | Surgery |
Primary outcome
Improvement of blood pressure as assessed by 24 hours blood pressure measurement
Time frame: At two years after intervention
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: 1. Normalization of hypertension without medical treatment 2. Unchanged or decreased blood pressure in patients with hypertension if the number or dose of the patient's antihypertensive drug (s) has been reduced 3. Unchanged normal blood pressure in patients who were normotensive at the time of randomization.
9 secondary outcomes
Normalization of diabetes mellitus
Time frame: At two years after intervention
Decreased body mass index (BMI) to < 30
Time frame: At two years post intervention
Bone density
Time frame: At two years post intervention
Blood lipids
Time frame: At two years post intervention
Cardiac function
Time frame: At two years post intervention
Cognitive function
Time frame: At two years after intervention
Quality of Life assessed by SF 36
Time frame: At two years after intervention
Atherosclerosis
Time frame: At two years after intervention
Adrenal cortical insufficiency
Time frame: At two years after intervention
Results and safety
The study was stopped early (reason given: Slow recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2024.
- Derived from this study: PubMed 40600855Ueland GA, Ragnarsson O, Heie A, Kjellbom A, Lindgren O, Muth A, Palazzo F, Poulsen PL, Rolighed L, Thordarson HB, Wernig F, Bergenfelz A. Randomized trial studying metabolic outcomes and quality of life after adrenalectomy versus conservative management for mild autonomous cortisol secretion. Endocr Connect. 2025 Jul 19;14(7):e250361. doi: 10.1530/EC-25-0361. Print 2025 Jul 1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anders OJ Bergenfelz, MD, PhD principal investigator
Department of Surgery, Skåne University Hospital, Lund, Sweden
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Adrenalectomy in people with Adrenal Tumour With Mild Hypercortisolism, run by Region Skane at 4 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Sweden, Denmark, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Slow recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement of blood pressure as assessed by 24 hours blood pressure measurement (time frame: At two years after intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01246739, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2024.