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

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ClinicalTrials.gov Identifier: NCT01246739
Recruitment Status : Recruiting
First Posted : November 23, 2010
Last Update Posted : January 16, 2018
Information provided by (Responsible Party):
Region Skane

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.

Condition or disease Intervention/treatment
Adrenal Tumour With Mild Hypercortisolism Procedure: Adrenalectomy

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Adrenalectomy Versus Follow-up in Patients With Mild Hypercortisolism: a Prospective Randomized Controlled Trial
Study Start Date : June 2011
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2022

Arm Intervention/treatment
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
Procedure: Adrenalectomy
Adrenalectomy (open or laparoscopic)

Primary Outcome Measures :
  1. 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:

    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.

Secondary Outcome Measures :
  1. 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

  2. Decreased body mass index (BMI) to < 30 [ Time Frame: At two years post intervention ]
    Standard assessment of BMI

  3. 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

  4. 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)

  5. 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)

  6. Cognitive function [ Time Frame: At two years after intervention ]
    Mini Mental State Examination (MMSE) for cognitive function

  7. Quality of Life [ Time Frame: At two years after intervention ]
    Quality of Life assessed by the generic instrument short form 36 (SF-36).

  8. 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

  9. 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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01246739

Contact: Anders OJ Bergenfelz, MD, PhD +4646172086 anders.bergenfelz@med.lu.se
Contact: Erik Nordenström, MD, PhD +4646172305 erik.nordenstrom@skane.se

Århus University Hospital Recruiting
Århus, Denmark, 8000
Contact: Per Poulsen, MD, PhD,DMSc    +4578462008    logstrup.@dadlnet.dk   
Haukeland University Hospital Recruiting
Bergen, Norway, 5021
Contact: Anette Heie, MD    +4797647525    anette.heie@helse-bergen.no   
Sub-Investigator: Grethe Åström Ueland, MD         
Principal Investigator: Hrafnkell B Thordarson, MD         
Sub-Investigator: Turid Aas, MD         
Sub-Investigator: Eystein S Husebye, MD, PhD         
Sahlgrenska University Hospital Recruiting
Gothenburg, Sweden, 41345
Contact: Oskar Ragnarsson, MD, PhD    +46707292228    oskar.ragnarsson@medic.gu.se   
Skåne University Hospital-Lund, Department of Surgery Recruiting
Lund, Sweden, 22185
Contact: Anders OJ Bergenfelz, PhD    +46703772086    anders.bergenfelz@med.lu.se   
Sub-Investigator: Erik Nordenström, MD, PhD         
Sub-Investigator: Martin Almqvist, MD, PhD         
Sponsors and Collaborators
Region Skane
Principal Investigator: Anders OJ Bergenfelz, MD, PhD Department of Surgery, Skåne University Hospital, Lund, Sweden

Responsible Party: Region Skane
ClinicalTrials.gov Identifier: NCT01246739     History of Changes
Other Study ID Numbers: 2010/297
First Posted: November 23, 2010    Key Record Dates
Last Update Posted: January 16, 2018
Last Verified: January 2018

Keywords provided by Region Skane:
mild hypercortisolism
adrenal tumour
surgical procedures, elective

Additional relevant MeSH terms:
Adrenal Gland Neoplasms
Cushing Syndrome
Adrenocortical Hyperfunction
Endocrine Gland Neoplasms
Neoplasms by Site
Adrenal Gland Diseases
Endocrine System Diseases