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

• ClinicalTrials.gov Identifier: NCT01246739
• Recruitment Status: Active, not recruiting
• First Posted: November 23, 2010
• Last Update Posted: April 3, 2023
• Sponsor: Region Skane
• Information provided by (Responsible Party): Region Skane

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.

Condition or disease	Intervention/treatment	Phase
Adrenal Tumour With Mild Hypercortisolism	Procedure: Adrenalectomy	Not Applicable

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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 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 2024
• Estimated Study Completion Date: December 2026

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. 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.

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 World Health Organization 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 assessed by SF 36 [ 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

Eligibility Criteria

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

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)

Contacts and Locations

Locations

Denmark

Århus University Hospital

Århus, Denmark, 8000

Norway

Haukeland University Hospital

Bergen, Norway, 5021

Sweden

Sahlgrenska University Hospital

Gothenburg, Sweden, 41345

Skåne University Hospital-Lund, Department of Surgery

Lund, Sweden, 22185

Sponsors and Collaborators

Region Skane

Investigators

• Principal Investigator: Anders OJ Bergenfelz, MD, PhD; Department of Surgery, Skåne University Hospital, Lund, Sweden

More Information

• Responsible Party: Region Skane
• ClinicalTrials.gov Identifier: NCT01246739
• Other Study ID Numbers: 2010/297
• First Posted: November 23, 2010
• Last Update Posted: April 3, 2023
• Last Verified: March 2023

Keywords provided by Region Skane:

mild hypercortisolism; adrenal tumour; surgical procedures, elective; indication

Additional relevant MeSH terms:

Adrenal Gland Neoplasms; Cushing Syndrome; Adrenocortical Hyperfunction; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Adrenal Gland Diseases; Endocrine System Diseases