Adrenalectomy Versus Follow-up in Patients With Subclinical Cushings Syndrome

NCT ID: NCT01246739

Last Updated: 2024-04-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2024-02-29

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

Conditions

Adrenal Tumour With Mild Hypercortisolism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Follow-up

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Surgery

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

Group Type: EXPERIMENTAL

Adrenalectomy

Intervention Type: PROCEDURE

Adrenalectomy (open or laparoscopic)

Interventions

Adrenalectomy

Adrenalectomy (open or laparoscopic)

Intervention Type: PROCEDURE

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Region Skane

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anders OJ Bergenfelz, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Surgery, Skåne University Hospital, Lund, Sweden

Locations

Århus University Hospital

Aarhus, , Denmark

Haukeland University Hospital

Bergen, , Norway

Sahlgrenska University Hospital

Gothenburg, , Sweden

Skåne University Hospital-Lund, Department of Surgery

Lund, , Sweden

Countries

Denmark; Norway; Sweden

References

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.

Reference Type: DERIVED

PMID: 40600855 (View on PubMed)

Other Identifiers

2010/297

Identifier Type: -

Identifier Source: org_study_id