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Adrenalectomy Versus Follow-up in Patients With Subclinical Cushings Syndrome

Adrenalectomy Versus Follow-up in Patients With Mild Hypercortisolism: a Prospective Randomized Controlled Trial

Status
Terminated
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01246739
Acronym
AUSC
Enrollment
34
Registered
2010-11-23
Start date
2011-06-30
Completion date
2024-02-29
Last updated
2024-04-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Adrenal Tumour With Mild Hypercortisolism

Keywords

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

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

Interventions

PROCEDUREAdrenalectomy

Adrenalectomy (open or laparoscopic)

Sponsors

Region Skane
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
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)

Design outcomes

Primary

MeasureTime frameDescription
Improvement of blood pressure as assessed by 24 hours blood pressure measurementAt two years after interventionBlood 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

MeasureTime frameDescription
Decreased body mass index (BMI) to < 30At two years post interventionStandard assessment of BMI
Bone densityAt two years post interventionBone density assessed with dual energy x-ray absorptiometry (DEXA) at the lumbar spine and hip
Blood lipidsAt two years post interventionTriglyceride 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 functionAt two years post interventionCardiac 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)
Normalization of diabetes mellitusAt two years after interventionNormalization of diabetes mellitus according to the criteria of the World Health Organization and assessed by oral glucose tolerance test
Quality of Life assessed by SF 36At two years after interventionQuality of Life assessed by the generic instrument short form 36 (SF-36).
AtherosclerosisAt two years after interventionCarotid ultrasound/duplex scans with evaluation of intimal thickness and plaques. Blood pressure measurement for ankle index
Adrenal cortical insufficiencyAt two years after interventionRate of patients with postoperative adrenal cortical insufficiency in patients operated due to subclinical Cushings syndrome
Cognitive functionAt two years after interventionMini Mental State Examination (MMSE) for cognitive function

Countries

Denmark, Norway, Sweden

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026