Adrenalectomy Versus Follow-up in Patients With Subclinical Cushings Syndrome

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.

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

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)