Effects of Metyrapone in Patients With Hypercortisolism

Inclusion Criteria:

• Patients with mild Cushing's Syndrome not candidate for surgery

• Current therapy with metyrapone since less than 1 week

• Cortisol levels at 08:00 after 1 mg-overnight dexamethasone suppression test (1mgDST) >1.8 μg/dL

• Confirmed with 2 mg two days dexamethasone suppression test (2mgx2dDST)

• Presence of at least one out of the following conditions: type 2 diabetes mellitus,impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT), arterialhypertension, bone mineral density (BMD) Z-score < -2.0 and/or fragility fracture atany skeletal site

• Stable anti-hypertensive therapies and blood pressure (BP) levels in the monthbefore enrolment

• Stable anti-diabetic therapies and glycometabolic control during the month beforeenrolment

• Stable body weight during the month before enrolment

Exclusion Criteria:

• Signs and/or symptoms of overt hypercortisolism (striae rubrae, moon facies, easybruising, buffalo hump, hypertrichosis)

• Malignant hypertension and/or BP <200/120 mmHg

• Severe hyperglycemia (i.e. FG >350 mg/dL)

• Urinary free cortisol (UFC) higher than 1.5 fold the upper normal range

• Presence of pheochromocytoma or primary hyperaldosteronism

• Possible adrenal metastases or radiological features suggestive for adrenalmalignancy (i.e. not homogeneous pattern, necrosis, calcifications, irregularmargins, local invasion and high density at computed tomography)

• Congenital adrenal hyperplasia

• Intake of drugs influencing cortisol metabolism and/or secretion

• Women in child-bearing age

• Patients with body mass index (BMI) >35 kg/m2