Metabolic, Pressor and Neuropsychological Effects of Metyrapone Treatment in Patients With Hypercortisolism
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Sponsor
- Istituto Auxologico Italiano
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Proportion of patients with a mean systolic BP reduction of ≥5 mm Hg
Study Overview
Brief Summary
The aims of the present study are to evaluate in patients with mild hypercortisolism the effect of metyrapone treatment on glycometabolic control, blood pressure, thrombotic risk parameters, lipid profile, bone turnover markers, mental health and cortisol circadian rhythm.
Detailed Description
This open prospective observational study will include patients with mild hypercortisolism of both adrenal and pituitary origin not candidate for surgery. Patients taking metyrapone since less than a week will be followed up for 24 weeks. During this period of time, patients will be re-evaluated as far as blood pressure control, glycometabolic control, thrombotic risk parameters, lipid profile, bone turnover markers and cortisol circadian rhythm is concerned.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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), arterial hypertension, bone mineral density (BMD) Z-score < -2.0 and/or fragility fracture at any skeletal site
- •Stable anti-hypertensive therapies and blood pressure (BP) levels in the month before enrolment
- •Stable anti-diabetic therapies and glycometabolic control during the month before enrolment
- •Stable body weight during the month before enrolment
Exclusion Criteria
- •Signs and/or symptoms of overt hypercortisolism (striae rubrae, moon facies, easy bruising, 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 adrenal malignancy (i.e. not homogeneous pattern, necrosis, calcifications, irregular margins, 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
Arms & Interventions
metyrapone treatment
hypercortisolemic patients taking metyrapone since less than a week (usually 250 mg/day, maximum dose 6000 mg/day)
Intervention: Metyrapone Capsules (Drug)
Outcomes
Primary Outcomes
Proportion of patients with a mean systolic BP reduction of ≥5 mm Hg
Time Frame: Baseline, 24 weeks
BP levels will be measured with arterial blood pressure monitoring (ABPM)
Secondary Outcomes
- Changes of bone turnover markers(Baseline, 12 and 24 weeks)
- Amelioration of psychological symptoms(Baseline, 12 and 24 weeks)
- Changes in glycometabolic control(12 and 24 weeks)
- Normalization of cortisol circadian rhythm(baseline, 12 weeks, 24 weeks.)
- Changes of lipid profile(Baseline, 12 and 24 weeks)
- Changes of thrombotic risk parameters(Baseline, 12 and 24 weeks)