Effects of Metyrapone in Patients With Hypercortisolism

Active, not recruiting

• Conditions: Hypercortisolism
• Interventions: Drug: Metyrapone Capsules

• Registration Number: NCT05255900
• Lead Sponsor: Istituto Auxologico Italiano

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 Timeline

• Study First Submitted: 2022-02-14
• Study First Submitted QC: 2022-02-24
• Study First Posted: 2022-02-25
• Study Start: 2022-04-28
• Primary Completion: 2025-06-30
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-02
• Last Update Posted: 2025-09-08
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
metyrapone treatment	Metyrapone Capsules	hypercortisolemic patients taking metyrapone since less than a week (usually 250 mg/day, maximum dose 6000 mg/day)

Primary Outcome Measures

Name	Time	Method
Proportion of patients with a mean systolic BP reduction of ≥5 mm Hg	Baseline, 24 weeks	BP levels will be measured with arterial blood pressure monitoring (ABPM)

Secondary Outcome Measures

Name	Time	Method
Changes in glycometabolic control	12 and 24 weeks	i) the proportion of patients without type 2 diabetes achieving normalization of FG (\<100 mg/dL) and/or the reduction of 2-hour glucose levels below 140 mg/dL after OGTT; ii) the proportion of patients with type 2 diabetes achieving HbA1c \<7% among those with baseline HbA1c ≥7%;
Normalization of cortisol circadian rhythm	baseline, 12 weeks, 24 weeks.	The cortisol circadian rhythm will be assessed by salivary cortisol levels determination (at 8 AM, 12 AM, 4 PM, 8 PM and 11 PM).
Changes of lipid profile	Baseline, 12 and 24 weeks	The lipid profile modifications will be evaluated by measuring total cholesterol, low-density lipoprotein, high-density lipoprotein and triglycerides
Changes of bone turnover markers	Baseline, 12 and 24 weeks	The bone turnover changes will be assessed by measuring calcium, phosphorous, osteocalcin (OC), carboxy-terminal cross-linked telopeptide of type I collagen (CTX) and 24-h urinary calcium/creatinine ratio
Amelioration of psychological symptoms	Baseline, 12 and 24 weeks	Psychological symptoms wil be evaluated with Beck Depression Inventory-II (BDI-II), a 21-item self-administered inventory designed to measure the intensity of depressive symptoms (Beck, Steer, \& Brown, 1996). Scores ranging between 0 and 13 are indicative of minimal depression; scores that fall between 14 and 19 are considered to reflect a mild level of depression; scores of 20 to 28 are considered moderate; and a score ranging from 29 to 63 is labeled severe.
Changes of thrombotic risk parameters	Baseline, 12 and 24 weeks	The thrombotic risk profile will be evaluated by measuring C-Protein, S-Protein, coagulation factor VIII and anti-thrombin III levels

Trial Locations

Locations (1)

Istituto Auxologico Italiano; 🇮🇹 Milan, Italy