TOPLINE:

Evening doses of metyrapone reduced arterial blood pressure (BP) at the supine position and the epicardial adipose lipid content after 12 weeks in patients with mild autonomous cortisol secretion.

METHODOLOGY:

• Researchers conducted a secondary analysis of a prospective, exploratory, open-label, single-centre study to assess the cardiovascular risk profile of the cortisol-lowering treatment metyrapone in patients with mild autonomous cortisol secretion.
• They included 15 patients with mild autonomous cortisol secretion (median age, 59 years; 80% women) who were treated with evening doses of metyrapone (500 mg at 6 PM and 250 mg at 10 PM) for 12 weeks; 12 patients with hypertension and concomitant intake of antihypertensive medications were enrolled.
• Outcomes including cardiac fat stores, morphology, and myocardial function were evaluated using cardiac MRI and spectroscopy at baseline and after 12 weeks of treatment; BP at supine and standing positions was evaluated using standardised tests.
• Other outcomes such as lipid profiles, renin-angiotensin-aldosterone system activity, and branched-chain amino acid levels were also assessed.

TAKEAWAY:

• In patients without changes in antihypertensive medication, the mean systolic BP at the supine position significantly decreased from 137 mm Hg at baseline to 122 mm Hg at 12 weeks (P = .041), and the mean diastolic BP at the supine position reduced from 89 mm Hg to 75 mm Hg (P = .045). No significant changes were reported in BP at the standing position.
• From baseline to 12 weeks, the mean epicardial adipose lipid content significantly reduced from 1032.70 to 929.37 mm² (P = .022). Paracardial adipose lipid content and intramyocardial lipid content remained unchanged.
• After 12 weeks, levels of low-density lipoprotein 2 — which was medium to large in size — dropped by 37%, and levels of high-density lipoprotein 4 reduced by 7%. The aldosterone-to-angiotensin 2 ratio also significantly decreased after metyrapone treatment (P = .042).
• No significant changes were observed in cardiac function and morphology and branched-chain amino acid levels after 12 weeks of treatment.

IN PRACTICE:

"The results of our study might reflect a causal role of hypercortisolism for the development of cardiovascular comorbidities in MACS [mild autonomous cortisol secretion], which could be affected by chronotherapy with evening doses of metyrapone," the authors wrote.

SOURCE:

This study was led by Helena Niziolek, Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. It was published online on June 11, 2026, in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study lacked a control group. The small sample size and the exploratory assessment of multiple endpoints may have increased the risk for false-positive results. The study did not standardise concomitant antihypertensive therapy and dose adaptations.

DISCLOSURES:

This study received financial support through an investigator-initiated grant from Esteve to the Medical University of Vienna. Several authors declared receiving honoraria for lectures and presentations, speaker and/or consulting fees, and support for attending meetings and serving on advisory boards for various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.