TOPLINE:
A notable proportion of patients with mild hypercortisolism achieved blood pressure (BP) control with low-dose evening metyrapone, without requiring the intensification of antihypertensive therapy. The treatment was particularly beneficial for those with higher baseline systolic BP and was well tolerated, with no adverse events reported.
METHODOLOGY:
- This prospective observational study assessed the impact of low-dose evening metyrapone on 24-hour ambulatory BP, glucose metabolism, and the cortisol circadian rhythm in 20 patients with mild hypercortisolism (median age, 70.5 years; 65% women).
- Eligible patients had cortisol levels > 1.8 μg/dL after a 1-mg dexamethasone suppression test on at least two separate occasions, fewer than two specific Cushing syndrome‑related symptoms, and either hypertension or impaired glucose metabolism.
- Patients received evening metyrapone 250 mg/d, with dose adjustments on the basis of clinical response and cortisol secretion; in 12 patients who showed no signs of hypoadrenalism after week 12, an additional 250-mg afternoon dose was given.
- The primary endpoint was BP control, defined as a reduction in mean 24-hour systolic BP of ≥ 5 mm Hg without increasing antihypertensive medication; ambulatory BP monitoring was done at baseline and weeks 12 and 24.
TAKEAWAY:
- At 24 weeks, 40% of patients had a clinically significant improvement in BP control without escalation of therapy, with reductions in both daytime and nighttime systolic BP; benefits were more pronounced in those with elevated baseline systolic BP.
- Glucometabolic control improved in four patients at 24 weeks; those with poorly controlled type 2 diabetes at baseline achieved the most pronounced glycaemic benefits.
- Salivary cortisol levels remained unchanged from baseline; no significant changes in hormonal, metabolic, or anthropometric parameters were observed from baseline, except for testosterone levels in women.
- The treatment was well tolerated, with no side effects or reports of adrenal insufficiency.
IN PRACTICE:
“Our findings support the notion that metyrapone may offer clinical benefits in patients with mH [mild hypercortisolism], particularly those with uncontrolled comorbidities. The observed improvements in BP and glycaemic control, despite minimal changes in UFC [urinary free cortisol] levels, underscore the need to re-evaluate traditional therapeutic targets and to adopt a more holistic approach to disease management,” the authors of the study wrote.
SOURCE:
This study was led by Antonio Musolino, University of Milan, Milan, Italy. It was published online on October 16, 2025, in the European Journal of Endocrinology.
LIMITATIONS:
This study was limited by its relatively short treatment duration, potential adherence bias, and an older cohort age, which may have limited generalisability. The sample size, although adequate for the primary endpoint, was limited. The absence of a control group restricted the ability to definitively attribute improvements to metyrapone therapy.
DISCLOSURES:
This study received financial support through an investigator-initiated study grant from ESTEVE (formerly HRA RD). Two authors reported receiving speaker or consultancy fees or honoraria from Corcept Therapeutics.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication
Filed under: Cushing's, Diagnostic Testing, symptoms | Tagged: blood pressure, dexamethasone suppression test, hypoadrenalism, Metyrapone, UFC, urinary free cortisol | Leave a comment »
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