TOPLINE

In adults with Cushing syndrome, treatment with metyrapone was associated with meaningful progressive improvements in health-related quality of life (HRQOL) over 36 weeks. The timing, pattern, and completeness of symptom recovery varied widely across symptom domains — some symptoms improved within weeks, others took months, and some remained elevated despite biochemical control.

METHODOLOGY

• Researchers conducted a longitudinal item-level analysis using data from a prospective, single-arm, open-label international trial to assess HRQOL in adults with Cushing syndrome who were treated with metyrapone.
• They included 49 adults with confirmed Cushing syndrome (mean age, 46.2 years; 69.4% women) who were ineligible for surgery or had persistent or recurrent disease following surgery. Patients underwent a 12-week titration period, after which those with clinical improvement and mean urinary free cortisol levels below twice the upper limit of normal at week 12 entered into a 24-week extension period (until 36 weeks).
• HRQOL was assessed using the CushingQoL questionnaire (a scale of 0-100; higher scores indicating better QOL) and the Tübingen Cushing's Disease Quality of Life Inventory (Tübingen CD-25; a scale of 0-100; higher scores indicating worse QOL) at baseline and weeks 4, 12, 24, and 36.
• A total of 47 patients completed the 12-week visit, and 41 of them entered the 24-week extension phase, of whom 40 and 35 were evaluated at weeks 24 and 36, respectively.
• Item-level analyses were performed, which tracked the pattern and timing of improvement in symptoms; items were classified into four response clusters on the basis of the first visit at which an absolute reduction of at least 10 percentage points from baseline was observed: very early (4 weeks), early (12 weeks), delayed (24-36 weeks), or persistent burden (no meaningful improvement).

TAKEAWAY

• The CushingQoL total score increased by 10.4 points from baseline to 36 weeks (P < .001), surpassing the minimal clinically important difference threshold of 10 points. The physical subscale score increased by 10.2 points and the psychosocial subscale score increased by 10.5 points at 36 weeks (P < .001 for both).
• The Tübingen CD-25 total score decreased by 7.8 points at 36 weeks (P = .010); eating behaviour symptoms significantly improved as early as 4 weeks (P = .002) and 12 weeks (P < .001). A significant improvement was observed in depression symptoms at the 4-week timepoint (P = .026).
• Sexual activity (P = .002) and environment or social domains (P = .028) improved later, reaching statistical significance only by 24 weeks. No significant improvement was observed in bodily restrictions and cognition at any timepoint.
• Women experienced statistically significant improvements across all CushingQoL scores: total score (+11.4 points; P < .001), psychosocial subscale score (+12.2 points; P < .001), and physical subscale score (+10.7 points; P = .001), whereas men showed numerically comparable improvements in the total score that did not reach statistical significance.

IN PRACTICE

"[The] descriptive findings illustrate the potential value of item-level reporting alongside aggregate scores in future Cushing's syndrome trials, and provide a basis for evaluating the complementary information yielded by the CushingQoL and Tübingen CD-25 instruments," the authors wrote.

SOURCE

This study was led by Emese Mezôsi, Department of Internal Medicine, University Medical School, Pécs, Hungary. It was published online on August 31, 2026, in the European Journal of Endocrinology.

LIMITATIONS

Improvements in HRQOL cannot be solely attributed to metyrapone because of the study's single-arm, uncontrolled design. Because all participants knew they were receiving active treatment, expectation and reporting bias cannot be completely ruled out. The small sample size reduced statistical power and may have introduced attrition bias.

DISCLOSURES

This study was funded by Esteve (formerly known as HRA Pharma Rare Diseases). Several authors declared receiving honoraria or speaking fees or serving as consultants and speakers for different pharmaceutical companies. Two authors declared being employees of Esteve.

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