European journal of endocrinology · 2025
Prospective study of metyrapone in endogenous Cushing's syndrome (PROMPT).
СтатьяМногоцентровое исследованиеКлиническое исследованиеНазвание и аннотация: Перевод в очереди
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Nieman Lynnette K, Boscaro Marco, Scaroni Carla, Deutschbein Timo, Mezôsi Emese, Driessens Natacha, Georgescu Carmen E, Motyka Marcin, Hubalewska-Dydejczyk Alicja, Jarzab Barbara, Maiter Dominique, Reincke Martin, Loli Paola, Zampetti Benedetta, Atmaca Aysegul, Badiu Corin, Beckers Albert, Bolanowski Marek, Cavagnini Francesco, Unger Nicole, Giordano Roberta, Hanzu Felicia Alexandra, Terzolo Massimo, Nader Myriam Bou, Sinaii Ninet, Tőke Judit, Tóth Miklós
Аннотация
OBJECTIVE: We evaluated the safety and efficacy of metyrapone treatment for Cushing's syndrome (CS).
DESIGN: International, prospective, single-arm, open-label study.
METHODS: Fifty adults with endogenous CS (either unsuitable for or uncontrolled after surgery) and 3 urinary free cortisol (UFC) concentrations each ≥1.5-fold the upper limit of normal (ULN) were enrolled. After 12 weeks of metyrapone titration, participants with mean 24 h UFC (mUFC) ≤ 2-fold ULN could enter a 24-week extension phase. Safety was assessed, and doses adjusted at weeks 1-5, 8, 12, and 24. Pre-defined endpoints included normalization of mUFC at weeks 12 (primary), 24, and 36, and proportion of "responders" (normalization or ≥50% decrease of baseline mUFC), time to eucortisolemia, salivary cortisol day-curve, and quality of life (QoL).
RESULTS: Of the 49 evaluable participants, 47 completed the 12-week visit; 40 were evaluated at week 24 and 35 at week 36. The primary endpoint was met in 46.9% of participants (95% CI 32.5%-61.7%), with efficacy maintained at week 24 (52.5%; 95% CI 37.5%-67.1%) and week 36 (48.6%; 95% CI 33.0%-64.4%). The responder rates were 80.9%, 77.5%, and 71.4% at weeks 12, 24, and 36, respectively. Forty-seven participants (94%) developed mild-to-moderate adverse events (AEs), mostly during the first 12 weeks and most commonly nausea (38%), fatigue (26%), and headache (22%); 8 experienced severe AEs. Six participants developed reversible adrenal insufficiency during titration. Clinical features and QoL improved.
CONCLUSION: Metyrapone is a safe and effective treatment for endogenous CS.
DESIGN: International, prospective, single-arm, open-label study.
METHODS: Fifty adults with endogenous CS (either unsuitable for or uncontrolled after surgery) and 3 urinary free cortisol (UFC) concentrations each ≥1.5-fold the upper limit of normal (ULN) were enrolled. After 12 weeks of metyrapone titration, participants with mean 24 h UFC (mUFC) ≤ 2-fold ULN could enter a 24-week extension phase. Safety was assessed, and doses adjusted at weeks 1-5, 8, 12, and 24. Pre-defined endpoints included normalization of mUFC at weeks 12 (primary), 24, and 36, and proportion of "responders" (normalization or ≥50% decrease of baseline mUFC), time to eucortisolemia, salivary cortisol day-curve, and quality of life (QoL).
RESULTS: Of the 49 evaluable participants, 47 completed the 12-week visit; 40 were evaluated at week 24 and 35 at week 36. The primary endpoint was met in 46.9% of participants (95% CI 32.5%-61.7%), with efficacy maintained at week 24 (52.5%; 95% CI 37.5%-67.1%) and week 36 (48.6%; 95% CI 33.0%-64.4%). The responder rates were 80.9%, 77.5%, and 71.4% at weeks 12, 24, and 36, respectively. Forty-seven participants (94%) developed mild-to-moderate adverse events (AEs), mostly during the first 12 weeks and most commonly nausea (38%), fatigue (26%), and headache (22%); 8 experienced severe AEs. Six participants developed reversible adrenal insufficiency during titration. Clinical features and QoL improved.
CONCLUSION: Metyrapone is a safe and effective treatment for endogenous CS.