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Metyrapone treatment in Cushing’s syndrome: a real-life study

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Introduction and aim

Medical treatment is increasingly used in patients with Cushing’s syndrome (CS). Metyrapone (MET) is an inhibitor of 11β-hydroxylase: retrospective studies reported a decrease of cortisol secretion in 50% of cases. We evaluated the effectiveness of MET in an observational study, considering the normalization of urinary-free cortisol (UFC) and late-night salivary cortisol (LNSC) levels.

Materials and methods

We enrolled 31 patients with CS, treated with MET for at least 1 month (16 for primary treatment and 15 after surgical failure). A planned dose-titration regimen considering baseline UFC levels was adopted; MET dose was uptitrated until UFC normalization, surgery, or side effect occurrence. UFC and LNSC levels were routinely measured by liquid chromatography–tandem mass spectrometry.


Patients were treated with a median dose of 1000 mg for 9 months. UFC and LNSC decreased quickly after the first month of treatment (−67 and −57% from baseline), with sustained UFC normalization up to 12 and 24 months (in 13 and 6 patients, respectively). UFC and LNSC normalized later (after 3–6 months) in patients with severe hypercortisolism (>5-fold baseline UFC). Regarding the last visit, 70 and 37% of patients normalized UFC and LNSC, respectively. Body weight reduction (−4 kg) was observed after UFC normalization. Severe side effects were not reported, half of the female patients complained of hirsutism, and blood pressure was not increased.


MET therapy is a rapid-onset, long-term effective, and safe medical treatment in CS patients, achieving UFC normalization (in 70% of patients) more than cortisol rhythm recovery (in 37% of subjects).

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Adrenal Cushing’s syndrome


Adverse events


Body mass index


Cushing’s syndrome


Cushing’s disease


Common Terminology Criteria for Adverse Events


Dexamethasone suppression test


Ectopic ACTH syndrome


Electronic case report/record form


Interquartile range


Liquid chromatography–tandem mass spectrometry


Late night salivary cortisol




Mean of 3 UFC


Mean of 2 LNSC


Urinary-free cortisol


Upper limit of normality


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Correspondence to Filippo Ceccato.

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F.C.: The Ph.D. grant was founded by Novartis. The remaining authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Ceccato, F., Zilio, M., Barbot, M. et al. Metyrapone treatment in Cushing’s syndrome: a real-life study. Endocrine 62, 701–711 (2018).

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