Metyrapone treatment in Cushing’s syndrome: a real-life study
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).
KeywordsCushing’s syndrome Metyrapone Liquid chromatography–tandem mass spectrometry Medical treatment
Adrenal Cushing’s syndrome
Body mass index
Common Terminology Criteria for Adverse Events
Dexamethasone suppression test
Ectopic ACTH syndrome
Electronic case report/record form
Liquid chromatography–tandem mass spectrometry
Late night salivary cortisol
Mean of 3 UFC
Mean of 2 LNSC
Upper limit of normality
Compliance with ethical standards
Conflict of interest
F.C.: The Ph.D. grant was founded by Novartis. The remaining authors declare that they have no conflict of interest.
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.
Informed consent was obtained from all individual participants included in the study.