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

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Abstract

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.

Results

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.

Conclusions

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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Abbreviations

ACS:

Adrenal Cushing’s syndrome

AE:

Adverse events

BMI:

Body mass index

CS:

Cushing’s syndrome

CD:

Cushing’s disease

CTCAE:

Common Terminology Criteria for Adverse Events

DST:

Dexamethasone suppression test

EAS:

Ectopic ACTH syndrome

eCRF:

Electronic case report/record form

IQR:

Interquartile range

LC-MS/MS:

Liquid chromatography–tandem mass spectrometry

LNSC:

Late night salivary cortisol

MET:

Metyrapone

mUFC:

Mean of 3 UFC

mLNSC:

Mean of 2 LNSC

UFC:

Urinary-free cortisol

ULN:

Upper limit of normality

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Author notes

  1. These authors contributed equally: Filippo Ceccato, Marialuisa Zilio.

Authors and Affiliations

  1. Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Padova, Italy

    Filippo Ceccato, Marialuisa Zilio, Mattia Barbot, Nora Albiger, Sara Watutantrige-Fernando, Chiara Sabbadin, Marco Boscaro & Carla Scaroni

  2. Laboratory Medicine Unit, Department of Medicine DIMED, University-Hospital of Padova, Padova, Italy

    Giorgia Antonelli & Mario Plebani

Authors
  1. Filippo Ceccato
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  2. Marialuisa Zilio
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Corresponding author

Correspondence to Filippo Ceccato.

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Conflict of interest

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

Ethical approval

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). https://doi.org/10.1007/s12020-018-1675-4

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