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Endocrine

, Volume 62, Issue 3, pp 701–711 | Cite as

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

  • Filippo Ceccato
  • Marialuisa Zilio
  • Mattia Barbot
  • Nora Albiger
  • Giorgia Antonelli
  • Mario Plebani
  • Sara Watutantrige-Fernando
  • Chiara Sabbadin
  • Marco Boscaro
  • Carla Scaroni
Original Article

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).

Keywords

Cushing’s syndrome Metyrapone Liquid chromatography–tandem mass spectrometry Medical treatment 

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

Notes

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.

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.

Informed consent

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

Supplementary material

12020_2018_1675_MOESM1_ESM.docx (1012 kb)
Supplementary Material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Filippo Ceccato
    • 1
  • Marialuisa Zilio
    • 1
  • Mattia Barbot
    • 1
  • Nora Albiger
    • 1
  • Giorgia Antonelli
    • 2
  • Mario Plebani
    • 2
  • Sara Watutantrige-Fernando
    • 1
  • Chiara Sabbadin
    • 1
  • Marco Boscaro
    • 1
  • Carla Scaroni
    • 1
  1. 1.Endocrinology Unit, Department of Medicine DIMEDUniversity-Hospital of PadovaPadovaItaly
  2. 2.Laboratory Medicine Unit, Department of Medicine DIMEDUniversity-Hospital of PadovaPadovaItaly

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