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Endocrine. 2018 Dec;62(3):701-711. doi: 10.1007/s12020-018-1675-4. Epub 2018 Jul 16.

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

Author information

1
Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Padova, Italy. ceccato.filippo@gmail.com.
2
Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Padova, Italy.
3
Laboratory Medicine Unit, Department of Medicine DIMED, University-Hospital of Padova, Padova, Italy.

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; Liquid chromatography–tandem mass spectrometry; Medical treatment; Metyrapone

PMID:
30014438
DOI:
10.1007/s12020-018-1675-4

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