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

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).

• Authors: Filippo Ceccato, Marialuisa Zilio, Mattia Barbot, Nora Albiger, Giorgia Antonelli, Mario Plebani, Sara Watutantrige-Fernando, Chiara Sabbadin, Marco Boscaro, Carla Scaroni
• Journal: Endocrine (Endocrine) Vol. 62 Issue 3 Pg. 701-711 (12 2018) ISSN: 1559-0100 [Electronic] United States
• PMID: 30014438 (Publication Type: Journal Article)

Chemical References

• Enzyme Inhibitors
• Steroid 11-beta-Hydroxylase
• Hydrocortisone
• Metyrapone

Topics

• Adult
• Aged
• Circadian Rhythm (physiology)
• Cushing Syndrome (drug therapy)
• Enzyme Inhibitors (therapeutic use)
• Female
• Humans
• Hydrocortisone (analysis)
• Male
• Metyrapone (therapeutic use)
• Middle Aged
• Saliva (chemistry)
• Steroid 11-beta-Hydroxylase (antagonists & inhibitors)
• Treatment Outcome