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

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


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.

MeSH terms

  • 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


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