A reappraisal of the medical therapy with steroidogenesis inhibitors in Cushing's syndrome

Clin Endocrinol (Oxf). 2012 Nov;77(5):735-42. doi: 10.1111/j.1365-2265.2012.04424.x.

Abstract

Objective: To evaluate the outcome of preoperative therapy with ketoconazole (KTZ) and/or metyrapone (MTP) in previously untreated patients with Cushing's syndrome (CS).

Design and patients: Sixty-two patients with CS (85% ACTH dependent), treated with steroidogenesis inhibitors prior to surgery between 1983 and 2010, were retrospectively studied. T(0) and t(1) defined baseline and end of preoperative medical treatment.

Results: Outcomes were based upon clinical and biochemical (normal UFC) control of hypercortisolism at t(1) : group CO (controlled) included 20 patients (32%) with eucortisolism and significant clinical improvement; group NC (not controlled) 30 (48%) with persistent hypercortisolism and no control of symptoms; and group PC (partially controlled) 12 patients (19%) who despite eucortisolism had no real clinical improvement. Median duration of treatment was 4 months (range: 1-30·7), and median cumulative dose of KTZ and MTP was 57 g (range: 3·6-240) and 120 g (range: 7·5-1215). CO patients were treated more with KTZ alone than the other groups (P < 0·05). MTP alone was administered more in PC than in CO patients (P < 0·01). No clinical differences were observed between groups at baseline. Systolic blood pressure at t(1) was higher in PC than in NC patients (P < 0·05). Hypertension persisted more in PC patients than in the other groups (P < 0·05) after a median postsurgery follow-up of 108 months (range: 4-276).

Conclusions: Preoperative administration of KTZ, MTP or both normalized UFC in 52% of patients with CS, but concomitant clinical improvement did not always follow. Larger, multicentre studies are needed to individualize preoperative medical treatment and improve outcome in patients with CS.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antimetabolites / therapeutic use*
  • Child
  • Cushing Syndrome / drug therapy*
  • Cushing Syndrome / surgery
  • Female
  • Humans
  • Ketoconazole / therapeutic use*
  • Male
  • Metyrapone / therapeutic use*
  • Middle Aged
  • Preoperative Period
  • Retrospective Studies
  • Young Adult

Substances

  • Antimetabolites
  • Ketoconazole
  • Metyrapone