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

Objective To evaluate the outcome of preoperative therapy with ketoconazole ( KTZ ) and/or metyrapone ( MTP ) in previously untreated patients with C ushing'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 .