Elena Valassi1, Iris Crespo, Ignasi Gich, José Rodríguez, Susan M Webb. 1. Department of Medicine/Endocrinology, Hospital Sant Pau, IIB-Sant Pau and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), ISCIII, Universitat Autònoma de Barcelona, Barcelona, Spain. evalassi@santpau.cat
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.
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.
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