Abstract
We evaluated the effect of ketoconazole (KT) treatment in two adolescents with pituitary dependent Cushing's disease. Case 1 :a girl, aged 12.9 years, was given orally KT (200 mg/day), which induced a significant decrease of plasma cortisol levels for 3-4 months (mean±SD: 29.1±8.3 at start vs 6.2±1.2 μg/dl at 3 months, p<0.01; blood samples were taken at 4-h intervals, 8 a.m.-12 p.m.) but not after 6 months(24.2 ± 4.0 μg/dl), despite an increase of KT dose up to 600 mg/day. Mean plasma ACTH levels were 36.2±4.7, 23.2±8.5 and 30.2±14.2 pg/ml, at start, 3 and 6 months, respectively. Similarly, in Case 2, a boy aged 14.8 years, KT (400 mg/day) reduced mean plasma cortisol levels for 3 months (25.8±2.3 vs 18.8±2.7 μg/dl; p<0.005) but not after 6 months (30.7±5.3 μg/dl), again despite an increase of KT dose up to 1000 mg/day. Mean ACTH levels remained unchanged for 3 months (45.1±5.3 at start vs 40.6±12.8 pg/ml at 3 months), but increased after 6 months (73.5±3.8 pg/ml; p<0.005 vs initial values). Both patients showed a good clinical improvement with reduction of body weight and normalization of blood pressure for six months; KT was well tolerated. Coincident with the reoccurence of clinical symptoms, magnetic resonance features of pituitary microadenoma became evident at six months and both patients underwent transsphenoidal surgery. Our experience shows that Ketoconazole may have a short reducing effect on plasma cortisol in children with pituitary dependent Cushing's disease while awaiting therapeutic surgery.
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