Cushing's syndrome (CS) is a serious condition requiring
drug management in diverse clinical settings. Fifty four patients (44 females, 10 males) with CS, aged 14-63, received
ketoconazole (KTZ) prior to surgery (n= 27), as complementary
therapy after surgery and/or
radiotherapy (n= 16), or as primary treatment (n= 11). It was given at a 600 (500 - 600) mg/day (median - Cl195) maintenance dose for periods ranging from 15 days to 13 years. Clinical signs, hepatic
enzymes and urinary free
cortisol (UFC) were evaluated before and during KTZ treatment. UFC normalised or decreased to subnormal values in 85% of the patients, in 5 to 150 days after starting treatment; although failing to normalise, UFC decreased to 12-48% of pre-treatment values in the remaining patients. Clinical signs improved throughout. Side effects were
adrenal insufficiency (18.5%), reversible hepatic toxicity (11%), allergic
skin rash (5.5%) and gastric intolerance (3.7%); in 11% of patients, an "escape phenomenon" was observed. Twenty-four out of the total (44.4%) were treated for prolonged periods, from one up to 13 years. In conclusion, this study confirms that KTZ is an effective and generally well tolerated treatment for CS particularly: a) shortly before surgery, b) because of persistent
hypercortisolism after surgery or awaiting the results of
radiotherapy, c) as a reasonable option in patients with CS of unknown aetiology and, d) as long-term
therapy in any case of unsolved
hypercortisolism after failure of current treatments.