The first-line treatment of Cushings disease is surgery, although it is effective in inducing a long-term remission in around 50% of patients with Cushings disease (CD). Nowadays, no pituitary tumor-directed medical treatment is available with the exception of cabergoline, which has been recently demonstrated to control cortisol secretion without major side effects in around 40% of patients with Cushings disease. Cabergoline has been recently demonstrated to induce cardiac valve insufficiency in patients with Parkinsons disease, usually long-term treated with high dose of the drug. A widely used adrenal-directed palliative medical treatment is represented by ketoconazole, which however can be associated with different side effects mainly including liver damage especially when used at high dose (until 1200 mg/day) for a long period of time. The aim of the current study was to evaluate the effectiveness and safety of the combined treatment with cabergoline and low-dose ketoconazole in patients with Cushings disease partially responsive to cabergoline mootherapy. Six patients with post-surgical persistent Cushings disease had been treated with cabergoline at the maximal dose of 3.5 mg/week with a significant reduction but not normalization of urinary cortisol levels (from 530.5±136.2 to 258.0±107.1 μg/day, P<0.05) associated with a partial clinical improvement after 6 months of treatment. Ketoconazole at the initial dose of 50 mg was added to cabergoline in all patients, and increased by 50 mg every month until normalization of urinary cortisol levels had been achieved. After 6 months of combined treatment with cabergoline (3.5 mg/week) and ketoconazole (50200 mg/day), urinary cortisol levels were 107.8±19.8 μg/day (P<0.05), and were in the normal range in all patients. A significant clinical improvement was observed in parallel with the decrease and normalization of cortisol levels. No cardiac valve disease occurred or worsened during the 1-year treatment with cabergoline, except a worsening of tricuspidal regurgitation in one patient. No liver damage was observed in any patient. In conclusion, the combined treatment with cabergoline and low dose ketoconazole seems to be effective and safe in the management of patients with Cushings disease, and can be considered in patients who had unsuccessful surgical treatment or are not candidates for alternative definitive treatments.
25 - 29 Apr 2009
European Society of Endocrinology