The medical treatment of Cushing's disease: effectiveness of chronic treatment with the dopamine agonist cabergoline in patients unsuccessfully treated by surgery.
Department of Molecular and Clinical Endocrinology and Oncology [R.P., M.C.D.M., M.D.L., A.F., G.L., A.C.], and Neurosurgery [P.C], "Federico II" University, Naples, Italy and Department of Internal Medicine [R.P., L.J.H., S.W.J.L.], Erasmus Medical Center, Rotterdam, The Netherlands.
J Clin Endocrinol Metab 2008 Oct 28.
Background: The role of dopamine agonists in the treatment of Cushing's disease (CD) has been previously debated. Aim: The aim of this study was to evaluate the effectiveness of short-term (3 months) and long-term (12-24 months) treatment with cabergoline in patients with CD.
Patients and Methods: Twenty patients with CD unsuccessfully treated by surgery entered the study. Cabergoline was administered at an initial dose of 1 mg/week, with a monthly increase of 1 mg, until urinary cortisol levels normalized or the maximal dose of 7 mg/week was achieved. The responsiveness to treatment was evaluated according to changes in urinary cortisol excretion: a decrease greater than 25% was considered as a partial response, whereas complete normalization was considered as a full response at short-term evaluation; persistence of normal cortisol excretion was the only criterion to evaluate the response at long-term evaluation.
Results: After short-term treatment, 15 (75%) patients were responsive to cabergoline treatment. Among these, normalization of cortisol excretion was maintained in 10 whereas treatment escape was observed in 5 patients after 6-18 months. Among the 10 long-term responsive patients, eight were followed for 24 months, whereas the remaining 2 were followed for 12 months, due to cabergoline withdrawal for intolerance. A sustained control of cortisol secretion for 24 months of cabergoline treatment at the maximal dose, ranging from 1 to 7 mg/week (median: 3.5 mg/week) without significant side effects, was obtained in 8/20 (40%) patients.
Conclusions: The results of this study demonstrated that cabergoline treatment is effective in controlling cortisol secretion for at least 1-2 years in more than one third of a limited population of patients with CD. If this evidence is confirmed by additional studies, this agent may be considered as a useful treatment option in patients with CD who are unsuccessfully treated by neurosurgery.