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The Medical Treatment of Cushing’s Disease: Effectiveness of Chronic Treatment with the Dopamine Agonist Cabergoline in Patients Unsuccessfully Treated by Surgery

Departments 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, 80131 Naples, Italy; and Department of Internal Medicine (R.P., L.J.H., S.W.J.L.), Erasmus Medical Center, Rotterdam 3015 CE, The Netherlands

Address all correspondence and requests for reprints to: Rosario Pivonello, M.D., Ph.D., Department of Molecular and Clinical, Endocrinology and Oncology, "Federico II" University, Via Sergio Pansini, 5, 80131 Naples, Italy. E-mail: rpivone{at}tin.it.

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: 20 patients with CD unsuccessfully treated by surgery entered the study. Cabergoline was administered at an initial dose of 1 mg/wk, with a monthly increase of 1 mg, until urinary cortisol levels normalized or the maximal dose of 7 mg/wk 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 five patients after 6–18 months. Among the 10 long-term responsive patients, eight were followed for 24 months, whereas the remaining two were followed for 12–18 months, due to cabergoline withdrawal for intolerance. A sustained control of cortisol secretion for 24 month cabergoline treatment at the maximal dose ranging from 1-7 mg/wk (median: 3.5) without significant side effects, was obtained in eight of 20 (40%) patients.

Conclusions: The results of this study demonstrated that cabergoline treatment is effective in controlling cortisol secretion for at least 1–2 yr 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.

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