Cabergoline treatment in Cushing's disease: effect of cabergoline withdrawal in patients with normalized cortisol secretion after long-term treatment
Rosario Pivonello, Monica De Leo, Alessia Cozzolino, Pasquale Vitale, Maria Cristina De Martino, Chiara Simeoli, Gaetano Lombardi & Annamaria Colao
The dopamine agonist cabergoline has been found to be effective in inducing normalization of cortisol secretion in 2550% of patients with Cushings disease after long-term treatment. Moreover, tumor shrinkage have been documented in selected patients with pituitary corticotroph tumors. The aim of the present study was to evaluate the effect of cabergoline withdrawal in patients with a stable normalization of cortisol secretion and stable or absent visualization of pituitary tumor after long-term treatment. Ten patients unsuccessfully treated by surgery and then successfully treated with cabergoline at the dose ranging from 1 to 7 mg/week for 3 years entered the study. All patients had normal urinary cortisol levels; five patients had a stable microadenoma for at least 1 year and the remaining five had no visible pituitary tumor at magnetic resonance imaging (MRI) before the drug withdrawal. The patients were followed-up every month through a clinical examination, biochemical evaluation together with the measurement of plasma ACTH and serum and urinary cortisol levels, whereas a pituitary MRI was performed every six months during the following year. A progressive increase of serum and urinary cortisol as well as plasma ACTH levels, together with a reappearance of clinical syndrome, was observed in four patients, starting from 36 months from cabergoline withdrawal. No significant change in tumor volume or features were observed after 1 year. A new treatment was re-started in these patients. Two patients had an increase of plasma ACTH levels associated with a persistently normal serum and urinary cortisol levels and no significant change in clinical symptoms and signs after 1 year from the drug withdrawal. In the remaining four patients, a completely normal ACTH and cortisol secretion and persistently negative pituitary MRI was observed during the year following the treatment withdrawal. No change in clinical syndrome was observed in these latter patients. In conclusion, the results of the present study suggested that a group of patients with Cushings disease, persistently controlled by cabergoline treatment for 3 years, maintain cortisol secretion in normal range during the year following treatment withdrawal. Further studies on a larger population of patients are mandatory to understand the mechanism underlying this phenomenon and the eventual persistence of this apparent remission of the disease.