Recurrence of hyperprolactinemia following dopamine agonist withdrawal and possible predictive factors of recurrence in prolactinomas

The optimal duration of cabergoline (CAB) treatment of prolactinomas that minimizes recurrences is not well established. 2011 Endocrine Society Guidelines suggested that withdrawal may be safely undertaken after 2 years in patients achieving normoprolactinemia and tumor reduction. We analyzed 74 patients (mean age = 46.9 +/- 14.4, M/F = 19/55, macro/micro = 18/56) bearing a prolactinoma divided in 3 groups: group A (23) treated for 3 years, group B (23) for a period between 3 and 5 years, and group C (28) for a period > 5 years. CAB therapy was interrupted according to Endocrine Society Guidelines. Prolactin (PRL) levels were measured 3, 6, 12 and 24 months after withdrawal. Recurrence was defined with PRL levels aeyen30 ng/ml. Groups did not differ in pretreatment PRL levels (123.2 +/- 112.1, 120.9 +/- 123.8, 176.6 +/- 154.0), pituitary deficit (4, 17, 17 %), mean CAB weekly dose (0.7 +/- 0.4, 0.6 +/- 0.3, 0.7 +/- 0.4) and PRL levels before withdrawal (17.1 +/- 19.6, 11.4 +/- 8.8, 13.8 +/- 13.5). Recurrence occurred within 12 months in 34 patients (45.9 %), without significant differences among groups. Neuroradiological evaluation showed a significantly higher presence of macroadenoma in group C (13, 17 and 39 %, respectively). Recurrence rate of hyperprolactinemia did not depend on sex, tumor size or CAB dose but it was significantly correlated with PRL levels at diagnosis and before withdrawal (p = 0.03). Finally, patients with pituitary deficit at diagnosis showed a significantly higher recurrence rate (p = 0.03). The study provides additional evidence that prolonging therapy for more than 3 years does not reduce recurrence rate. In particular, recurrence risk was similar in micro- and macroadenomas, and higher in patients with pituitary deficits at diagnosis.