Recurrence of hyperprolactinemia after withdrawal of long-term cabergoline therapy

Context: Recurrence of hyperprolactinemia after cabergoline withdrawal ranges widely from 36 to 80%. The Pituitary Society recommends withdrawal of cabergoline in selected patients. Objective: Our aim was to evaluate recurrence of hyperprolactinemia in patients meeting The Pituitary Society guidelines. Design: Patients were followed from the date of discontinuation to either relapse of hyperprolactinemia or the day of last prolactin test. Setting: We conducted the study at an academic medical center. Patients: Forty-six patients meeting Pituitary Society criteria (normoprolactinemic and with tumor volume reduction after 2 or more years of treatment) participated in the study. Interventions: After withdrawal, if prolactin returned above reference range, another measurement was obtained within 1 month, symptoms were assessed by questionnaire, and magnetic resonance imaging was performed. Main Outcome Measures: We measured risk of and time to recurrence estimates as well as clinical predictors of recurrence. Results: Mean age of patients was 50 ± 13 yr, and 70% were women. Thirty-one patients had microprolactinomas, 11 had macroprolactinomas, and four had nontumoral hyperprolactinemia. The overall recurrence was 54%, and the estimated risk of recurrence by 18 months was 63%. The median time to recurrence was 3 months (range, 1-18 months), with 91% of recurrences occurring within 1 yr after discontinuation. Size of tumor remnant prior to withdrawal predicted recurrence [18% increase in risk for each millimeter (95% confidence interval, 3-35; P = 0.017)]. None of the tumors enlarged in the patients experiencing recurrence, and 28% had symptoms of hypogonadism. Conclusions: Cabergoline withdrawal is practical and safe in a subset of patients as defined by The Pituitary Society guidelines; however, the average risk of long-term recurrence in our study was over 60%. Close follow-up remains important, especially within the first year.