Recurrence of Hyperprolactinemia after Withdrawal of Long-Term Cabergoline Therapy

Abstract

Recurrence of hyperprolactinemia after cabergoline withdrawal ranges widely from 36 to 80%. The Pituitary Society recommends withdrawal of cabergoline in selected patients. Our aim was to evaluate recurrence of hyperprolactinemia in patients meeting The Pituitary Society guidelines. Patients were followed from the date of discontinuation to either relapse of hyperprolactinemia or the day of last prolactin test. We conducted the study at an academic medical center. Forty-six patients meeting Pituitary Society criteria (normoprolactinemic and with tumor volume reduction after 2 or more years of treatment) participated in the study. 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. We measured risk of and time to recurrence estimates as well as clinical predictors of recurrence. 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. 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.