Recurrence of Hyperprolactinemia After Withdrawal of Long-Term Cabergoline Therapy

Abstract

The dopamine agonist cabergoline (CAB) may produce a long-term normalization of serum prolactin and maintain markedly reduced tumor size in most patients with hyperprolactinemia. Long-term therapy is problematic from both a clinical and economic perspective. A previous study using criteria for CAB withdrawal based on multiple parameters obtained remission rates in hyperprolactinemia patients selected for withdrawal of 32% and rates in unselected patients of 70% to 90%. Specific criteria for selecting patients for withdrawal were recommended by the Pituitary Society in its 2006 guidelines. However, treatment outcomes using these guidelines have not been critically examined in a clinical setting. This retrospective study determined the rate of recurrence of hyperprolactinemia in 46 selected patients who met these guidelines (normoprolactinemic and with marked tumor volume reduction after 2 or more years of treatment) and investigated clinical predictors of recurrence. The study was conducted between 2002 and 2007 at a pituitary center. All patients were followed from the date of CAB withdrawal to either recurrence of hyperprolactinemia, or the day of last available prolactin test extracted from patient histories. Following withdrawal, prolactin measurements were obtained monthly, then quarterly in the first year and at 6-month intervals and 1-year intervals, thereafter. If a prolactin value was above the reference range, another prolactin measurement was obtained within 1 month, and if abnormal, an MRI was performed. Symptoms of hyperprolactinemia were assessed by use of a short questionnaire. The median age of patients was 45 years (range: 18-50) and 70% were women. Of the 46 patients, 31 (67%) had microprolactinomas, 11 (24%) had macroprolactinomas, and 4 (9%) had nontumoral hyperprolactinemia. At the time of study completion, 54% of all patients had recurred. At 18 months, the estimated risk of recurrence was 63%. Ninety-one percent of recurrences occurred within 1 year of CAB withdrawal at a median time of 3 months (range, 1-18 months). Recurrence after CAB withdrawal was predicted by the size of the tumor remnant: Each millimeter of size reduction from the original tumor size was associated with an 18% decrease in risk. At the time of recurrence, none of the residual tumors showed evidence of enlargement or regrowth on the MRI and overt symptoms of hypogonadism were reported by 28% of patients. The investigators conclude from these findings that CAB withdrawal in a subset of patients according to Pituitary Society guidelines is safe and effective. However, the risk of recurrence is high, especially during the first year, and frequent monitoring is important.