Second attempt to withdraw cabergoline in prolactinomas: a pilot study

According to Pituitary and Endocrine Society recommendations, cabergoline (CAB) therapy can be discontinued after 2 years in hyperprolactinemic patients who fit certain criteria. Previous studies found recurrence rates ranging between 26 and 69 %. Whether CAB therapy can be successfully discontinued after one unsuccessful withdrawal is unknown.

We conducted a pilot prospective two-center study on a second attempt of CAB withdrawal. Inclusion criteria were: (1) recurrence of hyperprolactinemia after first withdrawal; (2) additional CAB therapy for at least 2 years; (3) normal serum prolactin; (4) CAB dose ≤ 1 mg/week. Prolactin level was monitored after discontinuing therapy. Median follow up for patients who are still in remission was 42 months (range = 24-60).

A total of 17 patients were recruited. Mean age was 41.0 ± 17.3 years. 65 % were female. Initial tumors were microadenoma in 64.7 %, and macroadenoma in 35.3 %. The average weekly CAB dose at second withdrawal was 0.38 ± 0.20 mg (median = 0.25, range = 0.175-1). Eleven of 17 patients (64.7 %) recurred. Median time to recurrence was 6 months. The incidence of recurrence was 44 events per 100 person-years. The estimated cumulative hazard of recurrence was 40 and 82 % at 6 and 12 months respectively. The probability to be recurrence-free at 6 and 12 months was 65 and 41 %, respectively.

Second attempt of CAB withdrawal after 2 additional years of therapy may be successful in some patients. A second withdrawal can be attempted with close monitoring of prolactin level. In this study, we could not identify any predictor of recurrence. Most of the recurrences occurred within the first 12 months after withdrawal.