Macroprolactinoma size reduction with dopamine agonists

Dopamine agonists have been shown to be remarkably effective in reducing prolactin (PRL) levels and tumor size in patients with prolactinomas. The most striking effect on tumor size reduction occurs in patients with macroadenomas (tumor > 1 cm in diameter). Most early studies focused on bromocriptine, the earliest dopamine agonist developed and the agent with which we have the greatest experience. In 21 different series totalling 248 patients with macroadenomas, 76% had some tumor size decrease in response to bromocriptine. Tumor size reduction was quantified in nine series totalling 112 patients; 45 (40.2%) had a >50% reduction, 32 (28.6%) had a 25 to 50% reduction, 14 (12.5%) had a <25% reduction, and 21 (18.7%) had no evidence of any reduction in tumor size. In seven studies totalling 31 patients with macroprolactinomas, 26 (83.9%) showed some tumor size decrease, with most showing a >50% reduction in tumor size in response to pergolide. However, tumor size reduction was quantified in only 17 patients, 10 (58.8%) having a >50% reduction, 2 (11.8%) having a 25 to 50% reduction, 1 (5.9%) having a <25% reduction, and 4 (23.5%) having no reduction in tumor size. Quinagolide (CV 205-502) has been studied in nine studies totalling 105 patients with macroprolactinomas, 90 (85.7%) experiencing a significant decrease in tumor size. In all but one patient the changes were quantified, 50 (48.1%) having a reduction of >50%, 21 (20.2%) having a reduction of 25 to 50%, 18 (17.3%) having a reduction of 0 to 25%, and 15 (14.4%) having no change in tumor size. Cabergoline, a long-acting dopamine agonist given only once or twice weekly, has been shown in six studies totalling 45 patients with macroprolactinomas to cause a reduction in tumor size in 38 (84.4%). In these 45 patients, 13 (28.9%) had a reduction of >50%, 19 (42.3%) had a reduction of 25 to 50%, 6 (13.3%) had a reduction of 0 to 25%, and 7 (15.5%) had no change in tumor size. The three newer dopamine agonists have been given to a limited number of patients with macroprolactinomas previously shown to be either intolerant of or resistant to bromocriptine. Of these, zero of three treated with pergolide, 16 of 37 treated with quinagolide, and 9 of 18 treated with cabergoline had some tumor size reduction. Analysis of data in these studies has shown that the extent of tumor size reduction does not correlate with basal PRL levels, nadir PRL levels achieved, the percent fall in PRL, or whether PRL levels reached normal. Some patients had excellent reduction in PRL levels into the normal range but only modest changes in tumor size, and others had persistent hyperprolactinemia (although >75% suppression from basal values) with almost complete disappearance of tumor. A reduction in PRL levels always preceded any detectable change in tumor size, and PRL nonresponders are also tumor size nonresponders. In summary, all four dopamine agonists are effective in decreasing tumor size. When comparing their efficacy for reductions of ≤25%, the following are achieved: bromocriptine, 68.8%; pergolide, 70.6%; quinagolide, 68.3%; cabergoline, 71.2%. In most studies, however, side effects were significantly less with cabergoline than with bromocriptine.