Cabergoline suppression test in distinguishing the variability of response to dopamine agonists in prolactinomas
Corin BADIU2, Daniela VOICU4, Andra Caragheorgheopol1, Dan Hortopan1 & Luigi Silvestro3
Primary therapy in prolactinomas, the most frequent pituitary adenomas, consists in ergot derivatives dopamine agonists (bromocriptine or cabergoline) which lowers prolactin levels and shrink the tumour. Bromocriptine was the first drug used, but the therapeutic levels are attained after several days/weeks, therefore an acute suppression test is not possible. However, the biological response is variable and 10% of prolactinomas are resistant to medical therapy. In order to evaluate the degree of response to dopamine agonists, we tempted a short (48 h) cabergoline (CAB) suppression test. Twenty-nine patients with hyperprolactinemia, 21 prolactinomas (14 women and 7 men), 2 GH-PRL secreting adenomas (2 women) and 6 idiopathic hyperprolactinemia (5 women, 1 man), received a single cabergoline dose (0.5 mg) and were sampled for PRL at baseline, 12 h, 24 h and 48 h after CAB administration. Simultaneously, CAB levels were determined by mass spectrometry. Subsequently, patients were treated with Cab in doses up to 2 mg/twice a week. The final response to treatment was evaluated after completion of 6 months of therapy. According to this the 21 prolactinomas were divided into 13 sensitive and 8 resistant to dopamine agonists.
Mean PRL levels decreased from 384.37 ng/mL to 101.9 ng/ml at 12 h, 94.7 ng/mL at 24 h and 73.31 ng/ml at 48 h, in the senstitive group, and from 1508.37 ng/mL to 1060.34 ng/ml at 12 h, 755.33 ng/mL at 24 h and 600.84 ng/ml at 48 h, in the resistant group. Average cabergoline levels were similar in both groups. PRL decrease at 48 h as compared to baseline, was at 40% from basal level in resistant and at 20% in responsive cases, P<0.005. In acromegalic patients, co-secretion of PRL was suppressed at 65% basal level at 48 h, while in functional hyperprolactinemia, normal values were attained at 48 h. Suppression level was not influenced by the tumour size. In conclusion, cabergoline suppression test could be used as early predictor of PRL suppression and biological response in prolactinomas.