Endocrine Abstracts

Cabergoline (CAB) is a selective dopamine D2-receptor agonist with long-lasting action, highly effective in treating micro- and macroprolactinoma. However, the clinical response to cabergoline can be seen only after several months of treatment, allowing the tumor shrinkage and decrease of prolactin. Despite most prolactinomas are responsive to CAB, there are up to 8% of cases in which tumor responsivity is limited. In order to asses the sensitivity to Cab, we aimed to develop a fast PRL suppression assay in patients with hyperprolactinemia, in a prospective interventional study.

Patients and methods: A total of 55 cases with hyperprolactinemia, naïve for dopamine agonists were included in a prospective study: 38 patients with prolactinoma and 17 with hyperprolactinemia from other causes, who served as controls. From the prolactinoma cases, eight proved in a longitudinal follow-up of 1 year to be resistant to dopamine agonists treatment. The test consist in assays of serum prolactin at basal, 12, 24 and 48 h after a dose of 0.5 mg CAB was given p.o. In addition, in order to assess the plasma levels of cabergoline, we used a mass-spectrometry based method developed for cabergoline assay. PRL levels were measured in serum samples using an automated immunoassay. Cabergoline measurements were performed using mass-spectrometry: instrumental analysis were performed on an HPLC tandem mass-spectrometer in the multiple-reaction monitoring method (MRM).

Results: Cabergoline determined the decrease of PRL of more than 50% of basal value in all sensitive prolactinoma cases, while in resistant, the decrease was much lower. The highest decrease is in the first 12 h after a dose of 0.5 mg Cab. In sensitive prolactinomas, basal PRL values decreased from 713.7 to 396.75 ng/ml at 12 h, 295.6 ng/ml at 24 h and 233 ng/ml at 48 h, while in resistant prolactinomas, basal PRL values decreased from 1508.7 ng/ml, at 1060.34 ng/ml at 12 h, 755.33 ng/ml at 24 h and 600.84 ng/ml at 48 h. However, the decrease of PRL in control group was much smaller. Cabergoline pharmacokinetics showed the highest value at 12 h, of 8.72 pg/ml, with a decrease at 5.64 pg/ml at 24 h and 4.23 pg/ml at 48 h.

Cabergoline suppression test can give information about the sensitivity to dopamine agonists in newly diagnosed prolactinomas, allowing a closer follow-up and a better management of patients with tumor hyperprolactinemia.