Endocrine Abstracts

Objective: To determine if the response to one single dose of 0.5 mg cabergoline (CAB) can be used as predictor for choosing personalized therapy of hyperprolactinaemia. Although CAB is a selective, long half-life D2-receptor agonist some patients proved to be resistant with minimum to no response in serum prolactin and tumour shrinkage, even after a few months of treatment.

Patients and methods: A dose of 0.5 mg CAB was administered orally to a number of 53 naive patients, in a prospective interventional study. Based on hyperprolactinaemia two groups were selected: the first group of 38 patients with prolactinoma and a second group of 15 patients with other causes of hyperprolactinaemia, who served as control. In the prolactinoma group all cases were prospectively evaluated, starting a maintenance phase with 2–3 mg cabergoline twice a week for at least 6 months. This second phase allowed us to divide the prolactinoma group into sensitive and resistant cases: 31 proved to be sensitive and seven resistant to CAB, when comparing the results of serum prolactin dosage and tumour shrinkage on CT/MRI scan. The main test consists of a first phase when a single dose of CAB is administered and the serum prolactin is measured at basal, 12 and 48 h comparing these results. For a more complete understanding and analysis of linkage mechanism the plasma CAB levels were also measured using a mass-spectrometry based method. The instrumental analysis was performed on a HPLC tandem mass-spectrometer in the multiple-reaction monitoring method (MRM).

Results: CAB determined prolactin decrease in both sensitive and resistant cases but with a significant difference. In sensitive prolactinoma the decrease showed to be from 2781 to 1099 ng/ml at 12 h (which means almost with 60%, P=0.001), 1075.1 ng/ml at 24 h and 843.63 at 48 h. The highest decrease was registered at 12 h after CAB administration. In resistant prolactinomas, the decrease went from 3675.7 ng/ml basal value to 2043 ng/ml at 12 h, 1679.71 at 24 h and 1586.6 ng/ml at 48 h (which means lower than 45% in the first 12 h). In the control group the decrease was also much smaller. In the follow up time: one patient with small response at CAB test proved to be long-time therapy responsive and another one with prolactin decrease on CAB test, proved to develop partial response in long time treatment. Meanwhile, CAB pharmacokinetics showed the highest value at 12 h, which was 9.50 pg/ml, with 6.44 pg/ml at 24 h and 4.73 pg/ml at 48 h.

Conclusions: CAB test can provide information about the sensitivity to treatment for a better future management and good results, which is allowing patients to receive personalized therapy in adapted method and time duration. Anyway, further studies with larger study population should be done in order to completely understand all possible determinants of a better or a more accurate therapy response.