Usefulness of cabergoline determination by mass spectrometry during prolactinoma treatment
Corin Badiu1,2, Andra Caragheorgheopol2, Simona Verzea Jercalau2 & Luigi Silvestro3
Prolactinoma (PRM) treatment is based upon dopamine agonists, cabergoline (CAB) being one of the most used in the last decade. Sensitivity to CAB varies in terms of tumour volume and PRL secretion, up to 815% of PRM being defined as resistant. Since it is known that increasing the dosage improves the response rate, we aimed to measure plasma CAB levels in PRM patients under this treatment in a prospective interventional study.
Patients and methods: A total of 27 cases, 12F/ 15M, aged 40.2±17.1 years were included: 2 micro- and 23 macro PRM, as well as two acromegaly with PRL co-secretion. Surgery was used in 11 cases. All were submitted to CAB treatment at 0.53 mg/week (2.06±0.82), for at least 3 months (15.2±11.52), with decrease of tumor volume and PRL levels under 20 ng/ml in 20 cases. Seven were defined CAB resistant, due to lack of tumor or PRL control. PRL levels were measured in serum samples using an automated immunoassay. Plasma levels of cabergoline were assessed by a mass-spectrometry based method on an HPLC tandem mass-spectrometer in the multiple-reaction monitoring method.
Results: Under CAB treatment, average PRL levels decreased after 3 months at 11.64±9.1 ng/ml, at 6 months at 5.44±5.4 ng/ml and at 1 year 5.1±5.3 ng/ml in sensitive cases; PRL levels decreased after 3 months at 137±192.1 ng/ml, at 6 months at 123.83±211.26 ng/ml and at 1 year at 23.41±26.68 ng/ml in resistant cases. At the time of evaluation, PRL levels were 6.36±7.6 ng/ml in sensitive cases and 96.4±156 ng/ml in resistant cases. In sensitive PRM, CAB levels were 17.15±15.8 pg/ml, while in resistant, 12.6±9.66 pg/ml. However, from the 7 resistant cases, 3 were with CAB levels above 20 pg/ml, 4 being with values between 211 pg/ml. This suggests a lack of absorption, explaining a pseudo-resistance and suggesting the increase of CAB doses.
Conclusion: CAB measurement by HPLC-MS could be used to monitor the treatment of PRM in apparently resistant PRM, suggesting in increase of dosage in those with low levels or alternate treatment methods, in normal CAB levels.