Abstract
Introduction: Prolactinomas are the most frequent pituitary-secreting tumors. Medical therapy with cabergoline (CAB), a dopamine agonist (DA), is the first line treatment, but 10% of prolactinomas are resistant to CAB. Recently, in vitro studies have shown anti-tumoral activity of metformin and other biguanids in human prolactinomas1, which prompted us to investigate that possibility in vivo. Aim: To evaluate the effect of metformin (MET) on Prolactin (PRL) secretion in patients with CAB resistant prolactinomas. Design and Setting: Prospective interventional study in a single referral center. Subjects: Ten patients (7 M; mean age: 44 ± 12y) with CAB resistant (PRL: 148 ± 125ng/ml; range: 38 - 386) prolactinomas (all macroadenomas) and metabolic syndrome on maximally tolerated CAB doses (4.3 ± 1.2 mg/week; range: 2.0-7.0) for ≥ 6 months (45 ± 39mo; range: 6-120). Intervention: Oral extended release metformin (p.o.) was prescribed according to patient’s tolerance (mean dose: 1.3 ± 0.4 g; range: 1.0-2.0). Main Outcome Measurements: Serum PRL (Elecsys, Roche, Indianapolis, USA), body weight (BW), fasting glycemia (FG) and HbA1C were evaluated before and at two time points during metformin treatment (30-60 and 120-180 days). Results: BW, FG, and/or HbA1C reductions were observed in 9/10 patients and mean FG decreased significantly (P=0.04). No significant changes were observed in serum PRL levels during metformin treatment [134 ± 124 ng/ml vs 138 ± 132 ng/ml vs 144 ± 129 ng/ml, before, at 30-60 days and at 120-180 days, respectively (P=0.499, mixed-effects analysis with the Geisser-Greenhouse correction)]. Individually, two patients exhibited a ≥ 50% decrease in PRL levels at a single timepoint (one at 30-60 days, with a further increase at 120-180 days and the other at 120-180 days). Conclusion: Metformin, at usual doses, did not inhibit prolactin secretion in patients with cabergoline-resistant prolactinomas. The discrepancy between our results and in vitro studies is not clear, but may be related to the much higher concentrations of metformin used in vitro1 as compared to the serum concentrations observed in patients during metformin treatment2.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
