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Prolactin Response to Metformin in Cabergoline-Resistant Prolactinomas: A Pilot Study

Authors
  • Portari, Luiz Henrique Corrêa
  • Correa-Silva, Silvia Regina
  • Abucham, Julio
Type
Published Article
Journal
Neuroendocrinology
Publisher
S. Karger AG
Publication Date
Jan 21, 2021
Volume
112
Issue
1
Pages
68–73
Identifiers
DOI: 10.1159/000514591
PMID: 33477154
Source
Karger
Keywords
Disciplines
  • Research Article
License
Green
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Abstract

Introduction: Cabergoline is the treatment of choice for prolactinomas. However, 10–20% of prolactinomas are resistant to cabergoline. Metformin, a biguanide widely used in the treatment of diabetes mellitus, has been shown to reduce prolactin secretion in various pituitary tumor-cell lineages both in vitro and in vivo and in human pituitary adenomas in vitro. The aim of this study is to test the effects of metformin addition to cabergoline treatment on prolactin levels in patients with resistant prolactinomas. Subjects and Methods: This is a prospective study performed in an outpatient clinic in a reference center. Ten adult patients (26–61 years) with prolactinomas (7 M), persistent hyperprolactinemia (38–386 ng/mL) under cabergoline treatment (2–7 mg/week) for at least 6 months (6–108 months), features of metabolic syndrome, and not taking metformin were included. Metformin (1.0–2.5 g v.o./day) was given according to patients’ tolerance. Cabergoline doses were kept unchanged. Serum prolactin levels were measured before and after short- (30–60 days) and long-term (120–180 days) metformin treatment. Results: Mean prolactin levels did not show any significant changes (148 ± 39 vs. 138 ± 42 vs. 133 ± 39 ng/mL, before, at 30–60 days, and at 120–180 days, respectively, p = 0.196) after metformin (mean dose: 1.25 g/day; range: 1.0–2.0 g/day). No patient reached a normal prolactin level during metformin treatment. Two patients were considered partial responders for exhibiting prolactin decreases ≥50% at a single time point during metformin. Conclusion: Metformin addition to ongoing high-dose cabergoline treatment in patients with cabergoline-resistant prolactinomas failed to show a consistent inhibitory effect in serum prolactin levels.

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