Influence of pegvisomant on serum ghrelin and leptin levels in acromegalic patients.

INTRODUCTION: Pegvisomant (peg) is a GH receptor antagonist. In de novo acromegalic patients with high GH levels, ghrelin and leptin levels are reduced, suggesting a direct GH-mediated effect. The aim of our study was to evaluate whether peg treatment in acromegalic patients may abolish the GH impact on ghrelin and leptin levels.
METHODS: Ghrelin, leptin and endogenous GH were measured in ten peg-treated acromegalic patients (three females/seven males, 47 years (28-57)), ten patients with active (act) and ten patients with inactive disease (inact) as well as in ten gender-, age- and body mass index (BMI)-matched healthy volunteers (controls). Endogenous GH was measured using a special in-house assay without interference by peg; total ghrelin and leptin were determined using a commercial RIA and an immunofluorometric in-house assay respectively.
RESULTS: Age and BMI did not differ significantly between groups. Endogenous GH was significantly higher in peg (6.3 μg/l (1.5-41)) and act (9.3 μg/l (1.7-70)) compared with controls (0.1 μg/l (0.1-3.1)) and inact (0.35 μg/l (0.1-2.0), P<0.001). Ghrelin was significantly higher in peg (232  ng/l (96-351)) compared with act (102 ng/l (33-232), P<0.01), whereas ghrelin was not significantly different between the other groups. Leptin was highest in controls (19 μg/l (4-57)) and lowest in act (6 μg/l (2-21)), but this difference did not reach significance.
CONCLUSION: Treatment with peg seems to disrupt the feedback loop of ghrelin and GH, leading to elevated ghrelin levels. Furthermore, peg therapy appears not to have a strong impact on leptin levels, as acromegalic patients with and without peg treatment showed similar leptin levels.