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


CONCLUSIONS
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.
Roemmler
J
J
Department of Internal Medicine (Endocrinology) - Innenstadt, LM-University of Munich, Ziemssenstrasse 1, 80336 Munich, Germany. josefine.roemmler@med.uni-muenchen.de
Otto
B
B
Arafat
A M
AM
Bidlingmaier
M
M
Schopohl
J
J
D000172:Acromegaly / Q000097:blood* / Q000188:drug therapy*; D000328:Adult; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D054439:Ghrelin / Q000097:blood*; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors*
D015415:Biomarkers; D054439:Ghrelin; D020738:Leptin; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; C406545:pegvisomant