Introduction: GH rises dose dependently during treatment with the GH receptor antagonist pegvisomant. Ghrelin stimulates GH secretion. In de novo acromegalic patients with high GH levels, ghrelin levels are lowered and fat mass is reduced. Leptin levels are positively correlated to fat mass. We performed this cross-sectional study to evaluate whether elevated endogenous GH in acromegalic patients on pegvisomant treatment (peg) reduces ghrelin and leptin levels.
Methods: Ghrelin, leptin, endogenous GH, glucose, insulin and IGF1 were measured in 10 peg (3f/7m, median age 47 years (2857)). Ten gender-, age- and BMI-matched healthy volunteers (controls), 10 acromegalic patients with active (act) and 10 with inactive disease (inact) without medication for acromegaly referred to as control groups. Endogenous GH was measured by special in-house assay without interference with pegvisomant, total ghrelin by a commercial radioimmunoassay, leptin by an immunfluorometric in-house assay and IGF1 by an automated chemiluminescent immunoassay.
Results: Age, BMI, glucose and insulin did not differ between groups. IGF1 was significantly higher in act (983 μg/l (3061560)) than in the other groups (peg: 178 μg/l (95680), controls 111 μg/l (90234), inact 160 μg/l (66383), P<0.005). Endogenous GH was significantly higher in peg (6.3 μg/l (1.541)) and act (9.3 μg/l (1.770)) compared to controls (0.1 μg/l (0.13.1)) and inact (0.35 μg/l (0.12.0), P<0.001). Ghrelin was significantly higher in peg (232 ng/l (96351)) compared to act (102 ng/l (33232), P<0.01), whereas ghrelin was not significantly different between the other groups. Leptin was the highest in controls (19 μg/l (457)) and the lowest in act (6 μg/l (221)), but this difference did not reach significance.
Conclusion: High endogenous GH in pegvisomant treated patients does not reduce ghrelin levels, whereas ghrelin is lowered in act. GH receptor seems to play a crucial role in the physiological regulation of ghrelin and GH.
Prague, Czech Republic
24 - 28 Apr 2010
European Society of Endocrinology