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Effects of Growth Hormone (GH) Replacement Therapy on Low-Density Lipoprotein Apolipoprotein B100 Kinetics in Adult Patients with GH Deficiency: A Stable Isotope Study

Department of Endocrinology and Diabetology (E.R.C.), University Hospital of Bern, Bern CH-3100, Switzerland; and Diabetes and Endocrinology (M.H.C., N.J., M.S., P.H.S. D.L.R.-J., A.M.U.) and Chemical Pathology (P.J.L., A.S.W.), Guy’s, King’s, and St. Thomas’ School of Medicine, St. Thomas’ Hospital, London SE1 7EH, United Kingdom

Address all correspondence and requests for reprints to: E. Christ, M.D., Ph.D., Department of Endocrinology and Diabetology, University Hospital of Bern, Inselspital, CH-3010 Bern, Switzerland. E-mail: emanuel.christ{at}insel.ch.

GH replacement therapy has been shown to improve the dyslipidemic condition in a substantial proportion of patients with adult GH deficiency. The mechanisms are not yet fully elucidated. Low-density lipoprotein (LDL) apolipoprotein B100 (apoB) formation and catabolism are important determinants of plasma cholesterol concentrations. This study examined the effect of GH replacement therapy on LDL apoB metabolism using a stable isotope turnover technique. LDL apoB kinetics was determined in 13 adult patients with GH deficiency before and after 3 months GH/placebo treatment in a randomized, double-blind, placebo-controlled study. LDL apoB ¹³C-leucine enrichment was determined by isotope-ratio mass spectrometry. Plasma volume was assessed by standardized radionuclide dilution technique.

GH replacement therapy significantly decreased LDL cholesterol, LDL apoB concentrations, and LDL apoB pool size compared with placebo. Compared with baseline, GH replacement therapy resulted in a significant increase in plasma volume and fractional catabolic rate, whereas LDL formation rate remained unchanged. LDL lipid content did not significantly change after GH and placebo.

This study suggests that short-term GH replacement therapy decreases the LDL apoB pool by increasing removal of LDL particles without changing LDL composition or LDL apoB production rate. In addition, it is possible that the beneficial effects of GH on the cardiovascular system contribute to these findings.

E.R.C. was supported by a grant from the Swiss National Foundation and the Walther and Margarethe Lichtenstein Foundation, Basel, Switzerland. M.H.C. was supported by a grant from the Special Trustees of St. Thomas’ Hospital.

Abbreviations: apoB, apolipoprotein B100; BMI, body mass index; CV, coefficient of variation; FCR, fractional catabolic rate; HDL-C, HDL cholesterol; IDL, intermediate density lipoprotein; IQR, interquartile range; -KIC, -ketoisocaproate; LDL, low-density lipoprotein; LDL-C, LDL cholesterol; LDL-RT, LDL residence time; Lp(a), lipoprotein(a); TC, total cholesterol; TG, triglyceride; VLDL, very LDL.

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