THE IMPORTANCE OF GROWTH-HORMONE IN THE REGULATION OF ERYTHROPOIESIS,RED-CELL MASS, AND PLASMA-VOLUME IN ADULTS WITH GROWTH-HORMONE DEFICIENCY

Total body water (TBW) is reduced in adult GH deficiency (GHD) largely due to a reduction of extracellular water. It is unknown whether tota l blood volume (TBV) contributes to the reduced extracellular water in GHD. GH and insulin-like growth factor I (IGF-I) have been demonstrat ed to stimulate erythropoiesis in vitro, in animal models, and in grow ing children. Whether GH has a regulatory effect on red cell mass (RCM ) in adults is not known. We analyzed body composition by bioelectrica l impedance and used standard radionuclide dilution methods to measure RCM and plasma volume (PV) along with measuring full blood count, fer ritin, vitamin B-12, red cell folate, IGF-I, IGF-binding protein-3, an d erythropoietin in 13 adult patients with GHD as part of a 3-month, d ouble blind, placebo-controlled trial of GH (0.036 U/kg.day). TEW and lean body mass significantly increased by 2.5 +/- 0.53 kg (mean +/- SE M; P < 0.004) and 3.4 +/- 0.73 kg (P < 0.004), respectively, and fat m ass significantly decreased by 2.4 +/- 0.32 kg (P < 0.001) in the GH-t reated group. The baseline RCM of all patients with GHD was lower than the predicted normal values (1635 +/- 108 vs. 1850 +/- 104 mt; P < 0. 002). GH significantly increased RCM, PV, and TBV by 183 +/- 43 (P < 0 .006), 350 +/- 117 (P < 0.03), and 515 +/- 109 (P < 0.004) mt, respect ively. The red cell count increased by 0.36 +/- 0.116 x 10(12)/L (P < 0.03) with a decrease in ferritin levels by 39.1 +/- 4.84 mu g/L (P < 0.001) after GH treatment. Serum IGF-I and IGF-binding protein-3 conce ntrations increased by 3.0 +/- 0.43 (P < 0.001) and 1.3 +/- 0.15 (P < 0.001) sn, respectively, but the erythropoietin concentration was unch anged after GH treatment. No significant changes in body composition o r blood volume were recorded in the placebo group. Significant positiv e correlations could be established between changes in TEW and TBV, le an body mass and TBV (r = 0.78; P < 0.04 and r = 0.77; P < 0.04, respe ctively), and a significant negative correlation existed between chang es in fat mass and changes in TBV in the GH-treated group (r = -0.95; P < 0.02). We conclude that 1) erythropoiesis is impaired in GHD; 2) G H stimulates erythropoiesis in adult GHD; and 3) GH increases PV and T BV, which may contribute to the increased exercise performance seen in these patients.