GROWTH-HORMONE (GH) SUBSTITUTION FOR ONE-YEAR NORMALIZES ELEVATED GH-BINDING PROTEIN-LEVELS IN GH-DEFICIENT ADULTS SECONDARY TO A REDUCTIONIN BODY-FAT - A PLACEBO-CONTROLLED TRIAL

The high affinity growth hormone binding protein (GHBP) in human serum derives from the extracellular domain of the GH receptor. It is well known that fat mass correlates positively to GHBP levels, but it is un certain whether GH secretory status influences GHBP levels. Since body composition is known to change during GH substitution in adult GHD pa tients, we determined the relation between GHBP and body composition d uring GH substitution in GHD adults. Twenty-five GHD adults aged 45.0 +/- 1.8 years, were examined before and after 12 months of placebo-con trolled GH substitution (2 IU/m(2)) in a parallel design. A group of 2 7 healthy age- and gender-matched normal-weight adults provided refere nce data. The participants underwent anthropometric measurements [body mass index (BMI), waist/hip ratio (W/H)], computer-tomography (CT-sca n) of femoral and abdominal regions, dual-energy X-ray absorptiometry (DEXA-scan), and bioimpedance (BIA), as well as blood sampling. At bas eline, the GHBP levels were increased compared to controls (1.63 +/- 0 .14 nmol/l vs 1.12 +/- 0.1 nmol/l, P = 0.01). During 12 months of GH s ubstitution, GHBP levels decreased to the levels of the control subjec ts. GHBP correlated positively to indices of adiposity in GHD patients at baseline: intra-abdominal fat (r = 0.54, P = 0.005), subcutaneous abdominal fat (r = 0.59, P < 0.002), body fat (BIA) (r = 0.41, P = 0.0 44), BMI (r = 0.58, P = 0.002), and total body fat (DEXA scan) (r = 0. 61, P < 0.001). After 12 months of GH substitution, different estimate s of body fat were significantly decreased in the GH treated group, bu t the positive relationship between GHBP and these estimates of body f at was maintained. In multiple linear regression analyses, fasting ins ulin levels were also a significant determinant of GHBP levels. We con clude that GHBP levels are increased in GHD patients and decrease to n ormal levels during 12 months of GH-substitution, Furthermore, GHBP is predominantly correlated to indices of adiposity also in GHD patients . (C) 1998 Churchill Livingstone