ALTERED ENDOGENOUS GROWTH-HORMONE SECRETORY KINETICS AND DIURNAL GH-BINDING PROTEIN PROFILES IN ADULTS WITH CHRONIC LIVER-DISEASE

OBJECTIVE Increased serum GH concentrations and GH responses to a variety of stimuli have been reported in patients with chronic liver disease (CLD). We investigated the pulsatile pattern of endogenous GH release and GH-binding protein (GHBP) and insulin-like growth factor-1 (IGF-I) diurnal profiles in adults with cirrhosis, in comparison with healthy, matched control subjects. DESIGN Case-control, cross-sectional. PATIENTS Seven patients with biopsy proven cirrhosis, and sex, age, height, weight and oestrogen status matched controls. MEASUREMENTS Serum immunoreactive GH concentrations in samples collected at 20-minute intervals for 24 hours were analysed using a multi-parameter deconvolution method to simultaneously resolve endogenous GH secretory and disappearance rates. Diurnal patterns of GHBP (specific immunoprecipitation method) and serum ICE-I (RIA after acid-ethanol extraction) were assessed. RESULTS The mean daily GH secretion rate in patients with CLD was increased (210+/-93 vs 100+/-55 mU/l/day; P = 0.025), and GH disappearance half-time was prolonged (43+/-10 vs 24+-9 min; P = 0.006) compared to controls, Detectable GH secretory bursts were more frequent in patients with CLD (10+/-1 vs 6+/-3/day; P=0.038), but of similar mean mass (21+/-10 vs 17+/-8 mu/l) compared to controls, In patients with CLD, mean serum GHBP was slightly lower (63+/-36 vs 71+/-14% pooled control; P > 0.1), Fasting serum IGF-I concentrations (after sire-exclusion HPLC) were lower in the patients with CLD (13+/-5 vs 21+/-2 nmol/l; P < 0.0001). Multiple regression analysis showed that GH secretion rate was increased in patients with CLD with higher Child's classifications (R(2) = 0.86; P = 0.002) and with lower serum IGF-I concentrations measured after HPLC (R(2) = 0.11; P = 0.044). CONCLUSIONS Adults with chronic liver disease have (1) increased total daily GH secretion rates, which appear to be influenced by disease severity and diminished serum IGf-I-mediated negative feedback; (2) markedly impaired endogenous GH clearance, possibly reflecting changes in hepatic GH-receptor Status; and (3) GHBP levels which do not correlate with GH kinetics or serum IGF-I concentrations.