TY - JOUR
T1 - Altered endogenous growth hormone secretory kinetics and diurnal GH-binding protein profiles in adults with chronic liver disease
AU - Cuneo, R. C.
AU - Hickman, P. E.
AU - Wallace, J. D.
AU - Bin Tean Teh, Tean Teh
AU - Ward, G.
AU - Veldhuis, J. D.
AU - Waters, M. J.
PY - 1995
Y1 - 1995
N2 - 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-I (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 IGF-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). Pasting serum IGF-I concentrations (after size-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 (R2 = 0.86; P = 0.002) and with lower serum IGF-I concentrations measured after HPLC (R2 = 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.
AB - 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-I (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 IGF-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). Pasting serum IGF-I concentrations (after size-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 (R2 = 0.86; P = 0.002) and with lower serum IGF-I concentrations measured after HPLC (R2 = 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.
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U2 - 10.1111/j.1365-2265.1995.tb02031.x
DO - 10.1111/j.1365-2265.1995.tb02031.x
M3 - Article
C2 - 7586594
AN - SCOPUS:0029166023
SN - 0300-0664
VL - 43
SP - 265
EP - 275
JO - Clinical Endocrinology
JF - Clinical Endocrinology
IS - 3
ER -