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

被引:63
作者
CUNEO, RC
HICKMAN, PE
WALLACE, JD
TEH, BT
WARD, G
VELDHUIS, JD
WATERS, MJ
机构
[1] UNIV QUEENSLAND, DEPT MED, BRISBANE, QLD 4000, AUSTRALIA
[2] UNIV QUEENSLAND, DEPT PHYSIOL PHARMACOL, BRISBANE, QLD 4000, AUSTRALIA
[3] PRINCESS ALEXANDRA HOSP, DEPT CHEM PATHOL, BRISBANE, QLD 4102, AUSTRALIA
[4] UNIV VIRGINIA, HLTH SCI CTR, DEPT MED, CHARLOTTESVILLE, VA 22908 USA
关键词
D O I
10.1111/j.1365-2265.1995.tb02031.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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收藏
页码:265 / 275
页数:11
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