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-I (IGF-I) diurnal profiles in adults with cirrhosis, in comparison with healthy, matched control subjects.


METHODS
Case-control, cross-sectional.


METHODS
Seven patients with biopsy proven cirrhosis, and sex, age, height, weight and oestrogen status matched controls.


METHODS
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/I/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/I) 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 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.
Cuneo
R C
RC
Department of Medicine, University of Queensland, Brisbane, Australia.
Hickman
P E
PE
Wallace
J D
JD
Teh
B T
BT
Ward
G
G
Veldhuis
J D
JD
Waters
M J
MJ
D000328:Adult; D002352:Carrier Proteins / Q000097:blood*; D016022:Case-Control Studies; D002908:Chronic Disease; D002940:Circadian Rhythm; D005246:Feedback; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008103:Liver Cirrhosis / Q000097:blood* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012636:Secretory Rate
D002352:Carrier Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C051815:somatotropin-binding protein