Altered endogenous growth hormone secretory kinetics and diurnal GH-binding protein profiles in adults with chronic liver disease

Clin Endocrinol (Oxf). 1995 Sep;43(3):265-75. doi: 10.1111/j.1365-2265.1995.tb02031.x.

Abstract

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/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carrier Proteins / blood*
  • Case-Control Studies
  • Chronic Disease
  • Circadian Rhythm
  • Feedback
  • Female
  • Growth Hormone / blood
  • Growth Hormone / metabolism*
  • Half-Life
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Liver Cirrhosis / blood*
  • Liver Cirrhosis / physiopathology
  • Male
  • Middle Aged
  • Secretory Rate

Substances

  • Carrier Proteins
  • Insulin-Like Growth Factor I
  • Growth Hormone
  • somatotropin-binding protein