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

R. C. Cuneo, P. E. Hickman, J. D. Wallace, Tean Teh Bin Tean Teh, G. Ward, Johannes D Veldhuis, M. J. Waters

Research output: Contribution to journalArticle

62 Citations (Scopus)

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/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.

Original languageEnglish (US)
Pages (from-to)265-275
Number of pages11
JournalClinical Endocrinology
Volume43
Issue number3
StatePublished - 1995
Externally publishedYes

Fingerprint

Growth Hormone
Liver Diseases
Chronic Disease
Insulin-Like Growth Factor I
Serum
Fibrosis
High Pressure Liquid Chromatography
Secretory Rate
somatotropin-binding protein
Immunoprecipitation
Estrogens
Ethanol
Regression Analysis
Biopsy
Weights and Measures
Acids
Liver

ASJC Scopus subject areas

  • Endocrinology

Cite this

Cuneo, R. C., Hickman, P. E., Wallace, J. D., Bin Tean Teh, T. T., Ward, G., Veldhuis, J. D., & Waters, M. J. (1995). Altered endogenous growth hormone secretory kinetics and diurnal GH-binding protein profiles in adults with chronic liver disease. Clinical Endocrinology, 43(3), 265-275.

Altered endogenous growth hormone secretory kinetics and diurnal GH-binding protein profiles in adults with chronic liver disease. / Cuneo, R. C.; Hickman, P. E.; Wallace, J. D.; Bin Tean Teh, Tean Teh; Ward, G.; Veldhuis, Johannes D; Waters, M. J.

In: Clinical Endocrinology, Vol. 43, No. 3, 1995, p. 265-275.

Research output: Contribution to journalArticle

Cuneo, RC, Hickman, PE, Wallace, JD, Bin Tean Teh, TT, Ward, G, Veldhuis, JD & Waters, MJ 1995, 'Altered endogenous growth hormone secretory kinetics and diurnal GH-binding protein profiles in adults with chronic liver disease', Clinical Endocrinology, vol. 43, no. 3, pp. 265-275.
Cuneo RC, Hickman PE, Wallace JD, Bin Tean Teh TT, Ward G, Veldhuis JD et al. Altered endogenous growth hormone secretory kinetics and diurnal GH-binding protein profiles in adults with chronic liver disease. Clinical Endocrinology. 1995;43(3):265-275.
Cuneo, R. C. ; Hickman, P. E. ; Wallace, J. D. ; Bin Tean Teh, Tean Teh ; Ward, G. ; Veldhuis, Johannes D ; Waters, M. J. / Altered endogenous growth hormone secretory kinetics and diurnal GH-binding protein profiles in adults with chronic liver disease. In: Clinical Endocrinology. 1995 ; Vol. 43, No. 3. pp. 265-275.
@article{15c9e44ff4324624b3d0919acd1f6954,
title = "Altered endogenous growth hormone secretory kinetics and diurnal GH-binding protein profiles in adults with chronic liver disease",
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/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.",
author = "Cuneo, {R. C.} and Hickman, {P. E.} and Wallace, {J. D.} and {Bin Tean Teh}, {Tean Teh} and G. Ward and Veldhuis, {Johannes D} and Waters, {M. J.}",
year = "1995",
language = "English (US)",
volume = "43",
pages = "265--275",
journal = "Clinical Endocrinology",
issn = "0300-0664",
publisher = "Wiley-Blackwell",
number = "3",

}

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, Johannes 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.

UR - http://www.scopus.com/inward/record.url?scp=0029166023&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029166023&partnerID=8YFLogxK

M3 - Article

VL - 43

SP - 265

EP - 275

JO - Clinical Endocrinology

JF - Clinical Endocrinology

SN - 0300-0664

IS - 3

ER -