Spontaneous pulsatility and pharmacokinetics of growth hormone in liver cirrhotic patients

Yaacov Baruch, Nimer Assy, Tamar Amit, Norberto Krivoy, Dorette Strickovsky, Zila Shen Orr, Zeev Hochberg

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Background/Aims: Liver cirrhosis is characterized by high serum growth hormone levels and low serum insulin-like growth factor I and growth hormone- binding protein levels. The present study was designed to characterize the serum profile of growth hormone and growth hormone pharmacokinetics in postnecrotic liver cirrhosis, correlating it with liver function and nutritional states. Methods: Fifteen patients were grouped by the ChildPugh score (group 1, score of 5 to 8; group 2, score of 9 to 12). Five healthy subjects served as controls. Nutritional status was assessed by the creatinine-height index. Baseline growth hormone, insulin-like growth factor, and growth hormone binding protein were measured, and growth hormone pharmacokinetics was followed for 48 h after administration of subcutaneous recombinant human growth hormone (0.06 mg/kg). Results: Trough serum growth hormone (μg/I) was higher in both patient groups (5.3±3.6) than in controls (1.0±0.3; p<0.01). More pulses were recorded in cirrhotic patients, and mean pulse amplitude (μg/I) was higher in cirrhotic patients than in controls (p<0.01). After subcutaneous recombinant human growth hormone injection, maximal growth hormone was higher in cirrhotic patients and the area under the curve over 24 h was greater (626±120) than in controls (330±54; p<0.01). Single regression analysis showed a weak correlation of both the Child-Pugh score and the creatinine-height index with the pharmacokinetic parameters. Conclusions: Due to decreased growth hormone clearance, patients with liver cirrhosis have increased trough and peak serum growth hormone levels, as well as lower serum growth hormone binding protein and insulin- like growth factor. Recombinant human growth hormone pharmacokinetics are typical of a high hepatic extraction substance administered to patients with liver disease and portal hypertension, and this may be relevant to the further use of growth hormone therapy.

Original languageEnglish
Pages (from-to)559-564
Number of pages6
JournalJournal of Hepatology
Volume29
Issue number4
DOIs
StatePublished - Oct 1998
Externally publishedYes

Bibliographical note

Funding Information:
Detailed clinical data of these patients were described in an earlier report by Assy et al. (13). The protocol for the present study was approved by the Helsinki Committee of the Rambam Medical Center and of the Israel Ministry of Health. Subjects were briefed on the experimental nature of the study and signed informed-consent forms.

Keywords

  • Growth hormone
  • Growth hormone pulsatility
  • Hormone clearance
  • Liver cirrhosis
  • Nutrition
  • Portal hypertension

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