Spontaneous pulsatility and pharmacokinetics of growth hormone in liver cirrhotic patients

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.