The altered plasma amino acid pattern is responsible for the paradoxical growth hormone response to the oral glucose tolerance test in liver cirrhosis.
Martina V. Tagliabue M. Bruno GA. Bonetti G. Brancaleoni V. Meineri I. Saracco G. Zumpano E. Manieri C. Camanni F.
Dipartimento di Medicina Interna, Universita degli Studi di Torino, Italy.
OBJECTIVE: An increased basal growth hormone (GH) secretion and a parodoxical GH response to the oral glucose tolerance test (OGTT) have been reported in patients with liver cirrhosis. It has been suggested that the ratio between branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) (BCAA/ AAA ratio) may determine in part the brain concentration of the AAAs, since the BCAAs compete with the AAAs for entry across the blood-brain barrier, leading to the accumulation of false neurotransmitters such as octopamine and phenylethanolamine, which are able to stimulate GH secretion (via alpha 2-adrenergic stimulation). In this study we investigated the role of amino acids, particularly the BCAA/AAA ratio, in the paradoxical response of GH to the OGTT in patients with liver cirrhosis. PATIENTS AND DESIGN: Twelve non-diabetic patients with biopsy-proven cirrhosis of the liver underwent an OGTT. Three of the five patients with a paradoxical response of GH to the OGTT underwent a second oral glucose administration associated with an infusion of BCAA solution from -30 min until 180 min. RESULTS: During the OGTT, glucose and insulin levels increased from 4.8 +/- 0.2 to 9.6 +/- 0.7 mmol/l (P < 0.001) and from 18.8 +/- 2.6 to 104.4 +/- 13.8 mU/l (P < 0.005), respectively. GH levels increased from 8.6 +/- 2.6 to 22.4 +/- 10.8 mU/l although not significantly. Five patients had a paradoxical GH response to the OGTT. A negative correlation between serum GH values and BCAA/AAA ratio in the plasma at every time point of the OGTT was found. After co-administration of glucose and BCAA in three patients the BCAA/AAAs ratio increased, abolishing the paradoxical GH secretion. CONCLUSIONS: Our data suggest that in liver cirrhosis the altered BCAA/AAA ratio may influence the altered basal GH secretion and the paradoxical GH response to the OGTT, probably by an increase of adrenergic mediators in the brain. Moreover, the increase of BCAA/AAA ratio seems to be able to abolish the GH paradoxical response to the OGTT.