CIRCULATING GROWTH-HORMONE AND INSULIN-LIKE GROWTH FACTOR-I IN NONALCOHOLIC LIVER-CIRRHOSIS WITH OR WITHOUT SUPERIMPOSED HEPATOCARCINOMA - EVIDENCE OF AN ALTERED CIRCADIAN-RHYTHM

Adult liver is considered the major source of circulating insulin-like growth factor-I (IGF-I). Growth hormone (GH) exerts its effects by st imulating IGF-I release from the liver, which then mediates the somato genic actions in target tissues. In turn, circulating IGF-I levels ope rate a negative feedback mechanism on GH release. In cirrhotic patient s, single daily determinations, performed after an overnight fast, ind icated that serum IGF-I are decreased, whereas GH levels are increased . To verify whether this phenomenon occurs through the 24-h period, we have studied the profiles of GH and IGF-I in cirrhotic patients with or without superimposed hepatocellular carcinoma (HCC) and in a group of control subjects. The results of the present studies suggest that i n cirrhotic patients, the above changes are constantly present through the 24-h period, and are associated with a loss of circadian rhythm f or both GH and IGF-I. These data are consistent with a failure of the liver to synthesize and release IGF-I in response to GH. In addition, the presence of constantly higher IGF-I levels in cirrhotic patients w ith superimposed HCC, compared with cirrhotic patients without HCC, ra ises the hypothesis of a causal relationship between IGF-I and the dev elopment of HCC.