Radioimmunoassay of serum IGF-I and IGF-II in patients with chronic liver diseases and hepatocellular carcinoma with or without hypoglycemia

Insulin-like growth factor (IGF) I and IGF-II were measured by radioimmunoassay in the sera of seven patients with acromegaly, 36 normal control subjects, 15 patients with chronic hepatitis, 15 patients with cirrhosis, 25 patients with hepatocellular carcinomas (HCCs) who did not have hypoglycemia, 20 patients with HCCs who did have hypoglycemia, and 10 patients with metastatic liver tumors. Both IGF-I and IGF-II levels decreased as liver disease progressed from the normal control stage to chronic hepatitis and cirrhosis, and both levels reflected the severity of liver disease. Patients with HCCs who had hypoglycemia had relatively higher IGF-II levels in their sera in comparison with those who did not have hypoglycemia (272 ± 167.5 ng/ml vs 110.4 ± 85.9 ng/ml [mean ± SD], p < 0.0005), despite the fact that those with hypoglycemia had more advanced liver cancer and had lower IGF-I levels in sera (16.7 ± 14.1 ng/ml vs 46.8 ± 47.9 ng/ml, p < 0.002). It is possible that a labile IGF-II-like material is produced by the cancer cells of patients with hypoglycemia. This factor is reactive to the IGF-II-receptor and partially cross-reacts with an antibody to IGF-II; it accounted for the mildly elevated levels of serum IGF-II. Hypoglycemia may be an integral effect of relatively elevated IGF-II-like material and an advanced liver cancer. Also, higher serum α-fetoprotein (AFP) levels were more frequently found in patients with hypoglycemia who had relatively elevated IGF-II levels and short survivals.