Tumor-Induced Hypoglycemia Caused by Excess Production of IGF-II (See also Chap. 339) Mesenchymal tumors, hemangiopericytomas, hepatocellular tumors, adrenal carcinomas, and a variety of other large tumors have been reported to produce excessive amounts of insulin-like growth factor type II (IGF-II) precursor, which binds weakly to insulin receptors and strongly to IGF-I receptors, leading to insulin-like actions. The gene encoding IGF-II resides on a chromosome 11p15 locus that is normally imprinted (that is, expression is exclusively from a single parental allele). Biallelic expression of the IGF-II gene occurs in a subset of tumors, suggesting loss of methylation and loss of. | Chapter 096. Paraneoplastic Syndromes Endocrinologic Hematologic Part 6 Tumor-Induced Hypoglycemia Caused by Excess Production of IGF-II See also Chap. 339 Mesenchymal tumors hemangiopericytomas hepatocellular tumors adrenal carcinomas and a variety of other large tumors have been reported to produce excessive amounts of insulin-like growth factor type II IGF-II precursor which binds weakly to insulin receptors and strongly to IGF-I receptors leading to insulin-like actions. The gene encoding IGF-II resides on a chromosome 11p15 locus that is normally imprinted that is expression is exclusively from a single parental allele . Biallelic expression of the IGF-II gene occurs in a subset of tumors suggesting loss of methylation and loss of imprinting as a mechanism for gene induction. In addition to increased IGF-II production IGF-II bioavailability is increased due to complex alterations in circulating binding proteins. Increased IGF-II suppresses growth hormone GH and insulin resulting in reduced IGF binding protein 3 IGFBP-3 IGF-I and acid-labile subunit ALS . The reduction in ALS and IGFBP-3 which normally sequester IGF-II causes it to be displaced to a small circulating complex that has greater access to insulin target tissues. For this reason circulating IGF-II levels may not be markedly increased despite causing hypoglycemia. In addition to IGF-II-mediated hypoglycemia tumors may occupy enough of the liver to impair gluconeogenesis. In most cases the tumor causing hypoglycemia is clinically apparent and hypoglycemia develops in association with fasting. The diagnosis is made by documenting low serum glucose and suppressed insulin levels in association with symptoms of hypoglycemia. Serum IGF-II levels may not be increased IGF-II assays may not detect IGF-II precursors . Increased IGF-II mRNA expression is found in most of these tumors. Any medications associated with hypoglycemia should be eliminated. Treatment of the underlying malignancy if possible may reduce
