Mechanisms of tumor-induced hypoglycemia with intraabdominal hemangiopericytoma.

Abstract

The association of hypoglycemia with nonislet cell tumors is well recognized and in nearly all instances has been related to the production of hormones with insulin-like activity. To determine the mechanism of such tumor-induced hypoglycemia and the response to pharmacological intervention, we studied a 54-yr-old man with refractory hypoglycemia and a large intraabdominal hemangiopericytoma. During a supervised fast, plasma glucose decreased to 2.2 mmol/L. Circulating insulin (< 7 pmol/L), C peptide (< 0.04 nmol/L), and GH levels (< 0.6 microgram/L) were all undetectable, insulin-like growth factor I (IGF-I; 5 nmol/L) was low, IGF-II was in the normal range (87 nmol/L), and free IGF-II and big IGF-II (E1-21 fragment) were elevated at 18 and 142 nmol/L, respectively. On another day, after maintaining euglycemia overnight with a 20% dextrose infusion, a euglycemic (5.0-5.5 mmol/L) glucose clamp study using [3-3H]glucose tracer infusion combined with arteriovenous leg catheterization was performed in the postabsorptive basal state and during 3 h of crystalline somatostatin infusion (0.08-0.24 pmol/kg min). In the postabsorptive state at euglycemia, free IGF-II and big IGF-II remained elevated at 16 and 162 nmol/L, respectively. Whole body glucose disposal was elevated at 21.1 mumol/kg.min, whereas the rate of glucose infusion was 12.1 mumol/kg.min, and depatic glucose output was 7.8 mumol/kg.min. The leg arterio-venous plasma glucose difference was increased at 0.6 mmol/L, as was leg glucose uptake at 203.9 mumol/min. After 3 h of somatostatin infusion, both free and big IGF-II decreased by 35-40% to 10 and 102 nmol/L, respectively. Whole body glucose disposal also decreased to near normal (12.8 mumol/kg.min), whereas leg arterio-venous plasma glucose difference and leg glucose uptake became negligible. The plasma glucose level remained at 5.0-5.5 mmol/L despite a marked fall in hepatic glucose output to 2.9 mumol/kg.min and a decrease in glucose infusion rate to 8.7 mumol/kg.min. During somatostatin treatment, GH remained suppressed at less than 0.6 microgram/L, and glucagon decreased from 99 to 78 ng/L. In this patient with a hemangiopericytoma, hypoglycemia was associated with increased circulating insulin-like activity from elevated free and big IGF-II, which stimulated glucose uptake primarily into muscle tissue. A continuous infusion of crystalline somatostatin effectively reduced the elevated levels of IGF-II and glucose uptake, but was unable to adequately control hypoglycemia without the simultaneous infusion of exogenous glucose or glucagon.