title: 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.
authors.affiliation: Department of Medicine, University of California-San Diego, La Jolla 92093, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chung
authors.forename: R R
authors.initials: RR
authors.lastname: Henry
mesh_terms: D000008:Abdominal Neoplasms / Q000150:complications* / Q000601:surgery; D001786:Blood Glucose / Q000032:analysis; D005947:Glucose / Q000378:metabolism / Q000627:therapeutic use; D006133:Growth Substances / Q000097:blood; D006393:Hemangiopericytoma / Q000150:complications* / Q000601:surgery; D006728:Hormones / Q000097:blood; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000188:drug therapy / Q000209:etiology*; D007866:Leg; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009765:Obesity / Q000378:metabolism; D010084:Oxidation-Reduction; D012871:Skin Diseases / Q000209:etiology; D013004:Somatostatin / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D006133:Growth Substances; D006728:Hormones; D013004:Somatostatin; D005947:Glucose