title: Increased levels of circulating free insulin-like growth factors in patients with non-islet cell tumour hypoglycaemia.
abstract: Non-islet cell tumour hypoglycaemia (NICTH) is characterised by severe and recurrent fasting hypoglycaemia, and is usually caused by secretion of insulin-like growth factor-II (IGF-II) by the tumour. This induces secondary changes in the circulating levels of insulin, growth hormone (GH), and the IGF-binding proteins (IGFBPs), resulting in an increased insulin-like hypoglycaemic activity of IGF-II. A participating role of IGF-I is not established. We measured serum levels of free IGF-I and free IGF-II, total IGF-I, total IGF-II, big IGF-II and IGFBP-1, IGFBP-2 and IGFBP-3 in patients with NICTH before (n=14) and after surgical removal of the tumour (n=3). A control group (n=20) was included for comparison. In NICTH patients, free IGF-II was 20-fold increased (26.8+/-8.1 [mean+/-SEM] vs. 1.3+/-0.1 microg/l), and free IGF-I was four fold increased (2.8+/-0.4 vs. 0.7+/-0.1 microg/l), as compared to control subjects (p < 0.0001). In accordance with earlier observations levels of total IGF-I, total IGF-II, and IGFBP-3 were decreased, whereas IGFBP-1 and IGFBP-2 were increased in NICTH (all p-values < 0.05). The highly elevated levels of free IGF-I and free IGF-II most likely imply a considerable hypoglycaemic insulin-like activity, and may, by negative feedback explain the marked suppression of the GH/IGF-I axis observed in NICTH. Finally, free IGF-II seems to be a powerful biochemical marker in the diagnosis of NICTH.
authors.affiliation: Institute of Experimental Clinical Research, Medical Research Laboratories, Aarhus University Hospital, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Frystyk
authors.forename: C
authors.initials: C
authors.lastname: Skjaerbaek
authors.forename: J
authors.initials: J
authors.lastname: Zapf
authors.forename: H
authors.initials: H
authors.lastname: Orskov
mesh_terms: D007516:Adenoma, Islet Cell / Q000097:blood*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000097:blood*; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood*; D011184:Postoperative Period; D011300:Preoperative Care
chemical_list: D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II