title: Regulation of the insulin-like growth factors and their binding proteins by glucocorticoid and growth hormone in nonislet cell tumor hypoglycemia.
abstract: Hypoglycemia in patients with nonislet cell tumors is often secondary to overexpression of tumor insulin-like growth factor (IGF) II. In these patients the formation of serum complexes between IGFs, IGF binding protein-3 (IGFBP-3), and the acid-labile subunit (ALS) is impaired. An 87-yr-old woman with nonislet cell tumor hypoglycemia resulting from a localized fibrous tumor of the pleura was treated for 97 days with graded doses of prednisolone (30, 10, and 5 mg/day) followed by GH (1, 4, 8, 4, and 2 U/day). Both prednisolone and GH alleviated the hypoglycemia, concomitantly with increases in IGF-I, IGFBP-3, and ALS levels. Pretreatment serum IGFBP-2 and IGFBP-6 levels were greatly elevated, but as glucose normalized with treatment, only IGFBP-2 decreased, showing an inverse correlation with glucose (r = 0.716). IGFBP-1 gave a variable pattern not clearly related to blood glucose. Both treatments caused a redistribution of serum IGFBP-3 from binary- to ternary-complexed forms. However, only prednisolone improved the ability of IGFBP-3 to bind ALS in vitro. Prednisolone also suppressed IGF-II, the effect being confined to pro-IGF-II forms. Compared with normal IGF-II, pro-IGF-II inhibited ALS binding to IGFBP-3 in vitro. Although prednisolone and GH reverse hypoglycemia by different mechanisms, with only prednisolone suppressing tumor IGF-II secretion, both increase the formation of ternary IGF-IGFBP-3 complexes. We conclude that the failure of serum IGFBP-3 and tumor IGF-II to complex with ALS is a primary cause of hypoglycemia in nonislet cell tumor hypoglycemia.
authors.affiliation: Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia.
authors.forename: R C
authors.initials: RC
authors.lastname: Baxter
authors.forename: S R
authors.initials: SR
authors.lastname: Holman
authors.forename: A
authors.initials: A
authors.lastname: Corbould
authors.forename: S
authors.initials: S
authors.lastname: Stranks
authors.forename: P J
authors.initials: PJ
authors.lastname: Ho
authors.forename: W
authors.initials: W
authors.lastname: Braund
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000378:metabolism*; D005260:Female; D005350:Fibroma / Q000150:complications; D013006:Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology* / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D010997:Pleural Neoplasms / Q000150:complications*; D011241:Prednisone / Q000627:therapeutic use*; D013002:Somatomedins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone; D011241:Prednisone