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Regulation of the insulin-like growth factors and their binding proteins by glucocorticoid and growth hormone in nonislet cell tumor hypoglycemia.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 1995 Sep; Vol. 80 (9), pp. 2700-8. - Publication Year :
- 1995
-
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.
- Subjects :
- Aged
Aged, 80 and over
Female
Fibroma complications
Humans
Hypoglycemia metabolism
Insulin-Like Growth Factor Binding Proteins
Insulin-Like Growth Factor II metabolism
Carrier Proteins metabolism
Growth Hormone therapeutic use
Hypoglycemia etiology
Pleural Neoplasms complications
Prednisone therapeutic use
Somatomedins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-972X
- Volume :
- 80
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 7545698
- Full Text :
- https://doi.org/10.1210/jcem.80.9.7545698