Abstract
Tumors of nonislet cell origin may overexpress insulin-like growth factor (IGF)-II, leading to hypoglycemia with suppressed serum insulin levels (NICTH). Most of the serum IGF-II in NICTH patients is in precursor forms of 10-15 kD, and may be abnormally glycosylated. In NICTH, IGFs and IGF-binding protein-3 (IGFBP-3) are mainly found in binary complexes of 50-60 kD, instead of the normal ternary complex of about 140 kD with the acid-labile subunit (ALS). Factors contributing to the defect are: (1) low ALS levels, secondary to suppressed growth hormone (GH); (2) defective IGFBP-3 binding to ALS; (3) reduced ability of pro-IGF-II forms to complex normally, and (4) very high levels of other IGFBPs, including IGFBP-2 and IGFBP-6, which might limit the formation of complexes with IGFBP-3. While both GH and glucocorticoids can restore normoglycemia and increase high-molecular-weight IGFBP-3 complexes, corticosteroid treatment suppresses tumor IGF-II, whereas GH can restore normoglycemia despite continuing high IGF-II levels. Both treatments increase serum ALS, IGFBP-3, and IGF-I levels, and decrease IGFBP-2, whereas IGFBP-6 is unaffected. The reversal of hypoglycemia, by surgery, GH, or glucocorticoid treatment, is always accompanied...Continue Reading
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