Insulinlike growth factor binding proteins and tumor hypoglycemia.

Hypoglycemia associated with nonislet cell tumors is a relatively rare metabolic disorder, which develops in the presence of low or unmeasurable serum insulin levels. Understanding of the pathogenetic mechanisms has been obscured by the lack of appropriate analytic methods. It now appears that this disorder can be classified as a paraneoplastic syndrome caused by the oversecretion of unprocessed (big) insulinlike growth factor (IGF) II propeptide by the tumor. In contrast to other paraneoplastic syndromes, however, this oversecretion does not lead to grossly elevated IGF II RIA values in the sera of the patients, but is masked by (a) a negative feedback that suppresses the production of mature (7.5-kD) IGF II, so that the total IGF II level remains more or less unchanged and (b) an altered distribution of the hormone between two specific IGF binding protein complexes in the circulation so that its bioavailability is essentially enhanced.