Glucocorticoid therapy suppresses abnormal secretion of big IGF-II by non-islet cell tumours inducing hypoglycaemia (NICTH)

OBJECTIVE To assess the relative efficacy of hGH and glucocorticoids in the treatment of non-islet cell tumour hypoglycaemia (NICTH) by examination of their influence on the composition of the various molecular species involving tumour and mature forms of IGF-II in association with IGFBP-3. DESIGN Two groups each of 4 patients, all diagnosed as cases of NICTH, were treated with either hGH or glucocorticoids. Through the use of acidic size exclusion chromatography serum levels of tumour (big) and mature IGF-II were evaluated. Neutral size exclusion chromatography was used in the separation of molecular species before assay for immunoreactive IGF-II and IGFBP-3 content. RESULTS High-dose hGH treatment produced increases in serum levels of big and mature IGF-II and IGFBP-3 but without generation of high molecular weight complexes, Glucocorticoid treatment suppressed big IGF-II permitting re-establishment of normal IGF/IGFBP association patterns. CONCLUSION Glucocorticoid therapy has been demonstrated to consistently reverse the biochemical abnormalities caused by tumour-derived big IGF-II compared with the potentially adverse stimulatory effects of hGH treatment in causing increases in serum levels of big IGF-II.