Non-islet cell tumour hypoglycaemia (NICTH) is a syndrome associated with overproduction of pro-IGF-II, a 14-18 kDa product of incomplete proteolytic cleavage of IGF-II pro-hormone, usually secreted by large mesenchymal tumours. The excess of pro-IGF-II in NICTH leads to a reduction in circulating insulin, GH, IGF-I, IGFBP-3 and acid-labile subunit (ALS) levels and to an increase in IGF binding protein-2 (IGFBP-2). IGFs and IGFBP-3 are found primarily in binary complexes of approximately 50-kDa, instead of the ternary complex of 150-kDa, increasing the bioavailability of IGF-II.
The determination of pro-IGF-II is currently laborious and cumbersome but we have optimised a rapid simple method for determining serum pro-IGF-II. Serum concentrations of pro-IGF-II from patients with NICTH were measured by RIA after size-exclusion acid chromatography and compared to the analyses of pro-IGF-II and IGF-II by immunoblot analysis after 16.5% tricine-sodium dodecyl sulphate polyacrylamide gel electrophoresis. The correlation between these two methods was 0.98 (95% CI 0.93 - 0.99, P =0.01).
The current optimum medical therapy for patients with NICTH is a combination of rhGH and glucocorticoids if surgical tumour removal is impossible. Previous studies suggest that GH and dexamethasone are working via different mechanisms in regulating pro-IGF-II and possibly in the control of hypoglycaemia observed clinically.
We have recently characterised a cell model of pro-IGF-II secreting tumour using rhabdomyosarcoma cells in vitro which will serve as the first step towards elucidating the regulation and role of pro-IGF-II in tumour cell proliferation.
04 - 06 Apr 2005
British Endocrine Societies