INCREASED LEVELS OF CIRCULATING FREE INSULIN-LIKE GROWTH-FACTORS IN PATIENTS WITH NON-ISLET CELL TUMOR HYPOGLYCEMIA

Non-islet cell tumour hypoglycaemia (NICTH) is characterised by severe and recurrent fasting hypoglycaemia, and is usually caused by secreti on of insulin-like growth factor-II (IGF-II) by the tumour. This induc es secondary changes in the circulating levels of insulin, growth horm one (GH), and the IGF-binding proteins (IGFBPs), resulting in an incre ased insulin-like hypoglycaemic activity of IGF-II. A participating ro le of IGF-I is not established. We measured serum levels of free IGF-I and free IGF-II, total IGF-I, total IGF-II, big IGF-II and IGFBP-1, I GFBP-2 and IGFBP-3 in patients with NICTH before (I? = 14) and after s urgical removal of the tumour (n = 3). A control group (n = 20) was in cluded for comparison. In NICTH patients, free IGF-II was 20-fold incr eased (26.8+/-8.1 [mean+/-SEM] vs. 1.3+/-0.1 mu g/l), and free IGF-I w as four fold increased (2.8 +/- 0.4 vs. 0.7 +/- 0.1 mu g/l), as compar ed to control subjects (p < 0.0001). In accordance with earlier observ ations levels of total IGF-I, total IGF-II, and IGFBP-3 were decreased , whereas IGFBP-1 and IGFBP-2 were increased in NICTH (all p-values < 0.05). The highly elevated levels of free IGF-I and free IGF-II most l ikely imply a considerable hypoglycaemic insulin-like activity, and ma y, by negative feedback explain the marked suppression of the GH/IGF-I axis observed in NICTH. Finally, free IGF-II seems to be a powerful b iochemical marker in the diagnosis of NICTH.