MULTIPLE ENDOCRINE ABNORMALITIES OF THE GROWTH-HORMONE AND INSULIN-LIKE-GROWTH-FACTOR AXIS IN PREPUBERTAL CHILDREN WITH EXOGENOUS OBESITY -EFFECT OF SHORT-TERM AND LONG-TERM WEIGHT-REDUCTION

We have studied the GH-insulin-like growth factor (IGF) axis in prepub ertal children with exogenous obesity at the time of clinical diagnosi s and at two time points during weight reduction on a calorie-restrict ed diet. Spontaneous GH secretion, IGF-I, free IGF-I (fIGF-I), IGF-II, their binding proteins (IGFBP-1, IGFBP-2, and IGFBP-3), and GH-bindin g protein (GHBP) values at the time of clinical diagnosis (n = 65), af ter a 25% decrease in the body mass index (BMI) expressed as the so sc ore (BMI so score; n = 29), and after a diminution of at least 50% of the the initial BMI so score (n = 9) are reported. GH secretion was si gnificantly reduced at diagnosis, and after a decrease of at least 25% in the initial BMI so score, it returned to normal in all patients. T otal IGF-I levels were not significantly different from those in contr ols at any point. In contrast, fIGF-I and IGF-II levels were significa ntly increased, both at diagnosis and after BMI so score reduction. Ob ese patients were hyperinsulinemic at diagnosis and remained so even a fter a 50% reduction of their BMI SD score. Serum IGFBP-1 and IGFBP-2 levels were significantly decreased at diagnosis and at the two points studied during weight reduction. Serum IGFBP-3 and GHBP levels were i ncreased significantly at diagnosis and returned to normal levels afte r a reduction in the BMI so score. A positive correlation between seru m GHBP levels and BMI was found in both controls and obese patients. S erum IGFBP-3 levels correlated positively with IGF-I, fIGF-I, and IGF- II in all groups, but these correlations were weaker in the obese pati ents at diagnosis. IGFBP-2 correlated significantly with IGF-II only i n the obese group at diagnosis (r = -0.760; P < 0.0001), but with fIGF -I in all groups. IGFBP-1 was negatively correlated with IGF-I and fIG F-I in all groups. In conclusion, the GH-IGF axis is dramatically alte red in patients with exogenous obesity. However, most changes in the p eripheral IGF system appear to be independent of the modifications in GH secretion. In addition, in contrast to current thought, not all of the observed abnormalities are reversed with a significant reduction i n the BMI so score.