Standard insulin RIAs frequently are unable to document elevated insulin levels in children with congenital hyperinsulinism (HI), resulting in the need to use indirect diagnostic methods such as the demonstration of hypoketonemia. Using a sensitive microparticle enzyme immunoassay (Imx0, Abbott), serum insulin levels in 23 HI patients (ages 3 days-34 years) were compared to 47 control children during controlled fasting. At blood glucose (BG) levels below 50 mg/dl, HI children had mean insulin levels significantly greater than control children (7.8 ± 1.6 μU/ml vs. 0.3 ± 0.08 μU/ml, p<0.0001). 21 of 23 HI children had insulin levels > 2 μU/ml (range 2.4-27.8 μU/ml) as compared to none of the controls (range 0-1.7 μU/ml). The 2 HI patients with insulin levels < 2 μU/ml had mild disease easily controlled with diazoxide. There was no correlation between BG (range 30-175 mg/dl) and serum insulin levels in children with HI (r = 0.08, p > 0.5). As expected, the controls showed a positive correlation between BG and insulin levels (r=0.7, p<0.0001).

Conclusions:1)Using an insulin value of 2 μU/ml as the upper limit of normal for BG levels less than 50 mg/dl, this immunoassay identified 91% of the cases of HI with 2 false negatives and no false positives. 2)The absence of a correlation between BG and insulin levels in children with HI suggests that the β-cell dysregulation includes lack of responsiveness to high as well as to low BG levels.