The GH/IGF-I axis in children with a meningococcal septic shock: striking differences between survivors and non-survivors

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Introduction

Meningococcal septic shock is a life-threatening clinical syndrome that may lead to pronounced neuro-endocrine and metabolic alterations. In critically ill adults a GH resistant state has been well documented. Less information is available in critically ill paediatric patients. In the present study we evaluated the time course and pulsatile pattern of the GH secretion and the levels of serum IGF-I, IGFBP-1 and IGFBP-3.

Methods

Children with a septic shock and petechiae/purpura requiring intensive care treatment were enrolled in this study. The paediatric risk of mortality (PRISM) score was used to monitor the severity of disease. A GH profile was done in the first 6 h after admission and at day 3. The serum IGF-I, IGFBP-1 and IGFBP-3 levels were measured on admission (T=0), and 24 and 48 h after admission. The serum levels of IGF-I and IGFBP-3 were corrected for sex and age, expressed as SDS-levels.

Results

Twelve patients fulfilled the inclusion criteria, 7 boys and 5 girls, with a median age of 22 months. The median PRISM score was 23. Three of the 12 patients died. The serum levels of IGF-I and IGFBP-3 were decreased in all patients, the median SDS being respectively -2.6 and -5.7. There was a significant difference between survivors and non-survivors regarding median GH levels during the first 6 h (7 mU/l vs 131 mU/l, P=0.01), serum IGF-I levels at T=0 (43 ng/ml vs 7 ng/ml, P=0.03), IGFBP-3 SDS levels at T=0 (-5.6 vs -7.7, P=0.05), and PRISM score (18 vs 34, P=0.01). The levels of serum IGFBP-1 at T=0 were increased in the non-survivors in comparison with the survivors (median being respectively 1315 and 262 ng/ml), but this difference didn't reach significance (P=0.15). Non-survivors showed very high GH levels without GH peaks during the first 6 h after admission. In survivors, the GH secretion pattern at day 1 showed a larger number of GH peaks and larger GH peak amplitudes than at day 1. A significant increase in serum IGF-I levels was found in all patients between T=0 and T=24 (P=0.04), followed by a significant decrease in serum IGF-I levels between T=24 and T=48 (P=0.01).

Conclusion

Mortality in children with a meningococcal septic shock is associated with extremely increased serum GH levels, no oscillatory GH secretion, high levels of IGFBP-1 and a high PRISM score. In those who survived there are significant changes during the first 48 h in the GH/IGF-I axis, suggesting a decrease in the GH resistance.