Acute stress response in children with meningococcal sepsis: important differences in the growth hormone/insulin-like growth factor I axis between nonsurvivors and survivors
Septic shock is the most severe clinical manifestation of meningococcal disease and is predominantly seen in children under 5 yr of age. Very limited research has been performed to elucidate the alterations of the GH/IGF-I axis in critically ill children. We evaluated the GH/IGF-I axis and the levels of IGF-binding proteins (IGFBPs), IGFBP-3 protease, glucose, insulin, and cytokines in 27 children with severe septic shock due to meningococcal sepsis during the first 3 d after admission. The median age was 22 months (range, 4-185 months). Eight patients died. Nonsurvivors had extremely high GH levels that were significant different compared with mean GH levels in survivors during a 6-h GH profile (131 vs. 7 mU/liter; P < 0.01). Significant differences were found between nonsurvivors and survivors for the levels of total IGF-I (2.6 vs. 5.6 nmol/liter), free IGF-I (0.003 vs. 0.012 nmol/liter), IGFBP-1 (44.3 vs. 8.9 nmol/liter), IGFBP-3 protease activity (61 vs. 32%), IL-6 (1200 vs. 50 ng/ml), and TNFalpha (34 vs. 5.3 pg/ml; P < 0.01). The pediatric risk of mortality score correlated significantly with levels of IGFBP-1, IGFBP-3 protease activity, IL-6, and TNFalpha (r = +0.45 to +0.69) and with levels of total IGF-I and free IGF-I (r = -0.44 and -0.55, respectively). Follow-up after 48 h in survivors showed an increased number of GH peaks, increased free IGF-I and IGFBP-3 levels, and lower IGFBP-1 levels compared with admission values. GH levels and IGFBP-1 levels were extremely elevated in nonsurvivors, whereas total and free IGF-I levels were markedly decreased and were accompanied by high levels of the cytokines IL-6 and TNFalpha. These values were different from those for the survivors. Based on these findings and literature data a hypothetical model was constructed summarizing our current knowledge and understanding of the various mechanisms.
|Adolescent, Blood Glucose/analysis, Child, Child, Preschool, Endopeptidases/blood, Female, Human Growth Hormone/*blood/secretion, Humans, Infant, Insulin-Like Growth Factor Binding Protein 1/blood, Insulin-Like Growth Factor Binding Protein 3/blood, Insulin-Like Growth Factor I/*metabolism, Insulin/blood, Interleukin-6/metabolism, Male, Meningococcal Infections/*complications, Shock, Septic/*blood/*microbiology/mortality, Tumor Necrosis Factor-alpha/metabolism|
|Journal of Clinical Endocrinology and Metabolism|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Maingay-de Groof, F, Joosten, K.F.M, de Kleijn, E.D, Hazelzet, J.A, Hop, W.C.J, Uitterlinden, P, … Janssen, J.A.M.J.L. (2002). Acute stress response in children with meningococcal sepsis: important differences in the growth hormone/insulin-like growth factor I axis between nonsurvivors and survivors. Journal of Clinical Endocrinology and Metabolism. Retrieved from http://hdl.handle.net/1765/9931