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Acute Stress Response in Children with Meningococcal Sepsis: Important Differences in the Growth Hormone/Insulin-Like Growth Factor I Axis between Nonsurvivors and Survivors

Department of Pediatrics, Divisions of Pediatric Intensive Care (F.d.G., K.F.M.J., E.D.d.K., J.A.H.) and Endocrinology (A.C.S.H.-K.), Sophia Children’s Hospital, and Departments of Biostatistics and Epidemiology (W.C.J.H.) and Internal Medicine III (J.A.M.J.L.J.), Erasmus University Medical Center, 3000 CB Rotterdam, The Netherlands; and Department of Pediatrics, Utrecht Medical Center, Wilhelmina Children’s Hospital (J.v.D.), 3508 AB Utrecht, The Netherlands

Address all correspondence and requests for reprints to: Dr. K. F. M. Joosten, Department of Pediatrics, Division of Pediatric Intensive Care, Sophia Children’s Hospital, Erasmus University, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands. E-mail: . joosten{at}alkg.azr.nl

Abstract

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 TNF (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 TNF (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 TNF. 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.

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