title: Euthyroid sick syndrome in meningococcal sepsis: the impact of peripheral thyroid hormone metabolism and binding proteins.
abstract: OBJECTIVE
  The objective of this study was to elucidate the influence of disease severity, deiodination, sulfation, thyroid hormone binding, and dopamine use on thyroid function in euthyroid sick syndrome.
  
  
  METHODS
  The study was performed at a university-affiliated pediatric intensive care unit (PICU).
  
  
  METHODS
  This was an observational cohort study.
  
  
  METHODS
  Sixty-nine children with meningococcal sepsis were studied.
  
  
  METHODS
  Differences in thyroid function among nonsurvivors, shock survivors, and sepsis survivors on PICU admission were the main outcome measures.
  
  
  RESULTS
  The main study group consisted of 45 non-dopamine-treated children. All children had decreased total T3 (TT3)/rT3 ratios without elevated TSH. T4 sulfate levels were decreased in 88%. Nonsurvivors had paradoxically higher TT3/rT3 ratios than shock survivors (0.71 vs. 0.30); this ratio also correlated with shorter duration of disease (r = -0.43). TT4 and T4-binding globulin (TBG) levels declined with increasing disease severity. TBG levels correlated inversely with elastase levels (r = -0.46). Only TSH levels were significantly lower in 24 dopamine-treated children compared with non-dopamine-treated children (0.65 vs. 0.84), whereas other thyroid hormones did not significantly differ. Both higher TT3/rT3 ratios and lower TT4 levels were predictive for mortality, but this disappeared when IL-6 was entered into the regression model.
  
  
  CONCLUSIONS
  All children with meningococcal sepsis showed signs of euthyroid sick syndrome. Alterations in peripheral thyroid hormone metabolism related inversely to the duration of disease and seemed to be enacted by profound induction of type 3 deiodinase rather than by down-regulation of type 1. Lower TT4 levels were related to increased turnover of TBG by elastase. Dopamine was found to suppress only TSH secretion, not other thyroid hormone levels, on PICU admission. Both the TT3/rT3 ratio and TT4 levels were predictive for mortality, but were not superior to IL-6.
authors.affiliation: Erasmus MC-Sophia Children's Hospital, Department of Pediatrics, Division of Endocrinology, Room SP-3435, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands. m.denbrinker@erasmusmc.nl
authors.forename: Marieke
authors.initials: M
authors.lastname: den Brinker
authors.forename: Koen F M
authors.initials: KF
authors.lastname: Joosten
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.forename: Wim C J
authors.initials: WC
authors.lastname: Hop
authors.forename: Yolanda B
authors.initials: YB
authors.lastname: de Rijke
authors.forename: Jan A
authors.initials: JA
authors.lastname: Hazelzet
authors.forename: Venje H
authors.initials: VH
authors.lastname: Boonstra
authors.forename: Anita C S
authors.initials: AC
authors.lastname: Hokken-Koelega
mesh_terms: D002316:Cardiotonic Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004298:Dopamine / Q000627:therapeutic use; D002149:Energy Intake; D005067:Euthyroid Sick Syndromes / Q000097:blood / Q000150:complications*; D005260:Female; D006801:Humans; D007223:Infant; D015278:Intensive Care Units, Pediatric; D007455:Iodine / Q000378:metabolism; D008297:Male; D008589:Meningococcal Infections / Q000097:blood / Q000150:complications*; D015999:Multivariate Analysis; D018805:Sepsis / Q000097:blood / Q000150:complications*; D013431:Sulfates / Q000378:metabolism; D013960:Thyroid Function Tests; D013963:Thyroid Hormones / Q000097:blood*; D013975:Thyroxine-Binding Proteins / Q000378:metabolism*
chemical_list: D002316:Cardiotonic Agents; D013431:Sulfates; D013963:Thyroid Hormones; D013975:Thyroxine-Binding Proteins; D007455:Iodine; D004298:Dopamine