title: Effect of tight glucose control with insulin on the thyroid axis of critically ill children and its relation with outcome.
abstract: BACKGROUND
  Tight glucose control (TGC) to normal-for-age fasting blood glucose levels reduced morbidity and mortality in surgical adult and pediatric intensive care unit (ICU) patients. In adults, TGC did not affect the illness-induced alterations in thyroid hormones. With better feeding in children than in adult patients, we hypothesized that TGC in pediatric ICU patients reactivates the thyroid axis.
  
  
  OBJECTIVE
  The aim of this study was to assess the impact of TGC on the thyroid axis in pediatric ICU patients and to investigate how these changes affect the TGC outcome benefit.
  
  
  METHODS
  We conducted a preplanned analysis of all patients not treated with thyroid hormone, dopamine, or corticosteroids who were included in a randomized controlled trial on TGC (n=700).
  
  
  METHODS
  Serum TSH, T4, T3, and rT3 were measured upon admission and on ICU day 3 or the last ICU day for patients discharged earlier. Changes from baseline were compared for the TGC and usual care groups. The impact on the outcome benefit of TGC was assessed with multivariable Cox proportional hazard analysis, correcting for baseline risk factors.
  
  
  RESULTS
  TGC further lowered the T)/rT3 ratio (P=0.03), whereas TSH (P=0.09) and T4 (P=0.3) were unaltered. With TGC, the likelihood of earlier live discharge from the ICU was 19% higher at any time (hazard ratio, 1.190; 95% confidence interval, 1.010-1.407; P=0.03). This benefit was statistically explained by the further reduction of T3/rT3 with TGC because an increase in T3/rT3 was strongly associated with a lower likelihood for earlier live discharge (hazard ratio per unit increase, 0.863; 95% confidence interval, 0.806-0.927; P<0.0001).
  
  
  CONCLUSIONS
  TGC further accentuated the peripheral inactivation of thyroid hormone. This effect, mimicking a fasting response, statistically explained part of the clinical outcome benefit of TGC.
authors.affiliation: Clinical Department and Laboratory of Intensive Care Medicine, Catholic University of Leuven, B-3000 Leuven, Belgium.
authors.forename: Marijke
authors.initials: M
authors.lastname: Gielen
authors.forename: Dieter
authors.initials: D
authors.lastname: Mesotten
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Wouters
authors.forename: Lars
authors.initials: L
authors.lastname: Desmet
authors.forename: Dirk
authors.initials: D
authors.lastname: Vlasselaers
authors.forename: Ilse
authors.initials: I
authors.lastname: Vanhorebeek
authors.forename: Lies
authors.initials: L
authors.lastname: Langouche
authors.forename: Greet
authors.initials: G
authors.lastname: Van den Berghe
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003422:Critical Care / Q000379:methods*; D016638:Critical Illness / Q000401:mortality*; D005215:Fasting / Q000502:physiology; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000401:mortality; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D013961:Thyroid Gland / Q000187:drug effects / Q000502:physiology*; D013963:Thyroid Hormones / Q000097:blood
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D013963:Thyroid Hormones