Euthyroid sick syndrome in meningococcal sepsis: The impact of peripheral thyroid hormone metabolism and binding proteins

Context and Objectives: 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. Setting: The study was performed at a university-affiliated pediatric intensive care unit (PICU). Design: This was an observational cohort study. Patients: Sixty-nine children with meningococcal sepsis were studied. Main Outcome Measures: 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 T-3 (TT3)/rT(3) ratios without elevated TSH. T-4 sulfate levels were decreased in 88%. Nonsurvivors had paradoxically higher TT3/rT(3) ratios than shock survivors (0.71 vs. 0.30); this ratio also correlated with shorter duration of disease (r = - 0.43). TT4 and T(4-)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/rT(3) 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/rT(3) ratio and TT4 levels were predictive for mortality, but were not superior to IL-6.