Serum 3,3',5'-triiodothyronine (rT3) and 3,5,3'-triiodothyronine/rT3 are prognostic markers in critically ill patients and are associated with postmortem tissue deiodinase activities.

INTRODUCTION AND METHODS Critical illness is associated with reduced TSH and thyroid hormone secretion, and with changes in peripheral thyroid hormone metabolism, resulting in low serum T3 and high rT3. In 451 critically ill patients who received intensive care for more than 5 d, serum thyroid parameters were determined on d 1, 5, 15, and last day (LD). All patients had been randomized for intensive or conventional insulin treatment. Seventy-one patients died, and postmortem liver and skeletal muscle biopsies were obtained from 50 of them for analysis of deiodinase (D1-3) activities. RESULTS Insulin treatment did not affect thyroid parameters. On d 1, rT3 was higher and T3/rT3 was lower in nonsurvivors as compared with survivors (P = 0.001). Odds ratio for survival of the highest vs. the lowest quartile was 0.3 for rT3 and 2.9 for T3/rT3. TSH, T4, and T3 were lower in nonsurvivors from d 5 until LD (P < 0.001). TSH, T4, T3, and T3/rT3 increased over time in survivors, but decreased or remained unaltered in nonsurvivors. Liver D1 activity was positively correlated with LD serum T3/rT3 (R = 0.83, P < 0.001) and negatively correlated with rT3 (R = -0.69, P < 0.001). Both liver and skeletal muscle D3 activity were positively correlated with LD serum rT3 (R = 0.32, P = 0.02 and R = 0.31, P = 0.03). CONCLUSION In critically ill patients who required more than 5 d of intensive care, rT3 and T3/rT3 were already prognostic for survival on d 1. On d 5, T4, T3, but also TSH levels are higher in patients who will survive. Serum rT3 and T3/rT3 were correlated with postmortem tissue deiodinase activities.

[1]  A. Uitterlinden,et al.  A new polymorphism in the type II deiodinase gene is associated with circulating thyroid hormone parameters. , 2005, American journal of physiology. Endocrinology and metabolism.

[2]  M. Iitaka.  [Nonthyroidal illness]. , 2005, Nihon rinsho. Japanese journal of clinical medicine.

[3]  G. Van den Berghe,et al.  Endocrine and metabolic effects of growth hormone (GH) compared with GH-releasing peptide, thyrotropin-releasing hormone, and insulin infusion in a rabbit model of prolonged critical illness. , 2004, Endocrinology.

[4]  G. Van den Berghe.  How does blood glucose control with insulin save lives in intensive care? , 2004, The Journal of clinical investigation.

[5]  G. Van den Berghe,et al.  Reduced activation and increased inactivation of thyroid hormone in tissues of critically ill patients. , 2003, The Journal of clinical endocrinology and metabolism.

[6]  G. Van den Berghe,et al.  Regulation of insulin-like growth factor binding protein-1 during protracted critical illness. , 2002, The Journal of clinical endocrinology and metabolism.

[7]  G. Van den Berghe,et al.  The combined administration of GH‐releasing peptide‐2 (GHRP‐2), TRH and GnRH to men with prolonged critical illness evokes superior endocrine and metabolic effects compared to treatment with GHRP‐2 alone , 2002, Clinical endocrinology.

[8]  P. Larsen,et al.  Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. , 2002, Endocrine reviews.

[9]  B. Bistrian,et al.  Intensive insulin therapy in critically ill patients. , 2002, The New England journal of medicine.

[10]  G. Van den Berghe.  Dynamic neuroendocrine responses to critical illness. , 2002, Frontiers in neuroendocrinology.

[11]  M Schetz,et al.  Intensive insulin therapy in critically ill patients. , 2001, The New England journal of medicine.

[12]  T. Visser,et al.  Plasma membrane transport of thyroid hormones and its role in thyroid hormone metabolism and bioavailability. , 2001, Endocrine reviews.

[13]  M. Bettendorf,et al.  Tri-iodothyronine treatment in children after cardiac surgery: a double-blind, randomised, placebo-controlled study , 2000, The Lancet.

[14]  G. Van den Berghe,et al.  Growth hormone-releasing peptide-2 infusion synchronizes growth hormone, thyrotrophin and prolactin release in prolonged critical illness. , 1999, European journal of endocrinology.

[15]  L. D. De Groot.  Dangerous dogmas in medicine: the nonthyroidal illness syndrome. , 1999, The Journal of clinical endocrinology and metabolism.

[16]  G. Van den Berghe,et al.  Clinical review 95: Acute and prolonged critical illness as different neuroendocrine paradigms. , 1998, The Journal of clinical endocrinology and metabolism.

[17]  E. Fliers,et al.  Decreased hypothalamic thyrotropin-releasing hormone gene expression in patients with nonthyroidal illness. , 1997, The Journal of clinical endocrinology and metabolism.

[18]  G. Van den Berghe,et al.  Thyrotrophin and prolactin release in prolonged critical illness: dynamics of spontaneous secretion and effects of growth hormone‐secretagogues , 1997, Clinical endocrinology.

[19]  C. Gorman,et al.  Euthyroid sick syndrome: an overview. , 1997, Thyroid : official journal of the American Thyroid Association.

[20]  W. Wiersinga,et al.  Thyroid hormone metabolism in nonthyroidal illness , 1996 .

[21]  J. Harney,et al.  Molecular biological and biochemical characterization of the human type 2 selenodeiodinase. , 1996, Endocrinology.

[22]  P. Rothwell,et al.  Prediction of outcome in intensive care patients using endocrine parameters. , 1995, Critical care medicine.

[23]  D. Ferguson,et al.  Thyroid hormone metabolism. A comparative evaluation. , 1994 .

[24]  E. Krenning,et al.  The sick euthyroid syndrome: changes in thyroid hormone serum parameters and hormone metabolism , 1993, Clinical endocrinology.

[25]  L. Bartalena,et al.  Relationship between nocturnal serum thyrotropin peak and metabolic control in diabetic patients. , 1993, The Journal of clinical endocrinology and metabolism.

[26]  J. Nicoloff,et al.  Influence of fasting and refeeding on 3,3',5'-triiodothyronine metabolism in man. , 1991, The Journal of clinical endocrinology and metabolism.

[27]  L. Bartalena,et al.  Lack of nocturnal serum thyrotropin (TSH) surge in patients with chronic renal failure undergoing regular maintenance hemofiltration: a case of central hypothyroidism. , 1990, Clinical nephrology.

[28]  M. Berry,et al.  Thyroid hormone regulates type I deiodinase messenger RNA in rat liver. , 1990, Molecular endocrinology.

[29]  W. Wiersinga,et al.  Decreased nocturnal surge of thyrotropin in nonthyroidal illness. , 1990, The Journal of clinical endocrinology and metabolism.

[30]  A. Pinchera,et al.  Lack of nocturnal serum thyrotropin surge after surgery. , 1990, The Journal of clinical endocrinology and metabolism.

[31]  E. Kaptein,et al.  Alterations in 3,3'5'-triiodothyronine metabolism in response to propylthiouracil, dexamethasone, and thyroxine administration in man. , 1989, The Journal of clinical investigation.

[32]  S. Kunitake,et al.  Mechanism of the heparin-induced increase in the concentration of free thyroxine in plasma. , 1987, The Journal of clinical endocrinology and metabolism.

[33]  G. Brent,et al.  Thyroxine therapy in patients with severe nonthyroidal illnesses and low serum thyroxine concentration. , 1986, The Journal of clinical endocrinology and metabolism.

[34]  P. Hamblin,et al.  Relationship between thyrotropin and thyroxine changes during recovery from severe hypothyroxinemia of critical illness. , 1986, The Journal of clinical endocrinology and metabolism.

[35]  U. Kabadi.  Impaired pituitary thyrotroph function in uncontrolled type II diabetes mellitus: normalization on recovery. , 1984, The Journal of clinical endocrinology and metabolism.

[36]  A. Mason,et al.  Hypermetabolic low triiodothyronine syndrome of burn injury , 1982, Critical care medicine.

[37]  E. Kaptein,et al.  RELATIONSHIP OF ALTERED THYROID HORMONE INDICES TO SURVIVAL IN NONTHYROIDAL ILLNESSES , 1982, Clinical endocrinology.

[38]  V. Bacci,et al.  The relationship between serum triiodothyronine and thyrotropin during systemic illness. , 1982, The Journal of clinical endocrinology and metabolism.

[39]  K. Burman,et al.  Alterations in thyroid function in patients with systemic illness: the "euthyroid sick syndrome". , 1982, Endocrine reviews.

[40]  E. Kaptein,et al.  Pattern of recovery of thyroid hormone indices associated with treatment of diabetes mellitus. , 1982, The Journal of clinical endocrinology and metabolism.

[41]  F. Nuttall,et al.  Hypothyroxinemia in critically ill patients as a predictor of high mortality. , 1981, JAMA.

[42]  B. N. Premachandra,et al.  Radioimmunoassay of reverse triiodothyronine. , 1978, The Journal of clinical endocrinology and metabolism.

[43]  T. Visser,et al.  Radioimmunoassay of reverse tri-iodothyronine. , 1977, The Journal of endocrinology.