New insights toward the acute non-thyroidal illness syndrome

Wajner, Simone Magagnin; Maia, Ana Luiza

doi:10.3389/fendo.2012.00008

Cited by 105Thyroid Disorders and TreatmentsAdrenal Hormones and DisordersGrowth Hormone and Insulin-like Growth Factors

New insights toward the acute non-thyroidal illness syndrome

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Wajner, Simone Magagnin, Maia, Ana Luiza·2012·Frontiers in Endocrinology

DOI 10.3389/fendo.2012.00008PMC PMC3356062

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Abstract

The non-thyroidal illness syndrome (NTIS) refers to changes in serum thyroid hormone levels observed in critically ill patients in the absence of hypothalamic-pituitary-thyroid primary dysfunction. Affected individuals have low T3, elevated rT3, and inappropriately normal TSH levels. The pathophysiological mechanisms are poorly understood but the acute and chronic changes in pituitary-thyroid function are probably the consequence of the action of multiple factors. The early phase seems to reflect changes occurring primarily in the peripheral thyroid hormone metabolism, best seen in humans since 80-90% of the circulating T3 are derived from the pro-hormone T4. The conversion of T4 to T3 is catalyzed by type 1 (D1) and type 2 (D2) deiodinases via outer-ring deiodination. In contrast, type 3 deiodinase (D3) catalyzes the inactivation of both T4 and T3. Over the last decades, several studies have attempted to elucidate the mechanisms underlying the changes on circulating thyroid hormones in NTIS. Increased inflammatory cytokines, which occurs in response to virtually any illness, has long been speculated to play a role in derangements of deiodinase expression. On the other hand, oxidative stress due to augmented reactive oxygen species (ROS) generation is characteristic of many diseases that are associated with NTIS. Changes in the intracellular redox state may disrupt deiodinase function by independent mechanisms, which might include depletion of the as yet unidentified endogenous thiol cofactor. Here we aim to present an updated picture of the advances in understanding the mechanisms that result in the fall of thyroid hormone levels in the acute phase of NTIS.

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Free radicals and antioxidants in normal physiological functions and human disease
Valko, M., Leibfritz, D., Moncol, J., Cronin, M. T. D., Mazur, M., & Telser, J. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2006.07.001 · Cited by 14,269 · see citing works
GLUTATHIONE
Meister, A., & Anderson, M. E. (1983) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.52.070183.003431 · Cited by 5,694 · see citing works
Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple
Schafer, F. Q., & Buettner, G. R. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00480-4 · Cited by 4,587 · see citing works
Human fibroblasts release reactive oxygen species in response to interleukin-1 or tumour necrosis factor-α
Meier, B., Radeke, H. H., Selle, S., Younes, M., Sies, H., Resch, K., & Habermehl, G. (1989) · Biochemical Journal · doi:10.1042/bj2630539 · Cited by 650 · see citing works
Low-T3 syndrome: a strong prognostic predictor of death in patients with heart disease
Iervasi, G., Pingitore, A., Landi, P., Raciti, M., Ripoli, A., Scarlattini, M., L’Abbate, A., & Donato, L. (2003) · Circulation · doi:10.1161/01.cir.0000048124.64204.3f · Cited by 472 · see citing works
Reduced Activation and Increased Inactivation of Thyroid Hormone in Tissues of Critically Ill Patients
Peeters, R. P., Wouters, P. J., Kaptein, E., van Toor, H., Visser, T. J., & Van den Berghe, G. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-022013 · Cited by 452 · see citing works
Thyroid hormone-induced oxidative stress
Venditti, P., & Meo, S. D. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-005-5457-9 · Cited by 379 · see citing works
Thyroxine Therapy in Patients with Severe Nonthyroidal Illnesses and Low Serum Thyroxine Concentration*
Brent, G. A., & Hershman, J. M. (1986) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-63-1-1 · Cited by 366 · see citing works
Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans
Luiza Maia, A. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25083 · Cited by 360 · see citing works
The sick euthyroid syndrome: changes in thyroid hormone serum parameters and hormone metabolism
Docter, R., Krenning, E. P., de Jong, M., & Hennemann, G. (1993) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1993.tb02401.x · Cited by 345 · see citing works
ERK and p38 MAPK, but not NF-κB, Are Critically Involved in Reactive Oxygen Species–Mediated Induction of IL-6 by Angiotensin II in Cardiac Fibroblasts
Sano, M., Fukuda, K., Sato, T., Kawaguchi, H., Suematsu, M., Matsuda, S., Koyasu, S., Matsui, H., Yamauchi-Takihara, K., Harada, M., et al. (2001) · Circulation Research · doi:10.1161/hh2001.098873 · Cited by 298 · cited 2× · see citing works
“The selenoenzyme D3 catalyzes essentially the inner ring of T4, promoting the conversion of T4 to rT3 and the conversion of T3 to 3,3′-T2, both biologically inactive.”
Background
Acute Effects of Triiodothyronine (T 3 ) Replacement Therapy in Patients with Chronic Heart Failure and Low-T 3 Syndrome: A Randomized, Placebo-Controlled Study
Pingitore, A., Galli, E., Barison, A., Iervasi, A., Scarlattini, M., Nucci, D., L’Abbate, A., Mariotti, R., & Iervasi, G. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2210 · Cited by 279 · see citing works
Tri-iodothyronine treatment in children after cardiac surgery: a double-blind, randomised, placebo-controlled study
Bettendorf, M., Schmidt, K. G., Grulich‐Henn, J., Ulmer, H. E., & Heinrich, U. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02576-9 · Cited by 254 · see citing works
Serum 3,3′,5′-Triiodothyronine (rT 3 ) and 3,5,3′-Triiodothyronine/rT 3 Are Prognostic Markers in Critically Ill Patients and Are Associated with Postmortem Tissue Deiodinase Activities
Peeters, R. P., Wouters, P. J., van Toor, H., Kaptein, E., Visser, T. J., & Van den Berghe, G. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0535 · Cited by 251 · see citing works
Thiol–Disulfide Balance: From the Concept of Oxidative Stress to that of Redox Regulation
Ghezzi, P., Bonetto, V., & Fratelli, M. (2005) · Antioxidants and Redox Signaling · doi:10.1089/ars.2005.7.964 · Cited by 241 · see citing works
Mechanistic and Kinetic Details of Catalysis of Thiol-Disulfide Exchange by Glutaredoxins and Potential Mechanisms of Regulation
Gallogly, M. M., Starke, D. W., & Mieyal, J. J. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2291 · Cited by 224 · see citing works
Type 1 iodothyronine deiodinase in human physiology and disease
Maia, A. L., Goemann, I. M., Meyer, E. L. D. S., & Wajner, S. M. (2011) · Journal of Endocrinology · doi:10.1530/joe-10-0481 · Cited by 220 · see citing works
Self-citation
Decreased Hypothalamic Thyrotropin-Releasing Hormone Gene Expression in Patients with Nonthyroidal Illness1
Fliers, E., Guldenaar, S. E. F., Wiersinga, W. M., & Swaab, D. F. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.12.4404 · Cited by 206 · see citing works
Association between serum interleukin-6 and serum 3,5,3'-triiodothyronine in nonthyroidal illness.
Boelen, A., Platvoet-Ter Schiphorst, M. C., & Wiersinga, W. M. (1993) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.77.6.8263160 · Cited by 196 · see citing works
Peripheral Serum Thyroxine, Triiodothyronine and Reverse Triiodothyronine Kinetics in the Low Thyroxine State of Acute Nonthyroidal Illnesses
Kaptein, E. M., Robinson, W. J., Grieb, D. A., & Nicoloff, J. T. (1982) · Journal of Clinical Investigation · doi:10.1172/jci110478 · Cited by 183 · see citing works
A trial of thyroxine in acute renal failure
Acker, C. G., Singh, A. R., Flick, R. P., Bernardini, J. Y., Greenberg, A., & Johnson, J. P. (2000) · Kidney International · doi:10.1046/j.1523-1755.2000.00827.x · Cited by 174 · see citing works
Cardiovascular Effects of Intravenous Triiodothyronine in Patients Undergoing Coronary Artery Bypass Graft Surgery
Bennett‐Guerrero, E. (1996) · JAMA · doi:10.1001/jama.1996.03530330031025 · Cited by 170 · see citing works
IL-6 promotes nonthyroidal illness syndrome by blocking thyroxine activation while promoting thyroid hormone inactivation in human cells
Wajner, S. M., Goemann, I. M., Bueno, A. L., Larsen, P. R., & Maia, A. L. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44678 · Cited by 168 · cited 1× · see citing works
“Recently, the effects of cytokines, at pathophysiological concentrations as observed in NTIS, were investigated in a human cell culture system that mimics the physiological actions of the endogenous deiodinase cofactor(s) and FT4 levels (Wajner et al., 2011).”
BackgroundSelf-citation
Superoxide Radical Generation, NADPH Oxidase Activity, and Cytochrome P-450 Content of Rat Liver Microsomal Fractions in an Experimental Hyperthyroid State: Relation to Lipid Peroxidation*
Fernández, V., Barrientos, X., KIPREOS, K., et al. (1985) · Endocrinology · doi:10.1210/endo-117-2-496 · Cited by 165 · see citing works
l-γ-Glutamyl-l-cysteinyl-glycine (glutathione; GSH) and GSH-related enzymes in the regulation of pro- and anti-inflammatory cytokines: a signaling transcriptional scenario for redox(y) immunologic sensor(s)?
Haddad, J. J., & Harb, H. L. (2004) · Molecular Immunology · doi:10.1016/j.molimm.2004.09.029 · Cited by 163 · see citing works
Altered Thyroid Function in Nonthyroidal Illness and Surgery — To Treat or Not to Treat?
Utiger, R. D. (1995) · New England Journal of Medicine · doi:10.1056/nejm199512073332310 · Cited by 156 · see citing works
Frequency and outcome of patients with nonthyroidal illness syndrome in a medical intensive care unit
Plikat, K., Langgartner, J., Buettner, R., Bollheimer, L. C., Woenckhaus, U., Schölmerich, J., & Wrede, C. E. (2007) · Metabolism · doi:10.1016/j.metabol.2006.09.020 · Cited by 156 · see citing works
Thyroid Physiology and Diagnostic Evaluation of Patients with Thyroid Disorders
Salvatore, D., Davies, T. F., Schlumberger, M.-J., HAY, I. D., & Larsen, P. R. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4377-0324-5.00011-0 · Cited by 155 · see citing works
Cardiovascular effects of intravenous triiodothyronine in patients undergoing coronary artery bypass graft surgery. A randomized, double-blind, placebo- controlled trial. Duke T3 study group
Bennett-Guerrero, E. (1996) · JAMA · doi:10.1001/jama.275.9.687 · Cited by 154 · see citing works
Skeletal muscle glutathione is depleted in critically ill patients
Hammarqvist, F., Luo, J., Cotgreave, I. A., Andersson, K., & Wernerman, J. (1997) · Critical Care Medicine · doi:10.1097/00003246-199701000-00016 · Cited by 135 · see citing works
Local control of thyroid hormone action: role of type 2 deiodinase
Williams, G. R., & Bassett, J. H. D. (2011) · Journal of Endocrinology · doi:10.1530/joe-10-0448 · Cited by 134 · see citing works
Rapid Down-regulation of Thyroid Hormones in Acute Myocardial Infarction
Friberg, L., Werner, S., Eggertsen, G., & Ahnve, S. (2002) · Archives of Internal Medicine · doi:10.1001/archinte.162.12.1388 · Cited by 133 · see citing works
Dynamic neuroendocrine responses to critical illness
den Berghe, G. V. (2002) · Frontiers in Neuroendocrinology · doi:10.1016/s0091-3022(02)00006-7 · Cited by 132 · see citing works
Antioxidant treatment attenuates pulmonary arterial hypertension-induced heart failure
Redout, E. M., van der Toorn, A., Zuidwijk, M. J., van de Kolk, C. W. A., van Echteld, C. J. A., Musters, R. J. P., van Hardeveld, C., Paulus, W. J., & Simonides, W. S. (2010) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00097.2009 · Cited by 117 · see citing works
Hypothalamic thyroid hormone feedback in health and disease
Fliers, E., Alkemade, A., Wiersinga, W. M., & Swaab, D. F. (2006) · Progress in brain research · doi:10.1016/s0079-6123(06)53011-0 · Cited by 113 · see citing works
The Redox State of SECIS Binding Protein 2 Controls Its Localization and Selenocysteine Incorporation Function
Papp, L. V., Lu, J., Striebel, F., Kennedy, D. D., Holmgren, A., & Khanna, K. K. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.02284-05 · Cited by 112 · see citing works
Identification of molecular mechanisms related to nonthyroidal illness syndrome in skeletal muscle and adipose tissue from patients with septic shock
Rodriguez‐Perez, A., Palos‐Paz, F., Kaptein, E., Visser, T. J., Dominguez‐Gerpe, L., Alvarez‐Escudero, J., & Lado‐Abeal, J. (2008) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.03102.x · Cited by 110 · see citing works
Relation between serum interleukin‐6 and thyroid hormone concentrations in 270 hospital in‐patients with non‐thyroidal illness
Davies, P. H. O., Black, E. G., Sheppard, M. C., & Franklyn, J. A. (1996) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1996.668489.x · Cited by 107 · see citing works
The Type II Iodothyronine Deiodinase Is Up-Regulated in Skeletal Muscle during Prolonged Critical Illness
Mebis, L., Langouche, L., Visser, T. J., & Van den Berghe, G. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0510 · Cited by 101 · see citing works
Thyroid axis function and dysfunction in critical illness
Mebis, L., & Van den Berghe, G. (2011) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2011.03.002 · Cited by 99 · see citing works
Stress activated protein kinase p38 is involved in IL-6 induced transcriptional activation of STAT3
Zauberman, A., Zipori, D., Krupsky, M., & ben-Levy, R. (1999) · Oncogene · doi:10.1038/sj.onc.1202738 · Cited by 98 · see citing works
Expression of thyroid hormone transporters during critical illness
Mebis, L., Paletta, D., Debaveye, Y., Ellger, B., Langouche, L., D'Hoore, A., Darras, V. M., Visser, T. J., & Van den Berghe, G. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0290 · Cited by 97 · see citing works
Acute and delayed effects of a single-dose injection of interleukin-6 on thyroid function in healthy humans
Torpy, D. J., Tsigos, C., Lotsikas, A. J., Defensor, R., Chrousos, G. P., & Papanicolaou, D. A. (1998) · Metabolism · doi:10.1016/s0026-0495(98)90338-9 · Cited by 95 · see citing works
Regulation of Hepatocyte Thyroxine 5′-Deiodinase by T3 and Nuclear Receptor Coactivators as a Model of the Sick Euthyroid Syndrome
Yu, J., & Koenig, R. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004866200 · Cited by 94 · see citing works
Oxidative stress is increased in critically ill patients according to antioxidant vitamins intake, independent of severity: a cohort study
Abilés, J., de la Cruz, A. P., Castaño, J., Rodrı́guez-Elvira, M., Aguayo, E., Moreno‐Torres, R., Llopis, J., Aranda, P., Argüelles, S., Ayala, A., et al. (2006) · Critical Care · doi:10.1186/cc5068 · Cited by 93 · see citing works
Relationship of the increased serum interleukin-6 concentration to changes of thyroid function in nonthyroidal illness
Bartalena, L., Brogioni, S., Grasso, L., Velluzzi, F., & Martino, E. (1994) · Journal of Endocrinological Investigation · doi:10.1007/bf03348974 · Cited by 91 · see citing works
Substitution of Cysteine for Selenocysteine in the Catalytic Center of Type III Iodothyronine Deiodinase Reduces Catalytic Efficiency and Alters Substrate Preference
Kuiper, G. G. J. M., Klootwijk, W., & Visser, T. J. (2003) · Endocrinology · doi:10.1210/en.2003-0084 · Cited by 83 · see citing works
The effects and interactions of substrates, inhibitors, and the cellular thiol-disulfide balance on the regulation of type II iodothyronine 5′-deiodinase
ST. GERMAIN, D. L. (1988) · Endocrinology · doi:10.1210/endo-122-5-1860 · Cited by 81 · see citing works
Expression and regulation of type II iodothyronine deiodinase in cultured human skeletal muscle cells
Hosoi, Y. (1999) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.84.9.3293 · Cited by 80 · see citing works
Thyroid Hormone Therapy for Postoperative Nonthyroidal Illnesses: A Systematic Review and Synthesis
Kaptein, E. M., Sanchez, A., Beale, E., & Chan, L. S. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1052 · Cited by 79 · see citing works
Effects of hormonal supplements on the maintenance of cardiac function in potential donor patients after cerebral death
Taniguchi, S., Kitamura, S., Kawachi, K., et al. (1992) · European Journal of Cardio-Thoracic Surgery · doi:10.1016/1010-7940(92)90082-9 · Cited by 75 · see citing works
Proinflammatory cytokines inhibit the expression and function of human type I 5'-deiodinase in HepG2 hepatocarcinoma cells
Jakobs, T., Mentrup, B., Schmutzler, C., Dreher, I., & Köhrle, J. (2002) · European Journal of Endocrinology · doi:10.1530/eje.0.1460559 · Cited by 72 · see citing works
Effects of proinflammatory cytokines on anterior pituitary 5'-deiodinase type I and type II
Baur, A., Bauer, K., Jarry, H., & Köhrle, J. (2000) · Journal of Endocrinology · doi:10.1677/joe.0.1670505 · Cited by 69 · see citing works
Alterations in thyroid function tests in aged hospitalized patients: prevalence, aetiology and clinical outcome
Iglesias, P., Muñoz, A., Prado, F., Guerrero, M. T., Macías, M. C., Ridruejo, E., Tajada, P., & Díez, J. J. (2008) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2008.03421.x · Cited by 67 · see citing works
Protective adaptation of low serum triiodothyronine in patients with chronic renal failure
LIM, V. S., Flanigan, M. J., Zavala, D. C., & Freeman, R. M. (1985) · Kidney International · doi:10.1038/ki.1985.162 · Cited by 62 · see citing works
Thyroid Hormone in the Treatment of Post-transplant Acute Tubular Necrosis (ATN)
Acker, C. G., Flick, R. P., Shapiro, R., Scantlebury, V. P., Jordan, M. L., Vivas, C., Greenberg, A., & Johnson, J. P. (2002) · American Journal of Transplantation · doi:10.1034/j.1600-6143.2002.020110.x · Cited by 60 · see citing works
Soluble cytokine receptors and the low 3,5,3'-triiodothyronine syndrome in patients with nonthyroidal disease.
Boelen, A., Schiphorst, M. C. P.-T., & Wiersinga, W. M. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.3.7883859 · Cited by 57 · see citing works
Effect of Interleukin-1 (IL-1) on Thyroid Hormone Metabolism in Mice: Stimulation by IL-1 of Iodothyronine 5′-Deiodinating Activity (Type I) in the Liver*
FUJII, T., Sato, K., Ozawa, M., Kasono, K., IMAMURA, H., KANAJI, Y., Tsushima, T., & SHIZUME, K. (1989) · Endocrinology · doi:10.1210/endo-124-1-167 · Cited by 54 · see citing works
Tissue Deiodinase Activity during Prolonged Critical Illness: Effects of Exogenous Thyrotropin-Releasing Hormone and Its Combination with Growth Hormone-Releasing Peptide-2
Debaveye, Y. A., Ellger, B., Mebis, L., Herck, E. V., Coopmans, W., Darras, V., & den Berghe, G. V. (2005) · Endocrinology · doi:10.1210/en.2005-0963 · Cited by 54 · see citing works
Intravenous thyroid hormone supplementation in heart failure with cardiogenic shock
Malik, F. S., Mehra, M. R., Uber, P. A., Park, M., Scott, R. L., & Meter, C. H. V. (1999) · Journal of Cardiac Failure · doi:10.1016/s1071-9164(99)90022-2 · Cited by 54 · see citing works
Oxidative Stress Regulates Type 3 Deiodinase and Type 2 Deiodinase in Cultured Rat Astrocytes
Lamirand, A., Pallud, S. E., Ramaugé, M., Pierre, M., & Courtin, F. (2008) · Endocrinology · doi:10.1210/en.2007-1462 · Cited by 48 · see citing works
Suppression of the thyrotropin response to thyrotropin-releasing hormone and its association with severity of critical illness
Sumita, S., Ujike, Y., Namiki, A., Watanabe, H., Kawamata, M., Watanabe, A., & Satoh, O. (1994) · Critical Care Medicine · doi:10.1097/00003246-199410000-00016 · Cited by 44 · see citing works
Iodothyronine 5'-deiodinase in rat kidney microsomes. Kinetic behavior at low substrate concentrations.
GOSWAMI, A., & ROSENBERG, I. N. (1984) · Journal of Clinical Investigation · doi:10.1172/jci111634 · Cited by 42 · see citing works
Concordant decreases of thyroxine and thyroxine binding protein concentrations during sepsis
Afandi, B. O., Vera, R., Schussler, G. C., & Yap, M. G. (2000) · Metabolism · doi:10.1053/meta.2000.6239 · Cited by 34 · see citing works
Substitution of Cysteine for a Conserved Alanine Residue in the Catalytic Center of Type II Iodothyronine Deiodinase Alters Interaction with Reducing Cofactor
Kuiper, G. G. J. M., Klootwijk, W., & Visser, T. J. (2002) · Endocrinology · doi:10.1210/endo.143.4.8738 · Cited by 31 · see citing works
Suppression of the thyrotropin response to thyrotropin-releasing hormone and its association with severity of critical illness
Sumita, S., Ujike, Y., Namiki, A., et al. (1994) · Critical Care Medicine · doi:10.1097/00003246-199422100-00016 · Cited by 31 · see citing works
Thioredoxin Stimulates Enzymatic Outer Ring Monodeiodination of Reverse Triiodothronine*
GOSWAMI, A., & Rosenberg, I. N. (1987) · Endocrinology · doi:10.1210/endo-121-6-1937 · Cited by 30 · see citing works
Thyroid hormone receptors are down-regulated in skeletal muscle of patients with non-thyroidal illness syndrome secondary to non-septic shock
Lado-Abeal, J., Romero, A., Castro-Piedras, I., Rodriguez-Perez, A., & Alvarez-Escudero, J. (2010) · European Journal of Endocrinology · doi:10.1530/eje-10-0376 · Cited by 29 · see citing works
10.1016/b978-1-4160-2911-3.50012-1
(2000) · Time to knit · doi:10.1016/b978-1-4160-2911-3.50012-1 · Cited by 28 · see citing works
Hormone levels and fuel flow in patients with weight loss and lung cancer. Evidence for excessive metabolic expenditure and for an adaptive response mediated by a reduced level of 3,5,3′-triiodothyronine
Axelrod, L., Halter, J. B., Cooper, D. S., Aoki, T. T., Roussell, A. M., & Bagshaw, S. L. (1983) · Metabolism · doi:10.1016/0026-0495(83)90208-1 · Cited by 27 · see citing works
Soluble cytokine receptors and the low 3,5,3'-triiodothyronine syndrome in patients with nonthyroidal disease
Boelen, A. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.80.3.971 · Cited by 26 · see citing works
Acute Effects of Triiodothyronine (T3) Replacement Therapy in Patients with Chronic Heart Failure and Low-T3 Syndrome: A Randomized, Placebo-Controlled Study
Schott, M. (2008) · Yearbook of Endocrinology · doi:10.1016/s0084-3741(08)79066-8 · Cited by 25 · see citing works
Inflammatory cytokines and type I 5′-deiodinase expression in Φ1 rat liver cells
Davies, P. H. O., Sheppard, M. C., & Franklyn, J. A. (1997) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(97)04058-6 · Cited by 19 · see citing works
Substitution of Serine for Proline in the Active Center of Type 2 Iodothyronine Deiodinase Substantially Alters Its in Vitro Biochemical Properties with Dithiothreitol But Not Its Function in Intact Cells
Goemann, I. M., Gereben, B., Harney, J. W., Zhu, B., Maia, A. L., & Larsen, P. R. (2009) · Endocrinology · doi:10.1210/en.2009-0980 · Cited by 16 · see citing works
Self-citation
Hormonal supplementation in endocrine dysfunction in critically ill patients.
Duława, A., Bułdak, Ł., Krysiak, R. G., & Okopień, B. (2007) · PubMed · Cited by 7 · see citing works

Flagged first, then by citations

Research works printed but not linked: 1

Lu J. Holmgren A. (2009). Selenoproteins. J. Biol. Chem. 284, 723– 727 10.1074/jbc.M109.016014 18757362 · DOI

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“This case report opened a new perspective in the understanding of the role of D3 in the euthyroid sick syndrome (23, 24).”
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Authors: Wajner, S. M., & Maia, A. L.
Affiliations: Universidade Federal do Rio Grande do Sul (BR)
Corresponding author: Maia, Ana Luiza
ORCID: Wajner, Simone Magagnin
Maia, Ana Luiza
Venue: Frontiers in Endocrinology
Publisher: Frontiers Media SA
Published: 2012
Volume: 3
Pages: 8-8
ISSN: 1664-2392 (ISSN-L)
DOI: 10.3389/fendo.2012.00008
PMC: PMC3356062
OpenAlex: W2121412391
Cited by: 105
References: 75
Citations by year: 2026: 11 · 2025: 8 · 2024: 9 · 2023: 8 · 2022: 12 · 2021: 13 · 2020: 8 · 2019: 5 · 2018: 6 · 2017: 6 · 2016: 5 · 2015: 5 · 2014: 5 · 2013: 4
FWCI: 3.59
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc
Locations: Frontiers in Endocrinology (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Americanae (AECID Library) (submittedVersion, other-oa)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords: low T3 syndrome, critically ill patients, thyroid hormone metabolism, deiodinases, type I deiodinase, type 2 deiodinase, type 3 deiodinase, reverse T3, thyroid-stimulating hormone, inflammatory cytokines, oxidative stress, reactive oxygen species, redox state

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