Euthyroid sick syndrome pathophysiology: Difference between revisions

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==Pathophysiology==
==Pathophysiology==


===Pathogenesis===
===Pathogenesis===  
<ref name="pmid8940342">{{cite journal |vauthors=Boelen A, Maas MA, Lowik CW, Platvoet MC, Wiersinga WM |title=Induced illness in interleukin-6 (IL-6) knock-out mice: a causal role of IL-6 in the development of the low 3,5,3'-triiodothyronine syndrome |journal=Endocrinology |volume=137 |issue=12 |pages=5250–4 |year=1996 |pmid=8940342 |doi=10.1210/endo.137.12.8940342 |url=}}</ref><ref name="GRASBERGERGOLCHER2002">{{cite journal|last1=GRASBERGER|first1=Helmut|last2=GOLCHER|first2=Henriette M.B.|last3=FINGERHUT|first3=Anja|last4=JANSSEN|first4=Onno E.|title=Loop variants of the serpin thyroxine-binding globulin: implications for hormone release upon limited proteolysis|journal=Biochemical Journal|volume=365|issue=1|year=2002|pages=311–316|issn=0264-6021|doi=10.1042/bj20020014}}</ref><ref name="pmid10554534">{{cite journal |vauthors=Schilling JU, Zimmermann T, Albrecht S, Zwipp H, Saeger HD |title=[Low T3 syndrome in multiple trauma patients--a phenomenon or important pathogenetic factor?] |language=German |journal=Med. Klin. (Munich) |volume=94 Suppl 3 |issue= |pages=66–9 |year=1999 |pmid=10554534 |doi= |url=}}</ref><ref name="WongHershman1992">{{cite journal|last1=Wong|first1=Timothy K.|last2=Hershman|first2=Jerome M.|title=Changes in thyroid function in nonthyroid illness|journal=Trends in Endocrinology & Metabolism|volume=3|issue=1|year=1992|pages=8–12|issn=10432760|doi=10.1016/1043-2760(92)90085-F}}</ref><ref name="DocterKrenning1993">{{cite journal|last1=Docter|first1=R.|last2=Krenning|first2=E. P.|last3=Jong|first3=M.|last4=Hennemann|first4=G.|title=The sick euthyroid syndrome: changes in thyroid hormone serum parameters and hormone metabolism|journal=Clinical Endocrinology|volume=39|issue=5|year=1993|pages=499–518|issn=0300-0664|doi=10.1111/j.1365-2265.1993.tb02401.x}}</ref><ref name="BartalenaBogazzi1998">{{cite journal|last1=Bartalena|first1=L|last2=Bogazzi|first2=F|last3=Brogioni|first3=S|last4=Grasso|first4=L|last5=Martino|first5=E|title=Role of cytokines in the pathogenesis of the euthyroid sick syndrome|journal=European Journal of Endocrinology|volume=138|issue=6|year=1998|pages=603–614|issn=0804-4643|doi=10.1530/eje.0.1380603}}</ref>
* [[T3]] ([[triiodothyronine]]) is the biologically active form of [[thyroid hormone]]. Normally most of the [[T3]] ([[triiodothyronine]]) is produced by peripheral deiodination of circulating [[T4]] ([[thyroxine]]) by the enzyme 5’-monodeiodinase (type I).  
* [[T3]] ([[triiodothyronine]]) is the biologically active form of [[thyroid hormone]]. Normally most of the [[T3]] ([[triiodothyronine]]) is produced by peripheral deiodination of circulating [[T4]] ([[thyroxine]]) by the enzyme 5’-monodeiodinase (type I).  
* In [[euthyroid]] sick syndrome there occurs [[inhibition]] of the [[enzyme]]  5’-monodeiodinase (type I) which leads to decrease conversion of [[T4]] to [[T3]] and an increase in [[reverse T3]] from decreased metabolism.  
* In [[euthyroid]] sick syndrome there occurs [[inhibition]] of the [[enzyme]]  5’-monodeiodinase (type I) which leads to decrease conversion of [[T4]] to [[T3]] and an increase in [[reverse T3]] from decreased metabolism.  
* [[Euthyroid]] sick syndrome is seen in [[conditions]] of [[starvation]] and [[critical illness]] such as [[sepsis]], [[surgery]], severe [[trauma]], [[burns]], [[metabolic disorders]], [[bone marrow transplantation]], and [[malignancy]].  
* [[Euthyroid]] sick syndrome is seen in [[conditions]] of [[starvation]] and [[critical illness]] such as [[sepsis]], [[surgery]], severe [[trauma]], [[burns]], [[metabolic disorders]], [[bone marrow transplantation]], and [[malignancy]].<ref name="pmid8940342">{{cite journal |vauthors=Boelen A, Maas MA, Lowik CW, Platvoet MC, Wiersinga WM |title=Induced illness in interleukin-6 (IL-6) knock-out mice: a causal role of IL-6 in the development of the low 3,5,3'-triiodothyronine syndrome |journal=Endocrinology |volume=137 |issue=12 |pages=5250–4 |year=1996 |pmid=8940342 |doi=10.1210/endo.137.12.8940342 |url=}}</ref><ref name="GRASBERGERGOLCHER2002">{{cite journal|last1=GRASBERGER|first1=Helmut|last2=GOLCHER|first2=Henriette M.B.|last3=FINGERHUT|first3=Anja|last4=JANSSEN|first4=Onno E.|title=Loop variants of the serpin thyroxine-binding globulin: implications for hormone release upon limited proteolysis|journal=Biochemical Journal|volume=365|issue=1|year=2002|pages=311–316|issn=0264-6021|doi=10.1042/bj20020014}}</ref><ref name="pmid10554534">{{cite journal |vauthors=Schilling JU, Zimmermann T, Albrecht S, Zwipp H, Saeger HD |title=[Low T3 syndrome in multiple trauma patients--a phenomenon or important pathogenetic factor?] |language=German |journal=Med. Klin. (Munich) |volume=94 Suppl 3 |issue= |pages=66–9 |year=1999 |pmid=10554534 |doi= |url=}}</ref><ref name="WongHershman1992">{{cite journal|last1=Wong|first1=Timothy K.|last2=Hershman|first2=Jerome M.|title=Changes in thyroid function in nonthyroid illness|journal=Trends in Endocrinology & Metabolism|volume=3|issue=1|year=1992|pages=8–12|issn=10432760|doi=10.1016/1043-2760(92)90085-F}}</ref><ref name="DocterKrenning1993">{{cite journal|last1=Docter|first1=R.|last2=Krenning|first2=E. P.|last3=Jong|first3=M.|last4=Hennemann|first4=G.|title=The sick euthyroid syndrome: changes in thyroid hormone serum parameters and hormone metabolism|journal=Clinical Endocrinology|volume=39|issue=5|year=1993|pages=499–518|issn=0300-0664|doi=10.1111/j.1365-2265.1993.tb02401.x}}</ref><ref name="BartalenaBogazzi1998">{{cite journal|last1=Bartalena|first1=L|last2=Bogazzi|first2=F|last3=Brogioni|first3=S|last4=Grasso|first4=L|last5=Martino|first5=E|title=Role of cytokines in the pathogenesis of the euthyroid sick syndrome|journal=European Journal of Endocrinology|volume=138|issue=6|year=1998|pages=603–614|issn=0804-4643|doi=10.1530/eje.0.1380603}}</ref>
** During these [[Stress (medicine)|stress]] conditions, there occurs [[hypermetabolism]], increased [[energy]] expenditure, [[hyperglycemia]], and [[muscle]] loss. It is speculated, that the body in order to contain this [[hypermetabolism]] induces some degree of [[hypothyroidism]] by inhibiting deiodination of [[T4]] to [[T3]] by the [[enzyme]] 5’-monodeiodinase. This is an [[adaptive]] process by which the [[Human body|body]] prevents further [[muscle]] and [[calorie]] loss.
** During these [[Stress (medicine)|stress]] conditions, there occurs [[hypermetabolism]], increased [[energy]] expenditure, [[hyperglycemia]], and [[muscle]] loss. It is speculated, that the body in order to contain this [[hypermetabolism]] induces some degree of [[hypothyroidism]] by inhibiting deiodination of [[T4]] to [[T3]] by the [[enzyme]] 5’-monodeiodinase. This is an [[adaptive]] process by which the [[Human body|body]] prevents further [[muscle]] and [[calorie]] loss.
** During illness, there is also [[downregulation]] of [[Thyrotropin-releasing hormone|TRH]] and [[Thyroid-stimulating hormone|TSH]] release from the [[hypothalamus]] and [[pituitary gland]] respectively. It may be signalled by a decrease in leptin caused by malnutrition. Under normal conditions, leptin prevents neuropeptide Y (NPY) and agouti-related protein (AGRP) induced downregulation of TRH.
** During illness, there is also [[downregulation]] of [[Thyrotropin-releasing hormone|TRH]] and [[Thyroid-stimulating hormone|TSH]] release from the [[hypothalamus]] and [[pituitary gland]] respectively. It may be signalled by a decrease in leptin caused by malnutrition. Under normal conditions, leptin prevents neuropeptide Y (NPY) and agouti-related protein (AGRP) induced downregulation of TRH.

Revision as of 17:59, 16 August 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

Overview

Euthyroid sick syndrome is not a primary thyroid disorder but instead results from changes induced by the nonthyroidal illness. The cause of euthyroid sick syndrome is multifactorial. It is thought that euthyroid sick syndrome is the result of severe illness and inflammation. During these stress conditions, hypermetabolism occur, that lead to increased energy expenditure, hyperglycemia, and muscle loss. It is speculated, that the body induces some degree of hypothyroidism by inhibiting deiodination of T4 to T3 by the enzyme 5’-monodeiodinase, in order to contain the hypermetabolism. This is an adaptive process by which the body prevents further muscle and calorie loss. Inflammation leads to increased production of cytokines that severely affect genes involved in the production and release of T4 and T3. There is also downregulation of TRH and TSH release from the hypothalamus and pituitary gland respectively. It may be signalled by a decrease in leptin caused by malnutrition. On gross pathology, euthyroid sick syndrome does not appear to be dysfunctional. On microscopic histopathological analysis, euthyroid sick syndrome presents with normal thyroid histology.

Pathophysiology

Pathogenesis

Genetics

Gene involved in the pathogenesis of euthyroid sick syndrome include mutation in LEP gene.

Associated Conditions

Euthyroid sick syndrome is seen with starvation and severe illness such as:[14][15]

Gross Pathology

In euthyroid sick syndrome the thyroid gland does not appear to be dysfunctional.

Microscopic Pathology

On microscopic histopathological analysis, euthyroid sick syndrome presents with normal thyroid histology.

Histology of normal thyroid gland. 1. Colloid 2. Cellular Epithelium Arrow: C-Cell - Source - By M-J-G (Own work) [CC BY-SA 4.0, via Wikimedia Commons

References

  1. Boelen A, Maas MA, Lowik CW, Platvoet MC, Wiersinga WM (1996). "Induced illness in interleukin-6 (IL-6) knock-out mice: a causal role of IL-6 in the development of the low 3,5,3'-triiodothyronine syndrome". Endocrinology. 137 (12): 5250–4. doi:10.1210/endo.137.12.8940342. PMID 8940342.
  2. GRASBERGER, Helmut; GOLCHER, Henriette M.B.; FINGERHUT, Anja; JANSSEN, Onno E. (2002). "Loop variants of the serpin thyroxine-binding globulin: implications for hormone release upon limited proteolysis". Biochemical Journal. 365 (1): 311–316. doi:10.1042/bj20020014. ISSN 0264-6021.
  3. Schilling JU, Zimmermann T, Albrecht S, Zwipp H, Saeger HD (1999). "[Low T3 syndrome in multiple trauma patients--a phenomenon or important pathogenetic factor?]". Med. Klin. (Munich) (in German). 94 Suppl 3: 66–9. PMID 10554534.
  4. Wong, Timothy K.; Hershman, Jerome M. (1992). "Changes in thyroid function in nonthyroid illness". Trends in Endocrinology & Metabolism. 3 (1): 8–12. doi:10.1016/1043-2760(92)90085-F. ISSN 1043-2760.
  5. Docter, R.; Krenning, E. P.; Jong, M.; Hennemann, G. (1993). "The sick euthyroid syndrome: changes in thyroid hormone serum parameters and hormone metabolism". Clinical Endocrinology. 39 (5): 499–518. doi:10.1111/j.1365-2265.1993.tb02401.x. ISSN 0300-0664.
  6. Bartalena, L; Bogazzi, F; Brogioni, S; Grasso, L; Martino, E (1998). "Role of cytokines in the pathogenesis of the euthyroid sick syndrome". European Journal of Endocrinology. 138 (6): 603–614. doi:10.1530/eje.0.1380603. ISSN 0804-4643.
  7. Légrádi G, Emerson CH, Ahima RS, Flier JS, Lechan RM (1997). "Leptin prevents fasting-induced suppression of prothyrotropin-releasing hormone messenger ribonucleic acid in neurons of the hypothalamic paraventricular nucleus". Endocrinology. 138 (6): 2569–76. doi:10.1210/endo.138.6.5209. PMID 9165050.
  8. Rogge, G.; Jones, D.; Hubert, G. W.; Lin, Y.; Kuhar, M. J. (2008). "CART peptides: regulators of body weight, reward and other functions". Nature Reviews Neuroscience. 9 (10): 747–758. doi:10.1038/nrn2493. ISSN 1471-003X.
  9. Froguel, Philippe; Clément, Karine; Vaisse, Christian; Lahlou, Najiba; Cabrol, Sylvie; Pelloux, Veronique; Cassuto, Dominique; Gourmelen, Micheline; Dina, Christian; Chambaz, Jean; Lacorte, Jean-Marc; Basdevant, Arnaud; Bougnères, Pierre; Lebouc, Yves; Guy-Grand, Bernard (1998). "A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction". Nature. 392 (6674): 398–401. doi:10.1038/32911. ISSN 0028-0836.
  10. Lechan RM, Fekete C (2005). "Role of thyroid hormone deiodination in the hypothalamus". Thyroid. 15 (8): 883–97. doi:10.1089/thy.2005.15.883. PMID 16131331.
  11. Abo-Zenah HA, Shoeb SA, Sabry AA, Ismail HA (2008). "Relating circulating thyroid hormone concentrations to serum interleukins-6 and -10 in association with non-thyroidal illnesses including chronic renal insufficiency". BMC Endocr Disord. 8: 1. doi:10.1186/1472-6823-8-1. PMC 2254394. PMID 18211669.
  12. Stouthard JM, van der Poll T, Endert E, Bakker PJ, Veenhof CH, Sauerwein HP, Romijn JA (1994). "Effects of acute and chronic interleukin-6 administration on thyroid hormone metabolism in humans". J. Clin. Endocrinol. Metab. 79 (5): 1342–6. doi:10.1210/jcem.79.5.7962327. PMID 7962327.
  13. Wawrzynska L, Sakowicz A, Rudzinski P, Langfort R, Kurzyna M (2003). "The conversion of thyroxine to triiodothyronine in the lung: comparison of activity of type I iodothyronine 5' deiodinase in lung cancer with peripheral lung tissues". Monaldi Arch Chest Dis. 59 (2): 140–5. PMID 14635503.
  14. Silva MH, Araujo MC, Diniz EM, Ceccon ME, Carvalho WB (2015). "Nonthyroidal illnesses syndrome in full-term newborns with sepsis". Arch Endocrinol Metab. 59 (6): 528–34. doi:10.1590/2359-3997000000111. PMID 26677087.
  15. Frączek MM, Gackowski A, Przybylik-Mazurek E, Nessler J (2016). "[The relation between the low T3 syndrome in the clinical course of myocardial infarction and heart failure]". Pol. Merkur. Lekarski (in Polish). 40 (240): 380–3. PMID 27403906.

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