Euthyroid sick syndrome pathophysiology: Difference between revisions
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* [[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]]. | ||
** 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. | ** 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. | ||
** [[In vitro]] studies have shown that high concentrations of [[cytokines]] severely affect [[genes]] involved in the production and release of [[T4]] and [[T3]].<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> | ** [[In vitro]] studies have shown that high concentrations of [[cytokines]] severely affect [[genes]] involved in the production and release of [[T4]] and [[T3]].<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> | ||
* [[Euthyroid]] sick syndrome presents with low serum [[T3]]. Depending upon the severity and duration of the [[Stress (medicine)|stress]] inducing [[condition]], the [[thyroid-stimulating hormone]]([[TSH]]), [[thyroxine]] ([[T4]]), and [[free T4]] ([[FT4]]) are affected in variable proportions. The drop in levels of [[T3]] and [[T4]] are more with more severe illnesses. [[Mortality rate]] is high when there is a marked decrease in serum [[T3]] and [[T4]].<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> | * [[Euthyroid]] sick syndrome presents with low serum [[T3]]. Depending upon the severity and duration of the [[Stress (medicine)|stress]] inducing [[condition]], the [[thyroid-stimulating hormone]]([[TSH]]), [[thyroxine]] ([[T4]]), and [[free T4]] ([[FT4]]) are affected in variable proportions. The drop in levels of [[T3]] and [[T4]] are more with more severe illnesses. [[Mortality rate]] is high when there is a marked decrease in serum [[T3]] and [[T4]].<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> | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
- The exact pathogenesis of [disease name] is not fully understood.
OR
- It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
- [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
- Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
- [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
- The progression to [disease name] usually involves the [molecular pathway].
- The pathophysiology of [disease/malignancy] depends on the histological subtype.
Pathophysiology
Pathogenesis
- 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.
- 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.
- During these 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 body prevents further muscle and calorie loss.
- During illness, 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. Under normal conditions leptin prevents neuropeptide Y (NPY) and agouti-related protein (AGRP) induced downregulation of TRH.
- In vitro studies have shown that high concentrations of cytokines severely affect genes involved in the production and release of T4 and T3.[1]
- Euthyroid sick syndrome presents with low serum T3. Depending upon the severity and duration of the stress inducing condition, the thyroid-stimulating hormone(TSH), thyroxine (T4), and free T4 (FT4) are affected in variable proportions. The drop in levels of T3 and T4 are more with more severe illnesses. Mortality rate is high when there is a marked decrease in serum T3 and T4.[2][3][4][5][6]
Genetics
Genes involved in the pathogenesis of euthyroid sick syndrome include IL6 gene, IL1B, and DIO2.[1][7][8][9]
IL6 gene encodes a cytokine that functions in inflammation and the maturation of B cells. The functioning of IL6 gene is implicated in a wide variety of inflammation-associated disease states. During illness A decrease in serum T3 during illness is significantly related to serum IL-6 concentrations.
Associated Conditions
Gross Pathology
- On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
Microscopic Pathology
- On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
References
- ↑ 1.0 1.1 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.