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| ==Overview== | | ==Overview== |
| Euthyroid sick syndrome is a [[thyroid hormone]] disorder where the levels of T3 ([[triiodothyronine]]) and/or T4 ([[thyroxine]]) are at unusual levels, in the setting of a nonthyroidal [[illness]]. Thyroid hormones play a major role in the metabolism, growth and maturation of the human body. [[Euthyroid]] sick [[syndrome]] is seen in conditions of [[starvation]] and [[critical illness]] such as [[sepsis]], [[surgery]], [[Physical trauma|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 [[Triiodothyronine|T3]] by the enzyme 5’-monodeiodinase. This is an adaptive process by which the body prevents further [[muscle]] and [[calorie]] loss. [[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([[Thyroid-stimulating hormone|TSH]]), [[thyroxine]] (T4), and [[free T4]] (FT4) are affected in variable proportions.<ref name="pmid9712558">{{cite journal |vauthors=Plank LD, Connolly AB, Hill GL |title=Sequential changes in the metabolic response in severely septic patients during the first 23 days after the onset of peritonitis |journal=Ann. Surg. |volume=228 |issue=2 |pages=146–58 |year=1998 |pmid=9712558 |pmc=1191454 |doi= |url=}}</ref><ref name="pmid21724536">{{cite journal |vauthors=Economidou F, Douka E, Tzanela M, Nanas S, Kotanidou A |title=Thyroid function during critical illness |journal=Hormones (Athens) |volume=10 |issue=2 |pages=117–24 |year=2011 |pmid=21724536 |doi= |url=}}</ref><ref name="pmid30020">{{cite journal |vauthors=Harris AR, Fang SL, Vagenakis AG, Braverman LE |title=Effect of starvation, nutriment replacement, and hypothyroidism on in vitro hepatic T4 to T3 conversion in the rat |journal=Metab. Clin. Exp. |volume=27 |issue=11 |pages=1680–90 |year=1978 |pmid=30020 |doi= |url=}}</ref>
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| ==Historical Perspective== | | ==Historical Perspective== |
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| ==Pathophysiology== | | ==Pathophysiology== |
| [[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΄-deiodinase (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 (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. [[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>
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| ==Causes==
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| Drugs leading to decreased 5'monodeiodinase are propranolol (high doses), amiodarone, and glucocorticoid therapy.
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| ==Differentiating {{PAGENAME}} from Other Diseases== | | ==Differentiating {{PAGENAME}} from Other Diseases== |
| [[Fasting]], [[starvation]], [[sepsis]], [[Physical trauma|trauma]], [[cardiopulmonary bypass]], [[malignancy]], [[heart failure]], [[hypothermia]], [[myocardial infarction]], [[chronic renal failure]], [[cirrhosis]], and [[diabetic ketoacidosis]].
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| __NOTOC__
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| ==Epidemiology and Demographics== | | ==Epidemiology and Demographics== |
| Euthyroid sick syndrome is seen in 40-100% patients of nonthyroidal illness.
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| ===Age===
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| Euthyroid sick syndrome is more commonly seen in elderly population. People over 65 have more chronic illnesses and have a greater probability of developing euthyroid sick syndrome.
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| ===Race===
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| Euthyroid sick syndrome has no racial predilection.
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| ===Sex===
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| Euthyroid sick syndrome affects men and women equally.
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| ==Risk Factors== | | ==Risk Factors== |
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| ==History and symptom == | | ==History and symptom == |
| The common symptoms and signs of clinical hypothyroidism are listed in the table below. The appearance of symptoms depends on the degree of hypothyroidism severity: <ref name="pmid25305308">{{cite journal |vauthors=Carlé A, Pedersen IB, Knudsen N, Perrild H, Ovesen L, Laurberg P |title=Hypothyroid symptoms and the likelihood of overt thyroid failure: a population-based case-control study |journal=Eur. J. Endocrinol. |volume=171 |issue=5 |pages=593–602 |year=2014 |pmid=25305308 |doi=10.1530/EJE-14-0481 |url=}}</ref><ref name="pmid25086165">{{cite journal |vauthors=Diaz A, Lipman Diaz EG |title=Hypothyroidism |journal=Pediatr Rev |volume=35 |issue=8 |pages=336–47; quiz 348–9 |year=2014 |pmid=25086165 |doi=10.1542/pir.35-8-336 |url=}}</ref><ref name="pmid25122491">{{cite journal |vauthors=Samuels MH |title=Psychiatric and cognitive manifestations of hypothyroidism |journal=Curr Opin Endocrinol Diabetes Obes |volume=21 |issue=5 |pages=377–83 |year=2014 |pmid=25122491 |pmc=4264616 |doi=10.1097/MED.0000000000000089 |url=}}</ref><ref name="pmid19949140">{{cite journal |vauthors=McDermott MT |title=In the clinic. Hypothyroidism |journal=Ann. Intern. Med. |volume=151 |issue=11 |pages=ITC61 |year=2009 |pmid=19949140 |doi=10.7326/0003-4819-151-11-200912010-01006 |url=}}</ref>
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| {| class="wikitable"
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| ! align="center" style="background: #4479BA; color: #FFFFFF; " |Symptoms
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| ! align="center" style="background: #4479BA; color: #FFFFFF; " |Constituitional
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| ! align="center" style="background: #4479BA; color: #FFFFFF; " | HEENT
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| ! align="center" style="background: #4479BA; color: #FFFFFF; " |Neuromuscular
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| ! align="center" style="background: #4479BA; color: #FFFFFF; " |Other findings
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| |-
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| | align="center" style="background: #DCDCDC; " |More common
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| * [[Fatigue]]
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| * Cold intolerance
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| * Decreased [[sweating]]
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| * [[Hypothermia]]
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| * Coarse skin
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| * [[Weight gain]]
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| * [[Hoarseness]]
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| * [[Goiter]]
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| * Fullness in the throat and neck
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| * [[Depression]]
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| * [[Emotional lability]]
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| * [[Attention deficit]]
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| * [[Macroglossia]]
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| * [[Obstructive sleep apnea]]
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| * [[Paresthesia]]
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| * Nerve entrapment syndromes ([[carpal tunnel syndrome]])
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| * [[Blurred vision]] (central hypothyroidism)
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| |-
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| | align="center" style="background: #DCDCDC; " |Less common
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| * Puffiness
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| * [[Hair loss]]
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| * [[Constipation]]
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| * [[Fever]]
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| ** If accompanied by [[thyroiditis]]
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| * [[Sore throat]]
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| * [[Periorbital edema]]
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| * Slowed speech and movements
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| * Pituitary hyperplasia followed by [[hyperprolactinemia]]
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| * [[Ataxia]]
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| * [[Myxedema coma]] (with [[Edema|non-pitting edema]])
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| * [[Cardiomegaly]]
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| * [[Pericardial effusion]]
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| * [[Ascites]]
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| * [[Hyperlipidemia]]
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| * [[Galactorrhea]]
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| * [[Infertility]]
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| |}
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| ===Physical Examination===
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| ===Laboratory Findings===
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| Laboratory findings consistent with the diagnosis of euthyroid sick syndrome include
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| {| class="wikitable"
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| !Euthyroid sick syndrome
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| !Laboratory test
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| |-
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| |Mild euthyroid sick syndrome
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| * Low [[Triiodothyronine|T3]]
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| * Normal [[T4]]
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| * Normal [[fT4]]
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| * Normal [[Thyroid-stimulating hormone|TSH]]
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| * Elevated [[reverse T3]]
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| |-
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| |Moderate euthyroid sick syndrome
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| * Low [[T3]]
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| * Normal [[T4]]
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| * Normal to elevated [[fT4]]
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| * Normal to elevated [[TSH]]
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| * Elevated [[reverse T3]]
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| |-
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| |Severe euthyroid sick syndrome
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| * Low [[T3]]
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| * Low [[T4]]
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| * Low [[Thyroid-stimulating hormone|TSH]]
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| * Normal to low [[fT4]]
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| * Elevated [[reverse T3]]
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| |}
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| ===Imaging Findings===
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| ===Other Diagnostic Studies===
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| In euthyroid sick syndrome the thyroid gland appears normal. Therefore, there is no role of thyroid uptake scan in euthyroid sick syndrome.
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| ==Treatment== | | ==Treatment== |