Euthyroid sick syndrome

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Euthyroid sick syndrome
Classification and external resources
Specialty Biochemical Genetics
ICD-10 E07.8
ICD-9-CM 790.94
eMedicine med/753
MeSH D005067

Euthyroid sick syndrome (ESS), sick euthyroid syndrome (SES), thyroid allostasis in critical illness, tumours, uremia and starvation (TACITUS), non-thyroidal illness syndrome (NTIS) or low T3 low T4 syndrome is a state of adaptation or dysregulation of thyrotropic feedback control[1] where the levels of T3 and/or T4 are at unusual levels, but the thyroid gland does not appear to be dysfunctional.

This condition is often seen in starvation, critical illness or patients in intensive care unit. Similar endocrine phenotypes are observed in fetal life and in hibernating mammals[2] The most common hormone pattern in sick euthyroid syndrome is a low total and unbound T3 levels with normal T4 and TSH levels.


Causes of euthyroid sick syndrome include a number of acute and chronic conditions, including pneumonia, fasting, starvation, anorexia nervosa, sepsis, trauma, cardiopulmonary bypass, malignancy, stress, heart failure, hypothermia, myocardial infarction, chronic renal failure, cirrhosis, and diabetic ketoacidosis.[1]

Euthyroid sick syndrome (non-thyroidal illness syndrome) has been assumed closely related with a series of diseases, (such as inflammatory bowel disease).[3]


In critical illness the activity of peripheral type I deiodinase is downregulated, while both the central Type 2 deiodinase and type 3 deiodinase activities are up-regulated. Humoral and neuronal inputs at the level of the hypothalamus may adjust the set point of thyroid homeostasis. This may play an important role in the pathogenesis of the central component of TACITUS.[4] In addition, both illness and medication (e.g. salicylates and heparin) may impair plasma protein binding of thyroid hormones, resulting in reduced levels of total hormones, while free hormone concentrations may be temporarily elevated.

Euthyroid sick syndrome probably represents an overlap of an allostatic response with pathologic reactions and drug interferences[2]. Allostatic overload may result in wasting syndrome and myxedema coma. Thyroid storm, on the other hand, represents allostatic failure, where the organism is unable to develop NTIS in the situation of thyrotoxicosis[2].


Affected patients may have normal, low, or slightly elevated TSH depending on the spectrum of illness. Total T4 and T3 levels may be altered by binding protein abnormalities, and medications. Reverse T3 levels are generally increased signifying inhibition of normal type 1 deiodinase or reduced clearance of reverse T3. Correspondingly, in the majority of cases calculated sum activity of peripheral deiodinases (SPINA-GD) is reduced.[3][5][6][7] Generally the levels of free T3 will be lowered, followed by the lowering of free T4 in more severe disease. Several studies described elevated concentrations of 3,5-T2, an active thyroid hormone, in NTIS.[7][8] 3,5-T2 levels were also observed to correlate with concentrations of rT3 (reverse T3)[7] in patients with euthyroid sick syndrome.

TACITUS syndrome is a component of a complex endocrine adaptation process. Therefore, affected patients might also have hyperprolactinemia and elevated levels of corticosteroids (especially cortisol) and growth hormone.


Several trials investigated a possible therapy for ESS. However, they yielded inconsistent and partly contradictory results. This may be caused by the fact that the investigated populations were too heterogeneous in the lack of a consistent definition of non-thyroid illness syndrome.[9]

Modern theories regard the TACITUS syndrome as an adaptive and therefore possibly beneficial response of thyroid homeostasis[2]. Their proponents are therefore reserved with respect to substitutive treatment.


  1. ^ a b "Euthyroid Sick Syndrome: Thyroid Disorders: Merck Manual Professional". Retrieved 2009-03-29. 
  2. ^ a b c d Chatzitomaris, Apostolos; Hoermann, Rudolf; Midgley, John E.; Hering, Steffen; Urban, Aline; Dietrich, Barbara; Abood, Assjana; Klein, Harald H.; Dietrich, Johannes W. (20 July 2017). "Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming". Frontiers in Endocrinology. 8. PMID 28775711. doi:10.3389/fendo.2017.00163. 
  3. ^ a b Liu, S; Ren, J; Zhao, Y; Han, G; Hong, Z; Yan, D; Chen, J; Gu, G; Wang, G; Wang, X; Fan, C; Li, J (February 2013). "Nonthyroidal illness syndrome: is it far away from Crohn's disease?". Journal of Clinical Gastroenterology. 47 (2): 153–9. PMID 22874844. doi:10.1097/MCG.0b013e318254ea8a. 
  4. ^ Hoermann, R; Midgley, JE; Larisch, R; Dietrich, JW (2015). "Homeostatic Control of the Thyroid-Pituitary Axis: Perspectives for Diagnosis and Treatment.". Frontiers in Endocrinology. 6: 177. PMC 4653296Freely accessible. PMID 26635726. doi:10.3389/fendo.2015.00177. 
  5. ^ Rosolowska-Huszcz D, Kozlowska L, Rydzewski A (August 2005). "Influence of low protein diet on nonthyroidal illness syndrome in chronic renal failure". Endocrine. 27 (3): 283–8. PMID 16230785. doi:10.1385/ENDO:27:3:283. 
  6. ^ Han G, Ren J, Liu S, Gu G, Ren H, Yan D, Chen J, Wang G, Zhou B, Wu X, Yuan Y, Li J (Sep 2013). "Nonthyroidal illness syndrome in enterocutaneous fistulas". Am J Surg. 206 (3): 386–92. PMID 23809674. doi:10.1016/j.amjsurg.2012.12.011. 
  7. ^ a b c Dietrich, JW; Müller, P; Schiedat, F; Schlömicher, M; Strauch, J; Chatzitomaris, A; Klein, HH; Mügge, A; Köhrle, J; Rijntjes, E; Lehmphul, I (2015). "Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling". European Thyroid Journal. 4: 129–37. PMC 4521060Freely accessible. PMID 26279999. doi:10.1159/000381543. 
  8. ^ Pinna G, Meinhold H, Hiedra L, Thoma R, Hoell T, Gräf KJ, Stoltenburg-Didinger G, Eravci M, Prengel H, Brödel O, Finke R, Baumgartner A. "Elevated 3,5-diiodothyronine concentrations in the sera of patients with nonthyroidal illnesses and brain tumors". J Clin Endocrinol Metab. 82: 1535–42. PMID 9141546. doi:10.1210/jcem.82.5.3939. 
  9. ^ Dietrich, JW; Stachon, A; Antic, B; Klein, HH; Hering, S (2008). "The AQUA-FONTIS study: protocol of a multidisciplinary, cross-sectional and prospective longitudinal study for developing standardized diagnostics and classification of non-thyroidal illness syndrome". BMC endocrine disorders. 8: 13. PMC 2576461Freely accessible. PMID 18851740. doi:10.1186/1472-6823-8-13. 

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