Euthyroid sick syndrome
|Euthyroid sick syndrome|
|Classification and external resources|
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 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. 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.
Euthyroid sick syndrome (non-thyroidal illness syndrome) has been assumed closely related with a series of diseases, (such as inflammatory bowel disease).
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 upregulated. 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. 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.
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. 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. 3,5-T2 levels were also observed to correlate with concentrations of rT3 (reverse T3) 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.
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