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Euthyroid Sick Syndrome

What is Euthyroid Sick Syndrome?

Euthyroid Sick Syndrome is a non-thyroidal systemic disorder characterized by low serum level of both triiodothyronine (T3) and thyroxine (T4) level, occurs due to multiple conditions like starvation, myocardial infarction, sepsis, surgery, bypass, bone marrow transplantation, etc.

It has been assumed that mostly all severe disorders have Euthyroid Sick Syndrome, as a characteristic feature.

Prolonged Euthyroid Sick Syndrome hampers metabolic functioning of the tissue and the condition is termed as nonthyroidal illness syndrome. ^1,2,3

Symptoms

Euthyroid Sick Syndrome is resultant of low thyroid level in serum, but not associated with hypothyroidism. Therefore the abnormality is only restricted in blood test report, but no symptomatic approaches are represented with Euthyroid Sick Syndrome.

The increased physiological stress occur due to illness causes the abnormal low serum hormone level and that can be overcome by disease condition passed^2,5.

The reduced level of the T3 level is most common laboratory findings of most of the disease condition. But prolonged illness causes reduction of the T4 level. In contrast, elevation of reverse T3 or rT3 is also found in laboratory test report, but no TSH (thyroid-stimulating hormone) have been raised with Euthyroid Sick Syndrome^2,3.

Pathophysiology

The exact pathophysiology is yet now not clear. But probably certain physiological alterations like peripherally decrease conversion from T4 to T3, reduction of clearance of rT3 synthesized from T4 and reduced binding of thyroid hormones to thyroxine-binding globulin (TBG).

The contributory factors for Euthyroid Sick Syndrome are pro-inflammatory cytokines and other inflammatory mediators, which are responsible for certain changes in hormonal imbalance.

Experts predict that cytokines or other mediators of inflammation may react with hypothalamus (present in brain where pituitary gland is located) and pituitary (master gland secretes TSH to control T4 and T3 level), the thyroid gland (secretes T4 and T3), and the hepatic deiodinase system (assists in conversion of T4 to T3), as well as on binding of thyroxine to thyroid binding globulin.

In chronic disease condition, multi-pharmacy also hinder the normal functioning of the thyroid gland. for example, amiodarone and iodine-rich contrast substances can impair peripheral conversion of thyroxine (T4) to triiodothyronine (T3), whereas corticosteroids and dopamine can decrease the secretion of TSH, result fo this low level of TSH in the systemic circulation and that also hinder T4 release, which subsequently reduces T3 conversion^2,3,4.

Diseases which Causes ESS

Some acute and chronic diseases enlisted in this section which alters the thyroid function test results:

Gastrointestinal diseases
Cardiovascular diseases
Myocardial infarction
Infiltrative and metabolic disorders
Pulmonary diseases
Renal diseases
Starvation
Bone marrow transplantation
Inflammatory conditions
Malignancy
Sepsis
Trauma
Burns
Surgery

All the above-mentioned diseases have the tendency to alter the thyroid hormone production rate by directly affecting the thyroid gland, or react with the hypothalamic-pituitary-thyroid axis, or modify thyroid hormones metabolism in the peripheral tissue. In some cases, a combination of these modifications alter the thyroid function test findings⁵.

Diagnosis

Euthyroid Sick Syndrome is usually diagnosed through clinical judgment in the case of acute and chronic ill patients, as no laboratory test result provide the definite result to indicate Euthyroid Sick Syndrome.

The usual laboratory test is conducted through blood sample evaluation for TSH level, Serum cortisol level. But test report is not specific to indicate that the patient has euthyroid sick syndrome or hypothyroidism.

TSH levelly is low, or normal or a little high in euthyroid sick syndrome, but in hypothyroidism, the TSH level is significantly high. This difference of TSH level is considered a good indicator to differentiate euthyroid sick syndrome and hypothyroidism.
In euthyroid sick syndrome, Serum rT3 level is higher, but this test is not frequently ordered.
Serum cortisol level is generally increased in euthyroid sick syndrome but decreased or below normal in hypothyroidism due to the pituitary-hypothalamic ailment.

The doctor may not prefer to do thyroid function test in ICU admitted patients, except the risk of thyroid dysfunction, is greatly assumed^2,3.

Treatment

Euthyroid Sick Syndrome is not a disease, but a condition arises due to some underlying disorder that increases physiological stress and responsible for decrease level of Both T3 and T4 level. Therefore, identification and treatment of underlying cause consequently elevate the thyroid hormones level and reduce the risk of related complications.

Direct treatment to elevate the thyroid level by thyroid hormone replacement therapy is not recommended for Euthyroid Sick Syndrome, as some research result showed that this therapy worsens the cardiovascular condition^2,3.

Prognosis

The extent of thyroid function disorder associated with the severity of the underlying disease and thyroid hormones levels reduction may relate with a poor prognosis in numerous ailments.

Experts predict that euthyroid sick syndrome may provide an adaptive response and therefore it can cause chronic thyroid hormonal unbalance. The resultant of this causes reduction of tissue energy level and that also cause different systemic illness.

In another side, chronic Euthyroid Sick Syndrome may cause a maladaptive reaction, which provokes destructive tissue hypothyroidism. A significant reduction of serum T₃ and T₄ in nonthyroidal illness syndrome is related to a high possibility of a fatality^1,3.

References

Leslie J. DeGroot; The Non-Thyroidal Illness Syndrome; Thyroid Disease Manager; http://www.thyroidmanager.org/chapter/the-non-thyroidal-illness-syndrome/
Jerome M. Hershman; Euthyroid Sick Syndrome; msdmanuals Professional Version; http://www.msdmanuals.com/professional/endocrine-and-metabolic-disorders/thyroid-disorders/euthyroid-sick-syndrome
McIver B, Gorman CA; Euthyroid sick syndrome: an overview; Thyroid. 1997 Feb;7(1):125-32; Online https://www.ncbi.nlm.nih.gov/pubmed/9086580
Amy C. Schroeder, Martin L. Privalsky; Thyroid Hormones, T3 and T4, in the Brain; Front Endocrinol (Lausanne) 2014; 5: 40. Published online 2014 Mar 31. doi: 10.3389/fendo.2014.00040; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978256/
Serhat Aytug; Euthyroid Sick Syndrome; http://emedicine.medscape.com/article/118651-overview