What is euthyroid sick syndrome?

Euthyroid Sick Syndrome

Euthyroid sick syndrome (ESS), also known as non-thyroidal illness syndrome (NTIS), is characterized by abnormal thyroid function tests in patients with acute or chronic systemic illnesses who do not have intrinsic thyroid disease. The syndrome represents an adaptive response to illness aimed at reducing the body's metabolic rate and conserving energy during severe physiological stress 1.

Biochemical Characteristics

• ESS typically presents with low serum triiodothyronine (T3) levels, elevated reverse T3 (rT3), and normal or inappropriately low thyroid-stimulating hormone (TSH) and thyroxine (T4) levels 1, 2.
• The degree of thyroid function impairment correlates with disease severity, with low levels of thyroid hormones (particularly T4) predicting poor prognosis 1.
• As illness progresses, more marked changes occur including a significant decline in thyroxine and an increase in T3 resin uptake 2.

Classification

ESS can be classified into subtypes based on the pattern of thyroid hormone alterations:

• Type I: Characterized primarily by low T3 levels (most common form, representing about 63% of cases) 3.
• Type II: Shows low T3 and T4 levels (less common, about 6.5% of cases) 3.
• Type III: Presents with low T3 but elevated T4 levels (approximately 30.5% of cases) 3.

Associated Conditions

ESS is commonly observed in:

• Chronic heart failure (affecting up to 44.29% of patients with long-standing heart failure) 4.
• Chronic kidney disease 4.
• Severe sepsis 4.
• Obstructive chronic bronchopneumopathy with acute respiratory failure 3.
• Diabetic ketoacidosis 3.
• Neoplasms 3.
• Ischemic heart disease and cardiac failure 3.
• Liver diseases 3.
• Acute cerebral vasculopathies 3.

Clinical Significance

• ESS is the most frequent cause of thyroid hormone alterations in hospitalized patients, with an incidence of approximately 23%, significantly higher than actual thyroid disease (5%) 3.
• The syndrome represents a marker of disease severity, with higher reverse T3 (rT3) values associated with more severe illness 5.
• In heart failure patients, there is a negative correlation between NT-proBNP levels (a marker of heart failure severity), Boston score, and total T3 levels 4.

Pathophysiology

• The primary mechanism involves reduced activity of the 5-deiodinase enzyme, which normally converts T4 to T3 3.
• This results in decreased T3 production and increased conversion of T4 to reverse T3 (rT3) 3.
• In Type III ESS, increased thyroxine-binding globulin (TBG) results in elevated T4 values due to increased binding capacity, leading to reduced peripheral hormone activity 3.

Diagnosis and Management

• Diagnosis requires careful differentiation from true thyroid dysfunction, particularly in patients without previous thyroid function tests 1.
• Despite marked alterations in thyroid function tests, patients remain euthyroid as confirmed by normal TSH levels 2.
• Supplemental thyroid hormone therapy has never been shown to be beneficial and may potentially be harmful in patients with ESS 2.
• Management should focus on treating the underlying condition rather than the thyroid abnormalities 1, 2.

Clinical Implications

• Recognition of ESS is vital to avoid unnecessary thyroid hormone therapy 2.
• Regular monitoring of thyroid function is recommended in critically ill patients, particularly those with heart failure 4.
• The presence of ESS should prompt more intensive monitoring and optimized management of the underlying condition 4.