What is euthyroid sick syndrome?

Euthyroid Sick Syndrome

Euthyroid sick syndrome (ESS) is a condition characterized by abnormal thyroid function tests in patients with non-thyroidal systemic illnesses, without intrinsic thyroid disease. 1, 2

Definition and Characteristics

• ESS, also known as "non-thyroidal illness syndrome" or "low T3 syndrome," represents alterations in thyroid hormone levels that occur during acute or chronic systemic illnesses, despite the absence of underlying thyroid disease 1, 3
• The syndrome affects approximately 60-70% of critically ill patients, making it the most common cause of thyroid hormone abnormalities in hospitalized patients 3, 4
• ESS is considered a mix of physiologic adaptation and pathologic response to acute illness, though the exact underlying mechanisms remain incompletely understood 5

Laboratory Findings

• The most common pattern in ESS is the "low T3 syndrome," characterized by decreased serum triiodothyronine (T3) levels and elevated reverse T3 (rT3) levels 1, 2
• In more severe illness, patients may develop "low T3-low T4 state," where both T3 and thyroxine (T4) levels are reduced 2, 3
• Thyroid-stimulating hormone (TSH) levels are typically normal or inappropriately low despite low thyroid hormone levels 1, 3
• The degree of thyroid hormone abnormalities correlates with disease severity, and particularly low T4 levels are associated with poor prognosis 1, 5

Pathophysiology

Multiple mechanisms contribute to ESS development:

• Decreased peripheral conversion of T4 to T3 due to reduced 5'-deiodinase activity (a selenoprotein) 2, 3
• Alterations in TSH regulation and secretion 3, 5
• Changes in thyroid hormone binding to transport proteins, with binding inhibitors displacing T4 2, 3
• Impaired transport of thyroid hormones into peripheral tissues 5
• Altered thyroid hormone receptor activity 5

Clinical Significance and Diagnosis

• ESS should be distinguished from true thyroid dysfunction, as it represents a response to systemic illness rather than primary thyroid disease 2, 4
• The syndrome can be classified into subtypes based on the pattern of hormone alterations 4:
  • Type I: Low T3, normal/low T4, normal/low TSH (most common, ~63% of cases)
  • Type II: Low T3, high T4, normal/low TSH (~6.5% of cases)
  • Type III: Low T3, low T4, normal/low TSH (~30.5% of cases)
• Common conditions associated with ESS include respiratory failure, diabetic ketoacidosis, malignancies, cardiac conditions, renal failure, liver diseases, cerebrovascular events, and sepsis 4

Management Considerations

• ESS typically resolves as the underlying illness improves, with thyroid function returning to normal during recovery 3
• There is significant controversy regarding whether thyroid hormone replacement is beneficial in ESS 1, 5
• Currently available data do not provide clear evidence of benefit from thyroid hormone treatment in ESS 5
• The focus of management should be on treating the underlying illness rather than correcting the thyroid hormone abnormalities 2, 3

Pitfalls and Caveats

• ESS can be mistaken for true hypothyroidism, potentially leading to unnecessary thyroid hormone treatment 2
• Interpretation of thyroid function tests in critically ill patients is challenging, particularly without baseline values from before the illness 1
• Medications commonly used in critically ill patients (such as glucocorticoids, dopamine, and amiodarone) can further alter thyroid function tests 3
• When evaluating abnormal thyroid function tests in acutely ill patients, clinicians should consider ESS before diagnosing primary thyroid dysfunction 2, 4