What is euthyroid sick syndrome (ESS)?

Euthyroid Sick Syndrome (ESS)

Euthyroid sick syndrome is a condition characterized by abnormal thyroid function tests in patients with acute or chronic systemic illnesses who do not have intrinsic thyroid disease, representing an adaptive response to illness aimed at reducing the body's metabolic rate during severe physiological stress. 1, 2

Definition and Characteristics

Euthyroid sick syndrome (ESS), also known as Non-thyroidal Illness Syndrome (NTIS) or "sick euthyroid syndrome," presents with the following laboratory findings:

• Primary features:

  • Low serum triiodothyronine (T3) levels
  • Normal or low thyroxine (T4) levels
  • Normal or low thyroid-stimulating hormone (TSH) levels
  • Elevated reverse T3 (rT3) levels 2, 3

• Clinical context:

  • Occurs in patients with acute or chronic systemic illnesses
  • No intrinsic thyroid disease present
  • Affects 60-70% of critically ill patients 2

Pathophysiology

Multiple mechanisms contribute to ESS development:

• Decreased peripheral conversion of T4 to T3 due to reduced 5'-deiodinase activity (a selenoprotein) 3
• Alterations in TSH regulation
• Changes in thyroid hormone binding to transport proteins
• Presence of binding inhibitors that displace T4 from binding proteins
• Altered receptor binding and intracellular uptake
• Medication effects on thyroid hormone metabolism 2, 4

Clinical Variants

ESS presents in different patterns:

1. Type I (Low T3 syndrome): Most common form (68.5% prevalence)

   • Decreased T3 with normal T4 and TSH
   • Due to decreased peripheral conversion of T4 to T3

2. Type II (Low T3, Low T4): More severe form (15.7% prevalence)

   • Associated with poorer prognosis
   • Low T3 and T4 levels with normal or low TSH

3. Type III (High T4): Least common form (1.9% prevalence)

   • Often seen in acute psychiatric and liver diseases 3, 5

Clinical Significance and Prognosis

• ESS typically develops around the third day of hospitalization in critically ill patients 5
• The severity of ESS correlates with disease severity and clinical outcome
• Type II ESS (low T3, low T4) is associated with higher mortality rates
• Elevated reverse T3 (rT3) >0.61 ng/mL has prognostic value for poor outcomes 5
• In heart failure patients, 44.29% exhibit low T3 levels, with a negative correlation between NT-proBNP levels, Boston score, and total T3 1

Diagnosis

• ESS is a diagnosis of exclusion after ruling out primary thyroid disorders
• Key diagnostic features:
  • Abnormal thyroid function tests in the context of acute or chronic illness
  • No history of thyroid dysfunction
  • No use of medications affecting thyroid function
  • Normalization of thyroid function as the underlying illness resolves 2

Management Approach

• Treatment of underlying condition:

  • ESS typically resolves as the primary illness improves
  • Thyroid function generally returns to normal as acute illness resolves 2

• Thyroid hormone supplementation:

  • Currently, there is insufficient evidence to support routine thyroid hormone replacement in ESS
  • Clinical studies have not demonstrated clear benefits of treatment with thyroid hormone in ESS 4
  • The condition appears to be a mix of physiologic adaptation and pathologic response to acute illness

Special Considerations

• ESS must be distinguished from true thyroid dysfunction
• Medications can significantly influence thyroid parameters in critically ill patients
• Nutritional status affects thyroid function and should be considered in evaluation
• In patients with suspected coexisting thyroid disease, further evaluation with thyroid antibodies, ultrasound, and thyroid scan may be necessary 3

Monitoring

• Regular monitoring of thyroid function as the underlying illness resolves
• In heart failure patients with ESS, monitoring for anemia is important (particularly in male patients) 1
• No specific therapeutic intervention with thyroid hormones is recommended for patients with various forms of ESS 3

ESS represents an important adaptive mechanism during critical illness, and understanding its patterns helps clinicians avoid unnecessary thyroid hormone treatment while focusing on managing the underlying condition.