Euthyroid sick syndrome

Overview

Euthyroid Sick Syndrome (ESS), also known as Non-Thyroidal Illness Syndrome (NTIS), is a condition in which individuals with no intrinsic thyroid disease exhibit abnormal thyroid function test results, typically during periods of acute or chronic illness. Despite the altered levels of thyroid hormones, the thyroid gland itself remains structurally and functionally normal. ESS is commonly seen in hospitalized or critically ill patients, and the changes are considered an adaptive response of the body to stress or illness rather than a sign of primary thyroid dysfunction.

Causes

Euthyroid Sick Syndrome occurs in response to systemic illness and is believed to result from altered metabolism of thyroid hormones. It can be triggered by:

• Acute illnesses: Sepsis, myocardial infarction, trauma, or surgery

• Chronic conditions: Chronic kidney disease, liver disease, cancer, or malnutrition

• Inflammatory states: Including autoimmune diseases or severe infections

• Use of certain medications: Glucocorticoids, dopamine, amiodarone, and others can interfere with thyroid hormone metabolism

• Fasting or starvation: Leads to reduced conversion of T4 to active T3

The exact mechanism involves altered deiodinase activity, changes in hormone binding proteins, and disrupted hypothalamic-pituitary-thyroid axis signaling.

Symptoms

There are typically no specific symptoms attributable solely to Euthyroid Sick Syndrome. Clinical features are usually overshadowed by the underlying illness. However, in rare cases with extremely low thyroid hormone levels, patients may exhibit signs resembling hypothyroidism, such as:

• Fatigue

• Bradycardia

• Cold intolerance

• Weight gain

• Constipation

These symptoms are nonspecific and usually attributed to the primary illness rather than ESS itself.

Diagnosis

ESS is diagnosed based on thyroid function tests in the context of acute or chronic illness. Key diagnostic findings include:

• Low total or free T3 (most common finding)

• Normal or low T4

• Normal or low TSH

• Reverse T3 (rT3) elevated: Due to impaired clearance and decreased T4 to T3 conversion

Diagnosis is made by excluding primary thyroid disorders and correlating with the patient’s overall clinical condition. A careful history and examination are critical to avoid misdiagnosis.

Treatment

In most cases, no specific treatment for ESS is required. Management focuses on treating the underlying illness. Considerations include:

• Supportive care: Stabilizing the patient’s primary condition usually results in normalization of thyroid function

• Avoiding unnecessary thyroid hormone replacement: As it may disrupt the body’s adaptive response and potentially cause harm

• Thyroid hormone therapy: Considered only in rare cases with persistent low T3/T4 and clear clinical hypothyroid features, or in prolonged critical illness, and always under endocrinology guidance

Routine thyroid hormone replacement is generally not recommended unless true hypothyroidism is also diagnosed.

Prognosis

The prognosis of Euthyroid Sick Syndrome largely depends on the underlying illness rather than the thyroid hormone abnormalities. In most cases, thyroid hormone levels return to normal once the illness resolves. However, persistently abnormal thyroid function tests in recovering patients may warrant further evaluation. ESS itself is not life-threatening but may be a marker of disease severity in critically ill individuals.