Is a low Thyroid-Stimulating Hormone (TSH) level concerning in the setting of viral sepsis?

From the Guidelines

Low TSH in the setting of viral sepsis is generally not concerning as it typically represents a normal physiological response known as non-thyroidal illness syndrome (NTIS) or sick euthyroid syndrome. During severe illness like viral sepsis, the body undergoes hormonal adaptations that temporarily alter thyroid function tests without indicating true thyroid disease. The hypothalamic-pituitary-thyroid axis is suppressed as part of the body's stress response, leading to low TSH levels. This is considered an adaptive mechanism to conserve energy during critical illness rather than a primary thyroid disorder requiring treatment. These changes usually resolve spontaneously as the patient recovers from the underlying viral sepsis. No specific thyroid treatment is typically needed for these transient abnormalities, and management should focus on treating the underlying viral sepsis. Thyroid function tests should be repeated after recovery from the acute illness if there is concern about underlying thyroid disease. This approach prevents unnecessary thyroid medication in patients whose thyroid function will likely normalize with resolution of their critical illness, as seen in guidelines for managing sepsis and septic shock 1. It's also important to note that the provided evidence on immune checkpoint inhibitor therapy 1 does not directly apply to the management of low TSH in viral sepsis, as it pertains to a different clinical context. Therefore, the primary focus should remain on treating the viral sepsis and monitoring thyroid function as necessary, without initiating unnecessary thyroid treatment based on transient abnormalities in thyroid function tests. Key points to consider include:

• Low TSH in viral sepsis is often a normal response to critical illness
• No specific thyroid treatment is typically needed for these transient abnormalities
• Management should focus on treating the underlying viral sepsis
• Thyroid function tests should be repeated after recovery from the acute illness if there is concern about underlying thyroid disease.

From the Research

Low TSH in Viral Sepsis

• The relationship between low TSH levels and viral sepsis is not directly addressed in the provided studies, which primarily focus on the association between thyroid hormone levels and sepsis outcomes 2, 3, 4, 5, 6.
• However, several studies suggest that thyroid hormone disorders, including changes in TSH levels, are common in septic patients and may be associated with poor outcomes 3, 4, 5, 6.
• One study found that patients with septic shock had lower levels of free T3 (FT3) and free T4 (FT4), but no significant difference in TSH levels between survivors and non-survivors 4.
• Another study found that severe lymphopenic COVID-19 patients had significantly lower plasma concentrations of TSH, T4, FT4, and T3 compared to patients without lymphopenia 5.
• A study published in 2023 found that the median fT3 level was lower in the septic shock group compared to the sepsis group, and there was a significant correlation between the SOFA score and fT3 levels 6.

Thyroid Hormone Levels and Sepsis Outcomes

• Several studies suggest that low levels of thyroid hormones, such as FT3 and FT4, are associated with poor outcomes in septic patients, including increased mortality and organ dysfunction 2, 3, 4, 6.
• One study found that patients who died within 30 days had significantly lower levels of FT4 than survivors, and that FT3 and FT4 levels were significantly lower among non-survivors compared to survivors 2.
• Another study found that the areas under the receiver operating characteristic curves for FT3 and FT4 levels were associated with 28-day mortality, and were higher than that for SOFA, CRP, and lactate 4.

Limitations and Future Directions

• The provided studies have several limitations, including small sample sizes and variability in study design and outcomes 2, 3, 4, 5, 6.
• Further research is needed to fully understand the relationship between thyroid hormone levels and sepsis outcomes, and to determine whether thyroid hormone disorders are a cause or consequence of sepsis 3, 5.