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

From the Guidelines

Low TSH in the setting of viral sepsis is generally not concerning and typically represents a normal physiological response known as non-thyroidal illness syndrome (NTIS) or sick euthyroid syndrome. This condition is characterized by a reduction in TSH production by the pituitary gland as part of the body's stress response, which helps conserve energy during critical illness, as seen in viral sepsis 1. The focus should be on treating the underlying viral sepsis with appropriate antiviral medications if available, supportive care, and management of complications rather than addressing the transient thyroid test abnormalities.

Key Considerations

• The body undergoes hormonal adaptations during severe illness like viral sepsis, temporarily altering thyroid function tests without indicating true thyroid disease.
• Low TSH levels are usually accompanied by low or normal T3 levels and normal or slightly decreased T4 levels.
• No specific treatment for these thyroid abnormalities is typically needed during acute illness, as they generally resolve once the underlying viral sepsis improves.
• If the patient has pre-existing thyroid disease or if thyroid function tests remain abnormal after recovery from sepsis, further evaluation would be warranted.

Management of Viral Sepsis

• Antiviral therapy should be initiated as early as possible in patients with severe sepsis or septic shock of viral origin, as recommended by the Surviving Sepsis Campaign 1.
• Empiric broad-spectrum therapy with one or more antimicrobials should be used to cover all likely pathogens, including bacterial and potentially fungal or viral coverage 1.
• The antimicrobial regimen should be reassessed daily for potential de-escalation, and the treatment duration should be optimized based on accepted pharmacokinetic/pharmacodynamic principles and specific drug properties 1.

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.