Objective:

To examine the association between thyroid-stimulating hormone (TSH) levels and risk of sepsis and severe infectious diseases using both observational and Mendelian randomization analyses.

Approach:

• Observational Analysis: Baseline TSH measurements were collected from adults in the Trøndelag Health Study (HUNT Study) and linked to hospital records for infectious diseases. Cox regression was used to assess the association between TSH levels and sepsis risk.
• Mendelian Randomization Analysis: Uncorrelated single-nucleotide polymorphisms associated with TSH levels were extracted from genome-wide association studies, and genetic associations with sepsis risk were analyzed using data from the UK Biobank.
• Secondary Analyses: Examined other thyroid function measures and their association with sepsis, lower respiratory tract infections (LRTI), and upper urinary tract infections (UUTI).

Key Findings:

• No association between baseline normal-range TSH and sepsis risk in observational analyses (HR 0.98, 95% CI 0.93–1.04 per mU/L increase).
• TSH levels <0.5 mU/L were associated with higher sepsis risk (HR 1.50, 95% CI 1.19–1.90).
• Mendelian randomization analyses showed no association between normal-range TSH and sepsis risk (OR 1.04, 95% CI 0.98–1.10 per SD increase).
• Secondary analyses indicated no link between thyroid function and risk of sepsis, LRTI, or UUTI.

Interpretation:

Variation in baseline thyroid function in the general adult population does not influence the risk of sepsis, LRTI, or UUTI.

Limitations:

• The study focused on a specific population and may not generalize to other demographics.
• Potential residual confounding despite adjustments in analyses.

Conclusion:

Mild deviations in thyroid function within the reference range are unlikely to be useful targets for sepsis risk assessment.