Thyroid antibodies and levothyroxine effects in subclinical hypothyroidism: A pooled analysis of two randomized controlled trials.

Positive anti-TPO antibody status did not modify the effect of levothyroxine on Hypothyroid Symptoms scores.

• Adjusted between-group difference for positive antibodies: -2.07 (95% CI: -6.04 to 1.90)
• Adjusted between-group difference for negative antibodies: 0.89 (95% CI: -1.76 to 3.54)
• P for interaction = 0.31, indicating no statistically significant effect modification
• Outcomes measured as 1-year change in Hypothyroid Symptoms score on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire

Positive anti-TPO antibody status did not modify the effect of levothyroxine on Tiredness scores.

• Adjusted between-group difference for positive antibodies: 1.75 (95% CI: -3.60 to 7.09)
• Adjusted between-group difference for negative antibodies: 1.14 (95% CI: -1.90 to 4.19)
• P for interaction = 0.98, indicating no statistically significant effect modification
• Outcomes measured as 1-year change in Tiredness score on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire

The pooled analysis included 660 participants aged 65 years or older with persistent subclinical hypothyroidism, of whom 28.5% had positive anti-TPO antibodies.

• Total sample: 660 participants, 54% women
• 188 participants (28.5%) had positive anti-TPO at baseline
• Data were pooled from two RCTs: the Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism trial and the IEMO 80+ trial
• Participants were randomly assigned to receive levothyroxine (LT4) or placebo

Positive anti-TPO antibodies were not associated with better quality of life, improvement in handgrip strength, or fewer cardiovascular outcomes with levothyroxine treatment.

• No statistically significant treatment effect modification by antibody status was found for any of the clinical outcomes assessed
• Outcomes assessed included hypothyroid symptoms, tiredness, handgrip strength, and cardiovascular outcomes
• The two primary outcomes were 1-year changes in Hypothyroid Symptoms and Tiredness scores

Antithyroid antibodies increase the likelihood of developing overt hypothyroidism, but no large RCT had previously assessed whether their presence modifies the benefit of levothyroxine treatment in older adults with subclinical hypothyroidism.

• The clinical utility of antithyroid antibody testing in the context of treatment decisions for subclinical hypothyroidism remained unclear prior to this study
• This pooled analysis of individual participant data from two RCTs was designed to address this gap
• The study focused specifically on adults aged ≥65 years with persistent subclinical hypothyroidism