Treatment of Hypothyroidism That Contains Liothyronine is Associated With Reduced Risk of Dementia and Mortality.

Patients with hypothyroidism showed approximately 1.4-fold higher risk of dementia compared to controls, even when TSH levels were normalized.

• Retrospective cohort study analyzed TriNetX data comparing 1.26 million patients with hypothyroidism to 3.32 million controls
• Follow-up period was 20 years
• Risks were most pronounced when TSH levels were off-target
• Propensity score matching was used to balance covariates for age, sex, and comorbidities
• Adjusted hazard ratios were obtained via Cox proportional hazard modeling

Patients with hypothyroidism showed greater than 2.0-fold increase in mortality compared to controls, even with normal TSH levels.

• Mortality risk was assessed over 20 years of follow-up
• The increased mortality risk was present even when TSH levels were normalized with standard LT4 therapy
• Risks were most pronounced when TSH levels were off-target
• The study population included 1.26 million hypothyroid patients and 3.32 million controls

A parallel systematic review and meta-analysis of 12 studies confirmed a 1.4-fold heightened dementia risk associated with hypothyroidism.

• Meta-analysis included 12 studies evaluating dementia risk in hypothyroidism
• The meta-analysis result of a 1.4-fold risk increase was consistent with the cohort study findings
• This was conducted as a parallel analysis alongside the retrospective cohort study

Combination therapy containing T3 (LT4 + T3 or desiccated thyroid extract) was associated with 27% lower dementia risk compared to LT4 monotherapy.

• Relative risk analysis in propensity score matched cohorts showed 27% lower dementia risk with combination therapy
• The adjusted Cox model (hazard ratio) showed a 16% reduction in dementia risk for combination therapy patients
• Comparison was made between LT4 monotherapy versus combination therapy (LT4 + T3 or desiccated thyroid extract)
• Propensity score matching was used to balance cohorts before comparison

Combination therapy containing T3 was associated with 31% lower mortality risk compared to LT4 monotherapy.

• Relative risk analysis in propensity score matched cohorts showed 31% lower mortality risk with combination therapy
• The adjusted Cox model (hazard ratio) showed a 25% reduction in mortality for combination therapy patients
• Three treatment groups were studied: LT4 alone, LT4 + T3, and desiccated thyroid extract
• The reduction in mortality was observed over 20 years of follow-up

Hypothyroidism remained associated with heightened risks of dementia and mortality despite standard LT4 therapy achieving normal TSH levels.

• Standard levothyroxine (LT4) therapy may not fully address all risks associated with hypothyroidism, especially cognitive decline, dementia, and mortality
• Risks of dementia (~1.4-fold) and mortality (>2.0-fold) persisted even with TSH normalization
• Risks were most pronounced when TSH levels were off-target, suggesting a dose-response relationship with thyroid function
• The study authors note that further studies are needed to confirm the cognitive and survival benefits of T3-containing regimens

Atrial fibrillation was included as an outcome measure in the study alongside dementia and mortality.

• Outcomes measured included dementia, atrial fibrillation, and mortality
• The study analyzed TriNetX data with 20 years of follow-up
• Specific results for atrial fibrillation were not detailed in the abstract