Levothyroxine-liothyronine combo helps lower dementia, death risks in hypothyroidism patients

Patients with hypothyroidism receiving standard levothyroxine (LT4) therapy remain at increased risk for dementia and death, reveals a recent study. However, adjunct liothyronine (T3) may help reduce this risk compared with LT4 alone.

Data for this retrospective cohort study was derived from TriNetX, comprising 1.26 million patients with hypothyroidism (on LT4, LT4 plus T3, or desicated thyroid extract) compared with 3.32 million controls.

The researchers assessed outcomes, including dementia, atrial fibrillation, and mortality, over 20 years of follow-up and used propensity score matching to balance covariates for age, sex, and comorbidities. They also calculated the adjusted hazard ratios using Cox proportional hazard modelling. A parallel systematic review and meta-analysis of 12 studies assessed the risk of dementia in hypothyroidism.

Patients with hypothyroidism had an approximately 1.4-fold greater risk of dementia and a more than twofold increase in mortality, even with normal thyroid-stimulating hormone (TSH). These risks were most noticeable among patients with off-target TSH levels.

In the parallel meta-analysis, a 1.4-fold increased dementia risk was also found.

The relative risk analysis in cohorts formed by propensity score matching comparing LT4 monotherapy with LT4 plus T3 revealed a 27-percent lower dementia risk and a 32-percent lower mortality risk in favour of the combination therapy. Likewise, the adjusted Cox model showed 16-percent and 25-percent reductions in dementia and mortality risk for patients treated with LT4 plus T3.

“Despite standard LT4 therapy, hypothyroidism remains associated with heightened risks of dementia and mortality,” the researchers said. “Adding T3 may more effectively mitigate these risks than LT4 alone, but further studies are needed to confirm the cognitive and survival benefits of T3-containing regimens.”