Selective Levothyroxine Discontinuation May Help Mitigate Neurologic and Cardiovascular Risks

Discontinuing levothyroxine treatment is feasible in a meaningful subset of older adults, according to the results of a Dutch prospective study published in JAMA. Nearly 26% of participants aged 60 years or older who remained off treatment for 1 year maintained a thyrotropin (TSH) level below 10 mIU/L and a free thyroxine level within the reference range. However, most participants did not successfully discontinue treatment. Given the increased risk of cognitive impairment, atrial fibrillation, and fractures associated with overtreatment and iatrogenic thyrotoxicosis, the authors suggest that evaluation of the need to continue levothyroxine therapy should be considered in adults aged 60 years or older, especially if they are taking a dose of 50 μg/d or lower.

The open-label, single-group prospective study enrolled 370 community-dwelling adults from 58 general practices in the Netherlands who had taken a stable levothyroxine dose of ≤150 µg/day for at least 1 year and had a baseline TSH level <10 mIU/L (median age, 70.5 years; 79.5% female; median baseline dose, 50 µg/day [mean, 84 μg/day]). Investigators used a protocol-driven stepwise dose-reduction schedule that included up to 6 reductions, with thyroid function testing at least every 6 weeks and a 1-year reassessment of thyroid status, symptoms, and patient-reported outcomes, including the Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO-39) scale and EuroQol Questionnaire.

Key Findings

• Successful discontinuation occurred in 95 of 370 participants (25.7%; 95% CI, 21.5% to 30.4%). At 1 year, those 95 participants had a median TSH of 5.03 mIU/L (range, 1.56 to 9.40 mIU/L) and a mean free thyroxine level of 1.01 ng/dL (range, 0.80 to 1.43 ng/dL).
• Lower baseline levothyroxine dose predicted success: 63.6% of participants taking 50 μg/day or less (n=88) and 44.9% taking 75 μg/day or less (n=176) discontinued treatment successfully.
• Thyroid-related quality of life, fatigue, and general health changes did not exceed minimal clinically important differences overall, and hypothyroid symptoms were reported less often in successful than unsuccessful discontinuers (15% vs 30%).
• Seventeen serious adverse events, including 2 deaths, occurred during follow-up, but none were considered study-related.

Source

Ravensberg J, Gussekloo J, Le Cessie S, et al. Discontinuation of levothyroxine in adults aged 60 years or older. JAMA. Published online April 06, 2026. doi:10.1001/jama.2026.2864