MON-371 - Levothyroxine Dosing to Narrow Thyroid Stimulating Hormone Targets in Older Individuals

Introduction: In the US, approximately 10% of adults aged 65+ take levothyroxine (LT4) to treat hypothyroidism. The TSH reference range was determined from distributions in younger individuals, with current upper limits ranging from 3.8 to 5.3 mU/L. The Dosing of LT4 (DOT4) trial was designed to test the hypothesis that allowing a TSH of up to 7.0 mU/L has no adverse clinical consequences in older individuals already taking LT4 for hypothyroidism. In a blinded analysis of the first 50 completers, we sought to assess changes in LT4 dose and accuracy of titration to achieve narrow TSH goals.

Methods: We are currently conducting a randomized, parallel, double-blind clinical trial of two 6-month dosing strategies of LT4 in patients aged ≥ 65 years who are taking a stable dose of ≥1.2 mcg/kg/day of LT4 therapy (target enrollment=228). After a run-in period to attain a TSH of 0.5-2.0 mU/L, participants are randomized to maintain a TSH level of 0.5-2.0 mU/L (lower TSH group) or to attain a TSH of 5.5-7.0 mU/L (higher TSH group). We performed a blinded assessment of mean change and percent change in LT4 dose between baseline and 6 months in the first 50 completers. We also evaluated the accuracy of LT4 titration to achieve TSH levels in the target ranges by the 6-month visit.

Results: Participants were taking 75-175 mcg/d of LT4 and had a TSH of 0.5-2.0 mIU/L at randomization. Among the 25 participants randomized to the lower TSH group, the mean LT4 dose change to maintain TSH 0.5-2.0 mU/L was -3 mcg/d (range -18 to +25 mcg/d) and percent change in LT4 dose was -3% (range -19 to +22%). Among the 25 participants in the higher TSH group, the mean LT4 dose change was -33 mcg/d (range -4 to -62 mcg/d) and percent change was -31% (range -4 to -69%), with final doses of 25-143 mcg/d. At the final participant visit, 18/25 participants in the lower TSH group had a TSH value within the goal range of 0.5-2.0 mU/L (median, 1.08 mU/L; mean, 1.47 mU/L), with an achieved range of 0.48-2.73 mU/L plus an outlier of 6.37 mU/L. For those in the higher TSH group, 5/25 participants had a TSH value within the goal range of 5.5-7.0 mU/L (median, 5.94 mU/L, mean, 7.13 mU/L), with an achieved range of 2.48-14.20 mU/L plus an outlier of 22.13 mU/L. Only 2 TSH values overlapped between groups: 6.37 mU/L in the lower TSH group and 2.48 mU/L in the higher TSH group.

Conclusion: Participants in the lower TSH group largely remained within the 0.5-2.0 mU/L TSH range during the study, with an overall slight decrease in dose from their run-in dose. Participants in the higher TSH group showed variability in dose reductions required and TSH levels achieved, with some requiring substantial dose reductions when targeting a TSH level of 5.5-7.0 mU/L. More than 6-8 weeks was needed between dose adjustments to equilibrate LT4 doses in some participants. Full results of this ongoing study will guide evidence-based management strategies for older adults with hypothyroidism who take LT4.

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