Comparison of Two Timings of Levothyroxine Intake in Hypothyroid Patients: A Cross-over Randomized Control Trial

Primary hypothyroidism is a common condition, affecting nearly 10% of the general population. Its treatment is levothyroxine, a synthetic thyroid hormone with a half-life of nearly eight days. Optimal absorption of levothyroxine occurs when it is taken on an empty stomach. It is generally recommended to take the medication in the morning, at least 30 minutes before breakfast. However, this treatment regimen can be challenging for some patients. Missed doses constitute a problem, leading some patients to choose another timing of intake. Other patients may find it difficult to wait before breakfast, resulting in suboptimal absorption, increased TSH levels, and poor disease control. Despite these challenges, American Thyroid Association guidelines recommend taking levothyroxine in the morning, in a fasting state, as the preferred timing of intake. They also suggest bedtime intake as a reasonable alternative, as long as the medication is taken at least three hours after the evening meal. As optimal levothyroxine absorption depends primarily on intake on an empty stomach, alternative treatment schedules could be considered, as long as the fasting requirement is respected to maintain stable TSH levels. To our knowledge, only one study has compared daytime levothyroxine intake, three hours after breakfast, with morning and bedtime intake. There was no significant difference in TSH levels between the different schedules. Confirming the stability of TSH levels with different schedules would offer patients with hypothyroidism greater flexibility in treatment timing, better adapted to their lifestyle habits. The aim of our study is to compare serum TSH levels according to two timings of levothyroxine intake in patients with hypothyroidism. Secondary objectives are to assess treatment adherence, quality of life, and patients' preferred timing of levothyroxine intake.