Matthew D Ettleson

Context The effectiveness of levothyroxine (LT4) in restoring thyroid hormone (TH) homeostasis, particularly serum thyroxine (T4) and triiodothyronine (T3) levels, remains debatable. Objective This work aimed to assess TH homeostasis in LT4-treated individuals using data from the Longitudinal Study of Adult Health in Brazil (ELSA-Brasil) study. Methods The ELSA-Brasil study follows 15 105 adult Brazilians (aged 35-74 years) over 8.2 years (2008-2019) with 3 observation points assessing health parameters including serum thyrotropin (TSH), free T4 (FT4), and free T3 (FT3) levels. We analyzed 186 participants that initiated treatment with LT4 during the study, and 243 individuals continuously treated with LT4 therapy. Results Initiation of therapy with LT4 resulted in an 11% to 19% decrease in TSH, an approximately 19% increase in FT4, and a 7% reduction in FT3 serum levels (FT3 dropped >10% in ∼40% of the LT4-treated patients). This was associated with an increase in triglyceride levels and utilization of hypolipidemic and antidiabetic medications. Participants continuously treated with LT4 exhibited a stable elevation in serum FT4 and a reduction in serum FT3 and TSH levels. While 115 participants (47.3%) had at least 1 serum FT4 levels above the control reference range (>1.52 ng/dL), 38 participants (15.6%) had at least 1 serum FT3 below the reference range (<0.23 ng/dL). Conclusion The present results challenge the dogma that treatment with LT4 for hypothyroidism restores TH homeostasis in all patients. A substantial number of LT4-treated patients exhibit repeated FT4 and FT3 levels outside the normal reference range, despite normal TSH levels. Further studies are needed to define the clinical implications of these findings.