Lower Serum Triiodothyronine Levels Constitute an Independent Risk Factor for Dyslipidemia in Levothyroxin-Treated Patients

Objective: Levothyroxine (LT4) is the standard treatment for hypothyroidism; yet many patients show reduced triiodothyronine (T3) levels despite normal thyrotropin (TSH). The clinical impact of the incomplete normalization of T3 homeostasis, including potential metabolic consequences, remains uncertain This study aimed to determine whether lower serum free T3 (FT3) levels in LT4-treated individuals constitute an independent risk factor for dyslipidemia. Methods: We analyzed data from the Longitudinal Study of Adult Health in Brazil (ELSA-Brasil), which followed 15 105 civil servants aged 35-74 over 3 study waves (2008-2019). Participants with preexisting dyslipidemia were excluded. Participants were categorized based on FT3 levels (≤0.28 ng/dL vs >0.28 ng/dL), and the incidence of dyslipidemia (defined as non-high-density lipoprotein cholesterol ≥160 mg/dL or statins use) was assessed. Multivariable logistic regression was used to determine the association between low FT3 level and development of dyslipidemia. Results: We identified 105 participants who developed hypothyroidism, initiated LT4 therapy, and achieved TSH normalization. Participants with FT3 ≤0.28 ng/dL had a significantly higher incidence of dyslipidemia (47.5% vs 27.3%, P = .036). FT3 ≤0.28 ng/dL remained a significant independent predictor of dyslipidemia after adjusting for confounders (adjusted OR: 3.558, 95% confidence interval: 1.173-12.045; P = .031). Other factors, including TSH, free thyroxine, body mass index, and smoking, were not significant. Conclusion: Low FT3 levels in LT4-treated patients represent an independent risk factor for dyslipidemia, even with normal TSH levels. This challenges the adequacy of TSH-centric management and supports the need for therapeutic strategies that ensure T3 homeostasis to mitigate dyslipidemia and cardiovascular risk.