Retinol-binding protein and retinol levels in levothyroxine- treated hypothyroid patients: A cross-sectional pilot study

Objectives: Persistent metabolic abnormalities may occur in hypothyroid patients despite levothyroxine (LT4) therapy. This study evaluated serum retinol and retinol-binding protein (RBP) levels in LT4-treated hypothyroid patients and their association with thyroid function, disease severity, and autoimmunity. Materials and Methods: A cross-sectional pilot study was conducted in 120 participants, including 60 LT4-treated hypothyroid patients and 60 healthy controls. Thyroid profile, lipid parameters, serum retinol, and RBP levels were measured. Subgroup analyses were performed based on Hashimoto’s thyroiditis and overt versus subclinical hypothyroidism, including patients receiving LT4 therapy (median duration 48 months). Statistical analysis: Data are presented as mean ± SD for parametric and median (interquartile range) for non-parametric variables. Student’s t -test/Analysis of variance for parametric and the Kruskal-Wallis test were used for non-parametric tests to compare between groups. Correlations were assessed using Spearman’s rank correlation test. Multivariate linear regression analysis was performed to identify independent predictors of serum retinol and RBP levels. p < 0.05 was considered statistically significant. Results: Hypothyroid patients showed significantly lower free triiodothyronine (T3) and free thyroxine (T4) levels, with higher thyroid-stimulating hormone levels than controls. Serum RBP levels were significantly reduced, whereas retinol showed a non-significant decline. Lower retinol and RBP levels were observed in Hashimoto’s thyroiditis and overt hypothyroidism. Free T3, free T4, and RBP independently predicted serum retinol levels. Conclusions: LT4-treated hypothyroid patients demonstrated alterations in retinoid biomarkers, particularly reduced RBP levels. These changes were more pronounced in autoimmune and overt hypothyroidism and were associated with persistent metabolic alterations despite therapy. Given the cross-sectional design, causal inferences cannot be made, and larger prospective studies are needed to determine the clinical utility of RBP in hypothyroidism.