Novel Nutraceutical Combination Restores Hepatic Deiodinase Activity Under Inflammatory Conditions: Evidence from an In Vitro Model<b><i></i></b>

Background/Objectives Thyroid hormones, mainly triiodothyronine (T3) and thyroxine (T4), regulate cardiovascular function via effects on endothelial cells, blood pressure, myocardial performance, and lipid metabolism. T3 is predominantly produced by peripheral conversion of T4 by iodothyronine deiodinases, especially type 1 deiodinase (DIO1). Thyroid hormone levels adapt to metabolic and systemic conditions through the hypothalamic-pituitary-thyroid axis. The objective is to evaluate the prognostic significance of free T3/free T4 (fT3/fT4) ratio as an indicator of thyroid hormone metabolism and disease outcomes. Methods: The review analyzed existing evidence on the regulation of thyroid hormones, focusing on DIO1 activity and its modulation by conditions such as inflammation and malnutrition. It examined clinical studies measuring individual free hormone levels and their ratio, assessing correlations with disease prognosis and thyroid function in various patient populations, including those with non-thyroidal illness syndrome. Results: Single measurements of free T3 or free T4 showed limited prognostic value. However, the fT3/fT4 ratio proved more reliable in reflecting DIO1 activity and thyroid function. Lower ratios correlated with impaired hormone conversion, especially under chronic inflammatory states. Experimental data demonstrated downregulation of DIO1 by inflammatory mediators in liver cells, contributing to altered peripheral thyroid hormone metabolism. Conclusion: The fT3/fT4 ratio outperforms single hormone levels as a prognostic marker, particularly in frail and cachectic patients. It reflects underlying changes in hormone conversion and deiodinase function linked to chronic illnesses. This ratio may serve as a valuable clinical tool for assessing thyroid hormone status and disease prognosis.