Zinc and selenium in the management of subclinical hypothyroidism: mechanistic insights, clinical evidence, and translational perspectives

Abstract Subclinical hypothyroidism (SCH) is a prevalent endocrine disorder characterized by elevated serum thyroid-stimulating hormone (TSH) concentrations in the presence of normal circulating free thyroxine (fT4). Although frequently asymptomatic, SCH has been increasingly associated with adverse metabolic, cardiovascular, reproductive, and neurocognitive outcomes, as well as progression to overt hypothyroidism. Therapeutic decision-making remains controversial, particularly in individuals with mild TSH elevation below 10 mIU/L, where the clinical benefit of levothyroxine replacement therapy is inconsistent. Growing attention has therefore been directed toward modifiable metabolic contributors to thyroid dysfunction, including micronutrient status. Zinc and selenium are essential trace elements that participate in thyroid hormone synthesis, peripheral activation, receptor-mediated signaling, antioxidant defense, and immune modulation. Zinc is critical for thyroid hormone receptor structure and hypothalamic–pituitary regulation, whereas selenium is incorporated into iodothyronine deiodinases and antioxidant selenoproteins that preserve thyrocyte integrity. This narrative review synthesizes current mechanistic and clinical evidence supporting the adjunctive role of zinc and selenium in the management of SCH. While emerging data suggest potential biochemical and immunological benefits, heterogeneity in study design and duration necessitates well-powered randomized trials to define optimal dosing strategies and long-term clinical outcomes.