Cardiometabolic Outcomes and Levothyroxine Treatment Effects in Subclinical Hypothyroidism: A Systematic Review

Subclinical hypothyroidism (SCH) is a common biochemical thyroid disorder characterized by elevated thyroid-stimulating hormone (TSH) concentrations despite normal circulating free thyroxine levels. However, its cardiometabolic consequences and the clinical benefits of levothyroxine therapy remain incompletely established. This systematic review aimed to synthesize clinical evidence on cardiometabolic outcomes in adults with SCH and evaluate the reported effects of levothyroxine therapy or restoration of euthyroidism. Searches were conducted across major biomedical databases and supplementary sources from database inception to August 31, 2025, followed by an updated search through August 4, 2026. Eligible studies included randomized, nonrandomized interventional, and observational studies reporting at least one cardiometabolic outcome. Pooling of clinically comparable studies, including randomized trials reporting lipid outcomes, was considered. However, substantial differences in populations, SCH definitions, comparators, follow-up durations, outcome measures, and the availability of compatible effect estimates and variance data precluded meaningful meta-analysis; findings were synthesized narratively. Fifty reports representing 48 distinct study populations and at least 46,746 participants were included. SCH was associated with adverse lipid, vascular, metabolic, and cardiovascular findings, although the consistency and strength of evidence varied across domains. The strongest available evidence from larger placebo-controlled trials in older adults with mild SCH showed no clinically meaningful improvement in symptoms, carotid atherosclerosis, cardiac function, or overall cardiometabolic biomarkers despite biochemical reductions in TSH. Smaller or selected-population studies reported improvements in some lipid, endothelial, blood pressure, biomarker, or functional outcomes, but these subgroup benefits remain hypothesis-generating rather than established. Overall, the cardiometabolic effects of SCH appear heterogeneous and may vary according to age, disease severity, and comorbid conditions. Current evidence supports individualized, risk-based management rather than routine treatment based on TSH normalization alone.