Levothyroxine treatment response of cardiometabolic biomarkers in older adults with subclinical hypothyroidism

CONTEXT: Randomized controlled trials (RCTs) found no cardioprotective effects of levothyroxine therapy in older adults with subclinical hypothyroidism. OBJECTIVE: To assess levothyroxine effects on cardiometabolic biomarkers, which may serve as more sensitive treatment indicators. DESIGN: Post hoc analysis using (baseline and 12-month) data from two double-blind randomised controlled trials in older adults (≥ 65 years) with subclinical hypothyroidism. MAIN OUTCOME MEASURE(S): Cardiometabolic biomarkers included seven clinically relevant lipid measures (apolipoprotein B (ApoB), total cholesterol (Total-C), non-high-density lipoprotein cholesterol (non-HDL-C), remnant cholesterol (RC), low-density lipoprotein cholesterol (LDL-C), HDL-C, and triglycerides (TG)) and 167 standardised metabolomic measures from nuclear magnetic resonance. Analyses were additionally stratified by baseline TSH levels. RESULTS: Among 286 included participants (48% women; median age 75 [70, 82] years; median baseline TSH 6.44 [5.36, 7.81] mIU/L), 142 were randomized to levothyroxine. Overall, levothyroxine showed no effects on ApoB (-0.03 [95% CI: -0.07, 0.00] g/L), Total-C (-0.17 [-0.34, 0.00] mmol/L), non-HDL-C (-0.15 [-0.31, 0.00] mmol/L), RC (-0.09 [-0.16, -0.01] mmol/L), LDL-C (-0.07 [-0.15, 0.02] mmol/L), and TG (-0.07 [-0.15, 0.01] mmol/L). In participants with baseline TSH ≥10 mIU/L (n=27), potentially beneficial changes (P-values < 0.05, but not significant after multiple-testing correction) were observed for all clinically relevant lipids except HDL-C, as well as for ApoB-containing lipoproteins, VLDL size and fatty acids. CONCLUSION: In older adults with subclinical hypothyroidism, levothyroxine treatment showed no effects on cardiometabolic biomarkers, although potentially favourable changes in lipids and lipoproteins were observed for individuals with baseline TSH ≥ 10 mIU/L.