Treatment with levothyroxine does not yield clear effects on cardiometabolic biomarkers in older adults with subclinical hypothyroidism, according to a study. However, individuals with baseline thyroid-stimulating hormone (TSH) ≥10 mIU/L show potentially favourable changes in lipids and lipoproteins.
“Levothyroxine treatment showed no lipid-lowering benefit in the general older population with subclinical hypothyroidism,” said the researchers, who conducted post hoc analyses using baseline and 12-month data from two randomized controlled trials (RCTs) in older adults aged ≥65 years with subclinical hypothyroidism.
Cardiometabolic markers assessed included clinically relevant lipid measures (apolipoprotein B [ApoB], total cholesterol [TC], nonhigh-density lipoprotein cholesterol [non-HDL-C], remnant cholesterol [RC], low-density lipoprotein cholesterol [LDL-C], HDL-C, and triglycerides) and 167 standardized metabolomic measures from nuclear magnetic resonance. Analyses were further stratified by baseline TSH levels.
Of the 286 participants (median age 75 years, 48 percent women, median baseline TSH 6.44 mIU/L), 142 were randomized to levothyroxine. [J Clin Endocrinol Metab 2026;111:2445-2455]
Levothyroxine treatment delivered no clear effects on ApoB (‒0.03 g/L, 95 percent confidence interval [CI], ‒0.07 to 0.00), TC (‒0.17 mmol/L, 95 percent CI, ‒0.34 to 0.00), non-HDL-C (‒0.15 mmol/L, 95 percent CI, ‒0.31 to 0.00), RC (‒0.09 mmol/L, 95 percent CI, ‒0.16 to ‒0.01), LDL-C (‒0.07 mmol/L, 95 percent CI, ‒0.15 to 0.02), and triglycerides (‒0.07 mmol/L, 95 percent CI, ‒0.15 to 0.01).
Notably, potential changes occurred in 27 participants with baseline TSH ≥10 mIU/L for all clinically relevant lipids except HDL-C, as well as for ApoB-containing lipoproteins, very LDL size, and fatty acids (p<0.05, but not significant after multiple-testing correction).
“Our findings support current guidelines that potential levothyroxine treatment in older adults with subclinical hypothyroidism should take into account baseline TSH concentrations, highlighting the importance of personalized treatment strategies and future well-designed clinical trials,” the researchers said.
Overt hypothyroidism
In previous studies, treatment with levothyroxine resulted in improved lipid profile for individuals with overt hypothyroidism, with noticeable effects on lowering TC, LDL-C, and ApoB. [J Clin Endocrinol Metab 2020;105:3683‐3694]
“However, the efficacy of levothyroxine treatment on the lipid profile in people with subclinical hypothyroidism is less clear, especially in the context of different population characteristics and sample sizes,” the researchers said.
Meta-analyses of RCTs revealed the effects of levothyroxine on lowering TC and LDL-C, and one study demonstrated lipid-lowering effects in individuals with mild subclinical hypothyroidism. [Endocr Connect 2017;6:188‐199; Clin Endocrinol (Oxf) 2017;87:1‐9]
“Although our study did not observe any significant effects for TC or other lipids in the full study population, the observed direction of estimates was consistent with those observed in previous studies,” the researchers said.
The null effects seen in the current study could be driven by a combination of modest effect sizes and a relatively small sample size, according to the researchers, adding that earlier studies focused on conventional lipids (ie, LDL-C and TC).
A previous report supports the current findings on RC, as well as suggestive evidence for other lipids, showing substantial reductions in TC, non-HDL-C, RC, and ApoB levels following levothyroxine use. [J Clin Endocrinol Metab 2007;92:608‐611]
Thyroid dysfunction has been linked to ageing processes and the development of age-related diseases, including cardiovascular disease, according to the researchers. [Nat Rev Endocrinol 2024;20:5‐15; Endocr Rev 2013;34:556‐589]