Effects of Thyroid Hormone Replacement Therapy on Lipid Profiles in Patients With Hypothyroidism

Hypothyroidism is associated with dyslipidemia and increased cardiovascular risk. Thyroid hormone replacement therapy (THRT) restores thyroid function and may improve lipid metabolism. This study evaluated the effects of THRT on lipid profiles in hypothyroid patients and identified predictors of cardiovascular risk reduction.

A retrospective analysis was conducted on 350 patients with hypothyroidism (183 females, 52.3%; 167 males, 47.7%). The mean age was 48.6 ± 13.2 years (range 18-82). The mean BMI was 27.4 ± 4.9 kg/m², with 105 (30.0%) normal weight, 145 (41.4%) overweight, and 100 (28.6%) obese. At baseline, mean thyroid-stimulating hormone (TSH) was 16.3 ± 7.4 mIU/L and free thyroxine (FT4) was 0.84 ± 0.32 ng/dL. Lipid levels showed dyslipidemia: total cholesterol (TC): 238.5 ± 42.3 mg/dL, low-density lipoprotein cholesterol (LDL-C): 142.8 ± 31.5 mg/dL, high-density lipoprotein cholesterol (HDL-C): 44.7 ± 9.5 mg/dL, and triglycerides (TG): 176.4 ± 56.2 mg/dL.

After an average treatment duration of 18.4 ± 8.7 months, significant reductions were observed in TC (201.3 ± 36.5 mg/dL; -37.2 mg/dL, p < 0.001), LDL-C (118.6 ± 27.2 mg/dL; -24.2 mg/dL, p < 0.001), and TG (156.1 ± 51.3 mg/dL; -20.3 mg/dL, p < 0.001). HDL-C improved modestly (47.9 ± 10.4 mg/dL; +3.2 mg/dL, p < 0.001). Greater benefits were seen in patients with high baseline TSH and LDL-C. Patients with diabetes (n = 102, 29.1%), hypertension (n = 84, 24.0%), or both (n = 67, 19.1%) had lower rates of lipid improvement compared with those without comorbidities (n = 97, 27.7%). Machine learning models demonstrated modest accuracy (receiver operating characteristic curve-area under the curve (ROC-AUC): 0.51-0.56) but confirmed baseline lipids, thyroid hormones, comorbidities, and medication type as key predictors.

THRT significantly improved lipid profiles and reduced cardiovascular risk in hypothyroid patients, supporting its role as a cornerstone of comprehensive management.