Lipoprotein Alterations, Hepatic Lipase Activity, and Insulin Sensitivity in Subclinical Hypothyroidism: Response to L-T4Treatment

Abstract

Subclinical hypothyroidism (sH) has been associated with atherosclerotic cardiovascular disease even in the absence of hypercholesterolemia. Our study was designed to assess the hypothesis that other pro-atherogenic parameters, such as qualitative lipoprotein changes and insulin resistance, might be present in sH. Twenty-one sH women were compared to 11 female controls matched for body mass index, menopausal status, and age. Before and after 6 months of levothyroxine (L-T(4)) treatment, we determined total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), apoB levels, hepatic lipase (HL) activity in postheparin plasma samples, the chemical composition and copper-induced oxidation in isolated LDL and homeostasis model assessment (HOMA), quantitative insulin sensitivity check index, and insulinogenic index. Lipid profiles were similar between the two groups. No differences in LDL oxidability or the insulin sensitivity assessment parameters were found. HL activity was significantly lower in the sH patients: median (range), 13.1 (2.5-26.7) vs. 18.7 (7.9-28.1) micromol free fatty acids/mL, p < 0.04. The LDL-cholesterol/LDL-TG ratio was decreased in sH: 3.9 (1.8-5.5) vs. 4.7 (3.5-6.8), p < 0.02. HL negatively correlated with thyroid-stimulating hormone (TSH) levels (r = - 0.504, p < 0.01) and positively with LDL-cholesterol/LDL-TG (r = 0.46, p < 0.02). Posttreatment results for all these parameters did not differ significantly compared to baseline. Increased levels of TSH are associated to a decrease in HL activity, explaining our findings of an LDL particle rich in TG. This qualitative lipoprotein alteration suggests a pro-atherogenic pattern in sH. Treatment with L-T(4), however, did not correct the basal lipid derangement.