Lipoprotein alterations, hepatic lipase activity, and insulin sensitivity in subclinical hypothyroidism:: Response to L-T4 treatment

Subclinical hypothyroidism (sH) has been associated with atherosclerotic cardiovascular disease even in the absence of hypercholesterolemia. Objective: Our study was designed to assess the hypothesis that other proatherogenic parameters, such as qualitative lipoprotein changes and insulin resistance, might be present in sH. Design and methods: 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. Main Outcome: 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) mu mol 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. Conclusions: 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 proatherogenic pattern in sH. Treatment with L-T-4, however, did not correct the basal lipid derangement.