Lipoprotein alterations, hepatic lipase activity, and insulin sensitivity in subclinical hypothyroidism: response to L-T(4) treatment

Thyroid. 2007 May;17(5):453-60. doi: 10.1089/thy.2006.0302.

Abstract

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 pro-atherogenic 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) 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.

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 pro-atherogenic pattern in sH. Treatment with L-T(4), however, did not correct the basal lipid derangement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cholesterol, LDL / blood
  • Female
  • Humans
  • Hypothyroidism / drug therapy*
  • Hypothyroidism / metabolism
  • Insulin Resistance*
  • Lipase / metabolism*
  • Lipoproteins, LDL / metabolism*
  • Middle Aged
  • Thyrotropin / blood
  • Thyroxine / therapeutic use*
  • Triglycerides / blood

Substances

  • Cholesterol, LDL
  • LIPC protein, human
  • Lipoproteins, LDL
  • Triglycerides
  • oxidized low density lipoprotein
  • Thyrotropin
  • Lipase
  • Thyroxine