Effects of Short-Term Hypothyroidism on the Lipid Transfer to High-Density Lipoprotein and Other Parameters Related to Lipoprotein Metabolism in Patients Submitted to Thyroidectomy for Thyroid Cancer

Abstract

Background: Elevation of low-density lipoprotein (LDL) cholesterol is the hallmark of the dyslipidemia observed in hypothyroidism, but alterations on high-density lipoprotein (HDL) plasma levels and metabolism are less understood. The aim of this study was to explore aspects of HDL metabolism and enzymes that act on HDL after a short period of overt hypothyroidism. Methods: Eighteen women (age 44 +/- 11 years; body mass index 27.9 +/- 5.2 kg/m(2)) were studied before total thyroidectomy for thyroid cancer, when they were euthyroid, and after thyroidectomy, in overt hypothyroidism for three weeks, following levothyroxine withdrawal for performance of a whole-body scan. Results: Thyrotropin and free thyroxine confirmed hypothyroidism; low thyroglobulin and radioiodine uptake indicated near absence of thyroid tissue. LDL cholesterol (125 +/- 35 vs. 167 +/- 40 mg/dL; p = 0.0002), HDL cholesterol (HDL-C; 39 +/- 8 vs. 46 +/- 10 mg/dL; p = 0.0025), non-HDL-C (149 +/- 38 vs. 201 +/- 46 mg/dL; p < 0.0001), unesterified cholesterol (53 +/- 10 vs. 70 +/- 16 mg/dL; p = 0.0003), apolipoprotein (apo) A-I (1.32 +/- 0.19 vs. 1.44 +/- 0.22 g/L; p < 0.04), and apo B (0.97 +/- 0.25 vs. 1.31 +/- 0.28 g/L; p < 0.0001) plasma concentrations were all higher in hypothyroidism compared to values in the euthyroid state, but triglycerides and Lp(a) were unchanged. There were no changes in HDL particle size and lipid composition, cholesteryl ester transfer protein and lecithin cholesterol acyltransferase concentrations and in paraoxonase-1 activity. Regarding the in vitro assay to estimate lipid transfer to HDL, there were no changes when comparing the euthyroid to the hypothyroid state, but when adjusted for HDL-C, the unesterified cholesterol (0.14 +/- 0.03 vs. 0.11 +/- 0.02; p < 0.0001), triglycerides (0.11 +/- 0.02 vs. 0.09 +/- 0.02; p < 0.0001), phospholipids (0.44 +/- 0.09 vs. 0.40 +/- 0.07; p = 0.0205), and esterified cholesterol (0.14 +/- 0.03 vs. 0.13 +/- 0.03; p = 0.0043) transfer to HDL were all diminished in hypothyroidism. Conclusions: In short-term hypothyroidism, HDL-C increased, but this did not increase the capacity of the HDL fraction to receive lipids or the activity of paraoxonase-1, the anti-oxidation enzyme associated to HDL.