Changes in the distribution and composition of high-density lipoproteins in primary hypothyroidism

Abstract

The distribution and composition of high-density lipoprotein (HDL) subclasses were investigated in 14 women with severe hypothyroidism who were studied before and during treatment. The plasma concentrations of triglycerides, total cholesterol, HDL cholesterol, and of the apoproteins (apo) A-I, B, and E were increased in the hypothyroid state, while the apo A-II levels did not change significantly. After normalization of the thyroid function tests, the lipid and apoprotein levels were similar to those of normal individuals. Isopycnic ultracentrifugation in the density range 1.020 to 1.210 g/mL showed increases of both cholesterol and apo B in very-low-density lipoprotein (VLDL) and in low-density lipoprotein (LDL). The distribution of the HDL subclasses was modified in the hypothyroid subjects; both the less dense HDL fraction (d 1.063 to 1.100 g/mL; HDL 2b), and the denser subclass (d 1.150 to 1.210 g/mL; HDL 3b+3c) were increased, while the intermediate density subfraction (d 1.100 to 1.150 g/mL; HDL 2a+3a) did not vary significantly. This redistribution of the HDL subfractions was associated with increased concentrations of cholesterol, phospholipid, and apo A-I in HDL 2b, and of phospholipid and apo A-I in DHL 3b+3c. Treatment of hypothyroidism decreased the concentrations of these fractions, and HDL 2a+3a became the major HDL subclass in the euthyroid state. The particle sizes within HDL subfractions, measured by polyacrylamide gradient gel electrophoresis, were identical in the untreated and treated patients. The increased mass of protein and lipid within HDL 2b and HDL 3b+3c could therefore be attributed to an accumulation of identical-sized particles. The overall lipid and protein composition of the HDL lipoproteins was similar before and during treatment. The apoprotein composition was however modified, due to the higher apo A-I to apo A-II ratio observed in the HDL subfractions. Analysis of the lipoprotein distribution of apo E by sepharose column chromatography revealed a marked increase in the apo E content of VLDL, while changes in HDL-associated apo E were less pronounced. The major effect of hypothyroidism on apo E metabolism therefore appears to be an enrichment of VLDL with apo E, resulting in a significant increase of the plasma apo E levels.