Conventional HDL Subclass Measurements Mask Thyroid Hormone-dependent Remodeling Activity Sites in Hypothyroid Individuals.

CONTEXT: Earlier nuclear magnetic resonance spectroscopy (NMR) studies of plasma lipoproteins estimated by size as small, medium, and large particles, demonstrated hypothyroidism was associated with increases in very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and intermediate-density lipoprotein (IDL) subclass particle number but variable changes in the high-density lipoprotein (HDL) subclasses. These disparate changes in HDL might be explained by reduced activity of the thyroid hormone-dependent remodeling proteins whose subclass specificity may be obscured when the 5 HDL subclasses identified by NMR are combined by size.

OBJECTIVE: This work aimed to determine whether directional changes in particle number of individually measured HDL subclasses correlate with reduced activity of their thyroid hormone-dependent remodeling proteins in hypothyroid individuals.

METHODS: VLDL, LDL, IDL, and HDL subclasses were measured by NMR in 13 thyroidectomized individuals 1 month following thyroid hormone withdrawal and 3 months after replacement. Changes in particle numbers in each subclass were compared when expressed individually and by size.

RESULTS: Following thyroid hormone withdrawal, plasma lipids and VLDL, LDL, and IDL subclass particle number increased. HDL particle number nearly doubled in very small HDL-1 ( P = .04), declined in small HDL-2 ( P = .02), and increased 2-fold in HDL-5 ( P = .0009).

CONCLUSION: The increment in HDL-1 and decline in HDL-2 subclasses is consistent with their precursor-product relationship and reduced lecithin cholesterol acyltransferase activity while the almost 2-fold increase in large HDL-5 is indicative of diminished action of hepatic lipase, phospholipid transfer protein, and endothelial lipase. These findings are inapparent when the 5 subclasses are expressed conventionally by size. This linking of specific HDL subclasses with HDL remodeling protein function provides new details about the specificity of their interactions.