Pathophysiology
— The primary mechanism for hypercholesterolemia in hypothyroidism is accumulation of LDL
cholesterol due to a reduction in the number of cell-surface receptors for LDL [24], resulting in
decreased catabolism of LDL. A decrease in LDL receptor activity has also been described [25].
The extent of upregulation of the LDL receptor by T4 therapy varies considerably in patients with
different polymorphisms of the LDL receptor gene. In one study, patients homozygous for one specific
genotype (-/-) had a fourfold greater reduction in serum cholesterol during T4 therapy than those who
were homozygous for a different genotype (+/+) [26].
Other mechanisms also may affect the serum cholesterol concentration in hypothyroidism:
●LDL oxidation is significantly increased in hypothyroid patients, the degree of which is directly related
to the serum LDL cholesterol concentration [27].
●Diminished secretion of cholesterol into bile has been demonstrated in hypothyroid rats [28].
●Reduced cholesteryl ester transfer (the net transfer of cholesterol from HDL to LDL and VLDL) in
hypothyroidism may minimize the increase in serum LDL cholesterol concentrations [29].
A different mechanism, reduced lipoprotein lipase activity, is responsible for the development of
hypertriglyceridemia in hypothyroidism [3,30]. The rate of synthesis of triglycerides was normal in one
study [30], but increased in another [31].
Chylomicron remnants accumulate in hypothyroidism and are cleared more rapidly during T4 treatment
[32].