抄録
An inherited deficiency of low density lipoprotein (LDL) receptors in familial hypercholesterolemia (FH) is assumed to be the cause of the decreased catabolism of LDL. In contrast, in hyperthyroidism there is an increased rate of LDL catabolism. A 58-year-old female patient with heterozygous FH revealed a normal level of serum cholesterol (193mg/dl) in coexistence of hyperthyroidism. After the therapy of hyperthyroidism with radioiodine the patient's lipid profile revealed an increased concentrations of cholesterol (Whole serum 338, VLDL 68, LDL 199, HDL 42mg/dl). There was a significant inverse correlation between her serum cholesterol levels and her serum thyroxine levels (r=-0.815, p<0.01).
Since LDL catabolism in vivo is thought to be mediated largely through the LDL receptor, the role of thyroid hormone in this receptor-mediated degradation of LDL was studied in human skin fibroblasts. Confluent cells were exposed to a medium containing 5% lipoprotein deficient serum prepared from a myxedematous patient by ultracentrifugation for 2 days with or without added triiodothyronine (T3). After 125I-LDL was added, the cells were incubated for 6 hours at 37°C for the determinations of 125I-LDL uptake and degradation. In the cells from 2 normal subjects, LDL uptake and degradation was enhanced 29% by preincubation with T3 (1.0μg/ml). In the cells from 2 heterozygous patients with FH, LDL uptake and degradation was enhanced 23% with T3(1.0μg/ml). While, in the cells from 2 homozygous patients with FH, no effect of T3 was observed. These results suggest that normal serum cholesterol levels in a heterozygous patient with FH result in part from an enhanced degradation of LDL by extrahepatic cells exposed to excess thyroid hormone.
