CHOLESTEROL 7-ALPHA-HYDROXYLASE ACTIVITY IN HYPOTHYROIDISM AND HYPERTHYROIDISM IN HUMANS

Alterations of serum cholesterol levels are well recognized findings i n hypothyroidism and hyperthyroidism. It remains unclear, whether thyr oid hormones may affect serum concentrations of cholesterol through ch anges in the activity of cholesterol 7 alpha-hydroxylase, the rate-lim iting enzyme in the catabolic conversion of cholesterol to bile acids. We determined serum concentrations of the bile acid precursor 7 alpha -hydroxy-4-cholesten-3-one, which reflects cholesterol 7 alpha-hydroxy lase activity in the liver, in 19 patients with hypothyroidism and in 10 patients with hyperthyroidism before and after treatment, respectiv ely. In patients with hypothyroidism, serum concentrations of choleste rol and LDL-cholesterol decreased by 33% (p < 0.0005) and 39% (p < 0.0 005), respectively, after replacement therapy with thyroid hormones. I n contrast, serum concentrations of 7 alpha-hydroxy-4-cholesten-3-one (21.7 +/- 15.8 ng/ml vs 24.5 +/- 18.1 ng/ml before treatment, n.s.) as well as serum HDL-cholesterol were unchanged during substitution ther apy. In patients with hyperthyroidism, serum concentrations of cholest erol and LDL-cholesterol increased by 27% (p < 0.01) and 39% (p < 0.01 ) after antithyroid treatment, respectively. Again, serum concentratio ns of 7 alpha-hydroxy-4-cholesten-3-one did not change significantly d uring treatment (15.8 +/- 12.6 ng/ml vs 14.7 +/- 8.1 ng/ml before trea tment, n.s.). These findings indicate that in humans, thyroid hormones influence serum lipid concentrations by other mechanisms than by affe cting the activity of cholesterol 7 alpha-hydroxylase.