Mechanism of serum cholesterol reduction by thyroid hormones in hypothyroidism.

Abstract

Abstract The mechanism of thyroid hormone-induced reduction of serum cholesterol was studied in 3 myxedematous patients given 3 H-cholesterol several weeks before the start of thyroid hormone therapy. The rate of cholesterol catabolism was measured by determining fecal end products of cholesterol metabolism, i.e., bile acids and cholesterol. The effect of thyroid hormones on cholesterol synthesis was assessed from the slope of the specific activity-time curve of serum cholesterol. The thyroid hormone-induced fall in the level of serum cholesterol was found to be associated with a marked increase in the fecal excretion of neutral steroids derived from circulating cholesterol. The output of bile acids and of unabsorbed dietary cholesterol increased less constantly. Enhanced cholesterol catabolism seemed to continue during the observation period of about 7 weeks when the serum cholesterol level was stabilized at a low level, indicating that either the synthesis of endogenous cholesterol was stimulated or the pool size of the exchangeable cholesterol was still decreasing. The unchanged or slightly decreased slope of the specific activity-time curve suggested, however, that synthesis was depressed or that cholesterol with a high specific activity was mobilized from the tissues to the circulation. Depending on the magnitude of this mobilization synthesis could actually have been even increased, and finally, when a new steady state on a low serum cholesterol level is attained, stimulated synthesis could alone balance the increased fecal steroid excretion.