Comparative Effects of Thyroxin Analogues

DRIED THYROID SUBSTANCE or the pure natural hormoue s, L-thyroxin and L-triiodothyronine, effect a reduction in the serum total cholesterol of euthyroid individuals when administered in sufficient allmount.1-3 Their general clinical use to reduce elevated serum cholesterol levels in the hope of favorably influencing the course of atherosclerosis has been limited by two factors. When given in moderate dosage, dried thyroid substance effected a prompt reduction in serum cholesterol, but despite continuation of the hormone the reduction was not sustained. 4 This "escape" is presumed to be due to suppression of thyrotropin secretion byr the administered thyroid and consequent decrease in production of endogenous thyroid hormone. When the dose of administered hormone is increased to maintain a reduced serum cholesterol level, hypermetabolisnm manifested by an increased basal metabolic rate, tachycardia, and weight loss may occur. An ominous consequence of thyroid hormone administration to patients with coronary artery disease is the frequent inerease in severity of angina pectoris.5 If some modification of the chemical structure of L-thyroxin or L-triiodothyronine resulted in an analogue that largely retained the effect of the natural hormones on cholesterol metabolism but was sufficiently less active in its other metabolic effects, a way out of this dilemma would be available. In the rat the formic acid analogue of thyroxin, tetraiodothyroforinic acid, has been