THE EFFECTS OF VARIOUS CHLORINE DERIVATIVES OF THYRONINE ON SERUM CHOLESTEROL CONCENTRATION AND MYOCARDIAL STIMULATION IN RATS AND HUMANS

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Abstract
Chlorinated and iodinated thyronine derivatives were studied for their effects on serum and liver cholesterol and on hypertrophy of the cardiac ventricle in the rat. Compounds characterized by higher ratios of cholesterol to cardiac effects were found among the derivatives with the D-configuration and with chlorine atoms in the 3 and 5 positions. In the rat, some compounds-notably 35-dichloro-3[image]:5[image]-diiodo-D-thyronine (DCl2l2T) and 3:5:3[image]-trichloro -5[image]-iodo-D-thyronine (DCl3lT) -exerted a much greater effect on cholesterol metabolism than on the myocardium. DCl2l2T, 3;5:3[image]-trichloro-D-thyronine (DCl3T) and 3:5-dichloro-D-thyronine (DC12T) were administered to 30 hyper-cholesterolemic men with coronary heart disease. Although DCl2l2T produced no significant reduction of serum cholesterol concentration, DCl3T and DCl2T did; and all 3 substances caused symptoms of myocardial stimulation, usually angina. Therefore none of these compounds is regarded as suitable for administration to patients with coronary heart disease. DCl3T and DCl2T produced striking depression of the serum protein-bound iodine level, and this effect is discussed.

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