l-Thyroxine contamination of pharmaceutical d-thyroxine: probable cause of therapeutic effect

Studies have shown that pharmaceutic preparations of the stereo isomers of thyroxine differ with respect to thyromimetic potency and lipid level-lowering effects. We applied a stereospecific assay for dextrothyroxine (DT₄) and levothyroxine (LT₄) to determine whether the biologic effects observed after the administration of (DT₄) (Choloxin; Flint Laboratories) resulted from inherent biologic activity of DT₄, conversion of (DT₄) to LT₄ in vivo, or LT₄ contamination of Choloxin tablets. Choloxin was administered in a dose of 8 mg/day for 5 mo to nine athyreotic subjects who were then treated with pharmaceutic LT₄ (Synthroid), 0.2 mg/day for an additional 5 mo. Analysis showed that LT₄ contamination of Choloxin tablets ranged from 0.50% to 2.30%. This degree of contamination resulted in physiologically significant doses of LT₄ in the 8 mg/day doses of Choloxin. During the treatment with two different lots of Choloxin, serum LT₄ accounted for 33% to 53% of the measurable serum total thyroxine. The degree of LT₄ contamination in Choloxin tablets was sufficient to account for the observed serum LT₄ levels and casts doubt on the conclusions derived from previous studies in which Choloxin was used as the source of "(DT₄)".