Evaluation of a hypocholesterolemic agent. Dextrothyroxine sodium (Choloxin).
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In an attempt to determine the minimum dose of D-Thyroxine (D-T4) which will suppress pituitary TSH response to TRH, we have treated 6 euthyroid, hypercholesterolemic patients with graded doses of D-T4. TSH response was suppressed in 3 patients with 3 mg and in the remaining 3 patients with 4 mg D-T4 administered once daily. The mean TSH suppressive dose of 3.5 mg, as determined in this study, is considerably less than the 6 mg daily dose given to patients treated with D-T4 in the Coronary Drug Project. This suggests that the adverse effects observed with D-T4 treatment in the Coronary Drug Project may have been due to mild, undetected hyperthryroidism. D-T4 treatment in our patients was not associated with an increase in heart rate or ventricular ectopic beats as determined by Holter monitoring. However, bile samples obtained at the time of TSH suppression showed a significant increase in lithogenic index. In four patients, TSH suppressive doses of D-T4 were associated with a 12% decrease in mean cholesterol and a 17% decrease in mean LDL cholesterol concentrations.
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The dextroisomer of thyroxine (D-T4) has been shown to have suppressive effects on pituitary TSH secretion in euthyroid individuals and patients with mild thyroid hormone resistance. We treated a 3-year-old boy with D-T4 who was homozygous for a T3 receptor defect, resulting in a complex clinical picture of tissue-specific hyperthyroidism and hypothyroidism. There was no evidence of significant alteration in thyroid physiology, including serum concentrations of basal and TRH stimulated TSH or echocardiographic parameters measuring systolic time interval. We conclude that D-T4 at a daily dose of 6 mg (0.65 mg/kg) was ineffective in this boy with homozygous dominant negative thyroid hormone resistance.
Two patients are reported who presented with clinical hyperthyroidism, increased serum thyroid function studies, and depressed radioactive iodine uptake, secondary to chronic ingestion of D-T4. Symptoms abated, and function studies returned to normal, following discontinuation of D-T4. This uncommon effect of D-T4 may be more prevalent than is generally realized and must be recognized as another potential cause of low radioiodine uptake in patients with clinical hyperthyroidism.
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