Increased urinary thyroxine sulfate excretion in thyroxine therapy

Although increased thyroxine sulfate (T4S) levels have recently been detected in fetal serum and amniotic fluid, changes in patients in a high thyroxine (T4) state remain unclarified. This study was conducted to determine the changes in T4S in thyroid hormone regulation in women receiving suppressive T4 therapy. With a highly sensitive and specific radioimmunoassay, we measured the serum and urinary concentrations of T4S in 16 premenopausal women with benign nodular goiter before and after three months administration of T4 (3.2 micrograms/kg/day). Serum levels of other thyroid hormones were also measured. Significant increases in mean serum T4 levels post-treatment (11.1 vs. 6.6 micrograms/dL pre-treatment; P < 0.01) were found, although only low T4S levels were detectable in serum both pre- and post-T4 treatment. The mean urinary or creatinine corrected urinary T4S values post-treatment were significantly increased (20 ng/dL or 396 ng/g creatinine vs. 12 ng/dL or 174 ng/g creatinine pre-treatment, P < 0.01). There was a significant correlation between increased creatinine-corrected urine T4S and increased serum free T4. Our results indicate that the sulfation of T4 may be related to the regulation of thyroid hormone metabolism in T4-treated subjects with relative hyperthyroxinemia.