A RADIOIMMUNOASSAY FOR MEASUREMENT OF THYROXINE SULFATE

A highly sensitive, specific, and reproducible RIA has been developed to measure T4 sulfate (T4S) in ethanol extracts of serum. rT3 sulfate (rT3S) cross-reacted 7.1%, and T3S Cross-reacted 0.59% in the RIA; T4, T3, rT3, and 3,3'-diiodothyronine cross-reacted 0.004% or less. The r ecovery of nonradioactive T4S added to serum averaged 95%. The detecti on threshold of the RIA was 18 pmol/L. The coefficient of variation av eraged 6.9% within an assay and 12% between assays. T4S was bound by T 4-binding globulin and albumin in serum. The free fraction of T4S in f our normal sera averaged 0.06% compared to a value of 0.03% for T4 (P < 0.001). The serum concentration of T4S was (mean +/- SE) 19 +/- 1.2 pmol/L in normal subjects, 33 +/- 10 in hyperthyroid patients with Gra ves' disease, 42 +/- 15 in hypothyroid patients, 34 +/- 6.9 in patient s with systemic nonthyroidal illnesses, 21 +/- 4.3 in pregnant women a t 15-40 weeks gestation, and 245 +/- 26 in cord blood sera of newborns ; the value in the newborn was significantly different from normal (P < 0.001). The mean concentration of T4S in amniotic fluid samples at 1 5-38 weeks gestation was 106 +/- 22 pmol/L (cf. normal adults; P < 0.0 01). Administration of sodium ipodate (Oragrafin; 3 g, orally) to hype rthyroid patients was associated with a transient increase in serum T4 S. The T4S content of the thyroid gland was less than 1/4000th that of T4. We conclude that 1) T4S is a normal component of human serum, and its levels are markedly increased in newborn serum and amniotic fluid ; and 2) the sulfation pathway plays an important role in the metaboli sm of T4 in man.