A RADIOIMMUNOASSAY FOR MEASUREMENT OF 3,5,3'-TRIIODOTHYRONINE SULFATE - STUDIES IN THYROIDAL AND NONTHYROIDAL DISEASES, PREGNANCY, AND NEONATAL LIFE

A highly sensitive, specific, and reproducible RIA has been developed to measure T3 sulfate (T3S). Only T4 sulfate cross-reacted significantly (approximately 3%) in the RIA; rT3 sulfate, T4, T3, rT3, and diiodothyronine cross-reacted less than 0.01%. T3S was bound by thyronine-binding globulin and albumin in serum. The free fraction of T3S in four normal sera averaged 0.25% compared to a value of 0.35% for T3. Therefore, T3S was measured in ethanol extracts of serum. Recovery of the nonradioactive T3S added to serum averaged 92%. The dose-response curves of inhibition of binding of [I-125]T3S to anti-T3S antibody by serial dilutions of serum extracts were essentially parallel to the standard curve. The detection threshold of the RIA was 20 pmol/L (1.5 ng/dL). The coefficient of variation averaged 7.8% within an assay and 11% between assays. The serum concentration of T3S was (mean +/- SE) 76 +/- 7.2 pmol/L in normal subjects, 268 +/- 29 in hyperthyroid patients with Graves' disease, 92 +/- 28 in hypothyroid patients, 201 +/- 32 in patients with systemic nonthyroidal illnesses, 40 +/- 6.2 in pregnant women (15-31 weeks gestation), and 429 +/- 39 in cord sera of newborns; the values in hyperthyroidism, nonthyroidal illnesses, and newborns were significantly different from normal (P < 0.01). The mean concentration of T3S in ammniotic fluid samples at 15-31 weeks gestation (90 +/- 1.3 pmol/L) was significantly higher than the corresponding value in maternal serum (P < 0.05) and significantly lower than the corresponding value in newborn cord blood serum (P < 0.001). Oral administration of sodium ipodate (Oragrafin; 3 g) to two hyperthyroid patients was associated with a 76-190% increase in serum T3S at 8 h, followed by a gradual decrease to a nadir that was 25-60% of the baseline value 2-3 days after ipodate ingestion. We conclude that 1) T3S is a normal component of human serum, and its levels change substantially in several physiological and pathological conditions; 2) sulfation pathway plays an important role in the metabolism of iodothyronines in man; and 3) high serum T3S levels in newborns and low normal levels in pregnancy despite elevated thyronine-binding globulin levels may signify markedly different metabolism of T3S in the mother and fetus.