Chopra I J, Wu S Y, Teco G N, Santini F
Department of Medicine, University of California-Los Angeles Center for Health Sciences 90024-1682.
J Clin Endocrinol Metab. 1992 Jul;75(1):189-94. doi: 10.1210/jcem.75.1.1619009.
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 [125I]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 less than 0.01). The mean concentration of T3S in amniotic fluid samples at 15-31 weeks gestation (90 +/- 1.3 pmol/L) was significantly higher than the corresponding value in maternal serum (P less than 0.05) and significantly lower than the corresponding value in newborn cord blood serum (P less than 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.
已开发出一种高灵敏度、特异性和可重复性的放射免疫分析法（RIA）来测定硫酸化三碘甲状腺原氨酸（T3S）。在该放射免疫分析法中，只有硫酸化甲状腺素（T4）有显著交叉反应（约3%）；硫酸化反三碘甲状腺原氨酸（rT3）、T4、T3、rT3和二碘甲状腺原氨酸的交叉反应小于0.01%。血清中的T3S与甲状腺素结合球蛋白和白蛋白结合。与T3的0.35%相比，四份正常血清中T3S的游离部分平均为0.25%。因此，采用血清乙醇提取物来测定T3S。添加到血清中的非放射性T3S的回收率平均为92%。血清提取物系列稀释对[125I]T3S与抗T3S抗体结合的抑制作用的剂量反应曲线与标准曲线基本平行。该放射免疫分析法的检测阈值为20 pmol/L（1.5 ng/dL）。批内变异系数平均为7.8%，批间变异系数为11%。正常受试者血清T3S浓度为（均值±标准误）76±7.2 pmol/L，格雷夫斯病甲亢患者为268±29，甲减患者为92±28，全身性非甲状腺疾病患者为201±32，孕妇（妊娠15 - 31周）为40±6.2，新生儿脐血为429±39；甲亢、非甲状腺疾病和新生儿的值与正常水平有显著差异（P＜0.01）。妊娠15 - 31周羊水样本中T3S的平均浓度（90±1.3 pmol/L）显著高于母体血清中的相应值（P＜0.05），且显著低于新生儿脐血血清中的相应值（P＜0.001）。两名甲亢患者口服碘泊酸钠（Oragrafin；3 g）后，8小时时血清T3S升高76 - 190%，随后逐渐下降至最低点，在碘泊酸钠摄入后2 - 3天降至基线值的25 - 60%。我们得出结论：1）T3S是人体血清的正常成分，其水平在几种生理和病理状态下有显著变化；2）硫酸化途径在人类碘甲状腺原氨酸代谢中起重要作用；3）尽管甲状腺素结合球蛋白水平升高，但新生儿血清T3S水平高而孕期正常水平低，这可能表明母体和胎儿中T3S的代谢明显不同。
