TSH-receptor Antibodies Determined by the First, Second and Third Generation Assays and Thyroid-stimulating Antibody in Pregnant Patients with Graves' Disease

Abstract

Abstract. The measurement of TSH receptor antibody (TRAb) has been recommended to predict the risk of neonatal hyperthyroidism (NH) in pregnant women with Graves' disease (GD). For the first generation TRAb (TRAb1) assay with commercial kit (Brahms, Berlin, Germany; or Cosmic co., Tokyo, Japan) an arbitrary limit of 40 U/l or 50% was suggested to indicate risk when measured late in pregnancy. In order to substitute TRAb1 with the second generation TRAb using porcine TSH receptor (pTRAb2) and human recombinant TSH receptor (hTRAb2) and the third generation TRAb (TRAb3) assay for this purpose, we measured TRAb in these four methods late in pregnancy in a total of 62 pregnant women with Graves' disease. The data showed that no cases with TRAb1 >50% has been missed if the TRAb1 assay was replaced by the pTRAb2, hTRAb2 or TRAb3 assay using their equivalent cut-off value of 70%, 10 IU/l, and 75%, respectively, but that an additional group of women would have been included in the risk group, especially in the TRAb3 assay. Next, the effect of maternal TRAb on thyroid function of offspring was studied in the 47 pregnant women with GD (43 with TRAb1 <50% and 4 with TRAb1 >50% during late pregnancy). In 2 women who gave birth to hyperthyroid children at days 6 and 14 of life, the maternal sera had strongly positive levels of TRAb1 (73.5% and 84.1%), pTRAb2 (84.9% and 91.5%), hTRAb2 (40.68 IU/L and 89.70 IU/L) and TRAb3 (92.1% and 93.5%) late in pregnancy, with one case displaying high positive (1114.3%) thyroid stimulating antibody (TSAb) level and the other case had moderate positive (433%) TSAb level. Of the remaining 45 women, 43 had TRAb1 <50% and the other 2 had TRAb >50% including 1 with low TSAb positive and 1 with positive thyroid stimulating blocking antibody (TSBAb) and negative TSAb; all of them gave birth to euthyroid children. Finally, a serial study regarding TRAb in 23 women with Graves' disease during pregnancy showed that TRAb1, pTRAb2, hTRAb2, TRAb3 value and TSAb level decreased significantly as pregnancy progressed. In conclusion, the present study supported TRAb as a useful marker to predict the risk of NH.

Persistent high TRAb values during pregnancy predict increased risk of neonatal hyperthyroidism following radioiodine therapy for refractory hyperthyroidism

“…Therefore, the occurrence of neonatal hyperthyroidism seems to be a matter of concern in pregnancies of severe Graves' patients after radioiodine treatment. However, in most cases, as reported by Tajiri, neonatal hyperthyroidisms do not occur because serum TRAb usually decreases during pregnancy even if the serum level of TRAb is high at the first trimester [10,14]. In this study, among patients with high serum TRAb at the first trimester, serum levels of TRAb of mothers Fig.…”

Predictive value of maternal second-generation thyroid-binding inhibitory immunoglobulin assay for neonatal autoimmune hyperthyroidism

“…Previous studies reported an increased risk if TBII level was over 40 IU/l (normal range, !10 IU/l) (25), or over 40 or 70% (26,27) (normal, !10-15%) in late T3. Today, the TBII first-generation assay has been widely replaced by the second-generation assay, and yet only one short study has investigated the TBII value predictive of neonatal hyperthyroidism using this assay (19). The authors compared TBII values determined by four assays, and tried to establish equivalence between first-and second-generation assays.…”

“…Instead of solubilized porcine receptors (14,15), these newer assays use recombinant TSHR coated on a solid-phase surface which provides a markedly improved sensitivity and specificity (16,17,18). To our knowledge, the threshold value indicating a risk for fetal or neonatal autoimmune hyperthyroidism with a second-generation TBII assay has only been investigated in one small study (19).…”

Kinetic analyses of changes in serum TSH receptor antibody values after total thyroidectomy in patients with Graves&rsquo; disease

“…Several studies reported that the serum TRAb values usually decreased during pregnancy [3,[15][16][17]. As a possible mechanism of this, Amino et al suggested that Th2-dependent humoral immunity is suppressed in human pregnancy [16].…”

“…five times the upper limit of the normal range [1,[20][21][22] or > 10 IU/L [15]. We therefore used 10 IU/L as the cut-off value for TRAb in the present study.…”