Prevalence and Pathogenesis of Macro-Thyrotropin in Neonates: Analysis of Umbilical Cord Blood from 939 Neonates and Their Mothers.

Autor: Hattori N; Department of Pharmaceutical Sciences, Ritsumeikan University, Shiga, Japan., Aisaka K; Department of Obstetrics and Gynecology, Hamada Hospital, Tokyo, Japan., Yamada A; Department of Pharmaceutical Sciences, Ritsumeikan University, Shiga, Japan., Matsuda T; Department of Pharmaceutical Sciences, Ritsumeikan University, Shiga, Japan., Shimatsu A; Advanced Medical Care Center, Omi Medical Center, Shiga, Japan.
Jazyk: angličtina
Zdroj: Thyroid : official journal of the American Thyroid Association [Thyroid] 2023 Jan; Vol. 33 (1), pp. 45-52. Date of Electronic Publication: 2022 Dec 20.
DOI: 10.1089/thy.2022.0457
Abstrakt: Background: Macro-thyrotropin (macro-TSH) is a large molecular weight TSH that causes elevated serum TSH concentrations due to its slow clearance. It is primarily a complex of TSH and anti-TSH autoantibodies. The aims of this study were to examine the prevalence and nature of macro-TSH in neonates and to determine how to cope with macro-TSH in neonates suspected to have congenital hypothyroidism through neonatal mass screening. Methods: The presence of macro-TSH was examined using polyethylene glycol (PEG), gel filtration chromatography (GFC), and 125 I-TSH binding studies in 939 umbilical cord blood samples from neonates and their mothers. Results: Among 138 serum samples with a PEG precipitation ratio of TSH >68.9% (mean + standard deviation), human anti-mouse antibodies were found in nine samples. The presence of macro-TSH was examined in the remaining 129 serum samples using a 125 I-TSH binding study and GFC. The 125 I-TSH binding study revealed that four babies (0.43%) had significantly high ratios of 125 I-TSH binding to their sera. Two of the babies were siblings, and their mother and the other two mothers also showed significantly high binding ratios. The 125 I-TSH binding was displaced by a large amount (1 μg) of unlabeled human TSH in a similar way between babies and their mothers in all cases, suggesting the presence of anti-TSH autoantibodies in their sera. Further characterization of the autoantibodies in one baby and its mother showed a low affinity and high specificity to human TSH, and the nature was very similar between them. These findings may indicate that the anti-TSH autoantibodies that developed in the mother were transferred to the baby through the placenta and formed macro-TSH by binding to neonatal TSH. GFC revealed macro-TSH in only one baby and its mother, probably because of the dissociation of TSH from autoantibodies during the analytical procedure. Conclusions: Macro-TSH was found in 0.43% of neonates, and their mothers all had macro-TSH as well. We recommend that if a baby's serum TSH concentration is high enough to consider levothyroxine treatment suspecting congenital hypothyroidism but the free thyroxine level is normal, their mother's macro-TSH should be checked.
Databáze: MEDLINE