Transient Neonatal Hypothyroidism Due to Transplacental Transfer of Maternal Immunoglobulins that Inhibit TSH Binding, TSH-Induced cAMP Increase and Cell Growth.

Abstract

Transient neonatal hypothyroidism due to transplacental transfer of maternal blocking type TSH receptor antibodies (TRAb) was found in a baby born to a 27-yr-old mother, who had been receiving thyroxine medication for primary myxedema. Maternal IgG inhibited radiolabelled TSH binding to its receptor (TBII), TSH-stimulated thyroid adenylate cyclase (AC) activation (TSII) and TSH-stimulated 3H-thymidine uptake (TGII) in cultured rat thyroid cells (FRTL-5). At birth, the baby's IgG showed similar activities to maternal IgG but all these activities decreased gradually, and disappeared from her serum within 12 weeks of age. In the baby, initially nonvisualized thyroid was clearly visualized on 99 m-Tc thyroid scintigraphy when all these blocking activities disappeared, TSII and TGII being decreased more slowly than TBII, and the baby remained euthyroid after discontinuation of thyroxine. This study suggests that such IgGs induced hypothyroidism and thyroid atrophy in the mother and were responsible for transient neonatal hypothyroidism in the baby.

Maternal Thyroid Deficiency during Pregnancy and Subsequent Neuropsychological Development of the Child

“…Antibodies responsible for compromising maternal thyroid function can cross the placenta and, in some instances, compromise fetal and neonatal thyroid function. [3][4][5][6][7][8] One such antibody, the thyrotropin-receptor-blocking antibody, has been implicated in cases of transient congenital hypothyroidism that were identified by screening programs for newborns. 9 In 1969, Man and Jones suggested that mild maternal hypothyroidism alone was associated with lower IQ levels in the offspring; their study involved a cohort of 1349 children, and measurements of serum butanol extractable iodine were used to distinguish between euthyroidism and hypothyroidism in women.…”

Transient Hypothyroidism in Infants Born to Mothers with Chronic Thyroiditis-A Nationwide Study of Twenty-three Cases.

“…There have been at least three other cases reported in the literature. (Connors and Styne, 1986;Fort, et al, 1988;Cho, et al, 1988) The presence of TSH receptor blocking antibodies, which were detected by radioreceptor assay of TSH (TBII) and TSBAb assay have been considered pathogenetic in this condition. These activities were contheir 17 newborn infants.…”

Role of Blocking TSH Receptor Antibodies on the Development of Hypothyroidism and Thyroid Atrophy in Primary Myxedema

“…The growth-blocking activity in these IgG preparations also correlated with their ability to inhibit TSH-stimulated cAMP increase. Moreover, we found a case of transient neonatal hypothyroidism due to transplacental transfer of maternal blocking type TRAb ( 9 ). These findings support the concept that these blocking antibodies are against the TSH receptor or closely related structures, and may play a role in primary myxedema causing hypothyroidism and atrophy by inhibiting TSH-stimulating cAMP generation ( 1 , 4 ).…”

“…Recent data indicate that primary myxedema may be associated with the presence of immunoglobulin G (IgG) which inhibits the binding of TSH to its receptor, blocking the effect of TSH on thyroid adenylate cyclase ( 1 – 4 ) and cell growth ( 4 – 6 ). It has been reported that transplacental transfer of maternal IgGs may lead to transient neonatal hypothyroidism ( 7 – 9 ). Thus these blocking type TSH receptor antibodies (TRAb) could play a role in the pathogenesis of hypothyroidism and thyroid atrophy.…”