Immunoglobulin G inhibitor of thyroid-stimulating antibody is a cause of delay in the onset of neonatal Graves' disease.

Abstract

A B S T R A C T Studies were carried out with the serum IgG from a mother and her two children who developed neonatal Graves' disease several weeks after birth. The maternal IgG: (a) stimulated the human thyroid in vitro, but maximal stimulation was found only with dilution of the IgG; (b) was very potent in the long-acting thyroid stimulator (LATS)-protector assay, but only when an inhibitor of the system was diluted out; (c) inhibited a standard preparation of LATS in the mouse bioassay; (d) was biphasic in the thyrotropin-binding inhibition (TBI) assay, i.e., enhanced binding at low concentrations of IgG and inhibited binding at high levels. Enhancement in the TBI assay was found only with particulate preparations of human thyroid membranes as receptor and not when that material was solubilized, nor with guinea pig fat cell membranes as receptor. Serial blood samples from the second child were obtained at birth and until 3 mo of age. In the thyroid slice (cyclic AMP) assay system there was a negative dose-response relationship in testing the IgG until age 45 d when it became positive, coinciding with the clinical recognition that hyperthyroidism had developed. The data are compatible with a concept that this mother's IgG contained thyroid-stimulating antibody (TSAb) and another moiety that inhibited TSAb through an action This work was initiated when Dr. Zakarija and Dr. McKenzie were members

Binding domains of stimulatory and inhibitory thyrotropin (TSH) receptor autoantibodies determined with chimeric TSH-lutropin/chorionic gonadotropin receptors.

“…Present evidence suggests that the sera of some patients with autoimmune thyroid disease contain a mixture of stimulatory or inhibitory TSH receptor antibodies (1,7,20). Although the epitopes for these antibodies are unknown, the present concept is that they correspond to the TSH binding site on the TSH receptor.…”

The thyrotropin receptor autoantigen in Graves disease is the culprit as well as the victim

“…Serum dilution also has a major effect on the detection of TSAb. In the presence of high TBAb activity, Zakarija and McKenzie observed that TSAb activity may emerge only after serum dilution or after the decline in neonatal TSHR Ab levels following transplacental passage from the mother (35).…”

Fetal neonatal hyperthyroidism: diagnostic and therapeutic approachment

“…This time period is 36-72 hours for methimazole (25). The clinical signs and symptoms may be delayed up to 7-10 days because of antithyroid drugs or TSHR blocking antibodies found in the serum (26). In another study, it was observed that the clinical picture appeared in the postnatal 1 st -3 rd days in babies of mothers who were not using medication, and in the postnatal 7 th -17 th days in the other babies (27).…”

“…Subsequently, the level in the fetus gradually increases and exceeds the mother's level in the term newborn (14). Although it has been proposed that the clinical picture may start from the 21 st week when the antibody level increases and the fetal TSH receptors become responsive, the picture of fetal hyperthyroidism generally becomes prominent in the [26][27][28] th weeks (5). Both sexes are affected equally.…”