Maternal thyroid-blocking immunoglobulins in congenital hypothyroidism.
We evaluated 24 mothers whose babies had congenital hypothyroidism (CH) for the presence of immunoglobulins (Igs) that inhibited [125I]bovine TSH binding and blocked TSH-induced growth and function of FRTL-5 cells. Results were compared with those from 2 mothers with known primary myxedema (atrophic thyroiditis) whose babies had transient CH and with normal controls. Only 1 prospectively evaluated CH mother had potent TSH binding inhibitory, growth inhibitory, and function inhibitory IgGs. Further study of this discordant mother's serum indicated that she was hypothyroid, probably due to atrophic thyroiditis. Both mothers with known primary myxedema had blocking IgGs. The thyroid growth-blocking activity was verified by cell count, could be absorbed by and eluted from Staphylococcal protein-A, indicating that it was an IgG, and was not an anti-TSH idiotype. Half-maximal inhibition was similar in the three different assays for thyroid-blocking activity, suggesting that TSH binding inhibitory, growth inhibitory, and function inhibitory IgGs in some patients with primary myxedema may be the same antibody population. There was no correlation with the titer of antimicrosomal antibodies. These data suggest that maternal thyroid-blocking IgGs interacting with the TSH receptor do not play a role in most cases of sporadic CH. Determination of TSH binding inhibitory IgGs, but not antimicrosomal antibodies, is a sensitive screening test for the presence of TSH receptor-blocking antibodies.
Brown
R S
RS
Department of Pediatrics, University of Massachusetts Medical School, Worcester 01655.
Keating
P
P
Mitchell
E
E
D000328:Adult; D001665:Binding Sites / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D003409:Congenital Hypothyroidism; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000276:immunology; D007074:Immunoglobulin G / Q000302:isolation & purification* / Q000494:pharmacology; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D009230:Myxedema / Q000276:immunology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology*; D011989:Receptors, Thyrotropin / Q000187:drug effects / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D013972:Thyrotropin / Q000037:antagonists & inhibitors / Q000502:physiology
D007074:Immunoglobulin G; D011989:Receptors, Thyrotropin; D013972:Thyrotropin