HUMORAL THYROID AUTOIMMUNITY IS NOT INVOLVED IN THE PATHOGENESIS OF MYXEDEMATOUS ENDEMIC CRETINISM

A role of thyroid autoimmunity in the pathogenesis of myxedematous end emic cretinism was suggested by reports indicating the presence of thy roid growth-blocking antibodies in the sera of these patients. To chec k this hypothesis, we searched for TSH receptor antibodies with thyroi d growth-blocking or adenylate cyclase (AC)-inhibiting (TSH-blocking) activity in immunoglobulin G (IgG) from 18 euthyroid and 21 hypothyroi d endemic cretins living in Italy and Peru. Among hypothyroid cretins, 12 had no palpable goiter. Stage I-III goiters were present in 12 of 18 euthyroid cretins. Controls included 25 euthyroid nongoitrous subje cts Living in the same endemic regions as cretins, and 10 normal subje cts from an iodine-sufficient area. IgG from 4 selected patients with autoimmune atrophic thyroiditis and from 2 neonates with sporadic tran sient congenital hypothyroidism due to maternal TSH-blocking antibodie s were included in the study. The blocking effect of the IgG was asses sed in FRTL-B cells by measuring TSH-stimulated [H-3]thymidine incorpo ration, DNA accumulation, and AC activation. A radioreceptor assay was used to detect TSH-binding inhibiting antibodies (TBIAb). No IgG from hypothyroid endemic cretins without goiter contained TBIAb, or inhibi ted TSH-stimulated cell growth or AC activation. The effect of IgG fro m hypothyroid nongoitrous cretins did not differ from that produced by IgG from hypothyroid cretins with goiter, euthyroid cretins with or w ithout goiter, or normal controls. In contrast to these results, IgG f rom patients with autoimmune atrophic thyroiditis and from neonates wi th sporadic transient congenital hypothyroidism contained TBIAb, that inhibited both TSH-stimulated cell growth and AC activation. In conclu sion, our results indicate that, similar to other types of endemic cre tinism, hypothyroid endemic cretins-without goiter do not have TSH rec eptor antibodies able to inhibit TSH-stimulated thyroid cell growth or function. These observations argue against a role of humoral thyroid autoimmunity in the development of myxedematous endemic cretinism.