Severe unsuspected maternal hypothyroidism discovered after the diagnosis of thyrotropin receptor-blocking antibody-induced congenital hypothyroidism in the neonate: failure to recognize and implications to the fetus.

Background: Whereas most adequately treated children with congenital hypothyroidism (CH) do well neurodevelopmentally, when both the maternal and fetal thyroid glands are compromised, significant cognitive delay can occur despite early and aggressive postnatal therapy. Maternal thyrotropin-stimulating hormone receptor (TSHR)-blocking antibodies (Abs) can be transmitted to the fetus and cause combined maternal-fetal hypothyroidism. Current guidelines recommend their measurement only if mothers have known autoimmune thyroid disease, there is a history of a previously affected sibling, or when transient CH is suspected.

Results: We report 3 infants in whom the diagnosis of maternal hypothyroidism was not known and was identified only after CH was diagnosed in their babies. One of these infants had developmental delay despite rapid normalization of thyroid function postnatally. All 3 mothers had potent TSHR Abs in serum, but thyroid peroxidase Abs and thyroglobulin Abs were detectable in only 2 of them.

Conclusions: TSHR-blocking Ab-induced CH should be suspected in any baby with CH irrespective of the known family history, especially if the hypothyroidism is severe and a eutopic thyroid gland is demonstrated on imaging. Measurement of TSHR Abs is necessary to establish the diagnosis; the presence of other thyroid Abs is insufficiently sensitive and may miss some cases.