Transient congenital hypothyroidism due to maternal thyrotrophin binding inhibiting immunoglobulin

Abstract

Transient congenital hypothyroidism due to maternal thyrotrophin binding inhibitor immunoglobulin (TBII), a thyroid-stimulating hormone (TSH)-receptor blocking antibody, is described in three male siblings born to a mother with autoimmune thyroiditis. These cases are believed to be the first described in Australia. The first child was found to have a serum TSH of 565 mU/L and had a negative thyroid scan when presented for neonatal screening. He was treated with thyroxine but became thyrotoxic at 3 months of age when he was on a dosage of 85 micrograms/m2 of body surface area. He was euthyroid 6 months after discontinuation of therapy. Nine years later a second hypothyroid sibling was born, with a serum TSH of 709 mU/L on day 4. Both mother and child were demonstrated to be strongly positive for TBII. Again this child was able to cease therapy by the age of 9 months. A third sibling, also TBII positive, was born 12 months after the second. His TSH was 90 mU/L and his serum thyroxine (T4) was 169 nmol/L. On this occasion, thyroid stimulation-blocking antibody was found to be present in the serum of both mother and child. Thyroxine therapy was ceased at 1 month. The family present a picture of varying degrees of transient neonatal hypothyroidism due to the transplacental passage of a maternal receptor blocking antibody. The condition is self-limiting, resolving when the immunoglobulin is cleared from the infant's circulation.

A novel bioassay for anti-thyrotrophin receptor autoantibodies detects both thyroid-blocking and stimulating activity

“…[8,10,11,[18][19][20][21][22][23]. Other investigations have focused on the role of TBAb in congenital and neonatal hypothyroidism associated with mothers with autoimmune thyroid disease [19,[24][25][26][27][28][29][30][31][32]. The importance of TBAb in congenital hypothyroidism, however, has been questioned [28].…”

Update on Neonatal Isolated Hyperthyrotropinemia: A Systematic Review

“…Two studies have demonstrated the presence of TRAbs in cases of neonatal HTT (Azzopardi P 2010), or in the mothers of those infants (Evans C 2011), suggesting transplacental transfer of maternal antibodies (31,32). Two additional studies have also reported transient HTT due to maternal autoimmune thyroid disease with the presence of anti-TSHR antibody activity in both maternal and infant serum (Tamaki H 1989, Schwingshandl J 1993 (33,34).…”

“…Different generations of competitive binding TRAb tests for the detection of TSHR-binding inhibitory immunoglobulin have been used in the serological diagnosis of thyroid disease, principally in Graves' disease. Of note, the TSHR stimulatory antibodies can only be detected by cell-based bioassays and should be differentiated from the TSHR-blocking antibodies (34). The presence of TSHRblocking antibodies is investigated by the measurement of TRAbs or thyrotrophin-binding inhibitor immunoglobulins.…”

Three siblings with self‐resolving congenital hyperthyrotropinaemia secondary to thyrotropin receptor blocking antibodies

“…In a retrospective case series of eight children with hyperthyropinaemia lasting greater than 3 months, only one child received thyroxine at 1 year of age when they became biochemically hypothyroid 8 . In an Australian case series of three children with hyperthyrotropinaemia related to TSHR antibody, one child became thyrotoxic at 3 months on replacement therapy 9 …”