Transient congenital hypothyroidism due to thyroid-stimulating hormone receptor blocking antibodies: a case series

We describe seven infants with transient congenital hypothyroidism (CH) due to maternal thyroid-stimulating hormone receptor (TSH-R) blocking antibodies (TRAb) identified over three decades of newborn screening for CH in Wales, UK that represents a minimum incidence of 1.6% of CH cases. Infants with transient CH due to maternal TRAb presented with a spectrum of clinical and biochemical hypothyroidism. Blood spot TSH concentrations ranged 60.5-332 mIU/L. CH was confirmed by plasma thyroid function tests in all cases (plasma TSH ranged 21-752 mIU/L). The seven infants belonged to five different families. On examination, four infants were clinically hypothyroid. Five infants had a thyroid ultrasound, of which three were abnormal. All infants were treated with thyroxine, which was subsequently withdrawn from three. Following thyroxine withdrawal, one infant resumed normal thyroid function and two developed compensated hypothyroidism. Of the five mothers, two had undiagnosed hypothyroidism and three were receiving thyroxine for longstanding hypothyroidism. Thyroid peroxidase antibody (aTPO) was measured in four and was negative in two, borderline positive in one and strongly positive in another. TRAb was measured in all five women and was strongly positive in all of them. This case series highlights the importance of identifying CH due to TRAb by investigating both the infant and the mother following a raised TSH found on newborn screening. The identification of those infants with transient CH caused by maternal transfer of TRAb is essential for optimizing management during childhood (including potential withdrawal of thyroxine replacement in the longer term) and in any subsequent pregnancy.