CONGENITAL HYPERTHYROIDISM

Congenital hyperthyroidism is a very rare disease. But, for each affec ted child it has to be considered as a serious condition because of th e negative impact of hyperthyroidism on fetal and postnatal developmen t. If the manifestation occurs during fetal life tachycardia, cardiac arrythmia, growth retardation and, most significant, prematurity are t he consequences. Postnatal signs of hyperthyroidism are irritability, tachycardia, hypertension, poor weight gain and thyroid enlargement. E ven cardiac failure may occur if hyperthyroidism is severe and treatme nt not adequate which explains the high early mortality rate of 16%. T he main complication of persistent hyperthyroidism in the neonatal per iod and during infancy is craniosynostosis. Severe developmental delay or even mental retardation can be the consequence of inadequate high T4-levels during fetal and neonatal life. Congenital hyperthyroidism w as first recognized in infants born to mothers with Graves' disease. T he description of transplacental passage of the maternal thyroid stimu lating antibodies elucidated the molecular mechanism in this major gro up of patients with ''autoimmune congenital hyperthyroidism''. In cont rast to this transient, self-limited character of ''autoimmune congeni tal hyperthyroidism'', due to the clearence of maternal antibodies fro m the infant's circulation, some cases of persistent congenital hypert hyroidism without signs of thyroid autoimmunity have been recognized. Activating mutations in the thyroid-stimulating hormone receptor were described recently as the underlying molecular pathogenesis in this gr oup of ''non-immune congenital hyperthyroidism'' Therefore the possibi lity of a molecular differential diagnosis of both groups of congenita l hyperthyroidism now exists and opens the opportunity of optimal trea tment for each patient.