Congenital
hyperthyroidism is a very
rare disease. But, for each affected child it has to be considered as a serious condition because of the negative impact of
hyperthyroidism on fetal and postnatal development. If the manifestation occurs during fetal life
tachycardia,
cardiac arrhythmia, growth retardation and, most significant, prematurity are the consequences. Postnatal signs of
hyperthyroidism are irritability,
tachycardia,
hypertension, poor
weight gain and thyroid enlargement. Even
cardiac failure may occur if
hyperthyroidism is severe and treatment not adequate which explains the high early mortality rate of 16%. The main complication of persistent
hyperthyroidism in the neonatal period 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 was first recognized in infants born to mothers with
Graves' disease. The description of transplacental passage of the maternal
thyroid stimulating antibodies elucidated the molecular mechanism in this major group of patients with "autoimmune congenital
hyperthyroidism". In contrast to this transient, self-limited character of "autoimmune congenital
hyperthyroidism", due to the clearance of maternal
antibodies from the infant's circulation, some cases of persistent congenital
hyperthyroidism 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 group of "non-immune congenital
hyperthyroidism". Therefore the possibility of a molecular differential diagnosis of both groups of congenital
hyperthyroidism now exists and opens the opportunity of optimal treatment for each patient.