ABSTRACT. The purpose of the present study was to assess thyroid-stimulating hormone (TSH), prolactin, and growth hormone responses to TRH stimulation in 12 congenitally hypothyroid children adequately treated with Lthyroxine from the first weeks of life. Although clinically euthyroid, six of these children were found to have abnormally high basal serum TSH concentrations despite clinical euthyroidism. Serum triiodothyroxine and L-thyroxine concentrations were normal and did not differ whether the children had elevated or normal basal serum TSH. All six of the children with high basal TSH had an exaggerated TSH response to TRH and 4 of them also had an augmented prolactin response to TRH. The children with normal basal TSH concentrations had normal TSH and prolactin responses to TRH. An abnormal ("paradoxical") elevation of growth hormone concentration in response to TRH was found in four of seven children in a separate group of patients who had prolonged, untreated primary hypothyroidism, but such responses were not found in any of the adequately treated children. These findings suggest the following conclusions: 1) the phenomenon of high serum concentrations of TSH ip conjunction with normal L-thyroxine and triiodothyronine levels (and clinical euthyroidism), is prevalent in congenital hypothyroid patients. 2) These patients have an exaggerated response of their pituitary thyrotroph and lactotroph cells to TRH, presumably caused by selective and relative resistance of these cells to the inhibitory effects of thyroid hormones. 3) Congenital hypothyroidism is not associated with abnormal somatotroph cell responses to TRH. (Pediatr Res 19: 1037-1039,1985 Abbreviations GH, growth hormone PRL, prolactin T3, triiodothyronine T4, L-thyroxine TRH, thyrotropin releasing hormone TSH, thyroid stimulating hormone CH, congenital hypothyroidism tary regulation are well known in hypothyroid patients. Two examples of these alterations are the increased PRL response to TRH (1, 2) and the stimulation of GH secretion by TRH in hypothyroid children (3) and adults (4); these responses do not occur in normal subjects (5). It has been shown that many children suffering from congenital hypothyroidism manifest high serum TSH concentrations for prolonged periods despite adequate replacement therapy, clinical euthyrodism, and normal serum levels of thyroid hormones (7-10). It was suggested that this is due to an elevated threshold for thyrotroph cell TSH suppression by thyroid hormones. The purpose of the present study was to examine both the pituitary-thyroid negative feedback relationship and lactotroph and somatotroph regulation in children with congenital hypothyroidism.
MATERIALS AND METHODSTRH tests were performed in 19 children. Group A consisted of 12 congenitally hypothyroid patients aged 1.6 to 9.3 yr attending our clinic for congenital hypothyroidism. All were diagnosed by neonatal thyroid screening during the first weeks of life, and all were treated from the time of diagnosis with T4 and followed by one of us (J.S.). Serum...