Thyroid-Stimulating Hormone, Prolactin, and Growth Hormone Response to Thyrotropin-Releasing Hormone in Treated Children with Congenital Hypothyroidism

Abstract

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...

T4 plus T3 Treatment in Children with Hypothyroidism and Inappropriately Elevated Thyroid-Stimulating Hormone despite Euthyroidism on T4 Treatment

“…Serum thyroid-stimulating hormone (TSH) concentrations remain elevated in 20–50% of L-T4 (levothyroxine)-treated congenital hypothyroid (CH) infants, despite clinical euthyroidism and normal serum thyroid hormone concentrations [1,2,3]. This relative hyperthyrotropinemia is most prevalent during the early months of life but, in some cases, persists after 5 years of age.…”

Early Identification of Congenital Hypothyroid Infants with Abnormalities in Pituitary Setpoint for T₄-lnduced TSH Release

“…The abnormality in these children also involves the pituitary lactotroph as well as the thyrotroph. We have previously shown that these chil dren have augmented prolactin as well as augmented TSH responses to exogenous TRH [12].…”

“…Mass population screening of newborn infants for con genital hypothyroidism (CH) was introduced in 1974 and has enabled early diagnosis and treatment [1][2][3][4][5], IQ mea surements of early and adequately treated children at old er ages have been normal, emphasizing the importance TSH suppression by thyroid hormones is increased, but the mechanism is not yet clear [11][12][13][14][15]. In practice, the frequency and persistence of high TSH levels in children with CH is still unclear, and it is unknown to what extent one should insist on normalizing serum TSH concentra tions during therapy [16][17][18][19][20][21], Several approaches have been proposed [10,20,21].…”

Paradoxical Growth Hormone Response following Thyroid-Stimulating Hormone Administration in the Polycystic Ovary Syndrome

“…This stimulatory effect of TRH on GH secretion in almost half of our PCO patients is difficult to explain. A paradoxical GH response has been encoun tered in various unrelated conditions, such as acromeg aly [14,15], renal failure [16,17], severe liver disease [18,19], mental illness including schizophrenia [20], depression [21], anorexia nervosa [14], primary acquired hypothyroidism [23] and during normal childhood and adolescence independent of age, sex or height [24,25] or in constitutionally tall children [26]. This nonspecific GH release has been attributed to an aberration of the CNS hypothalamic somatotropic axis which regulates GH secretion, caused either by an alteration of the cellu lar receptors of the somatotroph cells in adenomatous tissue, as postulated in acromegaly [27,28] and/or to disruption of the normal neuroendocrine regulatory mechanisms [14,17,26].…”