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Context: Typically, growth failure in Turner syndrome (TS) begins prenatally, and height sd score (SDS) declines progressively from birth., Objective: This study aimed to determine whether GH treatment initiated before 4 yr of age in girls with TS could prevent subsequent growth failure. Secondary objectives were to identify factors associated with treatment response, to determine whether outcome could be predicted by a regression model using these factors, and to assess the safety of GH treatment in this young cohort., Design: This study was a prospective, randomized, controlled, open-label, multicenter clinical trial (Toddler Turner Study, August 1999 to August 2003)., Setting: The study was conducted at 11 U.S. pediatric endocrine centers., Subjects: Eighty-eight girls with TS, aged 9 months to 4 yr, were enrolled., Interventions: Interventions comprised recombinant GH (50 mug/kg.d; n = 45) or no treatment (n = 43) for 2 yr., Main Outcome Measure: The main outcome measure was baseline-to-2-yr change in height SDS., Results: Short stature was evident at baseline (mean length/height SDS = -1.6 +/- 1.0 at mean age 24.0 +/- 12.1 months). Mean height SDS increased in the GH group from -1.4 +/- 1.0 to -0.3 +/- 1.1 (1.1 SDS gain), whereas it decreased in the control group from -1.8 +/- 1.1 to -2.2 +/- 1.2 (0.5 SDS decline), resulting in a 2-yr between-group difference of 1.6 +/- 0.6 SDS (P < 0.0001). The baseline variable that correlated most strongly with 2-yr height gain was the difference between mid-parental height SDS and subjects' height SDS (r = 0.32; P = 0.04). Although attained height SDS at 2 yr could be predicted with good accuracy using baseline variables alone (R(2) = 0.81; P < 0.0001), prediction of 2-yr change in height SDS required inclusion of initial treatment response data (4-month or 1-yr height velocity) in the model (R(2) = 0.54; P < 0.0001). No new or unexpected safety signals associated with GH treatment were detected., Conclusion: Early GH treatment can correct growth failure and normalize height in infants and toddlers with TS.

Context: Little information exists regarding FSH values in very young girls with Turner syndrome (TS)., Objectives: The objective of the study was to evaluate the pattern, natural progression, and karyotype-related differences in FSH secretion in young, prepubertal girls with TS., Study Design: FSH was measured at study entry and annually for 2 yr., Setting: The Toddler Turner study was conducted at 11 U.S. pediatric endocrine centers., Study Participants: Eighty-eight girls with karyotype-proven TS aged 9 months to 4 yr participated in the study., Main Outcome Measures: By-karyotype differences in FSH concentration and age-related changes in FSH were measured., Results: Mean (+/- SD) FSH was markedly elevated in the 45,X (n = 56: 68.3 +/- 36.0 IU/liter) and Other groups [n = 15 (excluding three subjects with Y-containing karyotypes): 52.7 +/- 50.8 IU/liter] but was minimally elevated in girls with 45,X/46,XX mosaicism (n = 14: 10.1 +/- 13.5 IU/liter, P < 0.005 both comparisons). Over the 2-yr period, FSH declined in the 45,X group (-13.4 IU/liter.yr, P < 0.0001). Nonetheless, only three of 159 FSH values fell within normal range for age at any time during the 2-yr study. FSH decline was similar in the Other group (-14.3 IU/liter.yr, P = 0.0032). In contrast, no significant decrease in FSH with age was observed in the 45,X/46,XX group., Conclusions: In contrast to the original report of FSH concentrations in individuals with TS, this study demonstrates distinct differences in patterns of FSH secretion between young girls with monosomy TS, who have persistent elevation of FSH to age 6 yr, and those with 45,X/46,XX mosaicism, whose FSH values suggest retained ovarian function in the majority. These findings have implications for patient management and family counseling.

GH influences the immune response. The mechanism is not known; however, the presence of receptors for GH on human lymphocytes as well as its ability to influence and modulate immune responses in animals suggest an association between GH and immune function in man. We evaluated the effect of recombinantly derived natural sequence human GH (hGH) on lymphocyte surface antigen expression, response to mitogenic stimulation, expression of interleukin-1 receptors, and production of anti-hGH antibodies in GH-deficient children. The only observed changes were a decrease in the percentage of B-cells and a transient increased reactivity to phytohemagglutinin stimulation. It appears from the results of our studies that the administration of hGH has a selective effect on lymphocyte immune function; however, we cannot eliminate a role for hGH in the initiation or regulation of antigen-mediated immune responses.

Dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), androstenedione (A), testosterone (T), estrone (E1), estradiol (E2) and gonadotropins were measured in 3 normal adult men before and after administration of 50 mg ovine prolactin for 5 days. No significant change as a result of ovine prolactin administration was observed in any of the parameters examined.

The purpose of this study was to determine if endogenous hGH release, hence growth, in hypopituitary children could be potentiated by therapy with dopaminergic (DA) drugs namely, L-dopa or bromocriptine. The effect of DA therapy on other endocrine function was also examined. Subjects were nine prepubertal children (four girls and five boys) with bone ages (BA) ranging from 1.5-9.5 yr. They were diagnosed as having idiopathic GH deficiency on the basis of: 1) failure to grow at normal rates 2) lack of GH response to two provocative stimuli (oral L-dopa, and insulin-induced hypoglycemia) and 3) low somatomedin-C concentrations for sex and age. They were divided into two groups. Group I (n = 4) received L-dopa (15 mg/kg, orally, every 6 h) for 6 months. Group II (n = 5) received bromocriptine (1.25 mg, orally, every 12 h) for 6 months. At the end of 6 months of DA therapy, both groups received human GH (hGH) im (0.1 IU/kg, thrice weekly) for 6 months. The growth rate in group I increased to 5.7 +/- 0.6 (+/- SE) cm/yr during the 6 months from a pretreatment rate of 3.4 +/- 0.2 cm/yr. Individual increments ranged from 30-94% above pretreatment growth rates. Three of the four children had significantly increased height increments, and two children achieved growth rates normal for their BA. Similarly, the growth rate in group II increased to 4.8 +/- 0.8 cm/yr from the pretreatment rate of 2.9 +/- 0.3 cm/yr. Individual increments ranged from 46-100% above pretreatment growth rates. Three children in group II had significantly increased height increments, and two children had normal growth rates for BA. The growth increments during L-dopa therapy occurred in the three children who had significant increases in hGH and somatomedin-C; of the three children with significant growth increments during bromocriptine therapy, two had increases in somatomedin-C, and one achieved a normal peak hGH value. hGH therapy caused further acceleration of growth velocities in the majority of patients. DA therapy had no significant effect on basal gonadotropin, gonadal steroids, T4, TSH, or morning cortisol concentrations in the majority of children compared with their pretreatment values. The following conclusions were reached. Dopaminergic therapy by itself, i.e. L-dopa or bromocriptine administration, induced linear growth in some hypopituitary children without significantly affecting basal concentrations of LH, FSH, gonadal steroids, T4, TSH, or cortisol. The effect this therapy could have in potentiating exogenous GH and/or possible GRH therapy is worthy of further investigation.

In a previous study we reported stimulation of growth velocity in hypopituitary children by dopaminergic therapy (DA), i.e. either L-dopa or bromocriptine. The purpose of the present study was to determine if DA stimulated endogenous GH release and growth in children with intrauterine growth retardation (IUGR), who also had microcephaly and psychomotor retardation. The effect of DA on serum LH, FSH, gonadal steroids, cortisol, T4, and TSH also was examined. Six prepubertal children [four girls and two boys; bone age (BA), 1.5-4 yr] with IUGR were divided into two study groups. Group I (n = 3) received L-dopa (15 mg/kg) orally every 6 h for 6 months. Group II (n = 3) received bromocriptine (1.25 mg) orally every 12 h for 6 months. At the end of the 6 months of DA therapy, both groups received human GH (hGH) (0.1 IU/kg) im thrice weekly for 6 months. The growth rate in group I was 6.5 +/- 0.1 (+/-SD) cm/yr after 6 months of DA compared with a pretreatment growth rate of 4.1 +/- 0.7 cm/yr. Individual increments ranged from 38-80%. All three children achieved normal growth rates for their BA. Similarly, the growth rate in group II increased to 7.7 +/- 0.9 cm/yr from a pretreatment growth velocity of 4.2 +/- 1.6 cm/yr. The growth increments of group II ranged from 43-133%. Two children of group II achieved normal growth rates for their BA, and all had a significant increase in height (P less than 0.05). Four of the six children achieved normal growth velocities after 6 months of hGH therapy. Five of the six children significantly increased their mean hGH responses to L-dopa or bromocriptine during chronic DA therapy compared with the pretreatment period. Maximum serum hGH values in group I increased from a pretreatment mean (and range) of 12 +/- 4 (+/-SE) ng/ml (5-18 ng/ml) to 46 +/- 12 ng/ml (21-64 ng/ml). The maximum hGH concentrations in group II increased from a pretreatment mean and range of 21 +/- 7 ng/ml (11-34 ng/ml) to 48 +/- 4 (42-56 ng/ml). Also, four of the six children had correspondingly increased somatomedin-C concentrations after DA therapy. The findings of this preliminary study indicate that dopaminergic therapy, i.e. L-dopa or bromocriptine, induced linear growth in patients with a form of IUGR associated with microcephaly and psychomotor retardation. DA therapy perhaps may be useful in treating other various forms of IUGR.

The purpose of this study was to determine if combined therapy with dopaminergic drugs (DA), i.e. L-dopa or bromocriptine, and exogenous human GH (hGH) could increase growth velocity in hypopituitary children. Twelve prepubertal hypopituitary children (eight boys and four girls; bone age, 1.5-9.5 yr), divided into two groups, each received hGH alone, DA alone, and DA and hGH. Group I (n = 6) received L-dopa (15 mg/kg, orally) at 6-h-intervals during DA and combined DA and hGH therapy. Group II (n = 6) received bromocriptine (1.25 mg, orally) every 12 h during DA and combined DA and hGH therapy. Both groups were given hGH (0.1 IU/kg) three times per week during hGH and combined hGH and respective DA treatment. The study included three 6-month treatment periods of DA, hGH, and combined DA and hGH therapy. The mean growth rates (centimeters per 6 months, +/- SD) before treatment and during the three study periods for group I were 1.7 +/- 0.2, 3.3 +/- 0.8, 3.4 +/- 0.4, and 3.9 +/- 0.7, respectively. Group II results were 1.4 +/- 0.3, 2.3 +/- 0.8, 5 +/- 1.6, and 3.7 +/- 1.1. Mean and peak hGH concentrations, measured every 30 min for 9 h at the end of each study period, increased significantly in five patients, from 15 +/- 3 (+/- SE) ng/ml during hGH therapy to 30 +/- 5 ng/ml during DA and hGH treatment. The mean peak hGH values rose from 24 +/- 4 to 45 +/- 5 (+/- SE) ng/ml. In conclusion, addition of dopaminergic agents to hGH therapy potentiates growth in some hypopituitary children. The increased growth and hGH responses to L-dopa or bromocriptine suggest impaired endogenous GH release. Dopaminergic therapy alone or in combination with exogenous hGH may be efficacious in some hypopituitary children.