Search

Objective To understand whether spontaneous vs induced puberty and the type and route of estrogen influence the height of girls with Turner syndrome on growth hormone (GH). Study design Search of an international database of children treated with GH revealed 772 girls with Turner syndrome followed from GH initiation to near adult height. Data from girls with sustained spontaneous puberty (n = 145) were compared with those requiring estrogens for induction or maintenance of puberty (n = 627). Results At GH start, mean age (7.5 vs 7.9 years), weight (−1.7 vs −1.7 SDS), and body mass index (0.2 SDS vs 0.1 SDS) were similar for girls with spontaneous puberty and with induced puberty. Although those girls with spontaneous puberty were shorter than those with induced puberty, when midparental height was taken into consideration, starting heights in both groups averaged −2.8 SDS. Both groups received approximately 0.3 mg/kg/week of GH. Girls with spontaneous puberty initiated puberty and reached near adult height earlier than girls with induced puberty (12.6 ± 1.8 years vs 13.4 ± 1.4 years and 16.0 ± 1.3 years vs 16.9 ± 1.4 years, respectively). Although girls with spontaneous puberty grew more in the first year of GH therapy and between the onset of puberty and near adult height (11.0 cm vs 9.3 cm), height SDS at near adult height and the length of time in puberty before reaching near adult height were comparable. A 45,X karyotype was detected in 22.1% of girls with spontaneous puberty and in 58.4% of girls with induced puberty. Patients receiving transdermal estrogens did not grow better than those on oral estrogens. Adverse event reporting was comparable between groups. Conclusions Girls with Turner syndrome with spontaneous puberty tended to grow better in response to GH than girls with induced puberty, but not enough to produce a difference in height SDS at near adult height.

Objective To determine whether coronary artery calcification (CAC), elevated fasting lipids, and lipoproteins and peripheral inflammatory markers are present in insulin-dependent diabetic adolescents and young adults several years after diagnosis. Study design Hispanic insulin-dependent diabetics (n = 32) diagnosed a mean of 7.8 ± 4.5 years ago (range, 3 to 16 years), with a mean glycosylated hemoglobin concentration at the time of the study of 8.8% ± 2.3% and a mean chronological age of 16.1 ± 4.4 years, were evaluated. Healthy patients (n = 15) with a chronological age (CA) of 15.2 ± 2.2 years served as control subjects. CAC was assessed by multiple slice computed tomography, and total CAC score in Agatston units was calculated. Fasting lipids, C-reactive protein, apolipoprotein (Apo) A, Apo B, and metalloproteinase-9 (MMP-9) concentrations were measured in all subjects. Results Neither adolescents with type 1 diabetes nor healthy control subjects presented with evidence of CAC. Fasting lipids, Apo A, Apo B, CRP, and MMP-9 concentrations were similar between diabetic subjects and control subjects. However, 34.4% and 25.0% of our type 1 diabetic subjects had elevated total and LDL cholesterol levels (>200 and >130 mg/dL, respectively), whereas 15.6% and 28.1% had elevated triglyceride and Apo B concentrations (>150 mg/dL and >100 mg/dL, respectively). In addition, 28.1% and 34.4% presented with elevated CRP and MMP-9 levels (>2 mg/L and >80 ng/mL, respectively). Total, LDL and HDL cholesterol, triglycerides, Apo B, CRP, and MMP-9 concentrations correlated positively with duration of the disease and with glycosylated hemoglobin levels. Conclusions Although the study adolescents with type 1 diabetes did not present any radiologic evidence of CAC at this stage of the disease, they remain a high-risk group for the development of microvascular and macrovascular artery disease, as risk factors such as elevated lipoproteins and proinflammatory markers are already present in a significant percentage of patients studied.

Objective To examine the impact of adolescent growth hormone deficiency (GHD) on circulating adiponectin levels and the relation between adiponectin, fasting insulin, plasma lipid, and lipoprotein levels. Study design Twelve children with GHD on GH treatment with a chronological age (CA) of 14.4 2.0 years and 12 untreated adolescents with GHD with a CA of 14.9 2.3 years were studied. Adiponectin concentrations were measured in all patients, and the association of adiponectin with fasting insulin, total, LDL, and HDL cholesterol, triglycerides, apolipoprotein A-1, and apolipoprotein B was evaluated. Twelve healthy adolescents served as control subjects. Results Adiponectin levels were significantly lower in untreated GHD adolescents than in treated GHD subjects or in control subjects (P < .008). Total and LDL cholesterol, triglycerides, and Apo B concentrations were increased in untreated GHD adolescents, whereas HDL cholesterol levels were similar in all three groups. Insulin levels were significantly increased in treated GHD adolescents when compared with control subjects (P < .05) but similar to those with untreated GHD. Adiponectin was found to be negatively associated with body mass index, waist-to-hip ratio, and with Apo B, total cholesterol, triglycerides, and LDL cholesterol concentrations in untreated GHD adolescents, whereas a positive correlation between adiponectin and HDL cholesterol was noted in both untreated and treated GHD subjects. Adiponectin correlated inversely with fasting insulin levels in untreated and treated GHD adolescents. Conclusions GHD in adolescence is associated with low levels of adiponectin and with an unfavorable plasma lipid and lipoprotein profile. Our data suggest that treatment with GH may improve the abnormalities seen. (J Pediatr 2006;149:324-9)

Objective The frequency of Y-chromosome material is high in Turner syndrome (TS), but the ocurrence of gonadoblastoma seems to be low. We performed a study to evaluate whether DNA analysis might be a useful tool in the evaluation of patients with TS. Subjects Unrelated patients with TS (n = 52) of Venezuelan mestizo ethnic origin were diagnosed by cytogenetic analysis as having TS. Methods Clinical assessment, karyotyping, endocrine evaluation, fluorescence in situ hybridization, and polymerase reaction chain analysis of the Y-chromosome loci. Results We found that 7.69% (4 of 52) patients with TS had Y-chromosome material. A low occurrence of gonadoblastoma was also found (2 of 52 [3.85%]). Two patients showed a 45,X/46,XY karyotype, and gonadoblastoma in the gonadal biopsy specimen was not found. Two patients had no Y chromosome on initial karyotype; they were positive on lymphocyte DNA to Y-sequences specific. Both patients (45,X) had bilateral gonadoblastoma. The four patients with Y-chromosome material in peripheral blood lymphocytes had Y-chromosome sequences on gonadal DNA. Fluorescence in situ hybridization confirmed their Y-chromosome origin. Conclusions Our results suggest that the detection of Y-chromosome material should be carried out in all patients with TS and not be limited to patients with TS with cytogenetically identifiable Y chromosome and/or virilization. (J Pediatr 2003;142:336-40)

Eighteen healthy, short children with normal growth during most of their childhood were evaluated after a sustained fall in weight and reduced linear growth. Growth was followed after nutritional counseling until final height. This report demonstrates the need for an appropriate-for-age weight gain in growing children as a relatively minor but prolonged caloric restriction, leading to a sustained fall in weight centiles, will affect growth velocities long term and may lead to reduced final heights.

Patients with growth hormone (GH) deficiency have impaired bone mineral metabolism; treatment with GH leads to an improvement in their bone mineral density (BMD). The effect of GH on the BMD of children with idiopathic short stature is unknown. We studied 14 short, slowly growing, otherwise healthy, prepubertal children without GH deficiency (7 girls and 7 boys) with a chronological age of 10.9 +/- 1.4 years, bone age of 8.8 +/- 1.5 years, and height of 127.8 +/- 8.5 cm (height SD score of -2.2 +/- 0.5). Growth velocity increased from 3.9 +/- 1.1 cm/y to 8.0 +/- 1.9 cm/y, and height SD score improved from -2.2 +/- 0.5 to -1.8 +/- 0.5 after 12 months of GH treatment (P.007 and P.001, respectively). Baseline lumbar spine BMD was decreased when compared with that of a control group of children matched for bone age and height (0.645 +/- 0.09 g/cm(2) vs 0.730 +/- 0.08 g/cm(2); P.003). Lumbar spine BMD increased in subjects with ISS after 1 year of GH treatment from 0.645 +/- 0.09 g/cm(2) to 0.808 +/- 0.04 g/cm(2) (P.05), reaching levels similar to those of control subjects, followed up without therapy (0.808 +/- 0.04 g/cm(2) vs 0.760 +/- 0.08 g/cm(2)); lumbar spine BMD increased 25.3% in the subjects with ISS and 4.1% in the control subjects. Femoral neck BMD did not change during treatment. Serum concentrations of the carboxy-terminal propeptide of type 1 collagen increased from 231.6 +/- 65.5 microg/L to 351.6 +/- 87.2 microg/L, and levels of the carboxy-terminal cross-linked telopeptide of type 1 collagen increased from 9.9 +/- 5.9 microg/L to 13.9 +/- 2.4 microg/L. Children with ISS have decreased lumbar spine BMD, which increases with GH therapy, reaching levels similar to those of control subjects. Bone turnover increased as indicated by a rise in bone formation and bone resorption markers.

Growth hormone levels were measured every 30 minutes during sleep over 9 hours in 20 prepubertal patients with constitutional delay of growth and puberty (CGD) and in 10 age-matched controls, all of whom had had normal GH responses to an orally administered dose of clonidine. We found no significant difference in the mean 9-hour overnight GH concentration between groups (4.5 +/- 1.8 ng/ml (mean +/- SD) in the CGD group, 4.4 +/- 2.8 ng/ml in the control group). Total GH output (258 +/- 99 U vs 222 +/- 135 U), total number of nocturnal GH pulses (3.6 +/- 0.8 vs 3.3 +/- 1.3), mean peak GH response during nocturnal sampling (13 +/- 1.2 ng/ml vs 13.2 +/- 1.3 ng/ml), and basal somatomedin C concentrations were not different in the children with growth delay and controls. We conclude that prepubertal patients with constitutional delay of growth and puberty secrete GH normally and do not seem to have any abnormality in GH regulation.

The effects of clonidine, metoclopramide, and insulin on growth hormone, cortisol, and glucose concentrations in the blood of 17 healthy prepubertal short children (Group A) and five prepubertal growth hormone-deficient children (Group B) were evaluated. The peak serum growth hormone values after insulin and clonidine were significantly higher than after metoclopramide administration. Growth hormone values did not rise above baseline values in Group B patients with any of these three stimuli. Plasma cortisol concentrations did not change with metoclopramide but increased significantly with insulin and decreased significantly after clonidine; no changes in glucose values were noted with either clonidine or metoclopramide. Clonidine appears to be a reliable, sensitive, and safe out-patient stimulation test of growth hormone reserve in prepubertal children, whereas metoclopramide seems not to be a suitable growth hormone-releasing agent in this age group.

We describe 12 of 1130 infants with Down syndrome in whom various degrees of thyroid dysfunction were detected by neonatal screening. These aberrations were confirmed subsequently in 11 patients. In eight of 11 children, persistent primary hypothyroidism, was diagnosed, whereas in the remaining three patients transient thyroid abnormalities were noted. The twelfth patient died and could not be retested. We found an incidence of persistent primary congenital hypothyroidism in infants with Down syndrome of 1:141, or about 28 times more than in the general population. The cause of thyroid aberrations in these infants remains unclear; none of the studied patients had agenesis or ectopia of the thyroid gland. On initial screening most infants with Down syndrome had only mild biochemical abnormalities, with gradual decompensation occurring thereafter. Infants with Down syndrome are therefore at high risk for congenital hypothyroidism and should have careful follow-up to prevent further deterioration of their mental development or growth.

The 24-hour integrated concentration of aldosterone, plasma renin activity, and 17-hydroxprogesteronewas measured simultaneously in 12 patients with congenital virilizing adrenal hyperplasia due to 21-hydroxylase deficiency. Eight were salt-losers and four nonsalt-lowers. Seven normal children served as control subjects. All patients were receiving glucocorticoid replacement therapy (32 mg/m 2 /day). All but one of the SL-CVAH patients were also being treated with 9α-fluorocortisol. The mean (±SD) IC-PRA of the control subjects was 1.6±0.7 ng/ml/hour and in the NSL-CVAH patients was similar (1.6±0.7 and 2.2±1.0 ng/ml/hour). The IC-PRA of the SL-CVAH patients (21.1±28.8 ng/ml/hour) was significantly ( P P