bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Treatment in Children with Hypopituitarism: Pubertal Development and Final Height
Authors: Birnbacher R. , Riedl S. , Frisch H. 
Published: April 2003

Auxological data, pubertal development and final height were analyzed in 25 patients with growth hormone (GH) deficiency who were treated only with pituitary GH in 3 doses/week. 15 patients had a spontaneous onset of puberty and in 10 puberty was induced. The duration of therapy was 7.5 years, the dosage was about 11 U/m<sup>2</sup>/week and was not changed during puberty. 80% of the patients with induced puberty, but only 33% of the children with spontaneous puberty reached final heights within the 2 SD range. Final height was correlated with height at the start of treatment only in patients with spontaneous puberty, which shows the necessity of early treatment initiation in this group. The lack of this correlation in patients with induced puberty might be attributed to gonadotropin deficiency. Height at the onset of puberty was related to final height only in the group with gonadotropin deficiency. A prediction model for calculation of the first year height velocity which was derived from present treatment procedures showed a too favorable prediction for our patients. The reasons for the insufficient final results may be due to impure GH preparations, suboptimal dosage, low frequency of injections and late onset of therapy.
Effects of Glucagon-Like Peptide 1 (7–36 Amide) on Glucose Kinetics during Somatostatin-Induced Suppression of Insulin Secretion in Healthy Men
Authors: Shalev Anath , Ninnis Ronald , Keller Ulrich 
Published: April 2003

Glucagon-like peptide 1 (GLP-1) is known to stimulate insulin secretion and biosynthesis, but has also been shown to decrease insulin requirements in type 1 diabetic subjects suggesting insulin-independent effects. To assess whether GLP-1 exerts also direct effects on whole-body glucose metabolism, 6,6-D<sub>2</sub>-glucose kinetics were measured in 8 healthy volunteers receiving once GLP-1, once saline during hyperglycemic glucose clamping, while somatostatin with replacement amounts of insulin, glucagon and growth hormone was infused. Even though endogenous insulin secretion could not be blocked completely (increased plasma concentrations of C-peptide and proinsulin), somatostatin infusion resulted in stable insulin and glucagon plasma levels in both protocols (GLP-1 vs. placebo: NS). After 3 h of GLP-1 infusion, peripheral glucose disappearance significantly increased compared to placebo (p < 0.03) despite of somatostatin-induced suppression of insulin and glucagon secretion. Thus, GLP-1 infusion seems to have direct stimulatory effects on peripheral glucose metabolism in man.
Apparent Functionality But Impractical Quantification of Neurotensin Receptors on Human Peripheral Lymphocytes
Authors: Lhiaubet Anne-Marie , Avard Claire , Schimpff Rose-Marie 
Published: April 2003

Neurotensin (NT), a neuromodulator, is also thought to play an immunomodulatory role. We sought to confirm the effects of NT on proliferation in human peripheral blood lymphocytes (PBLs; n = 10), to characterize the binding properties of the NT receptor using Scatchard analysis, and to measure NT receptors using blood volumes (50 ml) applicable to clinical investigation. Incubation of phytohemagglutinin-stimulated PBLs with NT (10<sup>–10</sup> to 10<sup>–13</sup> <i>M</i>) in the presence of 0.07% normal human serum (72 h at 37°C) significantly enhanced proliferation (p < 0.001), which is consistent with PBLs possessing functional NT receptors. However, the various experimental conditions tested constantly yielded low specific NT binding to human PBLs, and hence Scatchard analysis was impossible for 50-ml blood samples. Our data confirm the existence of a link between NT and the immune system and support a physiological significance for this link. However, measurement of NT receptor binding in readily available cells proved unsuitable for clinical investigation.
Late Development of Resistance to Bromocriptine in a Patient with Macroprolactinoma
Authors: Delgrange E. , Crabbé J. , Donckier J. 
Published: April 2003

We report the case of a man with an invasive macroprolactinoma who developed resistance to bromocriptine to which he had previously responded satisfactorily for 5 years. Subsequently, hyperprolactinemia was controlled equally well with 600 µg quinagolide daily and later with 4.5 mg cabergoline weekly. This observation suggests that a loss of dopamine receptors at the tumoral cell surface might be the mechanism underlying acquired resistance to bromocriptine. In addition, no tumor growth was observed over a 10-year follow-up, which virtually excludes a malignant transformation of the prolactinoma. This case emphasizes the need for close supervision of patients with macroprolactinoma, even after the serum prolactin concentration has been normalized by bromocriptine. It furthermore illustrates the usefulness of quinagolide and cabergoline when resistance to bromocriptine develops after a prolonged period of adequate response to this drug.
Predictive Value of Serum Follicle-Stimulating Hormone Levels in the Differentiation between Hypogonadotropic Hypogonadism and Constitutional Delay of Puberty
Authors: Odink Roelof J. , Schoemaker Joop , Schoute Erik , Herdes Erik , Delemarre-van de Waal Henriette A. 
Published: April 2003

<b>Objective: </b>Gonadotropin secretion was evaluated to predict hypogonadotropic hypogonadism (HH) in 36 children suspected of having HH. <b>Methods: </b>LH was measured for 24 h at 10-min intervals, and FSH and estradiol or testosterone at 1-hour intervals. Twenty boys (age 15.7, range 13.2–19.3 years) and 16 girls (age 16.1, range 13.0–20.6 years) were studied. <b>Results: </b>LH pulses were detected in 9 boys and 5 girls. HH was confirmed in all 11 LH apulsatile boys and in 8 of 11 LH apulsatile girls. Random FSH values of ≤1.11 and ≤2.86 IU/l in boys and girls, respectively, discriminated patients with LH pulses from patients without (sensitivity for lack of LH pulses 97 and 100%, respectively). In boys testicular volume was not discriminatory. In 1 girl LH pulses were observed without estradiol production, suggesting LH neurosecretory dysfunction. <b>Conclusions: </b>Low FSH levels in adolescence are strongly related to a lack of LH pulses. Lack of LH pulses is highly suspect for HH. FSH may be a tool in the differentiation between HH and delayed puberty.
Growth Hormone Treatment in Growth Hormone-Sufficient and -Insufficient Children with Intrauterine Growth Retardation/Russell-Silver Syndrome
Authors: Azcona C. , Albanese A. , Bareille P. , Stanhope R. 
Published: April 2003

Fifty-eight short prepubertal children with IUGR received GH treatment (mean dose: 28 IU/m<sup>2</sup>/week) for a mean (SEM) period of time of 3.4 (0.13) years (range 1–4 years). They were subdivided according to their GH response to a pharmacological test. Twenty-six were GH insufficient (GHI) (group 1) and 32 were non-GHI (group 2). At the commencement of GH therapy mean chronological age was 6.1 (0.4) years in both groups, mean height SDS (SEM) was –3.5 (0.2) in group 1 and –3.6 (0.2) in group 2, mean growth velocity (GV) SDS (SEM) was –1.9 (0.3) in group 1 and –0.3 (0.2) in group 2. GH therapy induced significant growth acceleration throughout the follow-up period without any significant differences between the two groups. GV SDS (SEM) increased to +3.0 (0.5) in group 1 and to +3.7 (0.4) in group 2 (p < 0.05 compared to baseline) during the first year of therapy. Subsequently, the growth-promoting effects of GH therapy diminished with time but GV remained significantly higher than baseline. This growth enhancement produced a significant rise in height SDS (SEM) reaching –1.4 (0.2) in group 1 and –1.7 (0.2) in group 2 after 4 years. In conclusion, our data did not show any significant differences in the growth response to GH therapy between GH-sufficient and -insufficient IUGR children who were only distinguishable by their GH secretion. This indicates that the decision to treat a short IUGR child with GH therapy should not be based upon the GH response to a provocative test.
Metabolic Status of Children with Growth Hormone Insensitivity Syndrome and Responses to Treatment with IGF-I
Authors: Brain C.E. , Hubbard M. , Preece M.A. , Savage M.O. , Aynsley-Green A. 
Published: April 2003

Studies to date on the treatment with insulin-like growth factor I (IGF-I) of children with growth hormone (GH) insensitivity syndrome (GHIS) have concentrated principally on the effects of IGF-I therapy on the GH-IGF-I axis and on growth velocity. Little is known, however, about the metabolic status of children with GHIS and the consequences of IGF-I treatment on circulating intermediary metabolites involved in glucose homeostasis. We have studied 5 children with GHIS, aged 4.5–9 years, 3 male and 2 female, before and after 3 months of treatment with recombinant IGF-I, 80 µg/kg s.c. twice a day. The children were short (height SDS –3.8 to –7.3) and growing slowly (height velocity 1.8–3.4 cm/year). All were neurodevelopmentally normal at the time of the study with no history of severe symptomatic hypoglycaemia, in particular during the neonatal period. Before treatment, 4 of the 5 children demonstrated spontaneous hypoglycaemia (blood glucose <2.6 mmol/l), particularly at night, accompanied by substantial hyperketonaemia (range 1.43–4.63 mmol/l) and hyperfattyacidaemia (range 1.11–3.08 mmol/l). After 3 months of IGF-I treatment, the blood glucose concentrations in the diurnal profile were increased, with improvement in spontaneous hypoglycaemia and with increased fasting tolerance. The postprandial insulin-to-glucose ratio was reduced. GHIS is thus associated with asymptomatic nocturnal hypoglycaemia without apparent neurological deficit. Despite functional GH deficiency, brisk counter-regulation to hypoglycaemia occurred as evidenced by hyperfattyacidaemia and hyperketonaemia. Treatment with IGF-I twice a day improved fasting glucose tolerance, diurnal blood glucose concentrations, and postprandial insulin-to-glucose ratios. There was no exacerbation of hypoglycaemia on treatment. We suggest that in severe GH resistance, a protective mechanism exists for the brain from the effects of hypoglycaemia, at least partially mediated by excessive production of counter-regulatory metabolic fuels.
Does a Positive Oestrogen Feedback on the Hypothalamic-Pituitary Axis Exist Concurrently with a Defective Testosterone Feedback in Klinefelter’s Syndrome?
Authors: Goh V.H.H. , Lee K.O. 
Published: April 2003

The oestrogen provocation and GnRH challenge tests were carried out in 5 subjects with Klinefelter’s syndrome who had no history of previous hormonal therapy. The oestrogen provocation test consisted of an intramuscular injection of 10 mg of oestradiol valerate and blood samples were collected daily from day 0 to day 5. In 2 subjects, three GnRH challenge tests were carried out before (day 0) and on days 2 and 4 after the intramuscular injection of oestradiol valerate. During each GnRH challenge test, 7 blood samples were collected at 30-min intervals, 30 min and immediately before and for 150 min after the bolus dose of GnRH. Plasma concentrations of FSH, LH, testosterone and oestradiol were measured by established radioimmunoassays. Plasma levels of oestradiol rose significantly a day following the intramuscular injection of 10 mg of oestradiol valerate, reaching a peak on day 2 and then falling significantly to lower levels by days 4 and 5, although these levels were still significantly higher than the corresponding baseline levels. In the presence of high levels of oestradiol, the high basal levels of FSH were significantly suppressed, and remained suppressed throughout the 5 days of the study. LH, on the other hand, had a biphasic response; an initial significant suppression by day 1 persisting to day 3, but by days 4 and 5 a rebound in basal LH levels was noted. However, the levels on day 5 were not significantly higher than baseline levels. The pituitary responsiveness as far as the LH and FSH secretions were concerned reflected the baseline levels. The results of the present study refuted the claim that a positive oestrogen feedback exists in men including Klinefelter’s syndrome as a result of the removal of or reduced testosterone. In addition, the attenuated testosterone feedback in Klinefelter’s syndrome is responsible for the greatly amplified pituitary responsiveness to the trophic action of GnRH and this, in part, may be responsible for the elevated levels of FSH and LH seen in such patients.
Altered Bone Mineral Density in Patients with Complete Androgen Insensitivity Syndrome
Authors: Bertelloni Silvano , Baroncelli Giampiero I. , Federico Giovanni , Cappa Marco , Lala Roberto , Saggese Giuseppe 
Published: April 2003

Androgens have major influences on the regulation of bone mineralization. Because of their unique peripheral metabolism androgens may act on bone via activation of the androgen and/or estrogen receptor. Patients with complete androgen insensitivity syndrome (cAIS) are natural models to assess androgen actions on bone. We studied bone mineral density (BMD) in 10 patients with cAIS (mean age 13.70, range 4.7–19.8 years); 3 patients were studied before gonadectomy; the others were castrated and 6 were on hormonal replacement therapy. The BMD area (aBMD) was measured by dual energy X-ray; lumbar ‘apparent’ volumetric density (vBMD) was calculated using the formula vBMD = aBMD × [4/(π × width)]. In the patients, aBMD (0.72 ± 0.16 g/cm<sup>2</sup>) and vBMD (0.23 ± 0.04 g/cm<sup>3</sup>) were significantly (p < 0.001) reduced in comparison with those of a control group (n = 15, age 5.0–20.5 years: aBMD 1.028 ± 0.20 g/cm<sup>2</sup>; vBMD 0.35 ± 0.04 g/cm<sup>3</sup>). Both aBMD and vBMD were also reduced in comparison with normal values for males (aBMD –2.66 ± 0.99 SDS, p < 0.001; vBMD –3.08 ± 1.53 SDS, p < 0.0005) and females (aBMD –2.88 ± 1.05 SDS, p < 0.001; vBMD –2.84 ± 1.18 SDS, p < 0.0007). Real lumbar bone density, assessed by computed tomography in 1 patient, was also reduced (–6.2 SDS and –3.5 SDS for male and female normal values, respectively). Biochemical markers of bone metabolism were normal and not significantly different in patients and controls. Girls with cAIS did not have more fractures than controls. In conclusion, both aBMD and vBMD are reduced in cAIS patients, while bone turnover and the fracture risk seem not to be increased. Our data indicate that both androgens and estrogens may be required for acquisition of bone density during childhood.
Leptin Values in Placental Cord Blood of Human Newborns with Normal Intrauterine Growth after 30–42 Weeks of Gestation
Authors: Gómez Lourdes , Carrascosa Antonio , Yeste Diego , Potau Neus , Riqué Susana , Ruiz-Cuevas Pilar , Almar Jordi 
Published: April 2003

<i>Objective:</i> To evaluate leptin values in placental cord blood of newborns with normal intrauterine growth after 30–42 weeks of gestation. <i>Design:</i> Leptin, a protein encoded by the ob gene, plays an important role in the regulation of feeding behaviour and energy balance in rodents, primates and humans. The presence of leptin in human amniotic fluid and cord blood has recently been reported in human gestations at term and the possible role of leptin in human fetal growth suggested. However, little is known of leptin synthesis during human foetal development. Thus, the aim of our work was to measure leptin (RIA, Linco Research, Inc.) in placental cord blood of human newborns at different fetal ages. <i>Patients:</i> One hundred and twenty-six healthy newborns with normal intrauterine growth were studied. Twenty-nine were preterm (15 males and 14 females; gestational age: 30–36 weeks) and 99 were at term (49 males and 48 females; gestational age: 37–42 weeks). <i>Results:</i> Leptin values increase progressively throughout gestation from 1.30 ± 0.53 ng/ml at 30 weeks of gestation to 7.98 ± 4.96 ng/ml (mean ± SD) at term, and correlate positively with birth weight (r = 0.56, p < 0.005, n = 126), length (r = 0.37, p < 0.005, n = 126), BMI (r = 0.57, p < 0.005, n = 126), head circumference (r = 0.37, p < 0.005, n = 126), gestational age (r = 0.48, p < 0.005, n = 126) and placental weight (r = 0.38, p < 0.003, n = 59). Leptin values are statistically significantly lower (p < 0.005) preterm (median: 2.05 ng/ml; range: 0.7–8.3 ng/ml) than at term (median: 7.0 ng/ml; range: 1.1–28.1 ng/ml). Leptin values are also significantly (p < 0.005) higher in females (median: 7.2 ng/ml; range: 0.9–23.6 ng/ml, n = 62) than in males (median: 4.8 ng/ml; range: 0.7–28.1 ng/ml, n = 64), although there are no differences in weight (2,864 ± 536 g in females vs. 2,937 ± 744 g in males). Multiple regression analysis shows weight to be a positive sex-independent predictor of serum leptin values (p < 0.0005). Sex also proves to be a predictor of leptin, independently of weight and is higher in females than in males (p < 0.003). <i>Conclusion:</i> Leptin is present in placental human cord blood after 30–42 weeks of gestation. Newborn weight and sex are independent predictors of leptin values.
Suppression of Growth Hormone by Oral Glucose in the Evaluation of Tall Stature
Authors: Holl Reinhard W. , Bucher Peter , Sorgo Wolfgang , Heinze Eberhard , Homoki Janos , Debatin Klaus-Michael 
Published: April 2003

Excess secretion of growth hormone is a rare diagnosis in children or adolescents with tall stature. An oral glucose tolerance test (OGT) with determination of growth hormone is generally recommended to exclude this disorder. In order to test the validity of this approach in pediatric subjects, OGT tests were performed in 126 tall subjects (age: 12.4 ± 1.8 years; height: 3.1 ± 0.8 SDS). Nonsuppression was present in 39 subjects, however, anthropometric analysis and follow-up excluded the diagnosis of eosinophilic pituitary adenoma in all patients. The lowest GH concentration was reached 90 min after ingestion of oral glucose, GH rose above baseline at 180 min. Plasma concentrations of glucose and insulin did not differ between suppressors and nonsuppressors. In conclusion, absent suppression of growth hormone by oral glucose is common in tall children and adolescents. The test is therefore not recommended as a general screening for excess growth hormone. Prolonging the test beyond 120 min does not increase the diagnostic value.
Acute N-Methyl-<i>D,L</i>-Aspartate Administration Stimulates the Luteinizing Hormone Releasing Hormone Pulse Generator in the Ovine Fetus
Authors: Bettendorf M. , de Zegher F. , Albers N. , Hart C.S. , Kaplan S.L. , Grumbach M.M. 
Published: April 2003

To assess whether fetal luteinizing hormone releasing hormone (LH-RH) neurosecretory neurons have the capacity to respond to an exogenous stimulus, a synthetic excitatory amino acid analogue, N-methyl-D-L-aspartate (NMDA; 15 mg/kg), was given rapidly intravenously to 8 chronically catheterized fetuses (130–142 days of gestation; term 147 ± 3 days). All 8 fetuses exhibited a rise in plasma ovine luteinizing hormone (oLH) and ovine follicle-stimulating hormone (oFSH) within 5 min. The mean maximal increments of oLH (2.25 ± 0.36 ng/ml) and oFSH (1.21 ± 0.32 ng/ml) were significantly greater than in 6 normal saline-injected controls (oLH p < 0.0002; oFSH p < 0.03). The secretion of ovine prolactin (oPRL) and ovine growth hormone (oGH) was unaffected. LH-RH (5 μg) evoked a greater oLH response (p < 0.0009) and a greater oFSH response (p < 0.03) than NMDA (n = 6). Desensitization of the fetal gonadotrope by a potent LH-RH agonist, D-Trp<sup>6</sup>Pro<sup>9</sup>NEt-LH-RH (10 μg/day i.v. × 4 days), abolished the fetal oLH and the oFSH response to NMDA (n = 5). Moreover, D,L-2-amino-5-phosphonovalerate, a specific competitive antagonist for the NMDA receptor, completely inhibited the fetal oLH and oFSH response to NMDA, whereas D-L-2-amino-5-phosphonovalerate alone did not affect the plasma oLH or oFSH levels, the gonadotropin response to LH-RH, or the release of oGH or oPRL (n = 3). In primary ovine fetal pituitary cell cultures, NMDA (10<sup>–10</sup> to 10<sup>–6</sup> M) had no effect on oLH, oFSH, oGH, or oPRL secretion, whereas LH-RH stimulated oLH (10<sup>–8</sup> M; p < 0.0004) and oFSH (10<sup>–8</sup> M; p < 0.0001) release, evidence that NMDA did not have a direct pituitary effect. The results suggest that NMDA induces oLH and oFSH secretion by stimulation of the fetal LH-RH pulse generator and is mediated by central NMDA receptors. Fetal LH and FSH secretion and the response to LH-RH decrease in late gestation in the ovine and human fetus. The relative importance of sex steroid dependent and sex steroid independent central nervous system inhibition in this developmental change is unclear. It appears that central neural inhibition in addition to sex steroid negative feedback contributes to the decrease in fetal gonadotropin concentrations in late gestation. NMDA did not affect fetal oGH or oPRL secretion.
Evidence for the Synthesis of Corticosteroid-Binding Globulin in Human Placenta
Authors: Misao Ryou , Iwagaki Shigenori , Sun Wen-Shu , Fujimoto Jiro , Saio Masanao , Takami Tsuyoshi , Tamaya Teruhiko 
Published: April 2003

We demonstrated the expression of corticosteroid-binding globulin (CBG) in human placenta using reverse transcription-polymerase chain reaction-Southern blot analysis and immunohistochemical and immunoblotting studies. In the RT-PCR-Southern blot analysis, only one predicted PCR product was detected without nonspecific products in all samples of human placenta and 3A (tPA-30-1) human placental cells. In Western blot analysis, polyclonal anti-CBG antibodies recognized a protein of approximately 55 kD in the protein extracts prepared from 3A (tPA-30-1) cells. Additionally, CBG mRNA expression was demonstrated by in situ hybridization in the syncytiotrophoblasts. Immunohistochemical studies performed on the placenta demonstrated the presence of specific immunoreactivity in the syncytiotrophoblast layer surrounding the chorionic villi. These findings suggest that CBG is synthesized in human placenta during pregnancy in addition to its synthesis in the liver.
Increased Urinary Excretion of Collagen Crosslinks in Type 1 Diabetic Children in the First 5 Years of Disease
Authors: Valerio G. , Franzese A. , Esposito-Del Puente A. , Formicola S. , Di Maio S. , Contaldo F. , Rubino A. 
Published: April 2003

To analyze possible early abnormalities in bone resorption in type 1 diabetes mellitus the urinary excretion of the collagen crosslinks pyridinoline and deoxypyridinoline was evaluated by immunoassay in 26 prepubertal diabetic patients (mean age 7.8 ± 1.6 years, mean duration 3.0 ± 1.1 years) and 46 healthy children (age 8.3 ± 1.3 years). Relationships with growth parameters (height-standard deviation score, body mass index and height velocity during the year preceding the study) and metabolic control were sought. Longitudinal and ponderal growth was normal in diabetic children. Urinary collagen crosslink excretion was 88.4 ± 25 nmol/mmol creatinine (median 86, range 44–146) in diabetic patients and 65.6 ± 19 nmol/mmol creatinine (median 61, range 32–108) in controls (p = 0.0002). It was positively influenced by diabetic status (beta = 20.5) and negatively by age (beta = –6.41), controlling by sex and BMI (p = 0.0001). A positive correlation was found between collagen crosslinks and blood glucose (r = 0.48, p = 0.01) or HbA1c levels (r = 0.44, p = 0.02) evaluated at the time of the study, while no significant correlation was found with the mean HbA1c values assessed in the last year or throughout the whole duration of diabetes. Collagen crosslink excretion was significantly increased in patients who presented worsening of their metabolic control in the last 3 months. No relationship was found with the duration of disease or growth parameters. In conclusion, the elevated urinary excretion of collagen crosslinks in diabetic children indicates that bone resorption may be disturbed. Poor metabolic control influences the increased rate of bone resorption and may expose growing diabetic patients to a risk of bone loss.