Biomedical subjects

K Albertsson-Wikland

Publications and source records attributed to K Albertsson-Wikland.

At least 73 records · Page 4Linked to original sources

PubMed1997

Twenty-four-hour profiles of luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol levels: a semilongitudinal study throughout puberty in healthy boys.

To follow and correlate gonadotropin and sex steroid changes throughout puberty, 24-h profiles of LH, FSH, testosterone, and estradiol were taken on several occasions for between 2-9.5 yr in 12 healthy boys, aged 8.7-18.2 yr. Serum concentrations of LH and FSH were measured every 20 min, whereas testosterone and estradiol were measured every 2-4 h during the 24-h period. The prepubertal boys (Tanner stage 1) were subdivided into two groups: Pre 1, with a testicular volume of 1-2 mL, and Pre 2, with a testicular volume of 3 mL. Pubertal stages were classified, according to testicular volume, as early puberty (pubertal stage 2; 4-9 mL), midpuberty (pubertal stages 3-4; 10-15 mL), and late puberty (pubertal stage 5; > or = 16 mL). Mean levels of LH and FSH increased with pubertal development, although the increase in LH was greater than that in FSH. These increases were due to elevated basal levels of LH and FSH as well as to increases in the number of peaks and the peak amplitudes of LH. No diurnal rhythm was found in boys at stage Pre 1. Thereafter, a clear diurnal rhythm appeared for LH, and later in puberty, an ultradian rhythm was superimposed, as shown by time-sequence analyses. A diurnal rhythm also existed for FSH, but was much less marked than that for LH despite a clear covariation between LH and FSH, as shown from cross-correlation studies. Testosterone also showed diurnal variations from the late prepubertal stage, followed by increasing levels during both day and night in puberty. We conclude that during puberty, gonadotropin levels rise differently for LH and FSH, which may be due to the development of differences in feedback mechanisms. Despite covariation between LH and FSH, only LH showed a clear diurnal variation. In parallel, nocturnal variations in testosterone and estradiol were found. Changes in mean levels of LH, testosterone, and estradiol as well as their mean daytime and nighttime levels follow each other from the prepubertal stages to late puberty.

Child↗

PubMed1997

Growth hormone (GH)-binding protein in prepubertal short children born small for gestational age: effects of growth hormone treatment. Swedish Study Group for Growth Hormone Treatment.

This study was undertaken to characterize the serum levels of GH-binding protein (GHBP) before and during GH treatment in prepubertal short children born small for gestational age (SGA) and their relationship with growth parameters. Sixty-seven prepubertal short children (49 boys and 18 girls; height SD score, -5.4 to -2.0; age, 2.0-12.8 yr) born SGA, 8 of whom (6 boys and 2 girls) had signs of Silver-Russell syndrome, participated in the study. Total GHBP was measured by a ligand-mediated immunofunctional assay. The mean (SD) change in height SD score during the year before the start of GH treatment (0.1 IU/kg.day) was 0.11 (0.20) SD score, and this value increased to a 0.84 (0.43) SD score during the first year (P < 0.001) and to a 1.27 (0.63) SD score during the 2-yr period of therapy (P < 0.001). The baseline GHBP values ranged from 49-392 pmol/L, and no relationships were found among sex, chronological age, and maximal GH response to an arginine-insulin tolerance test. A positive correlation between GHBP and body composition, expressed as weight for height SD score, was found in the whole group (r = 0.28; P < 0.05) and in boys (r = 0.44; P < 0.01). No relationship was found between GHBP and spontaneous 24-h GH secretion, in terms of either GH secretion rate or pulsatile pattern, whereas GHBP was positively correlated with insulin-like growth factor I (IGF-I) SD score (r = 0.28; P < 0.05) and IGF-binding protein-3 SD score (r = 0.39; P < 0.01). Using a multiple stepwise linear regression analysis, the model using the IGF-binding protein-3 SD score and the weight for height SD score at the start of GH therapy accounted for 33% of the variance in the baseline GHBP values. A mean increase of 27 (51)% in GHBP levels was found after 1 yr of therapy. However, a high degree of variability in the response of individuals to GH treatment in terms of GHBP levels was observed: in some children GHBP levels increased, whereas in others they decreased. In conclusion, GHBP levels in short prepubertal children born SGA were mostly within the normal range previously reported and correlated directly with body composition. An increase in GHBP levels was observed during GH treatment in some SGA children. No correlation was found between pretreatment GHBP levels and growth response to GH treatment.

Body Composition↗

PubMed1997

Increased proportion of circulating non-22-kilodalton growth hormone isoforms in short children: a possible mechanism for growth failure.

Current knowledge about the interaction between GH and its receptor suggests that the molecular heterogeneity of circulating GH may have important implications for growth. The aim of this study was to investigate the proportion of circulating non-22-kDa GH isoforms in prepubertal children with short stature (height less than -2 SD score) of different etiologies. We have also evaluated the relationships among the ratio of non-22-kDa GH isoforms, auxology, and spontaneous GH secretion. The study groups consisted of 17 girls with Turner's syndrome (TS), aged 3-13 yr, 25 children born small for gestational age (SGA) without postnatal catch-up growth, aged 3-13 yr; and 24 children with idiopathic short stature (ISS), aged 4-15 yr. The results were compared with those from 23 prepubertal healthy children of normal stature (height +/- 2 SD score), aged 4-13 yr. Serum non-22-kDa GH levels, expressed as a percentage of the total GH concentration, were determined by the 22-kDa GH exclusion assay, which is based on immunomagnetic extraction of monomeric and dimeric 22-kDa GH from serum and quantitation of non-22-kDa GH using a polyclonal antibody-based GH assay. All samples were selected from spontaneous GH peaks in 24-h GH profiles. The median proportion of non-22-kDa GH isoforms was increased in children born SGA (9.8%; P = 0.05) and girls with TS (9.9%; P = 0.01), but not in the group of children with ISS (8.9%), compared with that in normal children (8.1%). Individually, increased proportions of non-22-kDa GH isoforms, with values more than 2 SD above the mean for the normal group, were observed in 5 girls with TS, 5 children born SGA, and 4 children with ISS. In children born SGA, the proportion of non-22-kDa GH isoforms was directly correlated with different estimates of spontaneous GH secretion [mean 24-h GH concentration (r = 0.41; P = 0.04), area under the curve over baseline (r = 0.41; P = 0.04), and GH peak area (r = 0.61; P = 0.003)], whereas it was inversely correlated with height SD score (r = -0.42; P = 0.04). In conclusion, an increased proportion of circulating non-22-kDa GH isoforms was observed at spontaneous GH peaks in some non-GH-deficient short children. Our results suggest that the ratio of non-22-kDa GH isoforms in the circulation may have important implications for normal and abnormal growth.

Adolescent↗

PubMed1997

Growth response to growth hormone (GH) treatment relates to serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 in short children with various GH secretion capacities. Swedish Study Group for Growth Hormone Treatment.

The purpose of the study was to evaluate the relationship between the 1-yr (n = 193) and 2-yr (n = 128) growth response and the individual serum concentrations of insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) before and during GH treatment. Our study group of prepubertal short children had from very low to high GH secretory capacity, estimated during an arginine-insulin tolerance test, and the ages ranged from 3-15 yr at the start of treatment. Their serum levels of IGF-I and IGFBP-3 were low before treatment compared to those in an age-related reference group of prepubertal children and increased significantly from the start to 1 month of GH treatment. The mean increase in height SD score was 0.80 SD score after 1 yr of GH treatment and 1.26 SD score after 2 yr, with a wide range. In univariate analyses the highest correlation coefficients to the 2-yr growth response were found to be vs. the following variables from the start of treatment: IGF-I SD score (r = -0.49), log maximum GH concentration (log GHmax) during the arginine-insulin tolerance test (r = -0.47), difference between the height SD score of the individual child and the midparental height SD score (diffSD score; r = -0.45), IGFBP-3 SD score (r = -0.39), age (r = -0.30), short term change in IGFBP-3 SD score (r = 0.37), and IGF-I SD score (r = 0.34). In multivariate stepwise regression analysis, 41% of the variation in the 2-yr growth response could be explained by IGF-I SD score or log GHmax together with age at the start of treatment, weight SD score at 1 yr of age, and diffSD score. When both IGF-I SD score and GHmax were included and when the short term changes in IGF-I SD score were added, 46% and 58% of the variation, respectively, could be explained. The regression algorithms using different combinations of variables and their corresponding prediction intervals are also presented.

Adolescent↗

PubMed1997

Changes in the isoforms of luteinizing hormone and follicle-stimulating hormone during puberty in normal children.

Concentrations of LH and FSH are known to increase during normal pubertal development, but changes in the isoforms of the gonadotropins at this time have not been investigated in depth. We examined the median charge of serum LH and FSH using agarose suspension electrophoresis in 81 normal children at pubertal stages I-V. In pubertal girls there were no significant (P > 0.05) differences in the median charge of LH, but there was a small (P = 0.05) shift to more acidic FSH isoforms between pubertal stages I and IV. In boys there was a significant (P < 0.01) shift to more acidic isoforms for both LH and FSH by pubertal stage II. Further changes were not found later in puberty. Except for LH at pubertal stage I, where the median charge was similar (P > 0.05) for both sexes, the median charge was more basic (P < 0.001) for both LH and FSH in girls compared with boys at all five pubertal stages. The degree of charge heterogeneity of FSH, estimated as the peak width at half the peak height, was significantly (P < 0.01) larger at pubertal stage I than at pubertal stages III-V in both boys and girls. The charge heterogeneity of LH was similar for all pubertal stages in both sexes. In conclusion, there were few qualitative changes in the gonadotropins during normal female puberty, whereas in the male there was a dramatic shift to more acidic isoforms of LH and FSH early in puberty. This information may assist our understanding of normal and pathological processes during puberty and may be of clinical relevance in detecting the initiation of puberty in boys.

Adolescent↗

PubMed1997

Leptin levels are strongly correlated with those of GH-binding protein in prepubertal children.

OBJECTIVE: Nutritional status is an important determinant of growth, and previous studies have indicated that this is due, at least in part, to an increased target-tissue sensitivity to GH. An attractive candidate for mediating this effect is leptin, a hormone secreted by the adipose tissue. The aim of this study was to investigate if there was a connection between GH-binding protein (GHBP) and leptin. DESIGN AND METHODS: We investigated the relationship between serum levels of leptin and those of GHBP in 229 prepubertal children. These included 107 healthy children with normal GH secretion, 55 GH-deficient (GHD) children and 55 children born small for gestational age (SGA) sampled on one occasion for GHBP and leptin, and 12 healthy children followed longitudinally at monthly interval for 1 year. RESULTS: In the healthy children and in those born SGA, the serum concentration of GHBP was positively correlated with that of leptin (r = 0.65, P < 0.001; r = 0.74, P < 0.001 respectively). There was no correlation between GHBP and leptin in the group of children with GHD (r = 0.27, not significant). This means that leptin alone explained 42% of the variation of GHBP in the healthy group and 55% in the SGA group. The correlation remained after adjustment for body mass index and age in the healthy children (r = 0.57, P < 0.0001, r2 = 0.33) and for children born SGA (r = 0.74, P < 0.0001, r2 = 0.55). There was a positive correlation between the intra-individual monthly changes in GHBP and changes in leptin respectively, in the 12 healthy children followed longitudinally, the mean of the correlation coefficients was 0.38 (median = 0.29; range 0.03 to 0.86; P < 0.05). CONCLUSIONS: There was a highly significant correlation between serum levels of leptin and those of GHBP, except in children with GHD. The possibility that leptin could mediate the effects of body fat mass on GH sensitivity, therefore, merits further investigation.

Adolescent↗

PubMed1997

Serum leptin in short children born small for gestational age: relationship with the growth response to growth hormone treatment. The Swedish Study Group for Growth Hormone Treatment.

The product of the obese (ob) gene, leptin, is an adipocyte-derived hormone that is involved in the regulation of appetite and body weight. This study was undertaken in order to describe the basal serum levels of leptin in prepubertal short children born small for gestational age (SGA) and their relationship with growth parameters, before and during growth hormone (GH) treatment. Eighty-nine prepubertal short children (66 boys, 23 girls; height standard deviation score (SDS), -5.4 to -2.0; age, 2.0 to 12.8 years) born SGA, 12 of whom (9 boys, 3 girls) had signs of Silver-Russell syndrome, were included in the study. Serum leptin concentrations were measured by radioimmunoassay. Leptin levels in the children born SGA were compared with those in a reference group of 109 prepubertal healthy children born at an appropriate size for gestational age (AGA). The mean (S.D.) change in height SDS was 0.11 (0.22) during the year before the start of GH therapy (0.1 IU/kg/day) and increased to 0.82 (0.44) during the first year (P < 0.001) and to 1.28 (0.59) during the 2-year period of GH therapy (P < 0.001). The children born SGA were significantly leaner than the reference group. An inverse correlation was found between leptin and chronological age in the SGA group (r = -0.31, P < 0.01). The mean serum level of leptin in the children born SGA who were older than 5.5 years of age was 2.8 micrograms/l which was significantly lower than the mean value of 3.7 micrograms/l found in the children born AGA of the same age range. The difference remained after adjustment of leptin levels for sex, age, body mass index (BMI) and weight-for-height SDS (WHSDSSDS). Leptin correlated with WHSDSSDS (r = 0.32, P < 0.001) and BMI (r = 0.36, P < 0.01) in the reference population, but not in the SGA group. No correlation was found between leptin and spontaneous 24-h GH secretion, insulin-like growth factor (IGF)-I or IGF-binding protein-3 levels, or with fasting insulin or cortisol levels. Leptin levels at the start of GH treatment were correlated with the growth response over both 1 year (r = 0.46, P < 0.001) and 2 years (r = 0.51, P < 0.001) of GH therapy. Using multiple regression analysis, models including leptin levels at the start of GH therapy could explain 51% of the variance in the growth response after 1 year and 44% after 2 years of GH treatment. In conclusion, serum leptin levels are reduced in short children born SGA and are inversely correlated with chronological age. Leptin concentrations correlate with the growth response to GH treatment and might be used as a marker for predicting the growth response to GH treatment.

Aging↗

PubMed1997

Ocular fundus morphology in preterm children. Influence of gestational age, birth size, perinatal morbidity, and postnatal growth.

PURPOSE: To determine the influence of gestational age, birth size, perinatal morbidity, and postnatal growth on fundus morphology in preterm children using digital image analysis of fundus photographs. METHODS: Thirty-nine preterm children (mean postmenstrual gestational age, 29.1 weeks; range, 24.6 to 32) were included in the study. Thirty-nine healthy children, born at term, were used as control subjects. Fundus photographs were obtained at a mean age of 4.8 years (preterm) and 6.1 years (control subjects). RESULTS: There was no difference in optic disc, excavation, or peripapillary crescent area between the two groups. In the group of preterm children, a large optic disc size was associated with a low birth weight (rs = -0.29, P = 0.07), duration of assisted ventilation (rs = 0.43, P = 0.006), and number of blood transfusions (rs = 0.33, P = 0.04). The girls born prematurely showed a negative relation between the length of gestation and the area of the optic disc (r2 = 0.28, P = 0.009). No such relation was found in boys. The preterm children had increased tortuosity of retinal vessels (P < 0.001 and P < 0.002 for arteries and veins, respectively) and reduced number of vascular branching points (P < 0.001) compared with those of the control subjects. There were no associations between these vascular abnormalities and the perinatal and postnatal variables studied. CONCLUSIONS: No difference in optic disc morphology between preterm children and control subjects was found. However, preterm birth seems to affect the retinal vascular pattern close to the optic disc, independently of retinopathy of prematurity. Among the girls born preterm, optic disc size was negatively correlated to gestational age.

Birth Weight↗

PubMed1997

Growth hormone (GH) assays: influence of standard preparations, GH isoforms, assay characteristics, and GH-binding protein.

The impact of the adoption of the new biosynthetic growth hormone (GH) WHO International Reference Preparation (IRP 88/624), and the recommendation to report results in microgram/L instead of mU/L, is described. Conversion factors were determined by comparing both the linear and nonlinear relations of the GH values. The Pharmacia polyclonal IRMA (p-IRMA) and the DELFIA monoclonal time-resolved immunofluorometric assay (trIFMA) with kit calibrators calibrated either against the pituitary-derived WHO IRP 80/505 or the new 88/624 were evaluated. Conversion factors of 4.17 mU/L = 1 microgram/L for the p-IRMA and 4.31 mU/L = 1 microgram/L for the trIFMA were necessary. Different cross-reactivity patterns for the deaminated and dimer 22-kDa, 20-kDa, and 17-kDa GH isoforms were found. Expected GH recovery was similar when the measured values were adjusted according to the results of the cross-reactivity study.

Adolescent↗

PubMed1996

Growth hormone status in six children with fetal alcohol syndrome.

OBJECTIVE: Prenatal alcohol exposure may cause fetal alcohol syndrome (FAS), which is associated with pre- and postnatal retardation. MATERIALS AND METHODS: Spontaneous 24-h growth hormone (GH) secretion was measured in six prepubertal short children with FAS (two boys and four girls) aged 4-14 years. The response to a GH stimulation test, and levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) were also measured. Comparisons were made between the children with FAS and healthy children of both normal and short stature, as well as children born small for gestational age (SGA). RESULTS: There were no differences in the mean area under the curve above the baseline or the maximum level of GH during a 24-h period (GHmax) between the children with FAS and the reference groups. However, the estimated rate of spontaneous 24-h GH secretion in children with FAS was similar to that of children born SGA, but lower than in children of normal stature (p = 0.02). The plasma concentrations of IGF-I and IGFBP-3 were in the lower parts of the normal range. CONCLUSION: We conclude that GH secretion in short children with FAS is similar to that in short children born SGA; that is, in the lower range of normal children.

Adolescent↗

PubMed1996

Born small for gestational age: consequences for growth.

A large number of studies have documented a strong correlation between size at birth and subsequent height, although the reported incidence of catch-up growth and consequently the impact on final height has varied with time and between countries. These variations may be real, but could also be related to a number of methodological problems. The aim of this study was to explore two important aspects related to postnatal growth after disturbed fetal growth: first, the definition of small for gestational age (SGA), including the selection of cut-off points in defining shortness; and, secondly, the importance of the general socio-economic status of the population with regard to the incidence of growth faltering in early life. Data were analysed from two longitudinal population-based studies, one from Sweden and one from Hong Kong. Of the Swedish cohort, 3.8% had a birth length below -2 SD scores; in the Hong Kong population the corresponding value was 11.9% (Swedish reference values were used in both studies). The following conclusions were made. Size at birth is important for postnatal growth, and the difference in length at birth of 9-10 cm between the two extreme birth length subgroups remains, on average, until maturity. This seems to be true for the two study populations with different degrees of socio-economic development. However, the rate of catch-up growth is highly dependent on the definition of SGA, on the rate of catch-up growth in early life and on the incidence of growth faltering between 6 and 18 months of age.

Adolescent↗

PubMed1996

Growth hormone treatment of short children born small for gestational age: metanalysis of four independent, randomized, controlled, multicentre studies.

A minority of children born small for gestational age (SGA) fail to achieve sufficient catch-up growth during infancy and remain short throughout childhood, apparently without being growth hormone (GH) deficient. The effect of GH administration was evaluated over 2 years in short prepubertal children born SGA. The children (n = 244), who were taking part in four independent multicentre studies, had been randomly allocated to groups receiving either no treatment or GH treatment at a daily dose of 0.1, 0.2 or 0.3 IU/kg (0.033, 0.067 or 0.1 mg/kg) s.c. At birth, their mean length SD score (SDS) was -3.6 and their mean weight SDS -2.6; at the start of the study, mean age was 5.2 years, bone age 3.8 years, height SDS -3.3, height SDS adjusted for parental height -2.4, weight SDS -4.7 and body mass index (BMI) SDS -1.4. The untreated children had a low-normal growth velocity and poor weight gain. Although bone maturation progressed more slowly than chronological age, final height prognosis tended to decrease, according to height SDS for bone age, GH treatment induced a dose-dependent effect on growth, up to a near doubling of height velocity and weight gain; BMI SDS was not altered. Bone maturation was also accelerated differentially; however, final height prognosis increased in all GH treatment groups. The more pronounced growth responses were observed in younger children with a lower height and weight SDS. In conclusion, GH administration is a promising therapy for normalizing short stature and low weight after insufficient catch-up growth in children born SGA. Long-term strategies incorporating GH therapy now remain to be established.

Age Determination by Skeleton↗

PubMed1996

Boy with a ring 7 chromosome: a case report with special reference to dermatological findings.

A ring chromosome 7 was found in an 8-year-old boy investigated on account of short stature and facial dysmorphism. He had a fair skin, almost white hair, cafe-au lait spots and many black atypical pigmented naevi. Electron microscopy of his skin revealed structural changes in melanocytes and keratinocytes, suggesting disturbed cell growth and differentiation.

Cafe-au-Lait Spots↗

PubMed1996

More basic isoforms of serum gonadotropins during gonadotropin-releasing hormone agonist therapy in pubertal children.

An acute challenge of exogenous GnRH elicits rapidly increased serum gonadotropin levels with qualitative changes to more basic isoforms of both FSH and LH. Chronic GnRH agonist therapy suppresses endogenous gonadotropins, and the serum levels of FSH and LH are low and fairly constant. A possible qualitative change in the gonadotropins during GnRH agonist therapy was investigated by determination of the median charge of the gonadotropin isoforms before and during therapy in 18 pubertal children. Two different GnRH agonists were studied: buserelin, given intranasally or as a sc implant for 1.5-34 months to five girls, aged 7-10 yr, and for 5-6 months to two boys, aged 11-13 yr; and triptorelin, administered as a depot preparation for 3-6 months to four girls, aged 9-12.5 yr, and for 1-24 months to seven boys, aged 10.5-12 yr. FSH and LH in serum and eluates after electrophoresis in 0.10% agarose suspension were measured with sandwich fluoroimmunoassays. The mean serum FSH and LH levels decreased significantly (P < 0.05) in girls during triptorelin therapy, whereas only the FSH level decreased (P < 0.05) in the boys. There were no significant (P > 0.05) changes in serum gonadotropin levels during buserelin therapy. All of the children had more basic serum isoforms of LH, and all but one had more basic forms of FSH during the GnRH agonist treatments. In a girl who had more basic gonadotropin isoforms after treatment with triptorelin for 2 and 6 months, a GnRH challenge elicited the release of still more basic isoforms. The changes in mean median charge to more basic gonadotropin isoforms were highly significant for both busereline (P < 0.01) and triptorelin (P < 0.001) treatment. An increased (P < 0.001) degree of charge heterogeneity was observed for FSH after triptorelin therapy. These findings show that there is a qualitative change in the isoforms of both FSH and LH in serum during GnRH agonist therapy in pubertal children. The changes in charge to more basic gonadotropin isoforms most likely reflect a direct effect at the pituitary level, leading to the synthesis and/or selective release of less sialylated and sulfated isoforms of the gonadotropins. The observed qualitative changes in the gonadotropin isoforms in these pubertal children may be part of the clinical effects of GnRH agonist therapy, leading to an arrest or regression of puberty.

Adolescent↗

PubMed1996

Changes in serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 levels during growth hormone treatment in prepubertal short children born small for gestational age.

The aims of this study were to describe the basal serum levels of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) and to evaluate their changes during daily GH treatment (0.1 IU/kg; 33 micrograms/kg) for up to 2 yr in prepubertal short children born small for gestational age (SGA) and to correlate these changes with the growth response to GH therapy. Seventy-two prepubertal short children (height SD score, -5.4 to -2.0; age, 2.0-12.9 yr) born SGA (54 boys and 18 girls), eight of whom (six boys and two girls) had signs of Silver-Russell syndrome, participated in the study. The serum concentrations of IGF-I and IGFBP-3 were converted into SDS using our reference values for prepubertal healthy children. The mean (+/-SD) change in height SDS during the year before the start of GH treatment was 0.1 (0.2) and increased to 0.8 (0.4) during the first year (P < 0.001) and to 0.6 (0.3) during the second year of therapy (P < 0.001). Basal levels of both IGF-I and IGFBP-3 were significantly reduced compared with the reference values. The mean (+/-SD) basal serum concentration of IGF-I was -0.6 (1.1) SD score, and 80% of the SGA children had IGF-I levels below the 50th percentile of the reference group. The corresponding values for IGFBP-3 were -0.4 (1.0) SD score and 63%. The mean IGF-I level increased significantly by 55% from baseline to day 10 of treatment, by 76% on day 90, by 90% after 1 yr, and by 123% after 2 yr of GH treatment. The mean increases in IGFBP-3 were not as great: 25%, 27%, 35%, and 43%, respectively. The 1-yr growth response, expressed as the change in height SD score, correlated negatively with both the basal serum concentration of IGF-I (r = -0.37; P < 0.001) and IGFBP-3 (r = -0.35; P < 0.01), whereas a positive correlation was found to the 10-day percent increase in IGF-I (r = 0.32; P < 0.05). No correlations were found with the initial changes in IGFBP-3. Using a multiple stepwise linear regression analysis, the model using chronological age at the start of GH therapy, the mother's height expressed as a SD score, and the short term percent increase in IGF-I accounted for 42% of the variance in the 1-yr growth response. With the inclusion of 24-h GH profiles, 59% of the variability of the growth response could be explained. It is concluded that short prepubertal children born SGA show an increased growth rate in response to GH therapy. Their mean IGF-I and IGFBP-3 levels before treatment were low and correlated negatively with the growth response to treatment, indicating GH insufficiency. Finally, up to 59% of the variability in the 1-yr growth response to GH treatment could be explained by models using auxological and biochemical variables.

Abnormalities, Multiple↗

PubMed1996

Diurnal rhythm of 17 beta-estradiol secretion throughout pubertal development in healthy girls: evaluation by a sensitive radioimmunoassay.

Puberty is initiated by a nocturnal rise in gonadotropin secretion, which, in boys, results in an increased nocturnal secretion of testosterone. To characterize any similar diurnal rhythm of 17 beta-estradiol in healthy girls, we determined the secretion of 17 beta-estradiol before and during puberty. The study group consisted of 45 healthy girls whose height SD scores ranged from -3.7 to +4.9 compared with Swedish growth reference values. One to 6 profiles of 17 beta-estradiol (7 samples/24 h) were obtained from each girl during puberty and from 21 of the girls before clinical signs of puberty (a total of 76 serum profiles). Serum 17 beta-estradiol concentrations were determined using a modified RIA. The detection limit for the RIA was 1.8 fmol/tube, which corresponded to a serum level of 7.8 pmol/L in extracted serum. It was considered that levels above 50 pmol/L could be determined accurately without extraction. The serum levels of 17 beta-estradiol in prepubertal girls were, in most cases, below the detection limit, except in the morning, when in 17 of the 21 prepubertal girls, serum 17 beta-estradiol levels were just above the detection limit. All girls in early puberty (Tanner breast stage 2) had measurable serum levels of 17 beta-estradiol in the morning, whereas 10 of these 15 girls had levels below the detection limit around midnight. Later in puberty (Tanner breast stages 3 and 4), but before menarche, the diurnal rhythm was more obvious, with high levels of 17 beta-estradiol during the latter part of the night and in the morning. This diurnal rhythm was lost by 1 yr after menarche. There was a high degree of correlation between serum concentrations of 17 beta-estradiol and bone age, whereas there was much less, if any, correlation between 17 beta-estradiol and levels of sex hormone-binding globulin or dehydroepiandrosterone sulfate during puberty. We conclude that the nocturnal rise in gonadotropin secretion during puberty in girls is accompanied by an increased secretion of 17 beta-estradiol in the morning. This diurnal rhythm is lost 1 yr after menarche. Determination of 17 beta-estradiol levels in the morning could be useful in determining the initiation of puberty, whereas determinations in the late evening could provide information on the tempo of puberty.

Adolescent↗

PubMed1996

Improved final height in girls with Turner's syndrome treated with growth hormone and oxandrolone.

The spontaneous growth process in Turner's syndrome is characterized by a progressive decline in height velocity during childhood and no pubertal growth spurt. Therefore, therapy aimed at improving height during childhood as well as increasing final height is desirable for most girls with Turner's syndrome. Forty-five girls with Turner's syndrome, 9-16 yr of age (mean age, 12.2 yr), were allocated to three study groups. Group 1 (n = 13) was initially treated with oxandrolone alone; after 1 yr of treatment, GH without (group 1a; n = 6) or with (group 1b; n = 7) ethinyl estradiol was added. Group 2 (n = 17) was treated with GH plus oxandrolone. Group 3 (n = 15) was treated with GH, oxandrolone, and ethinyl estradiol. The dosage were: GH, 0.1 IU/kg.day; oxandrolone, 0.05 mg/kg.day; and ethinyl estradiol, 100 ng/kg.day. A height of 150 cm or more was achieved in 61%, 75%, and 60% of the girls in groups 1, 2, and 3, respectively. The most impressive increase in height was seen in group 2. In this group the mean final height was 154.2 cm (SD = 6.6), which is equivalent to a mean net gain of 8.5 cm (SD = 4.6) over the projected final height. In group 3, in which ethinyl estradiol was included from the start of therapy, the initially good height velocity decelerated after 1-2 yr of treatment. Their mean final height was 151.1 (SD = 4.6) cm, equivalent to a mean net gain of 3.0 cm (SD = 3.8). A similar growth-decelerating effect of ethinyl estradiol was seen in group 1b. We conclude that in girls with Turner's syndrome who are older than 9 yr of age, treatment with GH in combination with oxandrolone results in significant growth acceleration, imitating that in normal puberty, leading to a more favorable height during childhood. This mode of treatment also results in a significantly increased final height, permitting a great number of the girls to attain a final height of more than 150 cm. However, early addition of estrogen decelerates the height velocity and reduces the gain in height.

Adolescent↗

PubMed1995

Reduced growth hormone secretion with maintained periodicity following cranial irradiation in children with acute lymphoblastic leukaemia.

OBJECTIVE: Low dose cranial irradiation in children with acute lymphoblastic leukaemia (ALL) has been reported to reduce GH secretion in puberty. A recent study also reported a disturbed periodicity of GH secretion during puberty. We have focused on the different stages of puberty in studying these two parameters of GH secretion and have also compared the effects of 18 vs 24 Gy radiation dose. PATIENTS AND MEASUREMENTS: Thirty-four children previously treated for ALL were compared with a control group of 208 healthy normally growing children. GH secretion was measured as 24-hour profiles. RESULTS: In children treated for ALL, GH secretion rate and GH peak amplitude were below the median values for controls, both before puberty and during all stages of puberty. The difference between patients and controls was most pronounced in late puberty. Radiation with 18 or 24 Gy gave similar results. However, time sequence analysis showed a similar periodicity of GH secretion in both patient and control groups before, as well as during, puberty. Thus, before puberty a broad range of cycles per 24 hours was seen. These synchronized during puberty to a predominant GH peak frequency of one every 3-4 hours. CONCLUSIONS: After low dose cranial irradiation with 18 or 24 Gy, the total amount of GH secreted is reduced both before and during puberty. We could not confirm previous findings of impaired periodicity of GH secretion in these children.

Adolescent↗