Biomedical subjects

S Rosberg

Publications and source records attributed to S Rosberg.

At least 37 records · Page 2Linked 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

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

Circulating non-22 kDa growth hormone isoforms in healthy children of normal stature: relation to height, body mass and pubertal development.

The proportion of non-22 kDa GH isoforms was evaluated in 93 healthy children (48 boys aged 6.8-18.4 years and 45 girls aged 3.9-18.4 years) of normal stature (height +/- 2 s.d. score) at different stages of puberty. In addition, correlations among the proportion of non-22 kDa GH isoforms, auxology, spontaneous GH secretion and biochemical measurements were investigated. Serum non-22 kDa GH levels, expressed as percentage of total GH concentration in the samples, were determined by the 22 kDa GH exclusion assay, in which monomeric and dimeric 22 kDa GH are removed from serum and the non-22 kDa GH isoforms are quantitated using a polyclonal antibody GH assay. Samples were selected from spontaneous GH peaks in 24-h GH profiles. For boys, the median proportion of non-22 kDa GH isoforms was 8.5% (range 3.2-26.6%) and for girls it was 9.6% (1.8-17.4%), with no influence of age and no sex-related difference in prepubertal (boys, 7.2%; girls, 8.8%) or pubertal children (boys, 9.1%; girls, 9.9%). However, the median proportion of non-22 kDa GH isoforms was significantly higher in pubertal boys (9.1%) than in prepubertal boys (7.2%; P = 0.03). In pubertal boys, height S.D. scores (SDS) were inversely correlated to the proportion of non-22 kDa GH isoforms (r = -0.38; P = 0.02), especially at mid-puberty (r = -0.7; P = 0.01), indicating that the presence of increased amounts of circulating non-22 kDa GH isoforms was associated with less growth. In prepubertal children, positive correlations between non-22 kDa GH and weight SDS (r = 0.46; P = 0.03), weight-for-height SDS (r = 0.51; P = 0.01) and body mass index (r = 0.42; P = 0.04) were observed. No significant correlations were seen with spontaneous GH secretion or measurements of IGF-1, IGF-binding protein-3, insulin and leptin. These findings in normal children indicate that the proportion of circulating non-22 kDa GH isoforms may have physiologic significance for growth and metabolism in different stages of development, and emphasize the importance of evaluating the circulating ratio of 22 kDa and non-22 kDa GH in children with growth disorders.

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

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

Interleukin (IL)-6 and IL-8 in children with febrile urinary tract infection and asymptomatic bacteriuria.

Urine and serum interleukin (IL)-6 and IL-8 responses were higher in children with febrile urinary tract infection (n = 61) than in those with asymptomatic bacteriuria (n = 39). By univariate analysis, cytokine levels were related to age, sex, reflux, renal scarring, urine leukocytes, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and bacterial properties (P fimbriae but not hemolysin). Multivariate modeling showed that urine IL-6 responses were higher in girls than boys, increased with age, and were positively associated with CRP, ESR, serum IL-6, and urine leukocyte counts. The urine IL-8 response was not influenced by age, but it was influenced by P fimbriae and was associated with ESR, CRP, urine leukocytes, and female sex. The results show that cytokine responses to urinary tract infection vary with the severity of infection and that cytokine activation is influenced by a variety of host and bacterial variables.

Bacteriuria↗

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↗

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↗

PubMed1995

Spontaneous 24-hour growth hormone profiles in prepubertal small for gestational age children.

To evaluate spontaneous GH secretion in terms of both secretory rate and pulsatile pattern in prepubertal children born small for gestational age (SGA) and still short (below -2 SD scores) at or after 2 yr of age, 24-h GH profiles were investigated in 106 such patients (75 boys and 31 girls; mean age, 7.3 +/- 0.3 yr), 14 of whom (10 boys and 4 girls) had Silver-Russell syndrome. The 24-h secretion of GH was compared with that in 2 reference populations of prepubertal children born at an appropriate size for gestational age (AGA): 179 short healthy children (143 boys and 36 girls; mean age, 10.2 +/- 0.2 yr) and 73 children of normal stature (54 boys and 19 girls; mean age, 10.4 +/- 0.3 yr). Plasma GH concentrations from the 24-h profiles were transformed to GH secretion rates by means of a deconvolution technique. For the SGA children, the mean GH secretion rate was 0.3 U/24 h, with a positive correlation with age, whereas for the reference groups it was higher, 0.5 U/24 h for the short children (P < 0.05) and 0.7 U/24 h for the children of normal stature (P < 0.001). Interestingly, the GH secretion rate correlated positively with weight for height, expressed as the SD score, in girls born SGA (r = 0.40; P < 0.05), whereas an inverse correlation was found for the short AGA girls (r = -0.44; P < 0.05). The mean baseline GH level in the SGA children correlated negatively with age (r = -0.53; P < 0.01), with the highest values found for children younger than 6 yr of age. On the average, 8 GH peaks/24-h period were found in all groups of children, and using Fourier time-series analyses, a similar rhythmicity was found in all groups. In the SGA group, the children younger than 6 yr of age had more GH peaks with lower amplitudes than the older children. It is concluded that children born SGA and still short at or after 2 yr of age spontaneously secrete less GH than healthy children of short stature born AGA. Both of these subgroups of prepubertal short children, however, secrete less GH than children of normal height. This finding might in part explain the growth failure in SGA children. Moreover, in the youngest SGA children (2-6 yr of age) there was another pattern of GH secretion, with a high basal GH level, a low peak amplitude, and a high peak frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities, Multiple↗

PubMed1994

Estimation of growth hormone secretory patterns in children with use of a numerical deconvolution technique: experimental design with use of computer simulation.

Growth hormone (GH) secretion rates were estimated from 24-hour plasma GH concentration profiles using a model-based numerical deconvolution method. The basic kinetic parameters describing GH distribution and elimination were obtained from studies using single intravenous injections in GH-deficient children. Computer simulation techniques were used to produce 24-hour GH secretion profiles, which could serve as reference curves for analysis of the impact of certain practical aspects of the estimation of GH secretion, such as the method of blood sampling (discrete or integrated), sampling frequency and analytical errors. The results show that sampling intervals of 20 min are acceptable even in the presence of analytical errors, and that with this sampling interval, discrete blood sampling does not seem to be preferable to continuous withdrawal of blood.

Blood Specimen Collection↗

PubMed1994

Analysis of 24-hour growth hormone profiles in healthy boys and girls of normal stature: relation to puberty.

To evaluate the developmental and sex-specific changes in spontaneous GH secretion in terms of both secretory rate and pulsatile pattern, we investigated 24-h GH profiles (integrated 20-min samples) in 208 healthy children (91 girls and 117 boys) of normal heights at all stages of puberty. The plasma GH concentrations were transformed to GH secretion rates by means of a deconvolution technique. In prepubertal boys and girls, the mean secretion rates were comparable (0.66 and 0.68 U/24 h), but increased during puberty differently: earlier in girls, already at stage 2, with the highest rates at stages 3 and 4 (1.70 and 1.96 U/24 h); later in boys, at stage 4 (1.66 U/24 h). In both sexes the GH secretion rate decreased to prepubertal values at stage 5. The GH secretion rate correlated negatively with weight for height expressed in SD scores only in puberty (boys, r = -0.44, P < 0.001; girls, r = -0.22; P < 0.05). The number of peaks with high amplitudes increased with the progress of puberty in both boys (stage 2) and girls (stages 3 and 4). In both prepubertal girls and boys, a marked day-night rhythm was observed, which disappeared in midpuberty in boys owing to a greater increase in peak amplitudes during the day than at night. The mean number of peaks per 24 h was unchanged in girls, but decreased in late pubertal boys. In summary, we found a sex-specific increase in the GH secretion rate during pubertal development that occurs at an earlier pubertal stage and is more pronounced in girls than in boys. There are underlying changes in the mean GH amplitudes in both boys and girls as well as an increased baseline secretion in girls. In puberty, body composition modulates the GH secretion rate in both sexes.

Adolescent↗

PubMed1994

Effect of growth hormone treatment on insulin secretion and glucose metabolism in prepubertal boys with short stature.

The purpose of this study was to evaluate the effect on insulin secretion and glucose metabolism of daily growth hormone (GH) treatment, 0.1 U/kg, for up to 3 years in 42 short prepubertal boys without GH deficiency. Their median height standard deviation (SD) score increased from -2.7 to -1.7, whereas their weight for height SD score was unchanged after 3 years of treatment. Fasting plasma glucose concentrations were unchanged, but median fasting insulin concentrations increased from 6.0 mU/l before treatment to 7.8 mU/l (p < 0.05) after the first year. No further increase was seen during the second or third years. The median insulin area under the curve 10-60 min after an intravenous glucose tolerance test increased from 480 mU.l-1.min-1 before treatment to 799 mU.l-1.min-1 (p < 0.05) after 1 year. The median glucose disposal rate (K value) before GH treatment, 2.2%/min, was unchanged after 1 year of treatment. A significant positive correlation was found between the change in the height SD score and the change in fasting insulin concentration during the first (r = 0.45; p < 0.01) and second (r = 0.56; p < 0.05) years of GH treatment. It was concluded that GH treatment in prepubertal children without GH deficiency caused a moderate increase in fasting and stimulated insulin concentrations during the first year of treatment. There was no further change during the following years of treatment, and there were no negative effects on fasting plasma glucose concentrations or glucose disposal rates. The increase in insulin concentration was related positively to the growth response.

Blood Glucose↗

PubMed1993

Longitudinal follow-up of growth in children born small for gestational age.

Postnatal growth was followed in a population-based group of 123 small-for-gestational-age (SGA, birth weight < -2 SD) children (66 boys and 57 girls) to four years of age in order to determine the incidence and time of catch-up growth. Gestational age was determined by ultrasound in gestational weeks 16-17 in all pregnancies, thus eliminating the problem of distinguishing between SGA and preterm infants. Infants with well-defined causes for slow growth rate, i.e. those infants with chromosomal disorders, severe malformations, intrauterine viral infections or cerebral palsy, were excluded. The boys showed an extremely fast weight catch-up, 85% of them reaching weights greater than -2 SD at the age of three months and remaining above this level to the end of the study period. Such a fast catch-up growth was observed in only two-thirds of the girls, but at four years of age 85% of the girls were also above -2 SD. Length catch-up was more gradual than weight catch-up. Of the boys, 54% had lengths below -2 SD at birth, 26% at 1 year of age, 22% at 2 years of age, 17% at 2.5 years of age and 11% (n = 8) at 4 years of age. Corresponding figures for girls were: 69% at birth, 28% at 1 year, 15% at 2 years, 12% at 2.5 years and 5% (n = 3) at 4 years. At 4 years of age, only six boys and three girls remained below -2 SD for both weight and height.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗

PubMed1993

Intranasal administration of human growth hormone (hGH) in combination with a membrane permeation enhancer in patients with GH deficiency: a pharmacokinetic study.

Recombinant human GH (hGH) combined with a permeation enhancer for the nasal mucosa, sodium tauro-24,25-dihydrofusidate (STDHF), was administered intranasally (in) in six patients with classical GH deficiency. Three different doses were tested (0.2, 0.4, and 0.8 IU/kg BW). The concentration of STDHF was 1% in all doses. As a comparison, all patients received a sc injection of hGH (0.1 IU/kg BW). Blood samples were obtained at frequent intervals for up to 8 h (in doses) or 24 h (sc dose) and analyzed for the plasma concentration of hGH. All three i.n. doses gave a rapid increase in hGH with peak maxima (Cmax) at 20-30 min, and a decline to baseline within 2-3 h. In contrast, the sc dose resulted in a Cmax 2-3 h after the injection, followed by a plateau phase for 2-3 h. The baseline was reached 12-14 h after administration. The uptake [area under the curve (AUC)] was considerably lower for all three in doses, i.e. 1.6-3% of the AUC obtained with the sc dose. However, the Cmax varied between 5.7 +/- 1.4% (0.8 IU/kg BW) and 15.8 +/- 2.1% (0.4 IU/kg BW) of the maximal peak with the sc dose. Of the in doses, 0.4 IU/kg BW resulted in the highest AUC and Cmax. A self-rating protocol was also used to estimate nasal sensations for up to 2 h after dosing. All sensations (itching, burning, sneezing, and running of the nose) were transient and tolerable. This study demonstrates that hGH can be administered intranasally in combination with STDHF. The in dosing results in a plasma peak of hGH very similar to the physiological endogenous peak. No side-effects were noted, other than a transient nasal irritation. Therefore, the nasal route for hGH administration offers a more physiological and more convenient alternative to injections for the treatment of GH deficiency.

Administration, Intranasal↗

PubMed1993

Serum levels of insulin-like growth factor I (IGF-I) and IGF binding protein 3 reflect spontaneous growth hormone secretion.

The relationship between 24-h GH secretion, insulin-like growth factor (IGF) I serum levels, IGF-binding protein 3 (IGFBP-3) levels and height was studied in 114 healthy children and adolescents (147 tests). A significant correlation was found between the spontaneous GH secretion expressed as the area under the curve above baseline (AUCb) or the calculated 24-h GH secretion rate (GHb) and IGF-I (n = 147, r = 0.65, or 0.78, respectively, P < 0.001) or IGFBP-3 levels (r = 0.48 or 0.62, P < 0.001). Correlations were also significant within the various subgroups [females (n = 51), males (n = 96), prepubertal children (n = 75), pubertal children (n = 72)]. The slopes of the regression lines of IGF-I levels vs. AUCb or GHb were clearly steeper in pubertal children than in prepubertal ones; this was not as evident with IGFBP-3. In prepubertal children, a significant correlation was found between height (compared to Swedish reference values) standard deviation scores (SDS) and IGF-I SDS (n = 75, r = 0.66, P < 0.001) or IGFBP-3 SDS (r = 0.61, P < 0.001). The reproducibility during repeated testing (19 individuals, 6 prepubertal) was best with IGFBP-3 as compared to AUCb, GHb, or IGF-I which showed considerable variability. The data suggest: 1) that IGF-I and IGFBP-3 serum levels reflect spontaneous GH secretion in healthy individuals; 2) IGF-I levels are more sensitive to GH regulation than IGFBP-3; 3) in puberty, there may be increased sensitivity of IGF-I regulation by GH as compared to the prepubertal stage; 4) short children have low IGF-I and IGFBP-3 levels, whereas tall children have high levels, a fact which is likely to contribute to the understanding of height variability in a healthy population; 5) the good reproducibility of IGFBP-3 on repeated testing makes it an interesting parameter for the evaluation of the GH-IGF-axis. IGFBP-3 measurements may substitute for GH profiles in many cases, when the goal is an estimation of the GH secretion rate.

Adolescent↗