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A Juul

Publications and source records attributed to A Juul.

At least 19 recordsLinked to original sources
PubMed1998

Collagen-derived markers of bone metabolism in osteogenesis imperfecta.

Markers of bone formation [C-terminal and N-terminal propeptides of procollagen I (PICP, PINP), osteocalcin and alkaline phosphatase] and bone resorption [C-terminal cross-linked telopeptide of collagen I (ICTP) and hydroxypyridinium cross-links, pyridinoline (Pyr) and deoxypyridinoline (Dpyr)] were measured in 78 osteogenesis imperfecta (OI) patients to investigate bone metabolism in vivo and relate marker concentrations to phenotype and in vitro collagen I defects, as shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). PICP and PINP were generally low, and the serum levels were lower in all children and adults with mild OI and a quantitative collagen defect than in patients with severe OI and a qualitative collagen I defect. ICTP, Pyr and Dpyr were generally normal or reduced, but elevated in severely affected adults with a qualitative collagen I defect. The in vivo findings correlated with in vitro results of collagen I SDS-PAGE. Bone turnover is reduced in OI children and mildly affected OI adults, whereas bone resorption is elevated in severely affected adults. These findings may prove helpful for diagnosis and decision-making regarding therapy in OI.

Adolescent↗
PubMed1998

Effects of growth hormone replacement therapy on IGF-related parameters and on the pituitary-gonadal axis in GH-deficient males. A double-blind, placebo-controlled crossover study.

It has been suggested that growth hormone (GH) may play a regulatory role in male reproductive function. To express full anabolic effect in immature boys testosterone apparently requires the presence of GH. In GH-deficient adults, GH replacement therapy exerts a variety of anabolic actions, some of which are similar to the effects of gonadal steroids. However, little is known about the potential effects of GH on gonadal steroids and on dynamic tests of pituitary-gonadal function in adults with GH deficiency. We evaluated the pituitary-gonadal axis in a 4-month double-blind, placebo-controlled GH study in 13 young males with childhood-onset GH deficiency of which 6 had isolated GH deficiency. GH treatment significantly increased serum levels of total IGF-I from 98 (68) to 323 (126) microg/l, free IGF-I from 0.48 (0.47) to 2.24 (1.66) microg/l, IGFBP-3 from 1,874 (1,178) to 3,520 (778) microg/l and ALS levels from 9,182 (5,524) to 16,872 (6,278) microg/l (all p < 0.0001). We found no differences in basal testosterone levels in the 13 patients between the GH and placebo treatment periods (21.9 (5.1) vs. 24.5 (8.1) nmol/l, nonsignificant). Furthermore, no effect of GH on the testicular response to hCG after 72 h was seen compared to placebo (36.2 (6.4) vs. 38.8 (10.3) nmol/l). In addition, no differences existed in basal SHBG, DHT, free testosterone, delta4-adion and DHEA-S levels. There were no statistically significant differences in maximal FSH and LH response to a GnRH challenge between the GH and the placebo periods (15.7 (5.3) vs. 18.0 (8.8) U/l and 47.0 (26.4) vs. 40.4 (26.5) U/l, respectively). Furthermore, there was no effect on cortisol responses after ACTH between the GH and the placebo periods. However, significantly higher estradiol levels were seen after GH treatment (110 (50) pmol/l) compared to after placebo (89 (34) pmol/l, p = 0.03). Prostate-specific antigen levels decreased after GH treatment compared to after placebo (0.42 (0.54) vs. 0.47 (0.48) microg/l) and this difference almost reached statistical significance (p = 0.059). Inhibin-B levels were significantly lower in hypogonadal patients substituted with androgens, but GH had no effect on inhibin-B levels. In conclusion, GH replacement therapy in 13 GH-deficient young adult males resulted in significant increases in total and free IGF-I as well as in ALS levels in all patients, but had no significant effect on: (1) the pituitary FSH and LH response to GnRH; (2) basal and hCG-stimulated levels of androgens and SHBG; (3) basal inhibin-B levels; (4) ACTH-stimulated cortisol secretion. By contrast, GH administration had subtle anti-androgenic effects in terms of elevated elevated estradiol levels and decreased prostate-specific antigen levels, although both parameters remained within the normal range. Thus, at the level of blood chemistry the effects of GH administration do not appear to involve major alterations in the pituitary-gonadal axis.

Adrenocorticotropic Hormone↗
PubMed1998

The acid-labile subunit of human ternary insulin-like growth factor binding protein complex in serum: hepatosplanchnic release, diurnal variation, circulating concentrations in healthy subjects, and diagnostic use in patients with growth hormone deficiency.

Circulating insulin-like growth factor-I (IGF-I) is predominantly bound in the trimeric complex comprised of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS). Circulating concentrations of IGF-I, IGFBP-3 and ALS are believed to reflect the GH secretory status, but the clinical use of ALS determination is not known. We therefore, determined the: 1) hepatosplanchnic release of ALS by liver vein catheterization (n=30); 2) 24-h diurnal variation of ALS (n=8); 3) normal age-related ranges of circulating ALS (n=1158); 4) diagnostic value of ALS in 108 patients with childhood-onset GH deficiency (GHD). We found: 1) no significant arteriovenous gradient over the liver ofALS, IGF-I, and IGFBP-3; 2) the diurnal variation of ALS was 12% (mean coefficient of variation percent); 3) ALS levels increased throughout childhood with maximal levels in puberty, with a subsequent decrease with age in adults; and 4) ALS levels were below -2 SD in 57 of 79 GHD patients (sensitivity 72%) and above 2 SD in 22 of 29 patients with normal GH response (specificity 76%), which was similar, compared with the diagnostic utility of IGF-I and IGFBP-3. Finally, our findings indicate that hepatic ALS production is not measurable by this approach or, alternatively, that the liver is not the primary source of circulating ALS, IGF-I, or IGFBP-3 in humans. In conclusion, we have provided extensive normal data for a novel ALS assay and found that circulating ALS levels exhibit minor diurnal variation. We suggest that ALS determination may be used in future classification of adults suspected of GHD.

Adolescent↗
PubMed1998

Serum leptin levels in children and adolescents with insulin-dependent diabetes mellitus in relation to metabolic control and body mass index.

The ob protein, termed leptin, is produced by adipocytes and is thought to act as an afferent satiety signal regulating weight through suppressing appetite and stimulating energy expenditure in humans and/or rodents. Insulin has been found to be a potent stimulator of leptin expression in rodents. It is unclear at present whether this insulin action is a direct or an indirect effect. To investigate whether leptin concentrations in children and adolescents with type 1 diabetes (IDDM) were related to metabolic status, body weight, body mass index and insulin treatment, we have measured leptin concentrations in serum from 13 newly diagnosed IDDM patients before the beginning of insulin treatment (8 girls, 5 boys, aged 4.7-17.5 years) and in 134 patients with IDDM during treatment (64 girls, 70 boys, aged 2.6-20.1 years) using a specific radioimmunoassay. The data from patients with diabetes were compared with normative data that were derived from a large cohort of healthy children and adolescents. Serum from children with newly diagnosed diabetes had significantly lower levels of leptin (mean 1.28+/-1.60 ng/ml, range 0.14-6.13 ng/ml) compared with healthy children (n=710) (mean 2.2 ng/ml, range 0.26-14.4ng/ml) and compared with insulin-treated children and adolescents (mean 5.18+/-5.48 ng/ml, range 0.26-29.77 ng/ml) (P<0.0001) even after adjustment for gender and body mass index (BMI). Serum leptin levels in patients with IDDM were significantly correlated with BMI (r=0.42, P<0.0001). Multiple regression analysis showed that age and BMI were significantly correlated with leptin levels, while duration of diabetes, mean HbA1c levels, insulin dose and plasma glucose, triglyceride and cholesterol levels were not. Females had higher serum leptin concentrations than males even when adjusted for BMI (P<0.0001). Surprisingly and most importantly, leptin levels in insulin-treated young adult (Tanner stage 5) patients were significantly higher than values found in the healthy nondiabetic reference population when adjusted for sex, Tanner stage and BMI. These findings suggest that leptin levels in IDDM patients show a similar dependency on adipose tissue and age as in healthy, normal children. The data provide evidence that insulin may be of importance as a regulator of serum leptin levels in vivo not only in rodents but also in humans. It is hypothesized that the elevated BMI-adjusted leptin levels in adolescents with IDDM could indicate either that these patients may be oversubstituted by the intensified insulin therapy that they are receiving or that their body composition and body fat content may differ from that of healthy adolescents in the sense that they have a relative increase in fat mass.

Adolescent↗
PubMed1997

[Prognostic value of insulin-like growth factor I-IGF-I--and its binding protein IGFBP-3 in alcoholic liver disease].

IGF-I is a single polypeptide chain with important anabolic and endocrine activities. The liver is the major source of IGF-I and its binding protein, IGFBP-3. Circulating concentrations of IGF-I and IGFBP-3 are decreased in patients with chronic liver disease and correlate with the severity. The aim of this study was to assess the additional prognostic value of IGF-I and IGFBP-3 in patients entered in a large multicentre study (EMALD). Three hundred and thirty-seven patients with alcoholic liver disease were studied in a randomised placebo-controlled trial of malotilate with a mean follow-up period of 569 days (range: 7-1544). A multivariate Cox regression analysis of pertinent clinical and biochemical variables revealed a significant independent prognostic value of years of alcohol intake, coagulation factors 2, 7, and 10, alkaline phosphatases, serum creatinine, and immunoglobulin M (IGM). When IGF-I or IGFBP-3 were added into this model, a Cox regression analysis showed that either had a significant independent prognostic value. As IGF-I and IGFBP-3 were closely correlated, they contained almost the same prognostic information. Inclusion of IGF-I gave these results: IGF-I (p < 0.03), alcohol intake (p < 0.02), coagulation factors 2, 7, and 10 (p < 0.01), creatinine (p < 0.001), and IgM (p < 0.01) contained independent prognostic information. Inclusion of IGFBP-3 gave these results: IGFBP-3 (p < 0.02), alcohol intake (p < 0.05), coagulation factor 2, 7, and 10 (p < 0.01), creatinine (p < 0.001), and IgM (p < 0.02) were independent predictors of survival. In conclusion IGF-I or IGFBP-3 provides important additional information on survival in patients with alcoholic liver disease.

Adult↗
PubMed1997

Prediction of the outcome of growth hormone provocative testing in short children by measurement of serum levels of insulin-like growth factor I and insulin-like growth factor binding protein 3.

Serum levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) reflect the secretion of endogenous growth hormone (GH) in healthy children and exhibit little diurnal variation, which makes them potential candidates for screening of GH deficiency (GHD). We evaluated serum IGF-I and IGFBP-3 levels in relation to the outcome of GH provocative testing in 203 children and adolescents (111 boys and 92 girls) in whom GHD was suspected. A total of 1030 children served as control subjects. In children less than 10 years of age, IGF-I levels were below the cutoff limit in 8 of 15 children with GHD (sensitivity 53.3%) and above the cutoff limit in 47 of 48 children with a normal GH response (specificity 97.9%). Similarly, IGFBP-3 levels were below the cutoff limit in 9 of 15 children with GHD (sensitivity 60%) and above the cutoff limit in 47 of 48 children with a normal GH response (specificity 97.9%). Consequently the predictive value of a positive test result in prepubertal children was 88.8% for IGF-I and 90% for IGFBP-3. In children and adolescents between 10 and 20 years of age, IGF-I levels were below the cutoff limit in 34 of 46 children with GHD (sensitivity 73.9%) and above the cutoff limit in 63 of 94 children with normal GH response (specificity 67%). IGFBP-3 levels were below the cutoff limit in 26 of 46 children with GHD (sensitivity 56.5%) and above the cutoff limit in 74 of 94 children with a normal GH response (specificity 78.7%). Accordingly the positive predictive value and in 10- to 20-year-old children was 52.3% for IGF-I and 56.5% for IGFBP-3. Combination use of IGF-I and IGFBP-3 gave additional diagnostic information. We conclude that a subnormal IGF-I level, and especially a subnormal IGFBP-3 level, are highly predictive of a subnormal GH response to a provocative test in prepubertal children in whom GHD is suspected. On the other hand, a normal IGF-I or IGFBP-3 level does not exclude GHD. The predictive value of IGF-I and IGFBP-3 in pubertal children is diminished in comparison with that in prepubertal children. We believe that IGF-I and IGFBP-3 are valuable tools in the evaluation of childhood GHD.

Adolescent↗
PubMed1997

Leptin levels in patients with anorexia nervosa are reduced in the acute stage and elevated upon short-term weight restoration.

Circulating leptin concentrations are known to be low in acute anorexia nervosa (AN), which is characterized by low weight, amenorrhea and specific psychopathological features. In this study plasma leptin concentrations were determined during inpatient treatment of 23 adolescent females with AN using a sensitive radioimmunoassay (RIA) and set into relationship to leptin levels of females matched for age, body mass index (BMI; kg m-2) and/or percent body fat. At referral patients had leptin concentrations well below the female controls. Weight gains led to steep increases of leptin levels which peaked at values well in excess of those observed in controls matched for BMI. In patients who reached the final treatment stage and who were followed-up after discharge, levels subsequently fluctuated and finally dropped into or below the control range. The low leptin levels at referral are likely to be involved in the pathogenesis of amenorrhea and the reduced metabolic state of acutely ill patients. Peak leptin levels reached after weight gain are possibly the cause of increased energy expenditure during this stage of the disorder.

Adolescent↗
PubMed1997

Effect of long-term refeeding on protein metabolism in patients with cirrhosis of the liver.

Patients with cirrhosis of the liver require an increased amount of protein to achieve N balance. However, the utilization of protein with increased protein intake, i.e. the slope from regression analysis of N balance v. intake, is highly efficient (Nielsen et al. 1995). In the present study, protein requirement and protein utilization were investigated further by measuring protein synthesis and degradation. In two separate studies, five or six patients with cirrhosis of the liver were refed on a balanced diet for an average of 2 or 4 weeks. Protein and energy intakes were doubled in both studies. Initial and final whole-body protein metabolism was measured in the fed state by primed continuous [15N]glycine infusion. Refeeding caused a statistically significant increase of about 30% in protein synthesis in both studies while protein degradation was only slightly affected. The increase in protein synthesis was associated with significant increases in plasma concentrations of total amino acids (25%), leucine (58%), isoleucine (82%), valine (72%), proline (48%) and triiodothyronine (27%) while insulin, growth hormone, insulin-like growth factor (IGF)-I and IGF-binding protein-3 were not changed significantly. The results indicate that the efficient protein utilization is due to increased protein synthesis, rather than decreased protein degradation, and suggest that increases in plasma amino acids may be responsible for the increased protein synthesis. A comparison of the patients who had a normal protein requirement with the patients who had an increased protein requirement suggests that the increased protein requirement is due to a primary increase in protein degradation. It is speculated that this is due to low levels of IGF-I secondary to impaired liver function, since initial plasma concentration of IGF-I was about 25% of control values and remained low during refeeding.

Dietary Proteins↗
PubMed1997

Changes in serum concentrations of growth hormone, insulin, insulin-like growth factor and insulin-like growth factor-binding proteins 1 and 3 and urinary growth hormone excretion during the menstrual cycle.

Few studies exist on the physiological changes in the concentrations of growth hormone (GH), insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) within the menstrual cycle, and some controversy remains. We therefore decided to study the impact of endogenous sex steroids on the GH-IGF-IGFBP axis during the ovulatory menstrual cycle in 10 healthy women (aged 18-40 years). Blood sampling and urinary collection was performed every morning at 0800 h for 32 consecutive days. Every second day the subjects were fasted overnight before blood sampling. Follicle stimulating hormone, luteinizing hormone (LH), oestradiol, progesterone, IGF-I, IGFBP-3, sex hormone-binding globulin, dihydroepiandrosterone sulphate and GH were determined in all samples, whereas insulin and IGFBP-1 were determined in fasted samples only. Serum IGF-I concentrations showed some fluctuation during the menstrual cycle, with significantly higher values in the luteal phase compared to the proliferative phase (P < 0.001). Mean individual variation in IGF-I concentrations throughout the menstrual cycle was 13.2% (SD 4.3; range 0.1-18.3%). There were no cyclic changes in IGFBP-3 serum concentrations and no differences in IGFBP-3 concentrations between the luteal and the proliferative phases. Mean individual variation in IGFBP-3 concentrations throughout the menstrual cycle was 8.8% (SD 2.7; range 3.2-14.1). IGFBP-1 concentrations were inversely associated with insulin concentrations, and showed a significant pre-ovulatory increase that returned to baseline at the day of the LH surge. Fasting insulin concentrations showed large fluctuations throughout the menstrual cycle without any distinct cyclic pattern. No cyclic changes in urinary GH excretion during menstrual cycle were detected. We conclude that, although IGF-I concentrations are dependent on the phase of the menstrual cycle, the variation in IGF-I concentrations throughout the menstrual cycle is relatively small. Therefore, the menstrual cycle does not need to be considered when evaluating IGF-I or IGFBP-3 serum values in women suspected to have GH deficiency.

Adolescent↗
PubMed1997

Knemometry, urine cortisol excretion, and measures of the insulin-like growth factor axis and collagen turnover in children treated with inhaled glucocorticosteroids.

Correlations between knemometric (lower leg length) growth rates and urine free cortisol excretion, respectively, and serum concentrations of IGF-I, IGF binding protein-3, osteocalcin, carboxy terminal propeptide of type I collagen (PICP), carboxy terminal pryridinoline cross-linked telopeptide of type I procollagen (ICTP), and amino terminal propeptide of type III procollagen (PIIINP) were investigated in 17 asthmatic children aged 7-14 y during treatment with fluticasone propionate, 200 micrograms, and beclomethasone dipropionate, 400 and 800 micrograms/d, taken from dry powder inhalers. The study was a double blind, crossover trial with three active treatment periods and two wash-out periods. All periods were 15 d long. Overnight urine free cortisol/ creatinine x 10(6) did not correlate with knemometric growth rates or any of the serum markers. Significant correlations (Pearson's correlation coefficient, P) between knemometric growth rates and IGF-I (0.41; 0.006), IGFBP-3 (0.35; 0.02), PICP (0.44; 0.003), ICTP (0.35; 0.001), and PIIINP (0.46; 0.002) were found. Compared with fluticasone propionate, 200 micrograms, beclomethasone dipropionate, 400 and 800 micrograms, caused significant suppression of lower leg growth rate (F = 12.41; p = 0.002, and F = 23.30; p = 0.0001, respectively) and of urine free cortisol/creatinine x 10(6) (F = 10.52; p = 0.003, and F = 13.74; p = 0.001). Beclomethasone, 800 micrograms, caused suppression of PICP compared with fluticasone propionate, 200 micrograms (F = 8.31; p = 0.008), and beclomethasone, 400 micrograms (F = 7.53; p = 0.01). Both low (F = 6.82; p = 0.02) and high (F = 23.35; p = 0.0001) doses of beclomethasone were associated with reduced concentrations of ICTP, the high dose being the most suppressive (F = 4.42; p = 0.05). Beclomethasone 400 (F = 9.75; p = 0.004) and 800 micrograms (F = 23.61; p = 0.0001) resulted in reduced levels of PIIINP. Reduced short-term knemometric growth rates in children treated with inhaled glucocorticosteroids reflect suppressive effects on type I and type III collagen turnover.

Administration, Inhalation↗
PubMed1997

Serum inhibin B in healthy pubertal and adolescent boys: relation to age, stage of puberty, and follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol levels.

Inhibin B levels were measured in serum from 400 healthy Danish prepubertal, pubertal, and adolescent males, aged 6-20 yr, in a cross-sectional study using a recently developed immunoassay that is specific for inhibin B, the physiologically important inhibin form in men. In addition, serum levels of FSH, LH, testosterone, and estradiol levels were measured. Serum levels of inhibin B, FSH, LH, testosterone, and estradiol all increased significantly between stages I and II of puberty. From stage II of puberty the inhibin B level was relatively constant, whereas the FSH level continued to increase between stages II and III. From stage III of puberty the FSH level was also relatively constant, although there was a nonsignificant trend of slightly decreased FSH levels at pubertal stage V compared to stage IV. The levels of serum LH, testosterone, and estradiol increased progressively throughout puberty. In prepubertal boys younger than 9 yr, there were no correlation between inhibin B and the other three hormones. In prepubertal boys older than 9 yr, a significant positive correlation was observed between inhibin B and FSH, LH, and testosterone. However, at this pubertal stage, each hormone correlated strongly with age, and when the effect of age was taken into account, only the partial correlation between inhibin B and LH/testosterone remained statistically significant. At stage II of puberty, the positive partial correlation between inhibin B and LH/testosterone was still present. At stage III of puberty, an negative partial correlation between inhibin B and FSH, LH, and estradiol was present, whereas no correlation between inhibin B and testosterone could be observed from stage III onward. The negative correlation between inhibin B and FSH persisted from stage III of puberty onward, whereas the correlation between inhibin B and LH and between inhibin B and estradiol was nonsignificant at stages IV and V of puberty. In conclusion, in boys, serum inhibin B levels increase early in puberty; by pubertal stage II the adult level of inhibin B has been reached. The correlation of inhibin B to FSH, LH, and testosterone changes during pubertal development. Early puberty is characterized by a positive correlation between inhibin B and LH/testosterone, but no correlation to FSH. Late puberty (from stage III) is characterized by a negative correlation between inhibin B and FSH (which is maintained in adult men), a diminishing negative correlation between inhibin B and LH, and no correlation between inhibin B and testosterone, suggesting that developmental and maturational processes in the hypothalamic-pituitary-gonadal axis take place, leading to the establishment of the closed loop feedback regulation system operating in adult men. The positive correlation between inhibin B and LH/ testosterone at the time when serum inhibin B levels rise early in puberty suggests that Leydig cell factors may play an important role in the maturation and stimulation of Sertoli cells in the beginning of pubertal development.

Adolescent↗
PubMed1997

Growth hormone (GH) provocative retesting of 108 young adults with childhood-onset GH deficiency and the diagnostic value of insulin-like growth factor I (IGF-I) and IGF-binding protein-3.

Serum levels of total insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) reflect the endogenous GH secretion in healthy children and exhibit little diurnal variation, which makes them good diagnostic markers for screening of GH deficiency (GHD) in short children, although some controversy still exists. In adults, the diagnostic value of IGF-I and IGFBP-3 suspected of GHD has been reported in only a few studies. We performed a GH provocative test, using oral clonidine, in 108 patients who had previously been treated with GH during childhood (73 men and 35 women). Basal IGF-I and IGFBP-3 levels were compared to those in 1237 healthy controls (312 controls > 18 yr) as well as to peak GH levels. Seventy-nine patients had peak GH values below a cut-off value of 7.5 micrograms/L (34 with isolated GHD), whereas 29 patients had a normal GH response (28 with previous isolated GHD), i.e. 45% of patients treated with GH during childhood because of isolated GHD had a normal GH response when retested in adulthood. Multiple regression analysis revealed that peak GH levels were dependent on the degree of hypopituitarism, body mass index, and duration of disease. IGF-I levels were below -2 SD in 60 of 79 GHD patients and above -2 SD in 21 of 29 patients with a normal GH response. IGFBP-3 levels were below -2 SD in 54 of 79 GHD patients and above -2 SD in 23 of 29 patients with a normal GH response. Multiple linear regression analysis demonstrated that IGF-I and IGFBP-3 were significantly dependent on peak GH levels and the number of other pituitary axes affected. In this analysis, duration of disease was significantly associated with both IGF-I and IGFBP-3, whereas body mass index was significantly associated with IGFBP-3, but not with IGF-I. We conclude that IGF-I and IGFBP-3 determinations predict the outcome of a GH provocative test in adults suspected of GHD and believe that IGF-I as well as IGFBP-3 serum concentrations are valuable diagnostic parameters in the evaluation of GHD in adults with childhood-onset disease. We suggest that children who have been treated with GH should undergo reassessment of their GH secretory status as young adults by provocative testing as well as by IGF-related peptides before continued adult GH replacement therapy is considered. However, our data suggest that it is not necessary to reconfirm GH deficiency by GH provocative testing in young adults who have two or more pituitary hormone deficiencies in addition to GHD.

Administration, Oral↗
PubMed1997

Free insulin-like growth factor I serum levels in 1430 healthy children and adults, and its diagnostic value in patients suspected of growth hormone deficiency.

Serum levels of total insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) reflect endogenous GH secretion in healthy children, which makes them good diagnostic markers for screening of GH deficiency (GHD) in short children, although some controversy still exists. Only a minor fraction of the total IGF-I circulates in its free form, which is believed to be the biologically active form. However, our knowledge of the clinical or physiological value of determination of free IGF-I in serum is limited at present. In adults, the diagnostic value of total IGF-I and IGFBP-3 determinations in patients suspected of GHD has only been reported in a few studies, whereas no previous reports on the diagnostic value of free IGF-I levels in adults suspected of GHD exist. Serum levels of free IGF-I were determined in 1430 healthy children, adolescents, and adults by a newly developed, commercially available immunoradiometric assay (Diagnostic Systems Laboratories) to establish valid normative data for this analysis. We studied the diagnostic value of free IGF-I in relation to total IGF-I and IGFBP-3 determinations in adults who were suspected of GHD. A GH provocative test, using oral clonidine, was performed in 108 adult patients who had previously been treated with GH in childhood. In healthy subjects, free IGF-I levels increased during childhood, with the highest mean values during puberty. After puberty, a subsequent decline in serum levels of free IGF-I was apparent. We found, unmeasurable free IGF-I values in 34 of the prepubertal children (3.3%). All individuals over 8 yr of age had measurable free IGF-I levels that amounted to approximately 1% of the total IGF-I concentrations. Free IGF-I levels were below--2 SD in 56 of 79 GHD patients (sensitivity, 71%) and above--2 SD in 24 of 29 patients with a normal GH response (specificity, 83%). Multiple linear regression analysis demonstrated that free IGF-I was significantly dependent on peak GH levels, duration of the disease, and number of other pituitary axes affected. We conclude that free IGF-I serum levels increase during childhood with a peak in puberty, whereafter free IGF-I levels return to prepubertal levels. Three percent of healthy prepubertal children had unmeasurable free IGF-I levels using this assay. We found that determination of the free IGF-I serum concentration may predict the outcome of a GH provocative test in adults suspected of GHD, but that a single determination of free IGF-I offered no significant advantage compared to determination of total IGF-I or IGFBP-3 serum levels.

Adolescent↗
PubMed1997

Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage, and testosterone.

Leptin, the product of the ob gene, is thought to play a key role in the regulation of body fat mass. Beyond this function, it appears to be an integral component of various hypothalamo-pituitary-endocrine feedback loops. Because childhood and puberty are periods of major metabolic and endocrine changes, leptin levels and various hormonal parameters were investigated in a large cohort of healthy children and adolescents (312 males, 401 females, age 5.8-19.9 yr). For this purpose, a specific and sensitive RIA was developed that allowed the accurate measurement of low leptin levels in young lean children. With this assay, leptin proved to be a comparatively stable protein under common conditions of blood sampling and storage. Leptin levels increased in girls with age (r = 0.47, P < 0.0001), but decreased in boys (r = -0.34, P < 0.0001). An analysis according to pubertal stage showed a steady increase in girls between 2.51 micrograms/L (median) at Tanner stage 1 to 6.24 micrograms/L at Tanner stage 5. In boys, leptin levels were highest at Tanner stage 2 (2.19 micrograms/L) and declined thereafter to 0.71 microgram/L at Tanner stage 5. A strong exponential relationship was observed for leptin levels with body mass index (BMI) and percentage body fat as determined by bioelectric impedance measurements in a subgroup of subjects. This relationship was similar between boys and girls at Tanner stages 1 and 2. In boys, there was a significant decline of leptin at a given BMI with further progression of puberty that was much less pronounced in girls. Although the relative increase of leptin with BMI and percent body fat was the same in both genders, the absolute values at a given BMI or percent body fat were significantly lower in boys in late puberty and in adolescents. In boys, but not in girls, there was an inverse correlation with testosterone concentrations (r = -0.43, P < 0.0001), which explained 10.5% of the variation of leptin levels in a multiple regression model. Since BMI proved to be the major influencing variable, reference ranges were constructed using a best-fit regression line of the form leptin = a*e(b*BMI) and stratifying ranges according to gender and pubertal stage. In conclusion, these data suggest that 1) plasma leptin levels increase in girls and decrease in boys after Tanner stage 2 as the pubertal development proceeds; 2) they show a significant gender difference especially in late puberty and adolescence, even after adjustment for BMI or percent body fat; 3) the lower levels in males may be explained at least in part by a suppressive effect of androgens; 4) reference ranges with BMI as the independent variable should be stratified according to gender and pubertal stage.

Adipose Tissue↗
PubMed1997

Prostate specific antigen in boys with precocious puberty before and during gonadal suppression by GnRH agonist treatment.

UNLABELLED: In healthy boys, the pituitary-gonadal axis exhibits diurnal variation in early puberty. Serum testosterone levels are higher during the night and low or immeasurable during the day. These fluctuating levels of circulating androgens in early pubertal boys are difficult to monitor. Prostate specific antigen (PSA) is a marker of the androgen-dependent prostatic epithelial cell activity and it is used in the diagnosis and surveillance of adult patients with prostatic cancer. We have measured PSA concentrations in serum from boys with precocious puberty before and during gonadal suppression with GnRH agonists to evaluate the effect of normal and precocious puberty on PSA levels and to study the correlation between testosterone and PSA in boys. METHODS: PSA was measured by an ultrasensitive immunofluorometric assay with a detection limit of 0.03 microgram/l. Testosterone was measured by an RIA with a sensitivity of 0.23 nmol/l, and sex hormone binding globulin was measured by a time-resolved immunofluorescence assay (sensitivity 0.23 nmol/l). Five boys with central precocious puberty (CPP) were studied before and after 12 months of GnRH agonist treatment. Sixty healthy boys (12 in each Tanner stage of puberty) and 37 healthy young males served as controls. RESULTS: PSA levels were immeasurable in all prepubertal boys, whereas PSA levels increased with increasing stage of pubertal maturation. There was a significant correlation between PSA and testosterone and free androgen indices (r = 0.61 and r = 0.65 respectively, both P < 0.001). All 5 boys with CPP had significantly elevated PSA levels which decreased to very low or immeasurable levels after GnRH agonist treatment. CONCLUSION: PSA may be a useful marker of testosterone activity in boys with normal or precocious puberty.

Adolescent↗
PubMed1996

[Reduced concentration of insulin-like growth factor I in patients with cystic fibrosis].

Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function and linear growth. Using radioimmunoassay we measured IGF-I once in 235 of our 240 patients (114 males, 121 females, median age 16.2 years, range 0.1-44.0 years). IGF-I was significantly reduced compared with a healthy Scandinavian control population: Mean (-2SD to +2SD) IGF-I-SD score -0.97 (-3.7 to 1.7) in males and -0.67 (-3.2 to 1.9) in females, both values were significantly different from zero (p < 0.001). Height SD score was -0.95 (-3.3 to 1.4) in males and -0.81 (-3.2 to 1.6) in females (p < 0.001). The low IGF-I concentrations may reflect the catabolic state of many patients with cystic fibrosis and play a part in their abnormal growth pattern.

Adolescent↗
PubMed1996

Prognostic value of insulinlike growth factor I and its binding protein in patients with alcohol-induced liver disease. EMALD group.

Insulinlike growth factor I (IGF-I) is a single-polypeptide chain with important anabolic and endocrine activities. The liver is the major source of IGF-I and its binding protein, IGFBP-3. Circulating concentrations of IGF-I and IGFBP-3 are decreased in patients with chronic liver disease and correlate with the severity. The aim of this study was to assess the additional prognostic value of IGF-I and IGFBP-3 in patients entered in a large multicenter study (EMALD). Three hundred thirty-seven patients with alcohol-induced liver disease were studied in a randomized placebo-controlled trial of malotilate with a mean follow-up period of 569 days (range, 7-1,544). A multivariate Cox regression analysis of pertinent clinical and biochemical variables showed a significant independent prognostic value of years of alcohol intake, coagulation factors 2, 7, and 10, alkaline phosphatases, serum creatinine, and immunoglobulin (Ig) M. When IGF-I or IGFBP-3 were added into this model, a Cox regression analysis showed that either had a significant independent prognostic value. Because IGF-I and IGFBP-3 were closely correlated, they contained almost the same prognostic information. Inclusion of IGF-I gave these results: IGF-I (P < .03), alcohol intake (P < .02), coagulation factors 2, 7, and 10 (P < .01), creatinine (P < .001), and IgM (P < .01) contained independent prognostic information. Inclusion of IGFBP-3 gave these results: IGFBP-3 (P < .02), alcohol intake (P < .05), coagulation factors 2, 7, 10 (P < .01), creatinine (P < .001), and IgM (P < .02) were independent predictors of survival. In conclusion, IGF-I or IGFBP-3 provide important additional information on survival in patients with alcohol-induced liver disease.

Adult↗