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  • Price, David A.  (3)
  • 1995-1999  (3)
  • 1
    Online Resource
    Online Resource
    The Endocrine Society ; 1997
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 2 ( 1997-02-01), p. 531-535
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 82, No. 2 ( 1997-02-01), p. 531-535
    Abstract: GH stimulation tests are widely used in the diagnosis of GH deficiency (GHD), although they are associated with a high false positive rate. We have examined, therefore, the performance of other tests of the GH axis[ urinary GH excretion, serum insulin-like growth factor I (IGF-I), and IGF-binding protein-3 (IGFBP-3) levels] compared with GH stimulation tests in identifying children defined clinically as GH deficient. Group I comprised 60 children (mean age, 10.3 ± 4.8 yr) whose diagnosis of GHD was based on a medical history indicative of pituitary dysfunction (n = 43) or on the typical phenotypic features and appropriate auxological characteristics of isolated GHD (n = 17). Group II comprised 110 short children (mean age, 9.8 ± 4 yr) in whom GHD was not suspected, but needed exclusion. The best sensitivity for a single GH test was 85% at a peak GH cut-off level of 10 ng/mL, whereas the best specificity was 92% at 5 ng/mL. The sensitivities of IGF-I, IGFBP-3, and urinary GH, using a cut-off of− 2 sd score were poor at 34%, 22%, and 25%, respectively, with specificities of 72%, 92%, and 76% respectively. Only 2 of 21 pubertal children in group I and none of the 27 subjects with radiation-induced GHD had an IGFBP-3 sd score less than −1.5. We devised a scoring system based on the positive predictive value of each test, incorporating data from the GH test and the IGF-I and IGFBP-3 levels. A specificity of 94% could be achieved with a score of 10 or more (maximum 17) (sensitivity 34%). The latter could not be improved above 81% with a score of 5 points or more (specificity, 69%). A high score was, therefore, highly indicative of GHD, but was achieved by few patients. A normal IGFBP-3 level, however, did not exclude GHD, particularly in patients with radiation-induced GHD and those in puberty. A GH test with a peak level more than 10 ng/mL was the most useful single investigation to exclude a diagnosis of GHD.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 1997
    detail.hit.zdb_id: 2026217-6
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  • 2
    Online Resource
    Online Resource
    Wiley ; 1997
    In:  Clinical Endocrinology Vol. 46, No. 6 ( 1997-06), p. 727-733
    In: Clinical Endocrinology, Wiley, Vol. 46, No. 6 ( 1997-06), p. 727-733
    Abstract: Leptin is the protein product of the recently cloned ob gene, that has been implicated in the control of body weight and thermogenesis, but also independently stimulates the reproductive axis. As major changes in body composition and gonadal function occur during human adolescence, we have assessed serum leptin concentration through childhood. SUBJECTS AND MEASUREMENTS Serum leptin was measured in a radioimmunoassay in samples from 235 healthy children from 5 to 18 years of age. Its relationship to body mass index (BMI) (expressed as standard deviation score (SDS)) and the changes in concentration both within and between sexes over the stages of puberty were analysed. RESULTS Serum leptin was present at similar concentrations in both sexes over the prepubertal years and increased in parallel into early puberty (breast stage (B) 2, genital stage (G) 2). Thereafter serum leptin in the boys declined to a nadir in G5. In contrast in girls, leptin remained constant in mid‐puberty rising to a peak at B5. Factors influencing leptin (BMI SDS, age and testicular volume) were assessed therefore in the pre‐ and peripubertal stages (B1–2, G1–2) compared to the later pubertal stages (B3–5, G3–5). In all groups, leptin was positively correlated to BMI SDS ( r 2 =38–41% in girls, r 2 =31–35% in boys). However in B1–2 and G1–2, leptin was also positively related to age, which contributed a further 27% and 20% respectively to the variability. In B3–5, age only accounted for an additional 5% in leptin variability. In contrast in G3–5, leptin was related positively to BMI SDS ( r 2 =35%) and negatively to testicular volume ( r 2 =24%). CONCLUSIONS The influence of BMI on leptin is a significant factor throughout the prepubertal and pubertal years of both sexes. The additional negative effect of testicular volume in the boys contributes to the sexual dichotomy in leptin concentration at the completion of puberty. The similar rise in leptin over the prepubertal years into early puberty in both sexes, related not only to BMI SDS but also independently to age, would suggest that leptin may have a facilitatory role in human pubertal development.
    Type of Medium: Online Resource
    ISSN: 0300-0664 , 1365-2265
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 1997
    detail.hit.zdb_id: 2004597-9
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  • 3
    In: Hormone Research in Paediatrics, S. Karger AG, Vol. 50, No. 2 ( 1998), p. 71-77
    Abstract: The relationship between peak growth hormone (GH), insulin-like growth factor I (IGF-I), IGF-I binding protein 3 (IGFBP-3) and IGFBP-3 protease activity was studied in 28 children and adolescents undergoing investigation of pituitary function 0.4–14.2 years after cranial or craniospinal irradiation for the treatment of CNS tumours distant from the hypothalamic-pituitary axis (n = 16) or prophylaxis against CNS leukaemia (n = 12). Seven out of 15 patients with GH deficiency (GHD) (defined as a peak GH concentration 〈 7.5 ng/ml in a stimulation test) had IGF-I 〈 –2 standard deviation score (SDS). None of the 28 patients had serum IGFBP-3 concentrations measured by radioimmunoassay (RIA) 〈 –1.5 SDS with no difference between those with and without GHD. IGFBP-3 concentrations measured by RIA were strongly correlated to IGFBP-3 band density on Western ligand blot (WLB) (r = 0.71; p 〈 0.0001). IGFBP-3 protease activity was negatively correlated to IGFBP-3 by RIA (r = –0.55; p 〈 0.01) and to IGFBP-3 by WLB (r = –0.51; p 〈 0.01). Twenty-two patients had normal IGFBP-3 protease activity ( 〈 30% of the activity in pregnancy serum) indicating that serum IGFBP-3 protease activity does not account for the normal levels of IGFBP-3 in RIA.Low serum IGF-I but normal IGFBP-3 concentrations and in the majority normal IGFBP-3 protease activity was found in patients in the years after CNS irradiation. Neither serum IGF-I nor IGFBP-3 can be used as a reliable index of the development of radiation-induced GHD.
    Type of Medium: Online Resource
    ISSN: 1663-2818 , 1663-2826
    Language: English
    Publisher: S. Karger AG
    Publication Date: 1998
    detail.hit.zdb_id: 2540224-9
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