Adult height in growth hormone (GH)-deficient children treated with biosynthetic GH. The Genentech Growth Study Group

Department of Pediatrics, State University of New York, Stony Brook 11794-8111, USA.
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.21). 03/1997; 82(2):418-20.
Source: PubMed

ABSTRACT Near-adult height (AH) was determined in 121 children (72 males and 49 females) with GH deficiency (GHD) who were prepubertal when they began treatment with recombinant DNA-derived preparations of human GH. AH as a SD score was -0.7 +/- 1.2 (mean +/- SD), significantly greater than the pretreatment height SD score (-3.1 +/- 1.2), the predicted AH SD score (-2.2 +/- 1.2; Bayley-Pinneau method), and the height SD score at the start of puberty (-1.9 +/- 1.3). In contrast to studies of GH treatment outcome, which used pituitary-derived GH (pit-GH) in lower doses, we found that males did not have a higher AH SD score than females, spontaneous puberty did not diminish AH, and AH was significantly greater than that predicted at the start of GH treatment. In a multiple regression equation, the statistically significant variables (all P < 0.0001) related to AH (r2 = 0.70) were the following: duration of treatment with GH, sex (males were taller than females, as expected for the normal population), age (younger children had a greater AH) and height at the start of GH, and growth rate during first year of GH. For the AH SD score (r2 = 0.47), pretreatment predicted AH, duration of GH, and bone age delay were significant (P < 0.0002) explanatory variables. Bone age delay (chronological age-bone age) had a negative impact on the AH SD score. Target height, etiology of GHD, previous treatment with pituitary GH, and the presence or absence of spontaneous puberty did not significantly improve the prediction of AH. Early diagnosis of GHD and continuous treatment with larger doses of GH to near AH should improve the outcome in children with short stature due to GHD.

9 Reads
  • Source
    • "Because the causes of ISS are regarded as a combination of a decrease of sensitivity and inappropriate secretion of growth hormone, it is thought that growth will be improved with growth hormone supplementation. After the introduction of rhGH treatment, this treatment was also widely used to treat patients with ISS as well as patients with GHD.5 "
    [Show abstract] [Hide abstract]
    ABSTRACT: After recombinant human growth hormone (rhGH) was introduced in the treatment of patients with growth hormone deficiency (GHD) and idiopathic short stature (ISS), many studies have addressed the effect of GH treatment and changes in the height standard deviation score (SDS) after GH treatment. However, few studies comparing the effect of GH in Korean patients with idiopathic GHD and ISS have been designed. Therefore, this study focused on the difference in effect of GH treatment between the two groups. We retrospectively reviewed the height SDS of 34 patients with idiopathic GHD and 12 patients with ISS. The mean ages of the patients with idiopathic GHD and ISS were 9.84±2.09 and 10.72±1.48 years, respectively. All patients were treated with GH for 1 year and body parameters were recorded before and after the GH treatment. Change in height SDS in patients with idiopathic GHD was significantly higher than that in patients with ISS (0.62±0.33 vs. 0.40±0.27, p=0.03). However, body mass index, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 were not significantly different between the two groups after GH treatment. These results suggest that GH treatment has a more powerful effect on increasing height SDS in patients with idiopathic GHD than in patients with ISS.
    Chonnam Medical Journal 08/2014; 50(2):63-6. DOI:10.4068/cmj.2014.50.2.63
  • Source
    • "The adult height of our 88 children with ISS of -0.71 SDS (0.74 SD) is equal to the adult height of -0.7 SDS (1.2 SD) achieved in 121 children (males and females) with GHD treated with 0.3 mg/kg/week, 3 or 6 times a week, reported by Blethem et al. [62]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Children with Idiopathic Short Stature do not attain a normal adult height. The improvement of adult height with treatment with recombinant human growth hormone (rhGH), at doses of 0.16 to 0.28 mg/kg/week is modest, usually less that 4 cm, and they remain short as adults. The benefit obtained seems dose dependent and benefits of 7.0 to 8.0 cm have been reported with higher doses of 0.32 to 0.4 mg/kg/week, but the number of studies is limited. The topic has remained controversial. Objective: The objective was to conduct a retrospective analysis of our experience with 123 children with ISS treated with 0.32 ± 0.03 mg/kg/week of rhGH, with the aim of comparing the different subgroups of non-familial short stature, familial short stature, normal puberty, and delayed puberty and to assess the benefit by comparison with 305 untreated historical controls, from nine different randomized and nonrandomized controlled studies. Results: Eighty eight of our children (68 males and 20 females) attained an adult height or near adult height of -0.71 SDS (0.74 SD) (95% CI, -0.87 to -0.55) with a benefit over untreated controls of 9.5 cm (7.4 to 11.6 cm) for males and 8.6 cm (6.7 to 10.5 cm) for females. In the analysis of the subgroups, the adult height and adult height gain of children with non-familial short stature were significantly higher than of familial short stature. No difference was found in the cohorts with normal or delayed puberty in any of the subgroups, except between the non-familial short stature and familial short stature puberty cohorts. This has implications for the interpretation of the benefit of treatment in studies where the number of children with familial short stature in the controls or treated subjects is not known. The treatment was safe. There were no significant adverse events. The IGF-1 values were essentially within the levels expected for the stages of puberty. Conclusion: Our experience was quite positive with normalization of the heights and growth of the children during childhood and the attainment of normal adult heights, the main two aims of treatment.
    International Journal of Pediatric Endocrinology 07/2014; 2014(1):15. DOI:10.1186/1687-9856-2014-15
  • Source
    • "Human growth hormone (GH), secreted from the somatotroph cells of the anterior pituitary gland, is involved in the regulation of lipid and glucose homeostasis and plays a pivotal role in the promotion of linear growth during childhood.1,2 In patients with GH deficiency, the secretion of GH is either deficient or absent and is phenotypically manifest in the form of growth failure, low lean body mass, abnormal lipid profiles, impaired cardiac function, and retardation of bone maturation.3–7 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Treatment of growth hormone disorders typically involves daily injections of human growth hormone (GH) over many years, incurring substantial costs. We assessed the extent of undesired GH loss due to leakage in the course of pen preparation prior to injection, and differences between the prescribed dose, based on patient weight, and the actual delivered dose based on pen dosing increments in five GH administration devices. Norditropin® prefilled FlexPro®, NordiFlex®, NordiLet®, and durable NordiPen®/SimpleXx® 5 mg pens (Novo Nordisk A/S, Bagsværd, Denmark) and durable Omnitrope® Pen-5 devices (Sandoz, Holzkirchen, Germany) were tested (n = 40 for each device type). Product wastage was measured in accordance with validated protocols in an ISO (International Organization for Standardization) 11608-1 and Good Manufacturing Practice compliant laboratory. The average mass of wasted GH from each device type was measured in simulations of dripping with the needle attached prior to injection and while setting a dose. Statistical significance (P < 0.05) was confirmed by Student's t-test, and a model was constructed to estimate mean annual GH wastage per patient in cohorts of pediatric patients with GH disorders. Mean GH mass wasted with the needle on prior to injection was 0.0 μg with Norditropin pens, relative to 98 μg with Omnitrope Pen-5. During dose dialing, 0.0-2.3 μg of GH was lost with Norditropin pens versus 0.8 μg with Omnitrope Pen-5. All Norditropin and Omnitrope device comparisons were statistically significant. Modeling GH wastage in a US cohort showed 5.5 mg of annual GH wastage per patient with FlexPro versus 43.6 mg with Omnitrope, corresponding to 7-8 additional pens per patient annually. Overall, Norditropin pens resulted in significantly less wastage than the Omnitrope Pen-5. The study suggests that GH devices of the same nominal volume exhibit differences that may affect the frequency of GH prescription refills required to remain adherent to therapy.
    Medical Devices: Evidence and Research 08/2013; 6(1):107-14. DOI:10.2147/MDER.S45909
Show more