Efficacy and Safety Results of Long-Term Growth Hormone Treatment of Idiopathic Short Stature

University of Arkansas at Little Rock, Little Rock, Arkansas, United States
Journal of Clinical Endocrinology & Metabolism (Impact Factor: 6.21). 10/2005; 90(9):5247-53. DOI: 10.1210/jc.2004-2513
Source: PubMed


Small clinical trials of GH treatment of idiopathic short stature (ISS) show variable efficacy.
The study was an analysis of a large GH registry for efficacy and safety of GH treatment of ISS. There was also a comparison with a specific clinical trial.
Up to 7 yr of GH treatment of ISS was evaluated for efficacy and safety in the National Cooperative Growth Study (NCGS).
The NCGS study was conducted at Genentech, Inc. and included 47,226 patients.
The ISS group included maximum stimulated GH 10 ng/ml or more and/or a report of ISS by investigator (n = 8018; all included for safety). Cohort 1 (n = 2520) was similar to the clinical trial, cohort 2 (n = 283) included subjects younger than 5 yr of age, and cohort 3 (n = 940) was pubertal at GH start.
GH, approximately 0.30 mg/kg.wk, was given.
These included growth velocities and height sd (HtSDS). Results: Mean first-year growth velocities in cohorts 1, 2, and 3 increased 4.6, 3.9, and 4.4 cm/yr over pretreatment, respectively. Measures included: baseline mean HtSDS, -2.9, -3.2, and -2.8; mean HtSDS at 1 yr, -2.4, -2.3, and -2.3, respectively. Mean HtSDS after 7 yr in cohorts 1 (n = 303) and 2 (n = 85) and 5 yr in cohort 3 (n = 58) were: -1.2, -1.0, and -1.5, respectively. Cohort 3 shorter treatment time was due to advanced baseline age (mean 13.8 yr) and puberty. Mean HtSDS gain in cohort 1 was comparable with the clinical trial. No new safety signals specific to the NCGS ISS population were observed.
ISS patients in the GH registry demonstrate a significant increase in HtSDS with the safety profile similar to GH-deficient patients. Results were similar to the clinical trial.

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Available from: Stephen F Kemp
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    • "A dose effect for children with ISS was shown by Wit et al. [66] with a mean adult height gain of 1.85 SDS (similar to ours) and a benefit of 7.2 cm with a dose of 0.37 mg/kg/week. Also in a randomized controlled study by McCaughey et al. [2], 8 girls (6 of them with FSS) treated with GH 0.35 mg/kg/week (range 0.4 to 0.31), were 7.5 cm taller than the controls; and by others: Buchlis et al. [8] 6.8 cm for females, Albertsson-Wikland et al. [3] 8 cm based on adult height gain, Hintz R et al. [12] 9.2 cm higher for boys and 5.7 cm for girls, and Kemp et al. [67] (Genentech registry) 1.7 to 2.0 SDS in AH gain in children treated for 7 years, results similar to ours. "
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    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.
    Full-text · Article · Jul 2014 · International Journal of Pediatric Endocrinology
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    • "The controlled studies up to final height in children with ISS were recently analysed in a meta-analysis66), and the results have shown that the adult height of the treated subjects exceeded that of the controls, with a mean difference of 0.65 SDS (about 4 cm). Overall, GH treatment in ISS has a favourable safety profile, similar to GH deficient patients67). "
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    ABSTRACT: Until 1985 growth hormone (GH) was obtained from pituitary extracts, and was available in limited amounts only to treat severe growth hormone deficiency (GHD). With the availability of unlimited quantities of GH obtained from recombinant DNA technology, researchers started to explore new modalities to treat GHD children, as well as to treat a number of other non-GHD conditions. Although with some differences between different countries, GH treatment is indicated in children with Turner syndrome, chronic renal insufficiency, Prader-Willi syndrome, deletions/mutations of the SHOX gene, as well as in short children born small for gestational age and with idiopathic short stature. Available data from controlled trials indicate that GH treatment increases adult height in patients with Turner syndrome, in patients with chronic renal insufficiency, and in short children born small for gestational age. Patients with SHOX deficiency seem to respond to treatment similarly to Turner syndrome. GH treatment in children with idiopathic short stature produces a modest mean increase in adult height but the response in the individual patient is unpredictable. Uncontrolled studies indicate that GH treatment may be beneficial also in children with Noonan syndrome. In patients with Prader-Willi syndrome GH treatment normalizes growth and improves body composition and cognitive function. In any indication the response to GH seems correlated to the dose and the duration of treatment. GH treatment is generally safe with no major adverse effects being recorded in any condition.
    Full-text · Article · Mar 2014
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    • "An analysis of patients in a large database27 showed that, between 1985 (when rhGH was first used) and 2003, over 8000 patients had been treated for ISS at a time when the database included data from 47,226 total patients. When subgroups of these patients were evaluated for their growth patterns, it was clear that they started GH therapy with very short stature (−3.2 to −2.8 SD). "
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    ABSTRACT: Growth hormone (GH) was first used to treat a patient in 1958. For the next 25 years it was available only from cadaver sources, which was of concern because of safety considerations and short supply. In 1985, GH produced by recombinant DNA techniques became available, expanding its possible uses. Since that time there have been three indications approved by the US Food and Drug Administration (FDA) for GH-deficiency states and nine indications approved for non-GH-deficiency states. In 2003 the FDA approved GH for use in idiopathic short stature (ISS), which may indirectly cover other diagnoses that have short stature as a feature. However, coverage for GH therapy is usually more reliably obtainable for a specific indication, rather than the ISS indication. Possible future uses for GH therapy could include the treatment of syndromes such as Russell-Silver syndrome or chondrodystrophy. Other non-short-stature indications could include wound healing and burns. Other uses that have been poorly studied include aging and physical performance, in spite of the interest already shown by elite athletes in using GH. The safety profile of GH developed over the past 25 years has shown it to be a very safe hormone with few adverse events associated with it. The challenge for the future is to follow these patients into adulthood to determine whether GH therapy poses any long-term risks.
    Full-text · Article · Aug 2011 · Drug Design, Development and Therapy
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