Final height after growth hormone therapy in non-growth-hormone-deficient children with short stature

Loche, Sandro; Cambiaso, Paola; Setzu, S.; Carta, Daniela; Marini, Romana; Borrelli, P.; Cappa, Marco

doi:10.1016/s0022-3476(94)70192-x

Cited by 97 publications

(48 citation statements)

References 14 publications

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“…During 1-4 years of GH therapy, short children increase their growth rate and height standard deviation score (SDS) similar to the response seen in classical GH deficiency (GHD) (1)(2)(3)(4). The long term results are variable, with reports of no increase in the final height (5,6), a small increase (7), or a marked increase (8,9). As the collaborative Israeli study of efficacy and safety of GH therapy was analyzed (10), we realized that in 65 boys with GHD or neurosecretory dysfunction, aged 3-15 years, treated with 3 times weekly 0.1 mg/kg s.c. GH, the child's age was the most significant determinant of therapy outcome; boys of the prepubertal age group gained over the course of 3 years an average 8 cm of predicted adult height, pubertal boys over the age of 12 years showed a negative correlation of their predicted height gain against age, and boys over the age of 14 years showed a loss of predicted height during GH therapy.…”

Section: Introductionmentioning

confidence: 99%

GH dependence and GH withdrawal syndrome in GH treatment of short normal children: evidence from growth and cardiac output

Lampit

Lorber²,

Vilkas³

et al. 1998

European Journal of Endocrinology

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The child's age is a significant determinant of the outcome of GH therapy; prepubertal children respond better on both short term and long term growth, whereas adolescents tend to accelerate their bone maturation more than growth. The present study was designed to evaluate the efficacy of an interrupted GH therapy protocol of young, short normal children. GH was given for a period of 3 years, or until they reached the 25th percentile, then discontinued at a young age (not more than 9 years), and then the children's growth followed until final height. Yet, after discontinuation of GH therapy, growth came close to a complete stand-still. The present report focuses on describing the period beyond GH withdrawal and its impact on growth and cardiac performance. Twenty-two children received daily s.c. injections of 0.9 mg/m 2 hGH and 12 children were the control, untreated group. Growth and echocardiography were followed during therapy and 2 years thereafter. During GH treatment growth velocity accelerated markedly over the first year; it slowed down over the second and third years, and decelerated after GH withdrawal to a velocity that was significantly lower than pretreatment values. Growth rate remained low for the next year, and recovered to pretreatment velocity by the fourth semiannual measurement. To evaluate the role of the GH-IGF-I axis during the growth deceleration, serum IGF-I, insulin-like growth factor-binding protein-3 (IGFBP-3), and an arginine stimulation test were performed at 1, 3 or 6 months after GH withdrawal, and compared with pretreatment response. GH response was 70% of pretreatment values by 1 month and recovered completely by 3 months post treatment. Serum IGF-I and IGFBP-3 levels were normal throughout. End-systolic and end-diastolic left ventricular dimensions as well as cardiac output did not change during the 2 year course of GH therapy, but fell significantly during the initial 6 months of GH withdrawal. Thus, daily injections of GH to prepubertal short normal children is associated with development of drug dependence, followed during the abstinence period by deceleration of growth and reduction of cardiac output to levels that are lower than pretreatment values. After GH therapy for 30-36 months the withdrawal syndrome persists for 18 months, and is not induced by alterations of serum levels of GH or IGF-I.

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Section: Introductionmentioning

confidence: 99%

GH dependence and GH withdrawal syndrome in GH treatment of short normal children: evidence from growth and cardiac output

Lampit

Lorber²,

Vilkas³

et al. 1998

European Journal of Endocrinology

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“…Furthermore, most, but not all, nonrandomized long-term studies suggest that GH increases adult height of children with idiopathic short stature (9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Thus, in the past, many children with idiopathic short stature received GH treatment despite a lack of definitive evidence for its efficacy.…”

Section: Efficacy Of Gh Treatment In Issmentioning

confidence: 99%

Management of children with idiopathic short stature

Dunkel

2006

eur j endocrinol

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The Food and Drug Administration (FDA) approved the use of biosynthetic GH for the treatment of children with idiopathic short stature (ISS) in the US in 2003. Primarily, the decision was based on two studies: a randomized placebo-controlled study and a dose-response study, both demonstrating an increase in adult height over the predicted height at baseline and over placebo-treated controls by an average of 4-7 cm. Despite these data and FDA approval of GH treatment for ISS, there is still a significant controversy among paediatric endocrinologists about how, and to what extent, GH should be used in this indication. GH is clearly efficacious in several growth disorders and has the potential to alleviate debilitating short stature. However, it has been questioned whether ISS should be considered a condition warranting pharmacological treatment, whether the degree of morbidity of untreated ISS is clinically significant, and whether improved psychosocial status or well-being is achieved through GH treatment and height gain. The benefits must outweigh treatment costs and risks to justify GH treatment in ISS. The safety of GH treatment in ISS has been the main subject in two recent articles from pharmaceutical companies that conducted the pioneering studies mentioned earlier. No new safety concerns were observed in the ISS populations, but there were some limitations in study designs that prevent clinicians, their patients and families from 'resting assured'. Studies addressing these controversial issues are needed before the widespread use of GH treatment in ISS is warranted. European Journal of Endocrinology 155 S35-S38

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“…18,20 -22 However, there is accumulating evidence to show that such a goal may be unattainable. 23,24 Unfortunately, just as it is difficult to define GH deficiency biochemically, in the era of recombinant human GH therapy, the medical community has no universally accepted standard definition for short stature. Clearly, both sex and age must be considered.…”

Section: Goals For Gh Administration To Children With Short Staturementioning

confidence: 99%

“…[25][26][27] However, it is not clear how many of these patients benefit psychologically or that increased adult height is achievable. 28 In addition to debate over proper criteria for therapy, controversy surrounds screening efforts to identify candidates. School-based screening for children of short stature has raised concerns about overidentification of candidates and stigmatization of short children.…”

Section: Goals For Gh Administration To Children With Short Staturementioning

confidence: 99%

Considerations Related to the Use of Recombinant Human Growth Hormone in Children

1997

Pediatrics

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ABSTRACT. Since 1985 molecular biology techniques have made possible the synthetic synthesis of pure human growth hormone in potentially unlimited amounts. With this increased availability, its use in patients other than children with growth hormone deficiency has been associated with clinical and ethical questions. This statement presents an analysis of the current status of the use of human growth hormone in children.

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Final height after growth hormone therapy in non-growth-hormone-deficient children with short stature

Cited by 97 publications

References 14 publications

GH dependence and GH withdrawal syndrome in GH treatment of short normal children: evidence from growth and cardiac output

GH dependence and GH withdrawal syndrome in GH treatment of short normal children: evidence from growth and cardiac output

Management of children with idiopathic short stature

Considerations Related to the Use of Recombinant Human Growth Hormone in Children

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