Growth hormone therapy needs to be tailored based on individual responsiveness in children with idiopathic short stature

Article Outline

• Question
• Design
• Data Sources
• Study Selection and Assessment
• Outcomes
• Main Results
• Conclusions
• Commentary
• Copyright

Deodati A, Cianfarani S. Impact of growth hormone therapy on adult height of children with idiopathic short stature: systematic review. BMJ 2011;342:c7157.

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Question 

Among children with idiopathic short stature, does growth hormone use impact adult height, compared with controls?

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Design 

Systematic review.

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Data Sources 

Cochrane Central Register of Controlled Trials, Medline, and the bibliographic references from retrieved articles of randomized and non-randomized controlled trials from 1985 to April 2010.

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Study Selection and Assessment 

Inclusion criteria were initial short stature (defined as height >2 SD score below the mean), peak growth hormone responses >10 μg/L, prepubertal stage, no previous growth hormone therapy, and no comorbid conditions that would impair growth. Adult height was considered achieved when growth rate was <1.5 cm/year or bone age was 15 years in females and 16 years in males. The authors assigned a quality rating (based on Endocrine Society standards) for each included study.

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Outcomes 

Height in adulthood and overall gain in height from baseline measurement in childhood.

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Main Results 

Three randomized controlled trials (115 children) met the inclusion criteria. The adult height of the growth hormone treated children exceeded that of the controls by 0.65 SDS (about 4 cm). The mean height gain in treated children was 1.2 SDS compared with 0.34 SDS in untreated children. A slight difference of about 1.2 cm in adult height was observed between the two growth hormone dose regimens. In the seven non-randomized controlled trials, the adult height of the growth hormone treated group exceeded that of the controls by 0.45 SDS (about 3 cm).

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Conclusions 

Growth hormone (GH) therapy in children with idiopathic short stature seems to be effective in partially reducing the deficit in height as adults, although the magnitude of effectiveness is, on average, less than that achieved in other conditions for which GH is licensed. The individual response to therapy is highly variable, and additional studies are needed to identify the responders.

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Commentary 

Does GH affect the adult height of children with idiopathic short stature? Yes, according to this systematic review by Deodati and Cianfarani. The review found that the overall height gain was 1.2 SDS versus 0.34 SDS, with a large inter-individual variation in growth response, ranging from 0 to 3 SDSs (approx. 18 cm), partly GH dose dependent. This large variation in individual responses indicates that the mean height gain for the group cannot predict the growth response in a single individual. To identify the responders, it is possible to use the models that predict the child's growth response. The GH-dependent growth of a child depends on the balance between GH-secretion and responsiveness. Tailoring the GH dose according to individual responsiveness reduces the inter-individual variation in both growth and non-growth effects. In addition, the GH dose should be tailored according the intra-individual variation due to the growth period (infancy, childhood, puberty, adulthood), known to normalize growth; this will hopefully minimize the long-term risks of cardiovascular, metabolic, malignant, cognitive, and psychosocial disease.