Achieving Optimal Short- and Long-term Responses to Paediatric Growth Hormone Therapy

Abstract

It is over sixty years since the first administration of human growth hormone (GH) to children with GH deficiency, and over thirty years since recombinant human GH has been available for treatment of GH deficiency and a wider range of non-GH deficiency disorders. From a diagnostic perspective, genetic analysis, using single gene or Sanger sequencing and more recently next generation or whole exome sequencing, has brought advances in the diagnosis of specific causes of short stature, which has enabled therapy to be targeted more accurately. Genetic discoveries have ranged from defects of pituitary development and GH action to abnormalities in intracellular mechanisms, paracrine regulation and cartilage matrix formation. The strategy of GH therapy using standard doses has evolved to individualised GH dosing, depending on diagnosis and predictors of growth response. Evidence of efficacy of GH in GH deficiency, Turner syndrome and short children born small for gestational age is reviewed. The importance of critical assessment of growth response is discussed, together with the recognition and management of a poor or unsatisfactory growth response and the organisational issues related to prevention, detection and intervention regarding suboptimal adherence to GH therapy.

Early versus late initiation of GH replacement in adult-onset hypopituitarism

“…Our results are reassuring in relation to current clinical practice, in which AGHD is usually the last deficiency to be substituted in hypopituitarism. However, they are in contrast to the effects of paediatric growth hormone therapy, in which age of treatment onset is predictive of both growth acceleration during the first year and final height outcome (9). However, growth velocity in children is dependent on more hormonal and anabolic influences than GH per se, such as tempo of puberty and nutritional status.…”

“…It is not known whether these changes in SD scores and the likely association of delayed initiation of GHRT result in poorer outcomes. In paediatric growth hormone therapy, it is well known that age of treatment onset is predictive of final height outcome (9). In addition, it has been shown that growth acceleration during the first year is more marked in younger children (10,11).…”

“…In paediatric growth hormone therapy, it is well known that age of treatment onset is predictive of final height outcome ( 9 ). In addition, it has been shown that growth acceleration during the first year is more marked in younger children ( 10 , 11 ).…”

Growth Hormone Therapy for Paediatric Growth Disorders: The Past, Present, and Future

“…The adult height data submitted to the EMA for registration of rhGH therapy indicated that both doses had similar effects on adult height; however, the higher dose tended to induce supraphysiological levels of serum IGF-1 during therapy. Hence, the lower dose of 33 μg/kg/day is now recommended by the EMA [26,27].…”

Deletion at an 1q24 locus reveals a critical role of long noncoding RNA DNM3OS in skeletal development

“…Development of the skeletal system that supports body structures and maintenance of its homeostatic state are highly complex processes orchestrated by an elaborate array of gene activities. A frequently occurring developmental skeletal abnormally is short stature, which can arise as part of systemic diseases [1][2][3]. Height gain as the result of bone elongation is driven by chondrogenesis occurring at the growth plate, which is a cartilaginous structure located near the ends of weight-bearing bones in children [4].…”