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.

Keywords: short stature; growth hormone therapy; growth hormone deficiency; Turner syndrome; small for gestational age; Paediatrics.

Figure 1

Growth disorders with approval for growth hormone therapy from the United States Food and Drug Administration and the European Medicines Agency

Figure 2

Management principles and strategy for patients with (A) a poor growth response and (B) non-adherence to GH therapy for short stature