OPTIMIZING GROWTH-HORMONE THERAPY IN CHILDREN

Over 12 years' experience with recombinant human growth hormone (rhGH) treatment has created a powerful and safe therapeutic tool. However, to fully optimize the potential of GH therapy and to provide a guide f or future GH research, several key issues must be addressed. These are the identification of specific patients or conditions for whom rhGH p rovides proven long-term benefit; an understanding of when treatment s hould be started and stopped; a determination of the best dose and reg imen; establishment of the most accurate parameter in measuring succes s of the treatment plan; and recognition of the therapy's potential ad verse effects and their relation to dosing. To date, approved pediatri c indications for GH therapy are GH deficiency, chronic renal insuffic iency and Turner syndrome. Long-term benefits for other indications ha ve yet to be clearly demonstrated. Although starting GH therapy at the youngest possible age yields better results, the treatment endpoint r emains controversial. Data so far has shown that daily injections are superior to thrice weekly dosing. Bedtime administration provides more physiologic GH profiles than morning injections. Subcutaneous adminis tration of GH is as efficacious as intramuscular GH and better tolerat ed. Published pilot studies and large ongoing pediatric trials suggest that the growth response is dose-dependent between 0.025 and 0.1 mg/k g per day. Studies in adults, however, show efficacy at lower doses. I t appears that both auxologic and biochemical parameters are useful in assessing treatment efficacy, but which marker is best suited for ind icating appropriate dose adjustments remains unclear. The normalizatio n of serum GH-dependent growth factors may have a role in individualiz ing the GH dose in a similar way to the approach used in managing othe r endocrine deficiencies.