Safety of growth hormone treatment in pediatric patients with idiopathic short stature.

CONTEXT Recombinant human GH was approved by the United States Food and Drug Administration in 2003 for the treatment of idiopathic short stature (ISS). However, to date, the safety of GH in this patient population has not been rigorously studied. OBJECTIVE The objective of this study was to address the safety of GH treatment in children with ISS compared with GH safety in patient populations for which GH has been approved previously: Turner syndrome (TS) and GH deficiency (GHD). DESIGN/SETTING The rates of serious adverse events (SAEs) and adverse events (AEs) of particular relevance to GH-treated populations were compared across the three patient populations among five multicenter GH registration studies. PATIENTS Children with ISS, TS, or GHD were studied. INTERVENTION Treatment consisted of GH doses ranging from 0.18-0.37 mg/kg.wk. MAIN OUTCOME MEASURES The main outcome measures were rates of SAEs and AEs of special relevance to patients receiving GH. Laboratory measures of carbohydrate metabolism were used as outcome measures for the ISS studies. RESULTS Within the ISS studies, comprising one double-blind, placebo-controlled study and one open-label, dose-response study, SAEs (mainly hospitalizations for accidental injury or acute illness unrelated to GH exposure) were reported for 13-14% of GH-treated patients. Overall AE rates (serious and nonserious) as well as rates of potentially GH-related AEs were similar in the GHD, TS, and ISS studies (for ISS studies combined: otitis media, 8%; scoliosis, 3%; hypothyroidism, 0.7%; changes in carbohydrate metabolism, 0.7%; hypertension, 0.4%). Measures of carbohydrate metabolism were not affected by GH treatment in patients with ISS. There was no significant GH effect on fasting blood glucose in either study (GH dose range, 0.22-0.37 mg/kg.wk) or on insulin sensitivity (placebo-controlled study only). CONCLUSION GH appears safe in ISS; however, the studies were not powered to assess the frequency of rare GH-related events, and longer-term follow-up studies of GH-treated patients with ISS are warranted.