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Context: GH at 0.22 mg/kg.wk has been shown to have no effect on pubertal onset or pace, whereas GH at 0.5 mg/kg x wk has been shown to advance pubertal onset and bone maturation., Objectives: Our objectives were to determine whether 0.37 mg/kg x wk GH advanced pubertal onset, pace, or bone maturation relative to 0.24 mg/kg x wk GH; whether 0.37 mg/kg x wk GH led to pubertal onset at an inappropriately early age; and whether age at start of GH therapy influenced pubertal onset., Design: We conducted a randomized, open-label study to final height., Patients: We studied children with idiopathic short stature., Intervention: Patients were treated with 0.24 mg/kg x wk, 0.24 increasing to 0.37 mg/kg x wk, or 0.37 mg/kg x wk., Main Outcome Measures: We assessed age at pubertal onset and rates of bone maturation, Tanner stage development, and increase in testicular volume (boys only)., Results: For the primary comparison between the 0.24 and 0.37 mg/kg x wk dose groups, median ages of pubertal onset (in years) were similar (13.7 vs. 13.5 for boys and 11.7 vs. 11.4 for girls) and were greater than those for the general population for each sex. Age at start of GH therapy did not appear to influence pubertal onset for either sex. Rates of pubertal pace and bone maturation were not significantly different between the 0.24 and 0.37 mg/kg x wk dose groups for either sex., Conclusion: GH at 0.37 mg/kg x wk does not appear to accelerate pubertal onset, pace, or bone maturation compared with GH at 0.24 mg/kg x wk in patients with idiopathic short stature. From a clinical standpoint, our results suggest that the approved dose range of up to 0.37 mg/kg x wk GH does not lead to pubertal onset at an inappropriately early age.

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.