Limited efficacy of growth hormone (GH) during transition of GH-deficient patients from adolescence to adulthood: A phase III multicenter, double-blind, randomized two-year trial

Context: Treatment of GH-deficient adolescents in transition to adulthood remains challenging. Objective: The objective was to assess the safety and efficacy of GH in GH-deficient adolescents in transition. Patients: Fifty-eight GH-deficient adolescents (mean age, 15.8 +/- 1.8 yr; 33 males) at near completion of their linear growth participated in the study. Intervention: Baseline studies were done while subjects were on GH. Subjects were retested (insulin-induced hypoglycemia) 4 wk after GH discontinuation and reclassified as persistently GH-deficient or controls (n = 18). GH-deficient subjects were randomized to GH (n = 25, similar to 20 mu g/ kg(.)d) or placebo (n = 15). Setting: The multicenter study was conducted over a 2-yr period. Main Outcomes: Changes in body composition, bone mineral density (BMD), quality of life (QOL), cardiovascular and metabolic markers were measured. Results: All groups had normal measures of lipid and carbohydrate metabolism, body composition, BMD, cardiac function, muscle strength, and QOL at baseline and after 2 yr. IGF-I concentrations decreased in all, but less so in the GH-group (P = 0.013). There was a greater increase in lean body mass (lesser adiposity) in the GH group than placebo at 12 months, but not at 24 months. Conclusions: 1) GH-deficient patients properly treated in childhood can have normal BMD, body composition, cardiac function, muscle strength, carbohydrate and lipid metabolism, and QOL when reaching adult height; and 2) continuation of GH therapy for 2 yr did not change these measures as compared to placebo-treated or control subjects. GH-deficient adolescents in good metabolic status at the time of epiphyseal fusion may safely discontinue GH for at least 2 yr. Follow-up is needed to determine whether GH therapy is eventually warranted in subjects treated with GH during childhood.