The growth and cardiovascular effects of high dose growth hormone therapy in idiopathic short stature

Abstract

OBJECTIVE It Is possible that high dose GH treatment may have beneficial effects on growth but important adverse effects on cardiac function. We have therefore Investigated the efficacy and cardiovascular effects of high dose biosynthetic human GH (r‐hGH) treatment in children with idiopathic short stature and a normal pretreatment height velocity. STUDY DESIGN Randomized controlled study. PATIENTS Twenty‐nine short (height SDS −1.5), prepubertal children referred to two specialist growth clinics. INTERVENTIONS Children were randomly assigned to an observation group or to receive ‘standard’ (20IU/m²/ week) or ‘high’ (40 IU/m²/week) dose r‐hGH by dally subcutaneous injection. At the end of 1 year the observation group were randomly assigned to ‘standard’ or ‘high’ dose r‐hGH therapy for the second year of the study. Regular growth, biochemical and echocardiographic monitoring were performed throughout the study period. MAIN OUTCOME MEASURES Change In height velocity, HtSDS for bone age (HtSDSBA), left ventricular mass Index (LVMI) and left ventricular function (fractional shortening) during 2 years treatment. RESULTS Twenty‐seven children completed the study. Ht velocity SDS Increased with r‐hGH therapy In a dose dependent fashion. First‐year height velocity SDS was +5.7 in the high dose r‐hGH group compared with +2.7 in the standard dose r‐hGH group and −0.5 In the observation group (P < 0.001). In those children treated for 2 years HtSDSBA was −0.5 In the high dose group but had not changed significantly In the standard dose group (−1.7) (P= 0.01). After one year r‐hGH treatment LVMI was 71g/m² (observation group), 73g/m² (20 IU/m²/week group) and 74g/m² (40 IU7m²/week group) (P= 0.77). LVMI Increased significantly from baseline to 76 g/m² after 2 years therapy with 40 IU/m²/week r‐hGH (P= 004) but nevertheless remained within the normal range. Fractional shortening did not change significantly over 2 years of r‐hGH therapy. CONCLUSIONS High dose (40 IU/m²/week) r‐hGH treatment of children with idiopathic short stature resulted in a greater short‐term acceleration In growth rate than ‘standard’ dose therapy without an excessive advance In skeletal maturity and probably represents the optimal growth promoting dose for short, normally growing children. Whether continued high dose r‐hGH therapy increases final height requires further study. Left ventricular morphology and function remained within the normal range during r‐hGH therapy but regular monitoring of cardiovascular status should continue In non‐GHD children receiving r‐hGH in high doses over a longer time period.