THE GROWTH AND CARDIOVASCULAR EFFECTS OF HIGH-DOSE GROWTH-HORMONE THERAPY IN IDIOPATHIC SHORT STATURE

OBJECTIVE It is possible that high dose GH treatment may have benefici al effects on growth but important adverse effects on cardiac function . We have therefore investigated the efficacy and cardiovascular effec ts of high dose biosynthetic human GH (r-hGH) treatment in children wi th idiopathic short stature and a normal pretreatment height velocity. STUDY DESIGN Randomized controlled study. PATIENTS Twenty-nine short (height SDS <1.5), normally growing (height velocity SDS >-1.5), prepu bertal children referred to two specialist growth clinics. INTERVENTIO NS Children were randomly assigned to an observation group or to recei ve 'standard' (20 IU/m(2)/week) or 'high' (40 IU/m(2)/week) dose r-hGH by daily subcutaneous injection. At the end of 1 year the observation group were randomly assigned to 'standard' or 'high' dose r-hGH thera py for the second year of the study. Regular growth, biochemical and e chocardiographic 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 fun ction (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 SD S was +5.7 in the high dose r-hGH group compared with +2.7 in the stan dard dose r-hGH group and -0.5 in the observation group (P < 0.001). I n 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 71 g/m(2) (ob servation group), 73 g/m(2) (20 IU/m(2)/week group) and 74 g/m(2) (40 IU/m(2)/week group) (P = 0.77). LVMI increased significantly from base line to 76 g/m(2) after 2 years therapy with 40 IU/m(2)/week r-hGH (P = 0.04) 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/m(2)/week) r-hGH treatment of children w ith idiopathic short stature resulted in a greater short-term accelera tion in growth rate than 'standard' dose therapy without an excessive advance in skeletal maturity and probably represents the optimal growt h promoting dose for short, normally growing children. Whether continu ed high dose r-hGH therapy increases final height requires further stu dy. Left ventricular morphology and function remained within the norma l range during r-hGH therapy but regular monitoring of cardiovascular status should continue in non-GHD children receiving r-hGH in high dos es over a longer time period.