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

被引:27
作者
BARTON, JS
GARDINER, HM
CULLEN, S
HINDMARSH, PC
BROOK, CGD
PREECE, MA
机构
[1] INST CHILD HLTH, GROWTH RES CTR, MED UNIT, LONDON WC1N 1EH, ENGLAND
[2] UCL, MIDDLESEX HOSP, SCH MED, DEPT MED, LONDON W1N 8AA, ENGLAND
[3] HOSP SICK CHILDREN, CARDIOTHORAC UNIT, LONDON WC1, ENGLAND
关键词
D O I
10.1111/j.1365-2265.1995.tb02689.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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), normally growing (height velocity SDS >-1.5), prepubertal children referred to two specialist growth clinics. INTERVENTIONS Children were randomly assigned to an observation group or to receive '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 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 71 g/m(2) (observation 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 baseline 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 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.
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页码:619 / 626
页数:8
相关论文
共 33 条
[21]   RECOMMENDATIONS REGARDING QUANTITATION IN M-MODE ECHOCARDIOGRAPHY - RESULTS OF A SURVEY OF ECHOCARDIOGRAPHIC MEASUREMENTS [J].
SAHN, DJ ;
DEMARIA, A ;
KISSLO, J ;
WEYMAN, A .
CIRCULATION, 1978, 58 (06) :1072-1083
[22]   ACROMEGALY AND THE HEART - ECHOCARDIOGRAPHIC STUDY [J].
SMALLRIDGE, RC ;
RAJFER, S ;
DAVIA, J ;
SCHAAF, M .
AMERICAN JOURNAL OF MEDICINE, 1979, 66 (01) :22-27
[23]   EFFECT OF HUMAN GROWTH HORMONE TREATMENT FOR 1 TO 7 YEARS ON GROWTH OF 100 CHILDREN, WITH GROWTH HORMONE DEFICIENCY, LOW BIRTHWEIGHT, INHERITED SMALLNESS, TURNERS SYNDROME, AND OTHER COMPLAINTS [J].
TANNER, JM ;
WHITEHOUSE, RH ;
HUGHES, PCR ;
VINCE, FP .
ARCHIVES OF DISEASE IN CHILDHOOD, 1971, 46 (250) :745-+
[24]  
TANNER JM, 1966, ARCH DIS CHILD, V41, P454, DOI 10.1136/adc.41.219.454
[25]   VARIABILITY OF GROWTH-HORMONE RESPONSE TO PHARMACOLOGICAL AND SLEEP TESTS PERFORMED TWICE IN SHORT CHILDREN [J].
TASSONI, P ;
CACCIARI, E ;
CAU, M ;
COLLI, C ;
TOSI, M ;
ZUCCHINI, S ;
CICOGNANI, A ;
PIRAZZOLI, P ;
SALARDI, S ;
BALSAMO, A ;
FREJAVILLE, E ;
CASSIO, A ;
ZAPPULLA, F .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1990, 71 (01) :230-234
[26]   THE GROWTH-HORMONE INDEPENDENT INSULIN-LIKE GROWTH FACTOR-I BINDING PROTEIN-BP-28 IS ASSOCIATED WITH SERUM INSULIN-LIKE GROWTH FACTOR-I INHIBITORY BIOACTIVITY IN ADOLESCENT INSULIN-DEPENDENT DIABETICS [J].
TAYLOR, AM ;
DUNGER, DB ;
PREECE, MA ;
HOLLY, JMP ;
SMITH, CP ;
WASS, JAH ;
PATEL, S ;
TATE, VE .
CLINICAL ENDOCRINOLOGY, 1990, 32 (02) :229-239
[27]  
TENBOSCH JJV, 1990, CLIN ENDOCRINOL, V32, P707
[28]  
THUESEN L, 1988, ACTA MED SCAND, V223, P337
[29]  
THUESEN L, 1988, DAN MED BULL, V35, P193
[30]   EFFECTS OF CHRONIC GROWTH-HORMONE HYPERSECRETION ON INTRINSIC CONTRACTILITY, ENERGETICS, ISOMYOSIN PATTERN, AND MYOSIN ADENOSINE-TRIPHOSPHATASE ACTIVITY OF RAT LEFT-VENTRICLE [J].
TIMSIT, J ;
RIOU, B ;
BERTHERAT, J ;
WISNEWSKY, C ;
KATO, NS ;
WEISBERG, AS ;
LUBETZKI, J ;
LECARPENTIER, Y ;
WINEGRAD, S ;
MERCADIER, JJ .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 86 (02) :507-515