ENDOGENOUS AND STIMULATED GH SECRETION, URINARY GH EXCRETION, AND PLASMA IGF-I AND IGF-II LEVELS IN PREPUBERTAL CHILDREN WITH SHORT STATUREAFTER INTRAUTERINE GROWTH-RETARDATION

OBJECTIVE The pathophysiological mechanisms underlying the failure of catch up-growth in children with short stature after Intrauterine grow th retardation (IUGR) remain obscure. Since GH secretion disturbances might play a role in the growth retardation of these children we have investigated various aspects of the GH/IGF axis. DESIGN Cross-sectiona l study in one group of patients. PATIENTS Forty prepubertal children (15 girls/25 boys; mean age (range) 7.5 years (3.4-10.8)) with short s tature (height below the third centile) after IUGR, defined as a birth length below the third centile for gestational age, were studied. MEA SUREMENTS GH secretion was determined by a 24-hour plasma GH profile ( sampling every 20 minutes) and, on a separate occasion, by a standard arginine provocation test (ATT). Plasma IGF-I and IGF-II levels were m easured at the start of the GH profile. Urine was collected to measure urinary GH levels. Plasma and urinary GH were determined by double an tibody RIA. IGF-I and IGF-II were determined by specific RIA after aci d chromatography. The 24-hour GH profiles were analysed using Pulsar. RESULTS Endogenous GH secretion was similar for boys and girls. Boys h ad significantly lower mean GH levels compared to healthy controls. Fo rty per cent of the children met our criteria for a normal 24-hour GH profile (group A; n = 16) and 60% (n = 24) did not. We subdivided thes e 24 children into two groups: group B (n = 14) (children with either mean GH levels less than controls but with at least one spontaneous GH peak above 20 mU/l and children with normal mean GH levels but with n o GH peak above 20 mU/l (subnormal 24-hour GH profile)) and group C (n = 10) (children with mean GH levels less than controls and no GH peak above 20 mU/l (low 24-hour GH profile)). The GH secretory abnormaliti es were due to a decrease in pulse amplitude, not in pulse frequency. Mean (SD) maximal GH response during ATT was 22.3 (12.1) mU/l. Ninetee n children (47.5%) had a maximal GH value <20 mU/l. Moderate, but sign ificant, correlations were found between several 24-hour GH profile ch aracteristics and the maximal GH response during ATT (r = 0.31-0.35; P < 0.05). Mean (SD) overnight urinary GH excretion was 3.8 (2.1) and 4 .4 (3.5) mu U/night for boys and girls, respectively. Compared to heal thy schoolchildren, overnight urinary GH was tower in boys, but not in girls. Mean (SD) IGF-I and IGF-II SDS levels for chronological age we re -0.88 (1.40) and -0.64 (1.48), respectively. Plasma IGF-I and IGF-I I, levels were significantly reduced compared to controls. Height SDSC A or height velocity SDSCA did not correlate with either spontaneous o r stimulated GH secretion, urinary GH excretion or plasma IGF-I or IGF -II levels. CONCLUSIONS Our study indicates that 50-60% of children wi th short stature after intrauterine growth retardation have 24-hour GH profile abnormalities and/or subnormal responses to arginine provocat ion, while mean plasma IGF-I and IGF-II levels are significantly reduc ed, indicating GH insufficiency. Urinary GH excretion is lower in boys , but not in girls. The precise mechanism of the failure to catch up g rowth needs further elucidation. It seems justified to start clinical trials in order to investigate whether treatment with exogenous GH mig ht be beneficial for these children.