Endogenous and stimulated GH secretion, urinary GH excretion, and plasma IGF‐I and IGF‐II levels in prepubertal children with short stature after intrauterine growth retardation*
Authors: de Waal W. J. , Hokken‐Koelega A. C. S. , Stijnen Th. , de Muinck Keizer‐Schrama S. M. P. F. , Dropt S. L. S. ,   the Dutch Working Group on Growth Hormone
Published: March 2008

OBJECTIVE The pathophysiological mechanisms underlying the failure of catch up‐growth in children with short stature after Intrauterine growth 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‐sectional study in one group of patients.

PATIENTS Forty prepubertal children (15 glrls/25 boys; mean age (range) 7·5 years (3·4‐10·8)) with short stature (height below the third centile) after IUGR, defined as a birth length below the third centile for gestational age, were studied.

MEASUREMENTS 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 measured at the start of the OH profile. Urine was collected to measure urinary OH levels. Plasma and urinary OH were determined by double antibody RIA. IGF‐I and IGF‐II were determined by specific RIA after acid chromatography. The 24‐hour OH profiles were analysed using Pulsar.

RESULTS Endogenous GH secretion was similar for boys and girls. Boys had significantly lower mean GH levels compared to healthy controls. Forty per cent of the children met our criterla for a normal 24‐hour GH profile (group A; n = 16) and 60% (n = 24) did not. We subdivided these 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 μ/I and children with normal mean GH levels but with no OH peak above 20 mull (subnormal 24‐hour GH profile)) and group C (n = 10) (children with mean GH levels less than controls and no OH peak above 20 μ/l (low 24‐hour GH profile)). The GH secretory abnormalities were due to a decrease in pulse amplitude, not in pulse frequency. Mean (SD) maximal GH response during ATT was 22·3 (12·1) μ/I. Nineteen children (47·5%) had a maximal OH value <20mU/I. Moderate, but significant, correlations were found between several 24‐hour GH profile characteristics and the maximal OH response during All (r = 0·31‐0·35; P<0·05). Mean (SD) overnight urinary GH excretion was 3·8 (2·1) and 4·4 (3·5) μU/night for boys and girls, respectively. Compared to healthy schoolchildren, overnight urinary GH was lower in boys, but not in girls. Mean (SD) IGF‐I and IGF‐II SDS levels for chronological age were −0·88 (1·40) and −0·64 (1·48), respectively. Plasma IGF‐I and IGF‐II levels were significantly reduced compared to controls. Height SDSCA or height velocity SDSCA did not correlate with either spontaneous or stimulated OH secretion, urinary OH excretion or plasma IGF‐I or IGF‐II levels.

CONCLUSIONS Our study indicates that 50‐60% of children with short stature after Intrauterine growth retardation have 24‐hour GH profile abnormalities and/or subnormal responses to arginine provocation, while mean plasma IGF‐I and IGF‐II levels are significantly reduced, indicating GH Insufficiency. Urinary GH excretion is lower in boys, but not in girls. The precise mechanism of the failure to catch up growth needs further elucidation. It seems justified to start clinical trials in order to investigate whether treatment with exogenous GH might be beneficial for these Children.