Growth hormone axis-independent growth

340

GRS'98 Abstracts

pronounced reduction of serum IGFs and less pronounced increase after treatment observed in sepsis. Multiple correlation analysis between IGFs, IGFBPs and ALS evidenced that in sepsis, when the formation of the ternary complex is limited by the lack of ALS, IGFBP-2 becomes the IGFBP determining IGF-I concentration. ]Funded in part by Pharmacia Upjohn, Milano, Italy.]

V PEDIATRIC GHD P - 4 2 S E C U L A R T R E N D I N I S R A E L I P O P U L A T I O N A N D ITS EFFECT O N T H E I C P G R O W T H M O D E L OF K A R L B E R G (20 Y E A R S OF C R O S S - S E C T I O N A L A N D L O N G I T U D I N A L DATA)

Zvi Zadik. Pediatric Endocrine Unit, Kaplan Med Center, Rehovot Affiliated with Hadassah Med School, Hebrew University Jerusalem, Israel. In order to create Israeli growth charts in a country of constant immigration, The Kaplan Medical Center growth study was initiated in 197Z Cross-sectional data from birth up to 19 years of age were collected in 19 852 healthy individuals. The country of origin of family, generation in Israel, height (Harpenden stadiometer in 14 650 subjects) and weight were recorded. In 220 children followed from birth to final height upper lower body ratio, age at menarche, first shave in boys and peak height velocity were recorded. In these cohorts, pubertal data were also obtained on parents and grandparents. These data allowed us to examine whether there is a secular trend in growth, body proportions, pubertal markers and peak height velocity. Results: in people born from 1990 to 199Z a distinct secular trend in height was detected in two dimensions: the generation born in the country was taller. In addition, a secular trend was noted with the years in the country. Attenuation of the secular trend was noted in the second, so that final height increased in men born from 1900 to 1944, from 166.3 + 0.8 to 172 + 0.8 in men. In 1997, final height was 176.8 + 0.9. In girls, secular trend was smaller (about 75% of that seen in men). No change in body proportions during the years was noted. Pubertal markers and peak height velocity appeared 2 years earlier as compared to 53 years ago. Analysis of the individual growth curves according to Karlbergs' equation (3 polynoms - infancy, childhood and puberty) revealed that the main effect of the secular trend was on the pubertal polynom. P-43 GH SECRETION IN OBESE CHILDREN AFTER HYPOCALORIC DIET

C Sgattoni ~, E Bartolotta% A Faeflda 2, L Guazzarotti% S Loche 2. 1Divisione di Pediatria, Ospedale S. Lucia, Recanati (Macerata); 2 Ospedale per le Microcitemie, Cagliari, Italia. We investigated the effect of 3 days of a protein sparing low calorie diet (PSLCD) on overnight spontaneous GH secretion in eight prepubertal (Prep, 4M/4E BMI 28 _+0.6), six early pubertal (EP, 3M/3F, Tanner Stage II-III, BMI 28 + 1.1) and five pubertal (Pub, 1 M/4F, Tanner Stage W-V, BMI 29 • 1.5) obese children. Blood samples were obtained at 20-min intervals from 20.00 to 08.00 h. Mean GH concentration (MGHC), pulse amplitude (PA), pulse frequency (PF) were calculated using the Pulsar algorhythm. Basal levels of Insulin-like growth factor-I (IGF-I), insulin, non-ester• fatty acids (NEFA) were measured before and after PSLCD. Pre-diet MGHC, PF, PA were significantly higher in Pub (3.5 _+0.7 gg/1, 5.6 • 0.5 pulses and 6.7 • 0.6 gg/1) than in Prep (1.8 • 0.3 btg/1, P < 0.05; 3.6 • 0.3 pulses, P < 0.005, and 4.2 • 0.5 •g/1, P < 0.02). MGHC and mean PF increased significantly in Prep(2.9 • 0.4 ug/1, P < 0.005; 5.2 • 0.5 pulses, P < 0.02). MGHC, mean Pg PA were unaffected by PSLCD in the EP and Pub. PSLCD caused: a significant decrease of serum IGF-I concentrations in Prep(from 208 • 21.6 to 86.6 • 35.6 gmg/1, P < 0.005), and EP (from 418 • 70 to 320 • 93 gmg/1, P<0.05), but

not in Pub(from 602 • 54.3 to 598 • 58.1 btg/1); a significant increase of mean serum NEFA in EP (from 0.6 • 0.1 to 0.9 • 0.1 mmol/1, P < 0.005), and in Pub(from 0.5 + 0.04 to 1.0 • 0.07 retool/l, P < 0.005) but not in Prep (from 0.7 • 0.1 to 1.1 _+ 0.1 mmol/1). Insulin was not significantly affected. In Prep, PSLCD caused a significant augmentation of GH release and a significant decrease of IGF-I concentrations, that may enhance GH secretion by a feed-back mechanism. The lack of a marked post-diet reduction of IGF-I concentrations, coupled with the significant increase of NEFA levels, might account for the lack of PSLCD-induced GH secretion in EP and Pub. These differences between prepubertal and pubertal children might be mediated by sex steroids. ]Funded by Azienda U.S.L 8.] P-44 GROWTH HORMONE AXIS-INDEPENDENT

GROWTH

EH Hathout, DJ Baylink, S Mohan. Loma Linda University School of Medicine, USA. Postnatal growth is usually stunted without growth hormone (GF0 production or peripheral action. We attempted to elucidate the mechanism of normal linear growth in a male with panhypopituitarism and a deficient GH/IGF axis. The patient was a 6.5-year-old prepubertal boy who presented with a hypoglycemic seizure and visual impairment. Height was 118.7 cm (35a~ centile) and weight was 26.5kg (90th centile). Growth velocity was 7.3 cm/year. Initial evaluation showed delayed bone age, ketotic hypoinsulinemic hypoglycemia, central hypothyroidism/hypocortisolism, normal serum and urine osmolalities, and low IGF-1. Further evaluation showed low IGFBP-3, high GHBP, and undetectable GH levels under basal and stimulated conditions. Leptin levels were markedly elevated. Brain MRI was consistent with septo-optic dysplasia, with absence of the septum pellucidum, pituitary and optic nerve hypoplasia, and an ectopic bright spot. Following 8 months of adequate thyroxine/glucocorticoid replacement, growth velocity was still normal for age, but the GH/IGF axis deficiency remained unaltered. GH was undetectable on stimulation. Serum IGF-I (48 ng/ml), IGF-II (194 ng/ml), IGFBP-3 (832 ng/ml), and IGFBP-5 (87 ng/ml) levels were extremely low compared to age-matched normal cMdren. Basal and GH-stimulated IGF-I levels were 37 and 101 ng/ml, respectively. H u m a n osteoblast cell proliferation in response to the patient's serum was normal, and was not stimulated by a supraphysiologic concentration of recombinant leptin. Molecular IGF-II sizing was normal. In conclusion, the case suggests the presence of an as yet unidentified growth factor or mechanism which may act, independent of the GH/IGF axis, to maintain normal linear growth. P - 4 5 IGF-I G E N E R A T I O N TEST: EFFECTS O N B O D Y COMPOSITION

S Longobardi, N Angelillo, D D'Amico, D De Felice, C Dent• B Di Costanzo, F Di Rella, G Lombard• B Merola, F Numis, M Sabatella. Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Napoli, Italy. Adult patients with GH deficiency (GHD) present changes of body composition. Moreover, little is known about body composition in children with GHD. The aim of the study was to evaluate the body composition in seven children with GHD and seven slow growing children before and after IGF-I generation test. Body composition was evaluated with bioelectrical impedance analysis (BIA), using a portable impedance analyser. After IGF-I generation test, all the children had a significant decrease of FBM (34.3 _+3.8 vs 2Z6 • 1%, P<0.001) and a significant increase of LBM (65.7 • 3.8 vs 72.4 -- 1%, P<0.001). No significant difference was found in TBW after IGF-I generation test. However, the TBW was differently distributed. In fact intracellular water was decreased after IGF-I generation test, whereas extracellular water was significantly increased (68.8 • 4.5 vs 64.7 • 4.7%,/-~ 31.3 • 4.5 vs 35.4 • 4.7%, P<0.05, respectively).