Increased melatonin concentrations in children with growth hormone deficiency

A relationship between melatonin and growth hormone (GH) is poorly understood. We compare circadian melatonin rhythms in short children with normal and decreased GH secretion. The analysis included 22 children (20 boys and 2 girls) aged 11.1-16.9 yr (mean +/- S.E.M. = 14.1 +/- 0.3 yr) with short stature (height SDS below -2.0). Based on the GH peak in stimulation tests patients were divided into two groups: idiopathic short stature (ISS, n = 11; GH peak > or = 10 ng/mL) and GH deficiency (GHD, n = 11; GH peak < 10 ng/mL). In all patients the circadian melatonin rhythm was assessed on the basis of nine blood samples, collected in 4-hr intervals during the daytime and 2-hr intervals at night, with dark period lasting from 22:00 to 06:00 hr. Magnetic resonance imaging examination excluded organic abnormalities in central nervous system in all patients. Melatonin concentration at 24:00, 02:00 and 04:00 hr as well as the area under curve of melatonin concentrations (AUC) were significantly higher in the patients with GHD than in individuals with ISS. Significant correlations between GH secretion and melatonin concentrations at 24:00, 02:00 and 04:00 hr, and AUC were also observed. On the basis of these data it seems that the assessment of nocturnal melatonin secretion might be a valuable diagnostic tool used for the improvement of the difficult diagnosis of short stature in children.     

Serum cholesterol and triglycerides in children with growth hormone deficiency

To test the hypothesis that hyperlipidemia is characteristic of growth hormone deficiency in childhood, we have measured serum cholesterol and triglyceride concentrations in 24 euthyroid children with growth hormone deficiency. Although modest elevations of cholesterol and/or triglyceride above the 95th percentile for age, race, and sex were present in 46% of the children studied, the mean (± 1 SD) cholesterol of 173 ± 36 mg/dl and the mean triglyceride of 80 ± 42 mg/dl were not significantly different from published normal mean values. Administration of human growth hormone for 4 mo to 15 of these subjects did not alter these mean cholesterol and triglyceride values, but did result in a marked improvement in the growth rate. Some individuals (n = 6) with a subnormal growth response to therapy and/or a low serum thyroxine and high serum cholesterol were treated for an additional 4 mo with growth hormone and thyroid hormone together. There was a statistically significant decrement in serum cholesterol in this group. We conclude that modest hyperlipidemia does exist in some children with growth hormone deficiency. Subclinical hypothyroidism may play a role in the hypercholesterolemia of some children, as may growth hormone deficiency itself. Any association of growth hormone and lipid metabolism remains to be clarified.     

Serum ghrelin, IGF-I and IGFBP-3 levels in children with normal variant short stature

This study is planned to investigate the role of ghrelin in normal variant short stature. Serum ghrelin, IGF-I and IGFBP-3 levels were measured in 17 children with constitutional delay of growth, 19 children with familial short stature and 11 age matched healthy children. Mean bone age of the constitutional delay of growth group was lower compared to other groups. Constitutional delay of growth group had lower mean weight compared to the controls. Serum IGF-I values were lower in the constitutional delay of growth group compared to the familial short stature and control groups. IGFBP-3 levels of the groups were similar. Ghrelin levels were higher in the short stature groups compared to the controls. In the multiple regression analyses, weight (beta = -.54, p < 0.0001) and height SDS (beta = -.33, p = 0.01) were the independent determinants of ghrelin. The results of this study, the first one in which ghrelin levels are investigated in normal variant short stature, suggest that ghrelin does not play a role as a cause, but as a consequence in these patients because it is negatively correlated with weight and height standard deviation score. These negative correlations can be attributed to the compensatory response of ghrelin, which deserves further attention in future studies.     

Serum lipid and leptin concentrations in hypopituitary patients with growth hormone deficiency

OBJECTIVE: To investigate the effects of growth hormone (GH) deficiency on serum lipid and leptin concentrations in hypopituitary patients taking conventional replacement therapy and to determine the relations between leptin and gender and anthropometric and metabolic variables. SUBJECTS: Twenty-one GH deficient adult hypopituitary patients (15 women, six men) and 21 (14 women, seven men) age, sex and body mass index (BMI) matched healthy controls. MEASUREMENTS: After an overnight fast, anthropometric parameters were measured and body composition was determined by a bioelectrical impedance analyser. Venous blood samples were obtained for the measurements of glucose, total cholesterol, high density lipoprotein (HDL) cholesterol, triglyceride, intact insulin, insulin-like growth factor 1 (IGF-1) and leptin concentrations. Serum leptin and hormones were analysed by radioimmunoassay. RESULTS: Hypopituitary patients with GH deficiency showed significantly higher triglyceride, total and low density lipoprotein (LDL) cholesterol and lower HDL cholesterol concentrations on conventional replacement therapy. The unfavourable lipid profile was particularly evident in women. Significantly higher leptin concentrations were found in patients compared with healthy controls with similar body fat content (23. 5+/-11.8 ng/ml vs 11.7+/-6.9 ng/ml, P=0.01). This difference remained significant even when leptin values were expressed in relation to fat mass percentage (0.79+/-0.40 vs. 0.42+/-0.17 ng/ml%, P<0.05) and fat mass kg (1.32+/-0.81 vs 0.66+/-0.30 ng/ml kg, P<0. 05). Significant positive correlations were observed between leptin concentrations and body fat percentage and age in the control group. In patients the sole significant relation between leptin and study parameters was the positive correlation observed between leptin and total cholesterol concentrations. Serum leptin concentrations were significantly higher in women than men in the control group, but not in the patients. No significant gender difference was observed when leptin concentrations were expressed in relation to fat mass (percentage and kg). CONCLUSION: Growth hormone deficient hypopituitary patients (particularly women) on conventional replacement therapy have a more atherogenic lipid profile. Leptin concentrations are increased in GH deficient adults even after adjustment for percentage body fat and body fat mass (kg). Although the nature of our data does not allow us to draw any conclusions on the mechanism(s) of increased leptin concentrations in GH deficiency, decreased central sensitivity to leptin and increased leptin production from per unit fat mass, or alterations in leptin clearance, might be operative.     

Novel application of IGF-I and IGFBP-3 generation tests in the diagnosis of growth hormone axis disturbances in children with beta-thalassaemia

OBJECTIVE: Children with beta-thalassaemia major (beta-thal) frequently have growth retardation in the presence of low serum IGF-I and a normal GH response to pharmacological stimulation suggesting that they have GH insensitivity (GHIS). This study was carried out to study the cause of their growth retardation. DESIGN: We studied IGF-I and IGFBP-3 generation after exogenous GH administration for four days, in 15 prepubertal controls (C) and 41 prepubertal beta-thal patients divided into three groups according to their growth status: (Group 1) 15 with normal growth (N-thal) (Group 2) 16 with decelerated growth (D-thal) and (Group 3) 10 with short stature (S-thal), in order to determine whether GHIS is the cause of their growth retardation. MEASUREMENTS: IGF-I and IGFBP-3 were measured daily, before and for 4 days after daily administration of 0.1 IU/kg hGH, in 3 groups of prepubertal beta-thal patients and normal controls. RESULTS: N-thal and C had similar basal serum IGF-I (142 +/- 52 and 196 +/- 56 ng/ml, respectively) and IGFBP-3 concentrations (2.07 +/- 0.49 and 2.66 +/- 0.41 mg/l, respectively) as well as a similar percent increase of IGF-I (101 +/- 23% and 104 +/- 37%, respectively) and IGFBP-3 (52 +/- 36%, and 38 +/- 14%, respectively) during the generation tests. S-thal and D-thal had significantly lower basal IGF-I and IGFBP-3 concentrations (85 +/- 42 and 101 +/- 36 ng/ml; and 1.60 +/- 0.49 and 1.79 +/- 0.52 mg/l, respectively) as compared to N-thal and C (P < 0.001 and P < 0.005, respectively), and a significantly higher percent increase of IGF-I and IGFBP-3 during the generation tests (249 +/- 43 and 161 +/- 76%; and 121 +/- 99 and 73 +/- 35%, respectively) as compared to N-thal and C (P < 0.0001 and P < 0.01, respectively). Twenty-five percent of the growth retarded patients had classic GH deficiency (GHD) and percent increases of IGF-I and IGFBP-3 in the generation tests (164 +/- 86% and 80 +/- 49%, respectively) which were similar to those of the remaining growth-retarded children. CONCLUSION: The greater percent increases of IGF-I and IGFBP-3 in the generation tests of the growth retarded beta-thal patients, both with and without GHD, strongly suggest impaired GH secretion rather than GHIS as the cause of their growth retardation. We conclude that the IGF-I and IGFBP-3 generation tests are useful tools for the study not only of GHIS but also of GH secretory disorders in patients with beta-thal and short stature that can easily be performed in an outpatient setting as an initial test to identify the patients that may benefit from GH therapy.     

Monitoring serum insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), IGF-I/IGFBP-3 molar ratio and leptin during growth hormone treatment for disordered growth

OBJECTIVE: Serum IGF-I levels are monitored during GH replacement treatment in adults with GH deficiency (GHD) to guide GH dose adjustment and to minimize occurrence of GH-related side-effects. This is not routine practice in children treated with GH. The aim of this study was to evaluate changes in (1) serum IGF-I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio, and (2) serum leptin, an indirect marker of GH response, during the first year of GH treatment in children with disordered growth. DESIGN: An observational prospective longitudinal study with serial measurements at five time points during the first year of GH treatment was carried out. Each patient served as his/her own control. PATIENTS: The study included 31 patients, grouped as (1) GHD (n = 20) and (2) non-GHD (Turner syndrome n = 7; Noonan syndrome n = 4), who had not previously received GH treatment. MEASUREMENTS: Serum IGF-I, IGFBP-3 and leptin levels were measured before treatment and after 6 weeks, 3 months, 6 months and 12 months of GH treatment, with a mean dose of 0.5 IU/kg/wk in GHD and 0.7 IU/kg/wk in non-GHD groups. IGF-I, IGFBP-3 and the calculated IGF-I/IGFBP-3 molar ratio were expressed as SD scores using reference values from the local population. RESULTS: In the GHD group, IGF-I SDS before treatment was lower compared with the non-GHD (-5.4+/-2.5 vs. -1.8+/-1.0; P<0.001). IGF-I (-1.8 SDS +/- 2.2) and IGFBP-3 (-1.1 SDS +/- 0.6) levels and their molar ratios were highest at 6 weeks and remained relatively constant thereafter. In the non-GHD group, IGF-I levels increased throughout the year and were maximum at 12 months (0.3 SDS +/- 1.4) while IGFBP-3 (1.1 SDS +/- 0.9) and IGF-I/IGFBP-3 molar ratio peaked at 6 months. In both groups, IGF-I SDS and IGF-I/IGFBP-3 during treatment correlated with the dose of GH expressed as IU/m2/week (r-values 0. 77 to 0.89; P = 0.005) but not as IU/kg/week. Serum leptin levels decreased significantly during GH treatment in the GHD (median before treatment 4.0 microg/l; median after 12 months treatment 2.4 microg/l; P = 0.02) but not the non-GHD (median before treatment 3.0 microg/l; median after 12 months treatment 2.6 microg/l). In the GHD group, serum leptin before treatment correlated with 12 month change in height SDS (r = 0.70, P = 0.02). CONCLUSIONS: The pattern of IGF-I, IGFBP-3 and their molar ratio during the first year of GH treatment differed between the GHD and non-GHD groups. Calculation of GH dose by surface area may be preferable to calculating by body weight. As a GH dose-dependent increase in serum IGF-I and IGF-I/IGFBP-3 may be associated with adverse effects, serum IGF-I and IGFBP-3 should be monitored routinely during long-term GH treatment. Serum leptin was the only variable that correlated with first year growth response in GHD.     

Serum levels of ghrelin, leptin, IGF-I, IGFBP-3, insulin, thyroid hormones and cortisol in prepubertal children with iron deficiency

The aim of the present study is to investigate possible alterations in ghrelin and other hormone levels related to appetite and somatic growth in children with iron deficiency anemia. Twenty-five patients and 25 healthy controls that were prepubertal and within normal limits regarding height and BMI standard deviation scores were recruited. Ghrelin, leptin, IGF-I, IGFBP-3, insulin, thyroid hormones and cortisol levels were studied. Ghrelin, insulin and IGF-I levels were significantly low in the study group (ghrelin 13.58 +/- 16.32 vs. 35.39 +/- 23.69 ng/ml, p<.001; insulin 3.41 +/- 2.42 vs. 5.67 +/- 1.09 mU/ml, p = .008 and IGF-I 126.94 +/- 92.82 vs. 203 +/- 105.1 ng/ml, p = .015). We concluded that low ghrelin and insulin levels might be causes of the appetite loss in iron deficiency and as a result of appetite loss and undernutrition as well as by direct effects they might be related with growth retardation, which could be also influenced by low IGF-I levels.     

Serum homocysteine concentrations in children with growth hormone (GH) deficiency before and after 12 months GH replacement

OBJECTIVE: This open, prospective study was designed to evaluate the effect of growth hormone deficiency (GHD) and GH replacement therapy on serum homocysteine (Hcy) concentration in children with GHD. SUBJECTS: Seventeen prepubertal children with GHD (11 boys and six girls) aged 8.6 +/- 1.9 years were studied before and after 12 months of GH replacement therapy at a dose of GH of 30 microg/kg/day. Seventeen healthy children acted as controls and were matched for age, sex and body mass index (BMI). METHODS: At study entry, height, weight, blood pressure, serum Hcy, serum IGF-I, total-low density lipoprotein (LDL)- and high density lipoprotein (HDL) cholesterol, triglycerides, free T4, free T3, vitamin B12, folate, glucose and creatinine were measured in all subjects. The atherogenic index (AI) was also calculated as the ratio of total cholesterol/HDL cholesterol (T/HDL). In GHD children these parameters were also revaluated after 12 months of GH therapy. RESULTS: At study entry height and serum IGF-I were significantly lower, as expected, in GHD patients than in controls (P < 0.0001 and P < 0.007, respectively). Serum Hcy levels were significantly higher in GHD patients than in healthy children (8.4 +/- 2.9 vs. 6.0 +/- 2.9 micromol/l; P < 0.03), although the absolute values were within the normal values for age and sex. There were no significant differences at baseline with respect to blood pressure, serum vitamin B12, folate, fT3, fT4, lipid profile, creatinine and glucose levels. After 12 months of GH replacement therapy height and serum IGF-I increased significantly compared to pretreatment values (P < 0.0001); serum Hcy levels decreased significantly (6.0 +/- 3.3 micromol/l; P < 0.002) compared to baseline values, becoming similar to control values. Total cholesterol (3.5 +/- 0.6 mmol/l) and the AI (2.5 +/- 0.8) decreased significantly with respect to both pretreatment (4.2 +/- 1.0 mmol/l; P < 0.0002 and 3.4 +/- 0.8; < 0.002, respectively) and control values (4.2 +/- 0.4 mmol/l; P < 0.0005 and 3.3 +/- 1.1; P = 0.02, respectively). CONCLUSIONS: GHD in children is associated with higher serum levels of Hcy compared to controls, without significantly affecting the lipid profile. GH replacement for 12 months significantly decreased the Hcy levels and improved the lipid profile with a decrease of total cholesterol and the total/HDL cholesterol ratio, compared to pretreatment values. Given the small number of patients, further larger studies are needed to clarify whether these results may have significant effects in the prevention of cardiovascular disease in adulthood.     

Serum resistin concentrations in growth hormone-deficient children during growth hormone replacement therapy

We performed this study to examine whether the serum resistin concentrations in growth hormone (GH)-deficient (GHD) children are influenced by administration of GH and to assess the relationship between serum resistin and free fatty acid levels during GH replacement therapy. The study included 20 prepubertal GHD children (16 boys and 4 girls) who were treated with recombinant human GH (hGH). The serum levels of resistin, insulin-like growth factor I, free fatty acid (FFA), triglyceride, cholesterol and glucose levels, leukocyte counts, and hemoglobin A(1c) were measured at baseline and after 1 month of hGH treatment. The serum resistin levels after hGH therapy were significantly higher than the basal resistin levels (median [range], 6.2 [4.9-11.8] vs 5.6 [4.4-8.3] ng/mL; P < .05), whereas the serum FFA levels were unchanged before and after treatment (0.51 [0.34-0.76] vs 0.37 [0.24-0.60] mEq/L). No significant relationship was found between serum resistin and FFA levels after hGH therapy. Body mass index, serum triglyceride, cholesterol and glucose levels, leukocyte counts, and hemoglobin A(1c) showed no significant differences before and after hGH treatment. Our results suggest that elevated serum resistin levels after 1-month hGH therapy in GHD children are not associated with the GH-induced lipolysis as found in GHD adults during short-time hGH therapy.     

Effect of growth hormone on small intestinal homeostasis relation to cellular mediators IGF-I and IGFBP-3

AIM: To evaluate the effects of growth hormone (GH) on the histology of small intestines which might be related to the role of insulin like growth factor (IGF)-I, IGF-binding protein 3 (IGFBP-3) and its receptors.METHODS: Twelve week-old adult male Wistar albino rats were divided into two groups.The study group ( n = 10), received recombinant human growth hormone (rGH) at a dose of 2 mg/kg per day subcutaneously for 14 d and the control group ( n = 10) received physiologic serum.Paraffin sections of jejunum were stained with periodic acid shift (PAS) and hematoxylin and eosin (HE) for light microscopy.They were also examined for IGF-I, IGFBP-3 and IGF-receptor immunoreactivities.Staining intensity was graded semi-quantitatively using the HSCORE.RESULTS: Goblet cells and the cells in crypt epithelia were significantly increased in the study group compared to that of the control group.We have demonstrated an increase of IGF-I and IGFBP-3 immunoreactivities in surface epithelium of the small intestine by GH application.IGF-I receptor immunoreactivities of crypt, villous columnar cells, enteroendocrine cells and muscularis mucosae were also more strongly positive in the study group compared to those of in the control group.CONCLUSION: These findings confirm the important trophic and protective role of GH in the homeostasis of the small intestine.The trophic effect is mediated by an increase in IGF-I synthesis in the small intestine, but the protective effect is not related to IGF-I.     

IGF-I but not the IGF-I variant long R(3)IGF-I increases serum IGFBP-3 in adolescent monkeys.

Previous work in rhesus monkeys has shown that both acute or chronic subcutaneous (s.c.) administration of insulin-like growth factor (IGF)-I elevates serum concentrations of IGF binding protein (IGFBP)-3. In order to determine whether an analog of IGF-I, which has a reduced affinity for the IGFBPs, has similar effects, a series of studies using adolescent female rhesus monkeys were conducted. In the first study, an s.c. injection of IGF-I (110 mg/kg;n = 6) significantly elevated serum IGFBP-3 concentrations through 7 h following treatment. In contrast, serum IGFBP-3 decreased throughout the day following an injection of Long R(3)IGF-I (110 mg/kg, s.c., n = 5). However, this decrease was not due to the analog treatment as serum IGFBP-3 also declined in a similar fashion in untreated females (n = 5) sampled on the same schedule. Serum GH levels were acutely suppressed by both IGFs but were not altered in untreated females. In the second study, serum IGFBP-3 were compared between untreated control females (n = 6) and females treated continuously by s.c. infusion with either Long R(3)IGF-I (120 mg/kg/day, s.c.;n = 5) or IGF-I (120 mg/kg/day, s.c.;n = 5) or IGF-I s.c.;n = 4). Serum IGFBP-3 was consistently elevated by IGF-I infusion, whereas levels in analog-treated monkeys were similar to those in control females. Although acute or chronic administration of Long R(3)IGF-I did not elevate serum IGFBP-3, chronic administration of the analog did not block the acute facilitating effects of IGF-I on serum IGFBP-3. The increase in serum IGFBP-3 following an acute injection of IGF-I (110 mg/kg, s.c.) was not significantly different between untreated females and females receiving a constant s.c. infusion of Long R(3)IGF-I. These data indicate either acutely or chronically administered IGF-I but not its analog Long R(3)IGF-I can elevate serum concentrations of IGFBP-3. Although the analog fails to increase serum IGFBP-3, it does not block the facilitating effects of IGF-I on concentrations of this IGFBP. Taken together, these data suggest that the increase in serum IGFBP-3 by exogenous IGF-I may not be a receptor mediated event but may be the result of IGF-I binding to IGFBP-3 and forming the binary and ternary complex, slowing IGFBP-3 degradation.     

Placental growth hormone and IGF-I in a pregnant woman with Pit-1 deficiency

The respective contributions of pituitary and placental GH to circulating IGF-I in pregnant women have not been well established. We measured the serum concentrations of placental growth hormone (PGH) and IGF-I in a woman with pit-1 deficiency before, during and after pregnancy, resulting in the birth of a healthy child (not pit-1 deficient). Both PGH and IGF-I concentrations were below the assay detection limit before and after pregnancy. During pregnancy, PGH and IGF-I levels increased steadily; the concentrations of PGH and IGF-I in late pregnancy were comparable with levels previously measured in normal pregnancies. PGH and IGF-I concentrations were strongly correlated throughout pregnancy (r = 0.90; P = 0.002). PGH was undetectable in cord serum, whilst the IGF-I concentration was within the normal range. The findings of this case study corroborate the notion that PGH is the prime regulator of maternal serum IGF-I during pregnancy.     

IGF-I measurements in the diagnosis of adult growth hormone deficiency

Although serum insulin-like growth factor I (IGF-I) concentrations have utility as a screening test for growth hormone (GH) deficiency in children and young adults, they are less accurate for screening in adults over 40 years of age. There are two main limitations in the clinical use of IGF-I levels as a marker of GH secretion. First, IGF-I synthesis is not only regulated by GH but also by nutrient supply and by other hormones; second, low IGF-I levels in the presence of normal or increased GH secretion may reflect a peripheral resistance to GH action. Although serum IGF-I cannot be used as a stand-alone test for the diagnosis of adult GH deficiency, very low IGF-I levels in the context of documented hypothalamic or pituitary disease may be helpful in identifying patients with a high probability of GH deficiency. In the presence of two or more additional pituitary hormone deficiencies, an IGF-I level <84 μg/l (assayed by Esoterix Endocrinology, Inc. Calabasas Hills, CA, USA) indicates a 99% probability of GH deficiency. As this cut-off value has not been validated for other IGF-I assays, an IGF-I standard deviation score (SDS) of <-3 may be considered in adults over age 28; an even lower IGF-I SDS is needed for diagnosis in younger adults. In clinical practice, other causes of low serum IGF-I such as malnutrition, diabetes, hypothyroidism, liver disease, etc., should be excluded before applying these diagnostic criteria.     

Effects of heterozygosity for the E180 splice mutation causing growth hormone receptor deficiency in Ecuador on IGF-I, IGFBP-3, and stature.

CONTEXT & OBJECTIVE: The Ecuadorian GH receptor deficiency (GHRD)/Laron syndrome population is the only large cohort with a single GHR mutation (E180 splice), permitting identification of numerous carrier and noncarrier first-degree relatives, to ascertain effects of heterozygosity on GH-dependent IGF-I and IGFBP-3 concentrations and on growth. DESIGN: First-degree relatives (n=212) of GHRD patients had specimens taken for IGF-I, IGFBP-3, and GHR genotyping. Normal statured (n=40) and short statured (n=40) unrelated controls had measurement of IGF-I, IGFBP-3, and stature. RESULTS: There were no significant differences between heterozygous and homozygous normal relatives in IGF-I or IGFBP-3 standard deviation scores (SDS). Heterozygous relatives had lower mean height SDS than did homozygous normals, but with extensive overlap between genotype groups in both child and adult relatives. Height SDS in general did not relate to IGF-I or IGFBP-3 concentrations. CONCLUSIONS: GH-dependent IGF-I and IGFBP-3 secretion is not affected by heterozygosity for the E180 splice mutation that causes GHRD/Laron syndrome in the Ecuadorian population. Heterozygosity is associated with reduction in mean statural SDS, but this is not sufficient to be clinically important and not mediated through measurable differences in circulating IGF-I or IGFBP-3 related to genotype.     

IGF-1、IGFBP-3在儿童生长激素缺乏症诊断和疗效判断中的应用

目的探讨胰岛素样生长因子1(IGF-1)及其结合蛋白3(IGFBP-3)在儿童生长激素缺乏症(GHD)诊断及疗效判断中的价值。方法68例GHD患儿予以国产0.1 IU/(kg.d)r-hGH治疗12个月,于治疗前及治疗后3、6、12个月分别测定身高、体重、骨龄及血清IGF-1、IGFBP-3,并与60例正常儿童进行对照。结果GHD患儿血清IGF-1和IGFBP-3水平明显低于正常对照组(P均<0.01);r-hGH治疗后身高增长速度明显加快,血清IGF-1、IGFBP-3水平显著升高;治疗前血清IGF-1与治疗6、12个月时的生长速度(GV6,GV12)呈负相关(r=-0.72-、0.78,P均<0.01);治疗3个月时IGFBP-3水平变化与GV6、GV12呈正相关(r=0.82、0.80,P均<0.01)。结论IGF-1、IGFBP-3可用于儿童GHD的诊断及疗效预测。     

Effects of the IGF-I/IGFBP-3 complex on GH and ghrelin nocturnal concentrations in low birth weight children

OBJECTIVE: There is limited information regarding the effects of IGF-I and/or IGFBP-3 on circulating ghrelin concentrations. To determine the effects of IGF-I on GH and ghrelin concentrations, we examined the GH and ghrelin nocturnal profiles before and after the administration of the IGF-I/-IGFBP-3 complex (Iplex) to low birth weight children. DESIGN: The children were studied on two separate occasions, the first under basal conditions, and the second time after the sc administration of 1 mg/kg of Iplex at 2100 h. Blood samples for determination of GH and ghrelin were obtained every 20 min between 2300 h and 0700 h, while the children were sleeping. In each patient, we calculated the mean GH and ghrelin area under the curve (GH AUC and GHR AUC), both under basal conditions and after the administration of the IGF-I/IGFBP-3 complex. SETTING: The study was performed at a University Research Centre located at a General Hospital in Santiago, Chile. PATIENTS: Twenty prepubertal children (11 boys and 9 girls), born after a full-term pregnancy with a birth weight below 2.8 kg were studied at a mean +/- SEM age of 7.3 +/- 0.5 years (range 4-11 years). Their mean height was -1.8 +/- 0.3 standard deviation score (SDS) and their mean BMI was 0.1 +/- 0.2 SDS at the time of the study. MAIN OUTCOME AND RESULTS: Mean nocturnal GH AUC exhibited a significant decrease (2903 +/- 185 vs 1860 +/- 122 ng/ml min, P < 0.01), whereas mean GHR AUC showed a significant increase after administration of the IGF-I/IGFBP-3 complex (68 +/- 16 vs 288 +/- 36 ng/ml min, P < 0.01). CONCLUSIONS: These findings indicate that the IGF-I/IGFBP-3 complex appears to have opposite effects on circulating GH and ghrelin concentrations in low birth weight children, suggesting that, in addition to its known negative feed-back effect on GH, IGF-I and/or IGFBP-3 may have a positive feed-back effect on ghrelin.