| BackgroundGrowth hormone deficiency (i.e. pituitary dwarfism) is characteristic of shortstature because of pituitary-derived growth hormone (GH) lacking or declining. Growth hormone deficiency (GHD) which results children's short stature is one of endocrinological diseases. The best treatment is recombinant human growth hormone (rhGH) replacement therapy. Foreign countries have used rhGH to cure GHD since 1985and in children with GHD showed that rhGH treatment results in significant catch-up growth. But the high price restricted its usage in China. In recent years, by the development of biochemistrical techniques, Chinese rhGH has been on the market, rhGH replacement therapy were used widely in clinics, the early reasonable treatment can improve final height. Recent studies have demonstrated thatrhGH alse regulated many metabolic parameters. Now the lipid metabolism in GHD children is controversial. Some scholars think it is abnormal, but some keep the opposite opinion. Adiponectin(APN), a novel adipocyte-derived hormone, may play an important role in lipid metabolism and glucose homeostasis, because more and more experimental data have suggested that adiponectin regulate plasma glucose and lipid metabolism. Hypoadiponectinemia is strongly associated with dyslipidemia and increased risk of atherosclerosis and cardiovascular diseases. No previously published data are available about the effects of rhGH treatment on APN and lipids in GHD children. Are there any changes about lipid levels of GHD children? Especially what about the connection is between serum APN levels and lipid profiles after rhGH replacement? All these problems need further research.ObjectiveThe aim of this study is to observe the lipid metabolism and adiponectin levels in GHD children (aged from 5 to 15 years) and to investigate the relationship between the lipid homeostasis and adiponectin levels after rhGH replacement.SubjectsIn this study, 53 children with GHD (37 males, 16 females, mean age 9.8±2.4 years, range: 5-15 years) in department of endocrinology (The Children's Hospital of Zhejiang University School of Medicine ) were enrolled from July 2003 to Oct 2005. All were in prepuberty (Tanner stage 1) and excluded the following disease: idiopathic short stature, hypothyroidism, chromosomal disorders, liver-kidney disease,chondrodysplasia, other chronic organic disease, malnutrition, it was clear that they were suffering from GHD. The diagnosis standards are: (2) Height is at least 2SD lower than the mean height of the same gender and age (from national statistics for Chinese school children in 1995). ?Bone age is below the chronological age more than two years. 5) The gain in height is slow less than 4cm/yr. <$) GH peak is lessthan lOug/L during two GH provocation tests. These cases consisted of 32 complete growth hormone deficiency (CGHD) (GH peak <10ug/L) and 21 partial growth hormone deficiency (PGHD) (GH peak 5.0-9.9ug/L). 33 healthy children matched by age and sex enrolled in the study. All were no previous or present using of drugs or hormones interfering with lipid metabolism in 6 months.MethodsHeight (m), weight (kg) and Tanner stage were examined, body mass index (MBI)= weight/(height)2 (kg/m2). Blood samples were drawn at 8 a,m. after an overnight fast approximately 10 hours after the last light food. Triglyeride (TG) and total cholesterol (TC) were measured at once, 3 ml Blood samples were preserved in -80 °C to measure insulin-like growth factor-1 (IGF-1) and adiponectin concentrationsafter blood serum was detached. TG was measured by technique of GPO-PAP method, TC by technique of COD-PAP method, Plasma IGF-1 concentrations were measured by enzyme immunoassays (DSL Systems);the interassay coefficients of variation for IGF-1 were of 4.0% and intraassay coefficients of variation 6.0%. Plasma APN concentrations were measured by enzyme immunoassays (R & D Systems and Phoenix Pharmaceuticals);the interassay coefficients of variation for APN were of3.8% and intraassay coefficients of variation 5.8%.All statistical analyses were performed with SPSS software 10.0, all normal or approximately normal distributions data were expressed as the mean + SD. Skewed data were transformed logarithmically before performing statistical analysis, x2 test was used to measure the enumeration data. The statistical significance between means was estimated by one-way ANOVA followed by LSD multiple comparisons or Student's t test when appropriate. Multiregression analysis were calculated to determine the relationship between variables. Differences were considered to be statistically significant when a p value of less than 0.05 was obtained.Results1, Of these 53 GHD children, 22 patients (41.5%) had hyperlipidemia (16 withincreased levels of TG, 9 with increased levels of TC, 3 with increased levels of TGand TC), serum lipid levels in children with GHD had significant differencescompared to controls and to children over 1 year of replacement therapy with rhGH(3^=18.407, Z^O.000;^=13.437, P=0.000) .2> There was no statistically significant difference of serum TG levels (1.6±1.6 vs 1.5±1.5 mmol/L, P=0.449) and serum TC levels (4.6±0.8 vs 4.3±0.9 mmol/L, P=0.265) in children with CGHD and PGHD, so blending. After rhGH replacement therapy, serum TG and TC levels decreased significantly, serum IGF-1 increased significantly compared to pretreatment, the differences were statistically significant;BMI levels showed a trend to decrease and APN levels showed a trend to increaseafter rhGH replacement therapy, but no statistically significant differences.3 n Taking APN as dependent and age > BMK IGF-1 > TG n TC as independent enter into multistepwise regression equation excluding interactive influence among variables. With regression analysis, APN levels negatively significantly correlated withTG (P=0.004) , IGF-1 positively significantly correlated with age (P=0.009) , not with other variables.4> 44 GHD children were examined with a routine medical thyroxin function. Among then, 2 patients had a little decrease in T4 after rhGH replacement therapy and restored to the normal range after levothyroxine replacement 25ug po qd. All patients were within the normal range in T3> TSH.ConclusionK Lipid profiles in GHD children were abnormal, rhGH replacement therapy significantly improved the lipid metabolism, thus GH may directly take part in the lipid profile controlling of GHD children. 2n No statistically significant difference of serum APN in GHD children before andafter rhGH replacement therapy, but APN levels negatively correlated with TG, APN may partly take part in the metabolism of TG... |
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