Determination And Analysis Of IGF-1, IGFBP-3 And Thyroid Hormones In Serum Of Children With Obstructive Sleep Apnea Hypopnea Syndrome

BackgroundObstructive sleep apnea hypopnea syndrome(OSAHS) is one of the common and frequently-occurring childhood diseases.The prevalence of OSAS in children has been reported to range from 1%to 3%.Child OSAHS means partial or complete obstruction in the upper airway frequently occurring in the sleep,which disrupts normal airflow and sleep architecture and was characterized by sleep apnea and hypopnea.The main pathophysiological changes are hypoxia and / or carbon dioxide retention which are caused by respiratory obstruction.Long time and untreated sleep apnea and hypopnea may affect the growth and development of the children,even cause some serious complications such as growth retardation,craniofacial deformities, mental retardation,pulmonary heart disease,psychological behavioral abnormalities and sudden death et al.In the recent years,the research on OSAHS has aroused wide attention from various doctors.Because children are in a period of growth and development,the impact on obstructive sleep apnea on the growth and development of the children can not be ignored.Although the exact cause of the poor growth is unknown,candidates include low caloric intake caused by poor appetite and dysphagia,high energy expenditure due to more difficult breathing during sleep,nocturnal acidosis,and nocturnal hypoxemia.Abnormal nocturnal growth hormone(GH) secretion has also been suggested. Hypothalamic-GH-IGF axis is the most important human endocrine and metabolic axes,which regulate the growth and development throughout the human life.GH is secreted by adenohypophysis and is one of the most important growth-promoting hormones.The primary role of GH is to stimulate the differentiation and proliferation of the epiphyseal cartilage cell.It plays a role in promoting growth directly or indirectly through insulin-like growth factor-1(IGF-1) and insulin-like growth factor-binding protein 3(IGFBP-3) which are secreted by the liver.IGF-1 is considered as the main mediator of the growth-promoting actions of GH.IGF-1 is closely related to the secretion of GH and it has been reported to correlate well with the physiological changes in GH secretion.IGFBP-3 is the major carrier protein of IGF-1 which has highest concentration in human blood and has the strongest effect.It can extend the remaining time of the IGF-1 in blood circulation and prolong the half-life of IGF-1 3 to 5 times.GH is released in a pulsatile fashion and its half-life is short.It is of little diagnostic value to determine the level of GH once.To determine the levels of IGF-1 and IGFBP-3 which are more stable and can better reflect the physiological state of individual GH secretory function in this study.Thyroid hormones have a broad physiological role,such as metabolism promotion,the development,differentiation and maturation of central nervous system and the development of bone and gonad et al.Thyroid hormones have synergy with GH to the growth,which are essential hormones about normal growth,especially to the brain and bone.This study is to study the secretary levels of thyroid hormones in children with OSAHS and to explore the impact of thyroid hormones on the growth of OSAHS child.At present,there is no report about the changes of growth-related endocrine hormones such as serum IGF-1,IGFBP-3 and thyroid hormones in children with OSAHS.ObjectiveDetermine the levels of serum IGF-1,IGFBP-3 and thyroid hormones(T₃,T₄,FT₃,FT₄) in children with OSAHS and to explore the relations between their levels and the growth of children with OSAHS. Methods1,Groupsâ‘ the group of OSAHS:25 child patients with OSAHS diagnosed by polysomnography for treatment in the Department of Otorhinolaryngology,Second Hospital of Shandong University,during the period of April 2008 and December 2008 were enrolled in the study.All children have no congenital anatomical abnormalities and neurological disorder phenomenon and have no acute infections in the latest month and have no liver and renal diseases and endocrine diseases.â‘¡the control group:15 healthy children checking up in the out-patient were enrolled as the control. There are no differences for age and sex ratio between the OSAHS children and controls.2,Anthropometric measurement Measure the height and weight of the children by the same person,then calculate BMI,HtSDS and WtSDS.3,Polysomonography All children underwent overnight PSG on the first night for seven hours in sleep laboratory.The nocturnal sleep was monitored for an oro-nasal thermisor,oxygen saturation,electroencephalogram,electromyogram, electro-oculogram,electrocardiogram,snoring and thoracoabdominal breathing et al. All recordings were manually checked by the same person after automatic analysis of computer software and were printed.4,Samples collections Venous blood samples were obtained in the morning. The serums were extracted from blood samples,centrifuged and stored frozen at -80℃.5,Samples measurement Serum IGF-1 and IGFBP-3 levels were determined by ELISA,serum thyroid hormones were determined by Radioimmunoassay.Results1,The height,weight,BMI,HtSDS and WtSDS of the OSAHS children were 1.16±1.66 m,24.58±9.53 kg,17.67±2.86 kg.m^-2,0.64±1.59 and 1.89±2.52;the height, weight,BMI,HtSDS and WtSDS of the healthy children were 1.23±1.17 m,25.27±5.96 kg,16.35±1.33 kg.m^-2,0.88±0.63 and 1.09±0.72.There were no significant statistical difference between the two groups(P＞0.05).Two out of twenty-five children with OSAHS have growth retardation(8 percent). 2,The level of serum IGF-1 was 70 603.65±15 843.17 pg.mL^-1,and the level of the control was 78 044.24±19 954.33 pg.mL^-1.There was no significant statistical difference between the OSAHS children and controls(P=0.268＞0.05).3,The level of serum IGFBP-3 was 338 801.7±167 899.1 pg.mL^-1,and the level of the control was 494 480.0±202 081.9 pg.mL^-1.There was significant statistical difference between the two groups(P=0.029＜0.05).4,The levels of serum TSH,T₃,T₄,FT₃ and FT₄ were 4.031±1.246 uIU.mL^-1,2.309±0.781 ng.ml^-1,132.4±30.7 ng.ml^-1,6.386±2.223 fmol.mL^-1 and 14.386±4.439 fmol.mL^-1,and the levels of the control were 4.021±2.402 uIU.mL^-1,2.644±0.618 ng.ml^-1,126.4±25.5 ng.ml^-1,5.484±2.820 fmol.mL^-1 and 14.713±4.160 fmol.mL^-1.There were no significant statistical difference between the OSAHS children and controls(P＞0.05).5,In the OSAHS group,there were significant positive correlation between IGF-1 and age(r=0.913,P=0.000),height(r=0.893,P=0.000),weight(r=0.827,P =0.000),BMI(r=0.842,P=0.000),HtSDS(r=0.962,P=0.000),WtSDS(r=0.678,P =0.000);in the control group,there were significant positive correlation between IGF-1 and age(r =0.983,P =0.000),height(r =0.976,P =0.000),weight(r =0.964,P =0.000),BMI(r =0.960,P =0.000),HtSDS(r =0.987,P =0.000),WtSDS(r =0.887,P =0.000).6,In the OSAHS group,there were significant positive correlation between IGFBP-3 and age(r =0.777,P =0.000),height(r =0.767,P =0.000),weight(r =0.838, P =0.000),BMI(r =0.946,P =0.000),HtSDS(r =0.804,P =0.000),WtSDS(r =0.984, P =0.000);in the control group,there were significant positive correlation between IGFBP-3 and age(r =0.938,P =0.000),height(r =0.899,P =0.000),weight(r =0.950, P =0.000),BMI(r =0.952,P =0.000),HtSDS(r =0.895,P =0.000),WtSDS(r =0.752, P =0.000).7,There were significant positive correlation between IGF-1 and IGFBP-3 in the OSAHS group(r =0.650,P =0.000) and the control group(r =0.938,P =0.000).8,There were no significant correlation between IGF-1 and TSH,T₃,T₄,FT₃, FT₄ in the OSAHS group and the control group(P＞0.05).9,There were no significant correlation between IGFBP-3 and TSH,T₃,T₄, FT₃,FT₄ in the OSAHS group and the control group(P＞0.05).Conclusion1,OSAHS may affect the growth of the children and cause the growth retardation of the children.2,OSAHS children have the reduced IGFBP-3 concentrations,which may play an important role in the growth impairment of the children with OSAHS.3,The children with OSAHS who had growth impairment may had abnormal GH-IGF axis.4,The levels of thyroid hormones with OSAHS children were normal,which indicated that OSAHS do not affect the secrection of thyroid hormones in children and the growth retardation of the child patients may have no relations with thyroid hormones.5,We should take intervention measures on children with OSAHS as early as possible,in order to decrease or avoid the bad impacts on the growth and development of children caused by OSAHS.