成人生长激素缺乏症诊断与治疗指南解读

成人生长激素缺乏症(GHD)最常见于下丘脑和(或)垂体结构破坏或功能损害,临床上主要根据一系列非特异性临床表现及相应的生化指标来确诊。由于生长激素(GH)的脉冲式分泌及正常人群随机GH测定值的波动,GHD患者不能仅依据随机GH结果与正常人群相鉴别。目前国际上公认的成人GHD诊断金标准是胰岛素低血糖试验(ITT),近年来认为生长激素释放激素(GHRH)+精氨酸试验,GHRH+生长激素释放肽(GHRP)及胰高血糖素兴奋试验的诊断价值与ITT相当。成人GHD常合并多种并发症,其中慢性心血管系统并发症可能是导致该类患者病死率增加的主要原因。而重组人生长激素(rhGH)替代治疗可以改善这部分患者的许多临床终点事件,包括生活质量的提高及心血管风险的降低等。     

吡啶斯的明与左旋多巴联合激发试验对儿童生长激素缺乏症的诊断价值

目的　评价吡啶斯的明 (PD)加左旋多巴 (L dopa)联合激发试验对儿童生长激素缺乏症(GHD)的诊断价值。方法　 79例生长迟缓儿童 ,根据生长学资料、临床表现及血胰岛素样生长因子Ⅰ(IGF Ⅰ )、胰岛素样生长因子结合蛋白 3 (IGFBP 3 )水平分为临床拟诊GHD组 ( 3 9例 )与非GHD (NGHD)组 ( 4 0例 ) ,全部进行PD L dopa联合激发并随机分别另行精氨酸激发试验 (ARG ,43例 )或胰岛素耐量试验 (ITT ,3 6例 )。比较三种试验的生长激素 (GH)激发峰值及诊断敏感度、特异度、精确度 ,绘制受试者工作特性曲线 (ROC)及精确度曲线。结果　PD L dopa联合激发试验GH峰值在NGHD组高于ARG(P <0 .0 1)或ITT(P <0 .0 5 ) ,在GHD组差异无显著性。PD L dopa联合激发试验的准确度、特异度明显高于ARG或ITT ,敏感度与ARG或ITT相近。GH峰值取 7μg/L为正常截断值时 ,PD L dopa联合激发试验的敏感度、特异度与准确度均最高 ,超过 80 %。结论　PD L dopa联合激发试验对儿童GHD诊断价值优于ARG或ITT ,是一种适合儿童的有效、简便、安全的检测手段     

生长激素缺乏症的诊断和治疗

生长激素缺乏症(GHD)在儿童主要以身材矮小、生长障碍为主要表现,成人患者表现多无特异性,可有身体组分改变、血脂紊乱、骨密度降低、运动耐力下降、胰岛素抵抗、心血管风险增加、生活质量下降等.临床一般需要结合病史、发育状况、症状、体征、影像学资料、生长激素(GH)-胰岛素样生长因子(IGF)轴相关生化指标及GH激发试验来作...     

成人生长激素缺乏症的诊断与治疗

1 成人生长激素缺乏症(GHD)的定义 1.1 除非有已知的基因突变、可引起多种激素分泌缺陷的胚胎病理损伤或不可逆的结构损伤/破坏,推荐儿童期发病的GHD,经生长激素(GH)治疗已获得成人身高的患者再次筛查GHD.1.2下丘脑/垂体有结构性病变、行外科手术或接受过放射线照射、头外伤或有其他垂体激素缺乏证据的成人患者,应接受评估以明确是否有获得性GHD.     

生长激素缺乏症生化检测综合分析

目的以临床诊断作为矮小症患儿(可疑GHD)诊断标准,评估生长激素激发试验、胰岛素样生长因子Ⅰ(IGFⅠ)及IGF结合蛋白3(IGFBP3)对GHD的诊断价值。方法放免方法检测84例可疑GHD患者及63例非GHD患者GH峰值、IGFⅠ及IGFBP3,运用ROC曲线方法选定各生化检测的最佳截定值,并计算各最佳截定值的敏感性(sensitivity,S)、特异性(specificity,Sp)及诊断有效率(diagnosticefficiency,DEf)。结果ROC曲线显示GH激发试验GH峰值7.65μg/L为最佳截定值,DEf达84.4%,S为75.9%,Sp达94.9%;IGFⅠSDS最佳截定值为-1.85,S为70.2%、Sp为83.1%、DEf为70.2%;IGFBP3SDS最佳截定值为-1.55,比传统-2SD高,DEf为64.3%,Sp较高(89.8%),但S仅为45.8%。联合使用上述3种测定有较佳的DEf(91.2%),S(89.3%)和Sp(93.7%)。结论GH激发试验如选取一个好的截定值(本研究为GH峰值7.65μg/L),则该试验对GHD具有较高诊断价值;单个IGFⅠ检测则逊于GH激发试验;IGFBP3单独诊断GHD价值不大。三者联合使用诊断率及准确率皆很高,最具诊断价值。     

生长激素缺乏症治疗前后胰岛素样生长因子及其结合蛋白的变化

20 0 1年 6月至 2 0 0 2年 1 0月 ,我们对 46例生长激素缺乏症 ( GHD)儿童进行生长激素类激素 ( r-h GH)替代治疗 ,观察其血清胰岛素样生长因子( IGF- 1 )、胰岛素样生长因子结合蛋白 ( IGFBP- 3)变化 ,从而为 GHD疗效观察提供依据。1　资料与方法1 .1　临床资料　本文 GHD患儿 46例 ,男 30例 ,女1 2例 ,年龄 4～ 1 2岁。患儿均有典型 GHD症状与生长发育特征 ,身高低于同性别同年龄儿童第三百分位数 ,年身高生长速度 <2 .5 cm,骨龄落后于同类正常儿童至少两年 ;两项生长激素 ( GH)药物激发试验(可乐宁、精氨酸 ) GH峰值 <1 0 μg…     

重组人生长激素治疗儿童生长激素缺乏症疗效观察及预测

矮身材是儿科临床常见症状,生长激素(GH)缺乏症(GHD)是其原因之一.自80年代基因重组人GH(r -hGH)问世以来,国外已普遍应用r-hGH治疗GHD,并取得肯定疗效.本文观察了国产r-hGH治疗GHD的疗效及患儿血清胰岛素样生长因子-1(IGF-1)和胰岛素样生长因子结合蛋白-3(IGFBP-3)在r-hGH治疗期间的变化,现报告如下. 　　……     

血清生长介素水平对内分泌性矮小儿的诊断价值

本文报告102例矮小病人血清生长介素(SM-C)水平及其对生长激素缺乏症(GHD)的诊断价值。51例单纯GHD患者血清SM-C水平为0.14±0.18kU/L,GHD合并甲低和GHD继发于脑肿瘤的11例病人血清SM-C水平分泌为0.09±0.06和0.09±0.08kU/L,与单纯GHD者无差别,均明显低于正常同龄儿童。34例GH正常矮小儿童血清SM-C水平0.89±0.98kU/L,高于GHD患儿水平而低于正常同龄儿童。本文提出1～8岁儿童血清SM-C水平<0.15kU/L、9～17岁者<0.45kU/L应高度怀疑GHD。     

生长激素释放激素

垂体前叶生长激素(GH)的分泌受下丘脑两种激素调节,即生长激素释放激素(GHRH)及生长激素释放抑制激素(GHRIH,或称生长抑素SRIH)。本文简述GHRH的发现、组成、性质及临床应用。以下仅摘译其临床应用部分。 临床上给GH缺乏患者摄取GHRH,以确定有无功能性GH分泌细胞存在,这对于确定治疗方案及用药之前是必需进行的试验。作者曾将GHRH给子由于各种病因所致的身材矮小的儿童,发现那些继发于宫内生长阻滞或家族性身材矮小的儿童有正常的GH应答作用,而大多数器质性垂体功能低下     

成人生长激素缺乏症的诊断和治疗

成人生长激素缺乏症(AGHD)是一组临床表现多样的综合征,可表现为身体组分的改变,糖、脂、骨代谢异常,心血管疾病及骨折风险增加,生活质量下降等.诊断主要依据临床病史特征以及生长激素激发试验.重组人生长激素( rhGH)替代治疗可以明显改善患者的身体组分、异常代谢状态,降低心血管风险因素,提高其生活质量.     

Growth hormone treatment and cancer risk.

Increasing numbers of children receive growth hormone (GH) to treat a range of growth disorders, including those rendered GH deficient (GHD) by tumors or their treatment. Young persons with persistent growth hormone deficiency (GHD) and adults with severe GHD are also eligible to receive GH treatment. As in vitro and in vivo studies and epidemiologic observations provide some evidence that the GH--insulin like growth factor-I (IGF-I) axis is associated with tumorigenesis, it is important to assess, in practice, the incidence of tumors related to GH treatment. Reassuringly, surveillance studies in large cohorts of children and in smaller cohorts of adults indicate that GH is not associated with an increased incidence of tumor occurrence or recurrence. Nevertheless, all children who have received GH, in particular cancer survivors and those receiving GH in adulthood, should be in surveillance programs to assess whether an increased rate od late-onset and rare tumours may occur.     

Update on the diagnosis of GH deficiency in adults

GH deficiency (GHD) in adults is associated with considerable morbidity and mortality. The diagnosis of GHD is generally straightforward in children as growth retardation is present; however, in adults, diagnosis of GHD is often challenging. Other markers are therefore needed to identify adults who have GHD and could potentially benefit from GH replacement therapy. Consensus guidelines for the diagnosis and treatment of adult GHD recommend provocative testing of GH secretion for patients who have evidence of hypothalamic-pituitary disease, patients with childhood-onset GHD, and patients who have undergone cranial irradiation or have a history of head trauma. Suspicion of GHD is also heightened in the presence of other pituitary hormone deficits. Tests for GHD include measurement of the hormone in urine or serum or measurement of stimulated GH levels after administration of various provocative agents. The results of several studies indicate that non-stimulated serum or urine measurements of GH levels cannot reliably predict deficiency in adults. Although glucagon and arginine tests produce a pronounced GH response with few false positives, the insulin tolerance test (ITT) is currently considered to be the gold standard of the GH stimulation tests available. Unfortunately, the ITT has some disadvantages and questionable reproducibility, which have prompted the development of several new tests for GHD that are based on pharmacological stimuli. Of these, GH-releasing hormone (GHRH) plus arginine and GHRH plus GH-releasing peptide (GHRP) appear to be reliable and practical. Thus, in cases where ITT is contraindicated or inconclusive, the combination of arginine and GHRH is an effective alternative. As experience with this test as well as with GHRH/GHRP-6 accumulates, they may supplant ITT as the diagnostic test of choice.     

Diagnostic and therapeutic uses of growth hormone-releasing substances in adult and elderly subjects

The aim of this review is to answer two questions. The first question is: is there any alternative provocative test equal to, or even better than, the insulin-tolerance test (ITT), the so-called gold standard, for the diagnosis of growth hormone deficiency (GHD) in adults and the elderly? The answer is 'yes'. In fact, when combined with arginine or pyridostigmine, growth hormone-releasing hormone (GHRH) becomes one of the most potent and reproducible tests for distinguishing patients with severe GHD from normal subjects. Owing to its tolerability and its suitability for use in the elderly, the GHRH + arginine test is the best alternative choice and is at least as sensitive as the ITT provided that appropriate cut-off limits are given. The second question is: is there any therapeutic approach alternative to recombinant human growth hormone (rhGH) for adult and elderly patients with GHD and/or for the somatopause? At present, the answer is 'no'. Growth hormone (GH)-releasing substances need the functional integrity of somatotroph cells to induce the release of growth hormone. Probably only patients with childhood-onset, isolated GHD (frequently hypothalamic-dependent) could benefit from treatment with GHRH or growth hormone secretagogues (GHS). Whenever restoration of the activity of the GH/insulin-like growth factor-1 (IGF-1) axis in the elderly would be of use, GHRH and/or GH secretagogues would be good candidates. In fact, the existence of a considerable pool of releasable growth hormone has been demonstrated in the elderly.     

Currently used growth-promoting treatment of children results in normal bone mass and density. A prospective trial of discontinuing growth hormone treatment in adolescents

BACKGROUND AND AIMS: The need for continued GH replacement in patients with childhood-onset GH deficiency (GHD) into adulthood has been recognized. The consequences of discontinuing GH treatment on bone mineralization in adolescent patients with GHD and short stature were examined over a period of 2 years. PATIENTS: Forty adolescents (aged 16-21 years) treated with GH for more than 3 years and 16 closely matched healthy controls were studied. After a baseline visit, GH treatment was discontinued. The patients were then re-examined with the same protocol after 1 and 2 years. Twenty-one patients had continuing severe GHD into adulthood, while 19 patients were regarded as having sufficient endogenous GH secretion (GHS). RESULTS: At baseline, there were no differences between the groups in total bone mineral content (BMC) or bone mineral density (BMD). After 2 years without GH treatment, BMC increased similarly in the GHD and GHS groups. BMC of the lumbar spine (L2-L4) increased only in the GHD group. Lumbar spine BMD increased in the GHD and the GHS groups. No changes were observed in the femoral neck region. Biochemical measurements showed that carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) and bone specific alkaline phosphates (ALP) were higher in the GHD and GHS groups at baseline compared with controls. Osteocalcin, carboxy-terminal propeptide of type I procollagen (PICP), ICTP and ALP decreased during the 2 years off treatment in both the GHD and GHS groups. PICP was also lower after 2 years in the GHD group compared with both the GHS group and controls. CONCLUSIONS: After discontinuation of GH therapy in adolescents at or near final height, there was a continued increase in BMC and BMD both for adolescents with growth hormone deficiency and for those classified as growth hormone sufficient. These groups did not differ from controls at baseline or after 2 years. In the growth hormone deficiency group, biochemical markers for bone formation decreased to levels below those in the growth hormone sufficient and healthy control groups. Although the number of patients and controls in this study were small, the results indicate that the present treatment of Swedish GH-deficient children to final height results in normal BMD.     

Obesity,growth hormone and weight loss

Growth hormone (GH) is the most important hormonal regulator of postnatal longitudinal growth in man. In adults GH is no longer needed for longitudinal growth. Adults with growth hormone deficiency (GHD) are characterised by perturbations in body composition, lipid metabolism, cardiovascular risk profile and bone mineral density. It is well established that adult GHD usually is accompanied by an increase in fat accumulation and GH replacement in adult patients with GHD results in reduction of fat mass and abdominal fat mass in particular. It is also recognized that obesity and abdominal obesity in particular results in a secondary reduction in GH secretion and subnormal insulin-like growth factor-I (IGF-I) levels. The recovery of the GH IGF-I axis after weight loss suggest an acquired defect, however, the pathophysiologic role of GH in obesity is yet to be fully understood. In clinical studies examining the efficacy of GH in obese subjects very little or no effect are observed with respect to weight loss, whereas GH seems to reduce total and abdominal fat mass in obese subjects. The observed reductions in abdominal fat mass are modest and similar to what can be achieved by diet or exercise interventions.     

Is growth hormone stimulation testing in children still appropriate?

The diagnosis of growth hormone deficiency (GHD) historically has relied on measurement of growth hormone (GH) concentrations following stimulation, usually with a non-physiologic provocative agent. Despite the use of more specific GH assays, the peak concentration of GH below which a child is considered GH deficient has risen. We examine the pitfalls associated with GH stimulation tests, specifically, the lack of reliability and accuracy of these tests, and their inability to predict who will benefit from GH therapy. We recommend that GH stimulation tests no longer routinely be used for the diagnosis of GHD in children.     

血清胰岛素样生长因子及其结合蛋白诊断儿童生长激素缺乏症的价值

为了解血清胰岛素样生长因子1（IGF－1），胰岛素样生长因子结合蛋白－3（IGFBP－3）浓度与生长激素缺乏症（GHD）患儿生长激素（GH）激发试验中血清生长激素峰值的关系，以确定血清IGF－1，IGFBP－3浓度诊断GHD的价值，为其代替GH激发试验提供依据，选择GHD患儿62例（男39例，女23例）为GHD组，60例健康儿童（男38例，女22例）为对照组。分别用放射免疫分析（RIA）法，免疫放射分析（IRMA）法检测GHD组血清IGF－1，IGFBP－3浓度，同时被GH激发试验，测定血清GH峰值，并比较其与IGF－1，IGFBP－3的关系，测定对照组血清IGF－1，IGFBP－3。结果显示，GHD组血清IGF－1，IGFBP－3均显著低于对照组（t分别为3.116,11.579,p均＜0．01）；GHD组血清IGF－1，IGFBP－3浓度与GH激发试验中的GH峰值呈显著正相关（r分别为。331，0。347，P均＜0．01）；GHD组血清IGF－1，IGFBP－3降低的阳笥率分别为97．58％，98．38％，与激发试验的阳性率（100％），比较无统计学意义（x^2分别为.3074,2.033,P均＞0．05）。表明血清中IGF－1，IGFBP－3浓度检测对诊断GHD有重要价值，认为检测血清中IGF－1，IGFBP－3浓度可以替代GH激发试验。     

Seasonality of growth response to GH therapy in prepubertal children with idiopathic growth hormone deficiency

OBJECTIVE: Longitudinal growth of children exhibits seasonal variation. In both healthy children and in children with growth hormone (GH) deficiency (GHD) receiving GH therapy, growth rate is maximal during spring and summer. In the present study, we analyzed the growth response to GH therapy in children with GHD as a function of the season when therapy was started. SUBJECTS AND METHODS: Anthropometric measurements and biochemical analyses of GH secretion status and bone formation were longitudinally assessed in a cohort of 52 prepubertal children with GHD (14 girls, mean age 7.6 years) who were treated with a fixed dose of GH (0.025 mg/kg/day). RESULTS: Auxological assessments over the 2-year observation period revealed a significantly better growth response to GH therapy in children who started therapy between the spring and summer (group 1) compared with children who started in the autumn or winter (group 2). The difference was largest in the initial 3-month treatment period (35%; P<0.01). The initial better gain in height of group 1 was sustained during the study period. Baseline peak GH levels during stimulation tests and insuin-like growth factor-I levels did not differ between the two groups. However, group 1 had significantly higher bone resorption and formation markers, either at the start or shortly after initiation of GH treatment. This suggests that children with GHD have higher bone turnover during spring and early summer, irrespective of GH therapy. CONCLUSIONS: In summary, this study suggests that the season of GH initiation is a determinant of the initial growth response to GH replacement in prepubertal children with GHD.     

Management of the growth hormone (GH)-treated patients with diagnosis of GH deficiency (DGH) during transition from childhood to adulthood

Growth hormone (GH) has many beneficial effects in patients with childhood-onset GH deficiency (GHD) in addition to its promotion of linear growth. The discontinuation of GH treatment in GHD patients, during the transition from childhood to adulthood, induces significant unfavorable changes in body composition, skeletal integrity, exercise capacity, and an adverse cardiovascular risk profile. These changes are reversed after the resumption of GH treatment. As the benefits of continuing GH therapy into adulthood has been well established, it is possible that GH replacement therapy will not be stopped once growth has been completed, but it will continue into adult life. Considering that a high proportion of patients with diagnosis of DGH in childhood are no longer GHD in adolescence, the GH status must be retested when growth is completed. Other factors such as clinical history, GH response in childhood, hipotalamic-pituitary MRI and IGF-1 concentration must be considered. Reconfirmation of GHD diagnosis through stimulation testing is usually required, unless there is a proven genetic or structural lesion persistent from childhood.