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.     

健康老年人生长激素分泌的变化及重组人生长激素应用的研究

重组人生长激素自问世以来,被广泛用于儿童及成人生长激素缺乏症的治疗,但在老年人中作为抗衰老治疗的手段仍存在较大的争议。健康老年人生长激素分泌随增龄而逐渐下降,存在生长激素相对不足的状态,重组人生长激素应用可改善老年人的身体成分,但还没有充足证据证实生长激素治疗可改善老年人的整体机能和提高骨密度及降低血脂,也无证据支持重组人生长激素治疗可延长寿命。重组人生长激素应用会引发较多的副反应,且有潜在致恶性肿瘤的风险,目前并不建议健康老年人使用生长激素。     

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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,GH-RH+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(rh-GH)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。     

生长激素缺乏对成人骨代谢的影响

生长激素在骨生成过程中起重要作用,可刺激骨生长.成人生长激素缺乏可引起骨代谢改变,包括生化学改变及骨矿物质密度下降,从而增加骨折危险性.确切机理还不十分明确,可能与起病年龄、达到骨量高峰年龄有关.重组人生长激素替代治疗对骨的疗效随疗程长短而不同,研究结果不完全一致,主要可能与研究时的给药剂量、给药持续时间、研究骨类型等不同有关.     

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。     

成人生长激素缺乏症治疗的研究进展

生长激素(GH)是由垂体前叶生长激素细胞以脉冲方式分泌的促蛋白合成类蛋白。成人GH的主要亚型是一个191个氨基酸的蛋白质(分子量为22 kD),GH在维持肌肉力量、改善心脏功能、延缓衰老、防止骨质疏松、减肥以及促进伤口愈合等方面具有重要作用。GH的缺乏可对机体产生许多不利影响,替代治疗可逆转或减轻这些影响。成人生长激素缺乏症     

生长激素和心力衰竭

近年来的研究表明 ,生长激素 (GH)不仅可以调节生长及营养代谢、骨胳肌的活动 ,而且在心血管生理中也起着重要作用。它是胚胎及儿时心脏发育及成年后维持心脏形态和功能的必不可少的激素 [1]。流行病学资料表明 ,生长激素缺乏 (GHD)尤其是先天性病人 ,心脏萎缩 ,心脏活动和运动耐量明显下降 ,心血管病死亡率高 ,大多死于心衰 ,此类病人对常用的抗心衰治疗无效 ,而生长激素替代治疗有效。随着对生长激素心脏生理功能研究的不断深入 ,人们试图开创一条用各种生长因子治疗心衰的途径。这种新的治疗策略与传统的治疗目的不同 ,不是要延缓心脏…     

生长激素治疗成人生长激素缺乏症对心血管系统短期和长期影响

０８０生长激素治疗成人生长激素缺乏症对心血管系统短期和长期影响［英］／ＴｈｕｅｓｅｎＬ…／／ＣｌｉｎＥｎｄ－ｏｃｒｉｎｏｌ，－１９９４，４１．－６１５～６２０自从生长激素（ＧＨ）用于治疗成人ＧＨ缺乏症后，ＧＨ替代治疗对心血管系统影响已引起临床上广泛兴...     

重组人生长激素对肝炎肝硬化患者生长激素抵抗状况改善的研究

评价重组人生长激素对不同Child -Pugh积分肝炎肝硬化患者生长激素抵抗的改善及对低蛋白血症的影响 ,根据Child -Pugh积分分为 <9组 ,2 5例 ; 9组 ,2 6例两组。再采用随机区组设计方法对上述患者分组治疗 ,治疗组 (各 16、15例 )用重组人生长激素 (0 2 5U/kg·d) ,对照组 (各 9、11例 )予人血白蛋白 (10g/d)治疗 10天。用放射免疫法测定治疗前、治疗后 2 4h及治疗结束时的血清生长激素 (GH ,μg/L)、类胰岛素生长因子 (IGF) - 1(μg/L)。肝硬化患者GH水平高于健康人 (P <0 0 5 ) ,但IGF - 1水平明显降低 (P <0 0 1)。经重组人生长激素治疗后 ,肝硬化患者生长激素抵抗均有不同程度改善 (P <0 0 1)。观察结束两治疗组比较 ,积分高组较之低组GH一直维持较高水平 (9 91± 7 6 1,4 75± 3 94 ,P <0 0 5 ) ,且IGF - 1上升幅度低 (4 8 4 3± 16 88,6 3 4 7± 2 2 19,P <0 0 5 )。两治疗组治疗后血清白蛋白 (ALB)均有明显升高。重组人生长激素可以克服肝硬化患者 ,尤其Child -Pugh积分低者的生长激素抵抗现象 ,并纠正其低蛋白血症     

成人生长激素缺乏的诊断治疗

近年来，利用重组人生长激素（ｒｈＧＨ）治疗成人生长激素缺乏症（ＧＨＤ）取得一些进展。成人ＧＨＤ属于临床综合征，临床表现复杂多样，除主要的各种物质代谢紊乱外，心血管系统，神经精神功能，肾功能，凝血机制均有不同程度障碍。关于成人ＧＨＤ的诊断标准尚无统一意见。一般认为，单一的刺激试验所反映的ＧＨ分泌常不可靠，而主张采用联合试验，如ＧＨＲＨ＋ＰＤ，ＧＨＲＨ＋ＡＲＧ等，文内对各种测验手段的评估和具体方法作了叙述。利用ｒｈＧＨ治疗后，对身体各系统功能有不同程度影响，以内分泌激素分泌和物质代谢强度较为明显，多数学者的治疗经验显示无明显副作用，但治疗时应慎重选择病例，控制适当剂量和疗程。     

Growth hormone secretion in diabetic retinopathy

Summary The plasma HGH response to insulin-induced hypoglycemia (0.2 U/kg) and the 24-h plasma HGH pattern during a normal day have been studied in 14 non obese long-term insulin-dependent diabetics with proliferative retinopathy, mean age 39 ± 2 (ranging between 24 and 50 years). Plasma glucose and FFA were also determined. The results were compared with those of 18 normal subjects of similar age and weight. The mean plasma HGH response to insulin in retinopathic diabetics was slightly lower (with no significant differences) than in controls in whom hypoglycemia was induced with a smaller dose of insulin (0.1 U/kg). This pattern of plasma HGH could be related to the delayed plasma glucose fall observed in retinopathic diabetics in comparison to normal subjects, even if the HGH peak after insulin in both groups (18.61 ± 4.32 ng/ml in retinopathic diabetics, 27.43 ± 4.19 in controls) did not seem to be correlated to the degree of hypoglycemia, but rather to the age of the subjects. Plasma HGH pattern, studied with blood samples taken every three hrs during a normal day, did not reveal differences between the diabetics and controls. Plasma glucose, however, was higher in retinopathic diabetics than in controls in spite of the insulin treatment. These results show that in diabetic patients with retinopathy, increased HGH secretion does not occur in conditions of ordinary life or after insulin-induced hypoglycemia, although the HGH plasma levels observed in retinopathic diabetics could be considered too high in relation to the elevated blood glucose levels. Traduzione a cura degli AA.     

Prader-Willi Syndrome and Growth Hormone Deficiency

Prader-Willi syndrome (PWS) is a rare multisystem genetic disorder demonstrating great variability with changing clinical features during patient’s life. It is characterized by severe hypotonia with poor sucking and feeding difficulties in early infancy, followed by excessive eating and gradual development of morbid obesity in later infancy or early childhood. The phenotype is most probably due to hypothalamic dysfunction which is also responsible for growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies, central adrenal insufficiency and hypogonadism. The multidimensional problems of patients with PWS can be managed with multidisciplinary approach. Reduced GH secretion, low peak GH response to stimulation, decreased spontaneous GH secretion and low serum IGF-1 levels in PWS patients have been documented in many studies. GH therapy has multiple beneficial effects on growth and body composition, motor and mental development in PWS patients. The recommended dosage for GH is 0.5-1 mg/m2/day. GH therapy should not be started in the presence of obstructive sleep apnea syndrome, adenotonsillar hypertrophy, severe obesity and diabetes mellitus. GH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental and life-style measures.     

Growth hormone (GH)–releasing hormone and GH secretagogues in normal aging: Fountain of Youth or Pool of Tantalus?

Although growth hormone (GH) is primarily associated with linear growth in childhood, it continues to have important metabolic functions in adult life. Adult GH deficiency (AGHD) is a distinct clinical entity, and GH replacement in AGHD can improve body composition, strength, aerobic capacity, and mood, and may reduce vascular disease risk. While there are some hormone-related side effects, the balance of benefits and risks is generally favorable, and several countries have approved GH for clinical use in AGHD. GH secretion declines progressively and markedly with aging, and many age-related changes resemble those of partial AGHD. This suggests that replacing GH, or stimulating GH with GH-releasing hormone or a GH secretagogue could confer benefits in normal aging similar to those observed in AGHD – in particular, could reduce the loss of muscle mass, strength, and exercise capacity leading to frailty, thereby prolonging the ability to live independently. However, while most GH studies have shown body composition effects similar to those in AGHD, functional changes have been much less inconsistent, and older adults are more sensitive to GH side effects. Preliminary reports of improved cognition are encouraging, but the overall balance of benefits and risks of GH supplementation in normal aging remains uncertain.     

Growth hormone deficiency in adults with hypopituitarism—What are the risks and can they be eliminated by therapy?

Growth hormone (GH) deficiency develops early in patients with hypothalamic-pituitary disorders and is therefore common among these patients. GH deficiency in adults is associated with increased morbidity, increased body fat mass, abdominal obesity, dyslipidaemia, reduced exercise capacity, impaired cardiac function as well as reduced self-reported well-being and impaired quality of life. Since recombinant human GH became available as replacement therapy more than 25 years ago, randomised controlled trials and long-term studies, together with meta-analyses, have shown improved outcomes in adult patients with hypopituitarism receiving GH. Many of the features associated with GH deficiency in adults improve, or even normalize, and the safety profile is reassuring. The increased interest in GH deficiency in adults with hypothalamic-pituitary disorders has also contributed to the identification of other factors of importance for an outcome such as the replacement of other pituitary hormone deficiencies, and the management of the underlying hypothalamic-pituitary disease, most commonly a pituitary tumour. In this narrative review, we summarize the burden of GH deficiency in adults with hypopituitarism, the impact of GH replacement on the outcome, as well as safety. Based on currently available data, GH replacement should be considered routine management of adults with hypopituitarism.     

Growth hormone response to L-Dopa in diabetes mellitus

Summary The effect of a single oral dose of 0.5 g L-Dopa on the serum levels of human growth hormone (HGH) was studied in 38 diabetics and 15 age and sex matched control subjects. The diabetics were divided into three clinical sub-groups:a) juvenile diabetics, 15;b) maturity onset diabetics, 15; andc) insulin dependent diabetics admitted in a state of ketoacidosis, 8. L-Dopa-induced HGH secretion in juvenile and maturity onset diabetics was studied before and after the control of diabetes mellitus. HGH was estimated by a homologous double antibody radioimmunoassay. The fasting serum HGH in maturity onset diabetics did not differ significantly from that of control subjects; it was significantly higher in juvenile diabetics and in ketotic diabetics during ketosis and after the control of diabetes. In juvenile diabetics the mean fasting serum HGH level decreased after the control of diabetes but was still significantly higher than in normal subjects. L-Dopa caused a significant rise in serum HGH in 14 control subjects. Among the diabetics the HGH response to L-Dopa was either absent or markedly attenuated in the uncontrolled state. After the control of diabetes a significant improvement in HGH response to L-Dopa was evident in juvenile diabetics but no improvement was seen in maturity onset diabetics. There is thus a considerable derangement in HGH secretion in diabetes mellitus. The various possibilities are discussed.     

Growth hormone release in unstable diabetes: Tests with saline,arginine, glucagon,and epinephrine

Summary Changes in plasma growth hormone (HGH) concentrations during tests with arginine, glucagon, epinephrine and saline were compared in 8 unstable and 4 stable diabetics, and 5 normal subjects. These same subjects had previously also been tested with insulin-induced hypoglycemia and their blood glucose variability had been quantified during near-normal (ambulatory-fed) living conditions. Compared with saline infusion, arginine induced higher HGH increases but glucagon and epinephrine did not. Compared to preinfusion levels, epinephrine decreased HGH concentrations. Patterns of mean HGH increase and decrease after arginine were similar in the 3 groups of subjects. Only during saline infusion did unstable diabetics have higher peak levels than did stable diabetics and normal subjects. The higher or similar increases of HGH in unstable diabetics always occurred at higher concentrations of blood glucose and frequently, but not invariably, at higher concentrations of serum free fatty acids and ketone bodies than in stable diabetics and in normals. HGH release is abnormal in unstable diabetics in that hyperglycemia does not inhibit the release of HGH. The abnormality is associated with impaired modulation of blood glucose and other variables through inability to secrete endogenous insulin. Traduzione a cura degli AA.     

Acceleration of Puberty During Growth Hormone Therapy in a Child with Septo-Optic Dysplasia

Septo-optic dysplasia (SOD) is a heterogeneous disorder of the central nervous system characterized by various endocrinological and neurological findings. It is a complex disease caused by a combination of genetic and environmental factors. Herein, we report the case of a 5.5-year-old girl who presented with short stature and strabismus. Ophthalmological examination revealed bilateral optic nerve hypoplasia. Ectopic posterior pituitary and bilateral optic hypoplasia were detected on brain magnetic resonance imaging. The presence of bilateral optic nerve hypoplasia and hypopituitarism led to the diagnosis of SOD. An abated growth hormone (GH) response was found in the GH stimulation test and GH replacement therapy was initiated. At the end of the first year of clinical follow-up, secondary hypothyroidism was detected and L-thyroxine was added to the treatment. At the age of 8.25 years, thelarche was noted and 6 months later, the patient presented with menarche. At this time, the bone age was 12 years and the basal luteinizing hormone level was 7 mIU/mL. These findings indicated acceleration in the process of pubertal development. We report this case (i) to emphasize the need to investigate hypopituitarism in cases with bilateral optic nerve hypoplasia and (ii) to draw attention to the fact that during the follow-up of SOD cases receiving GH therapy, inappropriate acceleration of growth velocity and rapid improvement in bone age may be predictive of central precocious puberty development.     

Evaluation of Asymmetric Dimethylarginine (ADMA) Levels in Children with Growth Hormone Deficiency

Ob­jec­ti­ve: To investigate serum asymmetric dimethylarginine (ADMA) levels in children with isolated growth hormone deficiency (GHD) and to determine the effect of GH replacement therapy on these levels.Methods: 31 patients diagnosed with isolated GHD and 29 age-and sex-matched healthy children were enrolled in the study. Height, weight and waist circumference were measured in all subjects. Fasting serum insulin-like growth factor-1 (IGF-1), IGF binding protein-3, glucose, insulin and lipid levels were evaluated. Serum ADMA levels were assessed using the enzyme-linked immunosorbent assay technique. The same evaluations were repeated on the 3^rd and 6^th months of treatment in 28 of the GHD cases.Results: There were no significant differences in ADMA levels between the patient and control groups [0.513±0.130 (0.291-0.820) µmol/L vs. 0.573±0.199 (0.241-1.049) µmol/L]. There was a positive correlation between serum ADMA and HbA1c levels in the control group. In the GHD cases, ADMA levels negatively correlated with high-density lipoprotein levels and positively correlated with low-density lipoprotein levels. There was also a significant increase in ADMA levels in patients receiving GH therapy compared to pre-treatment levels [serum ADMA level, 1.075±0.133 (0.796-1.303) µmol/L at the 3rd month and 0.923±0.121 (0.695-1.159) µmol/L at the 6th month of treatment]. There was a negative correlation between ADMA levels and homeostasis model assessment of insulin resistance values at the 6th month evaluation. There were no relationships between ADMA levels and age, sex, or pubertal state either before or during the treatment.Conclusion: Serum ADMA levels were found to be similar in patients with GHD and in healthy children. However, serum ADMA levels showed a significant increase in GHD patients following GH replacement therapy.     

Hormone replacement therapy. An analysis of efficacy based on evidence

Hormone replacement therapy (HRT) has long been a staple of management of the postmenopausal life phase. Over time, and after estrogen therapy was modified to include progestin, an increasing number of observational reports suggested that HRT conferred benefits well beyond those of managing or minimizing not flashes, mood swings, and vaginal dryness. In short, HRT was believed to improve women's health and even extend life. One of the most significant theorized benefits was protection against cardio- and cerebrovascular events. Other benefits--protection against osteoporosis, reduction in incontinence symptoms, and improved cognition--have also been linked with HRT. The validity of these theories depended largely on observational studies and anecdotal reports, and only lightly (or not at all) on randomized clinical trial data. Nevertheless, significant clinical data refuting HRT's proposed benefits has been available for several years. Findings from these investigations, including new results from two very large trials, show that beyond managing traditional menopause symptoms, HRT has little or no role in protection against certain diseases or conditions associated with aging. Indeed, long-term use of HRT may be contraindicated in most older women with intact uteruses.     

Hormone replacement therapy and fractures in older adults

Estrogen deficiency in women is associated with accelerated bone loss, and estrogen replacement therapy has been proven to be effective in preventing osteoporosis and fractures in postmenopausal women. The introduction of selective estrogen receptor modulators that have an estrogen-like effect on the skeleton but have a different pattern of effects on other tissues may have an important role in the management of osteoporosis in women in the near future. In men, androgen deficiency has been shown to be associated with osteoporosis. Although androgen replacement in hypogonadal men may decrease bone resorption and increase bone mass, long-term placebo-controlled trials are needed to better define the benefits and risks of such therapy before it can be recommended. Sex hormone deficiency is linked to the development of osteoporosis in both women and men. In women, hormonal replacement by estrogen or the newly developed selective estrogen receptor modulators may prevent the development of osteoporosis and its related fractures. In men, there is early evidence that testosterone replacement therapy may enhance bone mass in hypogonadal men.