重组人生长激素在成人生长激素缺乏症的应用

近20年来,重组生长激素已可以无限量的制备。近年来的研究已阐明成人生长激素缺乏的影响及生长激素替代治疗的益处。成人生长激素缺乏症对人影响最大的是生活质量、骨骼健康及包括血清脂质谱、身体构成变化的心血管危险因子的改变,而这也正是生长激素替代治疗获益最显著之处。大量的证据显示了重组人生长激素治疗的疗效,尤其在改善骨代谢和改善心血管危险因素等多方面发挥作用,并且是安全的。     

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.     

Effects of Growth Hormone and Estrogen on Rat Angiotensinogen Quantified by an Enzyme Linked Immunosorbent Assay

An enzyme linked immunosorbent assay for rat angiotensinogen was developed based on one monoclonal antibody with high affinity for angiotensinogen and des-angiotensin 1–angiotensinogen and rabbit polyclonal antibodies for angiotensinogen was developed. Serum levels of angiotensinogen were lower in female than in male rats but increased significantly after hypophysectomy. Estrogen substitution after hypophysectomy had no further stimulatory or inhibitory influence. In hypophysectomized animals continuous and intermittent growth hormone administration had clearly different effects. The results indicate that the sexually dimorphic secretion of growth hormone is involved in the regulation of circulating angiotensinogen concentrations in the rat.     

Right Colon, Sigmoid Colon, and Transverse Colon Diverticulitis in the Same Patient: Report of a Case

Although sigmoid colon diverticulitis is frequently seen, right colon and transverse colon diverticulitis remain rare forms of the disease. This case report examined the disease course of a 46-year-old female who first presented to our institution in 1990 with perforated right-sided diverticulitis. During the next 11 years, she developed sigmoid colon diverticulitis and then transverse colon diverticulitis. The right and sigmoid colon diverticulitis were treated with surgery and the transverse colon diverticulitis was managed conservatively. This is the first reported case of a single patient who had separate episodes of diverticulitis in the right, transverse, and sigmoid colon. The evaluation and management of this patient has mirrored a trend in the literature and clinical practice.Reprints are not available.     

Structural,Functional and Autonomic Changes in the Cardiovascular System in Growth Hormone Deficient Patients

Background: Growth hormone deficiency (GHD) is known to cause higher rates of cardiovascular mortality. The purpose of the study was to analyze the structural and functional changes in the heart and investigate their relation to autonomic function as assessed with heart rate variability (HRV). Methods: Eleven untreated GHD patients (mean age 50.4 ± 10.7 years, M/F: 3/8) and 15 age‐ and sex‐matched healthy persons (mean age 45.3 ± 10.4 years, M/F: 5/10) were compared. Both groups were examined with echocardiography, HRV, and exercise testing and findings were analyzed. Results: The groups were similar in height, weight, body mass index, body surface area, systolic and diastolic blood pressure, heart rate. The GHD patients had lower exercise duration and metabolic equivalent (MET) compared to controls (7.94 ± 1.26 vs. 9.8 ± 1.9 min, P < 0.001, for MET 8.85 ± 0.86 vs. 10.7 ± 2.23, P = 0.03). On echocardiography, GHD patients had lower interventricular septum diastolic diameter (9 ± 0.89 vs. 10.7 ± 0.88 mm, P < 0.001) and posterior wall thickness (8.4 ± 0.93 vs. 9.8 ± 0.91 mm, P = 0.002), and lower left ventricle mass index (90.9 ± 20 vs. 112 ± 8 g/m², P = 0.01). Left ventricular ejection fraction was lower in the GHD patients (57.4 ± 5.12% vs. 65.5 ± 4.1%, P < 0.001). Time and frequency domain heart rate variability parameters, SDNN, SDANN, VLF, LF ve LF/HF were lower in GHD patients compared to controls. There was a significant correlation between left ventricle diastolic diameter and LF (r = 0.62, P = 0.02). Conclusion: GHD seemed to cause decreased left ventricle mass and decreases in the sympathetic components of HRV that may have a bearing on the increased cardiovascular risk seen in these patients.     

脑出血患者血清生长抑素、生长激素与白蛋白相关分析

目的：分析急性脑出血患者的血清白蛋白与血清生长抑素、生长激素改变的相关性，探讨蛋白质合成代谢变化对血清白蛋白的影响。方法：连续收集发病1d以内、出血量20～60mL的脑实质出血患者20例。动态测定脑出血后15d内的血清生长抑素、生长激素和白蛋白。应用逐步回归方法分析血清生长抑素、血清生长激素与血清白蛋白之间的相关性。结果：血清白蛋白与血清生长抑素、血清生长激素呈线性相关（r=0．876，P〈0．01）。结论：血清生长抑素、血清生长激素明显影响血清白蛋白的变化。     

GH/IGF-1治疗心力衰竭作用机制的研究进展

生长激素(growth hormone,GH)是腺垂体合成和分泌的重要激素之一,大部分通过其介质胰岛素样生长因子-1(insu lin-like growth factors-1,IGF-1)发挥作用。GH/IGF-1对心血管系统具有促进心肌生长,增强心肌收缩力等特殊效应。因而在心力衰竭的治疗中有着重要的价值,现对GH/IGF-1治疗心力衰竭的可能机制作一综述。     

The Effect of Pinealectomy on Plasma Levels of Gonadotrophins and Growth Hormone in the Pigeon (Columba livid)

The effects of pinealectomy on plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), and growth hormone (GH) concentrations were studied for a period of 9 weeks in pigeons reared under naturally increasing day length. After pinealectomy, plasma LH and GH concentrations decreased in both sexes when compared with sham-operated birds. In pinealectomized female pigeons, the plasma level of FSH was elevated, while in male birds the effect on FSH was negligible. A trend toward increased weight of testis, ovary, and oviduct was also seen after pinealectomy, but the increase was not statistically significant.
The present results suggest that pinealectomy is able to modify the secretion of gonadotrophins and GH in the pigeon and indicate a stimulatory role for the pineal gland in LH and GH secretion and, in female pigeons, an inhibitory role in FSH secretion.     

Low Molecular Weight Iron Dextran Increases Fibroblast Growth Factor‐23 Concentration,Together With Parathyroid Hormone Decrease in Hemodialyzed Patients

Fibroblast growth factor (FGF)‐23 inhibits PTH production. Elevated FGF‐23 and parathyroid hormone (PTH) levels are characteristic of hemodialyzed patients. Iron polymaltose was shown to increase FGF‐23 concentration. The effect of intravenous low molecular weight iron dextran (LMID) on these hormones and bone metabolism has not been studied in hemodialysis (HD). Twelve HD patients were prospectively followed up for 3 weeks after a single infusion of LMID. Calcium, phosphate, FGF‐23, PTH, degradation products of C‐terminal telopeptides of type I collagen (CTX) and procollagen I N‐terminal propeptide (PINP) were measured prior to, and at week 1 and week 3 after the LMID administration. FGF‐23 increased significantly from 453.4 (68.6–3971.5) pg/mL at baseline to 971.8 (779.5–3361.4) pg/mL (P = 0.001) at week 1 and started to decrease toward the initial value at week 3. The changes were accompanied by a significant decline in PTH from 367.6 (21.4–1487.4) pg/mL at baseline to 315.7 (16.4–1339.8) pg/mL (P = 0.018) at week 1 and subsequently began to increase toward the initial values. Phosphate, calcium, CTX and PINP did not change over the study course. LMID causes an increase in FGF‐23 concentration together with a decrease in PTH. Our study highlights a pathophysiological element, which may connect suppression of parathyroid glands with intravenous iron supplementation.     

Different Growth Responses to Recombinant Human Growth Hormone in Three Siblings with Isolated Growth Hormone Deficiency Type 1A due to a 6.7Kb Deletion in the GH1 Gene

Isolated growth hormone deficiency (IGHD) type 1A is a rare, autosomal recessive disorder caused by deletion of the GH1 gene and characterized by early onset severe short stature and typical phenotype. Lack of exposure to GH during fetal life often leads to formation of anti-GH antibody following exposure even the least immunogenic recombinant human GH (rhGH). Some patients with circulating anti-GH antibodies demonstrate lack of growth response to GH while others do not. However, the clinical significance of this antibody is unclear; hence testing is not routinely recommended. Three siblings, born of a consanguineous union, were referred with severe short stature. They were evaluated and IGHD was diagnosed in all of them. Genetic analysis revealed that all three had homozygous 6.7 Kb deletion in GH1 gene, while their parents displayed a pattern of heterozygous 6.7 Kb deletions. rhGH was started at 10, 6 and 1.58 years of age, respectively. Growth and hormonal parameters were monitored throughout the course of treatment. The eldest sibling demonstrated expected growth velocity (9.5 cm/year) for the first year of rhGH that rapidly waned thereafter (2.5 cm/year). The youngest sibling experienced excellent growth response even after the third year (10.3 cm/year) while the middle sibling displayed sub-optimal response from rhGH initiation (6.3 cm/year). Change of rhGH brand did not work in the two elder sisters. Such a different growth response with rhGH in three siblings harbouring similar genetic abnormality has not been described previously.     

Growth Hormone Replacement Therapy: Transition from Adolescence to Adulthood

Consideration of GH re-testing should be performed in all adolescents reaching the transition period (if not at start of puberty) who had been previously diagnosed with idiopathic, isolated GH deficiency. In the presence of multiple hormone deficiencies and/or clear-cut evidence of organic disease, persistence of severe GH deficiency is much more likely. Thus, GH deficiency may be "confirmed" by a low serum IGF-I concentration. During the transition period, the optimal time to reassess the integrity of the GH-IGF-I axis after prior GH treatment, the specific testing protocol to use, and the definition of GH deficiency all remain unknown. During the transition period, patients should have their GH dose lowered with (upward) adjustments made on the basis of age-and gender-adjusted serum IGF-I concentrations. GH treatment during the transition period has been shown in most, but not all, studies to be beneficial in preventing development of the features of the adult GH deficiency syndrome. It is important to remember that, during the transition period in teenagers with GH deficiency, there must be initiation of a careful plan for transfer of care to an intermist-endocrinologist with expertise in management of hypothalamic-pituitary disease in young adults.     

基因重组生长激素在COPD急性加重期的治疗

目的　研究基因重组生长激素 (r- h GH)在慢性阻塞性肺疾病 (COPD)急性加重期治疗中的临床应用价值。方法　 30例 COPD急性加重期患者随机分成生长激素组和对照组。两组均给予抗感染、氧疗及营养支持等。生长激素组在上述治疗基础上加用 r- h GH,每晚 1次皮下注射 ,连续应用 7～ 10日。观察各组的治疗疗程 ,治疗前后的血糖峰值及胰岛素的用量。结果　生长激素组平均疗程 9.9± 3.8日 ,少于对照组 (13.8± 4 .3日 ) (p<0 .0 5 ) ,两组治疗前后的血糖峰值及胰岛素用量无显著差异。结论　 r- h GH能够缩短 COPD急性加重期患者的治疗疗程     

重组生长激素治疗肝硬化低蛋白血症的临床研究

目的：探讨重组生长激素对肝硬化低蛋白血症的治疗作用。方法：116例肝硬化患者随机分为治疗组62例和对照组54例,在相同的治疗基础上治疗组加用重组生长激素,4．5u/次,隔日1次。观察治疗前、后和治疗后1个月、3个月及6个月的血清白蛋白水平。结果：治疗组血清白蛋白水平显著改善,与对照组相比有显著性差异。结论：生长激素可有效地改善肝硬化低蛋白血症。     

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.     

Growth Hormone Deficiency in a Child with Neurofibromatosis-Noonan Syndrome

Neurofibromatosis-Noonan syndrome (NFNS) is a distinct entity which shows the features of both NF1 (neurofibromatosis 1) and Noonan syndrome (NS). While growth hormone deficiency (GHD) has been relatively frequently identified in NF1 and NS patients, there is limited experience in NFNS cases. The literature includes only one case report of a NFNS patient having GHD and that report primarily focuses on the dermatological lesions that accompany the syndrome and not on growth hormone (GH) treatment. Here, we present a 13-year-old girl who had clinical features of NFNS with a mutation in the NF1 gene. The case is the first NFNS patient reported in the literature who was diagnosed to have GHD and who received GH treatment until reaching final height. The findings in this patient show that short stature is a feature of NFNS and can be caused by GHD. Patients with NFNS who show poor growth should be evaluated for GHD.