垂体性侏儒症

垂体性侏儒症是儿童期垂体前叶生长激素(GH)缺乏而引起的生长发育障碍。 一、病因 本病可分为特发性和继发性,可有单一性GH缺乏或伴有促性腺激素缺乏,也可伴有垂体前叶其他激素缺乏。特发性垂体性侏儒症无病因可寻,约占本病的60％～70％,男孩多见,男、女比率为2～4∶1。继发性者常继发于下丘脑和垂体及其     

垂体生长激素分泌瘤分子生物学的研究进展

垂体生长激素分泌瘤分子生物学的研究进展唐丹综述史轶蘩审校垂体生长激素分泌瘤（ＧＨ瘤）系人垂体前叶生长激素细胞的腺瘤，其分泌过多的生长激素（ＧＨ），导致肢端肥大症或巨人症。本文将近年来有关垂体ＧＨ分泌瘤发生和发展中的几种基因突变、下丘脑神经内分泌激素的...     

无功能性垂体腺瘤围手术期内分泌水平的变化及诊断进展

无功能性垂体腺瘤起源于垂体前叶上皮细胞,约占垂体腺瘤的1/3,大多数患者临床表现为头痛、视物模糊。但是部分患者术前及术后出现垂体功能减退。肿瘤对门静脉及垂体柄的压迫导致垂体前叶缺血坏死是引起垂体功能低下的主要机制,术中操作、肿瘤大小及残留都可导致新发垂体功能低下。术前主要以生长激素缺乏为主,而术后出现各个激素轴的改变。垂体功能减退容易被忽视,仅靠激素基础值的检测诊断远远不够,必要时需行刺激试验确诊。一旦明确垂体功能减退,充足的激素替代治疗能够提高患者的生活质量。     

PIT-1及PROP-1与联合垂体激素缺乏症

垂体前叶特异性转录因子(PIT)-1及其祖先蛋白(PROP)-1异常可致联合垂体激素缺乏症(CPHD)。其中PIT-1与胚胎期垂体前叶的发育和促甲状腺激素(TSH)、催乳素(PRL)及生长激素(GH)基因的表达有关，其基因突变者典型表现为血TSH、PRL、GH完全缺乏，MRI示垂体萎缩。而PROP-1也是一种垂体特异转录因子，启动胚胎期PIT-1基因的起始表达及维持个体出生后的持续表达，并可直接促使PIT-1细胞系的前体分化为促性腺细胞系，其基因突变患者除GH、PRL、TSH缺乏外，尚有促黄体激素、促卵泡激素或促肾上腺皮质激素缺乏。     

垂体腺瘤与女性生育功能

育龄期女性垂体腺瘤的发生率越来越高,由于垂体的重要位置和功能,垂体腺瘤与育龄期女性的生育功能有密切关系.性腺功能的破坏、高催乳素血症及腺体本身的高分泌状态是各类型垂体腺瘤影响生育功能的共同机制.另外,垂体腺瘤本身或是手术治疗后引起垂体前叶激素缺乏也可影响生育功能.对有生育要求的育龄期垂体腺瘤女性,选择合适的治疗方法以及对垂体前叶激素缺乏患者早期正确替代治疗,对恢复生育功能有重要意义.     

垂体特异性转录因子研究进展

垂体特异性转录因子于垂体前叶表达，是垂体生长激素细胞，催乳素细胞以及促甲状腺素细胞基因转录的调节者，能特异地识别基因上的ＤＮＡ序列，并与之结合，进而影响该基因转录。本文阐述已发现的两种垂体特异性转录因子（Ｐｉｔ－１和Ｐｉｔ－２）对垂体激素分泌功能及垂体疾病发病机理的重要意义。     

1例LHX3基因突变致联合垂体激素缺乏症3型患儿的临床资料及基因检测结果分析

目的 通过对1例LHX3基因突变致联合垂体激素缺乏症3型（CPHD3）患儿的临床资料及基因检测信息分析，总结LHX3基因突变致CPHD3的临床特点及遗传学特征。方法 对1例LHX3基因突变致CPHD3患儿的临床资料及基因检测信息作回顾性分析。结果 患儿，女，11月，因“体质量不增3月，发现肝功异常6天”就诊。患儿出生史正常，查体发现运动发育落后，垂体内分泌功能检测提示患儿存在中枢性甲状腺功能低下、生长激素缺乏、低泌乳素血症，完善垂体MRI检查未发现异常，初步诊断为联合垂体激素缺乏症（CPHD）。取患儿及父母外周血进行全外显子检测，结果显示，患儿存在LHX3基因2号外显子c. 247T>A(p. Cys83Ser)杂合变异，来源于父亲；3号外显子c. 355＿357dupCAC(p. His119dup)杂合变异，来源于母亲。结合基因检测结果，明确诊断为CPHD3。患儿使用优甲乐及生长激素治疗，效果良好。结论 CPHD3为罕见遗传病，表现为多种垂体激素缺乏，完善基因检测有助于明确诊断。LHX3基因突变可导致CPHD3,LHX3基因2号外显子c. 247T>A(p. Cys83...     

PIT-1及PROP-1与联合垂体激素缺乏症

垂体前叶特异性转录因子(PIT)-1及其祖先蛋白(PROP)-1异常可致联合垂体激素缺乏症(CPHD)。其中PIT-1与胚胎期垂体前叶的发育和促甲状腺激素(TSH)、催乳素(PRL)及生长激素(GH)基因的表达有关,其基因突变者典型表现为血TSH、PRL、GH完全缺乏,MRI示垂体萎缩。而PROP-1也是一种垂体特异转录因子,启动胚胎期PIT-1基因的起始表达及维持个体出生后的持续表达,并可直接促使PIT-1细胞系的前体分化为促性腺细胞系,其基因突变患者除GH、PRL、TSH缺乏外,尚有促黄体激素、促卵泡激素或促肾上腺皮质激素缺乏。     

垂体特异性转录因子研究进展

垂体特异性转录因子（ＰｉｔｕｉｔａｒｙＳｐｅｃｉｆｉｃＴｒａｎｓｃｒｉｐｔｉｏｎＦａｃｔｏｒ）于垂体前叶表达，是垂体生长激素（ＧＨ）细胞，催乳素（ＰＲＬ）细胞以及促甲状腺素（ＴＳＨ）细胞基因转录的调节者，能特异地识别基因上的ＤＮＡ序列，并与之结合，进而影响该基因转录。本文阐述已发现的两种垂体特异性转录因子（Ｐｉｔ－１和Ｐｉｔ－２），对垂体激素分泌功能及垂体疾病发病机理的重要意义。     

继发性甲状腺功能减退患儿垂体-甲状腺激素改变及治疗探讨

探讨继发于伞垂体功能减退的甲状腺功能减退(继发性甲减)患儿的激素改变及治疗.测定1999年9月至2006年3月以生长迟缓就诊于山东省市医院儿科的57例继发性甲减患儿垂体-靶腺激素,同时观察激素替代治疗的合适剂量.57例继发性甲减患儿FT_4均降低,初诊时19例(33.3%)TSH低于正常,38例(66.7%)TSH正常或略高,但L-T_4有效治疗后55例(96.5%)TSH低于正常.57例患儿均伴有生长激素缺乏及垂体MRI影像异常.继发性甲减常伴有全垂体功能减退和MRI异常,其治疗目标应使FT_4尽快达到并维持在正常上限.     

Gigantism with hypopituitarism

A forty-one year old man described in 1963 as having hypo-pituitarism with gigantism due to normal or excessive growth hormone secretion associated with a deficiency of other pituitary hormones was reevaluated with specific tests of growth hormone reserve. Deficiency of thyrotropin, corticotropin and gonadotropins was confirmed. Immunoreactive growth hormone was virtually absent in the fasting state and failed to be released during insulin-induced hypoglycemia or with the administration of arginine, glucagon or Pitressin®. These new methods for the direct measurement of pituitary hormones suggest that this patient has insufficiency of all pituitary hormones, including growth hormone, and that his tall stature was due to eunuchoid growth rather than to pituitary gigantism.     

Isolated growth hormone deficiency

Isolated growth hormone deficiency (IGHD) represents conditions of GH deficiency that are not necessarily associated with other pituitary hormone deficiencies or with an organic lesion. Three sub-categories of IGHD have been clinically identified (IGHD types 1–3), and IGHD type 1 has been further separated into IGHD types 1a and b. However, this clinical sub-categorization of IGHD may need reconsideration due to the recent identification of molecular heterogeneity within each sub-type of IGHD. In a small number of children with IGHD, defects in the GH, GH-releasing hormone receptor (GHRH-R), and GH1 genes have been identified. In most cases, no cause for IGHD can be identified; however, the proportion of idiopathic IGHD cases may be decreasing due to identification of causative factors. The phenotype of IGHD is variable depending in part on the underlying genetic disorders in the affected individuals. Several studies have focused on the usefulness of MRI findings in patients with GHD but anatomic abnormalities of the pituitary gland are variable. We review current studies and the clinical, biochemical, and molecular features described for different groups of affected individuals with IGHD.     

Impaired social status of growth hormone deficient adults as compared to controls with short or normal stature

OBJECTIVES In adults with growth hormone deficiency (GHD) social problems have been reported, but so far the relative contributions of GHD, additional pituitary deficiencies and short stature have not been distinguished. We therefore compared social data from GHD patients with social data from controls with short or normal stature. Furthermore we Investigated whether social problems are caused solely by the deficiency of GH or also by the associated absence of other pituitary hormones. DESIGN A questionnaire was sent to patients and controls with Items on education, profession, Income, partner and living situation. PATIENTS Two hundred and ten GHD patients treated In childhood but not In adulthood with GH (93 Isolated GHD (IGHD), 111 patients with multiple pituitary deficiency (MPD)) were compared with 53 short controls (height In childhood < third percentile for population) and 39 normal stature controls. RESULTS There were no differences between short and normal controls. There were also no differences between IGHD and MPD patients In any of the Investigated Items. GHD patients did not differ from controls on education level, but scored lower on the profession scale, had a lower Income and had a partner less often; If they had a partner they less often had children; also, more of them lived with their parents. CONCLUSION Since patients with multiple pituitary deficiency did not differ from patients with Isolated growth hormone deficiency, this suggests that the lower scores on the social parameters are the result of the growth hormone deficiency Itself. Since short stature controls had higher scores than patients with growth hormone deficiency and did not differ from normal stature controls in any of the aspects Investigated, It seems unlikely that the problems of the patients with growth hormone deficiency can be attributed to short stature.     

IGF-I measurements in the diagnosis of adult growth hormone deficiency

Although serum insulin-like growth factor I (IGF-I) concentrations have utility as a screening test for growth hormone (GH) deficiency in children and young adults, they are less accurate for screening in adults over 40 years of age. There are two main limitations in the clinical use of IGF-I levels as a marker of GH secretion. First, IGF-I synthesis is not only regulated by GH but also by nutrient supply and by other hormones; second, low IGF-I levels in the presence of normal or increased GH secretion may reflect a peripheral resistance to GH action. Although serum IGF-I cannot be used as a stand-alone test for the diagnosis of adult GH deficiency, very low IGF-I levels in the context of documented hypothalamic or pituitary disease may be helpful in identifying patients with a high probability of GH deficiency. In the presence of two or more additional pituitary hormone deficiencies, an IGF-I level <84 μg/l (assayed by Esoterix Endocrinology, Inc. Calabasas Hills, CA, USA) indicates a 99% probability of GH deficiency. As this cut-off value has not been validated for other IGF-I assays, an IGF-I standard deviation score (SDS) of <-3 may be considered in adults over age 28; an even lower IGF-I SDS is needed for diagnosis in younger adults. In clinical practice, other causes of low serum IGF-I such as malnutrition, diabetes, hypothyroidism, liver disease, etc., should be excluded before applying these diagnostic criteria.     

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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。     

Growth hormone: Historical notes

A brief review of important contributions to our present knowledge of growth hormone is given. In 1887 it had been noted that a pituitary tumor was present in most patients with acromegaly. Even at the beginning of the 20. Century relationship between growth disorders and the pituitary was contested. From 1908 pituitary surgery became established treatment in GH hypersecretion. In 1922 it was demonstrated that injection of pituitary extract to animals caused excessive growth and soon after the opposite: removal of the pituitary caused growth retardation. A huge number of studies on the effects of GH were subsequently reported as were trials with GH treatment. They were impeded by failure to recognize the impact of species specificity of GH. After this issue was clarified in 1957, treatment with human growth hormone proved effective. In 1985 it was realized that Creutzfeldt-Jakob’s disease might be transmitted through human growth hormone. At this time recombinant GH had become available. In 1971 the structure of human GH was established. In the same period both GH releasing and inhibiting hormones were identified and an analogue of somatostatin had evolved into the first effective pharmacological treatment for acromegaly.     

Comparison of the pharmacological properties of pituitary and biosynthetic human growth hormone. Demonstration of antinatriuretic/antidiuretic and barbital sleep effects of human growth hormone in rats

Biosynthetic human growth hormone was compared with pituitary human growth hormone and pituitary 22 K in the weight gain and the tibia test. The three preparations were found to be equipotent. Furthermore, the growth hormones were compared in various pharmacological test systems. All three preparations were found to have a marked antidiuretic and antinatriuretic effect in the rat and to cause a significant shortening of the hexobarbital sleeping time in mice. Biosynthetic and pituitary preparations had the same diabetogenic activity in obese mice, and the growth hormones did not differ with respect to pharmacological profiles in the test systems applied.     

生长激素在健康老年人中的抗衰老作用

人生长激素是由腺垂体分泌的由191个氨基酸残基组成的直链多肽,它可以直接或通过胰岛素样生长因子间接地对生长和代谢发挥作用,既往主要用于儿童生长激素缺乏症的治疗.随着预期寿命的延长,人们越来越重视生活质量的提高,各种抗衰老药物不断出现,根据衰老学说之一的神经内分泌衰竭学说,生长激素近来被用于抗衰老治疗.在成人,生长激素可增加去脂肪体重,增加骨密度,改善生活质量.本文就生长激素的一般理化特性和其在健康老年人群中抗衰老的作用作一综述.     

Evaluation of adult idiopathic growth hormone deficiency with other pituitary hormones deficiency

The type and percentage of multiple pituitary hormone deficiency (MPHD) were studied in 42 patients with idiopathic growth hormone deficiency (IGHD). It was found that the development of secondary sexual characteristics was poor or absent in 39 patients (93%) with gonadotropin deficiency (GnD). Mean serum testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the 39 patients were significantly less than those of normal adult males (P less than 0.01). Mean testicular volume in 36 patients with GnD was significantly less than that in 3 with normal T level. We also found that 24-hour urinary free cortisol level (24 hour UFC) was low in 24 (57.1%) of 42 patients, but it is important that none had obvious symptoms of hypoadrenocorticism such as hypoglycemia, hypotension etc and received adrenal-corticosteroid treatment. 22 (52.4%) of the 42 patients suffered from hypothyroidism, with serum thyroxine (T4) level lower than normal but thyrotrophin (TSH) within normal range. 6 patients with hypothyroidism had moderate symptoms such as cold intolerance, constipation, rough and dry skin, slowing down both mentally and physically. 17 patients have treated with thyroxine. From the results mentioned above, 14 of the 41 patients with MPHD had pan-pituitary hormones (LH, FSH, TSH, ACTH) deficiency, only one had isolated growth hormone deficiency. Among all the patients, 23 underwent breech delivery and 11 patients had birth asphyxia. We therefore conclude that: (1) most of the IGHD cases are complicated with other pituitary hormone deficiency; (2) most of the IGHD cases have with MPHD; (3) Breech delivery and birth asphyxia were important etiological factors of IGHD.     

Stimulation of longitudinal bone growth by hypophyseal hormones in the hypophysectomized rat.

The stimulating effect of different pituitary hormones on longitudinal bone growth was determined with tetracycline as intravital marker in hypophysectomized rats. Growth hormone was found to be the most effective growth stimulating pituitary hormone. At considerably higher doses, thyrotrophic hormone (TSH) and prolactin also showed growth stimulating pituitary hormone. At considerably higher doses, thyrotrophic hormone (TSH) and prolactin also showed growth stimulating activity. TSH exerts its effect via the production of thyroxine, whereas the growth stimulation by prolactin seems to be a direct effect of this hormone, similar to the effect of growth hormone. The LH, FSH, ACTH, MSH, vasopressin and oxytocin preparations did not stimulate longitudinal bone growth.