内分泌系统疾病

311 ,72326特发性垂体性生长激素缺乏症下丘脑一垂体一靶腺轴完整性探讨/沈永年一//临床儿科杂志一1996,14(6)一363一365 对25例典型的垂体性GH缺乏症进行下丘脑一垂体一甲状腺、肾上腺和性腺轴功能评价。经TRH、ITT和LHRH激发试验结果表明:单一GH缺乏症3例,占12%,多种垂体激素缺乏22例,占88%。其’中垂体TSH、ACTH、F’SH或LH储备和分泌功能低下分别’为一4(56%)、3(12%)和20(8(〕%)例。伴随TSH和FSH/LH同时受累n例(44 .0%),TSH和ACTH同时受累2例(8%),TSH、ACTH和FSH/LH同时受累1例(4%)。了解垂体其它激素不足,及时…     

先天性小阴茎治疗进展

先天性小阴茎（以下简称小阴茎）是指阴茎伸展长度低于相同年龄或相同性发育状态人群平均值2．5个标准差以上者，部分伴有隐睾、尿道下裂等畸形。临床上并不罕见，其病因复杂，治疗上有较大难度。有的可能是多种垂体激素缺乏（multiple pituitary hormone deficiency, MPHD） 的唯一外在表现，未及时诊治可造成严重后果甚至死亡；有的需作转性别处理；有的存在发育不良的睾丸组织，具有恶变倾向。故对小阴茎患儿应根据具体病因作出及时恰当的诊治。     

儿童垂体功能减退症

垂体是维持生命的重要器官,包括垂体前叶和垂体后叶,垂体前叶也称"腺垂体",由5种细胞分泌6种激素,分别为生长激素(GH)、促肾上腺皮质激素(ACTH)、促甲状腺素(TSH)、促黄体生成激素(LH)、促卵泡刺激激素(FSH)及催乳素(PRL);垂体后叶为神经垂体,分泌血管加压素.垂体前叶激素TSH、ACTH、LH、FSH促使其相应腺体(靶器官)分泌三碘甲状腺原氨酸(T3)及甲状腺素(T4)、肾上腺皮质激素、性激素包括睾酮(T)和雌二醇(E2),GH、PRL则直接与相应的细胞受体蛋白相结合发挥其各自的生理效应.     

空蝶鞍患儿的垂体激素改变及治疗剂量观察

目的探讨空蝶鞍（ES）患儿垂体激素的改变及激素替代治疗（HRT）的剂量。方法测定1999年9月～2006年3月以生长迟缓就诊的20例ES患儿（经下丘脑-垂体MRI确诊）垂体激素,并与年龄匹配的正常对照组进行比较;同时观察HRT的合适剂量。结果20例中18例有难产史,所有患儿均伴有多种垂体激素缺乏症（MPHD）：ES患儿FT4和F显著低于对照组,其中12例〉10岁的男性患儿FSH、LH、T均显著低于对照组（P〈0.001）,E2和PRL均显著高于对照组,6例禁水加压素试验和MRI检查证实为垂体性尿崩症。相应HRT剂量：重组人生长激素为（0.11±0.01）U/（kg·d）,左旋甲状腺素钠（1.6±0.7）μg/（kg·d）,氢化可的松（10.2±2.4）mg/m^2,弥凝（0.11±0.03）mg/m^2。中枢性甲减患儿甲状腺素用量小于先天性甲减患儿。结论ES患儿常伴MPHD,需全面激素替代治疗才能使其安全生长。有难产史或MPHD表现者应常规做下丘脑垂体MRI,以了解其形态结构改变,协助治疗及改善预后。     

小儿慢性胃十二指肠炎测定胃泌素、ACTH、生长激素的意义

胃十二指肠疾病主要发病机理是胃的激素调节障碍,胃泌素具有重要作用,它是由胃窦部G细胞分泌,是消化腺主要兴奋剂,能刺激胃酸、胃蛋白酶分泌,释放组织胺,分泌胰岛素,对胃粘膜的营养有刺激作用。G细胞还分泌促肾上腺皮质激素(ACTH)生长激素(GH)和内啡肽。无论来源于垂体或胃的ACTH、GH对胃泌素的合成均有增强作用。现已证实垂体激素直接参与胃消化功能调节,在其相互关系失调时可产生胃十二指肠病变(应激反应)。作者用放射免疫法测定157例8～14岁慢性胃十二指肠炎患儿血中胃泌素、ACTH、GH含量,其中极期95例,缓解期62例,并以15例正常儿童作为对照,探讨激素含量与疾病的关系,用于诊断。检查结     

类固醇疗法与肾上腺

皮质类固醇疗法是肾上腺萎缩最常见的原因。肾上腺皮质是丘脑下部/垂体/肾上腺皮质(简称HPA)轴的组成部分。皮质醇的分泌受垂体前叶激素——促肾上腺皮质素(ACTH)的调节,而ACTH又受丘脑下部激素——促肾上腺皮质激素释放因子(简称CRF)的调节。因此,丘脑下部或垂体功能障碍,或     

内分泌疾病引发的儿童高血压的诊断和治疗

内分泌疾病引起的儿童高血压以前一直认为是少见病 ,多数临床医师对其诊疗不很熟悉。近年来 ,随着认识和诊断手段的提高 ,此类疾病的报告逐渐增多[1～ 3 ] ,本文介绍几种相对常见的儿童内分泌疾病所致高血压的诊断与治疗。1　皮质醇增多症1.1　概念与临床特征　皮质醇增多症 (hypercortisolism ,HT)是由肾上腺糖皮质激素分泌过多引起的一种临床症候群 ,部分患者还伴有盐皮质激素和雄激素过多的表现。有人将HT分为垂体性、肾上腺性和异位性 3种 ,垂体性又称库欣病 ,是指因垂体肿瘤或垂体细胞增生 ,促肾上腺皮质激素 (ACTH)分泌增多引起的…     

生长激素缺乏症患儿垂体MRI检查的临床应用价值

目的 研究特发性生长激素缺乏症(GHD)儿童垂体MRI检查的临床应用价值,为进一步探索GHD病理机制提供临床依据.方法 选取100例2005-2007年内分泌专科就诊的GHD儿童乖体MRI资料,其中男74例,女26例;平均年龄为(8.82±3.68)岁.于SE序列T1WI头颅正中矢状及冠状面上观测垂体大小形态及信号特征,并比较其与临床的联系.结果 在10～15岁GHD患儿头颅MRI检查垂体矢状高径明显优于其他各径线(P<0.01);在联合垂体功能缺陷(MPHD)中垂体后叶异位(EPP)的发生率(92.3%)显著高于CHD(7.7%,P<0.01).结论 对GHD儿童应重视头颅MRI检查,其垂体形态、结构的阳性发现可有助于临床疾病的诊断及鉴别诊断,必要时应随访MRI,结合临床综合判断诊治及其预后.     

危重病肾上腺功能障碍的研究进展

相对肾上腺皮质功能不全(RAI)在危重病患儿中具有较高的发生率.下丘脑-垂体-肾上腺轴的机械性损伤、炎症细胞因子或有毒代谢产物和激素抵抗是发生RAI的原因.脓毒症患儿出现儿茶酚胺抵抗的难治性休克或充分容量复苏前提下,血管活性药物反应不良时应高度警惕RAI.促肾上腺皮质激素(ACTH)刺激试验是判断RAI的主要方法,在标准剂量ACTH(250 μg)刺激试验的基础上,研究发现小剂量ACTH(1 μg)刺激试验可能具有高敏感性和安全有效等特点.     

短期糖皮质激素对新生儿肾上腺皮质功能及形态的影响

肾上腺糖皮质激素(简称激素)已被广泛应用于治疗多种疾病。长期应用外源性激素可抑制下丘脑-垂体-肾上腺皮质(HPA)轴达数月之久,而短期大剂量激素是否可致HPA功能受抑仍有争议。临床上短期大剂量激素治疗新生儿疾病时,对新生儿HPA轴和肾上腺皮质功能,以及组织形态和超微结构的影响,国内至今尚未见有这方面的报道。国外的研究由于实验方法、观察指标和种族不同等因素,其结果也不尽一致。     

Circulating immunoreactive growth hormone releasing hormone concentrations and growth hormone response to growth hormone releasing hormone in short children

To study the role of peripheral immunoreactive growth hormone releasing hormone (ir-GHRH) concentrations and the GHRH test in the evaluation of growth hormone (GH) secretion in short stature, 46 children with a mean age of 9.4 years (range 1.6–16.3 years) and a mean relative height score of –3.2 SD (range –5.0–2.1 SD) were investigated. The children were divided into prepubertal (n=35) and pubertal (n=11) and the prepubertal children further into three groups based on their maximal GH responses to insulin-induced hypoglycaemia (IIH) and clonidine: (1) GH deficient subjects (maximal GH<10 g/l in both test); (2) discordant responders (maximal GH<10 g/l in one test and 10 g/l in the other); and (3) normal responders (maximal GH10 g/l in both test). Peripheral ir-GHRH concentrations were measured during the IIH test by radioimmunoassay after purification of plasma samples on Sep-pak cartridges. Among the prepubertal children 10 fell into group 1, 16 into group 2 and 9 into group 3. Children in group 1 were older, than those in group 3. There were no significant differences in relative heights and weights or absolute and relative growth velocities between the groups. Subjects in groups 1 and 2 had lower maximal GH responses to GHRH than those in group 3. There were no significant differences in the basal plasma ir-GHRH concentrations between the groups. Nine children (19.6%) had somatotrophs with a poor response to a single dose of exogenous GHRH (maximal GH<10 g/l). These subjects had increased basal plasma ir-GHRH concentrations. All of them had a decreased GH response to IIH and/or clonidine. Pubertal children had higher circulating ir-GHRH levels than the prepubertal subjects. There was an inverse correlation (r=–0.46;P<0.001) between the maximal GH response to GHRH and calendar age in the whole series. These observations suggest that: (1) a substantial proportion of short children have a heterogenous GH response to pharmacological stimuli necessitating complementary evaluation of their spontaneous GH secretion; (2) a poor response to exogenous GHRH is associated with increased ir-GHRH levels in the peripheral circulation; (3) all children with normal GH responses in pharmacological tests respond normally to GHRH and (4) the pituitary sensitivity to GHRH decreases with increasing age. Peripheral ir-GHRH concentrations do not differentiate between short children with growth hormone deficiency (GHD) and those with undefined short stature. The GHRH test is of limited value in the diagnosis of GHD, since a normal GH response does not exclude GHD, although a subnormal response appears to reflect dysfunctional GH secretion.     

Comparison of growth hormone releasing hormone therapy and growth hormone therapy in growth hormone deficiency

Seven children with growth hormone deficiency of hypothalamic origin responded to an i.v. bolus of growth hormone releasing hormone (GHRH) (1–29)-NH2 with a mean serum increase of 10.7 ng/ml growth hormone (GH) (range 2.5–29.3 ng/ml). Continuous s.c. administration of GHRH of 4–6 g/kg twice daily for at least 6 months did not improve the growth rate in five of the patients. One patient increased his growth rate from 1.9 to 3.8 cm/year and another from 3.5 to 8.2 cm/year; however, the growth rate of the latter patient then decreased to 5.4 cm/year. When treatment was changed to recombinant human growth hormone (rhGH) in a dose of 2 U/m² daily, given s.c. at bedtime, the growth rate improved in all patients to a mean of 8.5 cm/year (range: 6.2 to 14.6). Presently GHRH cannot be recommended for the routine therapy of children with growth hormone deficiency since a single daily dose of rhGH produced catch-up growth which GHRH therapy did not.Abbreviations GH growth hormone - GHD growth hormone deficiency - GHRH growth hormone releasing hormone - hGH human growth hormone - rhGH recombinant human growth hormone - SM C/IGF I somatomedin C/insulin-like growth factor I On the occasion of the 85th birthday of Prof. Dr.Dr.h.c. mult. Adolf Butenandt     

Growth hormone releasing hormone and growth hormone: genetic studies in familial growth hormone deficiency

Four families with growth hormone (GH) deficiency, either isolated or with other pituitary hormonal deficits are described. Members of each underwent pharmacological testing for GH secretion and infusions of GH releasing hormone (GHRH) to determine the locus of the defect in GH secretion. In addition, we have extracted DNA from white blood cells to characterize the GHRH and GH genes. All members tested had the normal complement of GH and GHRH genes. Four generations of one family with isolated GH deficiency, autosomal dominant were studied. The younger members showed minimal GH responsiveness to a single infusion of GHRH. However, the older members did not respond even after 30 doses of GHRH given intravenously every 3 h. Two members of a family with the autosomal recessive type of isolated GH deficiency had large GH increases after GHRH infusion. Thus in these families the GH secretory defect lies within the hypothalamus. Members of two families with pituitary deficiency (GH and other tropic hormones) of the autosomal recessive type had variable responses to GHRH and varying amounts of pituitary tissue seen on high resolution CT scans. Although it is not possible to delineate the precise location of the secretory defects in these latter two families, a hypothalamic defect is probable based on the responses to multiple trophic stimuli. Heterogeneity of structure and function exists within and between families with isolated GH deficiency and within and among families with pituitary deficiency. It is from the study of such families in which all members presumably have the same underlying defect that one can more readily decide on a pathogenetic mechanism.     

Growth hormone releasing hormone. Review

Growth hormone-releasing hormone was isolated 1982 from human pancreatic tumours. They were found to consist of three peptides (GHRH1-44, GHRH1-40, GHRH1-37) which in vivo and in vitro were specific stimulators of pituitary growth hormone secretion. These tumor-derived GHRHs were demonstrated to be identical to human hypothalamic GHRHs. Extrahypothalamic GHRH is present in some brain regions and in the gastrointestinal tract. Circulating GHRH is detectable in human plasma, but little is known about its function. Above all binding of GHRH to a specific receptor stimulates growth hormone secretion through formation of cyclic AMP. GHRH secretion is modulated by somatostatin, the somatomedins and growth hormone itself. Following single injection of GHRH1-44 i.v. the equilibration half-time is 1.0 +/- 0.2 min and elimination half-time is 6.8 +/- 1.2 min. Maximal growth hormone response is achieved after injection of 1 microgram/kg GHRH. Using higher GHRH-doses growth hormone can be stimulated via subcutaneous or intranasal application. A single i.v. GHRH-test is not sufficient to prove a pituitary defect since growth hormone can be stimulated following repetitive injections in some cases. About 50% of patients with growth hormone deficiency have a hypothalamic defect of GHRH release. In some of these patients GHRH s.c. can promote linear growth to the same degree as growth hormone treatment.     

Growth hormone secretion following administration of growth hormone releasing hormone in constitutional short stature and idiopathic growth hormone deficiency

A stimulation test using 1 microgram growth-hormone-releasing factor (GRF 1-29 X NH2)/kg bodyweight was performed in children with familial short stature and in children with constitutional delay of growth and development. The GH secretion induced by this means was not different in these groups, but there was a difference in the response between normal children and children with idiopathic growth hormone deficiency (GHD). GH secretion after GRF administration was significantly lower in the GHD group than in the other groups. However, 6 of 24 patients with GHD responded to the test with a normal increase in GH (greater than 10 ng/ml), and 11 with an intermediate response (2-10 ng/ml). Thus, the test does not differentiate individual patients with defective growth hormone secretion from normal short children.