长效奥曲肽在恶性肿瘤患者治疗中的护理

新型长效奥曲肽制剂是一种人工合成的天然生长抑素的八肽衍生物,其保留了与生长抑素相同的药理作用,作用持久,能抑制生长激素以及胃肠胰内分泌系统产生的多肽和血清素的病理性分泌增加,每月肌内注射1次即可达到稳定的血浆药物浓度,产生持久的抑制生长激素和胰岛素样生长因子-1（IGF-1）,从而保证良好的临床疗效。2011年8月-2012年8月,我科对10例恶性肿瘤患者应用长效奥曲肽,现将其护理报告如下。     

垂体促甲状腺激素分泌瘤六例误诊分析并文献复习

目的 探讨垂体促甲状腺激素(TSH)分泌瘤的临床特点及误诊原因.方法 对2007年12月至2009年3月在北京天坛医院诊断和治疗的6例院外误诊的垂体TSH分泌瘤患者的临床资料进行回顾性分析,并参阅相关文献资料进行分析.结果 6例患者首发症状均为甲状腺毒症,甲状腺自身抗体(TG-Ab、TPO-Ab、TRAb)均为阴性,院外均误诊为原发性甲状腺功能亢进症并接受抗甲状腺药物治疗,误诊时间1～11年;6例患者均为垂体大腺瘤,其中1例为垂体生长激素(GH)和TSH混合型大腺瘤;5例患者术前应用抗甲状腺药物,不能将甲状腺激素水平降到正常,然后应用奥曲肽治疗,甲状腺激素水平降至正常.结论 甲状腺毒症患者血清TSH水平升高或不被抑制时应进一步行鞍区MRI检查,以免误诊,奥曲肽可用于TSH分泌瘤术前准备.     

长效奥曲肽的特性及对晚期肝细胞肝癌的作用

<正> 近年来,奥曲肽(善宁,诺华制药)广泛用于多种临床疾病的防治,能有效缓解症状,提高患者的生活质量。而维持长期稳定的血浆药物浓度需每日多次注射奥曲肽。新型长效奥曲肽制剂(LAR,善龙)每月使用1次即可达到稳定的血浆药物浓度,产生持久的抑制GH(生长激素)和IGF-1(胰岛素样生长因子-1)分泌的作用,从而保证良好的临床疗效。这种药物可每隔28d肌肉注射1次(即1次/月),作用持久。     

奥曲肽和垂体后叶素治疗食管胃底静脉曲张疗效观察及护理

目的：观察奥曲肽与垂体后叶素治疗食管胃底静脉曲张破裂出血的疗效。方法：将100例肝硬化合并食管胃底静脉曲张破裂出血患者分为奥曲肽组和垂体后叶素组每组50例,观察和比较药物的治疗效果和产生的副作用情况。结果：奥曲肽治疗组效果优于垂体后叶素组。结论：通过临床观察和护理,为医生临床用药提供参考。     

奥曲肽治疗食管胃底静脉曲张破裂出血疗效观察

目的比较奥曲肽与垂体后叶素治疗食管胃底静脉曲张破裂出血疗效。方法在禁食、输液、输血等治疗基础上分别予奥曲肽25～50μg/h静滴或垂体后叶素0.2～0.3u/min静滴,观察止血效果。结果奥曲肽48h内止血成功率78%,明显高于垂体后叶素止血成功率56%。结论奥曲肽疗效优于垂体后叶素,副作用少。     

奥曲肽对消化系肿瘤的作用

奥曲肽（Octreofide）是一种长效生长抑素（Somatostafin．SS）的类似物，商品名善得定（Sandostatin）。其分子结构为一环形肽，具有活性的四个氨基酸排列顺序与SS相同，故可与广泛存在于中枢神经系统、垂体和胰腺β细胞等处的SS受体结合产生生物学效应。奥曲肽的生物学活性明显强于SS，其抑制生长激素（GH）、胰岛素、胰高糖素、胃泌索及胃酸分泌等作用均强于SS，特异性也较高，同时由于结构较稳定不易为酶降解，其半减期延长至80～160min。目前奥曲肽主要应用于消化道疾病和多种内分泌肿瘤的治疗。临床试用发现奥曲肽对胃泌素瘤、血管活性肠肽（VIP）瘤、类癌综合征、胰岛素瘤、生长激素释放激素瘤、胰高糖素瘤、胰源性异位Cushing＇s综合征等多种消化道内分泌肿瘤均可控制症状，部分病人肿瘤生长亦可受控制。笔者就其在治疗消化系内分泌肿瘤的应用进展作一综述。     

奥曲肽与垂体后叶素治疗门脉高压性胃病出血的疗效观察

目的 探讨奥曲肽与垂体后叶素治疗门脉高压性胃病出血的疗效。方法 将2000年1月～2004年12月收治的门脉高压性胃病出血患者随机分组，分别用奥曲肽与垂体后叶素治疗，并对其疗效进行比较和分析。结果 奥曲肽治疗组有效率83．9％，垂体后叶素治疗组有效率77．4％，奥曲肽及垂体后叶素对门脉高压性胃病出血的疗效基本相当（P〉0．05），垂体后叶素不良反应比奥曲肽多，两者的差异有显著性（P〈0．05）。结论 奥曲肽与垂体后叶素治疗门脉高压性胃病出血患者的疗效基本相当，垂体后叶素价格显著低于奥曲肽，但垂体后叶素不良反应较多，临床应根据患者具体情况选择用药。     

奥曲肽与垂体后叶素治疗肝硬化上消化道出血60例

目的了解奥曲肽与垂体后叶素对肝硬化上消化道出血的止血效果。方法在消化道出血常规治疗的基础上,分别加用奥曲肽和垂体后叶素,观察两组的止血率和止血时间。结果奥曲肽止血率及止血时间均明显优于垂体后叶素（P〈0．05）。结论奥曲肽治疗肝硬化上消化道出血疗效肯定,安全可靠。     

垂体后叶素联合硝酸甘油治疗食管胃底曲张静脉破裂出血35例

肝硬化门脉高压患者,发生食管胃底曲张静脉破裂出血,是内科常见急危症之一。急性出血的早期通常采用药物治疗,常用药物有垂体后叶素,奥曲肽等。奥曲肽疗效肯定,但价格昂贵,我院应用垂体后叶素联合硝酸甘油治疗35例,取得了良好效果,现总结如下。1资料与方法1.1病例选择选择我院1     

奥曲肽联合垂体后叶素治疗消化道大出血62例分析

目的观察奥曲肽联合垂体后叶素治疗消化道大出血的疗效。方法对62例消化道大出血的患者采用奥曲肽（25～50μg/h）及垂体后叶素（3～6 U/h）维持泵入治疗。结果 24 h内及24～72 h止血率分别为48.4%和43.5%,总有效率为91.9%,不良反应少。结论奥曲肽联合垂体后叶素治疗消化道大出血疗效显著,使用安全。     

Analgesic effect of octreotide in headache associated with acromegaly is not mediated by opioid mechanisms. Case report.

We report a patient with acromegaly who had severe, intractable headache unrelated to tumor size which dramatically resolved with the somatostatin analog octreotide. The analgesic effects of octreotide were neither related to significant inhibition of growth hormone nor influenced by naloxone. Our data suggest that octreotide should be considered in patients with intractable headache associated with pituitary adenomas. Mechanisms other than tumor size or interaction with the opioid system, such as non-opioid algesic peptide secretion, may be the explanation for severe head pain in some pituitary adenomas.     

Population pharmacodynamic analysis of octreotide in acromegalic patients

INTRODUCTION: Octreotide is an octapeptide analog of somatostatin used to normalize growth hormone levels in acromegaly. This article presents a population analysis of the relationship between octreotide and growth hormone concentrations in 94 patients with acromegaly, including 10 patients responding incompletely to subcutaneous treatment (poor responders). METHODS: Growth hormone and octreotide concentrations were recorded hourly over 12-hour time periods during long-term subcutaneous treatment. Twelve-hour profiles were also collected on different days up to 2 months after intramuscular injection of the long-acting formulation. We modeled the inhibition of growth hormone secretion by octreotide with a direct maximum inhibition model. A joint analysis of both formulations was performed with NONMEM (GloboMax, LLC, Hanover, Md). During model building, we examined the relationships between parameters and demographic covariates or formulations with the use of likelihood ratio tests. RESULTS: The baseline growth hormone level was higher in poor responders and was best described by a bimodal distribution. The maximum inhibition was common to both formulations and had a mean of 90%, with low interindividual variability. Sensitivity to octreotide (50% inhibitory concentration) was found to be slightly lower on average with intramuscular administration than with subcutaneous administration. CONCLUSION: Given adequate doses of octreotide, in 72% of 94 patients, growth hormone would decrease to levels below 2.5 ng. mL(-1), considered to be a desirable target concentration in acromegaly. This study provides a way to identify poor responders during subcutaneous treatment, allowing an early clinical decision to be made to switch nonresponders to alternative therapies.     

Somatostatin receptor (SSTR) subtype-selective analogues differentially suppress in vitro growth hormone and prolactin in human pituitary adenomas. Novel potential therapy for functional pituitary tumors.

Previously, we have shown somatostatin receptor (SSTR) subtype-specific regulation of growth hormone (GH), thyroid-stimulating hormone, and prolactin (PRL) secretion in human fetal pituitary cultures, where GH and thyroid-stimulating hormone are mediated by both SSTR2 and SSTR5, whereas SSTR2 preferentially mediates PRL secretion. We now tested SSTR subtype-selective analogues in primary human GH- and PRL-secreting pituitary adenoma cultures. Analogue affinities determined by membrane radioligand binding in cells stably expressing human SSTR forms were either SSTR2 or SSTR5-selective. Analogues preferential either for SSTR2, including octreotide, lanreotide, and novel compounds with improved affinity for SSTR2, or new SSTR5-selective compounds suppressed GH in tumor cell cultures (up to 44% of control; P < 0.0005). However, novel analogues from both groups were 30-40% more potent than octreotide and lanreotide in suppressing GH (P < 0.05). Heterologous analogue combinations containing both SSTR2- and SSTR5-selective compounds were more potent in decreasing GH than analogues used alone (P < 0.05), or than combinations of compounds specific for the same receptor subtype (P < 0.005). In contrast, SSTR2-selective analogues did not suppress PRL release from six cultured prolactinomas studied. However, new SSTR5-selective analogues suppressed in vitro PRL secretion (30-40%; P < 0.05) in four of six prolactinomas. These results suggest that both SSTR2 and SSTR5 are involved in GH regulation in somatotroph adenoma cells, whereas SSTR5 exclusively regulates PRL secretion from prolactinoma cells. Thus, somatostatin analogues with improved selective binding affinity for these receptor subtypes may be effective in the treatment of either GH- or PRL-secreting adenomas.     

Inhibitory effects of antivascular endothelial growth factor strategies in experimental dopamine-resistant prolactinomas

Prolactin-secreting adenomas are the most frequent type among pituitary tumors, and pharmacological therapy with dopamine agonists remains the mainstay of treatment. But some adenomas are resistant, and a decrease in the number or function of dopamine D2 receptors (D2Rs) has been described in these cases. D2R knockout [Drd2(-/-)] mice have chronic hyperprolactinemia and pituitary hyperplasia and provide an experimental model for dopamine agonist-resistant prolactinomas. We described previously that disruption of D2Rs increases vascular endothelial growth factor (VEGF) expression. We therefore designed two strategies of antiangiogenesis using prolactinomas generated in Drd2(-/-) female mice: direct intra-adenoma mVEGF R1 (Flt-1)/Fc chimera (VEGF-TRAP) injection for 3 weeks [into subcutaneously transplanted pituitaries from Drd2(-/-) mice] and systemic VEGF neutralization with the specific monoclonal antibody G6-31. Both strategies resulted in substantial decrease of prolactin content and lactotrope area, and a reduction in tumor size was observed in in situ prolactinomas. There were significant decreases in vascularity, evaluated by cluster of differentiation molecule 31 vessel staining, and proliferation (proliferating cell nuclear antigen staining) in response to both anti-VEGF treatments. These data demonstrate that the antiangiogenic approach was effective in inhibiting the growth of in situ dopamine-resistant prolactinomas as well as in the transplanted adenomas. No differences in VEGF protein expression were observed after either anti-VEGF treatment, and, although serum VEGF was increased in G6-31-treated mice, pituitary activation of the VEGF receptor 2 signaling pathway was reduced. Our results indicate that, even though the role of angiogenesis in pituitary adenomas is contentious, VEGF might contribute to adequate vascular supply and represent a supplementary therapeutic target in dopamine agonist-resistant prolactinomas.     

内镜经鼻蝶术后垂体腺瘤患者腺垂体功能低下情况分析

[目的]检测垂体腺瘤患者内镜经鼻蝶术后相关激素水平变化,分析影响垂体功能低下的因素,指导其激素替代治疗.[方法]总结本院神经外科2008年至2013年内镜下经鼻蝶手术82例垂体腺瘤患者的临床资料及治疗方法,测定患者术前及术后d3甲状腺轴、肾上腺轴及性腺轴相关激素水平并进行比较.[结果]患者术后d3甲状腺轴及肾上腺轴激素水平较术前有所降低,发生腺垂体功能低下者共34例,占41.5%(34/82).高龄、术前存在垂体功能低下、无功能型、大型肿瘤患者术后发生垂体功能低下比例较高,其中微腺瘤发生率为16.7%(2/12),大腺瘤45.7%(32/70),45例无功能腺瘤发生腺垂体功能减低者16例,占35.5%.而术后腺垂体功能低下发生与患者性别无关.[结论]垂体腺瘤术后垂体相关各项激素水平较术前会有不同程度的下降;术前高龄、垂体功能低下、无功能性垂体腺瘤及肿瘤体积较大的患者,术后发生腺垂体功能低下可能性较高,合理的激素替代疗法有利于患者康复.     

生长分化因子-15在垂体腺瘤中的表达及意义

目的探讨生长分化因子(GDF)-15在垂体腺瘤中的表达及意义。方法选择100例垂体腺瘤患者组织标本,根据是否具有侵袭性分为侵袭性垂体腺瘤63例和非垂体腺瘤37例,并选择同期在本院接受体检的健康人员50例作为对照组。比较各组受试者GDF-15的表达,并分析GDF-15和垂体腺瘤侵袭性的相关性。结果泌乳素垂体腺瘤与生长激素垂体腺瘤患者GDF-15均显著高于无功能性垂体腺瘤患者(P0.50);侵袭性垂体腺瘤患者GDF-15水平显著高于非侵袭性组及对照组(P0.05);GDF-15和侵袭性垂体腺瘤呈正相关(r=0.328,P=0.001)。结论在垂体腺瘤患者中,GDF-15的表达较高,且GDF-15水平和垂体瘤侵袭性存在相关性。     

The pituitary gland in hyperthyroidism.

The pituitary glands of 33 patients (24 women and 9 men, 18 to 78 years old) who died in thyrotoxicosis (18 with Graves' disease and 15 with toxic multinodular goiter [Plummer's disease]) were examined by histologic and immunocytologic methods. Thirteen patients (39%) died in "thyroid storm." The avidin-biotin-peroxidase complex immunostaining method was used to demonstrate the spectrum of pituitary hormones, including growth hormone, prolactin, adrenocorticotropic hormone, thyrotropin, follicle-stimulating hormone, luteinizing hormone, and alpha-subunit. The most striking finding was a pronounced decrease or loss of immunoreactivity to thyrotropin in all thyrotoxic cases, a consistent change that allowed ready distinction of thyrotoxic from euthyroid pituitary glands. When immunoreactive thyrotrophs were identified, they were sparse and small and demonstrated only faint thyrotropin reactivity. No morphologic differences were noted between the pituitary glands of patients with Graves' disease or Plummer's disease or between sexes. Loss of thyrotropin immunoreactivity was found to be reversible in that thyrotropic cells in the pituitary glands of 16 additional concurrently studied patients, who had thyrotoxicosis but were treated and subsequently had normal thyroid function or hypothyroidism, appeared normal or even hyperplastic. Other types of adenohypophysial cells in both the thyrotoxic and the successfully treated groups exhibited no abnormalities. Pituitary adenomas were incidental findings in 6 of the 33 patients (18%). Their immunotypic spectrum included three prolactin-immunoreactive tumors, two growth hormone-containing adenomas (one of which was plurihormonal), and one tumor with follicle-stimulating hormone and luteinizing hormone; no thyrotropin-containing adenomas were noted. No examples of pituitary hyperplasia were encountered in pituitary glands of thyrotoxic patients, and no hypophysitis or fibrosis was noted.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of octreotide delivered by continuous subcutaneous infusion with intermittent injection in the treatment of acromegaly

This study was undertaken to evaluate GH, IGF1 and drug levels during incremental continuous subcutaneous infusion of octreotide and compare these parameters following long-term treatment of 300 micrograms 24 h-1 by intermittent injection in a group of acromegalic patients. Ten patients were treated by continuous subcutaneous infusion in increasing dose from 200 micrograms 24 h-1 to 1600 micrograms 24 h-1; this resulted in consistent 24-h growth hormone suppression (less than 5.0 mU l-1), and normalisation of IGF1; the optimum dose was 400 micrograms 24 h-1, the maximum dose was tolerated without any untoward effects. There was no deterioration in carbohydrate tolerance despite a marked decrease in fasting and stimulated insulin levels. After 1 year of maintenance treatment, 300 micrograms 24 h-1 by intermittent injection, patients were re-evaluated; GH levels were not so consistently suppressed over the 24-h period and carbohydrate tolerance had deteriorated. A sub-group of patients with sub-optimal GH suppression on this regimen were identified and reassessed after 6 weeks treatment with an increased dose, 600 micrograms 24 h-1 by intermittent injection; both mean GH suppression and carbohydrate tolerance improved. The dose of drug and method of administration is best adjusted for each patient to achieve optimum GH suppression, thereby minimise compensatory hyperinsuliaemia and hopefully reduce morbidity and mortality. Alterations in pituitary tumour size and acquisition of gallstones during treatment have been observed which substantiate the need to re-evaluate these parameters on routine follow-up of acromegalic patients on long-term octreotide.