垂体泌乳素微腺瘤治疗进展简

垂体泌乳素（prolactin，PRL）腺瘤是最常见的功能性垂体腺瘤，在临床上占到了垂体肿瘤的40％，是引起高泌乳素血症的最常见原因。垂体泌乳素微腺瘤（micmprolactinoma，MIP）是直径〈10mm的PRL腺瘤，约占女性PRL腺瘤的60％。生育期女性多表现为少经或闭经、不育、溢乳。     

男性巨大垂体泌乳素腺瘤的临床特征及手术治疗

目的 探讨男性巨大垂体泌乳素（PRL）腺瘤的临床特征及手术治疗效果。方法 回顾性分析2018年7月~2019年7月手术治疗的8例男性巨大垂体PRL腺瘤的临床资料。结果 术前血清PRL水平在50.8~9 852 ng/ml,平均3 505.6 ng/ml。肿瘤全切除3例,近全切除4例,大部分切除1例。术后血清PRL恢复正常4例。8例术后症状均有好转。结论 男性巨大垂体PRL腺瘤,可首选溴隐亭治疗,若颅内压增高症状明显,可选择手术治疗。术中尽可能全切除肿瘤,保护正常垂体,术后酌情继续应用溴隐亭治疗或放疗。     

男性垂体泌乳素腺瘤的诊断与治疗

目的 分析总结男性垂体泌乳素腺瘤的诊断和治疗特点方法 对10年间23例男性垂体泌乳素腺瘤患者的临床表现和肿瘤的病理学、内分泌学、影像学及治疗特点进行分析。结果 患者平均年龄38.7岁。临床表现以性功能、视力视野障碍多见。患者平均血清泌乳素水平为2705.22+-　　3.85ng/ml.肿瘤平均高度为30.41+-11.86mm,78%的肿瘤呈侵袭性生长或向鞍上.鞍旁不规则生长。经手术及药物治疗后,患者泌乳素降至641．54+-15.21ng/ml(p〈0.001);18例性功能障碍患者8例改善;13例视力下降的患者11例视力恢复正常或有不同程度改善;12例视野缺损的患者10例视野恢复正常或改善。结论 男性泌乳素腺瘤患者具有年龄高、肿瘤大且多侵袭性生长、泌乳素水平高等特点。单一疗法难以取得满意效果,应结合病人具体情况采用综合治疗。     

经蝶手术对男性青壮年垂体泌乳素腺瘤患者性腺功能的影响（附70例分析）

目的：探讨经蝶垂体泌乳素腺瘤切除手术对男性青壮年患者性腺功能的影响。方法：回顾性分析复旦大学附属华山医院神经外科2005年10月至2007年11月接受经蝶手术的70例男性青壮年（18-45岁）垂体泌乳素腺瘤（平均年龄36．4岁）患者的年龄和性别分布情况、发病特点、肿瘤分型、治疗与预后等情况。确诊主要依靠血泌乳素与MRI及术后病理检查;随访其术后内分泌指标及MRI以及患者的性功能恢复情况。结果：70例男性患者中垂体大腺瘤者56例,肿瘤具有侵袭性者28／70例（40％）;患者治愈率为55．7％（39／70）,未愈为44．3％（31／70）;患者性功能恢复正常者16／70例（22．9％）,部分改善者23／70例（32．9％）,无改善者31／70例（44．3％）。结论：在男性青壮年垂体泌乳素瘤患者中,大腺瘤所占比例较高,巨大型及侵袭性大腺瘤的比例也较高。男性垂体微腺瘤患者手术后性功能恢复良好,巨大型及侵袭性垂体腺瘤患者手术后性功能恢复不佳。     

垂体瘤转化基因在垂体大腺瘤中表达的研究

目的 探讨垂体瘤转化基因（PTTG）在垂体大腺瘤中的表达及意义。方法收集经手术和病理证实的垂体大腺瘤患者40例，其中无功能腺瘤22例，生长激素（GH）腺瘤8例，泌乳素（PRL）腺瘤10例。同期经手术和病理证实的垂体微腺瘤11例为对照组，其中促肾上腺皮质激素（ACTH）腺瘤8例。PRL腺瘤3例。采用免疫组化技术（LSAB法）检测垂体大腺瘤和垂体微腺瘤中PTTG的表达水平。结合临床资料及影像学分级标准，分析PTTG表达水平与垂体大腺瘤发生机制、生物学行为之间的联系。结果40例垂体大腺瘤中均发现PTTG的表达显著高于垂体微腺瘤组（P〈0．01）。在侵袭性垂体大腺瘤中，PTTG的表达显著高于非侵袭性垂体大腺瘤（P〈0．01）。PTTG的表达与大腺瘤向鞍上生长的高度和向海绵窦侵袭性生长的程度显著相关（P〈0.05）。结论PTTG表达增高与垂体大腺瘤的生长以及肿瘤的侵袭性密切相关。PTTG的表达水平及结合影像学资料可以为患者预后及术后的辅助治疗提供可靠的判断依据。     

多激素分泌性垂体泌乳素腺瘤的激素分泌谱及克隆分析

目的 对多激素分泌性垂体泌乳素腺瘤的克隆状态以及激素分泌谱进行分析。方法 对26例女性垂体泌乳素腺瘤患者（单激素分泌性PRL腺瘤7例，多激素分泌性PRL腺瘤19例）进行肿瘤标本的免疫组化分析，并且提取DNA行HUMARA分析。结果免疫组化分析提示本组多激素分泌性垂体PRL腺瘤具有10种不同的激素分泌谱，现代分子生物学HUMARA克隆分析提示11／13例（85％）多激素分泌性垂体PRL腺瘤为单克隆起源。结论 结果提示垂体泌乳素腺瘤除了分泌泌乳素外，还可以分泌多种垂体激素，而且绝大多数多激素分泌性垂体腺瘤的起源是单克隆性的。     

手术治疗男性垂体泌乳素腺瘤73例临床分析

目的分析男性垂体泌乳素腺瘤的临床特点,探讨其综合治疗方法。方法回顾性分析73例经手术治疗男性泌乳素腺瘤病人的临床资料。根据血清泌乳素水平,分为泌乳素≥200 ng/ml组(n=59)及泌乳素<200 ng/ml组(n=14),分析两组的临床和病理特点。结果泌乳素≥200 ng/ml组病人的性功能障碍发生率明显高于泌乳素<200 ng/ml组(P<0.05)。泌乳素与肿瘤平均直径具有相关性(r=0.747,P<0.01)。肿瘤全切37例,大部切除36例。术后病理证实均为垂体泌乳素腺瘤,其中55例为侵袭性腺瘤。术后性功能恢复正常者29例,视力、视野改善者31例。术后辅助药物治疗58例。随访65例,时间36个月,复发11例。结论男性泌乳素腺瘤多呈侵袭性生长,肿瘤大小与泌乳素水平呈正相关。对于压迫症状较重、肿瘤囊变、肿瘤卒中的男性病人,手术联合药物综合治疗是合理选择。     

垂体泌乳素腺瘤的治疗进展

垂体泌乳素(PRL)腺瘤占垂体肿瘤的40％～60％，是引起高PRL血症的最常见原因。生育期女性多表现为少经或闭经、不育和溢乳。男性和绝经期女性多为垂体占位表现(头痛、视力障碍和垂体功能减退)。PRL腺瘤绝大多数为微腺瘤，其中90％微腺瘤患者为女性，而PRL大腺瘤患者中60％为男性。血     

雌激素受体及多巴胺受体在泌乳素腺瘤的表达

目的研究雌激素受体(ESR)及其亚型mRNA、多巴胺受体(D2R)及其亚型mRNA在泌乳素腺瘤中的表达。方法应用逆转录酶聚合酶链式反应(RT-PCR)测定30例泌乳素腺瘤标本ESR1mRNA、ESR2mRNA、第五外显子缺失的1型雌激素受体(△5-Del-ESRl mRNA)及D2RmRNA的表达,研究其表达水平与患者性别、肿瘤体积、侵袭性及泌乳素(PRL)水平的关系。结果男性和绝经后女性患者肿瘤ESR1 mRNA表达高于育龄女性患者;侵袭性泌乳素腺瘤高于非侵袭性肿瘤;PRL≥1 000 ng/ml的患者△5-Del-ESRl mRNA表达水平较PRL1 000 ng/ml的患者明显增高。D2RmRNA异构体的表达水平与泌乳素腺瘤生物学行为有关系,D2SmRNA的表达水平在侵袭性与非侵袭性泌乳素腺瘤中存在显著差异,D2SmRNA在侵袭性泌乳素腺瘤中呈低水平表达。结论 ESR1及其亚型△5-Del-ESRl mRNA、D2R及其亚型mRNA表达与泌乳素腺瘤PRL分泌及肿瘤侵袭有关。     

影响垂体生长激素腺瘤经蝶手术疗效的因素分析

目的 评价垂体生长激素腺瘤经蝶手术的疗效和分析影响手术疗效的相关因素。方法 回顾性分析62例资料完整经蝶手术治疗的垂体生长激素腺瘤病人的临床资料．根椐肿瘤大小、术前生长激素水平、侵袭性、肿瘤病理类型等进行分类。按肢端肥大症的治愈标准．采用术后激素水平结合影像学复查评价手术疗效。结果 总缓解率为66．1％，微腺瘤、大微腺、巨大腺瘤术后缓解率分别为87．5％、71．8％和40．0%．侵袭性和非侵袭性腺瘤则为36．8％和79．7％。微腺瘤与巨大腺瘤（P〈0．05）、侵袭性与非侵袭性腺瘤术后缓解率有统计学差异（P〈0．001）。结论 微腺瘤和非侵袭性大腺瘤采用经蝶手术可取得满意疗效，侵袭性腺瘤或巨大腺瘤采用经蝶手术治愈率较低。     

侵袭性巨大泌乳素腺瘤的综合治疗（附30例报告）

目的探讨侵袭性巨大泌乳素腺瘤的综合治疗方法及临床治疗效果。方法纳入侵袭性巨大泌乳素腺瘤(IGPs)的标准是:(1)肿瘤直径>4cm;(2)血浆PRL>200ng/ml;(3)高泌乳素分泌或占位效应引起的临床症状。并根据治疗方式的不同分为两组:A组常规的先给以手术治疗,术后给以药物治疗和/(或)放疗,本组18例;B组先给以药物治疗,或配合放疗,必要时再给以手术治疗,本组12例。结果A组失访5例,其余13例在平均随访的42.5个月内肿瘤体积平均缩小76.5%,而B组在随访的23个月内肿瘤体积平均缩小91.3%;肿瘤在MRI上消失A组6例,B组4例;PRL水平控制在200ng/ml以内者A组7例(7/13),B组8例(8/12);A组视力改善者2例(2/13),而B组视力改善者6例(6/12);平均治疗费用A组明显为高。结论对侵袭性巨大泌乳素腺瘤,可先给以药物,能有效地缩小肿瘤体积和控制PRL水平,部分病例可以达到治愈的目的,从而避免手术风险,降低治疗费用。     

男性垂体泌乳素腺瘤手术治疗疗效分析

目的总结男性垂体泌乳素(PRL)腺瘤的手术疗效。方法回顾性分析102例行手术治疗的男性垂体PRL腺瘤病人的临床资料。平均年龄36.55岁。血清泌乳素63.5～150000ng/ml,肿瘤最大径4～70mm。本组头痛50例,视力障碍47例,视野缺损41例,性功能障碍59例。根据Knosp分级方法,其中侵袭性腺瘤60例。结果肿瘤全切除56例,次全切除46例。经手术及综合治疗后,PRL水平降至正常15例(14.71%),明显下降21例(20.59%);性功能障碍恢复正常17例,头痛消失或明显改善38例,视力障碍恢复正常或改善39例,视野缺损恢复正常或改善37例。结论男性PRL腺瘤病人具有年龄高、肿瘤大且多呈侵袭性生长及PRL水平高等特点,单纯手术治疗疗效差,难以取得满意效果。应结合病人具体情况,采用手术、药物及放射治疗等综合治疗方法。     

二甲双胍治疗抗精神病药所致高催乳素血症患者的初步观察

目的：探讨二甲双胍对抗精神病药所致高催乳素血症（HPRL）的治疗效果。方法：选择抗精神病药治疗过程中出现HPRL的住院精神疾病患者共24例,给予二甲双胍0．75g/d口服,观察12周。分别于治疗前和治疗4周、8周和12周后测定PRL水平。结果：24例患者二甲双胍治疗前PRL水平平均（80．62±56．26）ng/ml,治疗4周后PRL水平降至（62．94±43．49）ng／ml,平均降低（17．69±25．30）ng/ml,治疗前后比较,差异有统计学意义（t=3．424,P〈0．01）。结论：二甲双胍对于抗精神病药所致HPRL可能具有降低PRL的作用。     

Elevated prolactin serum levels and history of alcohol withdrawal seizures

BACKGROUND: Prolactin has been discussed to be useful for differential diagnosis in epilepsia. Aim of the present study was to investigate the association between prolactin serum levels and previous alcohol withdrawal seizures. METHODS: We assessed 118 male patients admitted for detoxification treatment. Previous withdrawal seizures were recorded and prolactin serum levels were measured using an enzymatic immunoassay. RESULTS: Patients with a history of alcohol withdrawal seizures had significantly higher prolactin levels (17.8 ng/ml, SD=12.1) than patients without previous seizures (13.0 ng/ml, SD=8.1, p<0.05). Logistic regression revealed significant predictive qualities for prolactin serum levels (B=0.05, Wald=5.30, p=0.021, OR=1.06, 95%CI=1.01-1.11). CONCLUSIONS: The present findings show an association between elevated prolactin serum levels and a history of withdrawal seizures. Hence, the results suggest that prolactin elevation at admission may be a clinical marker for an increased risk of withdrawal seizures.     

Improvement in hyperprolactinemia and reproductive comorbidities in patients with schizophrenia switched from conventional antipsychotics or risperidone to olanzapine

This open-label, prospective, 4-month study in hyperprolactinemic patients with schizophrenia explored whether prolactin levels decrease after switching antipsychotic therapy to olanzapine. A secondary objective was to determine if reproductive morbidities and sexual dysfunction occurring with hyperprolactinemia improved with prolactin normalization. Clinically stable patients with schizophrenia, who had hyperprolactinemia defined as >18.8 ng/ml for males and >24.2 ng/ml for females, were randomized to: remain on current therapy (n=27) or switch to olanzapine, 5-20 mg/day, (n=27). Baseline prolactin levels in female patients randomized to receive olanzapine (n=14) were 66.3+/-38.7 ng/ml and were 82.0+/-37.6 (p=.32) in those remaining on their pre-study antipsychotic medication (n=14). In male patients, baseline prolactin levels were 33.7+/-12.1 and 33.5+/-13.8 ng/ml (p=.97), respectively, for those randomized to olanzapine (n=13) or remaining on pre-study treatment (n=13). At study end, patients switched to olanzapine experienced significant reductions in mean serum prolactin levels of 19.8+/-18.1 ng/ml in males (p=.02), and 32.3+/-47.5 ng/ml in females (p=.01), but prolactin continued to be elevated in patients who remained on pre-study antipsychotic treatment. After switching to olanzapine treatment, male patients experienced significantly (p=.03) increased free testosterone levels but there were no significant improvements in total testosterone levels; some female patients experienced improved menstrual cycling, as well as resolution of galactorrhea and gynecomastia, and sexual functioning was significantly improved in both genders. Patients switched to olanzapine, as well as those remaining on their pre-study medication, maintained clinical stability, their symptoms continued to improve, although there were no significant between-treatment differences in improvement. Treatment-emergent adverse events did occur in both treatment groups; however, they were not significantly different between groups. Olanzapine-treated patients experienced significantly lower eosinophil counts and higher elevations in low-density lipoproteins and standing blood pressure than non-switched patients. Olanzapine treatment may offer sustained reduction in serum prolactin and improvement in sexual and reproductive comorbid symptoms in patients with schizophrenia who have treatment-emergent hyperprolactinemia.     

Sexual dysfunction and hyperprolactinemia in Japanese schizophrenic patients taking antipsychotics

This study aimed to estimate the prevalence of sexual dysfunction, evaluated by the Nagoya Sexual Function Questionnaire (NSFQ), and hyperprolactinemia in patients with schizophrenia and examine a relationship between sexual dysfunction and serum prolactin levels. This cross-sectional, comparative study was performed using a sample comprising 195 Japanese schizophrenic in- and outpatients treated with antipsychotics (117 males and 78 females). Data were collected from October 2009 to January 2010 using single, cross-sectional ratings of sexual function assessed by the NSFQ and concurrent measurement of serum prolactin levels. The prevalence of sexual dysfunction in patients with schizophrenia was high (males 66.7%; females 79.5%). Hyperprolactinemia (>25ng/ml) was highly prevalent among schizophrenia patients, affecting 53.8% of females and 51.3% of males. Among female patients, 16.7% had prolactin levels>100ng/ml. There was no relationship between sexual dysfunction and serum prolactin levels. The present study demonstrated a higher prevalence of sexual dysfunction and hyperprolactinemia in Japanese schizophrenia patients. Clinicians should keep these problems in mind and discuss potential solutions with patients to improve patients' quality of life and adherence to therapy.     

Prolactin in partial epilepsy: an indicator of limbic seizures

A study was performed to evaluate changes in serum prolactin levels after simple and complex partial seizures, and to identify which specific anatomical structures must be involved in seizures for postictal elevation of prolactin levels to occur. Seventy-eight seizures were studied in patients with electrodes implanted bilaterally into amygdala, hippocampus, hippocampal gyrus, and frontal sites. All 38 complex partial seizures had bilateral limbic ictal discharges, and each was followed by a significant increase in prolactin concentration (mean peak, 50.8 ng/ml; range, 16.0 to 150.0 ng/ml). Eight of 10 simple partial seizures with unilateral high-frequency regional limbic discharges were followed by prolactin elevation (mean peak, 28.2 ng/ml; range, 13.4 to 44 ng/ml). Thirty simple partial seizures with other ictal limbic discharges or without limbic discharges were not followed by an elevated prolactin level. The data indicate that serum prolactin levels always rise after complex partial seizures involving the temporal lobes, and rise after certain simple partial seizures involving limbic structures. Thus, measurement of the prolactin level can help identify which simple partial seizures involve mesial temporal lobe structures. Limbic structures serve to trigger prolactin release, which may depend upon spread of the seizure to subcortical structures.     

急性脑梗死患者血清IL-35、MMP-9与颈动脉粥样硬化斑块稳定性的关系

目的探讨急性脑梗死患者血清白细胞介素-35(IL-35)、基质金属蛋白酶9(MMP-9)与颈动脉粥样硬化斑块稳定性的关系。方法选择急性脑梗死患者89例,应用彩色多普勒超声检查颈动脉斑块,根据颈动脉粥样硬化斑块稳定性分为易损斑块组和稳定斑块组。采用酶联免疫吸附法检测患者血清IL-35、MMP-9水平,并分析IL-35、MMP-9与斑块稳定性的关系。结果颈动脉粥样硬化易损斑块组的患者41例,稳定斑块组的患者48例。易损斑块组血清IL-35水平(17.89±7.21 ng/ml)明显高于稳定斑块组(9.08±3.45 ng/ml)(P<0.05)。MMP-9水平易损斑块组(430.36±72.78 ng/ml)亦显著高于稳定斑块组(305.16±45.63 ng/ml)(P<0.01),差异均有统计学意义。结论脑梗死患者血清IL-35、MMP-9水平可能与颈动脉斑块稳定性有关。