Expression of Prolactin Gene in Rat Prolactinoma Induced by 17-β-Estradiol

Rats were implanted subcutaneously with silastic capsules containing 10 mg 17-β-estradiol. After 30, 60 and 120 days, their pituitary weights and plasma PRL levels were found to increase significantly. The administration of β-estradiol also produced a marked rise of PRL mRNA concentrations in the rat total RNA, but the sharper rise of serum PRL levels indicates that estradiol not only promotes transcription of prolactin gene, but also improves the efficiency of translation of the transcription product.

Correlations between Expression of Estrogen and Androgen Receptors and the Clinical Characteristics of Prolactinoma~*

Objective： To study the correlations between estrogen receptor （ER） and androgen receptor （AR） and the clinical presentations of prolactinoma and investigate the effect of ER and AR expression on the pathogenesis of prolactinoma in sexual difference. Methods： The clinical data of 30 patients who had undergone transsphenoidal operations in Tongji Hospital from December 2000 to December 2001 were reviewed retrospectively. The clinical information included sex, age, serum-prolactin, size, tumor invasiveness, history of use of bromocriptine and frequency of recurrence. In 20 out of the 30 patients, the ER and AR expression was detected by using immunohistochemistry method. With help of Chi-square test, the relationship between ER, AR and the clinical presentations was analyzed. Results： The statistical values revealed that there was no significant correlation between the ER and AR expression levels with the clinical presentations such as sex, age, tumor size or tumor invasiveness among the 20 patients studied （P〉0.05）. Conclusion： The expression of ER or AR is not influenced by the clinical data of prolactinoma such as sex, age, tumor diameter or extent of tumor invasiveness. The tumor is more aggressive in males than in females. In maroadenoma or tumor with hyperprolactineamia （〉200 ng/mL） simple surgical treatment can＇t successfully cure the prolactinoma. Post-operative bromocriptine therapy can＇t be determined by the sex of the patients, but is greatly related to the tumor size and serum-prolactin level before operation.

The Expression of Estrogen Receptor Subtypes in Prolactinomas and Their Relationship to Tumor Biological Behavior

Dopamine agonists （DA） are a first-line therapy for prolactinomas （PA）. However, nearly 10% of prolactinomas do not respond to DA therapy. A considerable number of studies have shown that estrogen plays an important role in the development of prolactinomas. However, the expression of estrogen receptors （ER） in prolactinomas has not been fully explored. Accordingly, we examined the levels of ESR1 and its subtypes A5-DeI-ESR1 and ESR2 mRNA in prolactinomas. In the present study,

Sex-related changes in tumor consistency in prolactinoma patients after bromocriptine pretreatment

Objective It has long been reported that prolactinomas treated with bromocriptine increase fibrosis and may affect surgical outcomes.We retrospectively studied 238 consecutive patients with histopathologically confirmed prolactinomas undergoing microsurgery in a single neurosurgery department of Tongji Hospital(Wuhan,China) from 2012 to 2015 in order to evaluate tumor consistency changes after bromocriptine pretreatment and surgical outcomes.Methods We divided the patients into four groups;males in the dopamine agonist(DA) group,females in the DA group,males in the no DA group,and females in the no DA group,and we compared the surgery process,specimen Masson staining,and clinical outcomes of the four groups.According to a previously published classification,the operative notes from an experienced neurosurgeon were reviewed to classify the consistency of tumors as "fibrous" or "nonfibrous".Results No differences in tumor consistency were found in male patients with or without DA treatment.However,in female patients with DA treatment,tumors were likely to be harder in texture than the tumors of female patients without DA treatment.Despite tumor consistency differences between sexes,the tumor biological remission rate was similar between groups,as was the rate of tumor resection.Discussion Our study indicates that preoperative DA therapy impacts tumor consistency in female patients but not male patients.Although the surgical and histopathological outcomes are not influenced,these findings may provide useful information for the choice of operative approach and surgery process for pituitary adenoma.

Diagnosis and treatment of prolactinoma:clinical analysis of 124 prolactinomas

Objective： To study the diagnostic and therapeutic features of prolactinoma. Methods： 124 patients with prolactinoma were studied in clinical manifestation, pathologic, endocrinological, radiographic and therapeutic features. Results： The average age of the male patients was 41.6 years, 32.3 years of females. The major clinical manifestation in males were sexual and visual disfunction. In females, disfunction of menstruates and galactorrhea. Average serum prolactin was 1875.22 in males, 376.6 ng/mL in females. Average diameter of the tumors was 38.05 mm in males, and 83.3% of the tumors were invasive, in females were 15.25 mm and 49%. After surgery, the average serum prolactin decreased to 385.84 ng/mL （P〈 0.05）, 13 of 15 patients improved in sexual function, 82.6% patients improved in eyesight and visual field. In females prolactin decreased to 23.93 ng/mL （P 〈 0.05）, and 81.25% infertility with microprolactinoma got pregnancy, higher than controls of drug therapy （P 〈 0.05）. Conclusion： In males, the tumors were usually larger and more invasive, and serum prolactin levels were higher. The patients were elder. But in females, much younger than males, most of the tumors were microadenoma, and after operation the prolactin usually decrease to normal level and more chance of pregnancy. Results of a single therapy were with less satisfaction, we advocate integrated therapy around operation.

BMP-4 accelerates PRL secreting,cell proliferation and invasiveness in human prolactinoma

Objective： The aim of the study was to explore the bone morphogenetic protein 4 （BMP-4） how to regulate pro- lactin （PRL） secreting, cell proliferation and invasiveness in human prolactinorna. Methods： Ten patients who diagnosed as prolactinoma by clinical characteristics and pathology were divided into two groups, one was sensitive to Brornocriptine, the other was insensitive to Brornocriptine. Every case was conducted by primal cell culture then treated by different concentrations of BMP-4. The cell configuration was observed and PRL hormone was measured in different times. The expressions of BMP-4 rnRNA and BMP-4 in 37 cases of prolactinorna and 8 cases of normal pituitary tissues samples were detected by immunohistochemical and in situ hybridization technique, and the results were analyzed by statistic methods. Results： BMP-4 （5 ng/rnL） could accelerate the secreting of PRL in prolactinorna cell, and it could reach the greatest effect in the concentration of 20 ng/mL. BMP-4 could increase prolactinoma cell proliferation, but when the concentration was 50 ng/rnL, the BMP-4 effect of increasing secreting decreased. When 100 ng/mL, the cell began to die. The effects of the BMP-4 in sensitive group and insensitive group had no difference. The BMP-4 was highly expressed in the prolactinornas and was positively related with the invasiveness grades. Conclusion： BMP-4 have positive regulation in prolactinoma secreting, proliferation, invasiveness effects, BMP-4 probably has the important role in prolactinoma pathogenesis.

Amyloidogenic Pituitary Prolactinoma

Prolactinomas are the most common benign pituitary neoplasms and the common cause of hyperprolactinemia. Most of them arise in women of reproductive age. In men, they are often functionally silent, but present with manifestations secondary to pressure effects when they become macro adenomas. We present a case of prolactinoma in a 54-year old male patient who presented with pressure effects because of the tumor, as head ache and bi-temporal hemianopsia. MRI Brain scan was done to identify the tumor. The patient underwent trans-sphenoidal resection of the pituitary macro adenoma. Histological examination revealed spheroid amyloid deposits, almost replacing the adenoma. No medical treatment was given but the tumor recurred after 6 months and a repeat surgery was done for total excision.

Combined Treatment with Buserelin+Cabergoline in Patient with Prostate Cancer and Pituitary Macroprolactinoma

Twelve years following hemicolectomy for colon adenocarcinoma, a 75-year-old patient with prostate cancer was treated for 4 weeks with the antiandrogen nilutamide and then with the long-acting GnRH agonist buserelin. The serum testosterone and prostate-specific antigen levels had decreased dramatically after 3 months of treatment. After 2 years of buserelin administration, the hormonal state was examined. Serum estradiol, testosterone, DHEA, DHEAS, FSH and LH levels proved to be suppressed, but the serum PRL concentration was extremely high (3 365 mIU/l). The pituitary MRI revealed a macroadenoma. The patient was treated with the dopamine agonist cabergoline, together with buserelin. After 9 months of this combined treatment, the prostate-specific antigen and testosterone levels were very low;the serum estradiol, DHEA, DHEAS, FSH and LH concentrations remained suppressed. The serum PRL level fell dramatically to 6.95 mIU/l, and a significant reduction in tumor size was observed on MRI. In conclusion: Combined buserelin + cabergoline treatment proved a highly successful procedure to cure this patient with prostate carcinoma and subsequent pituitary macroprolactinoma.

Optimization of transfection efficiency of small interfering RNA in purified human prolactinoma cells

Background Control of hypersecretion of certain hormones is one of the key targets in the treatment of pituitary adenomas. RNA interference has been shown to inhibit protein expression, and thus it may represent a promising method for the treatment of pituitary adenomas. In the present study, transfection efficiency of small interfering RNA （siRNA） was optimized in human prolactinoma cells. Methods First, a method was optimized to extract highly purified human prolactinoma cells in vitro. The extracted cells were verified to retain the physiological features of prolactin （PRL） secretion. Second, three conditions for siRNA transfection were tested by the evaluation of transfectfon efficiency and cell viability. The proper transfection condition was verified for human prolactinoma cells. Third, the siRNA for prolactin was transfected into the human prolactinoma cells, and the suppression of PRL mRNA was evaluated by quantitative real-time reverse transcription-PCR. Results The siRNA of 100 pmol with Lipofectamine 2000 of 5 μl for 1×10^6 cells was proved preferable, with transfection efficiency being 53.3% and cell viability being 69.7%. In the preliminary experiment the siRNA against PRL decreased the mRNA of PRL by 34.0%. Conclusion It is possible to inhibit hormone hypersecretion by RNA interference, that may eventually enable therapeutic siRNA drugs developed.

Prolactinoma coexisting with cerebrospinal fluid rhinorrhea and cavernous internal carotid aneurysm: Case report and literature review

Pituitary adenoma coexisting with cerebrospinal fluid(CSF) rhinorrhea and carotid aneurysm is extremely rare. CSF rhinorrhea may cause pneumocephalus and intracranial infection. Rupture of the aneurysm may cause fatal consequence. The authors report such a rare case to draw more attentions. A 55-year-old man presented with sexual dysfunction for 2 years. The serum prolactin was tested as 1,600 ng/ml(normal range, 1.39–24.2). Enhanced cranial MR showed an evident lesion at the sellar area, invading the right cavernous sinus. Prolactinoma was diagnosed. He took bromocriptine for one year and received gamma knife therapy thereafter. Four months after the treatment of gamma knife, he got CSF rhinorrhea and nasal bleeding. The endoscopic transnasalsphenoidal approach was performed to resect the tumor and repair the dura defect.The CSF rhinorrhea stopped after the surgery, however his nasal bleeding continued. The digital subtraction angiography(DSA) showed an aneurysm at the right cavernous internal carotid. The endovascular coil embolization was performed to treat the aneurysm. The patient recovered well. The coexistence of CSF rhinorrhea and pituitary adenoma is a high risk factor for the rupture of cavernous internal carotid aneurysm. When treating patients with pituitary adenoma and CSF rhinorrhea, doctors should exclude the aneurysm. When nasal bleeding occurs, the hemorrhage of internal carotid should be considered, and appropriate measures should be taken immediately.

One hemodialysis patient with headache, blurred vision, and hypotension induced by pituitary prolactinoma

We reported a rare case of a dialysis patient coincident pituitary prolactinoma with calcification. A 55-year-old woman who had undergone hemodialysis for 8 years was admitted to the nephrology unit because of headache, blurred vision, and hypotension. Physical examination was normal; endocrinological examination demonstrated elevated serum levels of prolactin （〉4240 mlU/L）, but other hormonal profiles, such as growth hormon, adrenocorticotropic hormone, thyroid stimulating hormone, free triiodothyronine, free thyroxine, follicle-stimulating hormone and luteinizing hormone, were absolutely or relatively lower. A cranial computed tomography （CT） suggested saddle area a high-density screenage with an anteroposterior diameter of 1.0 cm. A cerebral magnetic resonance scan confirmed the pituitary adenoma accompanied with calcification. Contrast-enhanced Tl-weighted images revealed a less enhancing tumor, 14 mm wide round lesion with a high intensity signal. It enlarges the sella turcica, but the optic chiasma is not displaced. We suggest that in the differential diagnosis of any hemodialysis patient with severe headache, hypotension, and visual disturbances, this syndrome should be considered as prompt pituitary adenoma.

Transsphenoidal surgery for prolactinomas in male patients:a retrospective study

Male patients with prolactinomas usually present with typical hyperprolactinemia symptoms,including sexual dysfunction and infertility.However,clinical factors related to sexual dysfunction and surgical outcomes in these patients remain unclear.This study aimed to investigate the outcomes of male patients with prolactinomas after transsphenoidal surgery and the risk factors affecting sexual dysfunction.This study was conducted on 58 male patients who underwent transsphenoidal surgery for prolactinomas between May 2014 and December 2020 at the First Affiliated Hospital of Sun Yat-sen University,Guangzhou,China.We evaluated the sexual function of patients before and after surgery through International Index of Erectile Function-5 scores,libido,and frequency of morning erection.Of the 58 patients,48(82.8%)patients had sexual intercourse preoperatively.Among those 48 patients,41(85.4%)patients presented with erectile dysfunction.The preoperative International Index of Erectile Function-5 scores in patients with macroprolactinomas were significantly higher than those in patients with giant prolactinomas(17.63±0.91 vs 13.28±1.43;P=0.01).Postoperatively,the incidence of erectile dysfunction was 47.9%,which was significantly lower than that preoperatively(85.4%;P=0.01).Twenty-eight(68.3%)patients demonstrated an improvement in erectile dysfunction.Tumor size and invasiveness were significantly correlated with the improvement of erectile dysfunction.Preoperative testosterone<2.3 ng ml^(-1)was an independent predictor of improvement in erectile dysfunction.In conclusion,our results indicated that tumor size and invasiveness were important factors affecting the improvement of sexual dysfunction in male patients with prolactinoma.The preoperative testosterone level was an independent predictor related to the improvement of erectile dysfunction.

垂体催乳素瘤的临床特点及诊治要点更新--基于《2022版ICCE/AME垂体催乳素瘤临床实践共识》解读

垂体催乳素瘤是一种由垂体催乳素细胞瘤过量合成和分泌催乳素引起的神经内分泌疾病,垂体催乳素瘤的规范化诊疗对于恢复并维持患者的正常垂体功能并提高其生活质量具有重要意义。2022年1月,《欧洲内分泌杂志》发布了国际临床内分泌学分会(ICCE)与意大利临床内分泌学家协会(AME)关于垂体催乳素瘤的临床实践最新共识申明——《2022版ICCE/AME垂体催乳素瘤临床实践共识》(简称2022版ICCE/AME新共识)。2022版ICCE/AME新共识立足最新循证医学证据,对于垂体催乳素瘤的临床诊治问题进行系统性阐述、分析和建议。本文围绕2022版ICCE/AME新共识关于垂体催乳素瘤的诊断、治疗、特殊人群、多巴胺激动剂抵抗及侵袭性疾病等诊治要点更新进行解读,希望有助于全科医生及内分泌专科医生对于垂体催乳素瘤的认识,为其临床实践的规范化诊疗提供参考。

垂体泌乳素瘤患者组织NR2C2、EMMPRIN水平变化及其与肿瘤侵袭性、临床预后的关系探讨

目的探讨垂体泌乳素瘤组织中核受体亚家族2c成员2(NR2C2)和细胞外基质金属蛋白酶诱导因子(EMMPRIN)的水平变化及其与肿瘤侵袭性、临床预后的关系。方法选择2019年6月—2021年6月本院收治的78例垂体泌乳素瘤患者为研究对象,患者均行手术切除,术后随访时间1年。采用免疫组化法检测NR2C2和EMMPRIN表达情况,对比癌组织、癌旁组织中NR2C2和EMMPRIN表达,分析垂体泌乳素瘤患者癌组织中NR2C2和EMMPRIN表达情况与临床病理参数的关系,分析影响垂体泌乳素瘤患者预后的因素。结果癌组织中NR2C2阳性表达率高于癌旁组织(P<0.05),EMMPRIN阳性表达率低于癌旁组织(P<0.05),NR2C2、EMMPRIN表达均是预后不良的独立危险因素(P<0.05);受试者工作特征曲线(ROC)分析显示,垂体泌乳素瘤组织NR2C2、EMMPRIN两者联合预测垂体泌乳素瘤患者预后不良的曲线下面积(AUC)为0.886,高于NR2C2、EMMPRIN单独预测的AUC(Z=5.245,P=0.014;Z=3.652,P=0.028)。结论垂体泌乳素瘤患者癌组织中NR2C2和EMMPRIN表达与肿瘤侵袭性、临床预后有关,NR2C2阳性患者预后不良风险高。

难治性催乳素瘤的临床应对:石以砥焉,化钝为利

垂体催乳素瘤是常见的垂体神经内分泌肿瘤,一般首选药物治疗,主要为多巴胺受体激动剂(DA)。大部分催乳素瘤患者对DA反应良好,然而,仍有少数患者对DA表现出抵抗性、耐药性。DA抵抗型难治性催乳素瘤临床少见,但其治疗极其困难,即使是药物治疗联合多次手术和放射治疗,也不能达到满意的疗效。因此,规范难治性催乳素瘤的诊疗流程和路径、探索更为有效的多学科协作治疗策略是目前亟待解决的难题。临床针对难治性催乳素瘤常需要综合患者情况,更换其他种类的DA,或考虑手术、放疗以及免疫治疗等,此过程需要多学科联合诊治。本文综合国内外最新文献,系统论述了难治性催乳素瘤的治疗药物、手术及放射治疗的最新进展,以期为难治性催乳素瘤的基础研究和临床诊治提供新的思路。

垂体泌乳素腺瘤经鼻神经内镜手术疗效分析

目的 探讨经鼻神经内镜手术治疗垂体泌乳素(prolactin,PRL)腺瘤患者的临床疗效。方法 回顾性分析47例垂体PRL腺瘤患者临床资料,均接受经鼻神经内镜手术。所有患者至少随访6个月,对比不同肿瘤特征患者的临床疗效差异。结果 本组患者女29例(61.7%),男18例(38.3%),中位年龄31岁,术前肿瘤中位直径1.80cm。Knosp分级0级13例(27.66%),1级12例(25.53%),2级7例(14.89%),3级7例(14.89%),4级8例(17.02%)。术前服用溴隐亭28例,其中多巴胺激动剂耐药患者18例(64.3%,18/28)。术后PRL完全缓解21例(44.7%);术后感染3例,垂体功能低下4例,脑脊液漏2例,死亡2例。进一步亚组分析发现,不同肿瘤直径(0~2cm组25例、2~3cm组11例、>3cm组11例)影像学全切率分别为96%、63.4%、0%,内分泌缓解率分别为76%、18.18%、0%。0~2cm组内分泌缓解率显著高于其他两组(P<0.001),且无术后感染、脑脊液漏、垂体功能减退等并发症。根据肿瘤是否侵袭海绵窦,分为非侵袭组(32例)及侵袭组(15例),发现非侵袭组影像学全切率(84.37%)较侵袭组(26.67%)显著升高(P<0.001),非侵袭组内分泌缓解率(62.5%)较侵袭组(6.67%)显著升高(P<0.001),非侵袭组手术时间和术中出血量显著减少(P<0.05)。联合肿瘤直径与侵袭性分析表明:非侵袭性0~2cm组内分泌缓解率显著高于2~3cm组(P=0.009),两组在手术时间、术中出血量、影像全切率无显著差异。进一步对比术前口服溴隐亭对经鼻神经内镜手术治疗的疗效表明:在非侵袭性0~2cm组患者中,术前服药组内分泌缓解率(73.33%)低于未口服药物组(88.89%)、术中出血量增多(P=0.016)。结论 对于肿瘤直径小于2cm的非侵袭性PRL腺瘤,经鼻神经内镜手术具有满意手术疗效,且无不良手术并发症。经鼻神经内镜手术对于该类型PRL腺瘤有望成为替代多巴胺激动剂的一线治疗备选手段。

侵袭性催乳素垂体瘤经内镜切除术后早期催乳素缓解因素分析

目的 探讨侵袭性催乳素垂体瘤经内镜切除术后早期催乳素缓解的影响因素。方法 回顾性收集2017年1月至2022年12月徐州医科大学附属医院经内镜下行垂体病损切除手术的141例侵袭性催乳素垂体瘤患者的临床资料,根据术后2周催乳素水平,分为术后早期缓解组与未缓解组。采用单因素分析2组患者的临床资料,并采用多因素logistic回归对术后早期催乳素缓解的独立预测因素进行分析。结果 在141例手术治疗的侵袭性催乳素垂体瘤患者中,有121例(85.82%)患者获得早期缓解,20例(14.18%)未缓解。早期缓解组与未缓解组在性别、肿瘤大小、肿瘤切除程度、术前催乳素水平、术后首日催乳素水平方面比较,差异具有统计学意义(P<0.05)。多因素logistic回归分析显示侵袭性催乳素垂体瘤术后首日催乳素水平是影响术后早期催乳素缓解的独立预测因素。结论 侵袭性催乳素垂体瘤的患者中,满足术后首日催乳素水平达到正常值的因素,且肿瘤侵袭性越低,肿瘤直径越小,术前测定催乳素<200μg/L,通过经神经内镜下手术治疗,做到肿瘤完全切除,患者术后2周催乳素水平更易达到早期缓解。

垂体泌乳素腺瘤患者溴隐亭耐药与血清PRL水平的关系

目的了解在对溴隐亭耐药和有效的泌乳素腺瘤患者间,早期血清PRL水平是否存在差异。方法收集了105例垂体泌乳素腺瘤患者的临床资料,根据溴隐亭疗效分为有效组和耐药组,其中有效组86例,耐药组19例。对两组患者药物治疗前血清PRL水平进行比较。结果有效组中患者早期血清PRL水平为(689.4±136.9)μg/L高于耐药组的(410.9±121.9)μg/L,差异有统计学意义(P<0.05)。结论血清PRL水平高的患者可能对药物有敏感性倾向,但要准确预测耐药现象,还应当结合分子生物学相关指标。多巴胺D2受体及其两种亚型D2 s(short)和D2 l(long)在肿瘤组织中的表达水平与耐药现象的相关性,值得进一步研究。

溴隐亭在泌乳素腺瘤治疗中的应用

82例泌乳素腺瘤中 ,直接予溴隐亭药物治疗 31例 ,行经蝶窦手术 5 1例 ;术后行放疗或药物治疗。对 12例复发型或残留者行再手术治疗、药物和放射治疗。平均随访时间为 3年。结果微腺瘤手术组与单纯药物组的月经好转率 (或男性性功能正常率 )分别为 78.6 % (11/ 14 )、74 .2 % (2 4 / 31) ;泌乳素大腺瘤的总术后复发率 2 7.0 % (10 / 37) ,其中手术加药物与放疗组16 .7% (1/ 6 ) ,手术加放疗组 2 2 .2 % (2 / 9) ,手术加药物组 2 5 .0 % (3/ 12 )和单纯手术组 4 0 .0 % (4 / 10 ) ;血清泌乳素正常率则分别为 10 0 % (6 / 6 )、88.9% (8/ 9)、91.7% (11/ 12 )和 70 .0 % (7/ 10 )。出现药物不良反应 4例。认为溴隐亭治疗对泌乳素水平的控制及减少肿瘤复发率有明显疗效 。

影响男性垂体泌乳素瘤疗效的因素分析

目的 探讨影响男性垂体泌乳素瘤疗效的因素。方法 回顾性分析38例男性泌乳素瘤患者的临床、病理及随诊资料,探讨影响其预后的因素。结果 治愈缓解16例,进步12例,无效10例。采用手术、放疗和/或药物综合治疗者较单纯手术者治愈缓解率显著高。术前PRL<1000μg/L者疗效较PRL>1000μg/L者显著好;年龄大于30岁者疗效较30岁以下者显著好。肿瘤大小及侵袭性程度和预后无关。结论 男性垂体泌乳素瘤对各种治疗方式的敏感性相对较差,手术、药物和/或放射治疗的综合治疗方式仍是其最有效的治疗方法,术前血清PRL水平和年龄是判断其预后的良好指标。