Microsurgical fronto-temporal approach to pituitary adenomas with extrasellar extension

In the present paper the microsurgical, fronto-temporal technique for the surgical treatment of chromophobe pituitary adenomas with extra-sellar extension is described in detail. The complete treatment of expansive chromophobe adenomas includes 4000 rad of external irradiation by the rotation technique and hormonal replacement therapy. The results of this treatment in 36 consecutive patients from 1971 through 1975 are given. There is no mortality nor recurrence of tumor in the follow-up period. The postoperative morbidity is low, especially in the group operated by the microsurgical fronto-temporal approach. The visual acuity improved or normalized in 86%, for the visual fields this percentage was 90%. These results are compared to those of our own series of 65 patients, treated from 1945 through 1959, and to some other data from the literature. Finally, some arguments in favour of the intracranial approach versus the transsphenoidal approach are presented.     

溴隐亭治疗侵袭性巨大泌乳素腺瘤的长期随访结果

目的　观察溴隐亭治疗侵袭性巨大泌乳素腺瘤的长期随访结果。方法　纳入侵袭性巨大泌乳素腺瘤 (IGPs)的标准是:⑴肿瘤直径 4cm以上,侵袭海绵窦或邻近其他结构;⑵血浆PRL>200ng/ml;⑶高泌乳素分泌或占位效应引起的临床症状。符合标准者 20例,其中 6例为术后给以溴隐亭治疗,其余 14例首发溴隐亭治疗。11例配合放疗。结果　所有患者临床症状均得到不同程度改善。在平均随访的 37 3个月内肿瘤体积平均缩小 93 3%, 11例肿瘤在MRI上消失。视力下降者除 1例外其余均获得改善(13 /14)。PRL水平控制正常者 8例,大于 200ng/ml者 7例。服药过程中出现脑脊液漏 1例,行经蝶修补。本组在治疗过程中无肿瘤卒中及耐药现象发生。结论　溴隐亭为侵袭性巨大泌乳素腺瘤的首选治疗,能在较短的时间内有效缩小肿瘤体积和控制PRL水平。部分患者服药后肿瘤消失,另一部分患者肿瘤局限后给以立体定向放射外科治疗,从而避免手术风险和手术费用。溴隐亭对控制PRL和缩小肿瘤体积不是同等敏感的。放疗的选择宜慎重。     

溴隐亭治疗垂体泌乳素腺瘤后并发脑脊液漏处理二例报道并文献复习

目的 探讨溴隐亭治疗侵袭性垂体泌乳素腺瘤后并发脑脊液漏的原因、临床表现及处理方法.方法 分析中山大学附属第三医院神经外科收治的2例溴隐亭治疗后并发脑脊液漏的垂体泌乳素腺瘤患者的临床资料,并复习相关文献.结果 2例肿瘤均广泛侵犯颅底,在溴隐亭治疗后1个月内发生脑脊液漏.1例经停药及脑室外引流处理后脑脊液漏停止,另一例经停药、经蝶手术修复漏口及腰大池置管外引流后脑脊液漏停止.在腩脊液漏好转2周后均继续予以较小剂量溴隐亭治疗,随诊3年和9个月无脑脊液漏复发,血泌乳素水平渐下降,肿瘤渐缩小.结论 溴隐亭治疗合并颅底破坏的垂体泌乳素腺瘤时有并发脑脊液漏的可能.停药、手术修复漏口及脑脊液外引流是治疗此类并发症的有效方法.继续小剂量溴隐亭治疗可使肿瘤缓慢缩小并减少脑脊液漏发生的可能.     

溴隐停影响泌乳素垂体腺瘤质地及肿瘤卒中的相关分析

目的分析溴隐停对泌乳素垂体腺瘤的治疗效果及对肿瘤质地的影响和腺瘤卒中的关系。方法回顾性分析我科自2002年1月至2006年1月行手术切除的具有完整影像学、病理学和随访资料的垂体泌乳素腺瘤93例。并且按照术前是否服用过溴隐停分为两组：溴隐停组（49例）和对照组（44例），进行比较研究。结果术中和术后病理发现溴隐停组的肿瘤体积缩小，组织质地较韧，纤维组织较多；对照组的肿瘤质地较稀软，纤维成分较少。两组具有明显差异（P〈0．01）。另外还发现溴隐停组的腺瘤较易发生卒中（P〈0．01）。结论服用溴隐停可以使泌乳素垂体腺瘤体积变小，质地变韧，泌乳素分泌水平下降，临床症状减轻，但可能是肿瘤卒中的潜在诱发因素。     

侵袭性泌乳素腺瘤溴隐亭治疗后的迟发性耐药现象:5例报告

溴隐亭（bromocriptine,BRC）作为治疗泌乳素腺瘤的一线药物，不仅能有效控制肿瘤体积，同时可使血清泌乳素（prolactin,PRL）下降至正常水平。但临床上仍有10%-20%泌乳素腺瘤患者在长时间溴隐亭治疗过程中血清PRL水平未能恢复正常，甚至出现肿瘤持续增长的情况，即耐药现象。     

Dystonia: treatment with bromocriptine

As with parkinsonism, certain dystonias may involve disturbances in dopaminergic neurotransmission. The effects of bromocriptine, 18-150 mg/day (mean, 72.5), were studied in 15 patients with a variety of dystonic disorders, using a double-blind, crossover format. Of the 13 patients completing several weeks of medication, seven improved more than 10% and two worsened, on clinical ratings, while five recognized improvement in disability. Dopaminomimetic agents such as bromocriptine, used in the dose range effective for treating parkinsonism, may yield symptomatic improvement with several patterns of dystonia.     

垂体催乳素腺瘤的治疗策略

目的 观察手术治疗垂体催乳素(PRL)腺瘤的疗效,探讨规范的个体化治疗方法.方法 回顾性分析158例术后病理证实为垂体PRL腺瘤患者的临床资料,分析手术前后血清PRL水平的变化,随访12 -45个月.结果 术前PRL为90 ng/ml时,与病理诊断符合率最高(91.0％).肿瘤全切129例(81.6％),近全切除24例(15.2％),部分切除5例(3.2％).术后1周内134例(84.8％ )PRL恢复正常.术后并发症以一过性尿崩(10.8％)和电解质紊乱(15.2％)最为常见.术后6个月、1年、2年的治愈率分别为83.5％、80.4％、78.7％.结论 手术治疗需严格把握适应证,长期随访手术与药物治疗的疗效相似.垂体PRL微腺瘤不建议首选手术治疗.放疗需慎重.应根据患者的具体情况采取个体化治疗方案.     

Zinc and bromocriptine long-term administration in patients with prolactinomas: effects on prolactin and thymulin circulating levels.

Several studies have demonstrated zinc (Zn), prolactin (PRL) and thymulin (Zn-FTS) interplay: Zn inhibits, in a dose related manner, PRL release from lactotropes in vitro and stimulates thymulin synthesis in vivo both in humans and in animals. PRL receptors are present on thymic epithelial cells (TEC); PRL stimulates TEC trophism and activity. Little is known about the influence of PRL on Zn metabolism, though in prolactinomas we found reduced Zn and thymulin circulating levels. For this reason, we evaluated PRL, Zn, bioactive thymulin (Zn-FTS) and total thymulin (T-FTS: Zn-bound plus Zn-unbound form) serum levels in 58 patients with prolactinomas (PRL: 253 +/- 263 micrograms/L), Zn (82 +/- 23 micrograms/dl), Zn-FTS (2.2 +/- 0.20 log2(-1] and T-FTS (3.7 +/- 0.25 log2(-1] were significantly lower (p less than .01) than those found in age matched controls. Zn-unbound bioinactive thymulin form (FTS) levels were in the normal range. Bromocriptine administration (Brc) (2.5-5 mg p.o., b.i.d. for 9 months) to 20 patients with microprolactinomas lowered serum PRL levels (10.5 +/- 6.2 micrograms/L) and significantly increased (p less than .01) Zn (118.6 +/- 14.7 micrograms/dl), Zn-FTS (3.96 +/- 0.7 log2(-1)) and T-FTS (4.66 +/- 0.7 log2(1)) circulating levels. ZnSO4 administration (400 mg p.o. daily for 3 months) to 6 patients with microprolactinomas, significantly increased (p less than .01) Zn (136 +/- 18 micrograms/dl), Zn-FTS (4.5 +/- 0.5 log2(-1)) and T-FTS (5.6 +/- 0.9 log2(-1)) levels, while caused only a slight decrease in serum PRL concentrations (from 95 +/- 8 to 75 +/- 9 micrograms/L; p: NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term treatment of Parkinson's disease with bromocriptine.

BRomocriptine (15-75 mg per day) alone or with L-dopa was studied during five to 29 months on 44 patients with Parkinson's disease. Used as sole therapeutic agent, it was found excellent in 12 patients who had never received regular L-dopa treatment either because it was never attempted or because of intolerance from the outset. Its anti-Parkinsonism activity was comparable with L-dopa. The gain was stable in the long term until this report. The side effects of L-dopa were not seen after bromocriptine. In cases where L-dopa had ceased to be active, bromocriptine produced a further improvement if mental deterioration was not associated. In very advanced forms of Parkinson's disease with associated dementia, bromocriptine did not produce durable results. Bromocriptine did not improve the "on-off" effects but reduced a number of the side effects of L-dopa, in particular cardiac, painful contractions, and dyskinesia without "on-off" effects.     

Antitumor effect of bromocriptine on estrogen-induced rat prolactinomas: special reference to changes in secretory granules by stereological analysis

Bromocriptine (CB) not only lowers serum prolactin (PRL) levels but also reduces tumor size of human prolactinomas. Gen et al and we have suggested that the size reduction of human prolactinomas by bromocriptine treatment results from the reduction in size of individual tumor cell as well as the reduction in number of tumor cells secondary to cell necrosis. This implies that bromocriptine has a cytosuppressive action and possibly a cytocidal action on human prolactinomas which causes reduction in cell size and cell necrosis, respectively. The mechanism of cytosuppressive action of CB has been investigated by using mostly non-neoplastic pituitary tissues of experimental animals. A decrease in exocytosis of secretory granules and a subsequent accumulation of granules within the cells are suggested to cause the reduction in serum levels of PRL in early stage of CB treatment. However we have reported that in spite of a pronounced reduction of serum PRL levels, the number of exocytosis of the granules in human prolactinomas treated with CB for 2 weeks increased to more than 4 times much as that in the untreated prolactinomas. This is a phenomenon which contradictory to the current hypothesis. The present study is intended to clarify whether the phenomenon we observed is specific for human prolactinomas or common also to the prolactinomas in experimental animals. Seventeen female SD rats were used. They were implanted subcutaneously with a pellet of 20 mg of 17 estradiol-benzoate (20% in cholesterol), and left to grow a pituitary tumor for 10 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuroleptic malignant syndrome: Successful treatment with dantrolene and bromocriptine

A patient with chronic schizophrenia treated with fluphenazine developed neuroleptic malignant syndrome, characterized by fever, obtundation, rigidity, and tremulousness. Hyperthermia and elevated serum creatine kinase were successfully corrected by parenteral treatment with dantrolene. Obtundation, rigidity, and tremulousness responded to high doses of bromocriptine.     

Clinical trial of the treatment of amyotrophic lateral sclerosis with bromocriptine

The authors accepting the hypotesis that in amyotrophic lateral sclerosis the hypothalamic dopamine receptor function is impaired tried to treat this disease with bromocryptine as an agonist of this receptor. The observation was carried out in 19 patients with moderately advanced amyotrophic lateral sclerosis. Bromocryptine was given to the patients in tablets Parlodel Sandoz 7.5 mg daily. No improvement was noted in the efficiency of the muscles of extremities in most patients. The improvement in the function of isolated muscles tested by Lovette's test was transient. A trial of treatment with low bromocryptine doses for short time periods (3 weeks to 4 months) was considered by the authors as unsuccessful.     

溴隐亭能否治愈垂体催乳素瘤

目的 通过溴隐亭治疗垂体催乳素瘤的临床和病理研究,探讨其临床效果和作用机制.方法 选择26例催乳素瘤,术前服用溴隐亭16例,另外7例术前未服用溴隐亭,手术切除的肿瘤标本作光镜和电镜检查;3例巨大催乳素瘤单纯用溴隐亭治疗,临床观察肿瘤体积变化.结果 手术前溴隐亭治疗的16例催乳素瘤瘤细胞的胞质体积缩小,核质比例增大,电镜下胞质内分泌颗粒明显减少,线粒体、粗面内质网数量明显减少.长期服药后肿瘤细胞核染色质有边聚现象,部分染色质透出核膜,以出芽方式向细胞质蔓延,并有凋亡小体形成.肿瘤细胞有空泡变性、核固缩和坏死自溶.单纯溴隐亭治疗的巨大催乳素瘤肿瘤体积平均缩小98.52%.结论 溴隐亭可以治愈催乳素瘤,其主要作用机制是使肿瘤细胞发生凋亡和继发性坏死.     

Hypothalamic mass and gigantism in neurofibromatosis: treatment with bromocriptine

A child with neurofibromatosis exhibited gigantism and acromegaly in association with a hypothalamic mass lesion. Bromocriptine, 5 mg daily, reduced somatic growth rate and restored biochemical homeostasis but had no effect on tumor growth. Radiation therapy arrested tumor enlargement and stabilized deteriorating visual function.     

伽玛刀治疗对垂体泌乳素腺瘤内分泌功能的影响

目的 分析不同放射剂量γ-刀治疗对功能性泌乳素(PRL)腺瘤的PRL水平的影响,判断PRL在γ-刀治疗功能性PRL腺瘤预后和指导激素替代治疗的作用.方法 回顾性分析山东淄博万杰医院和广东深圳罗湖人民医院自2004年9月至2008年3月应用γ-刀治疗的248例功能性PRL腺瘤患者的临床资料,按治疗剂量将患者分组:Ⅰ组:50 Gy≤中心剂量<60 Gy;边缘剂量:20～30 Gy;Ⅱ组:40 Gy≤中心剂量<50 Gy;边缘剂量:15～25 Gy;Ⅲ组:30 Gy≤中心剂量<40Gy;边缘剂量12～20 Gy;术前、术后1月、3月、12月采用放射免疫法检测患者血清PRL水平,术后1年、2年复查头颅MRI观察肿瘤大小的变化.结果 3组患者术前PRL水平的差异有统计学意义(p<0.05),与Ⅰ、Ⅱ组比较,Ⅲ组PRL值偏低,术后12个月与Ⅰ组比较,Ⅲ组PRL值偏高;与术前相比,3组患者术后PRL水平均降低,差异有统计学意义(P<0.05);术后1年MRI显示肿瘤缩小198例(80%);术后2年肿瘤消失203例(82%),增大19例(7.7%),无变化26例(10.4%).结论 不同剂量γ-刀治疗功能性PRL腺瘤对术后内分泌的恢复有很大的影响,中心剂量和边缘剂量(尤其是中心剂量)较高时,术后PRL易恢复正常.但远期是否会造成垂体低功需要长期随访.

Abstract：

Objective To analyze the effects of-γ-knife treatment with different dosages on level of prolactin (PRL) in patients with different sizes of functional pituitary prolactinomas, and determine an index to guide hormone replacement therapy and the prognosis of -γ-knife treatment in patients with functional pituitary prolactinomas through comparing the changes of tumor sizes and the levels of PRL before and after -γ-knife treatment. Methods A retrospective analysis of the clinical data of 248 patients with functional pituitary prolactinomas was performed; gamma knife treatment was performed on these patients from September 2004 to March 2008. We divided the patients into 3 groups: group Ⅰ (50 Gy≤central dose<60 Gy, 20 Gy＜marginal dose<30 Gy), group Ⅱ (40 Gy≤ central dose＜50 Gy, 15 Gy＜marginal dose<25 Gy) and group Ⅲ (30 Gy ≤ central dose<40 Gy, 12 Gy＜marginal dose<20 Gy). The irradiation dose on optic nerves in the 3 groups was under 9 Gy. Radioimmunoassay was employed to detect the serum PRL level before and 1, 3 and 12 months after γ-knife treatment. The changes of the tumor sizes were observed and compared with cranial MRI 1 and 2 years after -γ-knife treatment.Results Significant differences on the PRL level were noted before -γ-knife treatment between each 2 groups (P<0.05); the PRL level in group Ⅲ was lower as compared with that in group Ⅰ and Ⅱ before γ-knife treatment; however, the PRL level in group Ⅲ was higher as compared with that in group 112 months after -γ-knife treatment; the PRL level in all the 3 groups after γ-knife treatment was significantly lower as compared with that before γ-knife treatment (P<0.05). MRI showed that the tumor had 80% partial response rate (198/248) in the 1st year, 82% complete response rate (203/248) in the 2nd year, increased volume in 19 patients (7.7%) and no change in 26 patients (10.4%). Conclusion Different treatment doses of Gamma knife on functional pituitary prolactinomas has great influences on postoperative recovery of endocrine; the higher doses of the center and edge (especially center), the higher normal rate of postoperative PRL level. Whether it will cause long-term hypopituitarism needs continue follow-up.