Intra- and postoperative plasma ACTH concentrations in patients with Cushing's disease cured by transsphenoidal pituitary surgery

Summary.  Background: The optimal treatment of choice for ACTH-producing pituitary adenomas is their complete removal by the transsphenoidal surgical approach. ACTH-producing pituitary adrenomas are, however, often small in size not detectable with neuro-imaging techniques, which may result in difficulties during their surgical removal. With the advent of rapid methods for plasma ACTH measurement, a few neurosurgical centers introduced intra-operative plasma ACTH determinations in peripheral and central blood samples to help improve the outcome of pituitary surgery in patients with Cushing's disease.  Method: To evaluate the usefulness of this new method, we performed, under standardized conditions, intra-operative plasma ACTH measurements with a rapid immunochemiluminometric method at different stages of transsphenoidal pituitary surgery in 7 patients with Cushing's disease.  Findings: We found that from the beginning of anesthesia until the end of operation, ACTH concentrations in venous plasma were highly variable by both the rapid and the standard methods. In most cases the changes in venous plasma ACTH concentrations that occurred until the end of surgery failed to indicate the removal of the ACTH-producing pituitary adenoma. However, a more than 50% decrease of venous plasma ACTH concentrations by the rapid assay was observed 2 h after completion of the operation in all but one of the patients. As evidenced by a long-term hormonal and clinical remission, these changes in plasma ACTH levels in all patients were accompanied by a complete removal of the ACTH-producing pituitary adenoma.  Interpretation: These findings indicate a slow disappearance of ACTH from the circulation after a successful pituitary surgery in patients with Cushing's disease. Published online October 10, 2002 Correspondence: Dr. K. Rácz, 2nd Department of Medicine, Semmelweis University Medical School, 1088 Budapest, Hungary     

Proliferation of exogenously injected primordial germcells （PGCs） into busulfan-treated chicken embryos

Aim: This study was designed to investigate the effect of busulfan treatment on the proliferation of chicken primordialgerm cells (Fgcs) in vivo, focusing on the preferential settlement of PGCs onto the germinal ridges of chicken em-bryos. Methods: Bustdfan (250 rig/egg) was injected into the egg white of freshly oviposited fertilized eggs, whichwere then incubated. Embryonic developnent and viability were examined, and exogenous PGCs collected from embry-onic blood vessels were injected into the germinal crescent region of recipient enthryos. The nttmber of PGCs residedonto germinal ridges of the right and left sides were compared. Results: Bustdfan had a slight harmful effect on theembryo viabihty and the PGCs proliferation. The number of PGCs resided onto the left side of germinal ridges wasslightly higher as compared with the right side. Conclusion: Busulfan suppressed the viability of embryos and the pro-liferation of endogenous PGCs in the recipient embryos. However, the number of exogenous PGCs proliferated washigher in embryos treated with busnlfan than those without busulfan. Data also suggest the possibihty of a preferentialresidence of PCCs toward the left side of the germinal crescent region as compared with the right, which may be due toa more advanced functional development of the left gonad than the right. (Asian JAndro11999 Dec; 1 : 187 - 190)     

异位ACTH综合征的诊断与外科治疗

目的 探讨异位ＡＣＴＨ综合征的诊断与外科治疗效果。方法 对１９８７年１０月～１９９９年５月收治的异位ＡＣＴＨ综合征异位ＡＣＴＨ综合征１２例的临床资料进行总结，８例行手术治疗，其中２例欠住院发现异位肿瘤者行肿瘤根治性切除术；６例库兴综合征症状严重但未找到异位肿瘤者，行双侧腺上切作术，术后加皮质扩素替代治疗，非手术治疗４例，其中放疗加化疗２例，单纯化疗２例。结果 １２例中１１例随记６个月～１０年，２例     

Treatment of Pituitary Carcinomas and Atypical Pituitary Adenomas: A Review

Atypical pituitary adenomas (APAs) are aggressive tumors, harboring a Ki-67 (MIB-1) staining index of 3% or more, and positive immunohistochemical staining for p53 protein, according to the World Health Organization (WHO) classification in 2004. Pituitary carcinomas (PC) usually develop from progressive APAs and predominantly consist of hormone-generating tumors, defined by the presence of disseminations in the cerebrospinal system or systemic metastases. Most of the cases with these malignant pituitary adenomas underwent surgeries, irradiations and adjuvant medical treatments, nevertheless, the therapies are mainly palliative. Recently, the efficacy of temozolomide (TMZ), an orally administered alkylating agent, has been reported as an alternative medical treatment. However, some recent studies have demonstrated a significant recurrence rate after effective response to TMZ. Further clinical and pathological researches of malignant pituitary adenomas will be required to improve the outcome of patients with these tumors.     

Pituitary apoplexy. Report of 25 patients

A series of 25 patients with a clinical diagnosis of pituitary apoplexy (PA) is reviewed. It included 14 men and 11 women aged between 20 to 79 years (mean age: 54 years). Twenty-two patients did not know that they had a pituitary tumor when the apoplexy occurred. A precipitating event was found in 3 cases. Symptoms and signs ranged from isolated ocular paresis to a deep coma. Seventeen patients experienced a decrease in their visual acuity. CTscan and MRI showed a pituitary adenoma in all cases, a hemorrhage was also present in 10 out of the 24 CTscans, and in all the 8 MRI performed. Twenty patients underwent surgery; 18 of them by a transsphenoidal approach. A complete recovery of visual acuity was observed in 75% of patients operated within the week following the onset of symptoms, and in 56% of patients operated later on. There was no case of complete visual recovery among the blind patients. Pituitary apoplexy is a clinical concept. It applies only to symptomatic cases. It is generally a complication of a pituitary adenoma which is in most cases unknown. There are different degrees of severity; PA can even be life-threatening. The principal aim of surgery in the acute phase is the improvement of visual prognosis. In our series, blind patients or those with a history of visual loss for more than a week or with a blindness had a poorer prognosis.     

垂体功能性促性腺激素腺瘤临床病例分析

目的研究分析垂体功能性促性腺激素腺瘤女性患者的临床特征,以期达到早期诊断及治疗的目的。方法回顾性分析我院收治的5例垂体功能性促性腺激素腺瘤女性患者的临床特点及诊治经过。结果 5例患者均为生育年龄女性,平均年龄38.8岁,临床表现为月经紊乱、溢乳、头痛和视野缺损。盆腔超声发现双侧卵巢增大,内见多房囊性无回声。性激素检查雌激素4 377.65～12 973.45pmol/L,均值7 800.66pmol/L,而FSH和/或LH并未被异常升高的雌激素负反馈抑制,泌乳素(PRL)升高至1 268.18～2 794.16nmol/L,均值1 726.95nmol/L。垂体磁共振(MRI)检查发现垂体大腺瘤样改变。5例患者均接受垂体腺瘤切除术,病理切片免疫组化检查提示FSH/LH阳性,术后随访至今(3～5年)无肿瘤复发迹象。结论当绝经前女性出现月经紊乱、溢乳、头痛、视野缺损、反复发生的卵巢多房囊肿、雌激素异常升高的同时促性腺激素未被负反馈抑制时,应行垂体核磁共振检查,如发现垂体肿瘤,应考虑垂体功能性促性腺激素腺瘤的诊断。垂体瘤切除手术是首选治疗。     

异位ACTH综合征32例诊断和疗效观察

目的 对异位促肾上腺皮质激素(ACTH)综合征病例进行临床分析,为临床诊治工作提供指导。方法 对1990年1月至2003年4月间收治的32例异位ACTH综合征患者资料进行总结。结果 所有病例临床表现和生化测定均符合库欣综合征的诊断。10例患者找到异位肿瘤,诊断明确;4例患者经体表肿物活检或岩下静脉及股静脉插管分段取血查ACTH提示为异位ACTH瘤,诊断基本明确;18例患者经临床及影像学检查高度怀疑异位ACTH综合征。15例(47％)患者因异位肿瘤定位不明确而行双侧或单侧肾上腺全切术,1年存活率60％;7例(22％)患者发现可疑异位肿瘤,未行手术治疗,1年存活率0;10例(31％)患者行根治性肿瘤切除,6例为支气管类癌,4例为胸腺类癌,1年存活率60％。结论 异位ACTH综合征异位肿瘤定位极为困难,仅少数病例可以找到异位肿瘤行手术切除。多数病例无法确定异位肿瘤,双侧肾上腺全切加激素替代治疗是一种有效方法。     

Failure in management of pituitary tumors discussion of 3 cases

Summary Three patients with pituitary adenomas (ACTH-secreting, non-secretory, and multi-secretory) with unfavorable course, in spite of repeated microsurgery, drag therapy, as well as radiotherapy and radiosurgery, are presented. Each case was re-evaluated for possible flaws in management. Two of the invasive tumors continued to grow, in spite of correct management. The third patient with a pituitary adenoma underwent microsurgical resection, and later following a false positive finding of recurrence, received radiotherapy and underwent radiosurgery. The lesion actually was chronic inflammatory tissue.     

Pituitary apoplexy: Endocrine,surgical and oncological emergency. Incidence,clinical course and treatment with reference to 799 cases of pituitary adenomas

Summary Authors analised retrospectively the incidence of pituitary apoplexy in a series of 799 pituitary adenomas with respect to the long term follow-up of the patients.Focal vascular abnormalities in histological specimens of tumours, regarded as morphological suggestion of past apoplexy (heamorrhage, ischaemic infarction or necrosis), were established in 113 out of 783 surgical cases (14.4%).Acute clinical onset, justifying the clinical diagnosis of pituitary apoplexy, occurred in 39 patients only (5% of the whole series), 19 of them were subjected to urgent surgical decompression due to severe neurological deficit. The haemorrhagic character of apoplexy was established in most cases requiring immediate surgery.The detailed clinical picture of this condition and its management are discussed with respect to the long term prognosis.On this basis the authors suggest the necessity of surgical treatment in every case of pituitary apoplexy, taking into account not only neurological recovery, but also endocrine and oncological aspects of the disease. The observation that pituitary apoplexy may be a marker of tumour invasiveness (even in small, enclosed adenomas) is highlighted.     

经单侧鼻孔-蝶窦入路镜下切除垂体腺瘤(附12例分析)

目的 总结经单侧鼻孔-蝶窦入路镜下切除垂体腺瘤的体会。方法 对12例垂体腺瘤病人均采用经单侧鼻孔-蝶窦入路行肿瘤切除术。结果 10例全切除，1例大部切除，1例部分切除。4例病人术后出现短期尿崩，合并不同程度的水电解质紊乱，经口服双氢克脲噻、及时补液3～4d缓解。2例未完全切除肿瘤者术后行X-刀放射治疗。本组无一例出现脑脊液漏。12例获随访，平均10．2（6．18）月，均无肿瘤复发，视力减退者均有不同程度改善，尿崩症者均获痊愈。结论 肿瘤质地较硬，向鞍上扩展较大时应慎重选择经蝶窦入路；窥鼻镜准确地置于蝶窦前壁的最佳位置，是减少手术创伤的关键；明胶海绵加上EC耳脑胶修复鞍底可避免出现脑脊液漏；出现尿崩、水电解质失衡时应及时纠正。     

ESM-1在复发性垂体腺瘤中的表达及意义

目的 探讨ESM-1在免疫组化水平的表达与垂体腺瘤复发的相关性。方法 对2018年2月至2021年4月就诊于我院的33例垂体腺瘤患者进行ESM-1抗体的免疫组化染色并进行分析研究。结果 复发组相较首发组有更高的ESM-1表达（P=0.004）,而年龄、性别及肿瘤最大径均与ESM-1表达无明显相关性,患者复发前后的ESM-1表达无明显差异,ki-67蛋白阳性表达指数与ESM-1表达之间无明显相关性。结论 ESM-1的表达与肿瘤复发有明显相关性,对于垂体腺瘤的治疗及预后有指导作用。     

改良翼点入路显微手术切除垂体巨腺瘤及术中垂体柄保护

目的 探讨巨大型垂体腺瘤显微手术切除及垂体柄保护方法。方法 采用改良翼点入路对48例巨大垂体腺瘤（直径〉40mm）行显微手术切除，术中注意保护垂体柄。结果 肿瘤伞切除36例，近全切除8例，大部切除4例，其中全切除患者垂体柄保留30例（83．3％）。所有病例无一例死亡。术后发生尿崩症31例（64．6％），其中21例在1～2周内恢复正常，7例在3个月内恢复，3例尿崩症状持续2年左右？随访2～3年，无复发病例，无其他并发症。结论 采用改良翼点入路治疗巨大垂体瘤效果确切，术中垂体柄保留是降低术后尿崩症发生率、提高手术疗效的关键措施。     

Discovery of a pituitary adenoma following a gonadotropin-releasing hormone agonist in a patient with prostate cancer

Gonadotropin-releasing hormone (GnRH) agonists have become the treatment of choice for locally advanced and metastatic prostate cancer. We report a case of prostate cancer in which this treatment led to severe symptoms of intracranial hypertension due to the concomitant presence of an asymptomatic functional pituitary adenoma. A 70-year-old white man was initially evaluated for a multifocal adenocarcinoma, Gleason score 6 (3+3) with perineural invasion suggesting an extracapsular extension. A conformational external beam radiation (74 Gy) with a concomitant GnRH agonist (leuprolide) was initiated. Almost 10 days after the administration of leuprolide the patient complained of visual disturbance, diplopia and other symptoms of intracranial hypertension. Magnetic resonance imaging (MRI) of the brain demonstrated a large sella mass lesion. To relieve the patient's symptoms, a transsphenoidal subtotal tumorectomy was necessary. The histopathological examination revealed an invasive gonadotroph pituitary adenoma. Two years later, there is no sign of progression either on his prostatic disease (prostate-specific antigen of 0.21 ng/mL) or on his pituitary disease (FSH, 4.7 UI/L, LH, 3.1 UI/L and total testosterone, 627 ng/dL) with values of the hypothalamic-pituitary axis in the normal range. We advocate that a high index of suspicion of pituitary tumor must be considered in any case of intracranial hypertension following the administration of GnRH agonist. Abarelix could have a place in such cases.     

A rare case of Maffucci's syndrome combined with tuberculum sellae enchondroma,pituitary adenoma and thyroid adenoma

Summary Maffucci's syndrome is a rare, congenital mesodermal dysplasia combined with dyschondroplasia and haemangiomatosis, and there are only about 150 reported cases. This syndrome is often combined with other neoplasms. Our case was associated with goitre, enchondroma of the tuberculum sellae and pituitary adenoma; the latter brought about disturbance of vision. Including ours, four cases of Maffucci's syndrome associated with pituitary adenoma are found in the literature. In the case of Maffucci's syndrome, it is necessary to examine associated disease as well as associated pituitary adenoma and skull base enchondroma, similar to the correlation of von Recklinghausen's disease with acoustic neurinoma.     

Discovery of a pituitary adenoma following treatment with a gonadotropin-releasing hormone agonist in a patient with prostate cancer

We report the case of a T3 prostate cancer in a 70-year-old white man. Hormone therapy represents a prominent branch in the treatment of locally advanced and metastatic prostate cancer. Gonadotropin-releasing hormone agonists have been proven to have a double effect on androgen metabolism: an initially stimulating, followed by an inhibitory, effect on the pituitary gland. This phenomenon may be noxious in the case of gonadotroph adenoma, with subsequent symptoms of intracranial hypertension. Gonadotropin-releasing hormone antagonists (abarelix), by avoiding the flare-up reaction, might be used in such instances.     

The Value of Intraoperative Cytology During Transsphenoidal Surgery for ACTH-Secreting Microadenoma

Summary  Background. Microsurgical selective adenomectomy is the best established method available for the treatment of Cushing's disease. However, this surgical method warrants still more efforts to improve the results in minute microadenomas. In this paper the authors evaluate a method of intraoperative cytological investigations during transsphenoidal surgery.  Method. Between January 1997 and September 1999, transsphenoidal surgery was performed in 75 patients with the diagnosis of Cushing's disease. Fifty-one cases of proven microadenomas were reviewed.  Findings. Of 51 cases, 33 tumors were 3 mm or less in diameter, here after called minute adenomas. In 49 of 51 (96.1%) microadenomas, adenoma tissue was identified by intraoperative cytological techniques. Postoperatively, only 35 of 51 ACTH-secreting microadenomas (68.6%) were confirmed by immunostaining methods. This lower percentage was most probably due to the small amount of tissue obtained. Therefore, in 14 cases (including 12 minute adenomas) the presence of the adenoma was only proven by cytological preparation and clinical outcome. The sensitivity of cytological preparations in cases of confirmed Cushing's disease was 100%.  Interpretation. The method described here was particularly well suited for the intraoperative discrimination and documentation of minute adenomas. Cytological preparation appears to be effective in improving the adenoma finding rate and the surgical outcome in cases of Cushing's disease.     

Direct intraoperative micromethod for hormone measurements of pituitary tissue in Cushing's disease

BACKGROUNDDuring transsphenoidal surgery (TSS) for Cushing’s disease, the surgeon depends on experience to find minute adenomas. Cytological slide preparations or frozen sections, even when successful, are not specific concerning the hormone activity. In an attempt to improve accurate localization of minute ACTH adenomas, we evaluated a new intraoperative method of ACTH measurements in adenoma and anterior lobe microsamples. As most ACTH adenomas are monohormonal, the possible benefit of a GH measurement was investigated.METHODSWe included pituitary tissue of 32 patients, 22 with Cushing’s disease and 10 endocrine inactive pituitary adenomas as control. All patients underwent TSS by one surgeon. Preoperative data, intraoperative and perioperative hormone measurements of homogenized, weighed pituitary tissue samples, and histological findings are presented.RESULTSIn ACTH adenomas, the median ACTH content was found to be 1,688 ng/mg, minimum 345 ng/mg. The median GH was measured at 36 ng/mg. Anterior lobe tissue contained median 80 ng ACTH/mg, maximum 279 ng/mg. Median GH was 2,200 ng/mg. In hormonally inactive adenomas ACTH was less than 0.1 ng/mg, median GH was 5.5 ng/mg. There was no overlap of ACTH content in the tissues investigated. Therefore, by adopting 300 ng ACTH/mg as a cutoff level, a clear discrimination is given. Additional GH measurements are not necessary.CONCLUSIONThis new intraoperative method permits a clear differentiation between adenoma and pituitary tissue. In addition to intraoperative cytology and histology, this method can serve as a specific proof that the ACTH adenoma has been identified during surgery. This may be valuable in difficult cases with unclear intraoperative findings, especially after previously negative exploration.     

肾窦异位肾上腺皮质腺瘤诊治分析

目的:提高对肾窦肿瘤及异位肾上腺病变的认识。方法:2011年7月我院收治1例男性肾窦异位肾上腺皮质腺瘤患者,对其临床资料进行回顾性分析,同时结合文献进行讨论。结果:术后普切及免疫组化考虑异位肾上腺皮质腺瘤。随访1年,患者临床症状消失,肿瘤未见复发。结论:肾窦肿瘤及成人异位肾上腺临床少见。影像学检查对明确诊断有一定帮助,最终需病理资料确诊。