Gamma knife radiosurgery for GH-secreting microadenoma with empty sella.

We report a case of a growth hormone secreting microadenoma associated with empty sella treated by gamma knife radiosurgery and we evaluate the effectiveness of radiosurgery for this lesion. A 58-year-old female complained of an acromegalic appearance for 10 years. Magnetic resonance imaging revealed an enlarged sella floor with a compressed, but slightly enlarged pituitary gland. Serum GH values were 8.52 ng/ml. From these results, we diagnosed the presence of a GH-secreting pituitary microadenoma with empty sella. Stereotactic gamma knife radiosurgery was performed to treat the adenoma. The treatment dose was 30 Gy for the tumour margin (50% isodose). The patient was monitored for 5 years without any reported problem. Serum GH values were gradually decreased to 4.1 and 3.5 ng/ml at 1.6 and 3 years. Serum GH values at 5 years after radiosurgery were 1.8 ng/ml within 2 h after glucose load and serum IGF-1 was normalized. We conclude that gamma knife radiosurgery can be an useful alternative treatment modality for GH-secreting adenoma with empty sella in the selected patients when surgery is contraindicated as the primary treatment.     

Coexistence of aneurysmal subarachnoid haemorrhage and pituitary apoplexy: Case report and review of the literature.

A case of aneurysmal subarachnoid haemorrhage with associated haemorrhagic infarction of a growth hormone secreting pituitary macroadenoma is presented. The subarachnoid haemorrhage was not identifiable on CT, but was apparent on MRI. Angiography revealed a 7mm right posterior communicating aneurysm, a 3mm left A1 segment anterior cerebral aneurysm, and vasospasm. Surgery was performed through a right pterional/subfrontal approach, clipping both aneurysms and debulking the tumour. The left A1 aneurysm was the site of subarachnoid haemorrhage. There was evidence of haemorrhagic infarction of the pituitary tumour. Although rupture of an aneurysm into a pituitary tumour has been previously reported, this is the first case reported of aneurysmal subarachnoid haemorrhage with coexisting pituitary apoplexy where the aneurysm had not bled directly into the pituitary tumour. The literature regarding the association between pituitary tumours and aneurysm is reviewed.     

A case of pituitary adenoma with simultaneous secretion of TSH and GH detected by double immunostaining method

A rare case of simultaneous hypersecretion of thyroid stimulating hormone (TSH) and growth hormone (GH) in a pituitary adenoma is reported. A 59-year-old male complaining of general fatigue, dyspnea on exertion and finger tremor was admitted. Examination on admission, he revealed with hyperthyroidism and hypersecretion of TSH and thyroid hormones. Administration of TRH did not further increase serum TSH level, and administration of T3 also had no effect on TSH secretion. CT scan showed a pituitary macroadenoma 13mm in diameter. MRI demonstrated a homogenously hypointense mass with Gd-DTPA enhancement in the left side of the sella turcica. The entire chromophobic adenoma was removed by trans-sphenoidal surgery. Immunostaining of the specimen showed that the cytoplasm of the adenoma cells was positive for both TSH and GH. Double immunostaining using avidin-biotin-peroxidase complex (ABC) method and immunogold silver staining (IGSS) method, showed that the adenoma cells had been secreting both GH and TSH at the same time. After the adenomectomy, the hyperthyroidism disappeared, and all altered indicators of pituitary function returned to normal.     

Bromocriptine-induced apoptosis in pituitary adenoma cells: relationship to p53 and bcl-2 expression

In an attempt to understand the roles of the tumour suppressor gene p53 and the proto-oncogene bcl-2 in cell death and survival in pituitary adenomas, we investigated the relationship of their expression to the apoptotic response of two pituitary adenoma cell lines (GH3 and AtT-20) to bromocriptine. An MTT (3–4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrasolium bromide) assay was performed after treatment with bromocriptine for various periods of time over a range of concentrations to determine the effect of this drug on cell growth. Bromocriptine inhibited growth of GH3 and ArT20 cells in a dose dependent manner. DNA fragmentation was assessed in GH3 and AtT-20 cells exposed to 10 ug/ml bromocriptinefor 48h and 72 h. The DNA of GH3 and ART-20 cells showed nucleosomal fragmentation, indicative of apoptosis. When assayed 2 days after adding bromocriptine, approximately 60% of GH3 and 58% of AtT-20 cells treated with bromocriptine displayed typical apoptotic morphology, including condensed chromatin and fragmented nuclei. There was a time dependent increase in the proportion of all tumour cells undergoing apoptosis. Decreased expression of bcl-2 and accumulation of wild-type p53 were associated with bromocriptine induced apoptosis in pituitary adenoma cells. DNA analysis confirmed the results obtained by the protein study. Different expression of p53 and bcl-2 genes is consistent with the expression of these gene products. These findings show that bromocriptine activated wild-type p53 and suppressed bcl-2 favouring occurrence of apoptosis in pituitary adenoma cells.     

Rathke囊肿并垂体腺瘤2例报告并文献复习

目的总结垂体腺瘤伴Rathke囊肿的临床特征与治疗方法。方法回顾性分析2例经手术病理证实伴有Rathke囊肿的垂体腺瘤病例资料。结合临床特征、影像学表现、手术治疗以及相关文献进行分析。结果 2例病人均经翼点入路行开颅手术,术后病理结果为垂体腺瘤合并Rathke囊肿。1例术后随访13个月复查MRI示未见肿瘤及囊肿复发,1例术后视力较术前好转。结论伴有Rathke囊肿的垂体腺瘤临床罕见,鞍区MRI提示垂体腺瘤旁存在囊性信号应考虑合并Rathke囊肿。临床明确诊断依赖于组织病理学观察及免疫组化标记。对于压迫症状明显且伴有Rathke囊肿的垂体腺瘤可手术治疗。     

神经内镜经鼻蝶窦入路手术治疗垂体生长激素细胞腺瘤后生化缓解的影响因素分析

目的探讨神经内镜经鼻蝶窦入路手术治疗垂体生长激素(GH)细胞腺瘤后生化缓解的影响因素。方法回顾性分析福建医科大学附属第一医院神经外科2017年1月至2021年3月采用神经内镜经鼻蝶窦入路行肿瘤切除术的80例垂体GH细胞腺瘤患者的临床资料。所有患者手术前、后均行全面的内分泌功能评估。术后根据2021版《中国肢端肥大症诊治共识》中的生化缓解标准判断患者是否达到生化缓解,并将其分为生化缓解组和生化未缓解组。比较两组的年龄、性别、病程、术前GH、胰岛素样生长因子1(IGF-1)、影像学评估结果、术中所见及病理学指标,将其中差异有统计学意义的因素纳入多因素logistic回归分析,判断影响垂体GH细胞腺瘤患者术后生化缓解的危险因素。结果80例患者术后GH中位数为6.2μg/L(0.4~128.2μg/L)(1μg/L=0.047 nmol/L),IGF-1为(407.5±191.4)ng/ml(122.9~804.6 ng/ml),均较术前明显降低[术前GH中位数:52.3μg/L(2.8~456.4μg/L)、IGF-1:(693.6±294.2)ng/ml(163.8~1970.0 ng/ml),均P<0.001]。根据2021版的生化缓解标准,47例患者达到生化缓解(生化缓解组),另33例未达到(生化未缓解组)。与生化未缓解组比较,生化缓解组患者的术前GH水平低,肿瘤最大径>3.0 cm、Knosp分级为3、4级、Hardy分期为E期的患者占比均低(均P<0.05)。多因素logistic回归分析结果显示,术前GH水平(OR=1.033,95%CI:1.001~1.066,P=0.046)和Knosp分级(OR=14.498,95%CI:3.534~59.317,P<0.001)是影响患者术后生化缓解的危险因素。结论术前GH水平越低、Knosp分级越低的垂体GH细胞腺瘤患者行神经内镜经鼻蝶窦入路肿瘤切除术后易达到生化缓解。     

Coexistence of a cerebellopontine epidermoid cyst with a pituitary adenoma

We report on an 18-year-old girl with the coexistence of an epidermoid cyst in the cerebellopontine angle (CPA) with a pituitary adenoma. The clinical course and histopathological characteristics were reviewed. The patient presented with headache, vision loss and amenorea. Computerised tomographic (CT) scan and magnetic resonance imaging (MRI) examinations demonstrated a solid sellar lesion with supra-sellar extension. There was another mass lesion in the CPA with prepontine extension. The tumours were removed surgically. Histopathological examination revealed an epidermoid cyst in the prepontine area and a pituitary adenoma in the sellar region. This has been the second case to be reported in the literature with the coexistence of an epidermoid cyst and a pituitary adenoma.     

CT findings of growth hormone secreting pituitary adenomas

The value of high-resolution computed tomography (CT) in the diagnosis of pituitary adenoma has recently been stressed, especially of the coronal view with contrast enhancement. Analysis of the CT scans of 33 growth hormone (GH) secreting pituitary adenomas was done (11 cases of microadenomas, 7 cases of intrasellar adenomas and 15 cases of macroadenomas with suprasellar extension). In macroadenomas, the density was high in five cases, high with isodense portion in two cases, mixed in four cases, isodense in three cases, and isodense and low dense in one case. Six adenomas showed homogeneous density and nine were heterogeneous. After contrast enhancement, two cases showed marked enhancement, ten cases mild and three cases ring enhancement. Margin of adenoma was smooth in nine cases and irregular in six. Among seven cases of intrasellar adenoma one accompanied primary empty sella. In microadenomas ten of eleven cases had hypodense mass inside the normally enhanced pituitary gland. The margin was ill-defined in seven cases and well-defined in three. Eight cases had pituitary height 7 mm or more. Upper surface of the pituitary gland was convex upward in five cases, flat in four and concave in two. Deviation of pituitary stalk was found in seven cases. Bony changes of sellar floor were recognized in three cases. There was a tendency that serum GH level increased with the increment of the size of adenoma. Serum GH levels in adenomas with ring enhancement were lower than those in the homogeneously enhanced adenomas of similar size. One case with marked enhancement showed the highest GH level among all adenomas of the presented series.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interleukin regulation of prolactin and corticotropin from pituitary adenoma

Recent findings indicate that lymphokines, leukocyte-derived hormones, interact with the hypothalamic-pituitary axis. We examined the role of neurotrophic lymphokines in the neuroendocrine system. Specifically, the action of Interleukin (IL)-1b, IL-2 and IL-6 upon the anterior pituitary hormones, growth hormone (GH), prolactin (PRL) and adrenocoticotropic hormone (ACTH) were studied in rodent pituitary adenoma cell lines. Hormone release by GH and PRL-producing rat adenoma cells (GH3) and ACTH-producing mouse adenoma cells (AtT-20) was analyzed by radioimmunoassay (RIA). Recombinant (r) IL-1beta decreased PRL release from GH3 in a dose-dependent fashion. IL-1 inhibition of PRL production occurred in parallel with IL-1 inhibition of DNA synthesis in GH3 as measured by [(3)H] thymidine incorporation. This result strongly indicates that IL-1 alters PRL production by adenoma cells at the translational level. Low dose IL-2 (10 U/ml) enhanced ACTH production from AtT-20, but higher concentrations of IL-2 failed to affect the release of ACTH. IL-2 did not change the incorporation of [(3)H] thymidine in AtT-20. Previous studies showed that IL-1 and IL-6 induce a significant secretion of ACTH via the hypothalamic-pituitary axis. However, IL-1 and IL-6 failed to affect ACTH secretion by AtT-20. Blood-derived cytokines have direct effects on hormone secretion by pituitary adenoma cells in vitro.     

内窥镜辅助下经单鼻腔蝶窦入路切除垂体腺瘤

目的　探讨局部麻醉下利用内窥镜辅助 ,经单鼻腔蝶窦入路切除垂体腺瘤的可行性、优缺点 ,适应证及注意事项。方法　采用MRI明确诊断 ,使用局部麻醉内窥镜电视监测下经单鼻腔蝶窦入路进行垂体腺瘤切除。结果　 30例病人中 2 5例肿瘤全切除 ,5例次全切除。术后 2～ 4小时病人即可下床活动 ,进食。术后平均 4天出院 ,无死亡、无感染。术后脑脊液鼻漏 1例 ,再次经鼻蝶入路修补后痊愈。随访 6～ 4 8个月 ,视力恢复到 1.0以上10例 ,内分泌功能正常 15例 ,月经恢复正常 10例。结论　内窥镜辅助下经单鼻腔切除垂体瘤使用局部麻醉是安全可行的 ,手术对病人的损伤和影响可以达到最低程度     

Spherical amyloid deposition in a prolactin‐producing pituitary adenoma

A 41‐year‐old man presented with headache, right‐sided ophthalmic pain and visual deficit. His neurological examination was normal except for bitemporal hemianopsia and right lower quadranopsia. MRI demonstrated a mass arising from the pituitary gland. Hormonal analysis revealed an elevated prolactin level of 4700 ng/mL (normal 4.04–15.2 ng/mL). MRI revealed hypointense signal on T2‐weighted images. Moreover, we also concluded that foci with no intravenous contrast enhancement represent the amyloid deposits. The patient underwent trans‐sphenoidal resection of the pituitary adenoma. Histological examination revealed an adenoma with spheroid amyloid deposits adjacent to prolactin‐staining adenoma cells. The patient recovered from the surgery without complications.     

Thyrotropin secreting pituitary adenoma accompanying a silent somatotropinoma

Thyroid stimulating hormone (TSH) secreting pituitary adenomas are rare tumors manifested as hyperthyroidism with goiter in the presence of elevated TSH. We present a case with pituitary adenoma secreting both TSH and growth hormone (GH) with the prominent clinical findings of hyperthyroidism but without clinical findings of acromegaly. Pituitary magnetic resonance imaging revealed a macroadenoma. Transsphenoidal surgery was performed twice. The immunohistochemical staining showed that tumor cells were strongly reactive to GH and relatively mildly reactive to TSH. Control pituitary imaging revealed a residual macroadenoma, and long acting octreotide treatment was administered. After two years of the treatment, tumor size remained the same while thyroid function tests and insulin-like growth factor 1 (IGF-I) values returned to normal ranges. In conclusion, we always recommend hormonal examinations for all patients who have pituitary adenoma without signs and symptoms of acromegaly.     

伴有Rathke囊肿的垂体腺瘤的临床诊断和治疗

目的总结伴有Rathke囊肿垂体腺瘤的临床特点、诊断和手术治疗方法。方法回顾性分析11例经手术病理证实伴有Rathke囊肿垂体腺瘤的临床特点,影像学表现及其手术治疗效果。结果 11例患者全切9例,次全切除2例,囊肿均切除,术后均进行临床随访,随访时间8～52个月,术前视力下降的7例患者术后视力得到明显改善,其中6例患者视力恢复正常,3例月经紊乱患者月经恢复,1例头痛患者术后头痛消失。术后复查垂体磁共振未见肿瘤或囊肿复发。结论伴有Rathke囊肿的垂体腺瘤临床罕见,垂体MRI提示肿瘤内存在囊性信号应考虑合并Rathke囊肿的存在,压迫症状明显的患者可选择手术治疗,预后良好。     

A growth hormone‐secreting adenoma with incomplete nerve bundle formation

We present a unique case of an adenoma secreting growth hormone (GH), showing incomplete nerve bundle formation without ganglion cells. A 47‐year‐old man presenting with acromegaly was revealed to have high serum GH and IGF‐1 levels. The concentrations of the other adenohypophysial hormones were within the normal range. Histology revealed an unusual pituitary adenoma containing many nerve bundle‐like structures. Adenoma cells with ovoid or round hyperchromatic nuclei and eosinophilic cytoplasms lacked the typical features of ganglion cells. The nerve bundles consisted of slender elongated cells. These fibers were arranged into groups in a roughly parallel fashion. By immunohistochemistry, many adenoma cells were positive for GH, prolactin, thyrotropin beta, synaptophysin and chromogranin. Fibrous bodies revealed by keratin immunostaining were found only in adenoma cells. Scattered star‐shaped adenoma cells showed the same immunoreactivity as folliculo‐satellite cells. Adenoma cells, but not the bundle‐like structures, were also positive for Pit‐1. Immunostaining for neurofilament protein, GFAP, vimentin, and S‐100 protein revealed variable amounts of fibrils within the bundle‐like structures. Scattered immunoreactivity for myelin basic protein and synaptophysin was also found in the bundle area. Our case is the first GH‐secreting pituitary adenoma showing incomplete nerve bundle differentiation and lacking mature ganglion cells.     

过氧化物酶体增殖物激活受体γ在垂体腺瘤中的表达

目的 通过检测过氧化物酶体增殖物激活受体γ(PPARγ)在人垂体腺瘤组织中的表达,探讨其在垂体腺瘤中的相关机制.方法 通过免疫组化法确定经手术切除的83例垂体腺瘤组织细胞来源;采用RT-PCR、适时定量PCR检测研究83例垂体腺瘤组织及6例正常垂体组织PPARγ的mRNA表达量,采用Western blot法检测组织PPARγ蛋白质表达水平,分析不同类型垂体腺瘤组织之间核酸及蛋白水平表达量的差异.结果 GH腺瘤17例、PRL腺瘤15例、ACTH腺瘤18例、多激素腺瘤(MCPAs)17例、无功能腺瘤(NFAs)16例及正常对照组6例;mRNA水平检测显示所有垂体腺瘤组织的表达量均高于正常对照组,其中GH腺瘤的表达量最高,与其他组比较P＜0.05;蛋白水平检测显示GH腺瘤、PRL腺瘤、ACTH腺瘤及MCPAs的表达量均高于正常对照组(P＜0.05),GH腺瘤的表达量最高,NFAs的表达量与正常对照组差异无统计学意义(P＞0.05).结论 PPARγ转录及蛋白表达水平在人GH、PRL、ACTH及MCPAs垂体腺瘤组织中高表达,该基因与垂体腺瘤有一定的相关性,而无功能垂体腺瘤在核酸水平的表达量增高,蛋白水平的表达量不高,可能与激素的分泌水平有关;在GH腺瘤中的表达量最高,且与其他组相比,差异有统计学意义(P＜0.05),说明该类肿瘤与PPARγ的关系最为密切,可能与生长激素能刺激PPARγ的表达有关.     

Pituitary adenoma calcification

Three hundred and eighteen cases of functioning and non-functioning pituitary adenoma were examined by histological, immunocytochemical and electronmicroscopic technique. Fourty-four of them (13.8%) showed evidence of calcospherites in the tumor tissues. A high incidence of calcospherite is found in functioning adenoma, but not in non-functioning adenoma. Calcification was seen most frequently in cases of prolactinoma (23), GH secreting (7), or GH + PRL tumor (2) and less in adrenocorticotropic hormone secreting adenoma (2) and follicle stimulating hormone secreting adenoma (1). Prolactin and growth hormone might be involved in the control of calcium metabolism. This is because, following adenomectomy in patients with prolactinoma or GH-secreting adenoma with hypercalcemia, there is normalization of serum PRL and GH with reduction in serum calcium. Calcospherite is produced in all of metastatic calcification, arterial calcification, dystrophic calcification and calcinosis. In cases of non-functioning adenoma however, the mechanism is believed to by dystrophic calcification.     

Difference of lectin binding sites of secretory granules between normal pituitary and adenoma cells

Summary Electron-immunocytochemical staining with lectin (concanavalin A: Con A) binding sites analysis was applied to study secretory granules of human pituitary adenomas and surrounding normal pituitary tissue using post-embedded serial ultrathin sections. Twelve cases of human pituitary adenoma and three specimens of normal pituitary tissue surrounding adenomas were studied: the cases were operated on between 1982 and 1984. The tumors consisted of four prolactin (PRL)-, six growth hormone (GH)-, and two adrenocorticotropic hormone (ACTH)-producing adenomas.In parallel with the detection of Con A binding sites of secretory granules, their secreting hormones were characterized electron-microscopically with the immunocytochemical horseradish peroxidase (HRP) labeling using the avidin-biotin technique. The two cases of ACTH-producing adenomas showed either weak or negative reactions with Con A on secretory granules, while normal ACTH-producing pituitary cells showed strong reactions with Con A on every secretory granule observed. Large secretory granules of PRL- or GH-producing cells showed negative reactions with Con A both in the pituitary adenoma and normal pituitary, while some small granulated or sparsely granulated adenoma cells also showed strong reactions with Con A.The complexity of human pituitary adenomas is illustrated as well as the difference in biochemical structure of normal pituitary cells and pituitary adenoma cells secreting the same specific hormone.     

动态MRI检查在Cushing病的临床应用价值

目的 为分析动态：MRI检查对普通MRI检查未发现垂体瘤的Cushing病(库欣病)的诊断价值。方法 回顾性分析7例普通：MRI检查未发现垂体微腺瘤的Cushing病人进行动态：MRI检查的结果，以及比较术中所见。7例均为女性，平均年龄33．5岁，平均病程2．7年，有典型的Cushing综合征的表现。结果动态MRI检查7例中，4例显示垂体微腺瘤，并经手术证实；3例未显示垂体腺瘤，但手术证实2例为垂体微腺瘤，1例为垂体细胞增生。随诊1—6个月，皮质醇降至正常6例。结论 对于临床症状和内分泌学检查符合Cushing病，而普通MRI检查未发现垂体腺瘤的病例，采用动态MRI检查能提高垂体ACTH微腺瘤的发现率。     

Pituitary reserve of growth hormone in adolescent patients with cerebral palsy and mental retardation

The pituitary reserve of growth hormone (GH) was studied in 11 severely handicapped boys (14 approximately 18 years old) with mental retardation and cerebral palsy (CP); athetotic type 4 cases, and spastic type 7 cases. Serum GH was determined before and after intravenous injection of 1 ng/kg growth hormone releasing factor (GRF) or oral administration of 0.1 mg/m2 clonidine. The athetotic type patients showed low somatomedin C (Sm C) concentrations (0.31 +/- 0.11 U/ml), poor responses to clonidine, and good responses to GRF. The spastic type patients showed subnormal responses to GRF although their Sm C was normal (0.91 +/- 0.43 U/ml). Clinically, the stature was small, and the puberty was delayed in the former. The levels of plasma testosterone were significantly lower than those in the latter. It is concluded that athetotic type CP was associated with hypothalamic GRF deficiency and spastic type CP was associated with reduced pituitary reserve of GH.     

Growth hormone response to edrophonium in Alzheimer's disease

Neuropathologic data from patients with Alzheimer's disease indicate the presence of neurofibrillary tangles in hypothalamic regions associated with regulation of pituitary hormone release. The authors explored the hypothesis that cholinergic projections to hypothalamic nuclei controlling pituitary growth hormone (GH) release degenerate in Alzheimer's disease. Integrity of cholinergic regulation was tested by assaying the GH response to a presynaptic cholinergic challenge. After administration of the choline esterase inhibitor edrophonium, the peak GH response was 14 ng/ml in healthy elderly control subjects and only 2 ng/ml in Alzheimer's patients. The magnitude of GH blunting was correlated with cognitive and functional deficits. Possible implications of these data for enhanced accuracy in the diagnosis of dementia are discussed.