Cushing's disease due to plurihormonal adrenocorticotropic hormone and gonadotropin-producing pituitary adenoma

A 67-year-old woman presented with clinical features of hypercortisolism in association with an invasive pituitary macroadenoma. Adrenocorticotropic hormone (ACTH)-dependent Cushing's disease was documented, and the resected tumor was chromophobic, weakly positive with periodic-Schiff reagent, and showed immunostaining for ACTH and beta-endorphin in a minority of adenoma cells. Both luteinizing hormone and alpha-subunit staining were also observed, but no follicle-stimulating hormone reactivity was seen. Ultrastructurally, the tumor showed typical features of a gonadotroph adenoma of female type. Immunoelectron microscopy showed that ACTH was not produced in corticotrophs, but in cells with the characteristic features of gonadotrophs. This represents the second report of a plurihormonal gonadotroph adenoma producing sufficient ACTH to result in pituitary-dependent Cushing's disease.     

Mammosomatotroph adenoma of the pituitary associated with gigantism and hyperprolactinemia. A morphological study including immunoelectron microscopy

Summary A 29-year old giantess with growth hormone excess and hyperprolactinemia underwent transsphenoidal surgery to remove her pituitary tumor. Electron microscopy revealed a mammosomatotroph adenoma composed of one cell type. Immunoelectron microscopy, using the immunogold technique, demonstrated predominantly growth hormone or prolactin or a varying mixture of both growth hormone and prolactin in the adenoma cells. The presence of growth hormone and prolactin was found not only in the cytoplasm of the same adenoma cells but also in the same secretory granules. In the nontumorous adenohypophysis, somatotrophs and lactotrophs showed ultrastructural signs of hyperactivity. This finding is in contrast with the presence of suppressed somatotrophs and lactotrophs seen in nontumorous portions of adult pituitaries harboring growth hormone or prolactin-secreting adenomas. Our morphological study reinforces the view that growth hormone-producing pituitary tumors, originating in childhood, are different from those of the adult gland.Supported in part by Grant MT-6349 of the Medical Research Council of Canada     

Management of ACTH-secreting supradiaphragmatic adenomas

Supradiaphragmatic adrenocorticotropic hormone (ACTH) secreting pituitary adenomas are exceptionally encountered (14 cases previously described) and raise issues concerning their nosology and management. If surgery is the treatment of choice, the nature of surgical approach (craniotomy, transsphenoidal approach) remains controversial. To illustrate this issue, we presented two cases of supradiaphragmatic ACTH secreting pituitary adenomas successfully excised via a subfrontal approach. Both patients were female (20 and 41 years) and had a typical Cushing's syndrome. MRI revealed, in both cases, a suprasellar mass in contact with the pars tuberalis of the pituitary. In the first case, the patient underwent initially a transsphenoidal approach with negative exploration and subsequent partial hypophysectomy. One year later, the patient was operated on again via a subfrontal approach, allowing excision of a supradiaphragmatic adenoma and a complete cure of Cushing's disease. In the second case, the patient underwent initially a subfrontal approach and was definitely cured. In both cases, the diaphragma sellae was found to be intact and the pituitary stalk could be preserved. Postoperative MRI demonstrated a clearly visible intact pituitary stalk in conjunction with normal aspect of the pituitary. Supradiaphragmatic pituitary adenomas are most likely adenomas of the pituitary stalk with extra-axial development. Surgery remains the treatment of choice. Should the superior approach be preferred, the transsphenoidal-transtuberculum sellae approach may represent a viable alternative when performed by a well-trained surgical team. Surgery may be difficult, and drawbacks are non negligible, particularly in elderly patients. In these cases, stereotactic radiosurgery should receive more consideration.     

Silent mixed corticotroph and somatotroph macroadenomas presenting with pituitary apoplexy

We discuss three unique cases of pituitary macroadenoma presenting with pituitary hemorrhage but without typical endocrine symptomatology. Immunohistochemical analysis indicated positive reactivity for adrenocorticotropic hormone (ACTH) and growth hormone (GH), and in situ hybridization indicated the expression of proopiomelanocortin (POMC) and GH mRNA. We designated these cases silent mixed corticotroph and somatotroph adenoma. Patient 1 was a 30-year-old man, patient 2 was a 29-year-old woman, and patient 3 was a 59-year-old woman. All patients presented with a headache of sudden onset and visual disturbance. The patients did not exhibit typical Cushing's or acromegalic features. Serum ACTH level was remarkably elevated in patient 1, and slightly elevated in patients 2 and 3. In all patients, serum GH levels were within normal range and magnetic resonance imaging revealed an intra- and suprasellar mass with pituitary hemorrhage. Transnasal pituitary surgery in the three patients disclosed a pituitary adenoma producing ACTH and GH. In patient 2, the residual adenoma reappeared along with an intratumoral hemorrhage, and was resected by secondary transnasal surgery. Silent mixed corticotroph and somatotroph adenomas are characterized by the following: no endocrine symptoms; presentation dominated by mass effect symptoms; macroadenoma presenting with acute pituitary hemorrhage; and production of both ACTH and GH.     

Ectopic pituitary adenoma. Case report and review of literature

Ectopic pituitary adenomas are very rare neoplasms. They are usually located in the sphenoid sinus or nasopharynx. Ectopic tumors derive from a residual pituitary fragment in the craniopharyngeal duct. They are similar in morphology, immunohistochemistry and hormonal activity to the typical pituitary adenoma. One third ectopic pituitary tumors reported in the literature are endocrine inactive, while the remaining ones indicate a hormonal activity and usually secrete ACTH, causing the Cushing disease. About 50% of pituitary adenomas are located at the skull base and present as aggressive neoplasms. The computed axial tomography (CAT) and magnetic resonance imaging (MRI) are very useful in revealing the presence of these tumors. Preoperative diagnosis of ectopic pituitary adenomas located at the skull base is difficult. Diagnostic procedures usually suggest another type of neoplasm, e.g. chordoma, nasopharyngeal carcinoma, or a metastatic tumor. Pathological examination including immunohistochemical studies of neuroendocrine markers is important in establishing the diagnosis. A unique case of ectopic, nonfunctioning pituitary adenoma involving the sphenoid sinus and nasopharynx and causing palsy of cranial nerves is presented. MRI examination revealed the presence of a large invasive tumor. The neoplasm was partially resected by transnasal approach. The diagnosis was confirmed by a pathological examination including immunohistochemical smears.     

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.     

Sellar gangliocytoma with adrenocorticotropic and prolactin adenoma

We report a case of a 60-year-old man who presented with weight gain, headaches, dizziness, erectile dysfunction and decreased libido. He was found to have elevated adrenocorticotropic hormone (ACTH) and prolactin serum levels. The imaging studies revealed a 1.4 cm sella/suprasellar mass which was compressing the optic chiasm. Histologic slides of the lesion showed a pituitary adenoma, marked by a proliferation of biphenotypic appearing cells, associated with a gangliocytoma, and marked by a proliferation of atypical appearing neuronal cells arranged against a glial-appearing background. Pituitary adenoma-gangliocytomas are benign combination tumors that rarely occur in the sellar region. Adenomas in this setting are sometimes functional, and rare patients with mixed adenomas (adenomas secreting more than one hormone) have been reported. To our knowledge, there has been only one other report of a combined ACTH and prolactin-producing adenoma with gangliocytoma, reported in a patient who also had acromegaly. In our patient, the immunohistochemical stains demonstrated that the bulk of the adenoma cells stained with prolactin antibody, and scattered clusters of cells within the adenoma stained positively for ACTH. The adenoma did not stain with antibodies to any of the other anterior pituitary hormones. Postoperatively, the elevated prolactin and ACTH levels returned to normal levels and there was no evidence of residual tumor. Adequate sampling and immunohistochemistry are important in rendering a correct diagnosis and in identifying the hormone status of mixed adenoma-gangliocytomas.     

亚临床型垂体腺瘤卒中的诊治

目的总结203例亚临床型垂体腺瘤卒中患者临床特点、诊断、处理与结果。方法回顾性分析亚临床型垂体腺瘤卒中病人203例,149例行经鼻蝶垂体腺瘤切除术,54例行开颅切除手术。患者术前术后均作内分泌学检查,影像学检查为cT或MRI。结果所有病人视觉损害、头痛或垂体功能得到不同程度改善。泌乳素腺瘤是本组病例中最常见病理类型。大腺瘤及巨腺瘤患者容易发生亚临床型垂体腺瘤卒中。术后随访有24例垂体腺瘤复发。19例接受放疗。9例术后长期服用甲状腺素替代药物,8例服用类固醇激素。结论亚临床型垂体腺瘤卒中的发病率比急性卒中高。亚临床型垂体腺瘤卒中的发病机制尚不清楚。磁共振优于cT诊断亚临床型垂体腺瘤卒中。经鼻蝶手术治疗亚临床型垂体腺瘤卒中安全有效。     

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.     

T cell lymphoblastic lymphoma/leukemia within an adrenocorticotropic hormone and thyroid stimulating hormone positive pituitary adenoma: A cytohistological correlation emphasizing importance of intra‐operative squash smear

We present a rare case of primary pituitary T cell lymphoma/leukemia (T‐LBL) in association with adrenocorticotropic hormone (ACTH) and thyroid stimulating hormone (TSH) expressing pituitary adenoma in a 55‐year‐old woman highlighting the importance of intra‐operative squash smears examination. The patient presented with complaints of headache, diminution of vision and recent onset altered sensorium. MRI revealed a mass lesion in the sellar‐suprasellar region with non‐visualization of pituitary gland separately, extending to involve adjacent structures diagnosed as invasive pituitary macroadenoma. Intra‐operative tissue was sent for squash smear examination. The cytology showed a tumor comprising of sheets of immature lymphoid cells intermixed with clusters of pituitary acinar cells with many mitoses and tingible body macrophages. A diagnosis of presence of immature lymphoid cells within the pituitary was offered and differentials of infiltration by lymphoma cells from systemic disease versus primary central nervous lymphoma‐like lymphoma arising in the pituitary adenoma were considered. Later paraffin section examination and immunohistochemistry corroborated with the squash findings and a final diagnosis of primary pituitary T cell lymphoma/leukemia in association with ACTH and TSH expressing pituitary adenoma was made. To date, only six cases of primary pituitary T cell lymphomas, including three T‐LBL cases, have been reported. This is the seventh case and first one additionally describing cytohistological correlation and importance of intra‐operative cytology.     

伽玛刀放射外科治疗垂体腺瘤的疗效评价

目的评价伽玛刀(Gamma Knife)放射外科治疗垂体腺瘤的疗效及安全性。方法对2010年1月~2013年12月期间采用OUR旋转式伽玛刀作为首选方法治疗的143例垂体腺瘤患者的临床资料进行回顾性研究,PRL型54例、GH型24例、ACTH型11例、混合型(GH+PPL)15例和无功能型(NFA)39例。肿瘤直径2 mm~64 mm(平均26.3 mm),30%~70%等剂量曲线包绕肿瘤,肿瘤平均周边剂量26.5Gy,平均中心剂量41.0Gy。对术后随访患者的临床症状、血液激素水平和鞍区MRI检查结果进行对比分析。结果随访期3~30个月,平均18月,临床症状改善或消失103例(72.0%),激素水平下降或恢复正常84例(80.8%),肿瘤缩小或消失87例(60.8%),平均肿瘤生长控制率为95.1%。结论伽玛刀放射外科对各种类型垂体腺瘤的治疗是安全有效的,能够改善和控制大部分患者的临床症状、激素水平和肿瘤生长。     

垂体ACTH腺瘤的诊断和治疗(附29例报告)

目的 分析和探讨垂体ACTH腺瘤的诊断和治疗。方法 对我科收治的29例垂体ACTH腺瘤患者的临床特点和治疗效果进行了回顾性分析。结果 垂体ACTH微腺瘤的诊断较为困难，有库欣氏综合征表现的患者，辅以血清ACTH、地塞米松抑制试验等并结合影像学资料方可确诊，经蝶手术切除肿瘤复发率仅为6．9％。结论 垂体ACTH腺瘤的诊断须依靠临床表现、实验室检查和影像学检查等。经蝶手术切除肿瘤是治疗垂体ACTH腺瘤的首选方法。     

儿童和青春期库欣病的诊断和治疗

目的 讨论20岁以下儿童和青春期库欣病的诊断和治疗。方法 男性11例，女性23例，平均年龄15.2岁，平均病程2.1年，表现库欣综合征占91.2%，内分泌学检查符合库欣病占70.6%。CT阳性率57.1%。MRI阳性率70%，均行经蝶窦手术，术后病理证实垂体ACTH腺瘤28例。垂体增生4例，病理阴性2例。结果 随诊3个月至10年，垂体ACTH腺瘤的治愈缓解率89.3%。垂体增生和病理阴性的治疗有效率为50%。结论 经蝶窦显微外科手术是治疗库欣病的最佳方法，当内分泌学检查符合库欣病但蝶鞍MRI未发现垂体腺瘤时，或者当蝶鞍MRI发现垂体腺瘤但内分泌学检查不符合库欣病时，应行经蝶窦垂体探查术。     

A neurological complication of inferior petrosal sinus sampling during investigation for Cushing's disease: a case report.

A 45 year old woman with hirsutism was found to have classic biochemical features of ACTH dependent Cushing''s disease, with partial cortisol suppression in response to dexamethasone. As no pituitary adenoma could be visualised by CT or MRI, she proceeded to bilateral simultaneous inferior petrosal sinus sampling before possible surgery. During the course of this procedure she had a stroke affecting the brainstem at the level of the pontocerebellar junction. This complication of petrosal sinus sampling has been previously described but is not widely recognised; the procedure should only be undertaken when results of less invasive tests are equivocal.     

神经内镜下双鼻孔入路垂体腺瘤切除术临床分析

目的总结分析内镜下双鼻孔经蝶入路垂体腺瘤切除术的经验和体会。方法回顾性分析60例内镜下双鼻孔经蝶入路垂体瘤切除术患者的临床资料,分析总结其疗效、并发症,总结该方法的优越性。结果 53例(88.3%)全切,6例(10.0%)次全切,1例(1.7%)部分切除。所有病例随访6～24个月,39例头痛症状明显缓解;27例视力、视野明显改善。术前泌乳素增高的26例中,16例术后降至正常,7例降低50%以上;生长激素增高的15例中,11例术后降至正常,2例降低50%以上。结论内镜下双鼻孔经蝶窦入路垂体腺瘤切除术,能够在有效的切除肿瘤组织,提高了切除率,降低了并发症的发生,临床应用前景好。     

垂体细胞增生所致库欣病术后复发的诊断和处理

目的讨论垂体细胞增生所致库欣病经蝶术后复发的诊断和处理。方法根据临床症状,内分泌学检查和蝶鞍区MRI检查,5例病人被诊断为垂体ACTH腺瘤而行经蝶手术,术后病理为垂体细胞增生。术后1例症状无改善,4例症状改善3～11个月后复发皮质醇增高为降低皮质醇例行垂体放疗和肾上腺切除术,。2,3例行肾上腺切除术。在肾上腺切除的例中例症状32再次复发复查,MRI发现垂体腺瘤并再次经蝶手术,术后病理为垂体腺瘤。结果随诊1～5年,行二次经蝶手术的2例病人皮质醇降至正常行垂体放疗和肾上腺切除术者因垂体功能低下用强的松替代治疗结论当垂体细胞增生病人术后症状复发影像学。检查发现垂体肿瘤时应再次经蝶手术没有发现垂体腺瘤时可行肾上腺切除和垂体放疗。     

侵袭性垂体腺瘤侵袭性的综合判断及其与临床预后的关系

目的分析经侵袭性垂体腺瘤侵袭性的判断标准及其与临床预后的关系。方法回顾性分析我科自2000年1月至2003年5月行经蝶手术切除的具有完整影像学、病理学和随访资料的侵袭性垂体腺瘤82例,随访时间5～30个月。结果侵袭性垂体腺瘤MR影像学特点为鞍底受侵下陷,部分肿瘤突入蝶窦;颈内动脉包绕;海绵窦受累,鞍隔突破等。病理检查以鞍底硬膜浸润的发生率最高。PRL腺瘤的全切率明显低于无功能腺瘤(P<0.01),无功能腺瘤、GH腺瘤与ACTH腺瘤之间相差不明显。PRL腺瘤的复发率较无功能腺瘤和GH腺瘤高(P<0.05)。结论垂体腺瘤的侵袭性生物学行为导致手术全切几率下降,是术后复发的主要原因。     

内镜经鼻垂体腺瘤切除术

目的 探讨内镜经鼻垂体腺瘤切除术的外科技术.方法 总结2003年9月至2006年3月100例内镜经鼻垂体腺瘤手术病人的临床资料.其中微腺瘤30例,大腺瘤35例,巨大腺瘤35例.功能性腺瘤68例,无功能性腺瘤32例.头痛82例,视力减退伴视野缺损76例,失明3例,闭经、泌乳36例,肢端肥大26例,垂体功能低下15例,其他症状者6例.结果 术中内镜下肿瘤全部切除93例,大部切除7例,7例均为质地硬韧的纤维型腺瘤.术后短暂性尿崩症32例;脑脊液鼻漏5例.术后随访平均28个月,肿瘤残余者10例;12例肿瘤复发,10例再次行经蝶手术,2例行开颅手术;术后内分泌症状改善不明显者,有11例行溴隐亭治疗,18例病人行伽玛刀治疗.结论 内镜经鼻垂体腺瘤切除术是一种安全、有效、微创的外科技术.