垂体生长激素瘤患者血清生长激素水平的改变及其与糖代谢异常的关系

目的 评价垂体生长激素瘤（GH-secreting pituitary adenoma）患者血清生长激素（GH）水平的改变及其与糖代谢异常的关系. 方法 检测GH-secreting pituitary adenoma （GH-secreting pituitary adenoma组）患者BP、血GH、IGF-1及泌乳素,并行75 g OGTT,计算ISI、稳态模型胰岛素抵抗指数（HOMA-IR）、葡萄糖及胰岛素曲线下面积（AUCg,AUCi）,将所得结果与垂体无功能瘤（NPA）组及糖代谢正常（NGT组）者进行比较. 结果 GH-secreting pituitary adenoma组血GH、IGF-1、IGF-1％及泌乳素高于其他两组（P＜0.01）.GH-secreting pituitary adenoma组IGR及糖尿病患病率高于NPA组及NGT组.GH-secreting pituitary adenoma组FPG、2 hPG高于NGT组,ISI则低于NGT组（P＜0.05或P＜0.01）;FIns、AUCg、AUCi及HOMA-IR高于其他两组（P＜0.05或P＜0.01）.根据75 g OGTT结果将GH-secreting pituitary adenoma组分为两亚组,高血糖亚组血GH高于血糖正常亚组.相关性分析结果显示,GH-secreting pituitary adenoma组血GH与FPG、2 hPG及AUCg呈正相关;IGF-1％与2hPG及AUCg呈正相关. 结论 GH-secreting pituitary adenoma患者高血糖患病率升高,且其原因与GH高分泌相关.     

Should aip gene screening be recommended in family members of FIPA patients with R16H variant?

Germline mutations of aryl-hydrocarbon-receptor interacting protein (AIP) are associated with pituitary adenoma predisposition. They occur in 20 % of familial isolated pituitary adenoma (FIPA) and in about 3–5 % of sporadic pituitary adenomas, especially in early onset somatotropinomas and prolactinomas. Our aim was to evaluate the clinical and genetic features of a large Italian FIPA family, where an AIP variant was identified. AIP direct sequencing from genomic DNA was carried out in 16 available family members. AIP R16H carriers also underwent magnetic resonance imaging and hormonal assessments. AIP mutations were also searched in 16 patients with sporadic growth hormone-secreting pituitary adenoma and in 6 unrelated patients in whom pituitary adenoma was excluded. We found an AIP R16H variation in two family members harbouring a pituitary adenoma and in 6 unaffected family members. No AIP mutation was found neither in growth hormone-secreting pituitary adenoma patients, nor in the unrelated patients without pituitary adenoma. We report a FIPA family harbouring an AIP R16H change, supporting the hypothesis that the latter represents a variant of unknown significance.     

Pituitary lymphoma developing within pituitary adenoma

Lymphoma occurring in the pituitary gland is an exceedingly infrequent event. Here, we describe a case of pituitary lymphoma complicating recurrent pituitary adenoma. A 56-year-old male with a history of pituitary adenoma was diagnosed with diffuse large B-cell lymphoma (DLBCL) of the left ocular adnexa, which was successfully treated by standard chemotherapy and local radiotherapy. Eight months later, he complained of diplopia and bitemporal hemianopia. Brain magnetic resonance imaging detected a suprasellar tumor. Transsphenoidal biopsy of the mass was performed, and histopathological examination revealed DLBCL admixed with pituitary adenoma. On a review of the literature, we found that pituitary lymphoma developing within adenoma is a recurrent phenomenon. The composite tumor is likely to be characterized by suprasellar involvement and presentation of visual disturbances. Moreover, in the present case, the suprasellar tumor remained visible after autologous peripheral stem cell transplant, likely due to the residual pituitary adenoma. We therefore recommend that refractory pituitary lymphoma should be vigorously biopsied in search of possibly underlying adenoma.     

垂体腺瘤合并Rathke囊肿27例并文献复习

目的分析垂体腺瘤合并Rathke囊肿的临床特征与治疗方法。 方法回顾性分析自2010年1月至2018年12月在哈尔滨医科大学附属第一医院神经外科二病房收治的27例行经鼻蝶窦入路手术切除垂体腺瘤合并Rathke囊肿患者的临床资料。所有患者均在术前、术后行垂体MRI检查及内分泌检查。由经验丰富的病理学专家对取出的标本作出病理诊断,以确保功能型垂体腺瘤的精确分类。观察患者术后的病情变化并且记录术后第1天和第7天的内分泌结果。结合27例垂体腺瘤合并Rathke囊肿的临床资料并结合相关文献进行分析。 结果垂体腺瘤合并Rathke囊肿的临床症状与垂体腺瘤类似;MRI在垂体区均发现两种质地不同的信号（一侧为实质性病变,一侧为囊性病变）,这两种信号之间有或无明显的间隔,且增强可见实性病变增强而囊性病变未增强;27例患者病变全切,术中可见实质性肿瘤和半流质Rathke囊肿内容物;随访期间,1例合并泌乳素型的垂体腺瘤患者复发,泌乳素增高,其余患者均未复发,且激素水平均恢复正常。 结论垂体腺瘤合并Rathke囊肿罕见,症状与垂体腺瘤相似,确诊依赖于病理。MRI垂体区囊性和实性病变共存,应考虑垂体瘤合并Rathke囊肿可能,经蝶窦入路切除术可有效治疗该病。     

Monosomy of chromosome 11 in pituitary adenoma in a patient with familial multiple endocrine neoplasia type 1

Multiple endocrine neoplasia type 1 (MEN 1) represents an endocrine syndrome characterized by complex pituitary, parathyroid and pancreatic neoplasia. Loss of heterozygosity of the specific region 11q13 has been reported in several tumours from patients with MEN 1 inherited disorder. We present a case of a young patient with familial MEN 1 syndrome with a pituitary adenoma exhibiting monosomy of chromosome 11. The patient presented with a large and rapidly growing pituitary adenoma associated with markedly elevated serum PRL levels, progressive bilateral visual loss and hydrocephalus. The resected adenoma was chromophobic, mainly PRL-producing and to a lesser degree immunoreactive for GH. Fluorescence in situ hybridization (FISH) using an alpha-satellite centromeric probe detected loss of one chromosome 11 copy in almost all pituitary adenoma cells. Clinical and biochemical studies revealed parathyroid hyperplasia and MRI studies detected a pancreatic tumour in addition to the pituitary adenoma. To our knowledge this is the first study reporting monosomy 11 in pituitary adenoma in a patient associated with familial MEN 1 syndrome.     

A null cell adenoma of the pituitary detected seven years after removal of a prolactinoma. Recurrence or de novo tumourigenesis?

We report an extremely unusual case of prolactinoma which emerged at recurrence as a null cell adenoma. A 53-year-old woman sought medical attention for progressive visual loss and headache. A pituitary tumour was detected by a computed tomographic scan, and hyperprolactinemia was noted. The tumour, removed by a transfrontal surgery, was a chromophobe adenoma, and immunohistochemically the adenoma cells were selectively positive for PRL, which indicated a prolactinoma. Postoperatively, her plasma PRL level was normalized. Seven years later, she noted blurred vision and again sought medical attention. A CT scan demonstrated recurrence of a pituitary tumour. On this occasion, however, she was not hyperprolactinemic. She underwent again a transfrontal resection of the pituitary tumour. Its histology was again a chromophobe adenoma, but the adenoma cells showed no positive immunostaining for any anterior pituitary hormone including PRL, which indicated a null cell adenoma. We have no clear explanation of the pathogenesis underlying her very unusual course. However, null cells (assuming that the original tumour was a mixed adenoma) left behind at the first surgery, or unidentified hypothalamic and/or pituitary derangements might possibly have been responsible for the recurrence. We learned from this patient that recurrent pituitary adenomas may not necessarily have the same endocrine features as did the original tumours. This information appears to make a valid clinical point, because if hormone levels alone are followed after pituitary surgery, recurrent pituitary tumours may be overlooked.     

Ultrastructural Characteristics of TSH-Producing Adenomas with Special Reference to its Close Similarity to BFA-Treated Pituitary Adenoma Cells

Two of 420 patients with pituitary adenoma who underwent operation from 1989 to 1997 had thyroid stimulating hormone (TSH) producing adenoma. We investigated these TSH cell adenomas with immunohistochemical and ultrastructural methods and compared their ultrastructural features with brefeldin A (BFA, 0.5 mg/ml) treated pituitary adenoma cells. BFA-treated pituitary adenomas include a prolactin (PRL) cell adenoma, a growth hormone (GH) cell adenoma, an adrenocorticotropic hormone (ACTH) cell adenoma, a gonadotroph adenoma, and a plurihormonal adenoma. Immunohistochemical staining disclosed that one of the TSH cell adenomas produced only TSH-;bgr and that another produces both TSH-b and FSH-b. Ultrastructural analysis showed the abundance of oval-shaped dilated rough endoplasmic reticulum (rER). Within the dilated rER, the mistlike deposit or deposit along the inner margin of the rER membrane was observed. On the other hand, BFA-treated cultured pituitary adenoma cells showed the opening of the cavity of the rER cisterna and they enlarged to an oval form with time and revealed an accumulation of electron-dense deposits within the dilated rER. These ultrastructural similarities between TSH cell adenoma and BFA-treated pituitary adenoma cells indicate the functional disturbances in the secretory passage through the Golgi apparatus in TSH cell adenoma cells.     

Cushing's syndrome with a large pituitary adenoma producing both corticotropin-releasing hormone (CRH) and adrenocorticotropin (ACTH)

A 57-year-old man showed high serum cortisol, plasma adrenocorticotropin (ACTH) and corticotropin-releasing hormone (CRH) levels with a large pituitary tumor and a prostatic cancer. High dose dexamethasone did not suppress cortisol secretion and CRH administration did not stimulate cortisol secretion. After surgical removal of the pituitary tumor, plasma CRH, ACTH and serum cortisol levels were normalized. Histological examinations showed pituitary adenoma and prostatic adenocarcinoma, and pituitary adenoma was stained with both anti-CRH and anti-ACTH antibodies, but prostatic cancer was not stained. A CRH-producing pituitary adenoma is a new type of Cushing's syndrome.     

Quality of Life in Patients with a Pituitary Adenoma

A validated quality of life (QOL) measure, the SF-36 questionnaire, was used to assess patients' perception of the impact of a pituitary adenoma, prior to treatment, on his or her physical and mental functioning. Of 270 new patients evaluated for pituitary disease at the University of Virginia Pituitary Clinic, 168 met the criteria for inclusion (pituitary hormone hypersecretion and/or pituitary adenoma) into this prospective study. Results of the SF-26 questionnaire in 36 patients with acromegaly, 42 patients with Cushing's disease, 39 patients with a prolactinoma and 51 patients with a non functioning macroadenoma prior to treatment were compared with those of the normal population; a comparison of results among patients with different types of pituitary adenomas was also performed. Patients with a pituitary adenoma had a significantly decreased QOL compared with the normal population in both physical and mental measures (p < 0.05). There were different degrees of perceived impairment depending on the type of pituitary adenoma. Patients with acromegaly had impairment in measures of physical function while patient with Cushing's disease had impairment in all but one measures compared with the normal population and with patients with other types of pituitary adenomas. Patients with a prolactinoma had impairment in mental measures and patients with a non-functioning adenoma had impairment in both physical and mental measures compared with the normal population. Patients with a pituitary adenoma have an impaired quality of life that should be routinely assessed in conjunction with endocrine and anatomic studies before and after treatment.     

Collision sellar lesions: experience with eight cases and review of the literature

The concomitant presence of a pituitary adenoma with a second sellar lesion in patients operated upon for pituitary adenoma is an uncommon entity. Although rare, quite a great variety of lesions have been indentified coexisting with pituitary adenomas. In fact, most combinations have been described before, but an overview with information on the frequency of combined pathologies in a large series has not been published. We present a series of eight collision sellar lesions indentified among 548 transsphenoidally resected pituitary adenomas in two Neurosurgical Departments. The histological studies confirmed a case of sarcoidosis within a non-functioning pituitary adenoma, a case of intrasellar schwannoma coexisting with growth hormone (GH) secreting adenoma, two Rathke’s cleft cysts combined with pituitary adenomas, three gangliocytomas associated with GH-secreting adenomas, and a case of a double pituitary adenoma. The pertinent literature is discussed with emphasis on pathogenetic theories of dual sellar lesions. Although there is no direct evidence to confirm the pathogenetic relationship of collision sellar lesions, the number of cases presented in literature makes the theory of an incidental occurrence rather doubtful. Suggested hypotheses about a common embryonic origin or a potential interaction between pituitary adenomas and the immune system are presented.     

垂体腺瘤患者的围手术期垂体激素监测及临床意义

为了对垂体腺瘤患者进行手术前后激素测定、分型、并监测术后垂体功能以及寻求一种判断手术切除程度及术后有无复发的方法，对50例垂体腺瘤手术患者采用放免法测定手术前、后激素水平，对测定值进行回顾性分析，判断检测结果的相互关系并分析其临床意义。结果：泌乳素(PRL)腺瘤及生长激素(GH)腺瘤全切组及末全切组术后激素水平均较术前明显降低(P＜0．05)，全切组术后激素水平与末全切组比较有明显差异(P＜0．05)。认为手术治疗可以明显改善垂体瘤患者术前高激素水平状态，手术治疗有着肯定的治疗价值。其切除程度将决定着术后内分泌的改善水平，应在不损害正常垂体前提下争取全切肿瘤。     

Corticotroph cell adenoma without typical manifestations of Cushing's disease presenting with cavernous sinus syndrome following pituitary apoplexy

This report presents a unique case of corticotroph cell adenoma in a 30-year-old man without acromegaly or features typical of Cushing's disease, who developed cavernous sinus syndrome following pituitary apoplexy. Magnetic resonance imaging revealed a large intrasellar/suprasellar mass with pituitary hemorrhage and extension of a hematoma to the anterior base of the skull. Urgent transnasal pituitary surgery revealed an acidophilic pituitary adenoma, with immunoreactivity for ACTH and GH and expression of proopiomelanocortin (POMC) and GH messenger ribonucleic acid (mRNA) demonstrated by in situ hybridization. To our knowledge, a silent corticotroph cell adenoma with GH production has never been reported. This type of adenoma may potentially enlarge and develop tumoral hemorrhage because it is free of endocrinological symptoms.     

Acromegaly with no pituitary adenoma and no evidence of ectopic source

More than 99% of patients with acromegaly harbor a growth hormone (GH) secreting pituitary adenoma. As the time from onset of signs/symptoms to diagnosis of acromegaly is long (symptom onset to diagnosis is often 4-10 years), pituitary adenomas that cause GH excess are often large and are nearly always visible on conventional magnetic resonance imaging (MRI). However, in rare circumstances, acromegalic patients without an ectopic source will not have imaging evidence of a pituitary adenoma. Management of these patients poses special challenge, and once ectopic source of GH/growth-hormone-releasing hormone (GHRH) is ruled out, an exploration of pituitary might be useful. We herein report a case of acromegaly with imaging evidence of sellar floor osteoma, but no pituitary adenoma, and negative work up for an ectopic source of GH/GHRH tumor, and on surgical exploration pituitary adenoma could be identified and removed and confirmed on histopathologic examination.     

Cushing's disease with cure by resection of a pituitary adenoma. Evidence against a primary hypothalamic defect

A patient with Cushing's disease was treated by transphenoidal resection of a pituitary adenoma. Pituitary-adrenal suppressibility, responsiveness to metyrapone and circadian rhythm were observed postoperatively. Reversion to physiologic regulation after resection of an adenoma implies that the lesion secreted ACTH autonomously (primary hyperpituitarism). Current evidence favors the pituitary adenoma, when present, as the primary etiologic factor in pituitary-dependent Cushing's syndrome. Since adenomas occur in a majority of cases, initial therapy is best directed at the pituitary.     

Coexistence of Thyrotropin-Producing Pituitary Adenoma with Papillary Adenocarcinoma of the Thyroid—A Case Report and Surgical Strategy

We report a very rare case of thyrotropin (thyroxin stimulating hormone, TSH)-producing pituitary adenoma coexisting with a papillary adenocarcinoma of the thyroid. A 45-year-old woman presented with hyperhidrosis and a nodule in the left thyroid that was first noticed one year earlier. An endocrinological examination showed elevated serum levels of free triiodothyronine (T3) and free throxin (T4) without inhibition of TSH, suggesting the presence of syndromes of inappropriate secretion of TSH. A specimen obtained by needle aspiration of the thyroid nodule revealed the presence of papillary adenocarcinoma. Magnetic resonance images demonstrated a pituitary macroadenoma.The patient was diagnosed as having a TSH-producing pituitary adenoma coexisting with a papillary adenocarcinoma of the thyroid. The patient underwent a total thyroidectomy with resection of the neighboring lymph nodes. Two weeks after this surgery, the pituitary adenoma was totally removed via a pterional approach. Histological and immunohistochemical examinations of the surgical specimens confirmed the lesion as a papillary adenocarcinoma of the thyroid and a TSH-producing pituitary adenoma. Serum TSH levels decreased to undetectable levels immediately after the surgery for the pituitary adenoma.Prolonged stimulation of the thyroid gland by TSH may be involved in the growth of thyroid carcinoma. In cases with a TSH-producing pituitary adenoma, the possible coexistence of thyroid carcinoma should be carefully ruled out. In such cases, a total thyroidectomy followed by TSH level normalization should be performed. Incomplete removal of the thyroid might enable the carcinoma to re-grow if TSH level can not be normalized after the pituitary adenomectomy.     

继发与不继发糖尿病的肢端肥大症型垂体腺瘤患者的临床比较分析

目的：比较分析继发与不继发糖尿病的肢端肥大症型垂体腺瘤患者的临床资料,初步探讨肢端肥大症垂体腺瘤继发糖尿病的可能病理免疫学机制。方法回顾性分析2008年1月至2013年6月济宁医学院附属医院神经外科采用单鼻孔直达蝶窦入路显微手术切除的84例肢端肥大症垂体腺瘤患者的临床资料,运用免疫化学发光法测定术前基础血生长激素（GH）水平,使用多田公式（xyz／2）计算MRI上肿瘤体积,采用免疫组织化学的方法检测肿瘤内分泌激素的表达,采用χ2或t检验比较继发与不继发糖尿病的肢端肥大症垂体腺瘤患者在发病年龄、性别、发病时间、瘤体大小、基础血GH水平以及肿瘤激素免疫反应等方面的差异。结果20例（24％）肢端肥大症垂体腺瘤患者继发糖尿病。继发和不继发糖尿病的肢端肥大症垂体腺瘤患者男女均可发病（χ2＝1.944,P＝0.163）,发病年龄多集中在41～50岁（P＝0.652）,MRI显示瘤体大小均有微腺瘤、大腺瘤、巨大腺瘤,差异均无统计学意义（P＝1.000）;发病时间分别集中在1～5年（55％）、6～10年（45％）,差异有统计学意义（P＝0.004）;术前基础血GH水平分别为（42.83±8.70）ng／ml、（38.91±36.46）ng／ml,差异有统计学意义（t＝5.253,P＝0.031）。继发糖尿病的肢端肥大症垂体腺瘤患者促甲状腺激素（TSH）免疫反应平均光密度值（0.545±0.023）明显高于不继发糖尿病者（0.408±0.019）,差异有统计学意义（t＝5.336,P＝0.001）;TSH免疫反应阳性率（70％）亦明显高于不继发糖尿病的肢端肥大症患者（14％）,差异有统计学意义（χ2＝23.971,P＝0.000）。结论继发与不继发糖尿病的肢端肥大症垂体腺瘤患者在发病年龄、性别、瘤体大小方面无明显差别,但二者在发病时间、术前基础血GH水平及肿瘤病理免疫反应方面存在明显差别,肿?     

An isolated pituitary metastasis as presentation of a differentiated hepatocellular carcinoma mimicking a nonfunctioning macroadenoma

The differential diagnosis of sellar masses may be complex. Metastatic disease constitutes 1% of all pituitary lesions and sometimes mimics the clinical-radiological presentation of pituitary adenoma. The definitive diagnosis usually relies on histology, but occasionally even histological features of pituitary metastasis may resemble those of adenomas. We present a patient initially diagnosed with pituitary adenoma, but whose clinical course finally revealed pituitary metastasis of a hepatocellular carcinoma. The existing literature on this topic is reviewed.     

Current perspectives on recurrent pituitary adenoma: The role and timing of surgery vs adjuvant treatment

The clinical course of pituitary adenoma can be highly variable. Aggressive pituitary tumours may require multimodal therapy with multiple operations. Even standard pituitary adenomas exhibit relatively high long-term recurrence rates and delayed intervention is often required. The indications for revision surgery in the endoscopic era are expanding for both functioning and nonfunctioning tumours, including access to the cavernous sinus and intracranial compartments. Although revision surgery can be challenging, it has been demonstrated to be both safe and effective. The question of the use of early radiotherapy in pituitary adenoma remains controversial. Our increasing understanding of pituitary tumour biology facilitates individualized treatment and surveillance protocols, with early intervention in high-risk adenoma subtypes. In this review, we discuss the treatment options for recurring pituitary tumours and focus on the role of revision surgery.     

Reduction of a pancreatic tumor after total removal of an ACTH secreting pituitary tumor: differential diagnosis of Cushing's syndrome

Endocrinologic tests sometimes fail to distinguish adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma from ectopic ACTH-secreting tumor. The authors experienced a case of Cushing's disease associated with a pancreatic tumor. Venous sampling contributed to the final diagnosis of Cushing's disease in this complex case, while endocrinologic tests showed paradoxical results. A 54-year-old woman presented with Cushing's syndrome and pancreatic tumor. Magnetic resonance imaging (MRI) failed to reveal a pituitary tumor, but a gadolinium-enhanced tumor with cystic components was seen in the pancreatic tail. Results of conventional endocrinologic tests suggested ectopic ACTH syndrome, but venous sampling including cavernous sinus sampling indicated an ACTH-secreting pituitary adenoma. Transsphenoidal surgery revealed a pituitary microadenoma, and total removal of the tumor was achieved. Postoperative abdominal MRI revealed that the pancreatic tumor diminished gradually without treatment. Selective cavernous sinus sampling was useful for distinguishing ACTH-secreting pituitary adenoma from ectopic ACTH syndrome in this complex case. This was a rare case in which the pancreatic tumor diminished after total removal of the ACTH-secreting pituitary adenoma.