Stereotactic radiosurgery for pituitary adenomas.

Pituitary adenoma is a radiosensitive disease and postoperative radiotherapy reduces the chance of relapse. Non-irradiated patients, followed in the modern era, suffer up to 20% five-year and up to 44% ten-year relapse. To some extent, predictors of relapse are available at the time of presentation or after surgery. Although conventionally fractionated radiotherapy has a very good track record with regard to controlling disease and safety in the modern age, there is considerable contemporary interest in the technique of radiosurgery (highly concentrated radiation therapy using stereotactic mapping). The usefulness of this technique in the treatment of pituitary adenoma is discussed in this review.     

Gamma knife radiosurgery for pituitary adenomas

Although surgical extirpation by transsphenoidal microsurgery is a major remedy for pituitary adenomas, adjuvant therapy also plays an important role in achieving tumor growth control and endocrine normalization in hormone-secreting tumors. Historically, the treatment options for pituitary adenomas included microsurgery, medical management, and fractionated radiotherapy, but radiosurgery has recently emerged as a practical treatment option. In this paper, we will describe the indications, radiosurgical procedure, results, histological change, and complications of gamma knife radiosurgery (GKS) for pituitary adenomas based on our experience since 1991 and a review of the literature.     

Stereotactic conformal radiotherapy for pituitary adenomas: technique and preliminary experience

OBJECTIVE: Stereotactic conformal radiotherapy (SCRT) is a high precision technique of fractionated radiotherapy which ensures accurate delivery of radiation with reduction in the volume of normal tissue irradiated as compared to conventional external beam radiotherapy. We describe the technique and preliminary experience of SCRT in patients with residual and recurrent pituitary adenomas. PATIENTS AND METHODS: Between February 1995 and March 1999, 22 patients (mean age: 45.3, range: 20-67 years) with residual or recurrent pituitary adenomas (13 nonfunctioning, nine secretory) were treated with SCRT. All were immobilized in a relocatable Gill-Thomas-Cosman (GTC) frame and tumour was localized on a postcontrast planning computerized tomography (CT) and MRI scan. The gross tumour volume (GTV) and the critical structures were outlined on contiguous 2-3 mm separated slices. A margin of 5 mm (12 patients) to 10 mm (10 patients) was grown around GTV in three-dimensions (3-D) to generate the planning target volume (PTV). The treatment was delivered by three (five patients) and four (17 patients) maximally separated conformal fixed fields with each field conformed to the shape of the tumour using customized lead alloy blocks (19 patients) or multileaf collimator (three patients). The patients were treated on a 6-MV linear accelerator to a dose of 45 Gy in 25 fractions (18 patients) and 50 Gy in 30 fractions (four patients). RESULTS: The technique of SCRT has become a part of the routine work of the radiotherapy department. The treatment was well tolerated with minimal acute toxicity. One patient developed transient quadrantanopia 2 weeks after treatment with full recovery after a short course of corticosteroids. One patient had a transient visual deterioration 7 months after treatment due to cystic degeneration of the tumour which fully recovered following surgical decompression. Nine of the 15 patients presenting with visual impairment had improvement after treatment and the visual status remained stable in all others. One patient with acromegaly and one with a prolactinoma achieved normalization of elevated hormonal abnormality four and 10 months after SCRT, respectively. The remaining seven patients with a secretory adenoma had declining hormone levels at last follow-up. Newly initiated hormone replacement therapy was required in five patients. At a median follow-up of 9 months (range 1-44 months), the 1 and 2 year actuarial progression free and overall survival were 100%. CONCLUSION: Stereotactic conformal radiotherapy is a high precision technique suitable for the treatment of pituitary adenomas requiring radiotherapy. Preliminary results suggest effective tumour control and low toxicity within the range expected for conventional external beam radiotherapy. While the technique is of potential benefit in reducing the volume of normal brain irradiated, the advantages in terms of sustained tumour control and reduced toxicity over conventional radiotherapy need to be demonstrated in long-term prospective studies.     

Stereotactic radiosurgery for treatment of Cushing disease: an Australian experience

Stereotactic radiation therapy has emerged as an alternative to conventional radiotherapy for treatment of Cushing disease. The aim of this study was to investigate the efficacy and safety of this treatment. Records of patients with Cushing disease treated with stereotactic radiation were reviewed. Seventeen patients underwent stereotactic radiosurgery. Ten achieved remission after a mean of 23 (95% confidence interval, 15–31) months, and two developed hormone deficiencies.     

立体定向放射外科治疗硬脑膜动静脉瘘

目的评估立体定向放射外科治疗硬脑膜动静脉瘘的安全性和有效性。方法采用伽玛刀治疗硬脑膜动静脉瘘16例，其中单纯伽玛刀治疗7例，经动脉途径栓塞或手术治疗后再行伽玛刀治疗9例。根据Congard分型，硬脑膜动静脉瘘Ⅰ型4例，Ⅱa型5例，Ⅱa b型3例，Ⅲ型3例，Ⅳ型1例。靶点边缘剂量16～20Gy，平均18Gy，靶点边缘被50％～70％等剂量曲线所包含。所有患者均获得随访，随访时间为5～108个月。结果14例患者术后症状消失，2例部分改善。12例MRI或造影证实瘘口完全或近全闭塞，4例部分闭塞。无放射治疗导致的并发症。结论立体定向放射外科是一种治疗硬脑膜动静脉瘘安全、有效的方法。对侵袭型硬脑膜动静脉瘘且伴有广泛皮质静脉引流的患者，血管内治疗或手术治疗结合放射外科是一种有效的治疗模式。     

Endocrine disorders after primary gamma knife radiosurgery for pituitary adenomas: A systematic review and meta-analysis

Pituitary - Gamma Knife radiosurgery (GKRS) is feasible for pituitary adenomas, but post-surgery GKRS may cause severe hormone deficits. We reviewed the literature on primary GKRS for pituitary...     

巨大垂体腺瘤的显微手术治疗

为提高巨大垂体腺瘤显微手术的疗效 ,回顾性分析 5 6例巨大垂体腺瘤患者的临床资料及治疗方法。依据肿瘤的生长方向及部位将 5 6例分为四型 ,据此分别采用经蝶、经额下、额下经蝶、扩大经蝶、扩大额下硬膜外、额下 -翼点等 10种入路进行显微手术。5 6例巨大垂体腺瘤全切 2 9例 ,近全切 2 0例 ,大部切除 7例。无死亡者。提示依据巨大垂体腺瘤的不同位置及生长方向选择适当的手术入路是提高全切率、降低死亡率及复发率的重要手段     

Diagnosis and treatment of pituitary adenomas

Pituitary tumors cause symptoms by secreting hormones (prolactin, PRL, responsible for amenorrhea-galactorrhea in women and decreased libido in men; growth hormone, GH, responsible for acromegaly; adrenocorticotropic hormone, ACTH, responsible for Cushing's syndrome; thyroid-stimulating hormone, TSH, responsible for hyperthyroidism), depressing the secretion of hormones (hypopituitarism), or by mass-related effects (headaches, visual field abnormalities...). All patients with pituitary tumors should be evaluated for gonadal, thyroid and adrenal function as well as PRL and GH secretion. Specific stimulation and suppression tests for pituitary hormones are performed in selected situations for detecting the type of hypersecretion or the response to treatment. Imaging procedures (mainly magnetic resonance imaging, MRI, nowadays) determine the presence, size and extent of the lesion. The classification of pituitary tumors is based on the staining properties of the cell cytoplasm viewed by light microscopy and immunocytochemistry revealing the secretory pattern of the adenoma. Treatment of pituitary adenomas consists of surgery (performed in more than 99% of cases via a transphenoidal route) and radiotherapy, generally fractionated or, in selected cases, using stereotactic techniques such as gamma-knife. The availability of medical treatment (dopamine, DA, agonists, somatostatin analogs, GH-receptor antagonists...) has profoundly modified the indications of radiotherapy, drugs being now generally used as a second-line treatment, after surgery (or even as first-line treatment). Based on the results of the different treatment modalities for each type of pituitary adenoma, recommendations will be proposed. They may be summarized as follows. For treatment of GH-secreting adenomas, trans-sphenoidal surgery is the first-line therapy except when the macroadenoma is giant or if surgery is contra-indicated; postoperative radiation therapy (fractionated, or by gamma-knife) is performed for partially resected tumors or when GH levels remain elevated (eventually after a trial of somatostatin analog). Somatostatin analogs, now available in slow release form, are proposed when surgery is contra-indicated, or has failed to normalize GH levels, or in waiting for the delayed effects of radiation therapy. If the probability of surgical cure is low (e.g. in patients with very large and/or invasive tumors), then somatostatin analogs may be reasonable primary therapeutic modality provided that the tumor does not threaten vision or neurological function. Pegvisomant, the new GH-receptor antagonist, is indicated in case of resistance to somatostatin analogs. Patients with PRL-secreting microadenomas may be treated either with trans-sphenoidal surgery or medically with DA agonists. In patients with macroadenomas, even in the presence of chiasmatic syndrome, DA agonists are now proposed as primary treatment. Indeed, effects on visual disturbances are often very rapid (within a few hours or days) and tumoral shrinkage is usually very significant. For patients with ACTH-secreting adenomas, primary therapy is generally trans-sphenoidal surgery by a skilled surgeon, whether or not a microadenoma is visible on MRI. Radiotherapy is reserved for patients who are subtotally resected or remain hyper-secretory after surgery. In waiting for the effects of radiotherapy, adrenal steroidogenesis inhibitors (mitotane, ketoconazole) may be indicated. If drugs are not available or not tolerated, bilateral adrenalectomy may be proposed. For patients with clinically non functioning adenomas (generally gonadotropin-secreting adenomas on immunocytochemistry), trans-sphenoidal surgery with or without postoperative radiation therapy is performed for almost all patients whether or not they have visual consequences of their tumor. Selected patients with small, incidentally discovered microadenomas may be carefully followed without immediate therapy.     

Surgical treatment of aggressive pituitary adenomas and pituitary carcinomas

Surgery of aggressive pituitary adenomas and pituitary carcinomas is part of the interdisciplinary management of these difficult to treat tumors. Invasion, giant size and unusual, asymmetric extent of these tumors frequently require modifications or extensions of the standard approaches for transsphenoidal and transcranial surgery. Frequently, only debulking procedures can be performed. In aggressive and hormone secreting adenomas, the remission rates achieved by surgery alone are relatively poor and adjuvant medical treatments or irradiation are needed. Safe resection of as much tumor as possible and symptomatic control is aimed at, rather than remission. Many procedures are required for rapid progression of lesions or recurrences, in order to extend the survival of the patients. Metastases of pituitary carcinomas within the cranial cavity or spine can be attacked. Since they can occur anywhere in the brain or spinal canal they require the entire battery of neurosurgical approaches. Unfortunately, in this group of pituitary tumors, the complication rates are higher than in primary operations of enclosed adenomas. The respective techniques with their facilities and limitations are reviewed in this article.

     

Glycoprotein-secreting pituitary adenomas: pathogenesis, diagnosis and treatment

The glycoprotein-secreting pituitary adenomas comprise two distinctive clinical and pathological entities, the gonadotroph and the thyrotroph cell pituitary adenomas. Although they can be grouped together for producing hormones and/or subunits that are glycoproteins, these tumors originate from distinctive cell types (gonadotrophes and thyrotrophes) that are only remotely related. Gonadotroph cell adenomas are among the commonest types of pituitary adenomas, corresponding to the majority of the so-called "nonfunctioning" or clinically silent adenomas, while thyrotroph cell adenomas are extremely rare and usually present with hyperthyroidism due to inappropriate TSH secretion. In this article, we review the literature covering epidemiological, pathological, pathogenetic, clinical, diagnostic and therapeutic aspects of gonadotroph and thyrotroph cell adenomas. Greater emphasis was given to the growing field of molecular pathogenesis of pituitary tumors in general, and a special effort was made to contrast molecular alterations found in these tumors with other tumor types. On the practical side, the authors extensive experience for more than two decades in the diagnosis and management of these tumors at the Neuroendocrine Unit (Endocrinology Division, Unifesp) was used to balance the extensive literature on this subject.     

老年人垂体腺瘤的手术治疗

目的：探讨显微外科治疗老年人垂体腺瘤的临床综合疗效，以选择对该类型肿瘤的最佳手术方法。方法：回顾性分析显微手术治疗的老年人垂体腺瘤190例，将其分为经蝶手术组和经颅手术组，对肿瘤的手术切除率、术后并发症、术后随访进行对比分析。结果：经蝶组158例，肿瘤全切除112例(71．0％)，次全切除30例，部分切除16例；经颅组32例，全切除8例(25．0％)，次全切除16例，部分切除8例。经蝶组住院时间短，治疗费用较少，手术后生活质量较高。结论：经蝶显微手术可作为大多数老年垂体腺瘤患者的首选手术方法。     

Radiosurgery for pituitary adenomas

Pituitary adenomas represent nearly 15% of all intracranial tumors. Multimodal treatment includes microsurgery, medical management and radiotherapy. Microsurgery is the primary recommendation for nonfunctioning and most of functioning adenomas, except for prolactinomas that are usually managed with dopamine agonist drugs. However, about 30% of patients require additional treatment after microsurgery for recurrent or residual tumors. In these cases, fractionated radiation therapy has been the traditional treatment. More recently, radiosurgery has been established as a treatment option. Radiosurgery allows the delivery of prescribed dose with high precision strictly to the target and spares the surrounding tissues. Therefore, the risks of hypopituitarism, visual damage and vasculopathy are significantly lower. Furthermore, the latency of the radiation response after radiosurgery is substantially shorter than that of fractionated radiotherapy. The goal of this review is to define the efficacy, safety and role of radiosurgery for treatment of pituitary adenomas and to present the preliminary results of our institution.     

Management of aggressive pituitary adenomas: current treatment strategies

Aggressive pituitary adenomas are notoriously difficult to manage due to their size, invasiveness, speed of growth and high frequency of recurrence. Except for prolactinomas, surgery (usually transsphenoidal but sometimes transcranial) is the first-line option, but re-growth of aggressive tumors is almost inevitable and monitoring and repeat surgery is required to control symptoms. In prolactinomas, dopamine agonists are the first-line treatment and they normalize prolactin levels in most patients even with macroprolactinomas. Somatostatin analogues offer another pharmacotherapy for pituitary adenomas either for primary therapy, pre-operatively to reduce the tumor volume and make it more amenable to surgical removal, or post-surgery to control re-expansion. When surgery and pharmacotherapy fail, radiotherapy is a useful third-line strategy that reduces recurrence, while extreme pituitary adenomas with metastases may potentially be managed with chemotherapy (although more data are needed). A combination of these therapies will be required for aggressive pituitary adenomas and careful follow-up is essential.     

Advances in pharmacological treatment of pituitary adenomas

In last years, advances in endocrinological and neuroradiological research have lead to an earlier recognition and more effective management of pituitary tumours. At the same time, pharmacological investigation has allowed the development of useful drugs in the treatment of pituitary adenomas, either as an exclusive therapy or as an aid to surgery and radiotherapy. In this article we review indications and dosage of recently developed drugs for different types of hormone-secreting pituitary adenomas.     

Bromocriptine treatment of prolactin-secreting pituitary adenomas may restore pituitary function

Six men with prolactin-secreting pituitary macroadenomas and deficiencies of pituitary hormones other than gonadotrophins were treated with bromocriptine for 6 months. During treatment the serum prolactin concentration decreased markedly in all six patients, and in four adenoma size decreased and visual function improved. Two patients who were hypothyroid before bromocriptine treatment were euthyroid during the sixth month of treatment, and the one patient who was hypoadrenal before treatment was euadrenal during treatment. Two of the six men who had subnormal growth hormone secretion before treatment had normal growth hormone secretion during treatment. We conclude that pituitary hormonal functions may improve during bromocriptine treatment for prolactin-secreting pituitary macroadenomas. This improvement may result from decompression of other pituitary cells, because correction of hypothyroidism by bromocriptine was accompanied by conversion from an absent to a normal thyrotrophin response to thyrotrophin-releasing hormone.     

经蝶入路显微外科治疗老年人垂体腺瘤

目的探讨老年人垂体腺瘤（ＳＰＡ）的手术疗效。方法总结经ＣＴ扫描或ＭＲＩ确诊的５６例ＳＰＡ经蝶显微外科治疗的临床资料，３５例经唇下－鼻中隔－蝶窦入路、２１例经鼻前庭－鼻中隔－蝶窦入路行肿瘤切除术。结果本组微腺瘤７例，大腺瘤３０例，巨大腺瘤１９例，术后无死亡。４８例获长期随访（平均３．５年），４１例恢复良好；７例术后平均３．４年肿瘤复发，其中２例再次手术，５例采用药物、放疗或放射外科治疗，于３个月时复查见患者恢复较为满意。结论采取经蝶显微外科治疗ＳＰＡ，是一种安全、有较的方法