Sample records for experimental pituitary tumor

  1. Pituitary Tumors (United States)

    ... Health and Human Development (NICHD) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) See all related organizations Publications Tumores de la glándula pituitaria Order NINDS Publications Definition The pituitary is a small, bean-sized gland ...

  2. Pituitary Tumors: Condition Information (United States)

    ... not they spread beyond the pituitary gland: 2 Pituitary adenomas (pronounced ad-n-OH-muhz ) are benign, meaning ... tumors fall into this category. Despite being benign, pituitary adenomas can make the pituitary gland produce too much ...

  3. Pituitary Tumors (United States)

    ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ...

  4. Pituitary Tumors (United States)

    ... and Conditions Adrenal Disorders Osteoporosis and Bone Health Children and Teen Health Diabetes Heart Health Men's Health Rare Diseases Pituitary Disorders Thyroid Disorders Transgender Health Obesity and Weight Management Women's Health You ...

  5. Pituitary tumors containing cholecystokinin

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    Rehfeld, J F; Lindholm, J; Andersen, B N


    We found small amounts of cholecystokinin in the normal human adenohypophysis and therefore examined pituitary tumors from 87 patients with acromegaly, Cushing's disease, Nelson's syndrome, prolactinoma, or inactive pituitary adenomas. Five adenomas associated with Nelson's syndrome contained......'s disease and 7 acromegaly with adenomas containing ACTH. The cholecystokinin peptides from the tumors were smaller and less sulfated than cholecystokinin from normal pituitary glands. We conclude that ACTH-producing pituitary cells may also produce an altered form of cholecystokinin....

  6. Pituitary tumors containing cholecystokinin

    DEFF Research Database (Denmark)

    Rehfeld, J F; Lindholm, J; Andersen, B N


    We found small amounts of cholecystokinin in the normal human adenohypophysis and therefore examined pituitary tumors from 87 patients with acromegaly, Cushing's disease, Nelson's syndrome, prolactinoma, or inactive pituitary adenomas. Five adenomas associated with Nelson's syndrome contained...... increased amounts of cholecystokinin, the concentrations being extremely high in two: 8281 and 13,453 pmol per gram as compared with less than 30 pmol per gram in normal pituitary glands. The cholecystokinin concentrations were moderately increased in adenomas from another 12 patients, of whom 5 had Cushing...

  7. Pituitary gland tumors; Hypophysentumoren

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    Jesser, J.; Schlamp, K.; Bendszus, M. [Radiologische Klinik, Universitaetsklinikum Heidelberg, Abteilung fuer Neuroradiologie, Heidelberg (Germany)


    This article gives an overview of the most common tumors of the pituitary gland and the differential diagnostics with special emphasis on radiological diagnostic criteria. A selective search of the literature in PubMed was carried out. Pituitary adenomas constitute 10-15 % of all intracranial tumors and are the most common tumors of the sellar region. Tumors smaller than 1 cm in diameter are called microadenomas while those larger than 1 cm in diameter are called macroadenomas. Approximately 65 % of pituitary gland adenomas secrete hormones whereby approximately 50 % secrete prolactin, 10 % secrete growth hormone (somatotropin) and 6 % secrete corticotropin. Other tumors located in the sella turcica can also cause endocrinological symptoms, such as an oversecretion of pituitary hormone or pituitary insufficiency by impinging on the pituitary gland or its stalk. When tumors spread into the space cranial to the sella turcica, they can impinge on the optic chiasm and cause visual disorders. A common differential diagnosis of a sellar tumor is a craniopharyngeoma. In children up to 10 % of all intracranial tumors are craniopharyngeomas. Other differential diagnoses for sellar tumors are metastases, meningiomas, epidermoids and in rare cases astrocytomas, germinomas or Rathke cleft cysts As these tumors are located in an anatomically complex region of the skull base and are often very small, a highly focused imaging protocol is required. The currently favored modality is magnetic resonance imaging (MRI) with the administration of a contrast agent. The sellar region should be mapped in thin slices. In cases of suspected microadenoma the imaging protocol should also contain a sequence with dynamic contrast administration in order to assess the specific enhancement characteristics of the tumor and the pituitary gland. (orig.) [German] Diese Arbeit ist eine Uebersicht ueber die haeufigsten Hypophysentumoren und deren Differenzialdiagnosen mit Augenmerk auf die

  8. Non-functioning pituitary tumors: 2012 update. (United States)

    Cámara Gómez, Rosa


    Non-functioning pituitary adenomas are the most common pituitary macroadenomas in adults, accounting for approximately 14%-28% of all clinically relevant pituitary tumors. They are a heterogeneous group of tumors that cause symptoms by compression and/or hormone deficiencies. The possibility of tumor growth is increased in macroadenomas and solid tumors as compared to microadenomas and cystic tumors. Diagnosis is based on imaging procedures (magnetic resonance imaging), but there are studies reporting promising potential biomarkers. Transsphenoidal surgery remains the first therapeutic option for large tumors with compressive symptoms. There is no evidence that endoscopic procedures improve outcomes, but they decrease morbidity. There is no unanimity in finding prognostic predictors of recurrence. Radiosurgery achieves tumor control and, sometimes, adenoma size reduction. Its adverse effects increase with higher doses and tumor sizes>4cm(3). Drug treatment is of little value. In aggressive non-functioning tumors, temozolomide (TMZ) may be used with caution because no controlled studies are available. TMZ achieves tumor control in 38%-40% of aggressive non-functioning tumors. The optimal treatment regimen and duration have not been defined yet. Lack of response to TMZ after 3 cycles predicts for treatment resistance, but initial response does not ensure optimal mid or long-term results. O6-methylguanine-DNA methyltransferase expression has a limited predictive value of response to treatment with TMZ in aggressive non-functioning tumors. It should therefore not be a determinant factor in selection of patients to be treated with TMZ. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  9. Management of incidental pituitary tumors

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    Nicholas F. Marko


    Full Text Available Pituitary incidentalomas are common lesions for which neurosurgical referrals may become progressively more frequent, given the increasing application of neuroimaging. The initial evaluation of a patient with radiographic evidence of an incidentaloma should focus on addressing two questions: (1 is the lesion causing neurological symptoms, and (2 is the lesion hormonally active? The answers to these two questions provide a framework for subsequent clinical management. The initial patient assessment should include a detailed history and physical examination, including the bedside assessment of visual fields. High-quality MRI imaging is essential, and formal visual field testing should be obtained in patients where the lesion abuts or compresses the optic apparatus. The initial biochemical workup is intended to assess potential pituitary hypo- or hyperfunction and should include measurement of serum levels of prolactin, insulin-like growth factor type-1, free thyroxine, testosterone, and an assessment of axis hypothalamic–pituitary–adrenal axis function. Additional testing may include serum thyroid-stimulating hormone, follicle-stimulating hormone, and luteinizing hormone levels. Neurologically-asymptomatic patients without endocrine dysfunction can be managed with observation at regular intervals, including MRI imaging at 6 months and 1 year and then annually for a period of 3 years. Follow-up biochemical assessment is not necessary in the absence of clinical symptoms or radiographic enlargement of the lesion. After 3 years the follow-up interval may be prolonged, although closer follow-up may be indicated for patients with lesions C1 cm. Most patients who either present with or who subsequently develop neurologic or endocrinologic symptoms should be considered for surgery as the first-line therapy.

  10. Autocrine IL-6 mediates pituitary tumor senescence (United States)

    Fuertes, Mariana; Ajler, Pablo; Carrizo, Guillermo; Cervio, Andrés; Sevlever, Gustavo; Stalla, Günter K.; Arzt, Eduardo


    Cellular senescence is a stable proliferative arrest state. Pituitary adenomas are frequent and mostly benign, but the mechanism for this remains unknown. IL-6 is involved in pituitary tumor progression and is produced by the tumoral cells. In a cell autonomous fashion, IL-6 participates in oncogene-induced senescence in transduced human melanocytes. Here we prove that autocrine IL-6 participates in pituitary tumor senescence. Endogenous IL-6 inhibition in somatotroph MtT/S shRNA stable clones results in decreased SA-β-gal activity and p16INK4a but increased pRb, proliferation and invasion. Nude mice injected with IL-6 silenced clones develop tumors contrary to MtT/S wild type that do not, demonstrating that clones that escape senescence are capable of becoming tumorigenic. When endogenous IL-6 is silenced, cell cultures derived from positive SA-β-gal human tumor samples decrease the expression of the senescence marker. Our results establish that IL-6 contributes to maintain senescence by its autocrine action, providing a natural model of IL-6 mediated benign adenoma senescence. PMID:27902467

  11. Endoscopic transnasal approach for removing pituitary tumors

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    Mirian Cabral Moreira de Castro


    Full Text Available To describe a series of 129 consecutive patients submitted to the resection of pituitary tumors using the endoscopic transsphenoidal approach in a public medical center. Method: Retrospective analysis based on the records of patients submitted to the resection of a pituitary tumor through the endoscopic transsphenoidal approach between 2004 and 2009. Results: One hundred and twenty-nine records were analyzed. The tumor was non-secreting in 96 (74.42% and secreting in 33 patients (22.58%. Out of the secretory tumors, the most prevalent was the growth hormone producer (7.65%, followed by the prolactinoma, (6.98%. Eleven patients developed cerebral spinal fluid (CSF fistulas, and four of them developed meningitis. One patient died due to intracerebral hemorrhage in the postoperative period. Conclusion: The endoscopic transsphenoidal approach to sellar tumors proved to be safe when the majority of the tumors were non-secreting. The most frequent complication was CSF. This technique can be done even in a public hospital with financial limits, since the health professionals are integrated.

  12. Pituitary tumor apoplexy Apoplexia em tumor hipofisário

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    Claudia V. Chang


    Full Text Available Pituitary tumor apoplexy is a medical emergency due to acute infarction or hemorrhage in the pituitary gland. In this review, the authors discuss the sellar anatomy, the pituitary gland and adenomas' vascularization and the general aspects of the syndrome such as its ethiopatogenesis, predisposing factors, clinical features, treatment and prognosis.A apoplexia em tumor hipofisário é uma emergência médica decorrente do infarto agudo ou hemorrágico na glândula hipófise. Nesta revisão os autores discutem a anatomia da região selar, a vascularização da hipófise e adenomas hipofisários, e demais aspectos da síndrome como etiopatogenia, fatores predisponentes, quadro clínico, tratamento e prognóstico.

  13. Dopamine receptor expression and function in corticotroph pituitary tumors

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    R. Pivonello (Rosario); S.W.J. Lamberts (Steven); D. Ferone (Diego); W.W. de Herder (Wouter); J.M. Kros (Johan); M.L. de Caro; M. Arvigo; L. Annunziato; G. Lombardi (Gaetano); A. Colao (Annamaria); L.J. Hofland (Leo)


    textabstractThe role of dopamine agonist treatment in corticotroph pituitary tumors is controversial. The aim of this study was to evaluate D(2) receptor expression in 20 corticotroph pituitary tumors and to correlate it to the in vitro effect of dopamine agonists on ACTH secretion

  14. Pituitary tumors in patients with MEN1 syndrome

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    Luis V. Syro


    Full Text Available We briefly review the characteristics of pituitary tumors associated with multiple endocrine neoplasia type 1. Multiple endocrine neoplasia type 1 is an autosomal-dominant disorder most commonly characterized by tumors of the pituitary, parathyroid, endocrine-gastrointestinal tract, and pancreas. A MEDLINE search for all available publications regarding multiple endocrine neoplasia type 1 and pituitary adenomas was undertaken. The prevalence of pituitary tumors in multiple endocrine neoplasia type 1 may vary from 10% to 60% depending on the studied series, and such tumors may occur as the first clinical manifestation of multiple endocrine neoplasia type 1 in 25% of sporadic and 10% of familial cases. Patients were younger and the time between initial and subsequent multiple endocrine neoplasia type 1 endocrine lesions was significantly longer when pituitary disease was the initial manifestation of multiple endocrine neoplasia type 1. Tumors were larger and more invasive and clinical manifestations related to the size of the pituitary adenoma were significantly more frequent in patients with multiple endocrine neoplasia type 1 than in subjects with non-multiple endocrine neoplasia type 1. Normalization of pituitary hypersecretion was much less frequent in patients with multiple endocrine neoplasia type 1 than in subjects with non-multiple endocrine neoplasia type 1. Pituitary tumors in patients with multiple endocrine neoplasia type 1 syndrome tend to be larger, invasive and more symptomatic, and they tend to occur in younger patients when they are the initial presentation of multiple endocrine neoplasia type 1.

  15. Recent Progress in the Medical Therapy of Pituitary Tumors

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    Fabienne Langlois


    Full Text Available Management of pituitary tumors is multidisciplinary, with medical therapy playing an increasingly important role. With the exception of prolactin-secreting tumors, surgery is still considered the first-line treatment for the majority of pituitary adenomas. However, medical/pharmacological therapy plays an important role in controlling hormone-producing pituitary adenomas, especially for patients with acromegaly and Cushing disease (CD. In the case of non-functioning pituitary adenomas (NFAs, pharmacological therapy plays a minor role, the main objective of which is to reduce tumor growth, but this role requires further studies. For pituitary carcinomas and atypical adenomas, medical therapy, including chemotherapy, acts as an adjuvant to surgery and radiation therapy, which is often required to control these aggressive tumors. In the last decade, knowledge about the pathophysiological mechanisms of various pituitary adenomas has increased, thus novel medical therapies that target specific pathways implicated in tumor synthesis and hormonal over secretion are now available. Advancement in patient selection and determination of prognostic factors has also helped to individualize therapy for patients with pituitary tumors. Improvements in biochemical and “tumor mass” disease control can positively affect patient quality of life, comorbidities and overall survival. In this review, the medical armamentarium for treating CD, acromegaly, prolactinomas, NFA, and carcinomas/aggressive atypical adenomas will be presented. Pharmacological therapies, including doses, mode of administration, efficacy, adverse effects, and use in special circumstances are provided. Medical therapies currently under clinical investigation are also briefly discussed.

  16. Subclinical hyperfunctioning pituitary adenomas: The silent tumors (United States)

    Cooper, Odelia; Melmed, Shlomo


    Pituitary adenomas are classified by function as defined by clinical symptoms and signs of hormone hypersecretion with subsequent confirmation on immunohistochemical staining. However, positive immunostaining for pituitary cell types has been shown for clinically nonfunctioning adenomas, and this entity is classified as silent functioning adenoma. Most common in these subtypes include silent gonadotroph adenomas, silent corticotroph adenomas and silent somatotroph adenomas. Less commonly, silent prolactinomas and thyrotrophinomas are encountered. Appropriate classification of these adenomas may affect follow-up care after surgical resection. Some silent adenomas such as silent corticotroph adenomas follow a more aggressive course, necessitating closer surveillance. Furthermore, knowledge of the immunostaining characteristics of silent adenomas may determine postoperative medical therapy. This article reviews the incidence, clinical behavior, and pathologic features of clinically silent pituitary adenomas. PMID:22863387

  17. Pregnancy promotes pituitary tumors by increasing the rate of the cell cycle (United States)

    Yin, Changjiang; Qi, Xiaoxia


    Pituitary tumors may secrete hormones that affect pregnancy. Pregnancy also induces pituitary tumor growth; however, how pregnancy increases the growth of pituitary tumors remains unclear. The present study investigated pregnant female mice with subcutaneous pituitary tumors. The time of tumor occurrence and tumor weight were detected in pregnant and control mice. Tumor weights were measured at the end of the experiment. Blood was collected from pregnant and control mice. Brain-derived neurotrophic factor (BDNF) levels in the blood were detected using an ELISA kit. The in vitro effects of BDNF on pituitary tumor AtT-20 cell proliferation and cell cycle were investigated. It was revealed that pregnancy promoted the growth of pituitary tumors. In comparison to non-pregnant mice, the pregnant mice exhibited increased BDNF levels in the blood. In vitro BDNF treatment was able to increase the rate of proliferation of pituitary tumor cells. Additional cell cycle analysis revealed that BDNF was able to alter the cell cycle distribution of pituitary tumor cells. These results indicated that pregnancy was able to increase the BDNF level and promote the growth of pituitary tumor cells by increasing the rate of the cell cycle, leading to increased tumor growth rate in vivo. The present study provides insights into how pregnancy affects the growth of pituitary tumors. Therefore, it may be beneficial to perform pituitary tumor diagnosis or therapy on pregnant patients. PMID:29085495

  18. The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. (United States)

    Lopes, M Beatriz S


    The 4th edition of the World Health Organization (WHO) classification of endocrine tumors has been recently released. In this new edition, major changes are recommended in several areas of the classification of tumors of the anterior pituitary gland (adenophypophysis). The scope of the present manuscript is to summarize these recommended changes, emphasizing a few significant topics. These changes include the following: (1) a novel approach for classifying pituitary neuroendocrine tumors according to pituitary adenohypophyseal cell lineages; (2) changes to the histological grading of pituitary neuroendocrine tumors with the elimination of the term "atypical adenoma;" and (3) introduction of new entities like the pituitary blastoma and re-definition of old entities like the null-cell adenoma. This new classification is very practical and mostly based on immunohistochemistry for pituitary hormones, pituitary-specific transcription factors, and other immunohistochemical markers commonly used in pathology practice, not requiring routine ultrastructural analysis of the tumors. Evaluation of tumor proliferation potential, by mitotic count and Ki-67 labeling index, and tumor invasion is strongly recommended on individual case basis to identify clinically aggressive adenomas. In addition, the classification offers the treating clinical team information on tumor prognosis by identifying specific variants of adenomas associated with an elevated risk for recurrence. Changes in the classification of non-neuroendocrine tumors are also proposed, in particular those tumors arising in the posterior pituitary including pituicytoma, granular cell tumor of the posterior pituitary, and spindle cell oncocytoma. These changes endorse those previously published in the 2016 WHO classification of CNS tumors. Other tumors arising in the sellar region are also reviewed in detail including craniopharyngiomas, mesenchymal and stromal tumors, germ cell tumors, and hematopoietic tumors. It is

  19. Melatonin and cortisol profiles in patients with pituitary tumors. (United States)

    Zielonka, Daniel; Sowiński, Jerzy; Nowak, Stanisław; Ciesielska, Anna; Moskal, Jakub; Marcinkowski, Jerzy T


    The optic tract section at the optic chiasm is expected to disturb the suprachiasmatic nucleus (SCN) rhythm, circadian rhythm and melatonin secretion rhythms in humans, although detailed studies have never been conducted. The aim of this paper was to describe melatonin and cortisol profiles in patients with a pituitary tumor exerting optic chiasm compression. Six patients with pituitary tumors of different size, four of whom had significant optic chiasm compression, were examined. In each brain, MRI, an ophthalmological examination including the vision field and laboratory tests were performed. Melatonin and cortisol concentrations were measured at 22:00 h, 02:00 h, 06:00 h, and 10:00 h in patients lying in a dark, isolated room. One of the four cases with significant optic chiasm compression presented a flattened melatonin rhythm. The melatonin rhythm was also disturbed in one patient without optic chiasm compression. Larger tumors may play a role in the destruction of neurons connecting the retina with the suprachiasmatic nucleus (SCN) and breaking of basic way for inhibiting effect to the SCN from the retina. Copyright © 2014 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  20. Sca1-positive murine pituitary adenoma cells show tumor growth advantage (United States)

    Donangelo, Ines; Ren, Song-Guang; Eigler, Tamar; Svendsen, Clive; Melmed, Shlomo


    The role of tumor stem cells in benign tumors such as pituitary adenomas remains unclear. We investigated whether cells within pituitary adenomas that spontaneously develop in Rb+/− mice are hierarchically distributed with a subset being responsible for tumor growth. Cells derived directly from such tumors grew as spheres in serum-free culture medium supplemented with EGF and bFGF. Some cells within growing pituitary tumor spheres (PTS) expressed common stem cell markers (Sca1, Sox2, Nestin, CD133), but were devoid of hormone-positive differentiated cells. Under subsequent differentiating conditions (matrigel-coated growth surface), PTS expressed all six pituitary hormones. We next searched for specific markers of the stem cell population and isolated a Sca1+ cell population that showed increased sphere formation potential, lower hormone mRNA expression, higher expression of stem cell markers (Notch1, Sox2, Nestin), and increased proliferation rates. When transplanted into NOD scid gamma mice brains, Sca1+ pituitary tumor cells exhibited higher rates of tumor formation (brain tumors observed in 11/11 [100%] vs. 7/12 [54%] of mice transplanted with Sca1+ and Sca1− cells, respectively). Magnetic resonance imaging and histological analysis of brain tumors showed that those derived from Sca1+ pituitary tumor cells were also larger and plurihormonal. Our findings show that Sca1+ cells derived from benign pituitary tumors exhibit an undifferentiated expression profile and tumor proliferative advantages, and we propose that they could represent putative pituitary tumor stem/progenitor cells. PMID:24481638

  1. Transformation of a Silent Adrencorticotrophic Pituitary Tumor Into Central Nervous System Melanoma

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    Brandon A. Miller MD, PhD


    Full Text Available Silent adrenocorticotrophic pituitary adenomas are nonfunctioning pituitary adenomas that express adrenocorticotrophic hormone (ACTH but do not cause the clinical or laboratory features of hypercortisolemia. Primary central nervous system (CNS melanoma is well documented, but rarely originates in the sellar region or pituitary gland. Here we report transformation of an aggressive silent adrenocorticotrophic pituitary adenoma that transformed into CNS melanoma and review other presentations of pituitary melanoma. A 37-year-old woman initially presented with apoplexy and an invasive nonfunctioning pituitary macroadenoma for which she underwent transphenoidal surgery. The patient underwent 3 subsequent surgeries as the tumor continued to progress. Pathology from the first 3 operations showed pituitary adenoma or carcinoma. Pathology from the final surgery showed melanoma and the magnetic resonance imaging characteristics of the tumor had changed to become consistent with CNS melanoma. Dermatologic and ophthalmologic examinations did not identify cutaneous or ocular melanoma. The patient’s disease progressed despite aggressive surgical, medical and radiologic treatment. To our knowledge, this is the first report demonstrating transformation of a primary pituitary tumor into melanoma. The mechanism of tumor transformation is unclear, but it is possible that a mutation in the original ACTH-producing tumor lead to increased cleavage of pro-opiomelanocortin or ACTH into α-melanocyte-stimulating hormone, which in turn stimulated the expression of microopthalmia transcription factor, leading to melanocytic phenotype transformation.

  2. MALDI mass spectrometry imaging analysis of pituitary adenomas for near-real-time tumor delineation (United States)

    Calligaris, David; Feldman, Daniel R.; Norton, Isaiah; Olubiyi, Olutayo; Changelian, Armen N.; Machaidze, Revaz; Vestal, Matthew L.; Laws, Edward R.; Dunn, Ian F.; Santagata, Sandro; Agar, Nathalie Y. R.


    We present a proof of concept study designed to support the clinical development of mass spectrometry imaging (MSI) for the detection of pituitary tumors during surgery. We analyzed by matrix-assisted laser desorption/ionization (MALDI) MSI six nonpathological (NP) human pituitary glands and 45 hormone secreting and nonsecreting (NS) human pituitary adenomas. We show that the distribution of pituitary hormones such as prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH), and thyroid stimulating hormone (TSH) in both normal and tumor tissues can be assessed by using this approach. The presence of most of the pituitary hormones was confirmed by using MS/MS and pseudo-MS/MS methods, and subtyping of pituitary adenomas was performed by using principal component analysis (PCA) and support vector machine (SVM). Our proof of concept study demonstrates that MALDI MSI could be used to directly detect excessive hormonal production from functional pituitary adenomas and generally classify pituitary adenomas by using statistical and machine learning analyses. The tissue characterization can be completed in fewer than 30 min and could therefore be applied for the near-real-time detection and delineation of pituitary tumors for intraoperative surgical decision-making. PMID:26216958

  3. Temozolomide (Temodar®) and capecitabine (Xeloda®) treatment of an aggressive corticotroph pituitary tumor. (United States)

    Thearle, Marie S; Freda, Pamela U; Bruce, Jeffrey N; Isaacson, Steven R; Lee, Yoomi; Fine, Robert L


    Only rarely do corticotroph pituitary tumors become invasive leading to symptoms caused by compression of cranial nerves and other local structures. When aggressive pituitary neuroendocrine tumors do develop, conventional treatment options are of limited success. A 50-year-old man developed a giant invasive corticotroph pituitary tumor 2 years after initial presentation. His tumor and symptoms failed to respond to maximal surgical, radio-surgical, radiation and medical therapy and a bilateral adrenalectomy was done. He subsequently developed rapid growth of his tumor leading to multiple cranial nerve deficits. He was administered salvage chemotherapy with capecitabine and temozolomide (CAPTEM), a novel oral chemotherapy regimen developed at our institution for treatment of neuroendocrine tumors. After two cycles of CAPTEM, his tumor markedly decreased in size and ACTH levels fell by almost 90%. Despite further decreases in ACTH levels, his tumor recurred after 5 months with increased avidity on PET scan suggesting a transformation to a more aggressive phenotype. Temozolomide had been reported to be effective against other pituitary tumors and this case adds to this literature demonstrating its use along with capecitabine (CAPTEM) against a corticotroph tumor. Further evaluation of the CAPTEM regimen in patients with pituitary neuroendocrine tumors which fail to respond to classic treatments is warranted.

  4. Temozolomide (Temodar®) and capecitabine (Xeloda®) treatment of an aggressive corticotroph pituitary tumor (United States)

    Thearle, Marie S.; Bruce, Jeffrey N.; Isaacson, Steven R.; Lee, Yoomi


    Only rarely do corticotroph pituitary tumors become invasive leading to symptoms caused by compression of cranial nerves and other local structures. When aggressive pituitary neuroendocrine tumors do develop, conventional treatment options are of limited success. A 50-year-old man developed a giant invasive corticotroph pituitary tumor 2 years after initial presentation. His tumor and symptoms failed to respond to maximal surgical, radio-surgical, radiation and medical therapy and a bilateral adrenalectomy was done. He subsequently developed rapid growth of his tumor leading to multiple cranial nerve deficits. He was administered salvage chemotherapy with capecitabine and temozolomide (CAPTEM), a novel oral chemotherapy regimen developed at our institution for treatment of neuroendocrine tumors. After two cycles of CAPTEM, his tumor markedly decreased in size and ACTH levels fell by almost 90%. Despite further decreases in ACTH levels, his tumor recurred after 5 months with increased avidity on PET scan suggesting a transformation to a more aggressive phenotype. Temozolomide had been reported to be effective against other pituitary tumors and this case adds to this literature demonstrating its use along with capecitabine (CAPTEM) against a corticotroph tumor. Further evaluation of the CAPTEM regimen in patients with pituitary neuroendocrine tumors which fail to respond to classic treatments is warranted. PMID:19960369

  5. Multicenter study on adult growth hormone level in postoperative pituitary tumor patients. (United States)

    Cheng, Jing-min; Gu, Jian-wen; Kuang, Yong-qin; Ma, Yuan; Xia, Xun; Yang, Tao; Lu, Min; He, Wei-qi; Sun, Zhi-yong; Zhang, Yan-chao


    The objective of this study is to observe the adult growth hormone level in postoperative pituitary tumor patients of multi-centers, and explore the change of hypophyseal hormones in postoperative pituitary tumor patients. Sixty patients with pituitary tumor admitted during March, 2011-March, 2012 were selected. Postoperative hypophyseal hormone deficiency and the change of preoperative, intraoperative, and postoperative growth hormone levels were recorded. Growth hormone hypofunction was the most common hormonal hypofunction, which took up to 85.0 %. Adrenocortical hormone hypofunction was next to it and accounted for 58.33 %. GH + ACTH + TSH + Gn deficiency was the most common in postoperative hormone deficiency, which took up to 40.00 %, and GH + ACTH + TSH + Gn + AVP and GH deficiencies were next to it and accounted for 23.33 and 16.67 %, respectively. The hormone levels in patients after total pituitary tumor resection were significantly lower than those after partial pituitary tumor resection, and the difference was statistically significant; growth hormone and serum prolactin levels after surgery in two groups were decreased, and the difference was statistically significant. The incidence rate of growth hormone deficiency in postoperative pituitary tumor patients is high, which is usually complicated with deficiency of various hypophyseal hormones. In clinical, we should pay attention to the levels of the hypopnyseal hormones, and take timely measures to avoid postoperative complications.

  6. Radiotherapy, especially at young age, increases the risk for de novo brain tumors in patients treated for pituitary tumors

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    Burman, Pia; Van Beek, André P.; Biller, Beverly M.K.; Camacho-Hubner, Cecilia; Mattsson, Anders F.

    Background: Excess mortality due to de novo malignant brain tumors was recently found in a national study of patients with hypopituitarism following treatment of pituitary tumors. Here, we examined a larger multi-national cohort to corroborate and extend this observation. Objective: To investigate

  7. Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas: Markers in the Differential Diagnosis of Neuroendocrine Tumors of the Sellar Region. (United States)

    Casar-Borota, Olivera; Botling, Johan; Granberg, Dan; Stigare, Jerker; Wikström, Johan; Boldt, Henning Bünsow; Kristensen, Bjarne Winther; Pontén, Fredrik; Trouillas, Jacqueline


    Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown. Facing a difficult diagnostic case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None of the pituitary tumors expressed serotonin, suggesting that serotonin immunoreactive sellar tumors represent primary or secondary NETs of nonpituitary origin. Normal expression of ATRX and DAXX in pituitary tumors suggests that ATRX and DAXX do not play a role in the pathogenesis of pituitary endocrine tumors that remain localized to the sellar and perisellar region. A lack of ATRX or DAXX in a sellar NET suggests a nonpituitary NET, probably of pancreatic origin. One of the 2 examined corticotroph carcinomas, however, demonstrated negative ATRX immunolabeling due to an ATRX gene mutation. Further studies on a larger cohort of pituitary carcinomas are needed to clarify whether ATRX mutations may contribute to the metastatic potential in a subset of pituitary NETs.

  8. Small-Animal PET with a sigma-Ligand, C-11-SA4503, Detects Spontaneous Pituitary Tumors in Aged Rats

    NARCIS (Netherlands)

    Kuzhuppilly Ramakrishnan, Nisha; Rybczynska, Anna A.; Visser, Anniek K. D.; Marosi, Krisztina; Nyakas, Csaba J.; Kwizera, Chantal; Sijbesma, Jurgen W. A.; Elsinga, Philip H.; Ishiwata, Kiichi; Pruim, Jan; Dierckx, Rudi A. J. O.; van Waarde, Aren

    Pituitary tumors are often detected only after death or at late stages of the disease when they are macroadenomas with a low surgical cure rate. Spontaneous pituitary tumors occur in rats over 1 y of age. In an ongoing study of changes in sigma-1 agonist binding related to aging, several of our rats

  9. Functional Toll-like receptor 4 expressed in lactotrophs mediates LPS-induced proliferation in experimental pituitary hyperplasia

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    Sabatino, María Eugenia; Sosa, Liliana del Valle; Petiti, Juan Pablo; Mukdsi, Jorge Humberto [Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Av. Enrique Barros y Enfermera Gordillo, Ciudad Universitaria, CP 5000, Córdoba (Argentina); Mascanfroni, Iván Darío; Pellizas, Claudia Gabriela [Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Av. Haya de la Torre y Medina Allende, Ciudad Universitaria, CP 5000, Córdoba (Argentina); Gutiérrez, Silvina; Torres, Alicia Inés [Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Av. Enrique Barros y Enfermera Gordillo, Ciudad Universitaria, CP 5000, Córdoba (Argentina); De Paul, Ana Lucía, E-mail: [Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Av. Enrique Barros y Enfermera Gordillo, Ciudad Universitaria, CP 5000, Córdoba (Argentina)


    Toll like receptor 4 (TLR4) has been characterized for its ability to recognize bacterial endotoxin lipopolysaccharide (LPS). Considering that infections or inflammatory processes might contribute to the progression of pituitary tumors, we analyzed the TLR4 functional role by evaluating the LPS effect on lactotroph proliferation in primary cultures from experimental pituitary tumors, and examined the involvement of PI3K-Akt and NF-κB activation in this effect. In addition, the role of 17β-estradiol as a possible modulator of LPS-induced PRL cell proliferation was further investigated. In estrogen-induced hyperplasic pituitaries, LPS triggered lactotroph cell proliferation. However, endotoxin failed to increase the number of lactotrophs taking up BrdU in normal pituitaries. Moreover, incubation with anti-TLR4 antibody significantly reduced LPS-induced lactotroph proliferation, suggesting a functional role of this receptor. As a sign of TLR4 activation, an LPS challenge increased IL-6 release in normal and tumoral cells. By flow cytometry, TLR4 baseline expression was revealed at the plasma membrane of tumoral lactotrophs, without changes noted in the percentage of double PRL/TLR4 positive cells after LPS stimulus. Increases in TLR4 intracellular expression were detected as well as rises in CD14, p-Akt and NF-κB after an LPS challenge, as assessed by western blotting. The TLR4/PRL and PRL/NF-κB co-localization was also corroborated by immunofluorescence and the involvement of PI3K/Akt signaling in lactotroph proliferation and IL-6 release was revealed through the PI3K inhibitor Ly-294002. In addition, 17β-estradiol attenuated the LPS-evoked increase in tumoral lactotroph proliferation and IL-6 release. Collectively these results demonstrate the presence of functional TLR4 in lactotrophs from estrogen-induced hyperplasic pituitaries, which responded to the proliferative stimulation and IL-6 release induced by LPS through TLR4/CD14, with a contribution of the PI3K

  10. Non-functioning pituitary adenoma database: a useful resource to improve the clinical management of pituitary tumors. (United States)

    Ferrante, Emanuele; Ferraroni, Monica; Castrignanò, Tristana; Menicatti, Laura; Anagni, Mascia; Reimondo, Giuseppe; Del Monte, Patrizia; Bernasconi, Donatella; Loli, Paola; Faustini-Fustini, Marco; Borretta, Giorgio; Terzolo, Massimo; Losa, Marco; Morabito, Alberto; Spada, Anna; Beck-Peccoz, Paolo; Lania, Andrea G


    The long-term outcome of non-functioning pituitary adenoma (NFPA) patients is not clearly established, probably due to the low annual incidence and prolonged natural history of these rare tumors. The aim of this study was to evaluate clinical data at presentation and long-term post-surgery and radiotherapy outcome in a cohort of patients with NFPA. A computerized database was developed using Access 2000 software (Microsoft Corporation, 1999). Retrospective registration of 295 NFPA patients was performed in seven Endocrinological Centers of North West Italy. Data were analyzed by STATA software. The main presenting symptoms were visual defects (67.8%) and headache (41.4%) and the most frequent pituitary deficit was hypogonadism (43.3%), since almost all tumors were macroadenomas (96.5%). Surgery was the first choice treatment (98% of patients) and total debulking was achieved in 35.5%. Radiotherapy was performed as adjuvant therapy after surgery in 41% of patients. At the follow-up, recurrence occurred in 19.2% of patients without post-surgical residual tumor after 7.5 +/- 2.6 years, regrowth in 58.4% of patients with post-surgical remnant after 5.3 +/- 4.0 years and residue enlargement in 18.4% of patients post-surgically treated with radiotherapy after 8.1 +/- 7.3 years. Our database indicates that the goal of a definitive surgical cure has been achieved during the last decade in a low percentage of patients with NFPA. This tumor database may help to reduce the delay between symptom onset and diagnosis, to assess prognostic parameters for the follow-up of patients with different risk of recurrence and to define the efficacy and safety of different treatments and their association with mortality/morbidity.

  11. Analysis of internet-based patient education materials related to pituitary tumors. (United States)

    Cherla, Deepa V; Sanghvi, Saurin; Agarwal, Nitin; Eloy, Jean Anderson; Couldwell, William T; Liu, James K


    The Internet has become a primary and ubiquitous information source for patient education material (PEM); however, the information provided may not be appropriate for the average patient to comprehend. Various national healthcare organizations have recommended that PEM be written at or below the sixth-grade level. The purpose of this study was to assess the readability of pituitary tumor-related PEMs available on the Internet. Fifty-one PEMs on pituitary tumors were downloaded from professional society and clinical practice websites. Analysis of readability was performed using 4 different readability indices: Flesch-Kincaid Grade Level (FKGL), Flesch Reading Ease Score (FRES), Simple Measure of Gobbledygook (SMOG), and Gunning Frequency Measure of Gobbledygook (Gunning FOG). Scores from the FKGL, SMOG, and Gunning FOG scales correspond to reading grade levels. Therefore, a higher number corresponds to higher difficulty and lower readability. The average grade level of the PEMs according to the readability indices were as follows: FKGL = 11.71 (11th to 12th grades), SMOG = 14.56 (college level), and Gunning FOG = 14.86 (college level). For the FRES, higher scores imply easier readability. The average FRES was 40.19 (fairly difficult-between 10th and 11th grades). These findings suggest that online pituitary tumor-related material may be too difficult for comprehension by the majority of the targeted patient population. Keeping the reading level of PEMs at or below the sixth grade may improve understanding of this disease and its management for pituitary tumor patients.

  12. GFAP-Cre-mediated transgenic activation of Bmi1 results in pituitary tumors.

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    Bart A Westerman

    Full Text Available Bmi1 is a member of the polycomb repressive complex 1 and plays different roles during embryonic development, depending on the developmental context. Bmi1 over expression is observed in many types of cancer, including tumors of astroglial and neural origin. Although genetic depletion of Bmi1 has been described to result in tumor inhibitory effects partly through INK4A/Arf mediated senescence and apoptosis and also through INK4A/Arf independent effects, it has not been proven that Bmi1 can be causally involved in the formation of these tumors. To see whether this is the case, we developed two conditional Bmi1 transgenic models that were crossed with GFAP-Cre mice to activate transgenic expression in neural and glial lineages. We show here that these mice generate intermediate and anterior lobe pituitary tumors that are positive for ACTH and beta-endorphin. Combined transgenic expression of Bmi1 together with conditional loss of Rb resulted in pituitary tumors but was insufficient to induce medulloblastoma therefore indicating that the oncogenic function of Bmi1 depends on regulation of p16(INK4A/Rb rather than on regulation of p19(ARF/p53. Human pituitary adenomas show Bmi1 overexpression in over 50% of the cases, which indicates that Bmi1 could be causally involved in formation of these tumors similarly as in our mouse model.

  13. Endoscopic augmented reality navigation system for endonasal transsphenoidal surgery to treat pituitary tumors: technical note. (United States)

    Kawamata, Takakazu; Iseki, Hiroshi; Shibasaki, Takao; Hori, Tomokatsu


    Endoscopes have been commonly used in transsphenoidal surgery to treat pituitary tumors, to compensate for the narrow surgical field. Although many navigation systems have been introduced for neurosurgical procedures, there have been few reports of navigation systems for endoscopic operations. This report presents our recently developed, endoscopic, augmented reality (AR) navigation system. The technology is based on the principles of AR environment technology. The system consisted of a rigid endoscope with light-emitting diodes, an optical tracking system, and a controller. The operation of the optical tracking system was based on two sets of infrared light-emitting diodes, which measured the position and orientation of the endoscope relative to the patient's head. We used the system during endonasal transsphenoidal operations to treat pituitary tumors in 12 recent cases. Anatomic, "real," three-dimensional, virtual images of the tumor and nearby anatomic structures (including the internal carotid arteries, sphenoid sinuses, and optic nerves) were superimposed on real- time endoscopic live images. The system also indicated the positions and directions of the endoscope and the endoscopic beam in three-dimensional magnetic resonance imaging or computed tomographic planes. Furthermore, the colors of the wire-frame images of the tumor changed according to the distance between the tip of the endoscope and the tumor. These features were superior to those of conventional navigation systems, which are available only for operating microscopes. The endoscopic AR navigation system allows surgeons to perform accurate, safe, endoscope-assisted operations to treat pituitary tumors; it is particularly useful for reoperations, in which midline landmarks may be absent. We consider the AR navigation system to be a promising tool for safe, minimally invasive, endonasal, transsphenoidal surgery to treat pituitary tumors.

  14. Pituitary tumor transforming gene and insulin-like growth factor 1 receptor expression and immunohistochemical measurement of Ki-67 as potential prognostic markers of pituitary tumors aggressiveness. (United States)

    Sánchez-Tejada, Laura; Sánchez-Ortiga, Ruth; Moreno-Pérez, Oscar; Montañana, Carmen Fajardo; Niveiro, Maria; Tritos, Nicholas A; Alfonso, Antonio M Picó


    The ability to predict recurrence of pituitary adenoma (PA) after surgery may be helpful to determine follow-up frequency and the need for adjuvant treatment. The purpose of this study was to assess the prognostic capacity of pituitary tumor transforming gene (PTTG), insulin-like growth factor 1 receptor (IGF1R), and Ki-67. In this retrospective study, the normalized copy number (NCN) of PTIG and IGF1R mRNA was measured using RT-PCR, and the Ki-67 index was measured by immunohistochemistry in 46 PA samples. Clinical data, histological subtype, and radiographic characteristics were collected to assess associations between variables and tumor behavior. Progression of tumor remnants and its association to markers was also studied in 14 patients with no adjuvant treatment after surgery followed up for 46±36 months. Extrasellar tumors had a lower PTTG expression as compared to sellar tumors (0.065 [1st-3rd quartile: 0.000-0.089] NCN vs. 0.135 [0.105-0.159] NCN, p=0.04). IGF1R expression changed depending on histological subtype (p=0.014), and was greater in tumor with remnant growth greater than 20% during follow-up (10.69±3.84 NCN vs. 5.44±3.55 NCN, p=0.014). Our results suggest that the IGF1R is a more helpful molecular marker than PTTG in PA management. Ki-67 showed no association to tumor behavior. However, the potential of these markers should be established in future studies with standardized methods and on larger samples. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  15. Testosterone Replacement and Bone Mineral Density in Male Pituitary Tumor Patients

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    Min Jeong Lee


    Full Text Available BackgroundHypopituitarism is associated with osteoporosis and osteopenia especially when hypogonadotropic hypogonadism is present. Despite hypopituitarism being an important cause of secondary osteoporosis, osteoporosis in patients receiving surgery for pituitary tumors in Korea has not been studied. In this study, we evaluated the effects of testosterone replacement therapy (TRT on bone mineral density (BMD in postoperative hypogonadal patients with pituitary tumors.MethodsTo examine the effect of TRT on BMD, we performed a retrospective observational study in 21 postoperative male patients who underwent pituitary tumor surgery between 2003 and 2012 at the Ajou University Hospital. Testosterone was replaced in postoperative hypogonadal patients by regular intramuscular injection, daily oral medication, or application of transdermal gel. BMD (g/cm2 measurements of central skeletal sites (lumbar spine, femoral neck, and total femur were obtained using dual-energy X-ray absorptiometry (GE Lunar. For lumbar spine BMD, L1 to L4 values were chosen for analysis. Femur neck and total femur were also analyzed.ResultsDuring the follow-up period (mean, 56 months; range, 12 to 99 months serum testosterone levels increased with the administration of TRT (P=0.007. There was significant improvement (4.56%±9.81% in the lumbar spine BMD compared to baseline BMD. There were no significant changes in the femur neck BMD or total femur BMD. We did not find any statistically significant relationships between changes in testosterone levels and BMD using Spearman correlation analysis.ConclusionOur results indicated that TRT used in the postoperative period for hypogonadal pituitary tumor surgery patients may have beneficial effects on the BMD of the spine.

  16. Genetic and epigenetic mutations of tumor suppressive genes in sporadic pituitary adenoma (United States)

    Zhou, Yunli; Zhang, Xun; Klibanski, Anne


    Human pituitary adenomas are the most common intracranial neoplasms. Approximately 5% of them are familial adenomas. Patients with familial tumors carry germline mutations in predisposition genes, including AIP, MEN1 and PRKAR1A. These mutations are extremely rare in sporadic pituitary adenomas, which therefore are caused by different mechanisms. Multiple tumor suppressive genes linked to sporadic tumors have been identified. Their inactivation is caused by epigenetic mechanisms, mainly promoter hypermethylation, and can be placed into two groups based on their functional interaction with tumor suppressors RB or p53. The RB group includes CDKN2A, CDKN2B, CDKN2C, RB1, BMP4, CDH1, CDH13, GADD45B and GADD45G; AIP and MEN1 genes also belong to this group. The p53 group includes MEG3, MGMT, PLAGL1, RASSF1, RASSF3 and SOCS1. We propose that the tumor suppression function of these genes is mainly mediated by the RB and p53 pathways. We also discuss possible tumor suppression mechanisms for individual genes. PMID:24035864

  17. Tumor infiltrating lymphocytes but not serum pituitary antibodies are associated with poor clinical outcome after surgery in patients with pituitary adenoma. (United States)

    Lupi, Isabella; Manetti, Luca; Caturegli, Patrizio; Menicagli, Michele; Cosottini, Mirco; Iannelli, Aldo; Acerbi, Giovanni; Bevilacqua, Generoso; Bogazzi, Fausto; Martino, Enio


    Serum pituitary antibodies (Pit Abs) and tumor-infiltrating lymphocytes (TILs) have been described in pituitary adenomas, but their clinical significance remains unknown. The objective of the study was to assess Pit Abs and TILs prevalence in pituitary adenomas and their influence on clinical outcome. This was a prevalence case-control study. Two hundred ninety-one pituitary adenoma cases (110 non-secreting, 30 ACTH-69 GH-71 prolactin- and 13 TSH-secreting adenoma; 177 operated and 114 untreated), 409 healthy controls, and 14 autoimmune hypophysitis were enrolled in a tertiary referral center. Pit Abs were measured using immunofluorescence in all cases and controls (n = 714). The presence of TILs was evaluated using CD45 staining in a subset of adenomas surgically treated (n = 72). Clinical response of pituitary adenoma after surgery was evaluated. Pit Abs prevalence was higher in adenomas (5.1%) than healthy subjects (0.7%, P < 0.0001) and lower than in autoimmune hypophysitis patients (57%, P < 0.0001). Similarly, TILs prevalence was higher in adenomas than normal pituitary (P = 0.01) and lower than in autoimmune hypophysitis (P < 0.0001). No correlation between Pit Abs and TILs was found (P = 0.78). A poor clinical outcome was more common in adenoma patients with TILs (11 of 18, 61%) than in those without (17 of 54, 31%, P = 0.026). Multivariate regression analysis identified the presence of TILs as independent prognostic factor for persistence/recurrence of pituitary adenoma. TILs and Pit Abs are present in a significant number of pituitary adenoma patients. Cell-mediated immunity appears to be predictive of a less favorable clinical outcome.


    NARCIS (Netherlands)



    A patient with acromegaly and hyperthyroidism due to a growth hormone-, thyrotrophin- and alpha-subunit-secreting pituitary adenoma is described. His deceased father had suffered from a pituitary tumour, and was likely to have had acromegaly as well. Plasma growth hormone and insulin-like growth

  19. Pituitary disorders as a predictor of apathy and executive dysfunction in adult survivors of childhood brain tumors. (United States)

    Fox, Michelle E; King, Tricia Z


    The relationship between apathy and endocrine dysfunction, both frequent outcomes of neurological insult, has not yet been investigated in brain tumor survivors. The present study aimed to assess the relationship between pituitary disorders and apathy and other facets of executive function in long-term adult survivors of childhood brain tumors and to differentiate between apathy and depression in this population. Seventy-six adult survivors of childhood brain tumors at least 5 years past diagnosis participated. An informant completed the Frontal Systems Behavior Scale (FrSBe), and 75 of the 76 participants completed a Structured Clinical Interview for the DSM-IV-TR (SCID). Information on neuroendocrine dysfunction was obtained through medical chart review. Clinically significant levels of apathy on the FrSBe were identified in 41% of survivors. Pituitary dysfunction significantly explained 9% of the variance in apathy scores and affected whether an individual presented with clinical levels of apathy. Pituitary dysfunction predicted higher levels of executive dysfunction but did not impact whether a participant reached clinical levels of executive dysfunction. A past major depressive episode (MDE) significantly predicted current apathy but showed no relationship with pituitary disorders. Radiation treatment predicted pituitary dysfunction but not the differences in apathy or executive functions. Apathy and executive dysfunction in survivors of childhood brain tumors are strongly predicted by pituitary dysfunction, and individuals with pituitary dysfunction are more likely to present with clinical levels of apathy as adults. Clinical levels of apathy may present absent of current depression, and pituitary dysfunction impacts apathy uniquely. © 2016 Wiley Periodicals, Inc.

  20. Differentiation of pituitary adenomas from other sellar and parasellar tumors by {sup 99m}Tc(V)-DMSA scintigraphy

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    Yamamura, Koji [Yokohama City Univ. (Japan). Medical Center; Suzuki, Shinichi; Yamamoto, Isao [Yokohama City Univ. (Japan). School of Medicine


    Pentavalent technetium-99m dimercaptosuccinic acid [{sup 99m}Tc(V)-DMSA] scintigraphy was evaluated for the differentiation of pituitary adenomas, especially non-functioning adenomas, from other sellar and parasellar lesions. Diffuse {sup 99m}Tc(V)-DMSA accumulation within the tumor was found in seven of seven non-functioning, three of four growth hormone-secreting, and seven of eight prolactin-secreting adenomas, but only partial accumulation in only two of 16 non-pituitary adenomas and normal pituitary glands. There were no significant relationship between tumor-to-background ratios and tumor size or serum hormone level. {sup 99m}Tc(V)-DMSA scintigraphy showed overall sensitivity of 81% (17/21 cases) for detecting pituitary adenomas, in particular 100% for non-functioning adenomas. {sup 99m}Tc(V)-DMSA may be useful for detecting pituitary adenomas, especially non-functioning adenomas, and for the differentiation of non-functioning pituitary adenomas from other sellar and parasellar lesions. (author)

  1. Endoscopic approach to a collision tumor of growth hormone-secreting adenoma and gangliocytoma in the pituitary gland. (United States)

    Tanriover, Necmettin; Aydin, Ovgu; Kucukyuruk, Baris; Abuzayed, Bashar; Guler, Huseyin; Oz, Buge; Gazioglu, Nurperi


    The authors share their experience on a collision tumor of growth hormone (GH)-secreting adenoma and gangliocytoma in the pituitary gland, which was reported by few articles in the literature. Also, an intraoperative view of this tumor, operated via endoscopic endonasal transsphenoidal approach, is presented for the first time. A 39-year-old female patient was admitted with clinical manifestation of acromegaly present in a 2-year period. Laboratory investigations revealed high levels of GH and insulinlike growth factor 1. Sellar computed tomography scan and magnetic resonance imaging showed a sellar mass diagnosed as a pituitary adenoma. Based on clinical, biochemical, and radiologic evaluations, GH-secreting pituitary adenoma was diagnosed and operated by endoscopic endonasal transsphenoidal approach achieving total removal of the tumor. Histopathologic examination revealed a collision tumor of GH-secreting adenoma and gangliocytoma. Postoperative radiologic and biochemical investigations showed no residual tumor and total remission. The endoscopic endonasal transsphenoidal approach promotes a close intraoperative view of sellar pathologies. We believe that a detailed histopathologic workup is necessary to diagnose collision tumors, because even a close intraoperative view does not facilitate to differentiate these tumors from a regular pituitary adenoma.

  2. Pituitary tumor (United States)

    ... 1 (IGF-1) level LH level Prolactin level Testosterone/estradiol levels Thyroid hormone levels: free T4 test , ... Wisse, MD, Associate Professor of Medicine, Division of Metabolism, Endocrinology & Nutrition, University of Washington School of Medicine, ...

  3. MRI Findings of Causalgia of the Lower Extremity Following Transsphenoidal Resection of Pituitary Tumor

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    D. Ryan Ormond


    Full Text Available Background. Causalgia is continuing pain, allodynia, or hyperalgesia after nerve injury with edema, changes in skin blood flow, or abnormal sudomotor activity. Here we report a case of lower extremity causalgia following elective transsphenoidal resection of a pituitary tumor in a young man. Clinical Presentation. A 33-year-old man with acromegaly underwent elective sublabial transsphenoidal resection of his pituitary tumor. During the three-hour surgery, the lower limbs were kept in a supine, neutral position with a pillow under the knees. The right thigh was slightly internally rotated with a tape to expose fascia lata, which was harvested to repair the sella. Postoperatively, he developed causalgia in a distal sciatic and common peroneal nerve distribution. Pain was refractory to several interventions. Finally, phenoxybenzamine improved his pain significantly. Conclusions. Malpositioning in the operating room resulted in causalgia in this young man. Phenoxybenzamine improved, and ultimately resolved, his symptoms. Improvement in his pain symptoms correlated with resolution of imaging changes in the distal sciatic and peroneal nerves on the side of injury.

  4. Multiple forms of immunoreactive beta-endorphin are present in an ectopic adrenocorticotropin-producing tumor but not in normal pituitary or pituitary adenomas. (United States)

    Suda, T; Tozawa, F; Yamaguchi, H; Shibasaki, T; Demura, H; Shizume, K


    Human ACTH-producing tumor and plasma have been examined by gel filtration and ion exchange chromatography to detect the possible presence of reported multiple forms of immunoreactive beta-endorphin (I-EP) Ion exchange chromatography of I-EP obtained from gel filtration showed four components of I-EP [two major peaks in the positions of EP-(1-31) and EP-(1-27) and two minor peaks in the positions of N-acetyl EP-(1-31) and N-acetyl EP-(1-27)] in two ectopic ACTH-producing lung cancers, and two components of I-EP [the major peak in the position of EP-(1-31) and minor peak in the position of N-acetyl EP-(1-31) in an ectopic ACTH-producing thyroid cancer. Only a single peak in the position of EP-(1-31) was present in plasma from a patient with Nelson's sindrome and a patient with Addison's disease, in the pituitary adenomas from six patients with Cushing's disease, and in the nontumorous pituitary tissues from a patient with Cushing's disease and a patient with acromegaly. These data suggest that the posttranslational processing of EP in human pituitary is different from that in the ectopic ACTH-producing tumor.

  5. Learning curve for the transsphenoidal endoscopic endonasal approach to pituitary tumors. (United States)

    Qureshi, Talha; Chaus, Fahad; Fogg, Louis; Dasgupta, Mona; Straus, David; Byrne, Richard W


    The transsphenoidal endoscopic approach is a relatively new procedure compared to the microscopic approach in pituitary adenoma resection. The endoscopic approach has shown to significantly decrease the rate of complications, time in the operating room and hospital, and patient post-op discomfort. However, this procedure requires the surgeon to make use of different visual and tactile clues that must be developed with experience. Therefore, it is important to understand the learning curve that the surgeon must overcome to become proficient with the endoscopic approach. Retrospective review of a single-surgeon consecutive series of 78 patients undergoing endoscopic pituitary tumor surgery from 2006 to 2012 at Rush University Medical Center has been used in this study. Patients were grouped according to an early (n = 9) and late group (n = 68) determined by a significant difference in outcomes. Our primary outcome measures were: duration of operation, CSF leak, hospital length of stay, visual field improvement, diabetes insipidus, panhypopituitarism, and subtotal resection. There was a significant reduction in OR time and intraoperative CSF leaks between the early and late groups. There was no difference in hospital LOS or visual field improvement between the groups. With regards to complication rates, there was no difference found for DI, panhypopituitarism, lumbar drain placement, sinusitis, or subtotal resection between the two groups. This study indicates that there may be a learning curve of approximately 9 cases before a surgical team can decrease OR times and reduce the rate of intraoperative CSF leaks for the endonasal endoscopic approach to pituitary adenoma resection.

  6. Thyrotropin-secreting pituitary tumor presenting with congestive heart failure and good response to dopaminergic agonist cabergoline

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    Yu-Hsi Kao


    Full Text Available Hyperthyroidism is an important inducing factor in patients with atrial fibrillation, and may trigger heart failure. Thyrotropin (thyroid stimulating hormone, TSH-secreting pituitary tumors are rare causes of hyperthyroidism. Here, we report a 66-year-old man with a pituitary TSH-secreting tumor who presented with hyperthyroidism and congestive heart failure. Endonasal trans-sphenoidal pituitary adenomectomy was performed. After the operation, the symptoms of hyperthyroidism and congestive heart failure were relieved, associated with normalization of thyroid function tests. Unfortunately, hand tremor and progressively elevated free T4 and TSH concentrations recurred 5 months after surgery. A dopaminergic agonist, cabergoline was administered and euthyroidism was restored for at least 11 months.

  7. MicroRNA-524-5p Functions as a Tumor Suppressor in a Human Pituitary Tumor-Derived Cell Line. (United States)

    Zhen, Wang; Qiu, Du; Zhiyong, Chen; Xin, Wang; Mengyao, Jian; Dimin, Zhu; Chonghui, Hu; Haijun, Wang; Yonghong, Zhu


    Clinical nonfunctional pituitary adenomas (NFAs) account for about 40% of pituitary adenomas with almost no clinically relevant hormonal symptoms. Increasing evidence shows that many microRNAs are involved in the development and progression of pituitary adenomas. MicroRNA-524-5p (miR-524-5p) has been reported to cause characteristic alterations in various tumors. However, the functional importance of miR-524-5p in NFAs remains unknown. The aim of this study was to explore the effects of overexpressing miR-524-5p on the proliferation, migration, invasion, and tumorigenicity of pituitary-derived folliculostellate (PDFS) cells using lentiviral transfection. Interestingly, the results showed that overexpressing miR-524-5p downregulated pituitary tumor-transforming gene 1 (PTTG1) binding factor (PBF) expression at both mRNA and protein levels and significantly attenuated cell proliferation, clonogenicity, migration, and invasion in vitro. Moreover, enhancing miR-524-5p blocked tumor growth in a nude mouse xenograft model in vivo. These findings suggest that miR-524-5p appears to play a critical role in the regulation of biological properties of PDFS cells, and may represent a potential therapeutic target for NFAs. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Effects of microRNA-21 targeting PITX2 on proliferation and apoptosis of pituitary tumor cells. (United States)

    Cui, M; Zhang, M; Liu, H-F; Wang, J-P


    Expression of pituitary homeobox 2 (PITX2) is significantly elevated in pituitary adenoma tissues, which also has lower microRNA (miR)-21 expression, indicating possible tumor-suppression role of miR-21. Bio-informatics analysis revealed targeting onto 3'-UTR of PITX2 by miR-21. This study aims to investigate the role of miR-21/PITX2 expression in proliferation and apoptosis of pituitary adenoma cells and pathogenesis. A total of 48 pituitary adenoma samples were collected in parallel with 12 normal brain tissues and were recruited in this study. Flow cytometry was employed to test Ki-67 expression and apoptosis. Expressions of miR-21 and PITX2 were compared, along with their targeted relationship by dual-luciferase reporter assay. Cultured HP75 cells were transfected with miR-21 mimic and/or si-PITX2. Caspase-3 activity was further quantified, followed by flow cytometry for apoptosis. MiR-21, cleaved caspase-3 and PITX2 expressions were tested. Invasive pituitary adenoma tissues had significantly higher Ki-67 and PITX2, and lower miR-21 expressions or apoptosis than non-invasive tumors. MiR-21 targeted 3'-UTR of PITX2 gene to inhibit its expression. Elevated miR-21 and/or silencing PITX2 significantly depressed PITX2 expression in HP75 cells, potentiating caspase-3 activity, decreasing cell proliferation and facilitating apoptosis. MiR-21 was down-regulated while PITX2 was up-regulated in pituitary adenoma tissues. MiR-21 can inhibit pituitary adenoma cell HP75 proliferation and facilitate apoptosis via inhibiting PITX2 expression.

  9. The incidence of cerebrovascular accidents and second brain tumors in patients with pituitary adenoma: a population-based study. (United States)

    Brown, Paul D; Blanchard, Miran; Jethwa, Krishan; Flemming, Kelly D; Brown, Cerise A; Kline, Robert W; Jacobson, Debra J; St Sauver, Jennifer; Pollock, Bruce E; Garces, Yolanda I; Stafford, Scott L; Link, Michael J; Erickson, Dana; Foote, Robert L; Laack, Nadia N I


    To assess the risk of cerebrovascular accidents (CVAs) and second brain tumors (SBTs) in patients with pituitary adenoma after surgery or radiotherapy. A cohort of 143 people from Olmsted County, who were diagnosed with pituitary adenoma between 1933 and 2000, was studied. Only patients from Olmsted County were included because of the unique nature of medical care in Olmsted County, which allows the ascertainment of virtually all cases of pituitary adenoma for this community's residents and comparisons to the general population in the county. Surgical resection was performed in 76 patients, 29 patients underwent radiotherapy (with 21 undergoing both surgery and radiotherapy), 5 patients were reirradiated, and 59 patients were managed conservatively and observed. Median follow-up was 15.5 years. There was no difference in CVA-free survival between treatment groups. On univariate analysis age > 60 years (hazard ratio [HR], 11.93; 95% CI, 6.26-23.03; P 60 years was associated with worse CVA-free survival. Compared with the general population, there was a 4-fold increase in the rate of CVAs in pituitary adenoma patients (HR, 4.2; 95% CI, 2.8-6.1). Two patients developed SBT (an irradiated patient and a surgically managed patient). CVA is a significant risk for patients with pituitary tumors, but treatment does not seem to impact the risk. Even with long-term follow-up, SBTs are a rare event regardless of treatment modality.

  10. Mice lacking pituitary tumor transforming gene show elevated exposure of DGalNAc carbohydrate determinants

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    Lutsyk A. D.


    Full Text Available Aim. To investigate the influence of pituitary tumor transforming gene (pttg-1 knockout on glycome of parenchimal organs by means of lectin histochemistry. Methods. DGalNAc, DGlcNAc, NeuNAc carbohydrate determinants were labelled with soybean agglutinin (SBA and wheat germ agglutinin (WGA, conjugated to peroxidase, with subsequent visualization of the lectin-binding sites with diaminobenzidine. The testes and kidneys of murine strain BL6/C57 with the pttg-1 gene knockout (PTTG-KO were compared to the wild type (PTTG-WT animals, both groups 1 month of age. Results. Knockout of the pttg-1 gene was accompanied by enhanced exposure of the DGalNAc sugar residues within the Golgi complex of secondary spermatocytes, in a brush border of renal tubules and on the lumenal surface of collecting ducts. Conclusions. This study suggests that knockout of the pttg-1 gene may lead to the changes in carbohydrate processing in mammalian organism.

  11. Intestinal neuroendocrine tumor in a patient with pituitary adenoma. A case report and review of the current screening recommendations

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    Boutros Cherif


    Full Text Available Abstract Introduction Multiple endocrine neoplasia type 1 (MEN-1 patients are prone to develop carcinoid tumors. Few cases report the development of gastrointestinal carcinoid tumors in patients with MEN-1 syndrome related tumors. This is the first paper to report the occurrence of an intestinal carcinoid tumour in association with a pituitary adenoma. Case presentation A sixty eight year old female presented with intestinal obstruction four years after transphenoidal pituitary resection for pituitary adenoma. During surgical exploration and lysis of adhesions, we accidentally discovered an intestinal carcinoid tumour. Resection of the involved small bowel segment and the draining lymph nodes was undertaken. Postoperative follow up showed no biochemical or radiological evidence of residual tumor. Neuroendocrine tumors (NETs may occur as part of familial endocrine cancer syndromes including MEN-1. It is recommended that clinicians search thoroughly for MEN-1 in patients presented with NETs, however, there is no current consensus for screening patients suspected to have MEN-1 to rule out NET. Conclusion We recommend screening patients suspected to have any familial type of endocrine tumors for the presence of NET.

  12. Succinate dehydrogenase (SDH) D subunit (SDHD) inactivation in a growth-hormone-producing pituitary tumor: a new association for SDH? (United States)

    Xekouki, Paraskevi; Pacak, Karel; Almeida, Madson; Wassif, Christopher A; Rustin, Pierre; Nesterova, Maria; de la Luz Sierra, Maria; Matro, Joey; Ball, Evan; Azevedo, Monalisa; Horvath, Anelia; Lyssikatos, Charalampos; Quezado, Martha; Patronas, Nicholas; Ferrando, Barbara; Pasini, Barbara; Lytras, Aristides; Tolis, George; Stratakis, Constantine A


    Mutations in the subunits B, C, and D of succinate dehydrogenase (SDH) mitochondrial complex II have been associated with the development of paragangliomas (PGL), gastrointestinal stromal tumors, papillary thyroid and renal carcinoma (SDHB), and testicular seminoma (SDHD). Our aim was to examine the possible causative link between SDHD inactivation and somatotropinoma. A 37-yr-old male presented with acromegaly and hypertension. Other family members were found with PGL. Elevated plasma and urinary levels of catecholamines led to the identification of multiple PGL in the proband in the neck, thorax, and abdomen. Adrenalectomy was performed for bilateral pheochromocytomas (PHEO). A GH-secreting macroadenoma was also found and partially removed via transsphenoidal surgery (TTS). Genetic analysis revealed a novel SDHD mutation (c.298_301delACTC), leading to a frame shift and a premature stop codon at position 133 of the protein. Loss of heterozygosity for the SDHD genetic locus was shown in the GH-secreting adenoma. Down-regulation of SDHD protein in the GH-secreting adenoma by immunoblotting and immunohistochemistry was found. A literature search identified other cases of multiple PGL and/or PHEO in association with pituitary tumors. We describe the first kindred with a germline SDHD pathogenic mutation, inherited PGL, and acromegaly due to a GH-producing pituitary adenoma. SDHD loss of heterozygosity, down-regulation of protein in the GH-secreting adenoma, and decreased SDH enzymatic activity supports SDHD's involvement in the pituitary tumor formation in this patient. Older cases of multiple PGL and PHEO and pituitary tumors in the literature support a possible association between SDH defects and pituitary tumorigenesis.

  13. Reproductive disturbances, pituitary lactotrope adenomas, and mammary gland tumors in transgenic female mice producing high levels of human chorionic gonadotropin. (United States)

    Rulli, Susana B; Kuorelahti, Aino; Karaer, Oznur; Pelliniemi, Lauri J; Poutanen, Matti; Huhtaniemi, Ilpo


    To assess the consequences of prolonged exposure to elevated levels of LH/human chorionic gonadotropin (hCG) in the female, we developed a transgenic (TG) mouse model (hCGbeta+) that overexpresses the hCGbeta-subunit cDNA. Because of the promoter used, ubiquitin C, the transgene is expressed in multiple tissues, including the pituitary gland, in which coupling with the endogenous common alpha-subunit results in synthesis of high levels of bioactive hCG. The TG females presented with precocious puberty, infertility, enhanced ovarian steroidogenesis, and abnormal uterine structure. Pituitary enlargement was evident from the age of 2 months, which progressed to adenomas by the age of 10-12 months. Immunohistochemical studies and electron microscopy demonstrated lactotrope origin for the adenomas, associated with severe hyperprolactinemia. The mammary glands of TG females showed marked lobuloalveolar development followed by mammary tumors with characteristics of adenocarcinoma at the age of 9-12 months. More than 90% of penetrance and high frequency of metastasis (47%) was observed. Formation of the pituitary and mammary gland tumors was totally abolished by ovariectomy despite persistently elevated hCG levels. Taken together, these findings suggest that the hCG-induced aberrations of ovarian function are clearly responsible for the extragonadal tumors observed in these TG mice.

  14. EZH2 upregulation correlates with tumor invasiveness, proliferation, and angiogenesis in human pituitary adenomas. (United States)

    Liu, Bin; Pang, Bo; Wang, Qirui; Yang, Shengji; Gao, Taihong; Ding, Qian; Liu, Huajie; Yang, Yihang; Fan, Haitao; Zhang, Rui; Xin, Tao; Xu, Guangming; Pang, Qi


    Enhancer of zeste homolog 2 (EZH2) is a critical component of the polycomb repressive complex 2, which epigenetically represses genes involved in tumorigenesis and is highly expressed in tumors. However, no studies have investigated EZH2 expression and its clinical significance in human pituitary adenomas (PAs). Therefore, we examined the expression pattern of EZH2 in PAs and studied the correlations between protein expression and invasiveness, proliferation, angiogenesis, hormone functioning, and some other factors. We measured EZH2 and MMP-14 protein and EZH2 mRNA expression in 62 samples of PAs by immunohistochemistry staining and quantitative real-time polymerase chain reaction and correlated protein expression relative to clinicopathologic features. The immunopositive rate of EZH2 was 88.7% (55/62). The extent of expression was associated with invasiveness, microvessel density, and proliferation (Ki-67 index). Moreover, EZH2 expression correlated with MMP-14 expression. We did not find any correlation between EZH2 overexpression and hormone-secreting function or patient age or sex. The quantitative real-time polymerase chain reaction analysis revealed that the amount of EZH2 mRNA was significantly higher in invasive than in noninvasive adenomas. This is the first report to describe EZH2 overexpression in human PAs, especially invasive adenomas. Thus, EZH2 is a potentially useful diagnostic marker and pharmacotherapeutic target for invasive PAs. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Dengue hemorrhagic fever: A rare cause of pituitary tumor hemorrhage and reversible vision loss

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    Vimal Kumar


    Full Text Available Dengue hemorrhagic fever leading to hemorrhage in pituitary adenoma is not reported till date: We herein report the first case of bilateral visual loss secondary to pituitary adenoma hemorrhage associated with dengue hemorrhagic fever. Urgent transnasal trans sphenoidal decompression of the macroadenoma prevented permanent visual loss in this patient. Pituitary apoplexy should be considered as differential diagnosis of visual deterioration apart from retinal hemorrhage, maculopathy, and optic neuropathy in cases of dengue hemorrhagic fever. Early decompression of optic nerves helped in the restoration of vision.

  16. Acetaldehyde - ethanol interactions on calcium-activated potassium (BK channels in pituitary tumor (GH3 cells

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    Astrid G. Handlechner


    Full Text Available Background: In the central nervous system ethanol (EtOH is metabolized to acetaldehyde (ACA primarily by the oxidative enzyme catalase. Evidence suggests that ACA is responsible for at least some of the effects on the brain that have been attributed to EtOH. Various types of ion channels which are involved in electrical signaling are targets of EtOH like maxi calcium-activated potassium (BK channels. BK channels exhibit various functions like action potential repolarization, blood pressure regulation, hormone secretion, or transmitter release. In most neuronal and neuroendocrine preparations at physiological intracellular calcium levels, EtOH increases BK channel activity. The simultaneous presence of ACA and EtOH reflects the physiological situation after drinking and may result in synergistic as well as antagonistic actions compared to a single application of either drug. The action of ACA on electrical activity has yet not been fully established.Methods: GH3 pituitary tumor cells were used for outside-out and inside-out patch-clamp recordings of BK activity in excised patches. Unitary current amplitude, open probability and channel mean open time of BK channels were measured. Results: Extracellular EtOH raised BK channel activity. In the presence of intracellular ACA this increment of BK activity was suppressed in a dose- as well as calcium-dependent manner. Mean channel open time was significantly reduced by internal ACA, whereas BK channel amplitudes were not affected. The EtOH counteracting effect of ACA was found to depend on succession of application. EtOH was prevented from activating BK channels by pre-exposure of membrane patches to ACA. In contrast BK activation by a hypotonic solution was not affected by internal ACA. Conclusions: Our data suggest an inhibitory impact of ACA on BK activation by EtOH. ACA appears to interact specifically with EtOH at BK channels since intracellular ACA had no effect when BK channels were activated by

  17. Studies on the influence of radiation and chemotherapy on pituitary-testicular axis in patients with testicular tumor

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    Ogawa, Katsuaki (Yokohama City Univ. (Japan). Faculty of Medicine)


    Radiation and chemotherapy have been known as the highly effective treatment of patients with testicular tumor. To evaluate the influences of the therapies on pituitary-testicular axis, plasma FSH, LH and testosterone were determined by radioimmunoassay in 60 patients with testicular tumor before and after 1 to 102 months in the completion of radiation and chemotherapy. The results were summarized as follows: 1) In 10 out of 24 patients, plasma FSH and LH levels significantly increased within 20 months after 2,100 - 4,500 rad/3 - 6 weeks of radiation therapy. 2) In combination chromotherapy popularly used for testicular tumor, plasma FSH and LH in 8 of 22 patients markedly elevated within 20 months after the treatment. 3) The elevated gonadotropins returned to normal levels in approximately 50 months in patients received radiation or chemotherapy. 4) Plasma testosterone revealed normal levels in any therapeutic programs employed in the present study. 5) From the results of Gn-RH test, the pituitary gland seemed to have normal function. 6) Plasma testosterone showed incomplete response to hCG stimulation after 1 to 35 months of radiation or chemotherapy. Therefore, it was suggested that radiation and chemotherapy for the treatment of testicular tumor may impair not only seminiferous tubules but also Leydig cell for a couple of years.

  18. Prediction of postoperative diabetes insipidus using morphological hyperintensity patterns in the pituitary stalk on magnetic resonance imaging after transsphenoidal surgery for sellar tumors. (United States)

    Hayashi, Yasuhiko; Kita, Daisuke; Watanabe, Takuya; Fukui, Issei; Sasagawa, Yasuo; Oishi, Masahiro; Tachibana, Osamu; Ueda, Fumiaki; Nakada, Mitsutoshi


    Diabetes insipidus (DI) remains a complication of transsphenoidal surgery (TSS) for sellar and parasellar tumors. Antidiuretic hormone (ADH) appears as hyper intensity (HI) in the pituitary stalk and the posterior lobe of the pituitary gland on T1-weighted magnetic resonance (MR) imaging. Its disappearance from the posterior lobe occurs with DI, indicating a lack of ADH. The appearance of HI in the pituitary stalk indicates disturbances in ADH transport. This retrospective study included 172 patients undergoing TSS for sellar tumors at our institute from 2006 to 2014. Sequential T1-weighted MR images without enhancement were evaluated for HI in the pituitary stalk and the posterior lobe to assess the localization of ADH before and at intervals after TSS. DI was assessed pre- and postoperatively. HI in the pituitary stalk showed the following morphology: (1) ovoid in the distal end of the pituitary stalk (group A), (2) linear in the distal part of the pituitary stalk (group B), (3) linear in the whole pituitary stalk (group C). Preoperative DI occurred in 6 patients (3.5 %) with no HI observed in the posterior lobe. Postoperative DI was transient in 82 patients (47.7 %), and permanent in 11 (6.4 %). One week after surgery, HI was absent in the posterior lobe in 74 patients (43.0 %), and present in the pituitary stalk in 99 patients (57.6 %); both were significantly correlated with postoperative DI (p < 0.001). The absence of HI in the posterior lobe (A, 48.9 %; B, 68.3 %; C, 92.3 %), persistence of DI (A, 3.7 days; B, 45.9 days; C, 20.5 months), and duration until HI recovery in the posterior lobe (A, 3.6 months; B, 6.8 months; C, 22.9 months) were greatest in group C, followed by group B, and then group A. Fourteen group A patients did not have postoperative DI despite having HI in the pituitary stalk and the posterior lobe. Four group C patients developed permanent DI with persistence HI in the pituitary stalk. HI in the pituitary stalk and its

  19. A case of pediatric virilizing adrenocortical tumor resulting in hypothalamic-pituitary activation and central precocious puberty following surgical removal. (United States)

    Miyoshi, Yoko; Oue, Takaharu; Oowari, Mitsugu; Soh, Hideki; Tachibana, Makiko; Kimura, Sadami; Kiyohara, Yuki; Yamada, Hiroyuki; Bessyo, Kazuhiko; Mushiake, Sotaro; Homma, Keiko; Hasegawa, Tomonobu; Sasano, Hironobu; Ozono, Keiichi


    We present a 6-year-old boy with a virilizing adrenocortical tumor who initially presented with peripheral precocious puberty. Development of facial acne, pubic hair and a growth spurt were noted at the age of five. A low-pitched voice as well as maturation of external genitalia was noted at the age of six. Both serum and urinary levels of adrenal androgens were elevated. Abdominal computed tomography revealed a large right suprarenal mass and he underwent surgical resection without any complications. The histological diagnosis was adrenocortical carcinoma according to the criteria of Weiss. Following surgical removal of the androgen-producing tumor, the patient subsequently developed hypothalamic-pituitary activation and demonstrated central precocious puberty. He was treated with a gonadotropin-releasing hormone agonist in order to delay further pubertal progression. Clinical follow-up of potential secondary effects of excess hormone secretion after removal is important in some pediatric patients with virilizing adrenocortical tumor.

  20. Successful Pregnancy in a Female with a Large Prolactinoma after Pituitary Tumor Apoplexy

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    Butheinah A. Al-Sharafi


    Full Text Available Pituitary apoplexy is a rare condition which may cause death of the patient in severe cases and many times leads to hypopituitarism. We report a case of apoplexy in a large prolactinoma resulting in empty sella syndrome followed by a successful pregnancy. Our patient is a 32-year-old female with a history of a macroprolactinoma for approximately 17 years who presented to our hospital with a history of severe headache, decreased level of consciousness, fever, nausea, vomiting, and diplopia of 12 hours duration. Magnetic resonance imaging done on admission showed an increase in the size of the pituitary adenoma with a subtle hemorrhage. The patient was admitted to the intensive care unit and treated conservatively. The condition of the patient improved within a few days. A few months later, she started having regular menstrual periods. A magnetic resonance imaging of the pituitary 1.5 years later was reported as empty sella syndrome, and approximately one year later she became pregnant. With the pituitary adenoma being resolved after developing pituitary apoplexy and continuing on cabergoline, the patient had a successful pregnancy with no recurrence of the adenoma after delivery and breastfeeding.

  1. First Report of Coexistence of Two Ectopic Pituitary Tumors: Rathke Cleft Cyst and Silent Adrenocorticotropic Hormone Adenoma. (United States)

    Pojskić, Mirza; Zbytek, Blazej; Beckford, Neal S; Boop, Frederick A; Arnautović, Kenan I


    Rathke cleft cysts (RCCs) and pituitary adenomas (PAs) are thought to have a common embryonic ancestry; however, PAs with a concomitant RCC inside the sella turcica are rarely observed. Ectopic pituitary tumors are also rare. We present the case of a 65-year-old woman with an ectopic RCC in the sphenoid sinus and outside the sella turcica concomitant with an adrenocorticotropic hormone (ACTH)-staining, clinically silent PA. The patient had headache but no endocrine or visual disturbances. Preoperative magnetic resonance imaging revealed infrasellar cystic lesion in the sphenoid sinus with erosion of the clivus and intact sellar floor. The patient underwent gross total microsurgical resection through the transnasal route with an uneventful postoperative course. To our knowledge, this is the first reported ectopic RCC located outside the sella turcica with a concomitant ACTH-staining PA. This also appears to be the first ACTH-staining adenoma concomitant with RCC reported in the literature, regardless of location, not presenting with Cushing disease. This case shows that we can now include pituitary adenoma with or without a concomitant RCC in the differential diagnosis of processes in the sphenoid sinus. As both PAs and RCCs are benign sellar lesions, surgical management of a concomitant occurrence of these tumors mainly depends on the size of the lesions and their clinical manifestations. For patients with PA and concomitant RCC, surgical resection should be considered, as there is an approximatrely 20% recurrence rate of the cyst after resection and the possibility of future clival erosion, if left untreated. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Octreotide and pasireotide (dis)similarly inhibit pituitary tumor cells in vitro. (United States)

    Ibáñez-Costa, Alejandro; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C; Gahete, Manuel D; Jiménez-Reina, Luis; Venegas-Moreno, Eva; de la Riva, Andrés; Arráez, Miguel Ángel; González-Molero, Inmaculada; Schmid, Herbert A; Maraver-Selfa, Silvia; Gavilán-Villarejo, Inmaculada; García-Arnés, Juan Antonio; Japón, Miguel A; Soto-Moreno, Alfonso; Gálvez, María A; Luque, Raúl M; Castaño, Justo P


    Somatostatin analogs (SSA) are the mainstay of pharmacological treatment for pituitary adenomas. However, some patients escape from therapy with octreotide, a somatostatin receptor 2 (sst2)-preferring SSA, and pasireotide, a novel multi-sst-preferring SSA, may help to overcome this problem. It has been proposed that correspondence between sst1-sst5 expression pattern and SSA-binding profile could predict patient's response. To explore the cellular/molecular features associated with octreotide/pasireotide response, we performed a parallel comparison of their in vitro effects, evaluating sst1-sst5 expression, intracellular Ca 2+ signaling ([Ca 2+ ] i ), hormone secretion and cell viability, in a series of 85 pituitary samples. Somatotropinomas expressed sst5>sst2, yet octreotide reduced [Ca 2+ ] i more efficiently than pasireotide, while both SSA similarly decreased growth hormone release/expression and viability. Corticotropinomas predominantly expressed sst5, but displayed limited response to pasireotide, while octreotide reduced functional endpoints. Non-functioning adenomas preferentially expressed sst3 but, surprisingly, both SSA increased cell viability. Prolactinomas mainly expressed sst1 but were virtually unresponsive to SSA. Finally, both SSA decreased [Ca 2+ ] i in normal pituitaries. In conclusion, both SSA act in vitro on pituitary adenomas exerting both similar and distinct effects; however, no evident correspondence was found with the sst1-sst5 profile. Thus, it seems plausible that additional factors, besides the simple abundance of a given sst, critically influence the SSA response. © 2016 Society for Endocrinology.

  3. Pituitary lymphoma developing within pituitary adenoma. (United States)

    Morita, Ken; Nakamura, Fumihiko; Kamikubo, Yasuhiko; Mizuno, Naoaki; Miyauchi, Masashi; Yamamoto, Go; Nannya, Yasuhito; Ichikawa, Motoshi; Kurokawa, Mineo


    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.

  4. Long-term results of radiotherapy for pituitary adenomas. Evaluation of tumor control and hypopituitarism after radiotherapy

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    Tsuchida, Emiko; Sakai, Kunio; Matsumoto, Yasuo; Sugita, Tadashi; Sasamoto, Ryuta [Niigata Univ. (Japan). School of Medicine


    To evaluate the results of conventional radiotherapy for pituitary adenomas assessed with computed tomography (CT) or magnetic resonance imaging (MRI). Endpoints include tumor control, normalization of hormone levels in functioning adenomas, and hypopituitarism after radiotherapy as an adverse effect. Forty-two patients were treated with radiotherapy from 1982 to 1995 at Niigata University Hospital. Forty patients were irradiated after surgery because of residual adenomas in 33 patients and tumor regrowth in 7 patients. One patient was treated with radiotherapy alone, and the remaining 1 patient was treated with preoperative radiotherapy. Tumor size and extension were evaluated using CT or MRI, and all tumors were macroadenomas. They consisted of 18 non-functioning and 24 functioning adenomas (growth hormone (GH)-secreting: 11, prolactinomas: 7, concomitant GH and prolactin (PRL)-secreting: 5, gonadotropin-secreting: 1). Treatment was given in 200 cGy daily fraction size and a total dose of 50 Gy was given to most patients. Sixteen patients with GH- and/or PRL-secreting adenomas received bromocriptine. Tumor progression was determined by increase in tumor size as shown by CT or MRI. Hypopituitarism after radiotherapy was evaluated using the functions of corticotropin (ACTH), thyrotropin (TSH), and gonadotropin. Median follow-up time from the end of radiotherapy was 103 months. Tumor progression occurred in 2 out of 42 patients and 10-year progression-free rate for all patients was 93.7%. Normalization of GH levels was obtained in 12 of 16 GH-secreting adenomas with a mean time of 27 months after radiotherapy, and 9 of 12 PRL-secreting adenomas achieved normalization of PRL levels with a mean time of 34 months. One gonadotropin-secreting adenoma achieved normalization of gonadotropin level at 21 months after radiotherapy. The incidence of hypopituitarism after radiotherapy increased with time, and cumulative risk of deficiencies of ACTH, TSH, and gonadotropin at 10

  5. Epstein-Barr virus-based vector improves the tumor cell killing effect of pituitary tumor in HVJ-liposome-mediated transcriptional targeting suicide gene therapy. (United States)

    Izumo, Tsuyoshi; Ohtsuru, Akira; Tokunaga, Yoshiharu; Namba, Hiroyuki; Kaneda, Yasufumi; Nagata, Izumi; Yamashita, Shunichi


    Although tissue-specific promoters offer a promising approach to the targeting of gene therapy, the activity of such promoters is generally low, which is thus a major limitation, especially when using non-viral vectors. To establish effective transcriptional targeting gene therapy for growth hormone (GH) producing pituitary tumors, an Epstein-Barr virus (EBV) based vector system expressing herpes simplex virus type 1 thymidine kinase (HSV1-TK) driven by a rat GH promoter (pEBGTK) was developed. This harbors an EBV nuclear antigen-1 (EBNA-1) gene with an origin of the latent viral DNA replication (OriP) gene of EBV. We constructed an EBV-based luciferase plasmid (pEBGL) as a reporter plasmid. We also generated pGTK and pGL, which are non-EBV counterparts. Metastatic GH3 (mGH3) cells were used in this study. The transfection of pEBGL to mGH3 resulted in approximately a 39 times greater luciferase activity than pGL in vitro. Its expression was also prolonged 144 h after transfection. According to the results of pEBGL gene transfer in in vivo experiments, the luciferase activity was only observed in the tumors, but not detected in other normal tissues. The luciferase activities in tumor tissues were found until day 25 post transfection. During in vitro gene therapy, the transfection by pEBGTK using hemmaglutinating virus of Japan (HVJ) liposome enhances the susceptibility of mGH3 to gancyclovir (GCV) 110 times more than that by pGTK. The in vivo anti-tumor effects of pEBGTK on mGH3-tumor-bearing nude mice were evaluated. The intratumoral injection of HVJ anionic lipososme-enveloped pEBGTK followed by the intra-peritoneal injection of GCV demonstrated a significant growth inhibition against tumors without toxicity, while the tumors treated by other treatment modalities grew progressively. These results demonstrated that the EBV-based vector system can therefore contribute to the improvement of the anti-tumor effects for the HVJ-liposome-mediated transcriptional

  6. Localization of carboxyl ester lipase in human pituitary gland and pituitary adenomas. (United States)

    La Rosa, Stefano; Vigetti, Davide; Placidi, Claudia; Finzi, Giovanna; Uccella, Silvia; Clerici, Moira; Bartolini, Barbara; Carnevali, Ileana; Losa, Marco; Capella, Carlo


    Carboxyl ester lipase (CEL) is an enzyme that hydrolyzes a wide variety of lipid substrates, including ceramides, which are known to show inhibitory regulation of pituitary hormone secretion in experimental models. Because no studies on CEL expression in human pituitary and pituitary adenomas have been reported in the literature, we investigated CEL expression in 10 normal pituitary glands and 86 well-characterized pituitary adenomas [12 FSH/LH cell, 17 α-subunit/null cell, 6 TSH cell, 21 ACTH cell, 11 prolactin (PRL) cell, and 19 GH cell adenomas] using IHC, immunoelectron microscopy, Western blotting, and quantitative RT-PCR. In normal adenohypophysis, CEL was localized in GH, ACTH, and TSH cells. In adenomas, it was mainly found in functioning GH, ACTH, and TSH tumors, whereas its expression was poor in the corresponding silent adenomas and was lacking in FSH/LH cell, null cell, and PRL cell adenomas. Ultrastructurally, CEL was localized in secretory granules close to their membranes. This is the first study demonstrating CEL expression in normal human pituitary glands and in functioning GH, ACTH, and TSH adenomas. Considering that CEL hydrolyzes ceramides, inactivating their inhibitory function on pituitary hormone secretion, our findings suggest a possible role of CEL in the regulation of hormone secretion in both normal and adenomatous pituitary cells.

  7. [Practice guideline for diagnosis and treatment of craniopharyngioma and parasellar tumors of the pituitary gland]. (United States)

    Venegas, Eva; Concepcion, Blanco; Martin, Tomas; Soto, Alfonso


    Craniopharyngiomas are rare, locally aggressive epithelial tumors usually located in the sellar and suprasellar region. Diagnosis of craniopharyngioma is usually suggested by clinical and radiological findings that should be confirmed histologically. Surgery is the treatment of choice for most patients. The goal of surgery is to relieve compressive symptoms and to remove as much tumor as safely possible. Radiation therapy is the usual treatment to control postoperative tumor remnants and local recurrences. Parasellar lesions are low prevalent lesions and include neoplastic, inflammatory, infectious, developmental, and vascular diseases. Both their diagnosis and treatment depend on the type of lesion. Copyright © 2014 SEEN. Published by Elsevier Espana. All rights reserved.

  8. Relative potencies of the somatostatin analogs octreotide, BIM-23014, and RC-160 on the inhibition of hormone release by cultured human endocrine tumor cells and normal rat anterior pituitary cells

    NARCIS (Netherlands)

    L.J. Hofland (Leo); P.M. van Koetsveld (Peter); M. Waaijers (Marlijn); J. Zuyderwijk; S.W.J. Lamberts (Steven)


    textabstractIn the present study we investigated the effects of the somatostatin (SS) analogs octreotide, RC-160, and BIM-23014 on GH release by cultured cells of human GH-secreting pituitary tumors, in normal rat anterior pituitary cells, and on gastrin release by

  9. Growth hormone deficiency in elderly patients with hypothalamo-pituitary tumors. (United States)

    Colao, A; Cerbone, G; Pivonello, R; Klain, M; Aimaretti, G; Faggiano, A; Di Somma, C; Salvatore, M; Lombardi, G


    In 18 patients with hypothalamo-pituitary diseases aged over 60 years and in 18 sex, age- and BMI-matched healthy subjects, the results of plasma IGF-I and IGF-BP3 levels and the GH response to GHRH + arginine test (GHRH + ATT) were correlated to the results of body composition, serum osteocalcin (OC) and urinary cross-linked N-telopeptides of type I collagen (Ntx) and the bone mineral density (BMD). In 10 patients and 10 controls, the GH response to ITT was also evaluated. The GH response to GHRH + ATT and ITT was markedly reduced in patients compared to controls (3.1 +/- 0.7 vs. 23.2 +/- 2.3 micrograms/L, P Body composition analysis revealed a significant increase of fat mass (37.4 +/- 2.2 vs. 28.0 +/- 1.0%, P body water (45.7 +/- 1.5 vs. 52.5 +/- 1.1%, P < 0.001) in patients compared to controls. Serum OC levels were lower (1.9 +/- 0.1 vs. 4.6 +/- 0.4 micrograms/L, P < 0.001) in patients than in controls, whereas urinary Ntx levels were similar. BMD values in lumbar spine (0.81 +/- 0.02 vs. 0.90 +/- 0.02 g/cm2, P < 0.001) and femoral neck (0.70 +/- 0.02 vs. 0.82 +/- 0.02 g/cm2, P < 0.001) were significantly lower in patients than in controls. A significant inverse correlation was found between GHD duration and lumbar spine (r = -0.73, P&1t; 0.001) or femoral neck (r = -0.81, P&1t; 0.001) BMD values and a significant direct correlation was found between GH peak after GHRH + ATT and lumbar BMD (r = 0.69, p = 0.001) in GHD patients. In conclusion, GHD in patients over 60 yrs aged with a characteristic history of hypothalamus-pituitary pathology is distinct from the physiological decline in GH secretion associated with aging.

  10. Succinate dehydrogenase (SDHx) mutations in pituitary tumors: could this be a new role for mitochondrial complex II and/or Krebs cycle defects? (United States)

    Xekouki, Paraskevi; Stratakis, Constantine A


    Succinate dehydrogenase (SDH) or mitochondrial complex II is a multimeric enzyme that is bound to the inner membrane of mitochondria and has a dual role as it serves both as a critical step of the tricarboxylic acid or Krebs cycle and as a member of the respiratory chain that transfers electrons directly to the ubiquinone pool. Mutations in SDH subunits have been implicated in the formation of familial paragangliomas (PGLs) and/or pheochromocytomas (PHEOs) and in Carney-Stratakis syndrome. More recently, SDH defects were associated with predisposition to a Cowden disease phenotype, renal, and thyroid cancer. We recently described a kindred with the coexistence of familial PGLs and an aggressive GH-secreting pituitary adenoma, harboring an SDHD mutation. The pituitary tumor showed loss of heterozygosity at the SDHD locus, indicating the possibility that SDHD's loss was causatively linked to the development of the neoplasm. In total, 29 cases of pituitary adenomas presenting in association with PHEOs and/or extra-adrenal PGLs have been reported in the literature since 1952. Although a number of other genetic defects are possible in these cases, we speculate that the association of PHEOs and/or PGLs with pituitary tumors is a new syndromic association and a novel phenotype for SDH defects.

  11. Tumor Shrinkage Assessed by Volumetric MRI in Long-Term Follow-Up After Fractionated Stereotactic Radiotherapy of Nonfunctioning Pituitary Adenoma

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    Kopp, Christine, E-mail: [Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich (Germany); Theodorou, Marilena; Poullos, Nektarios; Jacob, Vesna; Astner, Sabrina T.; Molls, Michael [Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich (Germany); Grosu, Anca-Ligia [Klinik fuer Strahlenheilkunde, Universitaet Freiburg, Freiburg (Germany)


    Purpose: To evaluate tumor control and side effects associated with fractionated stereotactic radiotherapy (FSRT) in the management of residual or recurrent nonfunctioning pituitary adenomas (NFPAs). Methods and Materials: We assessed exact tumor volume shrinkage in 16 patients with NFPA after FSRT. All patients had previously undergone surgery. Gross tumor volume (GTV) was outlined on contrast-enhanced magnetic resonance imaging (MRI) before and median 63 months (range, 28-100 months) after FSRT. MRI was performed as an axial three-dimensional gradient echo T1-weighted sequence at 1.6-mm slice thickness without gap (3D MRI). Results: Mean tumor size of all 16 pituitary adenomas before treatment was 7.4 mL (3.3-18.9 mL). We found shrinkage of the treated pituitary adenoma in all patients. Within a median follow-up of 63 months (28-100 months) an absolute mean volume reduction of 3.8 mL (0.9-12.4 mL) was seen. The mean relative size reduction compared with the volume before radiotherapy was 51% (22%-95%). Shrinkage measured by 3D MRI was greater at longer time intervals after radiotherapy. A strong negative correlation between the initial tumor volume and the absolute volume reduction after FSRT was found. There was no correlation between tumor size reduction and patient age, sex, or number of previous surgeries. Conclusions: By using 3D MRI in all patients undergoing FSRT of an NFPA, tumor shrinkage is detected. Our data demonstrate that volumetric assessment based on 3D MRI adds additional information to routinely used radiological response measurements. After FSRT a mean relative size reduction of 51% can be expected within 5 years.

  12. Prediction of Long-term Post-operative Testosterone Replacement Requirement Based on the Pre-operative Tumor Volume and Testosterone Level in Pituitary Macroadenoma (United States)

    Lee, Cheng-Chi; Chen, Chung-Ming; Lee, Shih-Tseng; Wei, Kuo-Chen; Pai, Ping-Ching; Toh, Cheng-Hong; Chuang, Chi-Cheng


    Non-functioning pituitary macroadenomas (NFPAs) are the most prevalent pituitary macroadenomas. One common symptom of NFPA is hypogonadism, which may require long-term hormone replacement. This study was designed to clarify the association between the pre-operative tumor volume, pre-operative testosterone level, intraoperative resection status and the need of long-term post-operative testosterone replacement. Between 2004 and 2012, 45 male patients with NFPAs were enrolled in this prospective study. All patients underwent transsphenoidal surgery. Hypogonadism was defined as total serum testosterone levels of operative magnetic resonance images. We prescribed testosterone to patients with defined hypogonadism or clinical symptoms of hypogonadism. Hormone replacement for longer than 1 year was considered as long-term therapy. The need for long-term post-operative testosterone replacement was significantly associated with larger pre-operative tumor volume (p = 0.0067), and lower pre-operative testosterone level (p = 0.0101). There was no significant difference between the gross total tumor resection and subtotal resection groups (p = 0.1059). The pre-operative tumor volume and testosterone level impact post-operative hypogonadism. By measuring the tumor volume and the testosterone level and by performing adequate tumor resection, surgeons will be able to predict post-operative hypogonadism and the need for long-term hormone replacement. PMID:26537232

  13. [Effect of transcutaneous acupoint electric stimulation on perioperative intravenous anesthesia in patients of transsphenoidal pituitary tumor resection]. (United States)

    Chen, Xue; Wang, Bao-Guo; Li, Jin; An, Li-Xin


    To observe the impacts of transcutaneous acupoint electric stimulation on hemodynamics, anesthetic and relevant complications in patients of transsphenoidal pituitary tumor resection (TPTR). Ninety cases of the selective TPTR were randomized into a transcutaneous acupoint electric stimulation group (group T), a sham-acupoint group (group S) and a control group (group C); 30 cases in each one. In group T, the transcutaneous acupoint electric stimulation at Hegu (LI 4), Waiguan (TE 5), Jinmen (BL 63), Taichong (LR 3), Zusanli (ST 36) and Qiuxu (GB 40). In group S, the transcutaneous acupoint electric stimulation was applied to the sham-acupoints. In group C, the acupoints selected were same as those in group T, but the electrode pads were just attached on the related points with no-electric stimulation. The electric stimulation lasted from analgesic induction till the end of the operation. The endotracheal intubation was done under the induction by propofol, fentanyl and vecuronium bromide. Propofol and remifentanil were maintained till the end of operation. Blood pressure, heart rate, bispectral index (BIS) value, anesthetic and postoperative recovery situation were recorded. The hemodynamics maintained stably in each group. In group T, the mean arterial pressure 1 min after intubation, after extubation and during directional force recovery was all lower than the other two groups respectively (all Pelectric stimulation improves the stability of hemodynamics in perioperative stage, reduces the intraoperative opi oids dosages and improves the quality of anesthetic recovery.

  14. Pituitary Tumor-Transforming Gene 1 Is Expressed in Primary Ductal Breast Carcinoma, Lymph Node Infiltration, and Distant Metastases

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    Fabio Grizzi


    Full Text Available Despite the advances that have been made in the fields of molecular and cell biology, there is still considerable debate explaining how the breast cancer cells progress through carcinogenesis and acquire their metastatic ability. The lack of preventive methods and effective therapies underlines the pressing need to identify new biomarkers that can aid early diagnosis and may be targets for effective therapeutic strategies. In this study we explore the pituitary tumor-transforming gene 1 (PTTG1 expression in primary ductal breast carcinoma, lymph node infiltration, and distant metastases. Three human cell lines, 184B5 derived from normal mammary epithelium, HCC70 from a primary ductal carcinoma, and MDA-MB-361 from a breast metastasis, were used for quantifying PTTG1 mRNA expression. The PTTG1 immunohistochemical expression was carried out on specimens taken from eight patients with invasive ductal breast cancer who underwent surgical treatment and followup for five years retrospectively selected. The study demonstrated that PTTG1 is expressed gradually in primary ductal breast carcinoma, lymph node infiltration, and distant metastases. Our findings suggest that the immunohistochemical evaluation of PTTG1 expression might be a powerful biomarker of recognition and quantification of the breast cancer cells in routine pathological specimens and a potential target for developing an effective immunotherapeutic strategy for primary and metastatic breast cancer.

  15. Identification and characterization of two novel truncated but functional isoforms of the somatostatin receptor subtype 5 differentially present in pituitary tumors. (United States)

    Durán-Prado, Mario; Gahete, Manuel D; Martínez-Fuentes, Antonio J; Luque, Raúl M; Quintero, Ana; Webb, Susan M; Benito-López, Pedro; Leal, Alfonso; Schulz, Stefan; Gracia-Navarro, F; Malagón, María M; Castaño, Justo P


    Somatostatin and its related peptide cortistatin exert multiple actions on normal and tumoral tissue targets through a family of receptors termed somatostatin receptor (sst)1-5. Despite the considerable advances in the knowledge on these receptors and their (patho)physiological roles, there is still evidence that additional receptors for these peptides should exist to fully explain their actions. The growing number of spliced variants found in similar receptor families, often present in tumors, and results from our group obtained on sst5 from other species (pig) led us to explore the existence of new human sst5 isoforms. A rapid amplification of cDNA ends PCR approach on samples from a human pituitary tumor and a cell line enabled identification of two novel alternatively spliced sst5 receptor variants. The sequences obtained encode putative proteins that correspond to truncated isoforms of five and four transmembrane domains (TMDs), accordingly named sst5TMD5 and sst5TMD4, respectively. Both novel receptors show a differential expression pattern in normal tissues and are also present in pituitary tumors of diverse etiology including nonfunctioning adenomas, corticotropinomas, somatotropinomas, and a prolactinoma. In contrast to the predominant plasma membrane localization of full-length sst5, both sst5TMD5 and sst5TMD4 show a preferentially intracellular localization. Despite their truncated nature, both receptors are functional, as shown by their ability to mediate selective, ligand-induced rises in free cytosolic calcium concentration. Specifically, whereas sst5TMD5 is selectivity activated by somatostatin compared with cortistatin, cells transfected with sst5TMD4 almost exclusively respond to cortistatin and not to somatostatin. Our results demonstrate the existence of two previously unidentified sst5 spliced variants with distinct distribution in normal tissues and pituitary tumors, unique ligand-selective signaling properties, and subcellular distribution

  16. Anatomy, Physiology, and Laboratory Evaluation of the Pituitary Gland. (United States)

    Hong, Gregory K; Payne, Spencer C; Jane, John A


    The pituitary gland functions prominently in the control of most endocrine systems in the body. Diverse processes such as metabolism, growth, reproduction, and water balance are tightly regulated by the pituitary in conjunction with the hypothalamus and various downstream endocrine organs. Benign tumors of the pituitary gland are the primary cause of pituitary pathology and can result in inappropriate secretion of pituitary hormones or loss of pituitary function. First-line management of clinically significant tumors often involves surgical resection. Understanding of normal pituitary physiology and basic testing strategies to assess for pituitary dysfunction should be familiar to any skull base surgeon. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Pituitary tumor evaluation

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    Albertson, B.; Binney, S.


    This paper describes research on the following: the structure of {sup 10}B{sub 10}-ovine corticotropin releasing hormone and {sup 10}B{sub 10}-growth hormone releasing hormone; the BNCT effect on AtT-20 cell {sup 10}B{sub 10}-CRH incubations in vitro; BNCT effects on GH{sub 4}C{sub 1} cell {sup 10}B{sub 10} growth hormone releasing factor incubation in vitro; and competitive inhibition of AtT-20 cell BNCT effect.

  18. Stages of Pituitary Tumors (United States)

    ... occur: Headache. Some loss of vision. Loss of body hair. In women, less frequent or no menstrual periods ... in the face, neck, and trunk of the body, and thin arms and legs. A lump of fat on ... bruising. Growth of fine hair on the face, upper back, or arms. Bones ...

  19. Granulocytes as effective anticancer agent in experimental solid tumor models. (United States)

    Jaganjac, Morana; Poljak-Blazi, Marija; Kirac, Iva; Borovic, Suzana; Joerg Schaur, Rudolf; Zarkovic, Neven


    The aim of the study was to elucidate the effects of murine granulocytes on the growth of solid murine tumors when administrated in the vicinity of W256 carcinoma growing in Sprague Dawley rats, and in the vicinity of Ehrlich ascites tumor (EAT) growing in BALBc mice. The administration of granulocytes significantly improved the survival of W256-bearing rats, and increased the tumor regression incidence from 17% up to 75%. Rats with regressing tumors had 2.5 times increased levels of granulocytes in peripheral blood, which were also cytotoxic in vitro for W256 carcinoma cells. However, blood levels of cytokine-induced neutrophil chemoattractant-2, tumor necrosis factor α and interleukin 6 were similar between rats with regressing tumors and control healthy rats, suggesting that the observed regression of W256 carcinoma was caused by specific anticancer effects of the applied granulocytes. Anticancer effects of granulocytes were also found in BALBc mice bearing solid form of EAT, resulting in a 20% increase of survival in EAT-bearing mice. Therefore, the administration of granulocytes, isolated from healthy animals and applied at the site of solid tumors in rats and in mice, reduced experimental tumor growth, and extended the survival of tumor-bearing animals, while in some rats it even caused a W256 regression. Copyright © 2010 Elsevier GmbH. All rights reserved.

  20. Influência dos níveis de prolactina e tamanho tumoral na função hipofisária pós-operatória em macroadenomas hipofisários clinicamente não-funcionantes Influence of hyperprolactinemia and tumoral size in the postoperative pituitary function in clinically nonfuncioning pituitary macroadenomas

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    Ana Luiza Vidal Fonseca


    Full Text Available OBJETIVO: Estudar a influência da hiperprolactinemia e de tamanho tumoral na função hipofisária em macroadenomas hipofisários clinicamente não funcionantes. MÉTODOS: Foram analisados 23 pacientes com macroadenomas hipofisários clinicamente não funcionantes, com exames de imagem (tomografia computadorizada ou ressonância magnética e dosagens hormonais basais; 16 tinham provas de função hipotálamo-hipofisária (megateste pré-operatórios. Todos os tumores tiveram diagnóstico histológico e em 17 foi realizado também estudo imuno-histoquímico para os hormônios adeno-hipofisários. A análise estatística foi feita por meio dos testes t de Student, qui-quadrado, exato de Fisher e de Mc Neman. O nível de significância adotado foi 5% (pOBJECTIVE: To study the influence of hyperprolactinemia and tumoral size in the pituitary function in clinically nonfuncioning pituitary macroadenomas. METHODS: Twenty three patients with clinically nonfuncioning pituitary macroadenomas were evaluated by image studies (computed tomography or magnetic resonance and basal hormonal level; 16 had preoperative hypothalamus-hypophysial function tests (megatests. All tumors had histological diagnosis and in seventeen immunohistochemical study for adenohypophysial hormones was also performed. Student's t test, chi square test, exact test of Fisher and Mc Neman test were used for the statistics analysis . The level of significance adopted was 5% (p<0.05. RESULTS: Tumoral diameter varied of 1.1 to 4.7 cm (average=2.99 cm ± 1.04. In the preoperative, 5 (21.7% patients did not show laboratorial hormonal deficit, 9 (39.1% developed hyperprolactinemia, 13 (56,5% normal levels of prolactin (PRL and 1 (4.3% subnormal; 18 (78.3% patients developed hypopituitarism (4 pan-hypopituitarism. Nineteen patients (82.6% underwent transsfenoidal approach, 3 (13% craniotomy and 1 (4.4% combined access. Only 6 patients had total tumoral resection. Of the 17 immunohistochemical

  1. Elevated plasma levels of the pituitary hormone Cthrc1 in individuals with red hair but not in patients with solid tumors.

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    Christine W Duarte

    Full Text Available An increasing number of studies report that Cthrc1 is expressed in various cancer cells. The present study sought to identify which cells in tumors and remodeling tissues express Cthrc1 and investigate the range of circulating human Cthrc1 levels in health and disease.Highly specific monoclonal antibodies were generated to detect Cthrc1 by ELISA in plasma and in tissues by immunohistochemistry. In human colon, gastric, breast, endometrial, pancreatic, kidney, lung and skin cancer, Cthrc1 was expressed by activated stromal cells and not the cancer cells themselves. Similarly, conditions evoking tissue remodeling, such as wound repair or angiotensin II-mediated hypertension, induced Cthrc1 expression in interstitial and adventitial fibroblasts and perivascular stromal cells. Levels of Cthrc1 in plasma from healthy subjects were near the lower detection limit except for individuals with red hair, who had up to several hundred fold higher levels. Elevated Cthrc1 was also found in patients with diabetes, inflammatory conditions, and infections, but not solid tumors. Transgenic mouse studies suggested that Cthrc1 expression by stromal cells does not contribute to circulating levels. In human pituitaries, Cthrc1 was expressed in the anterior and intermediate lobes with unencapsulated Cthrc1 accumulations typically surrounded by chromophobe cells.We identify Cthrc1 as a marker for activated stromal cells. Cthrc1 is a pituitary hormone with significantly elevated levels in subjects carrying variant alleles of the melanocortin-1 receptor as wells as in patients with inflammatory conditions.

  2. Tumorigenic potential of pituitary tumor transforming gene (PTTG) in vivo investigated using a transgenic mouse model, and effects of cross breeding with p53 (+/-) transgenic mice. (United States)

    Fong, Miranda Y; Farghaly, Hanan; Kakar, Sham S


    Pituitary tumor-transforming gene (PTTG) is an oncogene that is overexpressed in variety of tumors and exhibits characteristics of a transforming gene. Previous transgenic mouse models to access the tumorigenic potential in the pituitary and ovary have resulted in dysplasia without formation of visible tumors, possibly due to the insufficient expression of PTTG. PTTG expression level is critical for ovarian tumorigenesis in a xenograft model. Therefore, the tumorigenic function of PTTG in vivo remains unclear. We generated a transgenic mouse that overexpresses PTTG driven by the CMV promoter to determine whether PTTG functions as a transforming oncogene that is capable of initiating tumorigenesis. Transgenic animals were generated by microinjection of PTTG transgene into the male pronucleus of FVB 0.5 day old embryos. Expression levels of PTTG in tissues of transgenic animals were analyzed using an immunohistochemical analysis. H&E staining and immunohistostaining were performed to examine the type of tumor in transgenic and PTTG transgenic/p53+/- animals. PTTG transgenic offspring (TgPTTG) were monitored for tumor development at various ages. H&E analysis was performed to identify the presence of cancer and hyperplastic conditions verified with the proliferation marker PCNA and the microvessel marker CD31. Immunohistochemistry was performed to determine transgene expression, revealing localization to the epithelium of the fallopian tube, with more generalized expression in the liver, lung, kidney, and spleen. At eight months of age, 2 out of 15 TgPTTG developed ovarian cancer, 2 out of 15 developed benign tumors, 2 out of 15 developed cervical dysplasia, and 3 out of 15 developed adenomyosis of the uterus. At ten months of age, 2 out of 10 TgPTTG developed adenocarcinoma of the ovary, 1 out of 10 developed a papillary serous adenocarcinoma, and 2 out of 10 presented with atypia of ovarian epithelial cells. Tumorigenesis is a multi-step process, often requiring

  3. Tumorigenic potential of pituitary tumor transforming gene (PTTG in vivo investigated using a transgenic mouse model, and effects of cross breeding with p53 (+/− transgenic mice

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    Fong Miranda Y


    Full Text Available Abstract Background Pituitary tumor-transforming gene (PTTG is an oncogene that is overexpressed in variety of tumors and exhibits characteristics of a transforming gene. Previous transgenic mouse models to access the tumorigenic potential in the pituitary and ovary have resulted in dysplasia without formation of visible tumors, possibly due to the insufficient expression of PTTG. PTTG expression level is critical for ovarian tumorigenesis in a xenograft model. Therefore, the tumorigenic function of PTTG in vivo remains unclear. We generated a transgenic mouse that overexpresses PTTG driven by the CMV promoter to determine whether PTTG functions as a transforming oncogene that is capable of initiating tumorigenesis. Methods Transgenic animals were generated by microinjection of PTTG transgene into the male pronucleus of FVB 0.5 day old embryos. Expression levels of PTTG in tissues of transgenic animals were analyzed using an immunohistochemical analysis. H&E staining and immunohistostaining were performed to examine the type of tumor in transgenic and PTTG transgenic/p53+/- animals. Results PTTG transgenic offspring (TgPTTG were monitored for tumor development at various ages. H&E analysis was performed to identify the presence of cancer and hyperplastic conditions verified with the proliferation marker PCNA and the microvessel marker CD31. Immunohistochemistry was performed to determine transgene expression, revealing localization to the epithelium of the fallopian tube, with more generalized expression in the liver, lung, kidney, and spleen. At eight months of age, 2 out of 15 TgPTTG developed ovarian cancer, 2 out of 15 developed benign tumors, 2 out of 15 developed cervical dysplasia, and 3 out of 15 developed adenomyosis of the uterus. At ten months of age, 2 out of 10 TgPTTG developed adenocarcinoma of the ovary, 1 out of 10 developed a papillary serous adenocarcinoma, and 2 out of 10 presented with atypia of ovarian epithelial cells

  4. Effects of bromocriptine on serum prolactin levels, pituitary weight and immunoreactive prolactin cells in estradiol-treated ovariectomized rats: an experimental model of estrogen-dependent hyperprolactinemia

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    M.F. Ribeiro


    Full Text Available The present study was designed to assess the effects of bromocriptine, a dopamine agonist, on pituitary wet weight, number of immunoreactive prolactin cells and serum prolactin concentrations in estradiol-treated rats. Ovariectomized Wistar rats were injected subcutaneously with sunflower oil vehicle or estradiol valerate (50 or 300 µg rat-1 week-1 for 2, 4 or 10 weeks. Bromocriptine (0.2 or 0.6 mg rat-1 day-1 was injected daily during the last 5 or 12 days of estrogen treatment. Data were compared with those obtained for intact control rats. Administration of both doses of estrogen increased serum prolactin levels. No difference in the number of prolactin cells in rats treated with 50 µg estradiol valerate was observed compared to intact adult animals. In contrast, rats treated with 300 µg estradiol valerate showed a significant increase in the number of prolactin cells (P<0.05. Therefore, the increase in serum prolactin levels observed in rats treated with 50 µg estradiol valerate, in the absence of morphological changes in the pituitary cells, suggests a "functional" estrogen-induced hyperprolactinemia. Bromocriptine decreased prolactin levels in all estrogen-treated rats. The administration of this drug to rats previously treated with 300 µg estradiol valerate also resulted in a significant decrease in pituitary weight and number of prolactin cells when compared to the group treated with estradiol alone. The general antiprolactinemic and antiproliferative pituitary effects of bromocriptine treatment reported here validate the experimental model of estrogen-induced hyperprolactinemic rats

  5. The Impact of Environmental Light Intensity on Experimental Tumor Growth. (United States)

    Suckow, Mark A; Wolter, William R; Duffield, Giles E


    Cancer research requires for consistent models that minimize environmental variables. Within the typical laboratory animal housing facility, animals may be exposed to varying intensities of light as a result of cage type, cage position, light source, and other factors; however, studies evaluating the differential effect of light intensity during the light phase on tumor growth are lacking. The effect of cage face light intensity, as determined by cage rack position was evaluated with two tumor models using the C57Bl/6NHsd mouse and transplantable B16F10 melanoma cells or Lewis lung carcinoma (LLC) cells. Animals were housed in individually-ventilated cages placed at the top, middle, or bottom of the rack in a diagonal pattern so that the top cage was closest to the ceiling light source, and cage face light intensity was measured. Following a two-week acclimation period at the assigned cage position, animals were subcutaneously administered either 1.3×106 B16F10 melanoma cells or 2.5×105 Lewis lung carcinoma cells. Weights of excised tumors were measured following euthanasia 18 days (melanoma) or 21 days (LCC) after tumor cell administration. Cage face light intensity was significantly different depending on the location of the cage, with cages closest to the light source have the greatest intensity. Mean tumor weights were significantly less (plight intensity mice compared to high and low light intensity mice. The environmental light intensity to which experimental animals are exposed may vary markedly with cage location and can significantly influence experimental tumor growth, thus supporting the idea that light intensity should be controlled as an experimental variable for animals used in cancer research. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  6. Preoperative volume determination for pituitary adenoma (United States)

    Zukic, Dženan; Egger, Jan; Bauer, Miriam H. A.; Kuhnt, Daniela; Carl, Barbara; Freisleben, Bernd; Kolb, Andreas; Nimsky, Christopher


    The most common sellar lesion is the pituitary adenoma, and sellar tumors are approximately 10-15% of all intracranial neoplasms. Manual slice-by-slice segmentation takes quite some time that can be reduced by using the appropriate algorithms. In this contribution, we present a segmentation method for pituitary adenoma. The method is based on an algorithm that we have applied recently to segmenting glioblastoma multiforme. A modification of this scheme is used for adenoma segmentation that is much harder to perform, due to lack of contrast-enhanced boundaries. In our experimental evaluation, neurosurgeons performed manual slice-by-slice segmentation of ten magnetic resonance imaging (MRI) cases. The segmentations were compared to the segmentation results of the proposed method using the Dice Similarity Coefficient (DSC). The average DSC for all datasets was 75.92%+/-7.24%. A manual segmentation took about four minutes and our algorithm required about one second.

  7. Pituitary infarction (United States)

    ... be replaced, including: Growth hormone Sex hormones (estrogen/testosterone) Thyroid hormone Vasopressin (ADH) Outlook (Prognosis) Acute pituitary ... Wisse, MD, Associate Professor of Medicine, Division of Metabolism, Endocrinology & Nutrition, University of Washington School of Medicine, ...

  8. Primary pituitary abscess: case report

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    Hanel Ricardo Alexandre


    Full Text Available Pituitary abscesses are potentially life-threatening lesions if not appropriately diagnosed and treated. The authors have operated on more than five hundred cases of pituitary tumors and only one represented a case of pituitary abscess. A 35-year-old woman was investigated for chronic frontal headache. CT scan showed a cystic sellar lesion with ring enhancement after contrast injection leading to an initial diagnosis of pituitary adenoma. She underwent a sublabial transsphenoidal approach to the pituitary gland. After dural opening, purulent material was obtained and no tumor or other associated lesion was detected. There was no evidence of current or previous septicemic illness, meningitis, cavernous sinus thrombosis or sinus infection. Cultures were negative. She was put on antibiotics and discharged after 4 weeks. Nowadays, 10 years after treatment, she is doing well, with no anterior pituitary hormone deficit. MRI shows a partially empty sella without residual lesion and the pituitary stalck is in the midline. The early diagnosis and adequate treatment of this life-threatening lesion may result in excellent prognosis.

  9. Pituitary apoplexy

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    Salam Ranabir


    Full Text Available Pituitary apoplexy is rare endocrine emergency which can occur due to infarction or haemorrhage of pituitary gland. This disorder most often involves a pituitary adenoma. Occasionally it may be the first manifestation of an underlying adenoma. There is conflicting data regarding which type of pituitary adenoma is prone for apoplexy. Some studies showed predominance of non-functional adenomas while some other studies showed a higher prevalence in functioning adenomas amongst which prolactinoma have the highest risk. Although pituitary apoplexy can occur without any precipitating factor in most cases, there are some well recognizable risk factors such as hypertension, medications, major surgeries, coagulopathies either primary or following medications or infection, head injury, radiation or dynamic testing of the pituitary. Patients usually present with headache, vomiting, altered sensorium, visual defect and/or endocrine dysfunction. Hemodynamic instability may be result from adrenocorticotrophic hormone deficiency. Imaging with either CT scan or MRI should be performed in suspected cases. Intravenous fluid and hydrocortisone should be administered after collection of sample for baseline hormonal evaluation. Earlier studies used to advocate urgent decompression of the lesion but more recent studies favor conservative approach for most cases with surgery reserved for those with deteriorating level of consciousness or increasing visual defect. The visual and endocrine outcomes are almost similar with either surgery or conservative management. Once the acute phase is over, patient should be re-evaluated for hormonal deficiencies.

  10. Cirurgia da hipófise por via trans-esfenoidal sob controle radiofluoroscópico e microdissecção novo tratamento da retinopatia diabética, tumores selares e neoplasias endocrinodependentes The surgery of the pituitary gland using a transphenoidal approach under radiofluoroscopic control and microdisection: a new treatment for diabetic retinopathy, pituitary tumors and endocrinodependent growths

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    Jules Hardy


    Full Text Available É apresentada nova técnica para a ablação total ou seletiva da hipófise utilizando via de acesso trans-esfenoidal, controle radiofluoroscópico e microdissecção, com traumatismo desprezível às estruturas circunvizinhas. Os autores comentam as aplicações do método à prática neurocirúrgica, relatando parte de uma série de mais 140 casos já operados. São discutidos os resultados obtidos no tratamento de 17 casos de retinopatia diabética, em 11 dos quais apenas o lobo anterior da hipófise foi removido, assim como aqueles obtidos na exérese de 20 casos de tumores selares. As indicações da hipofisectomia por via trans-esfenoidal no controle da sintomatologia das neoplasias endòcrinodependentes é estudada à luz dos resultados obtidos em 17 casos, sendo os resultados comparados com casos nos quais foi feita a implantação selar de ítrio90. As complicações operatorias em relação às três entidades nosológicas acima estudadas são também analisadas. Os autores salientam que a técnica descrita constitui, no presente estado das técnicas neurocirúrgicas utilizadas para a produção de uma insuficiência hipofisária duradoura, a intervenção de escolha.A new neurosurgical technique for the partial or total exéresis of the pituitary gland, using a transphenoidal approach under radiofluoroscopic control and microdisection is described. Part of a series of more than 140 cases operated upon by this method is reported. Results obtained in the treatment of diabetic retinopathy in 17 cases, 11 of which had only the pars anterior removed, are discussed. The applications of the transphenoidal route in 20 cases of pituitary fossa tumors are analysed. The indications of this type of operation in the management of endocrinodependent cancer is studied in 17 cases and compared with the results of 36 cases submitted to implant of Yttrium90 in the sella turcica. The operative complications following transphenoidal exéresis of the

  11. Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS. (United States)

    Kertesz, Vilmos; Calligaris, David; Feldman, Daniel R; Changelian, Armen; Laws, Edward R; Santagata, Sandro; Agar, Nathalie Y R; Van Berkel, Gary J


    Described here are the results from the profiling of the proteins arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) from normal human pituitary gland and pituitary adenoma tissue sections, using a fully automated droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS system for spatially resolved sampling, HPLC separation, and mass spectrometric detection. Excellent correlation was found between the protein distribution data obtained with this method and data obtained with matrix-assisted laser desorption/ionization (MALDI) chemical imaging analyses of serial sections of the same tissue. The protein distributions correlated with the visible anatomic pattern of the pituitary gland. AVP was most abundant in the posterior pituitary gland region (neurohypophysis), and ATCH was dominant in the anterior pituitary gland region (adenohypophysis). The relative amounts of AVP and ACTH sampled from a series of ACTH-secreting and non-secreting pituitary adenomas correlated with histopathological evaluation. ACTH was readily detected at significantly higher levels in regions of ACTH-secreting adenomas and in normal anterior adenohypophysis compared with non-secreting adenoma and neurohypophysis. AVP was mostly detected in normal neurohypophysis, as expected. This work reveals that a fully automated droplet-based liquid-microjunction surface-sampling system coupled to HPLC-ESI-MS-MS can be readily used for spatially resolved sampling, separation, detection, and semi-quantitation of physiologically-relevant peptide and protein hormones, including AVP and ACTH, directly from human tissue. In addition, the relative simplicity, rapidity, and specificity of this method support the potential of this basic technology, with further advancement, for assisting surgical decision-making. Graphical Abstract Mass spectrometry based profiling of hormones in human pituitary gland and tumor thin tissue sections.

  12. Pituitary Apoplexy After Thyrotropin-releasing Hormone Stimulation Test in a Patient with Pituitary Macroadenoma

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    Huei-Fang Wang


    Full Text Available Pituitary apoplexy is a rare complication of pituitary tumors. We report a case of a 41-year-old female with acromegaly due to a pituitary macroadenoma, who developed pituitary apoplexy after a thyrotropin-releasing hormone (TRH 200 mg intravenous injection stimulation test. Neither emergency computed tomography (CT scans nor magnetic resonance imaging (MRI, performed 6 hours and 12 hours, respectively, after the active episode, disclosed the evidence of acute hemorrhage or infarction. Two days later, the pituitary mass, removed by transsphenoidal approach, showed ischemic necrosis and acute hemorrhage. The TRH test is generally safe for evaluating pituitary function, but pituitary apoplexy may occur after the procedure. CT and MRI may miss the diagnosis of pituitary apoplexy, especially if performed immediately after the acute episode.

  13. Characterization of pancreatic glucagon-producing tumors and pituitary gland tumors in transgenic mice overexpressing MYCN in hGFAP-positive cells

    NARCIS (Netherlands)

    Fielitz, K. (Kathrin); Althoff, K. (Kristina); De Preter, K. (Katleen); J. Nonnekens (Julie); Ohli, J. (Jasmin); Elges, S. (Sandra); Hartmann, W. (Wolfgang); G. Kloppel (Günter); Knösel, T. (Thomas); Schulte, M. (Marc); L. Klein-Hitpass (Ludger); Beisser, D. (Daniela); Reis, H. (Henning); Eyking, A. (Annette); Cario, E. (Elke); J.H. Schulte (Johannes); A. Schramm (Alexander); U. Schüller (Ulrich)


    textabstractAmplification or overexpression of MYCN is involved in development and maintenance of multiple malignancies. A subset of these tumors originates from neural precursors, including the most aggressive forms of the childhood tumors, neuroblastoma and medulloblastoma. In order to model the

  14. Modelo de tumor experimental em rim de ratos

    Directory of Open Access Journals (Sweden)

    Silva Lúcio Flávio Gonzaga


    Full Text Available O carcinossarcoma 256 de Walker tem despertado o interesse de muitos pesquisadores como modelo experimental para estudo da biologia tumoral. OBJETIVO: estabelecer um modelo de tumor renal que possa ser usado para estudar in vivo e in vitro, as alterações impostas pelas neoplasias. MÉTODOS: utilizados vinte ratos Wistar, machos, adultos, pesando entre 250-300 g, oriundos do Laboratório de Cirurgia Experimental da Universidade Federal do Ceará. Sob anestesia inalatória procedia-se uma pequena incisão supraumbilical, e com manobra delicada fazia-se a exposição do rim direito. Neste órgão eram inoculadas 3x10(5 células tumorais viáveis. Os animais então eram mantidos em gaiolas individuais com as mesmas condições ambientais e com água e dieta ad libitum. RESULTADOS: o Carcinossarcoma 256 de Walker, implantado no parênquima do rim direito de ratos Wistar apresentou índice de pega de 100%, e crescimento rápido, invadiu por contiguidade as estruturas vizinhas, porém sem apresentar metástases, no entanto, levando os animais a óbito no curso médio de 14 dias. CONCLUSÃO: o modelo de implante de tumor de Walker no parênquima do rim direito de ratos Wistar é eficiente, tem reprodutibilidade, apresentando um índice de pega de 100%, e permitindo seu uso em linhas de pesquisa.

  15. Clinical experience and outcome of pituitary surgery in Kenyan ...

    African Journals Online (AJOL)

    Introduction Surgical extirpation of pituitary lesions and can be perfomed by craniotomy or trans-sphenoidal hypophysectomy. This could be for pituitary ablation, excision of pituitary adenomas, craniopharyngiomas, suprasellar meningiomas and other types of tumors of the sellar region. Despite this being a common ...

  16. Contemporary issues in the evaluation and management of pituitary adenomas. (United States)

    Pekic, S; Stojanovic, M; Popovic, V


    Pituitary adenomas are common benign monoclonal neoplasms accounting for about 15% of intracranial neoplasms. Data from postmortem studies and imaging studies suggest that 1 of 5 individuals in the general population may have pituitary adenoma. Some pituitary adenomas (mainly microadenomas which have a diameter of less than 1 cm) are exceedingly common and are incidentally diagnosed on magnetic resonance imaging (MRI) performed for an unrelated reason (headache, vertigo, head trauma). Most microadenomas remain clinically occult and stable in size, without an increase in tumor cells and without local mass effects. However, some pituitary adenomas grow slowly, enlarge by expansion and become demarcated from normal pituitary (macroadenomas have a diameter greater than 1 cm). They may be clinically silent or secrete anterior pituitary hormones in excess such as prolactin, growth hormone (GH), or adrenocorticotropic hormone (ACTH) causing diseases like prolactinoma, acromegaly, Cushing's disease or rarely thyroid-stimulating hormone (TSH) or gonadotropins (LH, FSH). The incidence of the various subtypes of pituitary adenoma varies but the most common is prolactinoma. Clinically non-functioning pituitary adenomas (NFPAs), which do not secrete hormones often cause local mass symptoms and represent one-third of pituitary adenomas. Given the high prevalence of pituitary adenomas and their heterogeneity (different tumor subtypes), it is critical that clinicians have a thorough understanding of the potential abnormalities in pituitary function and prognostic factors for behavior of pituitary adenomas in order to timely implement specific treatment modalities. Regarding pathogenesis of these tumors genetics, epigenetics and signaling pathways are the focus of current research yet our understanding of pituitary tumorigenesis remains incomplete. Although several genes and signaling pathways have been identified as important factors in the development of pituitary tumors, current

  17. Clinical characteristics of pituitary adenomas with radiological calcification. (United States)

    Ogiwara, Toshihiro; Nagm, Alhusain; Yamamoto, Yasunaga; Hasegawa, Takatoshi; Nishikawa, Akihiro; Hongo, Kazuhiro


    Radiographic detection of calcification in pituitary adenoma is relatively rare, and the clinical characteristics of pituitary adenoma with calcification remain unclear. Herein, the clinical characteristics of pituitary adenoma with radiological calcification were investigated. A total of 160 patients who underwent surgical resection of pituitary adenomas between February 2004 and December 2016 were reviewed. Eighty-one patients had hormone-secreting pituitary adenomas, and 79 patients had nonfunctioning pituitary adenoma. Among these 160 patients, cases with radiological calcifications on preoperative neuroimaging were included in this study, and clinical characteristics with intraoperative findings were analyzed, retrospectively. Pituitary adenoma with calcification on preoperative neuroimaging was observed in only nine cases (5.6%). The study population consisted of these nine patients with nonfunctioning pituitary adenoma (n = 5), mixed growth hormone and prolactin-secreting pituitary adenomas (n = 3), and a prolactinoma (n = 1). In 89% of cases (n = 8), calcified pituitary adenoma was soft enough for suction despite the presence of a granular gritty texture intraoperatively. Besides, in a single patient (11%), evidence of hard thick capsular calcification was seen surrounding a soft tumor component; however, it did not interfere with adequate removal of the soft part, and tumor resection was possible in all cases without any complications. Pituitary adenoma presenting with calcification is relatively rare, but should be kept in mind to avoid making a wrong preoperative diagnosis. As not all pituitary adenomas with calcification are hard tumors, preoperative radiological calcification should not affect decision-making regarding surgical indications.

  18. Pituitary spindle cell oncocytoma

    Directory of Open Access Journals (Sweden)

    Soledad Sosa


    Full Text Available Spindle cell oncocytoma is an infrequent benign non-endocrine sellar neoplasm. Due to its similar morphology to pituitary adenomas, consideration of this differential diagnosis would conduce to a more careful surgical approach in order to avoid intraoperative bleeding and aiming to a complete resection, on which depends long-term outcomes. We present the case of a 60-year-old male who complained about visual abnormalities, with computerized visual field confirmation. On biochemistry, a panhypopituitarism was detected. The brain magnetic resonance images showed a sellar mass. A non-functioning pituitary macroadenoma was presumptively diagnosed and due to the visual impairment, surgical transesphenoidal treatment was indicated. The histological diagnosis was spindle cell oncocytoma. Five months after surgery, the control image demonstrated a lesion that was considered as remnant tumor, hence radiosurgery was performed. During the follow-up, the tumor reduced its size and four years after initial treatment, the sellar resonance imaging showed disappearance of the residual tumor. Communication of new cases of this rare entity will enlarge the existing evidence and will help to determinate the most effective treatment and prognosis.

  19. Impulse cytophotometric DNA analysis in pituitary adenomas. (United States)

    Ahyai, A; Hori, A; Bockermann, V; Rama, B; Blech, M; Markakis, E


    Flow cytometric DNA analysis was carried out on 32 microsurgically removed pituitary adenomas. Additionally, the histograms of tumor cell nuclei of 7 patients were compared with those of the cultured cells from the same tumor samples. The tumors were classified into 3 groups according to the proliferation index (PI) of the flow cytometric results: 1) tumors with DNA patterns of slow proliferation (PI under 10), to which the majority of the examined pituitary adenomas belonged; 2) pituitary adenomas with diploid karyograms and PI values from 10 to 15; 3) diploid or aneuploid karyograms with PI values above 15. The third group were characterized histologically by increased chromatin content, nuclear polymorphism, mitoses, and extrapituitary infiltration of the tumor cells, and were, therefore, no longer benign. However, there was no direct relationship between the intensity of hormone secretory activity of the tumors and DNA ploidy. Cultured adenoma cells examined by flow cytometry remained stable in all cases but one.

  20. Diagnostic criteria in invasive pituitary adenomas

    Directory of Open Access Journals (Sweden)

    Moldovan Ioana-Maria


    Full Text Available Pituitary adenomas are benign pituitary primary tumors, the most frequent type of tumor in the pituitary fossa. An important part, around 1/3 of the pituitary adenomas manifests an aggressive behavior, growing faster and invading into parasellar areas (cavernous sinus, neural tissues and bones. Objectives: the first aim of this paper is to review the last findings about invasiveness diagnostic criteria, imagistic and biomarkers, which can be used in the classification of pituitary tumors and also to predict the probability of invasiveness, tumor recurrence and suspicion of malignancy. The second aim is to highlight the morphological and clinic types of invasive pituitary adenomas. Materials and methods: we performed a systematic review and analysis of the published articles, searching PubMed between January 1985 and December 2015. There were selected articles published in English, reviews and abstracts. During the advanced search type in PubMed, combinations of the following keywords were used: “pituitary adenoma”, “invasive”, “aggressive”, “biomarkers”, “classification”, “histological subtypes”, ‘”immunohistochemical markers”. Results: 215 articles were selected, regarding diagnostic, prognostic and therapeutic aspects. There were some histological subtypes of pituitary adenomas known as having an aggressive clinical behavior. Several biomarkers were identified as being associated with the invasive feature: proliferation markers (Ki-67 index, number of mitoses, p53 & p27 expression, microvascularization density, telomerase, topoisomerase 2 Alpha, matrix metalloproteinases, protein kinase C, cyclooxygenase-2, E-cadherin, transcription Factors, genetic alterations (PTTG gene, Galectin-3 protein/ LGALS3 gene, apoptosis markers. Based on their invasion and proliferation characteristics, pituitary tumors are proposed to be classified into five grades (1a, 1b, 2a, 2b, 3, the grade 2b tumor with high risk of recurrence

  1. Imaging of giant pituitary adenomas

    Energy Technology Data Exchange (ETDEWEB)

    Majos, C.; Coll, S.; Aguilera, C.; Pons, L.C. [Bellvitge Univ., Barcelona (Spain). Inst. de Diagnostice per la Imatge; Acebes, J.J. [Department of Neurosurgery, Ciutat Sanitaria i Universitaria de Bellvitge, L`Hospitalet de Llobregat, Barcelona (Spain)


    We present five proven giant pituitary adenomas studied by CT and MRI, and review the clinical and imaging findings. Our aim was to examine the radiologic appearances and to search for criteria useful in distinguishing these tumors from other sellar and suprasellar tumours, mainly craniopharyngioma. The main differences from small adenomas were high prevalence of macrocysts, a more invasive behaviour and a clinical picture dominated by mass effect rather than endocrine disturbance. Factors supporting the diagnosis of pituitary adenoma in a giant intra- and suprasellar mass include: infrasellar extension, absence of calcification and presence of low-signal cysts on T1-weighted images. (orig.) (orig.) With 4 figs., 2 tabs., 9 refs.

  2. Astrocytoma of the pituitary gland (pituicytoma): case report

    Energy Technology Data Exchange (ETDEWEB)

    Uesaka, T.; Miyazono, M.; Nishio, S. [Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka (Japan); Iwaki, T. [Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University (Japan)


    A 34-year-old man presented with a 4-month history of visual obscuration. Magnetic resonance imaging showed a solid, discrete, contrast-enhancing pituitary mass with suprasellar extension. Surgery, which was performed via a transsphenoidal approach, disclosed the pituitary tumor to be a fibrillary astrocytoma (pituicytoma). This case report contains the clinical and neuroimaging features of this rare tumor of the neurohypophysis, which masqueraded as a pituitary adenoma. (orig.)

  3. Autonomic nervous system and hypothalamic-pituitary-adrenal axis response to experimentally induced cold pain in adolescent non-suicidal self-injury--study protocol. (United States)

    Koenig, Julian; Rinnewitz, Lena; Warth, Marco; Kaess, Michael


    Adolescent non-suicidal self-injury (NSSI) is associated with altered sensitivity to experimentally induced pain. Adolescents engaging in NSSI report greater pain threshold and pain tolerance, as well as lower pain intensity and pain unpleasantness compared to healthy controls. The experience of pain is associated with reactivity of both the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis. However, previous research has not yet systematically addressed differences in the physiological response to experimentally induced pain comparing adolescents with NSSI and age- and sex-matched healthy controls. Adolescents with NSSI and healthy controls undergo repeated painful stimulation with the cold pressor task. ANS activity is continuously recorded throughout the procedure to assess changes in heart rate and heart rate variability. Blood pressure is monitored and saliva is collected prior to and after nociceptive stimulation to assess levels of saliva cortisol. The study will provide evidence whether lower pain sensitivity in adolescents with NSSI is associated with blunted physiological and endocrinological responses to experimentally induced pain compared to healthy controls. Extending on the existing evidence on altered pain sensitivity in NSSI, measured by self-reports and behavioural assessments, this is the first study to take a systematic approach in evaluating the physiological response to experimentally induced pain in adolescent NSSI. Deutsche Register Klinischer Studien, Study ID: DRKS00007807; Trial Registration Date: 13.02.2015.

  4. Pituitary apoplexy within a macroprolactinoma. (United States)

    Watt, Alastair; Pobereskin, Louis; Vaidya, Bijay


    A 61-year-old lady was admitted to hospital with sepsis due to a urinary tract infection. Three days after admission, she suddenly started to have severe headache with visual disturbance and right third nerve palsy. Urgent magnetic resonance angiography excluded internal carotid artery aneurysm but showed a large lesion extending superiorly from the clivus towards the right cerebral peduncle, which was confirmed by a CT scan of the brain. The lesion was initially thought to be a primary or a metastatic brain tumor. CT scans of the thorax, abdomen and pelvis showed no evidence of metastatic disease. MRI scan revealed a huge pituitary adenoma containing hemorrhage. Subsequent pituitary function tests indicated a grossly elevated serum prolactin level and hypopituitarism. Magnetic resonance angiography of the head; CT scans of the brain, thorax, abdomen and pelvis; MRI scan of the pituitary gland; and baseline and dynamic anterior pituitary function testing. Pituitary apoplexy within a macroprolactinoma. Steroid replacement, careful control of fluid and electrolyte balance and conservative nonsurgical management with the dopamine agonist cabergoline resulted in resolution of the patient's headache, improvement of the third nerve palsy and subsequent normalization of the prolactin level, with reduction in size of the prolactinoma on MRI scan.

  5. A 23-Year-Old Female with a Mixed Germ Cell Tumor of the Pituitary Infundibulum: The Challenge of Differentiating Neoplasm from Lymphocytic Infundibuloneurohypophysitis—A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Sann Yu Mon


    Full Text Available The pathologic spectrum of diseases that infiltrate the pituitary infundibulum includes a broad variety of clinical entities. There are significant differences in the prevalence of these etiologies depending on the age of presentation. Lymphocytic infundibuloneurohypophysitis (LINH predominates over other causes of infundibular disease in adults over age 21. Differentiating LINH from other causes of infundibular disease can be difficult because the various etiologies often have similar clinical presentations and radiologic imaging characteristics. We report the first case in an adult of a mixed germ cell tumor comprised of germinoma and embryonal cell carcinoma infiltrating the pituitary infundibulum. In our case, a 23-year-old female was initially misdiagnosed as having LINH. She presented with panhypopituitarism and diabetes insipidus, which is the most common initial presentation in both entities. The two diagnoses are difficult to distinguish based on MRI imaging, CSF findings, and histopathological examination. Our case demonstrates the need for close follow-up of patients with isolated lesions of the pituitary infundibulum and reinforces the need for biopsy of an infundibular lesion when progression of disease is demonstrated. In our case, biopsy with comprehensive immunohistochemical staining was the sole means of making a definitive diagnosis.

  6. Mouse Hepatic Tumor Vascular Imaging by Experimental Selective Angiography.

    Directory of Open Access Journals (Sweden)

    Sang Kyum Kim

    Full Text Available Human hepatocellular carcinoma (HCC has unique vascular features, which require selective imaging of hepatic arterial perfusion and portal venous perfusion with vascular catheterization for sufficient evaluation. Unlike in humans, vessels in mice are too small to catheterize, and the importance of separately imaging the feeding vessels of tumors is frequently overlooked in hepatic tumor models. The purpose of this study was to perform selective latex angiography in several mouse liver tumor models and assess their suitability.In several ectopic (Lewis lung carcinoma, B16/F10 melanoma cell lines and spontaneous liver tumor (Albumin-Cre/MST1fl/fl/MST2fl/fl, Albumin-Cre/WW45fl/fl, and H-ras12V genetically modified mouse models, the heart left ventricle and/or main portal vein of mice was punctured, and latex dye was infused to achieve selective latex arteriography and/or portography.H-ras12V transgenic mice (a HCC and hepatic adenoma model developed multiple liver nodules that displayed three different perfusion patterns (portal venous or hepatic artery perfusion predominant, mixed perfusion, indicating intra-tumoral vascular heterogeneity. Selective latex angiography revealed that the Lewis lung carcinoma implant model and the Albumin-Cre/WW45fl/fl model reproduced conventional angiography findings of human HCC. Specifically, these mice developed tumors with abundant feeding arteries but no portal venous perfusion.Different hepatic tumor models showed different tumor vessel characteristics that influence the suitability of the model and that should be considered when designing translational experiments. Selective latex angiography applied to certain mouse tumor models (both ectopic and spontaneous closely simulated typical characteristics of human HCC vascular imaging.

  7. General Information about Pituitary Tumors (United States)

    ... occur: Headache. Some loss of vision. Loss of body hair. In women, less frequent or no menstrual periods ... in the face, neck, and trunk of the body, and thin arms and legs. A lump of fat on ... bruising. Growth of fine hair on the face, upper back, or arms. Bones ...

  8. Treatment Option Overview (Pituitary Tumors) (United States)

    ... occur: Headache. Some loss of vision. Loss of body hair. In women, less frequent or no menstrual periods ... in the face, neck, and trunk of the body, and thin arms and legs. A lump of fat on ... bruising. Growth of fine hair on the face, upper back, or arms. Bones ...

  9. Treatment Options for Pituitary Tumors (United States)

    ... occur: Headache. Some loss of vision. Loss of body hair. In women, less frequent or no menstrual periods ... in the face, neck, and trunk of the body, and thin arms and legs. A lump of fat on ... bruising. Growth of fine hair on the face, upper back, or arms. Bones ...

  10. Identification of metastases in the pituitary stalk

    Energy Technology Data Exchange (ETDEWEB)

    Schubiger, O.


    Two cases of metastasis in the pituitary stalk are presented. In both cases, presenting with diabetes insipidus, the demonstration of a small (under 1 cm) metastasis in the pituitary stalk was possible using a current generation scanner. Patients with known primary tumors presenting with a diabetes insipidus should be examined by CT before therapy with antidiuretic hormone is initiated. In cases of visible metastasis, a specific therapy together with the hormone-substitution should be discussed.

  11. Oxygenation level and hemoglobin concentration in experimental tumor estimated by diffuse optical spectroscopy (United States)

    Orlova, A. G.; Kirillin, M. Yu.; Volovetsky, A. B.; Shilyagina, N. Yu.; Sergeeva, E. A.; Golubiatnikov, G. Yu.; Turchin, I. V.


    Using diffuse optical spectroscopy the level of oxygenation and hemoglobin concentration in experimental tumor in comparison with normal muscle tissue of mice have been studied. Subcutaneously growing SKBR-3 was used as a tumor model. Continuous wave fiber probe diffuse optical spectroscopy system was employed. Optical properties extraction approach was based on diffusion approximation. Decreased blood oxygen saturation level and increased total hemoglobin content were demonstrated in the neoplasm. The main reason of such differences between tumor and norm was significant elevation of deoxyhemoglobin concentration in SKBR-3. The method can be useful for diagnosis of tumors as well as for study of blood flow parameters of tumor models with different angiogenic properties.

  12. Clusterin and FOXL2 Act Concordantly to Regulate Pituitary Gonadotroph Adenoma Growth (United States)

    Chesnokova, Vera; Zonis, Svetlana; Wawrowsky, Kolja; Tani, Yuji; Ben-Shlomo, Anat; Ljubimov, Vladimir; Mamelak, Adam; Bannykh, Serguei


    Pituitary tumors grow slowly and despite their high prevalence are invariably benign. We therefore studied mechanisms underlying pituitary tumor growth restraint. Pituitary tumor transforming gene (PTTG), the index human securin, a hallmark of pituitary tumors, triggers pituitary cell proliferation and murine pituitary tumor development. We show that human gonadotroph cell pituitary tumors, unlike other secreting tumor types, express high levels of gonadotroph-specific forkhead transcription factor FOXL2, and both PTTG and Forkhead box protein L2 (FOXL2) stimulate gonadotroph clusterin (Clu) expression. Both Clu RNA isoforms are abundantly expressed in these nonhormone-secreting human tumors, and, when cultured, these tumor cells release highly abundant levels of secreted Clu. FOXL2 directly stimulates the Clu gene promoter, and we show that PTTG triggers ataxia telangiectasia mutated kinase/IGF-I/p38MAPK DNA damage/chromosomal instability signaling, which in turn also induces Clu expression. Consequently, Clu restrains pituitary cell proliferation by inducing cyclin dependent kinase inhibitors p16 and p27, whereas Clu deletion down-regulates p16 and p27 in the Clu−/− mouse pituitary. FOXL2 binds and suppresses the PTTG promoter, and Clu also suppresses PTTG expression, thus neutralizing protumorigenic PTTG gonadotroph tumor cell properties. In vivo, murine gonadotroph LβT2 tumor cell xenografts overexpressing Clu and FOXL2 both grow slower and elicit smaller tumors. Thus, gonadotroph tumor cell proliferation is determined by the interplay between cell-specific FOXL2 with PTTG and Clu. PMID:23051594

  13. Pituitary abscess: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Apostolos K A Karagiannis


    Full Text Available Pituitary abscess is a rare life-threating entity that is usually misdiagnosed as a pituitary tumor with a definite diagnosis only made postoperatively. Over the last several decades, advances in healthcare have led to a significant decrease in morbidity and mortality due to pituitary abscess. We report a case of a 34-year-old woman who was admitted to our department for investigation of a pituitary mass and with symptoms of pituitary dysfunction, headaches and impaired vision. During her admission, she developed meningitis-like symptoms and was treated with antibiotics. She eventually underwent transsphenoidal surgery for excision of the pituitary mass. A significant amount of pus was evident intraoperatively; however, no pathogen was isolated. Six months later, the patient was well and had full recovery of the anterior pituitary function. Her menses returned, and she was only on treatment with desmopressin for diabetes insipidus that developed postoperatively.

  14. Visualization of the normal pituitary gland during the endoscopic endonasal removal of pituitary adenoma by narrow band imaging. (United States)

    Akutsu, Nobuyuki; Taniguchi, Masaaki; Kohmura, Eiji


    Narrow band imaging (NBI) is an endoscopic technology that enhances the visualization of the superficial and submucosal vasculature. The aim of the present study was to evaluate the feasibility of NBI in visualizing the normal pituitary gland during the endoscopic endonasal removal of pituitary adenoma. A total of 25 patients with pituitary adenoma underwent endoscopic endonasal transsphenoidal surgery using a rigid endoscope with conventional imaging. The NBI of the surgical field was conducted under air and/or continuous irrigation of artificial cerebrospinal fluid using a flexible videoscope before and/or after the gross removal of the tumor. The capillaries of the normal pituitary gland had a characteristic appearance that could be confirmed in 16 cases. In contrast, the adenomas exhibited no characteristic vascular enhancement under NBI. The reasons why NBI failed to visualize the pituitary gland included the presence of a blood clot or a certain amount of tumor obscuring the normal pituitary gland and difficulty in steering the videoscope within the sella to approach the assumed site of the residual pituitary gland. NBI observation during the endoscopic endonasal removal of pituitary adenoma may be useful for visualizing the normal pituitary gland after the gross removal of the tumor. The absence of a typical vascular pattern suggests the presence of a residual tumor, which may justify further exploration in cases where gross total removal is considered necessary.

  15. [Preservation of the pituitary stalk and the gland in transsphenoidal microsurgery for pituitary adenomas]. (United States)

    Li, Haoyu; Yuan, Xianrui; Liao, Yiwei; Xie, Yuanyang; Zhang, Chi; Li, Juan; Su, Jun; Wang, Xiangyu; Chen, Xiaoyu; Liu, Qing


    To improve the surgical outcome of pituitary adenomas by identifying and preserving the pituitary stalk and the gland during surgery. From October 2010 to September 2012, the author from the Department of Neurosurgery of Xiangya Hospital, Central South University operated on 51 patients with pituitary adenoma. During the operations, we carefully identified the normal adenohypophysis, pituitary stalk, neurohypophysis and the abnormal tissues either by direct observation or by medical images, aiming to excise the tumor thoroughly, protect the pituitary function and reduce the postoperative complications. Totally 37 patients (72.5%, 37/51) had total resection of the tumor, 12 (23.5%, 12/51) had subtotal tumor resection and the other 2 had major removal. The gland and the pituitary stalk were well identified and reserved. Detection of hormone content proved that the operation had little effect on the free triiodothyronine (FT3) and adrenocorticotropic hormone (ACTH), while for free tetraiodothyronine (FT4) and thyroid stimulating hormone (TSH) and postoperative followup significant alleviation was found. There was no significant fluctuation for the testosterone in the men preoperatively and postoperatively (all the above results were obtained without hormone replacement therapy). The main postoperative complications were as follows: temporary diabetes insipidus in 5 patients (9.8%, 5/51); electrolyte disorder (the appearance of hyponatremia) in 17 (33.3%, 17/51); and cerebrospinal fluid rhinorrhea and postoperative intracranial infection in 1 (2%, 1/51). No one died during the perioperation period. Microscopic transsphenoidal surgery is effective for pituitary adenomas including tumors violating the cavernous sinus. Accurate identification of the pituitary stalk, the gland and the abnormal tissue during the microscopic transsphenoidal operation plays a critical role in preserving the pituitary function and promoting postoperative rehabilitation.

  16. Experimental model of ultrasound thermotherapy in rats inoculated with Walker-236 tumor Modelo experimental de termoterapia ultrassônica em ratos inoculados com tumor de Walker-236

    Directory of Open Access Journals (Sweden)

    José Antonio Carlos Otaviano David Morano


    Full Text Available PURPOSE: To develop a model to evaluate the effects of focal pulsed ultrasound (US waves as a source of heat for treatment of murine subcutaneous implanted Walker tumor. METHODS: An experimental, controlled, comparative study was conducted. Twenty male Wistar rats (160-300 g randomized in 2 equal groups (G-1: Control and G-2: Hyperthermia were inoculated with Walker-256 carcinosarcoma tumor. After 5 days G-2 rats were submitted to 45ºC hyperthermia. Heat was delivered directly to the tumor by an ultrasound (US equipment (3 MHz frequency, 1,5W/cm³. Tumor temperature reached 45º C in 3 minutes and was maintained at this level for 5 minutes. Tumor volume was measured on days 5, 8, 11, 14 e 17 post inoculation in both groups. Unpaired t-test was used for comparison. POBJETIVO: Desenvolver um modelo para avaliar os efeitos do ultra-som focal pulsado como fonte de calor para o tratamento de tumores de Walker subcutâneos implantados em ratos. MÉTODOS: Um estudo experimental, controlado, comparativo foi realizado. Vinte ratos Wistar machos (160-300 g divididos em dois grupos (G-1: Controle e G-2: hipertermia foram inoculados com tumor de Walker carcinossarcoma-256. Após cinco dias os ratos do grupo G-2 ratos foram submetidos a hipertermia (45ºC. O calor foi aplicado diretamente no tumor por um equipamento de ultrassonografia (3 MHz, 1,5 W/cm³. A temperatura no tumor atingiu 45ºC em 3 minutos e foi mantida nesse nível por 5 minutos. O volume do tumor foi medido nos dias 5, 8, 11, 14 e 17 após a inoculação, em ambos os grupos. Teste t não pareado foi utilizado para comparação. P <0,05 foi considerado significante. RESULTADOS: O volume do tumor foi significativamente maior no 5º dia e diminuiu nos dias 11, 14 e 17 nos ratos tratados. Animais submetidos à hipertermia sobreviveram mais tempo que os animais do grupo controle. No 29º dia após a inoculação do tumor, 40% dos ratos do grupo controle e 77,78% dos ratos tratados com

  17. Infrared Spectra of Human Breast Tumor Tissue and Experimental Animal Tumors (United States)

    Tolstorozhev, G. B.; Belkov, M. V.; Skornyakov, I. V.; Pekhnyo, V. I.; Kozachkova, A. N.; Tsarik, H. V.; Kutsenko, I. P.; Sharykina, N. I.; Butra, V. A.


    We have used Fourier transform IR spectroscopy methods to conduct comparative studies of human breast tumors and sarcoma 180 tumor grafted into mice. The IR spectral parameters used to identify tumor tissue in mice with the sarcoma 180 strain proved to be identical to the parameters for human breast tissue in cancer. In the presence of a malignant tumor in humans, the most intense C=O vibrational bands in the protein molecules are observed in the interval 1710-1680 cm-1. For a benign tumor, in the IR spectra of breast tissue the intense bands are located in the interval 1670-1650 cm-1. We spectroscopically monitored the diagnosis and the chemotherapy process using the model of sarcoma 180 in mice. As the therapeutic drugs, we used synthesized coordination compounds based on palladium complexes with diphosphonic acid derivatives. We demonstrate the promising potential of palladium complexes with zoledronic acid as an effective cytostatic. In therapy using a palladium complex with zoledronic acid, the effect of tumor growth inhibition is accompanied by a change in its spectral characteristics. The parameters of the IR spectra for tumor tissue after treatment are close to those of the IR spectra for healthy tissue.

  18. Requirement for Tumor Necrosis Factor Receptor 2 Expression on Vascular Cells To Induce Experimental Cerebral Malaria


    Stoelcker, Benjamin; Hehlgans, Thomas; Weigl, Karin; Bluethmann, Horst; Grau, Georges E.; Männel, Daniela N.


    Using tumor necrosis factor receptor type 2 (TNFR2)-deficient mice and generating bone marrow chimeras which express TNFR2 on either hematopoietic or nonhematopoietic cells, we demonstrated the requirement for TNFR2 expression on tissue cells to induce lethal cerebral malaria. Thus, TNFR2 on the brain vasculature mediates tumor necrosis factor-induced neurovascular lesions in experimental cerebral malaria.

  19. Tumorer

    DEFF Research Database (Denmark)

    Prause, J.U.; Heegaard, S.


    oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer......oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer...

  20. The Role of Genetic and Epigenetic Changes in Pituitary Tumorigenesis (United States)

    FUKUOKA, Hidenori; TAKAHASHI, Yutaka


    Pituitary adenomas are one of the most common intracranial tumors. Despite their benign nature, dys-regulation of hormone secretion causes systemic metabolic deterioration, resulting in high mortality and an impaired quality of life. Tumorigenic pathogenesis of pituitary adenomas is mainly investigated by performing genetic analyses of somatic mutations in the tumor or germline mutations in patients. Genetically modified mouse models, which develop pituitary adenomas, are also used. Genetic analysis in rare familial pituitary adenomas, including multiple endocrine neoplasia type 1 and type 4, Carney complex, familial isolated pituitary adenomas, and succinate dehydrogenases (SDHs)-mediated paraganglioma syndrome, revealed several causal germline mutations and sporadic somatic mutations in these genes. The analysis of genetically modified mouse models exhibiting pituitary adenomas has revealed the underlying mechanisms, where cell cycle regulatory molecules, tumor suppressors, and growth factor signaling are involved in pituitary tumorigenesis. Furthermore, accumulating evidence suggests that epigenetic changes, including deoxyribonucleic acid (DNA) methylation, histone modification, micro ribonucleic acids (RNAs), and long noncoding RNAs play a pivotal role. The elucidation of precise mechanisms of pituitary tumori-genesis can contribute to the development of novel targeted therapy for pituitary adenomas. PMID:25446387

  1. Cushing's Syndrome From Pituitary Microadenoma and Pulmonary Nodules. (United States)

    Tating, Dan Louie Renz P; Montevirgen, Natasha Denise S; Cajucom, Loyda


    Cushing's syndrome is a state of cortisol excess, possibly from a tumor in the pituitary gland, the adrenal gland, or an ectopic nonpituitary ACTH-secreting source. The first form, pituitary in origin, was originally described by Harvey Cushing, MD, and was labeled as Cushing's disease. Long-term therapy with glucocorticoids also can lead to iatrogenic Cushing's syndrome.

  2. Breast Cancer Metastasis to Pituitary Infandibulum

    Directory of Open Access Journals (Sweden)

    Maryam Poursadegh Fard


    Full Text Available Metastasis from breast cancer to other parts of the body is very common, but the spread of the tumor to pituitary gland, especially to infandibulum, is a rare presentation. At the time of pituitary metastasis, a majority of the patients have clinical and radiological evidence of the disease. It seems that the posterior area of the gland is the most common site of metastasis, probably due to highly rich blood supply through the hypophyseal artery. The present report introduces a case of a 55-years-old woman presented with diabetes insipidus resulting from metastasis of the tumor to pituitary infandibulum, which is a rare site for metastasis, without significant complaint resulting from metastasis to other part of the body, or other primary diseases. Further evaluation revealed that in spite of previous reports, which metastasis usually happens in end stage of cancer, the patients had primary breast cancer. In subsequent evaluations of the case, hypofunction of adenohypophysis was also detected

  3. Experimental Transmission of Bighorn Sheep Sinus Tumors to Bighorn Sheep (Ovis canadensis canadensis) and Domestic Sheep. (United States)

    Fox, K A; Wootton, S; Marolf, A; Rouse, N; LeVan, I; Spraker, T; Miller, M; Quackenbush, S


    Bighorn sheep sinus tumors are a recently described disease affecting the paranasal sinuses of Rocky Mountain bighorn sheep (Ovis canadensis canadensis). Several features of this disease suggest an infectious cause, although a specific etiologic agent has not been identified. To test the hypothesis that bighorn sheep sinus tumors are caused by an infectious agent, we inoculated 4 bighorn sheep lambs and 4 domestic sheep lambs intranasally with a cell-free filtrate derived from a naturally occurring bighorn sheep sinus tumor; we held 1 individual of each species as a control. Within 18 months after inoculation, all 4 inoculated domestic sheep (100%) and 1 of the 4 inoculated bighorn sheep (25%) developed tumors within the ethmoid sinuses or nasal conchae, with features similar to naturally occurring bighorn sheep sinus tumors. Neither of the uninoculated sheep developed tumors. Histologically, the experimentally transmitted tumors were composed of stellate to spindle cells embedded within a myxoid matrix, with marked bone production. Tumor cells stained positively with vimentin, S100, alpha smooth muscle actin, and osteocalcin, suggesting origin from a multipotent mesenchymal cell. A periosteal origin for these tumors is suspected. Immunohistochemical staining for the envelope protein of JSRV (with cross-reactivity to ENTV) was equivocal, and PCR assays specific for these agents were negative. © The Author(s) 2016.

  4. Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas

    DEFF Research Database (Denmark)

    Casar-Borota, Olivera; Botling, Johan; Granberg, Dan


    Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker...... in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown. Facing a difficult diagnostic...... case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None...

  5. Mortality in patients with pituitary disease.

    LENUS (Irish Health Repository)

    Sherlock, Mark


    Pituitary disease is associated with increased mortality predominantly due to vascular disease. Control of cortisol secretion and GH hypersecretion (and cardiovascular risk factor reduction) is key in the reduction of mortality in patients with Cushing\\'s disease and acromegaly, retrospectively. For patients with acromegaly, the role of IGF-I is less clear-cut. Confounding pituitary hormone deficiencies such as gonadotropins and particularly ACTH deficiency (with higher doses of hydrocortisone replacement) may have a detrimental effect on outcome in patients with pituitary disease. Pituitary radiotherapy is a further factor that has been associated with increased mortality (particularly cerebrovascular). Although standardized mortality ratios in pituitary disease are falling due to improved treatment, mortality for many conditions are still elevated above that of the general population, and therefore further measures are needed. Craniopharyngioma patients have a particularly increased risk of mortality as a result of the tumor itself and treatment to control tumor growth; this is a key area for future research in order to optimize the outcome for these patients.

  6. Long-Term Outcome and MGMT as a Predictive Marker in 24 Patients With Atypical Pituitary Adenomas and Pituitary Carcinomas Given Treatment With Temozolomide

    DEFF Research Database (Denmark)

    Bengtsson, Daniel; Schrøder, Henrik Daa; Andersen, Marianne


    CONTEXT/OBJECTIVE: Locally aggressive pituitary tumors (LAPT) and pituitary carcinomas respond poorly to conventional therapy and cytotoxic drugs. Temozolomide (TMZ) is an oral alkylating drug with good tolerability, approved for treatment of malignant gliomas. The experience of its use...... in pituitary tumors is limited. DESIGN AND SETTING: We report on 24 patients with aggressive pituitary tumors (16 LAPTs, 8 carcinomas) treated with TMZ for a median of 6 months (range 1-23). Follow-up ranged from 4 to 91 months with a median of 32.5 months. 19/24 tumors were hormone secreting (PRL 9, ACTH 4...... MGMT staining was 9% (5-20%) in responders vs 93% (50-100%) in nonresponders. Loss of MSH2 and MSH 6 was observed in a single patient who had a rapid development of resistance to TMZ. CONCLUSIONS: This study shows that TMZ is a valuable treatment option for patients with uncontrolled pituitary tumors...

  7. [Primary Pituitary Malignant Lymphoma that was Difficult to Differentiate from Nonfunctioning Pituitary Adenoma:A Case Report]. (United States)

    Murakami, Yuta; Sato, Taku; Jinguji, Shinya; Kishida, Yugo; Watanabe, Tadashi; Suzuki, Osamu; Ikeda, Kazuhiko; Homma, Miyuki; Midorikawa, Sanae; Saito, Kiyoshi


    We report a rare case of primary pituitary lymphoma in a 75-year-old immunocompetent woman. The patient was blind in the right eye and presented with visual disturbance in the left eye that started 2 months previously. She also exhibited right third and fifth cranial nerve palsy. Magnetic resonance imaging(MRI)revealed an intrasellar mass lesion with right cavernous sinus invasion and suprasellar extension with compression of the optic chiasm. The mass lesion was isointense on both T1WI and T2WI, and showed less enhancement than a normal pituitary gland on gadolinium-enhanced T1WI. We therefore suspected the tumor to be a nonfunctioning pituitary adenoma. The patient underwent endoscopic endonasal transsphenoidal surgery. The tumor was firm and grayish, and had an ill-defined border along the normal pituitary gland. Histological examination revealed a malignant CD5-positive diffuse large B-cell lymphoma. After surgery, the patient received both chemotherapy and radiotherapy. Although the visual acuity of the right eye did not improved, other symptoms improved. At the 34-month follow-up, no recurrence was detected on serial MRI. Patients with primary pituitary lymphoma often exhibit ophthalmoplegia and/or panhypopituitarism more frequently than expected from radiological findings. In cases of pituitary tumors with atypical symptoms, a biopsy and general physical examination should be performed immediately to determine the diagnosis and perform adjuvant therapy even when the tumor is assumed as nonfunctioning pituitary adenoma from the image findings.

  8. Comparison of (68)Ga DOTATATE to 18F-FDG uptake is useful in the differentiation of residual or recurrent pituitary adenoma from the remaining pituitary tissue after transsphenoidal adenomectomy. (United States)

    Zhao, Xiaobin; Xiao, Jianqi; Xing, Bing; Wang, Renzhi; Zhu, Zhaohui; Li, Fang


    The evaluation of the remaining pituitary tissue and recurrent or residual tumor after the pituitary adenoma resection is difficult. However, it is essential to assess the size of the recurrent tumor and remaining pituitary reserve before resurgery. This study aimed to distinguish the remaining pituitary tissue from pituitary adenoma with Ga 1,4,7,10-tetraazacyclododecane-N,N',N″,N″'-tetraacetic acid-D-Phe,Tyr3-octreotate (DOTATATE) and F-FDG PET imaging in patients status post transsphenoidal adenomectomy. Thirty-five patients with suspected recurrent/residual pituitary tumors were retrospectively evaluated. All of these patients underwent DOTATATE and FDG PET/CT within 1 week before additional surgery. The DOTATATE and FDG uptake levels were compared. The image findings were then compared with pathology results after the additional surgery. Residual or recurrent pituitary adenoma were confirmed pathologically in all 35 patients. One recurrent pituitary adenoma did not have either DOTATATE or FDG uptake. In the remaining 34 adenomas, 33 had higher FDG uptake than DOTATATE uptake. In comparison, DOTATATE had significant higher uptake than FDG in the remaining pituitary tissues in all cases. Different degree of uptake of Ga DOTATATE and F-FDG PET/CT in the remaining pituitary tissue and recurrent/residual pituitary tumor indicated that combined analysis of Ga DOTATATE and F-FDG PET/CT might be of clinical value in differentiating recurrent/residual pituitary adenoma from the remaining pituitary tissue.

  9. Efficacy of tumor necrosis factor-alpha and antibiotics in therapy of experimental murine staphylococcal mastitis. (United States)

    Sanchez, M S; Ford, C W; Yancey, R J


    The mouse model was used to determine the efficacy of the cytokine, tumor necrosis factor-alpha, and antibiotic in treatment of experimentally induced staphylococcal mastitis. Recombinant human tumor necrosis factor-alpha alone administered to the mammary glands of lactating mice recruited significantly more polymorphonuclear neutrophils into the gland by 4 h posttreatment than did the untreated control. One hundred times less recombinant mouse tumor necrosis factor-alpha than human tumor necrosis factor-alpha was required to enhance the killing of Staphylococcus aureus within the gland. Human tumor necrosis factor-alpha effectively enhanced the killing of the bacteria when it was administered 4 to 0 h prior to infection, but not 4 h after infection. When mice were first pretreated with tumor necrosis factor-alpha, infected, and then treated with antibiotics (ciprofloxacin and pirlimycin, but not cloxacillin), the combination of antibiotic and cytokine significantly reduced the number of bacteria within the gland compared with that for mice treated with antibiotic alone, cytokine alone, or placebo. Recombinant tumor necrosis factor-alpha may be an effective adjunct to antimicrobial therapy in treatment of staphylococcal mastitis in the bovine.

  10. Immediate postoperative complications in transsphenoidal pituitary surgery: A prospective study

    Directory of Open Access Journals (Sweden)

    Tumul Chowdhury


    Full Text Available Background: Considering the important role of pituitary gland in regulating various endocrine axes and its unique anatomical location, various postoperative complications can be anticipated resulting from surgery on pituitary tumors. We examined and categorized the immediate postoperative complications according to various tumor pathologies. Materials and Methods: We carried out a prospective study in 152 consecutive patients and noted various postoperative complications during neurosurgical intensive care unit stay (within 48 hrs of hospital stay in patients undergoing transsphenoidal removal of pituitary tumors. Results: In our series, various groups showed different postoperative complications out of which, cerebrospinal fluid leak was the commonest followed by diabetes insipidus, postoperative nausea and vomiting, and hematoma at operation site. Conclusion: Various immediate postoperative complications can be anticipated in transsphenoidal pituitary surgery even though, it is considered to be relatively safe.

  11. MRI of the hypothalamic-pituitary axis in children

    Energy Technology Data Exchange (ETDEWEB)

    Argyropoulou, Maria I. [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); Kiortsis, Dimitrios Nikiforos [University of Ioannina, Department of Physiology, Medical School, Ioannina (Greece)


    In childhood, the MR characteristics of the normal pituitary gland are well established. During the first 2 months of life the adenohypophysis demonstrates high signal. Pituitary gland height (PGH) decreases during the 1st year of life and then increases, reaching a plateau after puberty. The magnetization transfer ratio (MTR) increases in both sexes up to the age of 20 years. On dynamic contrast-enhanced studies, the posterior pituitary lobe enhances simultaneously with the straight sinus, and the adenohypophysis later, but within 30 s. In genetically determined dysfunctional states, the adenohypophysis may be normal, hypoplastic, or enlarged. Pituitary enlargement, observed in Prop 1 gene mutations, is characterized by a mass interposed between the anterior and posterior lobes. An ectopic posterior lobe (EPP), associated with a hypoplastic or absent pituitary stalk, may be observed in patients with hypopituitarism. Tumors of the hypothalamic-pituitary (HP) axis may be the origin of adenohypophyseal deficiencies. A small hypointense adenohypophysis is found in iron overload states and is often associated with hypogonadotrophic hypogonadism. Absence of the posterior lobe bright signal, with or without a thick pituitary stalk or a mass at any site from the median eminence to the posterior pituitary lobe, may be found in diabetes insipidus. Hydrocephalus, suprasellar arachnoid cysts, hypothalamic hamartomas and craniopharyngiomas may result in central precocious puberty (CPP). Increased PGH in girls with idiopathic CPP is useful for its differential diagnosis from premature thelarche (PT). Pituitary adenomas, observed mainly in adolescents, present the same MR characteristics as those in adults. (orig.)

  12. Familial Isolated Pituitary Adenomas (FIPA) and the Pituitary Adenoma Predisposition due to Mutations in the Aryl Hydrocarbon Receptor Interacting Protein (AIP) Gene (United States)

    Aaltonen, Lauri A.; Daly, Adrian F.


    Pituitary adenomas are one of the most frequent intracranial tumors and occur with a prevalence of approximately 1:1000 in the developed world. Pituitary adenomas have a serious disease burden, and their management involves neurosurgery, biological therapies, and radiotherapy. Early diagnosis of pituitary tumors while they are smaller may help increase cure rates. Few genetic predictors of pituitary adenoma development exist. Recent years have seen two separate, complimentary advances in inherited pituitary tumor research. The clinical condition of familial isolated pituitary adenomas (FIPA) has been described, which encompasses the familial occurrence of isolated pituitary adenomas outside of the setting of syndromic conditions like multiple endocrine neoplasia type 1 and Carney complex. FIPA families comprise approximately 2% of pituitary adenomas and represent a clinical entity with homogeneous or heterogeneous pituitary adenoma types occurring within the same kindred. The aryl hydrocarbon receptor interacting protein (AIP) gene has been identified as causing a pituitary adenoma predisposition of variable penetrance that accounts for 20% of FIPA families. Germline AIP mutations have been shown to associate with the occurrence of large pituitary adenomas that occur at a young age, predominantly in children/adolescents and young adults. AIP mutations are usually associated with somatotropinomas, but prolactinomas, nonfunctioning pituitary adenomas, Cushing disease, and other infrequent clinical adenoma types can also occur. Gigantism is a particular feature of AIP mutations and occurs in more than one third of affected somatotropinoma patients. Study of pituitary adenoma patients with AIP mutations has demonstrated that these cases raise clinical challenges to successful treatment. Extensive research on the biology of AIP and new advances in mouse Aip knockout models demonstrate multiple pathways by which AIP may contribute to tumorigenesis. This review assesses

  13. Evaluation of pituitary lesions on magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Sakurai, Takashi; Sakamoto, Tatsuo; Sekino, Hiroaki; Inada, Yoichi; Ishikawa, Toru; Sato, Mitsuya (St. Marianna Univ., Kawasaki (Japan). School of Medicine)


    We evaluated the magnetic resonance imaging (MRI) of seventeen patients with pituitary adenomas (10 cases of prolactin secreting ; 2, growth hormone secreting and 5, non-functioning adenomas) and three patients with pituitary enlargement due to hypothyroidism. The volume of the functional adenomas or the enlarged pituitary glands correlated by MRI correlated with the level of serum pituitary hormone. We evaluated the points of differences on the T[sub 1] weighted images of MRI between microadenomas and pituitary enlargements. The microadenomas appeared as the enlarged pituitary gland with isointensity area, but following administration of Gd-DTPA, the adenomas were recognized as a low intensity area (mass) with in an enhanced high intensity area of the normal gland with a shift of the pituitary stalk. On the other hand, the pituitary enlargements appeared as a large iso intensity area on T[sub 1] weighted images, and were homogeneously enhanced as a high intensity area after Gd-DTPA administration, but without a shift of the pituitary stalk. Signal intensity ratios (SIR) and contrast enhancement ratios (CER) of all cases with pituitary adenomas were calculated using MRI. Differences in SIR and CER could not be demonstrated among the hormone-secreting adenomas. Thus, it is difficult to differentiate the various types of adenomas by using the differences in SIR or CER, since there are many, interfering factors, including hemorrhage, cyst, and necrosis. Postoperative permanent diabetes insipidus (DI) appeared in the cases that had no visualization of posterior high signal intensity area and a tumoral mass effect on the hypothalamus on preoperative MRI. The reason for postoperative permanent DI is thought to be the result of a disturbance of blood circulation in the pituitary gland due to a mass effect and surgical burden to the proximal pituitary stalk or the hypothalamus. (author).

  14. Oncolytic efficacy of recombinant vesicular stomatitis virus and myxoma virus in experimental models of rhabdoid tumors. (United States)

    Wu, Yushui; Lun, Xueqing; Zhou, Hongyuan; Wang, Limei; Sun, Beichen; Bell, John C; Barrett, John W; McFadden, Grant; Biegel, Jaclyn A; Senger, Donna L; Forsyth, Peter A


    Rhabdoid tumors are highly aggressive pediatric tumors that are usually refractory to available treatments. The purpose of this study was to evaluate the therapeutic potential of two oncolytic viruses, myxoma virus (MV) and an attenuated vesicular stomatitis virus (VSV(DeltaM51)), in experimental models of human rhabdoid tumor. Four human rhabdoid tumor cell lines were cultured in vitro and treated with live or inactivated control virus. Cytopathic effect, viral gene expression, infectious viral titers, and cell viability were examined at various time points after infection. To study viral oncolysis in vivo, human rhabdoid tumor cells were implanted s.c. in the hind flank or intracranially in CD-1 nude mice and treated with intratumoral (i.t.) or i.v. injections of live or UV-inactivated virus. Viral distribution and effects on tumor size and survival were assessed. All rhabdoid tumor cell lines tested in vitro were susceptible to productive lethal infections by MV and VSV(DeltaM51). I.t. injection of live MV or VSV(DeltaM51) dramatically reduced the size of s.c. rhabdoid tumor xenografts compared with control animals. I.v. administration of VSV(DeltaM51) or i.t. injection of MV prolonged the median survival of mice with brain xenografts compared with controls (VSV(DeltaM51): 25 days versus 21 days, log-rank test, P = 0.0036; MV: median survival not reached versus 21 days, log-rank test, P = 0.0007). Most of the MV-treated animals (4 of 6; 66.7%) were alive and apparently "cured" when the experiment was arbitrarily ended (>180 days). These results suggest that VSV(DeltaM51) and MV could be novel effective therapies against human rhabdoid tumor.

  15. Acromegaly with negative pituitary MRI and no evidence of ectopic source: the role of transphenoidal pituitary exploration? (United States)

    Daud, Sameera; Hamrahian, Amir H; Weil, Robert J; Hamaty, Marwan; Prayson, Richard A; Olansky, Leann


    Growth hormone (GH) producing adenomas of the pituitary gland are usually macroadenomas (>10 mm in size). Often these adenomas are locally invasive by the time of diagnosis. Acromegaly secondary to a very small pituitary microadenoma not visualized on pituitary magnetic resonance (MR) imaging is rare. We report a patient with acromegaly and an unremarkable pituitary MR imaging who had negative work up for ectopic growth hormone-releasing hormone (GHRH) or GH secreting tumors. Transsphenoidal pituitary exploration revealed a pituitary adenoma located on the left side of the sella against the medial wall of the cavernous sinus extending posteriorly along the floor of the sella all the way to the right side. The acromegaly was treated with resection of the pituitary adenoma and normalization of serum insulin-like growth factor 1 (IGF-1) and GH levels. In a patient with acromegaly and unremarkable pituitary MR imaging, with no evidence of ectopic GH and GHRH production, transsphenoidal pituitary exploration is a reasonable approach and may result in clinical improvement and biochemical cure in the hand of experienced surgeon. This approach may avoid long term medical treatment with its associated cost.

  16. Surgical strategy for giant pituitary adenoma based on evaluation of fine feeding system and angioarchitecture

    Directory of Open Access Journals (Sweden)

    Yoshikazu Ogawa, M.D., Ph.D.


    Conclusion: Major blood supply was different from the normal supply to the anterior pituitary gland and did not necessarily correspond to tumor shape and extension. Surgical strategy should be established based on the tumor feeding systems and hemodynamics in giant pituitary adenomas.

  17. Angiotensins Inhibit Cell Growth in GH3 Lactosomatotroph Pituitary Tumor Cell Culture: A Possible Involvement of the p44/42 and p38 MAPK Pathways

    Directory of Open Access Journals (Sweden)

    Dorota Ptasinska-Wnuk


    Full Text Available The local renin-angiotensin system is present in the pituitary. We investigated the effects of angiotensins on GH3 lactosomatotroph cells proliferation in vitro and the involvement of p44/42 and p38 MAPK inhibitors in the growth-regulatory effects of angiotensins. Materials and Methods. Cell viability using the Mosmann method and proliferation by the measurement of BrdU incorporation during DNA synthesis were estimated. Results. Ang II and ang IV decreased the viability and proliferation of GH3 cells. Inhibitor of p44/42 MAPK attenuated the effects of ang II on cell viability and proliferation but did not affect the ang 5-8-dependent actions. Inhibitor of p38 MAPK prevented the decrease in the number of GH3 cells in ang-II- and ang-IV-treated groups. Conclusions. The growth-inhibitory effect of ang II is possibly mediated by the p44/42 MAPK. The p38 MAPK appears to mediate the inhibitory effects of both ang II and ang 5–8 upon cell survival.

  18. Recent highlights of experimental research for inhibiting tumor growth by using Chinese medicine. (United States)

    He, Xi-ran; Han, Shu-yan; Li, Ping-ping


    To give an overview of contemporary experimental research using Chinese medicine (CM) for the treatment of cancer. As an integral part of mainstream medicine in the People's Republic of China, CM emphasizes improvements in holistic physical condition instead of merely killing tumor cells, which is consistent with the current medical model that advocates patient-oriented treatment. Great progress has been made in experimental research, and the principle aspects include anti-tumor angiogenesis, inducing apoptosis and differentiation, reversing multidrug resistance, and improving immune function. As a current hot topic in cancer research, tumor microenvironment (TME) highlights the mutual and interdependent interaction between tumor cells and their surrounding tissues, and the CM treatment concept bears a striking resemblance to it. To date, primary points of TME include extracellular matrix remodeling, inflammation, hypoxia, and angiogenesis, but trials using CM with a focus on TME are rare. Despite considerable recent development, experimental research on CM for solving cancer issues appears insufficient. Greater efforts in this field are urgently needed.

  19. Glioma Surgical Aspirate: A Viable Source of Tumor Tissue for Experimental Research

    Directory of Open Access Journals (Sweden)

    Perry F. Bartlett


    Full Text Available Brain cancer research has been hampered by a paucity of viable clinical tissue of sufficient quality and quantity for experimental research. This has driven researchers to rely heavily on long term cultured cells which no longer represent the cancers from which they were derived. Resection of brain tumors, particularly at the interface between normal and tumorigenic tissue, can be carried out using an ultrasonic surgical aspirator (CUSA that deposits liquid (blood and irrigation fluid and resected tissue into a sterile bottle for disposal. To determine the utility of CUSA-derived glioma tissue for experimental research, we collected 48 CUSA specimen bottles from glioma patients and analyzed both the solid tissue fragments and dissociated tumor cells suspended in the liquid waste fraction. We investigated if these fractions would be useful for analyzing tumor heterogeneity, using IHC and multi-parameter flow cytometry; we also assessed culture generation and orthotopic xenograft potential. Both cell sources proved to be an abundant, highly viable source of live tumor cells for cytometric analysis, animal studies and in-vitro studies. Our findings demonstrate that CUSA tissue represents an abundant viable source to conduct experimental research and to carry out diagnostic analyses by flow cytometry or other molecular diagnostic procedures.

  20. [Cerebral infarction after pituitary apoplexy: Description of a case and review of the literature]. (United States)

    Serramito García, Ramón; Santín Amo, José María; Román Pena, Paula; Pita Buezas, Lara; González Gómez, Lara; García Allut, Alfredo

    Pituitary apoplexy is usually the result of hemorrhagic infarction in a pituitary adenoma. The clinical presentation varies widely and includes asymptomatic cases, classical pituitary apoplexy and even sudden death. Cerebral ischemia due to pituitary apoplexy is very rare. It may be caused by vasospasm or direct compression of cerebral vessels by the tumor. We report a case of pituitary apoplexy associated with cerebral infarction and discuss the relationship between the two events. Copyright © 2016 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Predicting difficult laryngoscopy in acromegalic patients undergoing surgery for excision of pituitary tumors: A comparison of extended Mallampati score with modified Mallampati classification

    Directory of Open Access Journals (Sweden)

    Ashish Bindra


    Full Text Available Background: There are numerous reports of difficult laryngoscopy and intubation in patients with acromegaly. To date, no study has assessed the application of extended Mallampati score (EMS for predicting difficult intubation in acromegalics. The primary aim of this study was to compare EMS with modified Mallampati classification (MMP in predicting difficult laryngoscopy in acromegalic patients. We hypothesized that since EMS has been reported to be more specific and better predictor than MMP, it may be superior to the MMP to predict difficult laryngoscopy in acromegalic patients. Materials and Methods: For this prospective cohort study with matched controls, acromegalic patients scheduled to undergo pituitary surgery over a period of 3 years (January 2008-December 2010 were enrolled. Preoperative airway assessment was performed by experienced anesthesiologists and involved a MMP and the EMS. Under anesthesia, laryngoscopic view was assessed using Cormack-Lehane (CL grading. MMP and CL grades of I and II were defined "easy" and III and IV as "difficult". EMS grade of I and II were defined "easy" and III as "difficult". Data were used to determine the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MMP and EMS in predicting difficult laryngoscopy. Results: Seventy eight patients participated in the study (39 patients in each group. Both MMP and EMS failed to detect difficult laryngoscopy in seven patients. Only one laryngoscopy was predicted to be difficult by both tests which was in fact, difficult. Conclusion: We found that addition of neck extension did not improve the predictive value of MMP.

  2. Microscopic surgery for pituitary adenomas to preserve the pituitary gland and stalk. (United States)

    Li, Hao-Yu; Feng, Cheng-Yuan; Zhang, Chi; Su, Jun; Yuan, Jian; Xie, Yuanyang; Liao, Yiwei; Yuan, Xianrui; Liu, Qing


    Surgery is the primary treatment of choice for all symptomatic pituitary adenomas except prolactinomas. Common postoperative complications include endocrinopathies, vision impairment and cerebrospinal fluid leak. The present study assessed 153 continuous microscopic surgeries for pituitary adenomas performed by an author of the present study between 2010 to 2014. Patients underwent either transphenoidal or transcranial surgery depending on their individual tumor characteristics. Five typical cases are presented in the present study and intraoperative identification and preservation of the gland and stalk were discussed. Postoperative complications were analyzed and compared with the literature. In the present analysis, 90.2% patients received transphenoidal surgery, and the rest underwent transcranial operation. Gross total resection was achieved in 81.2% patients in the transphenoidal group and 46.7% patients in the transcranial group. No new hypopituitarism or worsening of the pre-existing pituitary dysfunctions was detected. The most common postoperative endocrinopathy was diabetes insipidus (transphenoidal group, 4.3%; transcranial group, 26.7%). All patients were fully recovered prior to discharge. The findings indicated the importance of pituitary gland and stalk preservation during the microscopic surgery to minimize postoperative morbidity and mortality, without compromising the extent of tumor resection. Based on preoperative imaging characteristics and intraoperative observations, surgeons should try all possible means to preserve the pituitary stalk and gland during surgery in order to minimize postoperative endocrinopathies and improve quality of life.

  3. Experimental iodine-125 seed irradiation of intracerebral brain tumors in nude mice

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    Haveman Jaap


    Full Text Available Abstract Background High-dose radiotherapy is standard treatment for patients with brain cancer. However, in preclinical research external beam radiotherapy is limited to heterotopic murine models– high-dose radiotherapy to the murine head is fatal due to radiation toxicity. Therefore, we developed a stereotactic brachytherapy mouse model for high-dose focal irradiation of experimental intracerebral (orthotopic brain tumors. Methods Twenty-one nude mice received a hollow guide-screw implanted in the skull. After three weeks, 5 × 105 U251-NG2 human glioblastoma cells were injected. Five days later, a 2 mCi iodine-125 brachytherapy seed was inserted through the guide-screw in 11 randomly selected mice; 10 mice received a sham seed. Mice were euthanized when severe neurological or physical symptoms occurred. The cumulative irradiation dose 5 mm below the active iodine-125 seeds was 23.0 Gy after 13 weeks (BEDtumor = 30.6 Gy. Results In the sham group, 9/10 animals (90% showed signs of lethal tumor progression within 6 weeks. In the experimental group, 2/11 mice (18% died of tumor progression within 13 weeks. Acute side effects in terms of weight loss or neurological symptoms were not observed in the irradiated animals. Conclusion The intracerebral implantation of an iodine-125 brachytherapy seed through a stereotactic guide-screw in the skull of mice with implanted brain tumors resulted in a significantly prolonged survival, caused by high-dose irradiation of the brain tumor that is biologically comparable to high-dose fractionated radiotherapy– without fatal irradiation toxicity. This is an excellent mouse model for testing orthotopic brain tumor therapies in combination with radiation therapy.

  4. Sex differences in the pituitary TGFβ1 system: The role of TGFβ1 in prolactinoma development. (United States)

    Recouvreux, M Victoria; Faraoni, Erika Y; Camilletti, M Andrea; Ratner, Laura; Abeledo-Machado, Alejandra; Rulli, Susana B; Díaz-Torga, Graciela


    Prolactinomas are the most frequent functioning pituitary adenomas, and sex differences in tumor size, behavior and incidence have been described. These differences have been associated with earlier diagnosis in woman, as well as with serum estradiol levels. Experimental models of prolactinomas in rodents also show a higher incidence in females, and recent findings suggest that gender differences in the transforming growth factor beta 1 (TGFβ1) system might be involved in the sex-specific development of prolactinomas in these models. The aim of this review is to summarize the literature supporting the important role of TGFβ1 as a local modulator of pituitary lactotroph function and to provide recent evidence for TGFβ1 involvement in the sex differences found in prolactinoma development in animal models. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Primary Pituitary Fibrosarcoma with Previous Adenoma. (United States)

    Bayoumi, Ahmed B; Chen, Jenny X; Swiatek, Peter R; Laviv, Yosef; Kasper, Ekkehard M


    Pituitary sarcomas are rare clinical entities most often encountered as secondary neoplasms representing late sequelae of radiation therapy to the sellar region. Primary pituitary fibrosarcomas (PPFS), in contrast, are exceptionally rare tumors with very few cases described in the literature thus far. Herein, we present a case of PFFS and describe it in the context of the existing literature. A 39-year-old woman presented with 2 months of headaches and rapidly progressive vision loss. She was found to have a 2.7-cm pituitary mass and initially underwent transnasal transsphenoidal resection from which pathology confirmed a pituitary adenoma. Eight months after surgery, she represented with vision changes and a recurrent tumor that postoperatively was found to be a primary fibrosarcoma with embedded adenoma remnants. On post-hoc examination of her original pathologic specimen, a prominent fibrous tissue component was suspected to be the source of her fibrosarcoma. This is a rare case of PFFS that highlights the need for close surveillance in affected patients. Through this case, we review the existing literature and discuss both surgical management and aggressive adjuvant therapy of this rare disease entity. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Global Gene Expression Profiling in Three Tumor Cell Lines Subjected to Experimental Cycling and Chronic Hypoxia (United States)

    Olbryt, Magdalena; Habryka, Anna; Student, Sebastian; Jarząb, Michał; Tyszkiewicz, Tomasz; Lisowska, Katarzyna Marta


    Hypoxia is one of the most important features of the tumor microenvironment, exerting an adverse effect on tumor aggressiveness and patient prognosis. Two types of hypoxia may occur within the tumor mass, chronic (prolonged) and cycling (transient, intermittent) hypoxia. Cycling hypoxia has been shown to induce aggressive tumor cell phenotype and radioresistance more significantly than chronic hypoxia, though little is known about the molecular mechanisms underlying this phenomenon. The aim of this study was to delineate the molecular response to both types of hypoxia induced experimentally in tumor cells, with a focus on cycling hypoxia. We analyzed in vitro gene expression profile in three human cancer cell lines (melanoma, ovarian cancer, and prostate cancer) exposed to experimental chronic or transient hypoxia conditions. As expected, the cell-type specific variability in response to hypoxia was significant. However, the expression of 240 probe sets was altered in all 3 cell lines. We found that gene expression profiles induced by both types of hypoxia were qualitatively similar and strongly depend on the cell type. Cycling hypoxia altered the expression of fewer genes than chronic hypoxia (6,132 vs. 8,635 probe sets, FDR adjusted pcycling hypoxia than by prolonged hypoxia, such as IL8, PLAU, and epidermal growth factor (EGF) pathway-related genes (AREG, HBEGF, and EPHA2). These transcripts were, in most cases, validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Our results indicate that experimental cycling hypoxia exerts similar, although less intense effects, on the examined cancer cell lines than its chronic counterpart. Nonetheless, we identified genes and molecular pathways that seem to be preferentially regulated by cyclic hypoxia. PMID:25122487

  7. Adenomas hipofisários: relação entre invasividade e índice proliferativo tumoral Pituitary adenomas: relationship between invasiveness and proliferative cell nuclear index

    Directory of Open Access Journals (Sweden)



    Full Text Available Analisamos 76 pacientes com adenomas hipofisários do ponto de vista clínico, radiológico e tratamento cirúrgico. Todos os casos foram estudados por imuno-histoquímica e em 49 pacientes foi pesquisado o anticorpo monoclonal PCNA. Os adenomas bi-hormonais foram os mais frequentes seguidos dos prolactinomas e os adenomas não secretantes. Os adenomas bi-hormonais não secretantes e os produtores de subunidade alfa foram proporcionalmente mais invasivos pelos critérios radiológicos. A maioria dos pacientes (59 foi operada por via transeptoesfenoidal, em seis casos a via transcraniana foi realizada e em 11 pacientes houve necessidade das duas abordagens. A ressecção foi total em 32 pacientes, a maioria em microadenomas, subtotal em 15 e parcial em 29. A complicação endócrina mais frequente foi diabetes insipidus. Houve tendência de associação positiva para os adenomas secretantes e PCNA mais elevado, assim como relação positiva quando analisamos os adenomas invasivos pela tomografia computadorizada ou ressonância magnética e o PCNA 3 e 4. A melhora visual foi observada em 85% dos macroadenomas, mesmo quando a ressecção foi parcial ou subtotal.We evaluated clinically, radiologically and surgically a series of 76 pituitary adenomas. All cases were assessed immunohistochemically and in 49 patients the PCNA monoclonal antibody was measured. The most frequent types found were the bihormonal adenomas, followed by prolactinomas and non secreting adenomas. The bihormonal adenomas, non secreting adenonas and the sub unit alfa producing adenomas were proportionally more invase as determined by radiological criteria (CTscan or MRI. In 59 patients a transphenoidal approach was used, six cases were operated on transcranially and in 11 patients we used a combination of both approach. Total resection were achieved in 32 cases, most of which were microadenomas, in 15 cases the resection was subtotal and partial in 29 cases. Diabetes insipidus

  8. Experimental study of anti-tumor effects of polysaccharides from Angelica sinensis. (United States)

    Shang, Peng; Qian, Ai-Rong; Yang, Tie-Hong; Jia, Min; Mei, Qi-Bing; Cho, Chi-Hin; Zhao, Wen-Ming; Chen, Zhi-Nan


    To investigate the in vivo anti-tumor effects of total polysaccharide (AP-0) isolated from Angelica sinensis (Oliv.) Diels (Danggui) on mice and the in vitro inhibitory effects of AP-0 and the sub-constituents (AP-1, AP-2 and AP-3) separated from AP-0 on invasion and metastasis of human hepatocellular carcinoma. Three kinds of murine tumor models in vivo, sarcoma 180 (S180), leukemia L1210 and Ehrlich ascitic cancer (EAC) were employed to investigate the anti-tumor effects of AP-0. For each kind of tumor model, three experimental groups were respectively given AP-0 at doses of 30, 100 and 300 mg/kg by ip once a day for 10 days. Positive control groups were respectively given Cy at a dose of 30 mg/kg for S180 and leukemia L1210, and 5-FU at a dose of 20 mg/kg for EAC. On d 11, mice bearing S180 were sacrificed and the masses of tumors, spleens and thymus weighed. The average living days of mice bearing EAC and of mice bearing L1210 were observed, and the rates of life prolongation of each treatment were calculated, respectively. The inhibitory effects of APs on hepatoma invasion and metastasis in vitro were investigated by employing human hepatocellular carcinoma cell line (HHCC) with the Matrigel invasion chamber, adhesion to extracellular matrix and chemotatic migration tests, respectively. AP-0 had no obviously inhibitory effect on the growth of S180, but it could significantly decrease the thymus weights of the mice bearing S180. AP-0 could significantly reduce the production of ascitic liquids and prolong the life of mice bearing EAC. AP-0 could also increase the survival time of mice bearing L1210. AP-0 and AP-2 had significantly inhibitory effects on the invasion of HHCC into the Matrigel reconstituted basement membrane with the inhibitory rates of 56.4 % and 68.3 %, respectively. AP-0, AP-1, AP-2 and AP-3 could influence the adhesion of HHCC to extracellular matrix proteins (Matrigel and fibronectin) at different degrees, among them only AP-3 had significant

  9. Experimental pain ratings and reactivity of cortisol and soluble tumor necrosis factor-α receptor II following a trial of hypnosis: results of a randomized controlled pilot study. (United States)

    Goodin, Burel R; Quinn, Noel B; Kronfli, Tarek; King, Christopher D; Page, Gayle G; Haythornthwaite, Jennifer A; Edwards, Robert R; Stapleton, Laura M; McGuire, Lynanne


    Current evidence supports the efficacy of hypnosis for reducing the pain associated with experimental stimulation and various acute and chronic conditions; however, the mechanisms explaining how hypnosis exerts its effects remain less clear. The hypothalamic-pituitary-adrenal (HPA) axis and pro-inflammatory cytokines represent potential targets for investigation given their purported roles in the perpetuation of painful conditions; yet, no clinical trials have thus far examined the influence of hypnosis on these mechanisms. Healthy participants, highly susceptible to the effects of hypnosis, were randomized to either a hypnosis intervention or a no-intervention control. Using a cold pressor task, assessments of pain intensity and pain unpleasantness were collected prior to the intervention (Pre) and following the intervention (Post) along with pain-provoked changes in salivary cortisol and the soluble tumor necrosis factor-α receptor II (sTNFαRII). Compared with the no-intervention control, data analyses revealed that hypnosis significantly reduced pain intensity and pain unpleasantness. Hypnosis was not significantly associated with suppression of cortisol or sTNFαRII reactivity to acute pain from Pre to Post; however, the effect sizes for these associations were medium-sized. Overall, the findings from this randomized controlled pilot study support the importance of a future large-scale study on the effects of hypnosis for modulating pain-related changes of the HPA axis and pro-inflammatory cytokines. Wiley Periodicals, Inc.

  10. Immunohistochemical Expression of p16 and p21 in Pituitary Tissue Adjacent to Pituitary Adenoma versus Pituitary Tissue Obtained at Autopsy: Is There a Difference? (United States)

    Manojlovic Gacic, Emilija; Skender-Gazibara, Milica; Soldatovic, Ivan; Dundjerovic, Dusko; Boricic, Novica; Raicevic, Savo; Popovic, Vera


    Normal pituitary tissue is frequently used for comparison with protein expression in tumor tissue, being obtained either at surgery or at autopsy. p16 and p21 proteins are cyclin-dependent kinase inhibitors, belonging to INK4 and Cip/Kip family, respectively. Their expression is increased in response to DNA damage or other cellular stressors, resulting in the activation of cell cycle checkpoints. They also play important roles in cellular senescence. The purpose of this study was to investigate differences in p16 and p21 immunohistochemical expression in normal pituitary tissue adjacent to pituitary adenoma obtained during neurosurgical procedure with pituitary tissue obtained at autopsy, from patients who died from non-endocrinological diseases. Our results show significant difference in p16 nuclear and p21 cytoplasmic immunohistochemical expression between two types of normal pituitary tissues. One of the reasons for this difference could be the age of subjects because those who underwent autopsy for a non-endocrinological disease were significantly older than subjects who underwent neurosurgery for a pituitary adenoma. Our finding that differences are probably not influenced by postmortem changes is supported by no significant correlation between postmortem interval and immunohistochemical p16 and p21 expression. The influence of the presence of a pituitary adenoma could not be evaluated in these specimens.

  11. Downregulation of Insulin-like growth factor binding protein 6 is associated with ACTH-secreting pituitary adenoma growth. (United States)

    Yang, Yakun; Sheng, Miaomiao; Huang, Fengming; Bu, Dechao; Liu, Xiaohai; Yao, Yong; Dai, Congxin; Sun, Bowen; Zhu, Jindong; Jiao, Yonghui; Wei, Zhenqing; Zhu, Huijuan; Lu, Lin; Zhao, Yi; Jiang, Chengyu; Wang, Renzhi


    Adrenocorticotrophic hormone (ACTH)-dependent Cushing's syndrome, called Cushing disease, is caused by a corticotroph tumor of the pituitary gland. Insulin-like growth factor binding protein 6 (IGFBP6), which regulates insulin-like growth factor (IGF) activity and inhibits several IGF2-dependent cancer growths, plays a pivotal role in the tumorigenesis of malignancy, but its roles in ACTH-secreting pituitary adenomas remain unclear. To investigate IGFBP6 expression in ACTH-secreting pituitary adenomas, and its involvement in tumor growth. Sporadic ACTH-secreting pituitary adenomas specimens (n = 41) and adjacent non-tumorous pituitary tissues (n = 9) were collected by transphenoidal surgery. IGFBP6 expression was assessed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and validated by Western blotting. Associations of IGFBP6 expression with maximum tumor diameter or Ki-67 labeling index were evaluated in ACTH-secreting pituitary adenomas. IGFBP6 mRNA and protein expression were both decreased in ACTH-secreting pituitary adenomas, compared to adjacent non-tumorous pituitary tissues (P pituitary adenomas. IGFBP6 attenuation in ACTH-secreting pituitary adenomas is associated with tumor growth, through activation of PI3K-AKT-mTOR pathway. The finding underlies IGFBP6 roles in Cushing disease and would potentially provide a novel target of medical therapies.

  12. Mechanisms of experimental cancer cachexia. Local involvement of IL-1 in colon-26 tumor. (United States)

    Strassmann, G; Masui, Y; Chizzonite, R; Fong, M


    In the colon-26 (C-26) tumor model, the cytokine IL-6 is an important factor involved in experimental cancer cachexia. Recent in vitro data indicated that IL-1 plays a role in the interaction between host macrophages and C-26 cells that express IL-1R, resulting in the amplification of tumor IL-6 production. To investigate the role of IL-1 on the development of C-26 cachexia in vivo, the effect of specific blockade of the action of IL-1 with reagents against IL-1R was evaluated. Both IL-1R antagonist (IL-1RA) and the mAb 35F5 directed against IL-1R type I, prevented binding of radioactive IL-1, and inhibited IL-1-induced IL-6 synthesis by the C-26 cell line. Whereas a systemic administration of these reagents did not reverse weight loss in C-26-bearing mice, intratumoral injections of IL-1RA significantly reduced cachexia. Furthermore, body composition analysis confirmed that this treatment improved lean tissue and fat, as well as hypoglycemia and serum IL-6 level. The fact that the treatment did not change the tumor burden suggests that it affected the host directly. These results support the hypothesis that, at the microenvironment of the C-26 tumor, IL-1 is involved in the cachexia endured by the host.

  13. An acute adrenal insufficiency revealing pituitary metastases of lung cancer in an elderly patient. (United States)

    Marmouch, Hela; Arfa, Sondes; Mohamed, Saoussen Cheikh; Slim, Tensim; Khochtali, Ines


    Metastases of solid tumors to the pituitary gland are often asymptomatic or appereas as with diabetes insipid us. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The presentation with an acute adrenal insufficiency is a rare event. A 69-year-old men presented with vomiting, low blood pressure and hypoglycemia. Hormonal exploration confirmed a hypopituitarism. Appropriate therapy was initiated urgently. The hypothalamic-pituitary MRI showed a pituitary hypertrophy, a nodular thickening of the pituitary stalk. The chest X Rays revealed pulmonary opacity. Computed tomography scan of the chest showed a multiples tumors with mediastinal lymphadenopathy. Bronchoscopy and biopsy demonstrated a pulmonary adenocarcinoma. Hence we concluded to a lung cancer with multiple pituitary and adrenal gland metastases. This case emphasizes the need for an etiological investigation of acute adrenal insufficiency after treatment of acute phase.

  14. Handheld confocal laser endomicroscopic imaging utilizing tumor-specific fluorescent labeling to identify experimental glioma cells in vivo. (United States)

    Martirosyan, Nikolay L; Georges, Joseph; Kalani, M Yashar S; Nakaji, Peter; Spetzler, Robert F; Feuerstein, Burt G; Preul, Mark C


    We have reported that handheld confocal laser endomicroscopy (CLE) can be used with various nonspecific fluorescent dyes to improve the microscopic identification of brain tumor and its boundaries. Here, we show that CLE can be used experimentally with tumor-specific fluorescent labeling to define glioma margins in vivo. Thirteen rats underwent craniectomy and in vivo imaging 21 days after implantation with green fluorescent protein (GFP)-labeled U251 (n = 7) cells or epidermal growth factor receptor (EGFR) overexpressing F98 cells (n = 6). Fluorescein isothiocyanate (FITC) conjugated EGFR fluorescent antibody (FITC-EGFR) was applied for contrast in F98 tumors. Confocal images of normal brain, obvious tumor, and peritumoral zones were collected using the CLE system. Bench-top confocal microscopy and hematoxylin and eosin-stained sections were correlated with CLE images. GFP and FITC-EGFR fluorescence of glioma cells were detected by in vivo visible-wavelength fluorescence CLE. CLE of GFP-labeled tumors revealed bright individual satellite tumor cells within peritumoral tissue, a definitive tumor border, and subcellular structures. Imaging with FITC-EGFR labeling provided weaker contrast in F98-EGFR tumors but was able to delineate tumor cells. Imaging with both methods in various tumor regions correlated with standard confocal imaging and clinical histology. These data suggest that in vivo CLE of selectively tagged neoplasms could allow specific interactive identification of tumoral areas. Imaging of GFP and FITC-EGFR provides real-time histologic information precisely related to the site of microscopic imaging of tumor.

  15. NS-398, a selective cyclooxygenase-2 inhibitor, reduces experimental bladder carcinoma outgrowth by inhibiting tumor cell proliferation.

    NARCIS (Netherlands)

    Smakman, N.; Schaap, N.P.M.; Snijckers, C.M.; Rinkes, M.J.; Kranenburg, O.


    OBJECTIVES: To evaluate the efficacy of the selective cyclooxygenase-2 (COX-2) inhibitor NS-398 in treating experimental T24 bladder carcinoma, and to assess its effect on tumor cell proliferation and survival and tumor vascularization. COX-2 overexpression is frequently observed in bladder

  16. Classical mathematical models for description and prediction of experimental tumor growth.

    Directory of Open Access Journals (Sweden)

    Sébastien Benzekry


    Full Text Available Despite internal complexity, tumor growth kinetics follow relatively simple laws that can be expressed as mathematical models. To explore this further, quantitative analysis of the most classical of these were performed. The models were assessed against data from two in vivo experimental systems: an ectopic syngeneic tumor (Lewis lung carcinoma and an orthotopically xenografted human breast carcinoma. The goals were threefold: 1 to determine a statistical model for description of the measurement error, 2 to establish the descriptive power of each model, using several goodness-of-fit metrics and a study of parametric identifiability, and 3 to assess the models' ability to forecast future tumor growth. The models included in the study comprised the exponential, exponential-linear, power law, Gompertz, logistic, generalized logistic, von Bertalanffy and a model with dynamic carrying capacity. For the breast data, the dynamics were best captured by the Gompertz and exponential-linear models. The latter also exhibited the highest predictive power, with excellent prediction scores (≥80% extending out as far as 12 days in the future. For the lung data, the Gompertz and power law models provided the most parsimonious and parametrically identifiable description. However, not one of the models was able to achieve a substantial prediction rate (≥70% beyond the next day data point. In this context, adjunction of a priori information on the parameter distribution led to considerable improvement. For instance, forecast success rates went from 14.9% to 62.7% when using the power law model to predict the full future tumor growth curves, using just three data points. These results not only have important implications for biological theories of tumor growth and the use of mathematical modeling in preclinical anti-cancer drug investigations, but also may assist in defining how mathematical models could serve as potential prognostic tools in the clinic.

  17. Classical Mathematical Models for Description and Prediction of Experimental Tumor Growth (United States)

    Benzekry, Sébastien; Lamont, Clare; Beheshti, Afshin; Tracz, Amanda; Ebos, John M. L.; Hlatky, Lynn; Hahnfeldt, Philip


    Despite internal complexity, tumor growth kinetics follow relatively simple laws that can be expressed as mathematical models. To explore this further, quantitative analysis of the most classical of these were performed. The models were assessed against data from two in vivo experimental systems: an ectopic syngeneic tumor (Lewis lung carcinoma) and an orthotopically xenografted human breast carcinoma. The goals were threefold: 1) to determine a statistical model for description of the measurement error, 2) to establish the descriptive power of each model, using several goodness-of-fit metrics and a study of parametric identifiability, and 3) to assess the models' ability to forecast future tumor growth. The models included in the study comprised the exponential, exponential-linear, power law, Gompertz, logistic, generalized logistic, von Bertalanffy and a model with dynamic carrying capacity. For the breast data, the dynamics were best captured by the Gompertz and exponential-linear models. The latter also exhibited the highest predictive power, with excellent prediction scores (≥80%) extending out as far as 12 days in the future. For the lung data, the Gompertz and power law models provided the most parsimonious and parametrically identifiable description. However, not one of the models was able to achieve a substantial prediction rate (≥70%) beyond the next day data point. In this context, adjunction of a priori information on the parameter distribution led to considerable improvement. For instance, forecast success rates went from 14.9% to 62.7% when using the power law model to predict the full future tumor growth curves, using just three data points. These results not only have important implications for biological theories of tumor growth and the use of mathematical modeling in preclinical anti-cancer drug investigations, but also may assist in defining how mathematical models could serve as potential prognostic tools in the clinic. PMID:25167199

  18. Heterogeneity of secretory granules of silent pituitary adenomas

    DEFF Research Database (Denmark)

    Holck, S; Wewer, U M; Albrechtsen, R


    Silent pituitary adenomas were compared with hormonally active tumors taking into account the size, number, and ultrastructural characteristics of secretory granules (SG). The study group (a total of 79 primary pituitary adenomas) comprised 27 silent, 21 growth hormone (GH)-producing-, 16 prolactin...... approximately 10 to 50% of the granules in each cell. These granules were not seen in hormonally active tumors and considered therefore diagnostic of silent pituitary adenomas....... (PRL)-producing-, 5 GH-PRL-producing- and 10 adrenocorticotropic hormone (ACTH)-producing adenomas. The SG of silent adenomas were significantly smaller than SG in endocrine active adenomas. All hormonally inactive tumors also contained small (mean, 94 nm) specific cytoplasmic granules, designated...

  19. Fractionated stereotactic radiotherapy in the treatment of pituitary adenomas

    Energy Technology Data Exchange (ETDEWEB)

    Kopp, C.; Theodorou, M.; Poullos, N.; Astner, S.T.; Geinitz, H.; Molls, M. [Technische Univ. Muenchen, Klinikum rechts der Isar (Germany). Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie; Stalla, G.K. [Max-Planck-Institut fuer Psychiatrie, Muenchen (Germany). Klinische Neuroendokrinologie; Meyer, B. [Technische Univ. Muenchen, Klinikum rechts der Isar (Germany). Neurochirurgische Klinik und Poliklinik; Nieder, C. [Nordland Hospital, Bodoe (Norway). Dept. of Oncology and Palliative Medicine; Tromsoe Univ. (Norway). Inst. of Clinical Medicine; Grosu, A.L [Freiburg Univ. (Germany). Klinik fuer Strahlenheilkunde


    Purpose: The purpose of this work was to evaluate tumor control and side effects associated with fractionated stereotactic radiotherapy (FSRT) in the management of residual or recurrent pituitary adenomas. Patients and methods: We report on 37 consecutive patients with pituitary adenomas treated with FSRT at our department. All patients had previously undergone surgery. Twenty-nine patients had nonfunctioning, 8 had hormone-producing adenoma. The mean total dose delivered by a linear accelerator was 49.4 Gy (range 45-52.2 Gy), 5 x 1.8 Gy weekly. The mean PTV was 22.8 ccm (range 2.0-78.3 ccm). Evaluation included serial imaging tests, endocrinologic and ophthalmologic examination. Results: Tumor control was 91.9 % for a median follow-up time of 57 months (range 2-111 months). Before FSRT partial hypopituitarism was present in 41 % of patients, while 35 % had anterior panhypopituitarism. After FSRT pituitary function remained normal in 22 %, 43 % had partial pituitary dysfunction, and 35 % had anterior panhypopituitarism. Visual acuity was stable in 76 % of patients, improved in 19 %, and deteriorated in 5 %. Visual fields remained stable in 35 patients (95 %), improved in one and worsened in 1 patient (2.7 %). Conclusion: FSRT is an effective and safe treatment for recurrent or residual pituitary adenoma. Good local tumor control and preservation of adjacent structures can be reached, even for large tumors. (orig.)

  20. Hemorrhagic chondroid chordoma mimicking pituitary apoplexy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, H.J.; Kalnin, A.J.; Holodny, A.I. [Dept. of Radiology, University Hospital, Newark, NJ (United States); Schulder, M.; Grigorian, A. [Dept. of Neurosurgery, University Hospital, Newark, NJ (United States); Sharer, L.R. [Dept. of Pathology, University Hospital, Newark, NJ (United States)


    We describe a hemorrhagic chondroid chordoma involving the sella turcica with suprasellar extension. The CT and MRI appearances mimiked a hemorrhagic pituitary adenoma. Chondroid chordoma is a variant composed of elements of both chordoma and cartilaginous tissue. An uncommon bone neoplasm, located almost exclusively in the spheno-occipital region, it is usually not considered in the differential diagnosis of a tumor with acute hemorrhage in the sellar region. We discuss the clinical and radiological characteristics which may allow one to differentiate chondroid chordoma from other tumors of this area. (orig.) With 3 figs., 9 refs.

  1. Incidence of Pituitary Apoplexy and Its Risk Factors in Chinese People: A Database Study of Patients with Pituitary Adenoma (United States)

    Zhao, Xuelan; Jiang, Cuiping; Zhang, Qiongyue; Jiang, Wenjuan; Wang, Yan; Chen, Haixia; Shou, Xuefei; Zhao, Yao; Li, Yiming; Li, Shiqi; Ye, Hongying


    Background There are few studies of the incidence and clinical characteristics of pituitary apoplexy (PA) in pituitary adenoma patients, and the findings have been inconsistent. Objective The aim of the study was to retrospectively assess the incidence, clinical presentation, surgical management and postoperative complications of PA in pituitary adenoma patients. Methods A database was specifically designed to collect clinical, therapeutic, prognostic and histological information about pituitary adenoma patients. Using multivariate logistic regression, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to identify associated factors. Results A total of 2021 pituitary adenoma patients were recruited. 97 (4.8%) patients had PA. The incidence of PA was 10.11% in patients with pituitary macroadenoma, and 0.36% in patients with microadenoma. Variables for the logistic regression model independently associated with PA were sex (male vs. female, OR = 2.54, 95% CI: 1.59~4.07), tumor type (negative staining vs. positive staining, OR = 2.04, 95% CI: 1.29~3.23), and tumor size (macroadenoma vs. microadenoma, OR = 26.46, 95% CI = 9.66~72.46). Headache, visual deterioration, and vomiting were the most common symptoms in patients with pituitary adenoma. Patients with and without PA had similar frequency of visual deterioration, head trauma, acromegalic appearance, galactorrhoea, cold intolerance and Cushingoid appearance, but headache, vomiting, ptosis, diplopia, fever and blindness were significantly more common in patients with PA. Pearson Chi-Square tests revealed a significant difference in surgical approach between patients with and without PA (95.88% vs. 85.57%, P = 0.01). Conclusion Our findings suggest that PA is not a rare event. Male sex, non-functioning tumor, and macroadenoma are associated with an increased risk of PA. Compared with pituitary adenoma patients without PA, patients with PA have more severe symptoms. PMID:26407083

  2. The result of radiotherapy for pituitary adenoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, H. J.; Yang, K. M.; Suh, S. H. [Inje Univ., Seoul (Korea, Republic of). Coll. of Medicine; Cho, H. L.; Shon, S. C. [Pusan Paik Hospital, Pusan (Korea, Republic of)


    To evaluate the prognostic factors for disease-free survival and long-term results of radiotherapy for pituitary adenoma. The study involved a retrospective review of outcome in a series of 27 patients with pituitary adenoma, between 1984 and 1995 at Paik hospital. The study included 20 patients treated with surgery and postoperative radiotherapy and 7 with radiotherapy alone. The patients were followed for 12-146 months (median: 97 months). Seventeen were men and 10 were women. The numbers of functioning and non-functioning pituitary adenoma were 22 and 5 respectively and those of microadenoma and macroadenoma were 4 and 23 respectively. The radiation doses of 5040-5580cGy(median: 5040cGy) were delivered over 5-7 weeks, using 4MV LINAC. The prognostic factors were analyzed by log-rank test. For radiation therapy alone, the 5 YSR was 100% and progression free survival rate was 85.8%. The tumor was controlled in 6/7 (85.8%). For surgery and postoperative radiotherapy , the 5YSR, progression free survival rate and local control rate were 95%, 84.8%, and 89.5% respectively. The parameters of tumor size, hormone secretion, radiation dose, radiotherapy field size were evaluated in a uni- and multivariate analysis and all the factors were not statistically significant (P>0.05). Eleven of 12 (92%) with visual field defect experienced normalization or improvement, and 5 for 7 evaluable patients with hyperprolactinoma achieved normalization in 4 and decrement in 5 patients. Only 2 patients developed mild degree of panhypopituitarism. The radiotherapy appears to be effective in controlling clinical symptoms and signs resulting from pituitary adenoma. Local control rate with radiotherapy alone or with surgery and postoperative radiotherapy was comparable. There was a trend toward high recurrence rate in patients with nonfunctioning or prolactin secreting tumor and larger radiation field sizes. (author).

  3. Dendritic cell-based vaccines for the therapy of experimental tumors

    Czech Academy of Sciences Publication Activity Database

    Piasecka, E.P.; Indrová, Marie


    Roč. 2, č. 2 (2010), s. 257-268 ISSN 1750-743X R&D Projects: GA AV ČR IAA500520807; GA ČR GA301/09/1024; GA MZd NS10660 Grant - others:Polish Ministry of Science and Higher Education(PL) NN401235334 Institutional research plan: CEZ:AV0Z50520514 Keywords : dendritic cells * preparation of vaccine s * experimental tumors Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.542, year: 2010

  4. Transsphenoidal surgery using a high definition video telescope for pituitary adenomas in dogs with pituitary dependent hypercortisolism: methods and results. (United States)

    Mamelak, Adam N; Owen, Tina Jo; Bruyette, David


    To (1) establish a technique for transsphenoidal removal of pituitary adenomas in dogs with pituitary dependent hypercortisolism (PDH) using a high definition video telescope, and (2) report initial outcomes. Prospective case series. Dogs with pituitary dependent hypercortisolism (PDH; n = 26) with suprasellar masses. Pituitary tumors were removed using a modification of a transoral transsphenoidal approach. Surgery was observed using a high definition video telescope (VITOM™) and localization of the sella was performed by drilling pilot holes in the basisphenoid bone followed by computed tomography (CT). Dogs had PDH confirmed by urinary cortisol to creatinine ratio (UCCR) and endogenous ACTH assays, and tumors confirmed by MRI. There were no postoperative cerebrospinal fluid leaks, wound dehiscence, or surgical site infections. Overall postoperative mortality was 19% with no mortality observed in the last 16 dogs, indicating an initial "learning curve" followed by good surgical results. All dogs that survived the immediate postoperative period (1 week) returned to their owners in good health, on hormonal replacement therapy. Follow-up ranged from 3 to 36 months. Sustained tumor control and hormonal remission based on normalized ACTH and UCCR measurements were observed in 20/21 (95%) dogs at 1-year follow-up. Modifications of a trans-oral transsphenoidal technique for surgical removal of pituitary tumors provides a safe and effective strategy for long-term remission of PDH with acceptable morbidity and mortality. © Copyright 2014 by The American College of Veterinary Surgeons.

  5. Hypersecretion of ACTH and PRL from pituitary adenoma in MEN1, adequately managed by medical therapy

    Directory of Open Access Journals (Sweden)

    Shinsuke Uraki


    Full Text Available A 54-year-old man had gastrinoma, parathyroid hyperplasia and pituitary tumor. His family history indicated that he might have multiple endocrine neoplasia type 1 (MEN1. MEN1 gene analysis revealed a heterozygous germline mutation (Gly156Arg. Therefore, we diagnosed him with MEN1. Endocrinological tests revealed that his serum prolactin (PRL and plasma adrenocorticotropic hormone (ACTH levels were elevated to 1699 ng/mL and 125 pg/mL respectively. Immunohistochemical analysis of the resected pancreatic tumors revealed that the tumors did not express ACTH. Overnight 0.5 and 8 mg dexamethasone suppression tests indicated that his pituitary tumor was a PRL-ACTH-producing plurihormonal tumor. Before transsphenoidal surgery, cabergoline was initiated. Despite no decrease in the volume of the pituitary tumor, PRL and ACTH levels decreased to 37.8 ng/mL and 57.6 pg/mL respectively. Owing to the emergence of metastatic gastrinoma in the liver, octreotide was initiated. After that, PRL and ACTH levels further decreased to 5.1 ng/mL and 19.7 pg/mL respectively. He died from liver dysfunction, and an autopsy of the pituitary tumor was performed. In the autopsy study, histopathological and immunohistochemical (IHC analysis showed that the tumor was single adenoma and the cells were positive for ACTH, growth hormone (GH, luteinizing hormone (LH and PRL. RT-PCR analysis showed that the tumor expressed mRNA encoding all anterior pituitary hormones, pituitary transcription factor excluding estrogen receptor (ER β, somatostatin receptor (SSTR 2, SSTR5 and dopamine receptor D (D2R. PRL-ACTH-producing tumor is a very rare type of pituitary tumor, and treatment with cabergoline and octreotide may be useful for controlling hormone levels secreted from a plurihormonal pituitary adenoma, as seen in this case of MEN1.

  6. 5′-AMP-activated Protein Kinase (AMPK) Supports the Growth of Aggressive Experimental Human Breast Cancer Tumors* (United States)

    Laderoute, Keith R.; Calaoagan, Joy M.; Chao, Wan-ru; Dinh, Dominc; Denko, Nicholas; Duellman, Sarah; Kalra, Jessica; Liu, Xiaohe; Papandreou, Ioanna; Sambucetti, Lidia; Boros, Laszlo G.


    Rapid tumor growth can establish metabolically stressed microenvironments that activate 5′-AMP-activated protein kinase (AMPK), a ubiquitous regulator of ATP homeostasis. Previously, we investigated the importance of AMPK for the growth of experimental tumors prepared from HRAS-transformed mouse embryo fibroblasts and for primary brain tumor development in a rat model of neurocarcinogenesis. Here, we used triple-negative human breast cancer cells in which AMPK activity had been knocked down to investigate the contribution of AMPK to experimental tumor growth and core glucose metabolism. We found that AMPK supports the growth of fast-growing orthotopic tumors prepared from MDA-MB-231 and DU4475 breast cancer cells but had no effect on the proliferation or survival of these cells in culture. We used in vitro and in vivo metabolic profiling with [13C]glucose tracers to investigate the contribution of AMPK to core glucose metabolism in MDA-MB-231 cells, which have a Warburg metabolic phenotype; these experiments indicated that AMPK supports tumor glucose metabolism in part through positive regulation of glycolysis and the nonoxidative pentose phosphate cycle. We also found that AMPK activity in the MDA-MB-231 tumors could systemically perturb glucose homeostasis in sensitive normal tissues (liver and pancreas). Overall, our findings suggest that the contribution of AMPK to the growth of aggressive experimental tumors has a critical microenvironmental component that involves specific regulation of core glucose metabolism. PMID:24993821

  7. 5'-AMP-activated protein kinase (AMPK) supports the growth of aggressive experimental human breast cancer tumors. (United States)

    Laderoute, Keith R; Calaoagan, Joy M; Chao, Wan-ru; Dinh, Dominc; Denko, Nicholas; Duellman, Sarah; Kalra, Jessica; Liu, Xiaohe; Papandreou, Ioanna; Sambucetti, Lidia; Boros, Laszlo G


    Rapid tumor growth can establish metabolically stressed microenvironments that activate 5'-AMP-activated protein kinase (AMPK), a ubiquitous regulator of ATP homeostasis. Previously, we investigated the importance of AMPK for the growth of experimental tumors prepared from HRAS-transformed mouse embryo fibroblasts and for primary brain tumor development in a rat model of neurocarcinogenesis. Here, we used triple-negative human breast cancer cells in which AMPK activity had been knocked down to investigate the contribution of AMPK to experimental tumor growth and core glucose metabolism. We found that AMPK supports the growth of fast-growing orthotopic tumors prepared from MDA-MB-231 and DU4475 breast cancer cells but had no effect on the proliferation or survival of these cells in culture. We used in vitro and in vivo metabolic profiling with [(13)C]glucose tracers to investigate the contribution of AMPK to core glucose metabolism in MDA-MB-231 cells, which have a Warburg metabolic phenotype; these experiments indicated that AMPK supports tumor glucose metabolism in part through positive regulation of glycolysis and the nonoxidative pentose phosphate cycle. We also found that AMPK activity in the MDA-MB-231 tumors could systemically perturb glucose homeostasis in sensitive normal tissues (liver and pancreas). Overall, our findings suggest that the contribution of AMPK to the growth of aggressive experimental tumors has a critical microenvironmental component that involves specific regulation of core glucose metabolism. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Silent corticotropic adenoma of pituitary gland--a case report. (United States)

    Lee, S P; Lin, H D; Wang, G G; Ho, D M; Lee, L S; Ching, K N; Chiang, B N


    A 79-year-old man complained progressive visual impairment and Diplopia for 2 weeks. A big pituitary tumor was found and partially removed by the surgeon eventually. The tumor cells were chromophobic with H&E stain and exhibited focal positive staining with PAS. Immunoperoxidase method demonstrated moderate positivity for adrenocorticotrophic hormone (ACTH), while staining for growth hormone (G.H) and prolactin were negative. The patient was eucorticoid clinically and biochemically. Since silent corticotropic adenoma of the human pituitary gland is rarely encountered clinically, a review of the literature is included in this article.

  9. Mortality in patients treated for Cushing's disease is increased, compared with patients treated for nonfunctioning pituitary macroadenoma

    NARCIS (Netherlands)

    Dekkers, O. M.; Biermasz, N. R.; Pereira, A. M.; Roelfsema, F.; van Aken, M. O.; Voormolen, J. H. C.; Romijn, J. A.


    Increased mortality in patients with pituitary tumors after surgical treatment has been reported. However, it is unknown to what extent excess mortality is caused by pituitary tumors and their treatment in general and to what extent by previous exposure to hormonal overproduction. The aim of the

  10. Random walk and graph cut based active contour model for three-dimension interactive pituitary adenoma segmentation from MR images (United States)

    Sun, Min; Chen, Xinjian; Zhang, Zhiqiang; Ma, Chiyuan


    Accurate volume measurements of pituitary adenoma are important to the diagnosis and treatment for this kind of sellar tumor. The pituitary adenomas have different pathological representations and various shapes. Particularly, in the case of infiltrating to surrounding soft tissues, they present similar intensities and indistinct boundary in T1-weighted (T1W) magnetic resonance (MR) images. Then the extraction of pituitary adenoma from MR images is still a challenging task. In this paper, we propose an interactive method to segment the pituitary adenoma from brain MR data, by combining graph cuts based active contour model (GCACM) and random walk algorithm. By using the GCACM method, the segmentation task is formulated as an energy minimization problem by a hybrid active contour model (ACM), and then the problem is solved by the graph cuts method. The region-based term in the hybrid ACM considers the local image intensities as described by Gaussian distributions with different means and variances, expressed as maximum a posteriori probability (MAP). Random walk is utilized as an initialization tool to provide initialized surface for GCACM. The proposed method is evaluated on the three-dimensional (3-D) T1W MR data of 23 patients and compared with the standard graph cuts method, the random walk method, the hybrid ACM method, a GCACM method which considers global mean intensity in region forces, and a competitive region-growing based GrowCut method planted in 3D Slicer. Based on the experimental results, the proposed method is superior to those methods.

  11. Tumor hypoxia - A confounding or exploitable factor in interstitial brachytherapy? Effects of tissue trauma in an experimental rat tumor model

    NARCIS (Netherlands)

    van den Berg, AP; van Geel, CAJF; van Hooije, CMC; van der Kleij, AJ; Visser, AG


    Purpose: To evaluate the potential effects of tumor hypoxia induced by afterloading catheter implantation on the effectiveness of brachytherapy in a rat tumor model. Methods and Materials: Afterloading catheters (4) Here implanted in subcutaneously growing R1M rhabdomyosarcoma in female Wag/Rij

  12. Gigantism caused by growth hormone secreting pituitary adenoma

    Directory of Open Access Journals (Sweden)

    Noorisaem Rhee


    Full Text Available Gigantism indicates excessive secretion of growth hormones (GH during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL. Magnetic resonance imaging (MRI of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL. Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings.

  13. Tumor (United States)

    ... peanut plants (aflatoxins) Excessive sunlight exposure Genetic problems Obesity Radiation exposure Viruses Types of tumors known to be caused by or linked with viruses are: Cervical cancer (human papillomavirus) Most anal cancers (human papillomavirus) Some ...

  14. Mixed Pituitary Gangliocytoma and Prolactinoma Resistant to the Cabergoline Treatment. (United States)

    Yano, Shigetoshi; Hide, Takuichiro; Uekawa, Ken; Honda, Yumi; Mikami, Yoshiki; Kuratsu, Jun-Ichi


    A gangliocytoma rarely coexists with a pituitary adenoma in a sellar lesion. Herein, we describe our experience in treating a mixed gangliocytoma and prolactinoma of the pituitary gland. A 16-year-old male presented with severe headache and vomiting. Magnetic resonance imaging showed a large pituitary tumor with hydrocephalus. Because of the increased levels of serum prolactin (PRL), we treated the patient with cabergoline, which decreased the tumor size and improved the hydrocephalus. Six months after the treatment, the tumor began to increase in size, despite the normalization of the PRL level with cabergoline treatment. An endoscopic transsphenoidal resection was performed and the tumor was mostly removed. Microscopic examination of the resected tumor showed a mixture of prototypical pituitary adenoma cells and the proliferation of mature ganglion cells. Immunohistochemistry showed that the ganglion cells were positively stained for synaptophysin, NeuN, and PRL as shown in the adenomatous component. A few cells were immunostained with both PRL and NeuN, and a few cells were immunopositive for nestin, but not PRL or synaptophysin. Our findings showed the existence of cells that are phenotypically intermediate between ganglion cells and adenoma cells, and the existence of stem cell-like cells, which support the hypothesis that adenoma cells can transform into ganglion cells or that both ganglion and adenoma cells derive from common stem cells. Furthermore, the ganglion cells seemed to grow rapidly and independently of dopamine, which is in contrast to prototypical prolactinoma cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Epigenetic mechanisms leading to overexpression of HMGA proteins in human pituitary adenomas

    Directory of Open Access Journals (Sweden)

    Daniela eD'Angelo


    Full Text Available Overexpression of the HMGA1 and HMGA2 proteins is a feature of all human pituitary adenoma subtypes. However, amplification and/or rearrangement of the HMGA2 have been described in human prolactinomas, but rarely in other pituitary subtypes, and no genomic amplification of HMGA1 was detected in pituitary adenomas. Here, we summarize the functional role of HMGA proteins in pituitary tumorigenesis and the epigenetic mechanisms contributing to HMGA overexpression in these tumors focusing on recent studies indicating a critical role of non coding RNAs in modulating HMGA protein levels.

  16. Pituitary insufficiency as a side effect after radiosurgery for pituitary adenomas: the role of the hypothalamus. (United States)

    Feigl, Guenther Christian; Pistracher, Karin; Berghold, Andrea; Mokry, Michael


    Causes of pituitary insufficiencies as a side effect of Gamma Knife surgery (GKS) following irradiation of the hypothalamopituitary axis are still under debate. In an investigation of pituitary insufficiencies after GKS, the authors' main focus is on what role can be attributed to the hypothalamus with regard to endocrinological changes in hypothalamopituitary function following GKS. A total of 108 patients consecutively treated between April 1992 and July 2003 were included in this retrospective study. All patients had undergone either transsphenoidal or transcranial surgery prior to GKS. The spot dosimetry method was used to determine doses delivered to structures of the hypothalamopituitary axis. For statistical analyses, endocrine insufficiency and deterioration in pituitary function were defined as a decrease in hormonal blood levels below the normal range for 1 or more anterior pituitary lobe hormones. Additionally, an analysis of the rate of patients requiring hormone replacement therapy after GKS due to new endocrinopathies was performed. Complete patient records of 61 male and 47 female patients with a mean age of 51.9 years (range 9.1–81.2 years) were available for our investigation. The overall tumor control rate was 97% and the endocrinological cure rate was 61.2%. Mean treatment doses in patients with and without new endocrine insufficiencies (shown as with/without insufficiencies and followed by probability values) were as follows: 1.3/0.8 Gy to the hypothalamus(p = 0.2); 2.2/1.6 Gy to the median eminence (p = 0.1); 6.5/4.1 Gy to the pituitary stalk (p = 0.004); and 12.4/9.5Gy to the pituitary gland (p = 0.05). The median overall duration of follow-up after GKS was 6.7 years, with 84 patients(77.7%) whose follow-up was longer than 12 months. The median follow-up time after GKS in patients who developed a new pituitary dysfunction was 79.5 months (6.6 years, SD 3.8 years), and the median follow-up time inpatients with no new insufficiencies was 78

  17. Atypical lung carcinoid metastasis to the pituitary gland

    Directory of Open Access Journals (Sweden)

    Xiao-ling YAN


    Full Text Available Objective To study clinicopathological features, diagnosis and differential diagnosis of atypical lung carcinoid metastasis to the pituitary gland based on clinical data of one patient. Methods and Results A 81-year-old female presented headache and sudden blindness, and head MRI showed that there was a lesion at the saddle area. The tumor was detected at intrasellar and in grayish red during surgery. The diameter of tumor was 2 cm. The tumor was soft with no envelop at and well-defined margins, and insufficiency in blood supply. The tumor was removed completely along its edge. Under optical microscopy, the tumor was consisted of small round cells of the same size. Tumor cells were distributed around blood vessels in a nest manner or diffuse manner with brisk mitotic activity and focal necrosis. By using immunohistochemical staining, the tumor cells were diffusely positive for synaptophysin (Syn, CD56 and thyoid transcription factor - 1 (TTF - 1, focal positive for cytokeratin (CK and P53, and negative for growth hormone (GH, prolactin (PRL, adrenocorticotropic hormone (ACTH, follicle stimulating hormone (FSH, thyroid stimulating hormone (TSH, luteinizing hormone (LH, S-100 protein (S-100, thyroglobulin (TG and calcitonin. Ki?67 labeling index was about 33%. Conclusions Pituitary metastasis is a rare tumor, and only a few cases of atypical lung carcinoid metastasis to the pituitary gland have been reported. Definite diagnosis could be made by history, typical histopathological characteristics and immunohistochemical expressions. DOI: 10.3969/j.issn.1672-6731.2017.09.010

  18. Action of hexachlorobenzene on tumor growth and metastasis in different experimental models

    Energy Technology Data Exchange (ETDEWEB)

    Pontillo, Carolina Andrea, E-mail: [Laboratorio de Efectos Biológicos de Contaminantes Ambientales, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires (Argentina); Rojas, Paola, E-mail: [Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires (Argentina); Chiappini, Florencia, E-mail: [Laboratorio de Efectos Biológicos de Contaminantes Ambientales, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires (Argentina); Sequeira, Gonzalo, E-mail: [Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires (Argentina); Cocca, Claudia, E-mail: [Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires (Argentina); Crocci, Máximo, E-mail: [Instituto de Inmunooncología Crescenti, Buenos Aires (Argentina); Colombo, Lucas, E-mail: [Instituto de Oncología Angel Roffo, Universidad de Buenos Aires, Buenos Aires,Argentina (Argentina); Lanari, Claudia, E-mail: [Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires (Argentina); and others


    Hexachlorobenzene (HCB) is a widespread organochlorine pesticide, considered a possible human carcinogen. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). We have found that HCB activates c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways and cell migration, in an AhR-dependent manner in MDA-MB-231 breast cancer cells. The aim of this study was to investigate in vitro the effect of HCB (0.005, 0.05, 0.5, 5 μM) on cell invasion and metalloproteases (MMPs) 2 and 9 activation in MDA-MB-231 cells. Furthermore, we examined in vivo the effect of HCB (0.3, 3, 30 mg/kg b.w.) on tumor growth, MMP2 and MMP9 expression, and metastasis using MDA-MB-231 xenografts and two syngeneic mouse breast cancer models (spontaneous metastasis using C4-HI and lung experimental metastasis using LM3). Our results show that HCB (5 μM) enhances MMP2 expression, as well as cell invasion, through AhR, c-Src/HER1 pathway and MMPs. Moreover, HCB increases MMP9 expression, secretion and activity through a HER1 and AhR-dependent mechanism, in MDA-MB-231 cells. HCB (0.3 and 3 mg/kg b.w.) enhances subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. In vivo, using MDA-MB-231 model, the pesticide (0.3, 3 and 30 mg/kg b.w.) activated c-Src, HER1, STAT5b, and ERK1/2 signaling pathways and increased MMP2 and MMP9 protein levels. Furthermore, we observed that HCB stimulated lung metastasis regardless the tumor hormone-receptor status. Our findings suggest that HCB may be a risk factor for human breast cancer progression. - Highlights: ► HCB enhances MMP2 and MMP9 expression and cell invasion in MDA-MB-231, in vitro. ► HCB-effects are mediated through AhR, HER1 and/or c-Src. ► HCB increases subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. ► HCB activates c-Src/HER1 pathway and increases MMPs levels in MDA-MB-231 tumors. ► HCB stimulates lung metastasis in C4-HI and LM3 in vivo models.


    NARCIS (Netherlands)



    The applicability of five different rodent tumors for experimental PET has been investigated. L-[1-C-11]Tyrosine was a better indicator for the growth activity of the tumors than [F-18]FDG. For experimental PET, the three mice models studied appeared inappropriate; the Lewis lung tumor and the

  20. Non-pituitary origin sellar tumours mimicking pituitary macroadenomas

    Energy Technology Data Exchange (ETDEWEB)

    Abele, T.A., E-mail: [University of Texas Southwestern Medical Center at Dallas, Dallas, TX (United States); Yetkin, Z.F.; Raisanen, J.M.; Mickey, B.E.; Mendelsohn, D.B. [University of Texas Southwestern Medical Center at Dallas, Dallas, TX (United States)


    Although the large majority of sellar tumours are pituitary adenomas, several other pituitary and non-pituitary origin tumours arise in the sellar and parasellar regions. Given their location, non-adenomatous lesions frequently mimic pituitary macroadenomas and can pose a diagnostic challenge for the radiologist. Distinguishing rare sellar lesions from the common macroadenoma helps to direct the correct surgical approach and reduce the risk of incomplete resection and/or complications such as cerebrospinal fluid leak with the potential for meningitis. The purpose of this article is to review the imaging features of non-pituitary-origin sellar tumours, focusing on characteristics that may distinguish them from pituitary macroadenomas. Lesions include meningioma, metastatic disease, epidermoid cyst, germinoma, chondrosarcoma, giant cell tumour, and giant aneurysm.

  1. Acromegaly with no pituitary adenoma and no evidence of ectopic source

    Directory of Open Access Journals (Sweden)

    Deepak Khandelwal


    Full Text Available 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.

  2. Identification of Differentially Expressed Genes in Pituitary Adenomas by Integrating Analysis of Microarray Data

    Directory of Open Access Journals (Sweden)

    Peng Zhao


    Full Text Available Pituitary adenomas, monoclonal in origin, are the most common intracranial neoplasms. Altered gene expression as well as somatic mutations is detected frequently in pituitary adenomas. The purpose of this study was to detect differentially expressed genes (DEGs and biological processes during tumor formation of pituitary adenomas. We performed an integrated analysis of publicly available GEO datasets of pituitary adenomas to identify DEGs between pituitary adenomas and normal control (NC tissues. Gene function analysis including Gene Ontology (GO, Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enrichment analysis, and protein-protein interaction (PPI networks analysis was conducted to interpret the biological role of those DEGs. In this study we detected 3994 DEGs (2043 upregulated and 1951 downregulated in pituitary adenoma through an integrated analysis of 5 different microarray datasets. Gene function analysis revealed that the functions of those DEGs were highly correlated with the development of pituitary adenoma. This integrated analysis of microarray data identified some genes and pathways associated with pituitary adenoma, which may help to understand the pathology underlying pituitary adenoma and contribute to the successful identification of therapeutic targets for pituitary adenoma.

  3. Optimization of chitosan nanoparticles for colon tumors using experimental design methodology. (United States)

    Jain, Anekant; Jain, Sanjay K


    Purpose Colon-specific drug delivery systems (CDDS) can improve the bio-availability of drugs through the oral route. A novel formulation for oral administration using ligand coupled chitosan nanoparticles bearing 5-Flurouracil (5FU) encapsulated in enteric coated pellets has been investigated for CDDS. Method The effect of polymer concentration, drug concentration, stirring time and stirring speed on the encapsulation efficiency, and size of nanoparticles were evaluated. The best (or optimum) formulation was obtained by response surface methodology. Using the experimental data, analysis of variance has been carried out to evolve linear empirical models. Using a new methodology, polynomial models have been evolved and the parametric analysis has been carried out. In order to target nanoparticles to the hyaluronic acid (HA) receptors present on colon tumors, HA coupled nanoparticles were tested for their efficacy in vivo. The HA coupled nanoparticles were encapsulated in pellets and were enteric coated to release the drug in the colon. Results Drug release studies under conditions of mimicking stomach to colon transit have shown that the drug was protected from being released in the physiological environment of the stomach and small intestine. The relatively high local drug concentration with prolonged exposure time provides a potential to enhance anti-tumor efficacy with low systemic toxicity for the treatment of colon cancer. Conclusions Conclusively, HA coupled nanoparticles can be considered as the potential candidate for targeted drug delivery and are anticipated to be promising in the treatment of colorectal cancer.

  4. Antioxidant oils and Salmonella enterica Typhimurium reduce tumor in an experimental model of hepatic metastasis

    Directory of Open Access Journals (Sweden)

    Sorenson BS


    Full Text Available Brent S Sorenson, Kaysie L Banton, Lance B Augustin, Arnold S Leonard, Daniel A SaltzmanDepartment of Surgery, University of Minnesota Medical School, Minneapolis, MN, USAAbstract: Fruit seeds high in antioxidants have been shown to have anticancer properties and enhance host protection against microbial infection. Recently we showed that a single oral dose of Salmonella enterica serovar Typhimurium expressing a truncated human interleukin-2 gene (SalpIL2 is avirulent, immunogenic, and reduces hepatic metastases through increased natural killer cell populations in mice. To determine whether antioxidant compounds enhance the antitumor effect seen in SalpIL2-treated animals, we assayed black cumin (BC, black raspberry (BR, and milk thistle (MT seed oils for the ability to reduce experimental hepatic metastases in mice. In animals without tumor, BC and BR oil diets altered the kinetics of the splenic lymphocyte response to SalpIL2. Consistent with previous reports, BR and BC seed oils demonstrated independent antitumor properties and moderate adjuvant potential with SalpIL2. MT oil, however, inhibited the efficacy of SalpIL2 in our model. Based on these data, we conclude that a diet high in antioxidant oils promoted a more robust immune response to SalpIL2, thus enhancing its antitumor efficacy.Keywords: antioxidants, colorectal cancer, tumor models, metastasis

  5. [Technical aspects and surgical strategy for removal of corticotroph pituitary adenoma]. (United States)

    Perrin, G; Stevenaert, A; Jouanneau, E


    The development of transsphenoidal microsurgery and the refinement of endocrinological and radiological diagnostic procedures have afforded therapeutic options appropriate for each individual case in patients with pituitary-dependent hypercortisolism. Compared with other secreting pituitary tumors, the corticotroph adenoma seems to be the most biologically active tumor. Clinical evidence of hypercortisolism mainly occurs at an early stage of tumor growth when the tumor is very small, below the detection threshold of modern imaging techniques. While the treatment of large tumors remains difficult due to the non-discrete boundary lines of the tumor and extension or invasion, surgical removal of very tiny tumors requires reliable preoperative or peroperative identification in order to achieve total tumor resection for clinical remission and pituitary preservation to prevent hypopituitarism. We reviewed all the current surgical techniques or clever surgical procedures used to achieve both goals with the lowest complication rate. We report here the state-of-the-art of surgical management of corticotroph pituitary adenoma focusing on preoperative radiological and biological data required for performing guided intrasellar surgical exploration and reliable tumor identification. Different technical aspects of the nasosphenoidal approaches are reported as well as the modified transdiaphragmatic or transtubercular transcisternal approaches to tumors in a suprasellar localization or lying along the pituitary stalk. The advantages of minimally invasive surgical techniques such as intrasellar endoscopic surgery are discussed. Adapted surgical techniques for second transnasal surgery indicated for recurrent tumors are described. Guidelines are given for peroperative tumor identification with macroscopic assessment or histological control with frozen section biopsies. Different techniques for tumor removal are discussed from selective microadenomectomy to enlarged pituitary

  6. Geometric survey on magnetic resonance imaging of growth hormone producing pituitary adenoma. (United States)

    Bakhtiar, Yuriz; Hanaya, Ryosuke; Tokimura, Hiroshi; Hirano, Hirofumi; Oyoshi, Tatsuki; Fujio, Shingo; Bohara, Manoj; Arita, Kazunori


    Apart from the radiologic features regarding size and invasiveness, we had noticed some differences in morphology among types of pituitary adenomas. We conducted this study to verify the differences in radiologic morphology between growth hormone producing pituitary adenomas (GHoma) and nonfunctioning pituitary adenomas (NFoma). Pre-surgical magnetic resonance images (MRIs) were assessed in 50 cases of GHoma and 50 cases of NFoma. Geometric parameters on MRI were set in accordance with sellar anatomy. Intensity of T1-weighted image was not different between the two groups, but hypo-intensity of T2-weighted image was more frequently seen in GHoma. Predominant inferior extension of tumor was seen mostly in GHoma (88 vs. 38%). Extension of the tumor to the superior compartment of cavernous sinus was more frequent in NFoma. Pituitary gland was generally located superior to GHoma and postero-superior to NFoma. Growth characteristics of pituitary adenoma were confirmed to differ between GHoma and NFoma.

  7. What Are the Symptoms of Pituitary Tumors? (United States)

    ... NICHD Research Information Find a Study More Information Pharmacology Condition Information NICHD Research Information Find a Study ... National Center for Medical Rehabilitation Research (NCMRR) Center History Funding Opportunity Announcements (FOAs) for NCMRR Partners Training & ...

  8. An acute adrenal insufficiency revealing pituitary metastases of lung ...

    African Journals Online (AJOL)

    The chest X Rays revealed pulmonary opacity. Computed tomography scan of the chest showed a multiples tumors with mediastinal lymphadenopathy. Bronchoscopy and biopsy demonstrated a pulmonary adenocarcinoma. Hence we concluded to a lung cancer with multiple pituitary and adrenal gland metastases.

  9. Progress in the Diagnosis and Classification of Pituitary Adenomas (United States)

    Syro, Luis V.; Rotondo, Fabio; Ramirez, Alex; Di Ieva, Antonio; Sav, Murat Aydin; Restrepo, Lina M.; Serna, Carlos A.; Kovacs, Kalman


    Pituitary adenomas are common neoplasms. Their classification is based upon size, invasion of adjacent structures, sporadic or familial cases, biochemical activity, clinical manifestations, morphological characteristics, response to treatment and recurrence. Although they are considered benign tumors, some of them are difficult to treat due to their tendency to recur despite standardized treatment. Functional tumors present other challenges for normalizing their biochemical activity. Novel approaches for early diagnosis, as well as different perspectives on classification, may help to identify subgroups of patients with similar characteristics, creating opportunities to match each patient with the best personalized treatment option. In this paper, we present the progress in the diagnosis and classification of different subgroups of patients with pituitary tumors that may be managed with specific considerations according to their tumor subtype. PMID:26124750

  10. 'Ectopic' suprasellar type IIa PRL-secreting pituitary adenoma. (United States)

    Zhou, Heng-Jun; Pan, De-Sheng; Ba, Xiao-Qun; Zhan, Ren-Ya; Zheng, Xiu-Jue; Ma, Yue-Hui


    Ectopic pituitary adenomas (EPAs) are rare, and the suprasellar cistern seems to be the most common location. At this time, no detailed original classification, diagnosis, or treatment protocols for suprasellar pituitary adenomas (SPAs) have been described. A 19-year-old man showed visual disturbances and lack of libido for 3 years, he suffered a sharp decline in vision with only light perception in the last week. Magnetic resonance imaging scans revealed a large suprasellar cystic lesion with a normal pituitary in the sella turcica. Endocrinological findings showed an extremely high prolactin level of 1250 ng/mL. Because of the sharp decline in vision, the patient underwent total removal of the suprasellar lesion using a transfrontal interhemispheric approach. The tumor pedicle originated in the lower pituitary stalk without any connection to the anterior pituitary gland in the sella turcica, while the diaphragma sellae was incomplete. Clinical and endocrinological cure criteria were fulfilled and postoperative pathology confirmed a prolactin-secreting pituitary adenoma. Ectopic suprasellar pituitary adenomas (ESPAs) are extremely rare intracranial extracerebral tumors. SPAs can be classified into three types according to their origin and their relationship with surrounding tissue. Only type III is theoretically a true ectopic, based on previous reports. Thus, ESPAs are uncommon compared to other EPAs. Our case is the first reported case of a type IIa 'E'SPA and the first description of this subtype classification until now. The pars tuberalis may be different from the pars distalis, and each subtype of adenohypophyseal cells may have different migration characteristics, which leads to different proportions of each hormone-secreting subtype in SPAs and EPAs. Transsphenoidal surgery is minimally invasive, but transcranial surgery may remain a universal option for the treatment of suprasellar lesions.

  11. Chronic cluster headache and the pituitary gland. (United States)

    De Pue, Annelien; Lutin, Bart; Paemeleire, Koen


    Cluster headache is classified as a primary headache by definition not caused by an underlying pathology. However, symptomatic cases of otherwise typical cluster headache have been reported. A 47-year-old male suffered from primary chronic cluster headache (CCH, ICHD-3 beta criteria fulfilled) since the age of 35 years. A magnetic resonance imaging (MRI) study of the brain in 2006 came back normal. He tried several prophylactic treatments but was never longer than 1 month without attacks. He was under chronic treatment with verapamil with only a limited effect on the attack frequency. Subcutaneous sumatriptan 6 mg injections were very effective in aborting attacks. By February 2014 the patient developed a continuous interictal pain ipsilateral to the right-sided cluster headache attacks. An indomethacin test (up to 225 mg/day orally) was negative. Because of the change in headache pattern we performed a new brain MRI, which showed a cystic structure in the pituitary gland. The differential diagnosis was between a Rathke cleft cyst and a cystic adenoma. Pituitary function tests showed an elevated serum prolactin level. A dopamine agonist (cabergoline) was started and the headache subsided completely. Potential pathophysiological mechanisms of pituitary tumor-associated headache are discussed. Neuroimaging should be considered in all patients with CCH, especially those with an atypical presentation or evolution. Response to acute treatment does not exclude a secondary form of cluster headache. There may be shared pathophysiological mechanisms of primary and secondary cluster headache.

  12. Advances in trans-sphenoidal pituitary surgery. (United States)

    Solari, D; Cavallo, L M; De Angelis, M; Villa, A; Somma, T; Esposito, F; Del Basso De Caro, M; Cappabianca, P


    Pituitary surgery is a continuous evolving speciality of the neurosurgeons' armamentarium, requiring precise anatomical knowledge, technical skills and integrated appreciation of the pituitary pathophysiology. Actually, it could be considered the result of a close cooperation between different specialists, i.e. the ophthalmologist, the neuroradiologist, the endocrinologist, the neurosurgeon, the pathologist, etc. In this teamwork environment each member plays his own role, offering his contribute to the final result; every effort is performed to provide patients with the best possible procedure, individually measured. The endoscopic pituitary surgery performed by means of a transsphenoidal approach perfectly fits this scenario, being though advocated as the result of an evolutionary process rather than a revolutionary one. The "pure" endoscopic transsphenoidal surgery - consisting of a whole procedure performed with the endoscope alone and without the use of any transsphenoidal retractor - offers some advantages due to the endoscope itself: a superior close-up view of the relevant anatomy, very important at the tumor/gland interface and an enlarged working angle are provided with an increased panoramic vision inside the surgical area. Results in terms of mass removal, relief of clinical symptoms, cure of the underlying disease and complication rate are similar to those reported in the major microsurgical series but patient compliance is by far better.

  13. Immunohistochemical detection of PPARγ receptors in the human pituitary adenomas: correlation with PCNA

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    Marek Pawlikowski


    Full Text Available The occurrence of peroxisome proliferator-activated receptors gamma (PPARγ was investigated in 51 human pituitary adenomas and in 6 non-tumoral human pituitary tissue samples. Moreover, the correlation between PPARγ and the proliferating cells nuclear antigen (PCNA - immunocytochemical proliferation marker was evaluated. The receptors and PCNA were detected by immunohistochemical methods using the polyclonal anti-PPARγ and the monoclonal anti-PCNA antibodies, respectively. PPARγ were found in all examined tissues. The mean percentage of cells with positive nuclear reaction was 3-fold higher in pituitary adenomas in comparison with non-tumoral pituitary tissues. The strongest expression of PPARγ was observed in somatotropinomas. Besides the nuclear reaction, which is typical for PPARγ, positive immunostaining was also observed in the cytoplasm. It was clearly stronger in pituitary adenomas than in non-tumoral pituitary tissues. A slight, statistically insignificant tendency towards negative correlation between PPARγ and PCNA was found in somatotropinomas, prolactinomas, corticotropinomas and gonadotropinomas. On the other hand, in null cell adenomas and "silent" corticotropinomas, a strong positve correlation between the expression of PPARγ and PCNA was observed. The strong expression of PPARγ in human pituitary adenomas and its possible involvement in control of cell proliferation in these tumors give a good reason for the attempts of their treatment with PPARγ ligands.

  14. Pituitary size alteration and adverse effects of radiation therapy performed in 9 dogs with pituitary-dependent hypercortisolism. (United States)

    Sawada, Harumi; Mori, Akihiro; Lee, Peter; Sugihara, Shiho; Oda, Hitomi; Sako, Toshinori


    The purpose of this study was to determine the therapeutic and/or adverse effects of radiation therapy (RT) against pituitary tumors in dogs with pituitary-dependent hypercortisolism, as monitored by frequent post-RT detailed MRI examinations, clinical signs, and changes in hormone concentrations. Nine dogs with an adrenocorticotropic hormone (ACTH)-secreting pituitary mass diagnosed by magnetic resonance imaging (MRI) underwent RT for 4weeks (total of 48Gy in 4-Gy fractions). Pituitary height/brain area (P/B) value, clinical signs, basal plasma ACTH concentrations, serum cortisol concentrations (pre- and post-ACTH stimulation test) and adverse effects of RT were evaluated before and post-RT. The P/B value was significantly lower in all nine dogs post-RT. One dog lacking any neurological signs demonstrated no change in clinical signs pre and post-RT. Out of 8 dogs which exhibited neurological signs pre-RT, half of them demonstrated complete resolution of their signs, whereas the other half showed transient resolution. In all animals with recurrence of neurological signs, pituitary tumor regrowth was not observed; however, MRI revealed moderate to severe pituitary hemorrhage. Late adverse effect (bilateral otitis media) was observed in three of nine dogs post-RT. RT did not induce any significant changes in the dogs' basal plasma ACTH concentration and pre- and post-ACTH serum cortisol concentrations. In conclusion, RT is effective to reduce pituitary size and the mass effect, but does not appear to affect blood hormone concentrations, necessitating additional medical treatment against hypercortisolism. Periodic MRI imaging post-RT enables early detection of adverse effects of RT. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Microspheres labelled with short-lived isotopes: Development and application for tumors treatment (Experimental study)

    Energy Technology Data Exchange (ETDEWEB)

    Drozdovsky, B.Y.; Rosiev, R.A.; Goncharova, A.Y.; Skvortsov, V.G.; Petriev, V.M.; Grigoriev, A.N.; Schischkanov, N.G. [Medical Radiological Research Centre RAMS, Kaluga Region, (Russian Federation)


    Analysis of the conducted studies strongly suggests the possibility of usage of the domestic protein microspheres as a vehicle for radionuclide. The neutron-activating method of RPP production enables to utilize a broad spectrum of short-living isotopes that can be delivered into the target organ and anchored there for a long time. Good treatment results were obtained in case of the experimentally induced rheumatoid arthritis in rats after intraarticular loading of {sup 165}Dy-hMSA. Mathematical calculations show that homogeneous distribution of RPP in human articulation cavity with the square of 100 cm{sup 2} can be achieved when the quantity of administered particles exceeds 3000. On the example of {sup 165}Dy-hMSA energy characteristic distribution we demonstrated that the absorbed dose for damaged cells at 2mm distance from the radioactive source is 7 times less than the one for a sphere of 2mm diameter. Analysis of dosimetric data in case of intratumoral loading of {sup 165}Dy-hMSA also point out the necessity of the absorbed dose calculation methods taking into account the distance from the source and possible heterogeneity of RPP distribution inside the tumor to be employed. The prolonged RPP detention in the target causing no essential morphological and functional changes was achieved by embolization on the level of septal and interlobular arteries and of efferent arterioles in the animal`s renal. The uniformity of microsphere distribution in the organ and their accumulation in tumors depends on the number of particles being administered. Investigations carried out suggest the efficacy of radionuclide therapy application for treatment of oncological and heavy somatic diseases. They also indicate the necessity of further investigations aimed to optimize the usage of microspheres as a radionuclide carrier usage and to work out the criteria of dosimetric planning 25 refs.

  16. A Well-Controlled Experimental System To Study Interactions Of Cytotoxic T Lymphocytes With Tumor Cells

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    Natalie Jessica Neubert


    Full Text Available While T cell-based immunotherapies are steadily improving, there are still many patients who progress, despite T cell-infiltrated tumors. Emerging evidence suggests that T cells themselves may provoke immune escape of cancer cells. Here we describe a well-controlled co-culture system for studying the dynamic T cell - cancer cell interplay, using human melanoma as a model. We explain starting material, controls and culture parameters to establish reproducible and comparable cultures with highly heterogeneous tumor cells. Low passage melanoma cell lines and melanoma-specific CD8+ T cell clones generated from patient blood were cultured together for up to three days. Living melanoma cells were isolated from the co-culture system by fluorescence-activated cell sorting. We demonstrate that the characterization of isolated melanoma cells is feasible using flow cytometry for protein expression analysis as well as an Agilent whole human genome microarray and the NanoString Technology for differential gene expression analysis. In addition, we identify five genes (ALG12, GUSB, RPLP0, KRBA2 and ADAT2 that are stably expressed in melanoma cells independent of the presence of T cells or the T cell-derived cytokines IFNγ and TNFα. These genes are essential for correct normalization of gene expression data by NanoString. Further to the characterization of melanoma cells after exposure to CTLs, this experimental system might be suitable to answer a series of questions including how the affinity of CTLs for their target antigen influences the melanoma cell response and whether CTL-induced gene expression changes in melanoma cells are reversible. Taken together, our human T cell - melanoma cell culture system is well suited to characterize immune-related mechanisms in cancer cells.

  17. A Well-Controlled Experimental System to Study Interactions of Cytotoxic T Lymphocytes with Tumor Cells. (United States)

    Neubert, Natalie J; Soneson, Charlotte; Barras, David; Baumgaertner, Petra; Rimoldi, Donata; Delorenzi, Mauro; Fuertes Marraco, Silvia A; Speiser, Daniel E


    While T cell-based immunotherapies are steadily improving, there are still many patients who progress, despite T cell-infiltrated tumors. Emerging evidence suggests that T cells themselves may provoke immune escape of cancer cells. Here, we describe a well-controlled co-culture system for studying the dynamic T cell - cancer cell interplay, using human melanoma as a model. We explain starting material, controls, and culture parameters to establish reproducible and comparable cultures with highly heterogeneous tumor cells. Low passage melanoma cell lines and melanoma-specific CD8+ T cell clones generated from patient blood were cultured together for up to 3 days. Living melanoma cells were isolated from the co-culture system by fluorescence-activated cell sorting. We demonstrate that the characterization of isolated melanoma cells is feasible using flow cytometry for protein expression analysis as well as an Agilent whole human genome microarray and the NanoString technology for differential gene expression analysis. In addition, we identify five genes (ALG12, GUSB, RPLP0, KRBA2, and ADAT2) that are stably expressed in melanoma cells independent of the presence of T cells or the T cell-derived cytokines IFNγ and TNFα. These genes are essential for correct normalization of gene expression data by NanoString. Further to the characterization of melanoma cells after exposure to CTLs, this experimental system might be suitable to answer a series of questions, including how the affinity of CTLs for their target antigen influences the melanoma cell response and whether CTL-induced gene expression changes in melanoma cells are reversible. Taken together, our human T cell - melanoma cell culture system is well suited to characterize immune-related mechanisms in cancer cells.

  18. Impact of Stroma on the Growth, Microcirculation, Metabolism of Experimental Prostate Tumors

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    Christian M. Zechmann


    Full Text Available In prostate cancers (PCa, the formation of malignant stroma may substantially influence tumor phenotype and aggressiveness. Thus, the impact of the orthotopic and subcutaneous implantations of hormone-sensitive (H, hormone-insensitive (HI, anaplastic (AT1 Dunning PCa in rats on growth, microcirculation, metabolism was investigated. For this purpose, dynamic contrast-enhanced magnetic resonance imaging and 1H magnetic resonance spectroscopy ([1H]MRS were applied in combination with histology. Consistent observations revealed that orthotopic H tumors grew significantly slower compared to subcutaneous ones, whereas the growth of HI and AT1 tumors was comparable at both locations. Histologic analysis indicated that glandular differentiation and a close interaction of tumor cells and smooth muscle cells (SMC were associated with slow tumor growth. Furthermore, there was a significantly lower SMC density in subcutaneous H tumors than in orthotopic H tumors. Perfusion was observed to be significantly lower in orthotopic H tumors than in subcutaneous H tumors. Regional blood volume and permeability-surface area product showed no significant differences between tumor models and their implantation sites. Differences in growth between subcutaneous and orthotopic H tumors can be attributed to tumor-stroma interaction and perfusion. Here, SMC, may stabilize glandular structures and contribute to the maintenance of differentiated phenotype.

  19. The ectopic posterior pituitary gland

    African Journals Online (AJOL)


    Nov 4, 2013 ... pituitary gland is absent, or attenuated and reduced in height, and the infundibular stalk may not be visible.[3] The infundibular stalk is best assessed after injection of gadolinium. Signal hyperintensity in the posterior aspect of the pituitary gland on T1-weighted images is related to the paramagnetic effect of ...

  20. TNF-α-Induced VEGF and MMP-9 Expression Promotes Hemorrhagic Transformation in Pituitary Adenomas

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    Qin Liu


    Full Text Available Pituitary apoplexy is a clinical syndrome with unknown pathogenesis. Therefore, identifying the underlying mechanisms is of high clinical relevance. Tumor necrosis factor alpha (TNF-α is a critical cytokine mediating various hemorrhagic events, but little is known about its involvement in pituitary apoplexy. Here we show that TNF-α may be an important regulator of hemorrhagic transformation in pituitary adenomas. In this study, sixty surgical specimens of hemorrhagic and non-hemorrhagic human pituitary adenomas were examined. Hemorrhagic pituitary adenomas displayed higher protein and mRNA levels of TNF-α, vascular endothelial growth factor (VEGF and matrix metalloproteinase-9 (MMP-9 compared with those of non-hemorrhagic tumors. Exposure of MMQ pituitary adenoma cells to TNF-α induced VEGF and MMP-9 expression in vitro. Additionally, TNF-α administration caused hemorrhagic transformation and enhanced VEGF and MMP-9 expression in MMQ pituitary adenoma cell xenografts in mice. Blockers of VEGF or MMP-9, either alone or in combination, attenuated but not abrogated TNF-α mediated hemorrhagic transformation in xenografts. This study suggests that TNF-α may play a role in the development of intratumoral hemorrhage in pituitary adenomas via up-regulation of VEGF and MMP-9.

  1. Pituitary carcinoma diagnosed on fine needle aspiration: Report of a case and review of pathogenesis

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    Yakoushina Tatiana


    Full Text Available Pituitary carcinoma (PC is a very rare entity (0.2% of all pituitary tumors, with only about 140 cases reported in English literature. There are no reliable histological, immunohistochemical or ultrastructural features distinguishing pituitary adenoma (PA from PC. By definition, a diagnosis of PC is made after a patient with PA develops non-contiguous central nervous system (CNS or systemic metastases. To date, only three cases of PC have been reportedly diagnosed on fine needle aspiration (FNA. Two of the reported cases were diagnosed on FNA of the cervical lymph nodes and one on FNA of the vertebral bone lesion. Herein, we present a case of PC, diagnosed on FNA of the liver lesion. In this case, we describe cytologic features of PC and compare them to histologic features of the tumor in the pituitary. Clinical behavior of tumor, pathogenesis of metastasis and immunochemical and prognostic markers will also be described.

  2. Pituitary adenoma and vestibular schwannoma: Case report and review of the literature

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    Niu Y


    Full Text Available The concurrence of the intracranial multiple primary tumors (MPTs consisting of acoustic neuroma (AN and pituitary adenoma is very rare. Here, we report a 42-year-old female who presented with left AN associated with pituitary adenoma. A total of three such cases have been reported before and which also presented with left AN with pituitary adenoma. Recently, a new "field cancerization" model has been proposed, which could explain MPTs and is consistent with the pathogenesis of such cases. The model also indicates that when a pituitary tumor or AN is detected separately, we might consider the development of "expanding field" after oncological treatment especially after radiotherapy in order to prevent the second field tumor occurring.

  3. Pituitary adenoma and vestibular schwannoma: case report and review of the literature. (United States)

    Niu, Y; Ma, L; Mao, Q; Wu, L; Chen, J


    The concurrence of the intracranial multiple primary tumors (MPTs) consisting of acoustic neuroma (AN) and pituitary adenoma is very rare. Here, we report a 42-year-old female who presented with left AN associated with pituitary adenoma. A total of three such cases have been reported before and which also presented with left AN with pituitary adenoma. Recently, a new "field cancerization" model has been proposed, which could explain MPTs and is consistent with the pathogenesis of such cases. The model also indicates that when a pituitary tumor or AN is detected separately, we might consider the development of "expanding field" after oncological treatment especially after radiotherapy in order to prevent the second field tumor occurring.

  4. Experimental drug STA-8666 causes complete tumor regression in animal models of pediatric sarcomas | Center for Cancer Research (United States)

    New studies from scientists in the NCI Center for Cancer Research’s (CCR) Pediatric Oncology Branch suggest that an experimental drug called STA-8666 could be an effective treatment for the childhood cancers Ewing sarcoma and rhabdomyosarcoma. In mouse models of these diseases, STA-8666 eliminated tumors and prolonged survival beyond that of animals treated with a related drug, irinotecan. Read more…

  5. Prothymosin-alpha and Ki-67 expression in pituitary adenomas

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    Iga Wierzbicka-Tutka


    Full Text Available Introduction: Prothymosin alpha (PTMA, a nuclear oncoprotein involved in cell cycle regulation, is used as a prognostic marker in many cancers. The histopathology of pituitary carcinomas and locally invasive adenomas is indistinguishable from that of benign tumors. A new marker is needed to differentiate these lesions. We evaluated PTMA in pituitary adenomas to determine its usefulness as a prognostic factor of tumor proliferation.Material/Methods: We conducted a retrospective analysis of a group of 27 patients, including 15 females (56% and 12 males (44% with a mean age of 58.6±12 years, who underwent pituitary tumor surgery between 2003 and 2012. The Ki-67 and PTMA-nuclear (PTMA-n and PTMA-cytoplasmic (PTMA-c indices were determined by immunohistochemical staining. We studied histopathological features, clinical symptoms, and magnetic resonance imaging or computed tomography performed before surgery and one year following surgery to evaluate tumor size and progression.Results: The expression of Ki-67 was revealed in 77.8% of adenomas, PTMA-n in 81.5% and PTMA-c in 92.6%. The mean value of the Ki-67 index was 1.8%, PTMA-n was 1.84%, and PTMA-c was 35.6%. There was a significant positive correlation between Ki-67 and PTMA-n (p=0.009. We did not find any correlation between Ki-67, PTMA-c, and tumor progression. PTMA-n was found to be correlated with tumor size (p=0.045 and was higher in the case of gonadotropinomas (p=0.026.Conclusions: The positive nuclear expression of Ki-67 and PTMA was observed in the majority of pituitary adenomas. Neither the expression of Ki-67 nor that of PTMA-c was related to tumor recurrence or local invasion.

  6. Metastatic pituitary carcinoma: a case report and review of literature

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    ZHANG Shang-fu


    Full Text Available Background As a kind of rare tumor, metastatic pituitary carcinoma is very difficult to diagnose clinically and is easy to be misdiagnosed. This article aims to discuss the clinical manifestations and histopathological features of this tumor. Methods The clinical presentations, histopathological features and immunophenotype were studied in one case of poorly differentiated lung adenocarcinoma metastatic to pituitary gland, and related literature was reviewed. Results A 47-year-old woman mainly presented with faint, headache and blurred vision. CT scan demonstrated abnormal signals in suprasellar cistern. During the resection, the tumor could be seen locating in sellar region, the size of which was about 2 cm × 1 cm × 1 cm. Histopathological examination revealed that the structure of pituitary gland was damaged and the tumor was composed of atypical round or oval cells arranged in nest or glandular patterns, in which a number of enlarged plump tumor cells contained abundant eosinophilic cytoplasm with eccentrical caryogenesis. The immunohistochemistry showed that epithelial membrane antigen (EMA, pan cytokeratin (PCK, thyroid transcription factor-1 (TTF-1 and cytokeratin 7 (CK7 were positive in tumor cells with Ki-67 labeling index being 15%, but chromogranin (CgA, cancer embryo antigen (CEA, human chorionic gonadotropin (hCG, placental alkaline phosphatase (PLAP, CD117, leukocyte common antigen (LCA, CD30, anaplastic lymphoma kinase-1 (ALK-1 were negative in tumor cells. After operation the patient received treatment with levothyroxine sodium and γ knife, but died 4 months later. Conclusion Histopathological examination and immunohistochemistry can confirm the diagnosis of metastatic pituitary carcinoma and locate the primary lesion. Postoperative comprehensive therapy is necessary.

  7. Regulation of pituitary hormones and cell proliferation by components of the extracellular matrix

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    M. Paez-Pereda


    Full Text Available The extracellular matrix is a three-dimensional network of proteins, glycosaminoglycans and other macromolecules. It has a structural support function as well as a role in cell adhesion, migration, proliferation, differentiation, and survival. The extracellular matrix conveys signals through membrane receptors called integrins and plays an important role in pituitary physiology and tumorigenesis. There is a differential expression of extracellular matrix components and integrins during the pituitary development in the embryo and during tumorigenesis in the adult. Different extracellular matrix components regulate adrenocorticotropin at the level of the proopiomelanocortin gene transcription. The extracellular matrix also controls the proliferation of adrenocorticotropin-secreting tumor cells. On the other hand, laminin regulates the production of prolactin. Laminin has a dynamic pattern of expression during prolactinoma development with lower levels in the early pituitary hyperplasia and a strong reduction in fully grown prolactinomas. Therefore, the expression of extracellular matrix components plays a role in pituitary tumorigenesis. On the other hand, the remodeling of the extracellular matrix affects pituitary cell proliferation. Matrix metalloproteinase activity is very high in all types of human pituitary adenomas. Matrix metalloproteinase secreted by pituitary cells can release growth factors from the extracellular matrix that, in turn, control pituitary cell proliferation and hormone secretion. In summary, the differential expression of extracellular matrix components, integrins and matrix metalloproteinase contributes to the control of pituitary hormone production and cell proliferation during tumorigenesis.


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    Oliveira Paulo Ferdinando de Melo


    Full Text Available A incidência de câncer gástrico espontâneo em ratos é extremamente rara. Por outro lado, embora o câncer experimental de estômago possa ser induzido por carcinógenos químicos, através da ressecção da região fúndica do estômago, pela vagotomia ou pelo refluxo, esses métodos apresentam um percentual de desenvolvimento tumoral baixo e errático. Além disso, geralmente decorre um longo período de tempo até o pleno crescimento do tumor. O presente trabalho procurou estabelecer um modelo de tumor experimental de crescimento rápido, uniforme e com elevado índice de pega, que permitisse a avaliação de novas terapêuticas para o tratamento do câncer gástrico. Para tanto, utilizou-se uma suspensão de células do carcinossarcoma 256 de Walker que foi inoculada no estômago através de uma cânula orogástrica. A implantação ocorreu na mucosa previamente lesionada por clampeadura da parede, nas regiões da junção esôfago-gástrica, pequena curvatura e grande curvatura. O crescimento tumoral ocorreu em todos os animais e, embora na junção esôfago-gástrica a incidência de pega tenha sido de apenas 20%, possivelmente em função do epitélio queratinizado, na pequena curvatura a incidência foi de 80% e na grande curvatura todos os animais apresentaram tumor. Esses dados demonstraram que é possível implantar o tumor em 100% dos animais inoculados, o que comprova a exequibilidade da técnica. A vantagem dessa metodologia sobre as outras já descritas na literatura, também usando o carcinossarcoma 256 de Walker, é que o tumor cresce a partir da mucosa, reproduzindo as condições de desenvolvimento do tumor gástrico espontâneo. A média de sobrevida dos animais inoculados é de 13,2±1,98 dias. Além disso, como o tumor se desenvolve em todos os animais inoculados, pode-se dispensar métodos radiológicos e ultra-sonográficos para evidenciar a sua presença. Trata-se, portanto, de um método simples e eficaz e que

  9. Feasibility of 99mTc-annexin V for repetitive detection of apoptotic tumor response to chemotherapy: an experimental study using a rat tumor model. (United States)

    Kuge, Yuji; Sato, Masayuki; Zhao, Songji; Takei, Toshiki; Nakada, Kunihiro; Seki, Koh-ich; Strauss, H William; Blankenberg, Francis G; Tait, Jonathan F; Tamaki, Nagara


    Annexin V (annexin A5), a human protein with a high affinity for phosphatidylserine, labeled with (99m)Tc can detect apoptosis in vivo. In the repetitive detection of apoptosis with (99m)Tc-annexin V, however, the specific binding of annexin V to phosphatidylserine might affect the subsequent detection of apoptosis with this compound. To determine whether there is interference with repetitive doses of annexin V, we evaluated the effects of previous administration of cold annexin V on accumulation of (99m)Tc-annexin V in tumors in an experimental tumor model. Rats bearing hepatoma received cyclophosphamide (150 mg/kg, intraperitoneally) 11 d after the tumor inoculation. Cold annexin V (20 microg/kg, intravenously) was administered 24 h before or after the cyclophosphamide treatment (n = 7/group). (99m)Tc-Annexin V was injected intravenously (radioactive dose, 5-23 MBq/kg; mass dose, 20 microg/kg), and radioactivity in tissues was determined 6 h later. Accumulation of (99m)Tc-annexin V in tumors was not significantly affected by previous treatment with cold annexin V before or after chemotherapy. These results demonstrate the feasibility of (99m)Tc-annexin V imaging for repetitive detection of apoptosis, which is highly required in the clinical setting.

  10. Delayed Onset of Isolated Unilateral Oculomotor Nerve Palsy Caused by Post-Traumatic Pituitary Apoplexy: A Case Report

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    Tomoki Ishigaki


    Full Text Available Post-traumatic pituitary apoplexy is uncommon, most of which present with a sudden onset of severe headache and visual impairments associated with a dumbbell-shaped pituitary tumor. We experienced an unusual case of post-traumatic pituitary apoplexy with atypical clinical features. A 66-year-old man presented with mild cerebral contusion and an incidentally diagnosed intrasellar tumor after a fall accident with no loss of consciousness. The patients denied any symptoms before the accident. After 4 days, the left oculomotor nerve palsy developed and deteriorated associated with no severe headache. Repeated neuroimages suggested that pituitary apoplexy had occurred at admission and showed that the tumor compressed the left cavernous sinus. The patient underwent endonasal transsphenoidal surgery at 6 days after head injury, and the mass reduction improved the oculomotor nerve palsy completely within the following 14 days. The pathologic diagnosis was nonfunctioning pituitary adenoma with hemorrhage and necrosis.



    Michiaki, YAKUSHIJI; Takashi, NISHIDA; Haruo, NISHIMURA; Tomihide, NISHIDA; Akitsu, TSUNAWAKI; Toshi, KATO; Department of Obstetrics and Gynecology Kurume University school of Medicihe, Kurume


    Female C_3H strain mice aged 5 to 6 weeks were exposed to a single does of 400 Rad irradiation to their lower abdbmens and the morphological changes of their ovaries were observed until 72 weeks after irradiation. The incidence of tumor development increased gradually from 34 weeks after irradiation till 72 weeks, when ovarian tumors were noted in more than 90% of the animals. Three types of ovarian tumors developed after a prolonged period, postirradiation : tubular adenoma, granulosa cell t...

  12. [Histopathological and autoradiographical studies of experimental brain tumors after continuous local chemotherapy--acute stage in rat models]. (United States)

    Shimura, T; Teramoto, A; Aihara, K


    Continuous local chemotherapy has been evaluated as being an effective administration method and as a possible adjuvant therapy in the sensitivity aspect of the cell cycle for malignant glioma. However, neurotoxicity of anti-cancer agents in the normal brain and non-effective methods for the deeper part of the tumor seem to be the most serious problems. This study was initiated to evaluate histological findings, the uptake distribution, and neurotoxicity of the continuous local administration of isotope labeled anti-cancer agents in the brain tumor of rats. The experimental brain tumor of rats and the method of continuous local chemotherapy were as follows. The tumor was produced by intracerebral inoculation of cultured cells derived from rat brain tumor induced by Rous sarcoma virus (Kumanishi et al. strain). One week later Fluorouracil (5-6-3H) (17.7 Ci/m mol) and methotrexate (L-glutamyl 3-4-3H) (41.0 Ci/m mol) were administered into the brain tumors of rats utilizing a mini osmotic pump (Alzet Model 2001), respectively. We used five rats of various groups. The rats were sacrificed at various time intervals (6 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs and 7 days). The tumor tissues for light microscopic autoradiography were fixed in 10% formalin for 24 hours. Sections for the light microscopic autoradiography were cut at 4 mu thick and coated with Sakura NR-M2 drips. Following exposure for one week at 4 degrees C, the sections were stained with Konidol X. Six hours after administration, slight radioactivity was distributed in the subarachnoid space and subpial brain tissue in the vicinity of the inserted tube. Twenty-four hours after administration, high radioactivity was clearly present in many tumor cells and phagocytes at the tube tip, but no radioactivity was observed in the deeper part of the tumor or normal brain tissue. In the vicinity of necrosis foci, acute toxic inflammation was also observed. In conclusion, this experimental study shows that these anti

  13. BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas. (United States)

    Ibáñez-Costa, Alejandro; López-Sánchez, Laura M; Gahete, Manuel D; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C; Gálvez, María A; de la Riva, Andrés; Venegas-Moreno, Eva; Jiménez-Reina, Luis; Moreno-Carazo, Alberto; Tinahones, Francisco J; Maraver-Selfa, Silvia; Japón, Miguel A; García-Arnés, Juan A; Soto-Moreno, Alfonso; Webb, Susan M; Kineman, Rhonda D; Culler, Michael D; Castaño, Justo P; Luque, Raúl M


    Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D 2 receptors-agonist, have emerged as promising new approaches to treat pituitary adenomas. However, information on direct in vitro effects of BIM-23A760 in normal and tumoral pituitaries remains incomplete. The objective of this study was to analyze BIM-23A760 effects on functional parameters (Ca 2+ signaling, hormone expression/secretion, cell viability and apoptosis) in pituitary adenomas (n = 74), and to compare with the responses of normal primate and human pituitaries (n = 3-5). Primate and human normal pituitaries exhibited similar sst2/sst5/D2 expression patterns, wherein BIM-23A760 inhibited the expression/secretion of several pituitary hormones (specially GH/PRL), which was accompanied by increased sst2/sst5/D2 expression in primates and decreased Ca 2+ concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca 2+ concentration, hormone secretion/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca 2+ signaling and/or hormone secretion, which was associated with the relative somatostatin/dopamine-receptors levels, especially sst5 and sst5TMD4. The chimeric sst2/sst5/D 2 compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D 2 expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760.

  14. Alternative splicing of iodothyronine deiodinases in pituitary adenomas. Regulation by oncoprotein SF2/ASF. (United States)

    Piekielko-Witkowska, Agnieszka; Kedzierska, Hanna; Poplawski, Piotr; Wojcicka, Anna; Rybicka, Beata; Maksymowicz, Maria; Grajkowska, Wieslawa; Matyja, Ewa; Mandat, Tomasz; Bonicki, Wieslaw; Nauman, Pawel


    Pituitary tumors belong to the group of most common neoplasms of the sellar region. Iodothyronine deiodinase types 1 (DIO1) and 2 (DIO2) are enzymes contributing to the levels of locally synthesized T3, a hormone regulating key physiological processes in the pituitary, including its development, cellular proliferation, and hormone secretion. Previous studies revealed that the expression of deiodinases in pituitary tumors is variable and, moreover, there is no correlation between mRNA and protein products of the particular gene, suggesting the potential role of posttranscriptional regulatory mechanisms. In this work we hypothesized that one of such mechanisms could be the alternative splicing. Therefore, we analyzed expression and sequences of DIO1 and DIO2 splicing variants in 30 pituitary adenomas and 9 non-tumorous pituitary samples. DIO2 mRNA was expressed as only two mRNA isoforms. In contrast, nine splice variants of DIO1 were identified. Among them, five were devoid of exon 3. In silico sequence analysis of DIO1 revealed multiple putative binding sites for splicing factor SF2/ASF, of which the top-ranked sites were located in exon 3. Silencing of SF2/ASF in pituitary tumor GH3 cells resulted in change of ratio between DIO1 isoforms with or without exon 3, favoring the expression of variants without exon 3. The expression of SF2/ASF mRNA in pituitary tumors was increased when compared with non-neoplastic control samples. In conclusion, we provide a new mechanism of posttranscriptional regulation of DIO1 and show deregulation of DIO1 expression in pituitary adenoma, possibly resulting from disturbed expression of SF2/ASF. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Pituitary microadenoma with prolactin, corticotropic and thyreotropic deficiency: from infertility to pregnancy : About a case

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    Diallo Moussa


    Full Text Available Pituitary adenomas are benign tumors developed at the expense of different cellular populations of the pituitary gland. Within the pituitary gland, several cell populations may be involved, but the lactotropic cells remain the most frequently affected by this hyperplasia. For both sexes, the overall frequency of adenomas is 100 per million, of which 40% are prolactinomas. The stimulating effect of estrogens (combined oral contraceptives and pregnancy on lactotropic cells has long been demonstrated, and in general, only large tumors (macroadenomas have an evolving risk to be feared during pregnancy. The diagnosis rests on the one hand on the evidence of a hormonal hypersecretion of the cell population concerned as well as a hormonal deficiency of the other cell groups which can be compressed by the tumor. On the other hand, this diagnosis uses hypophyseal magnetic resonance imaging (MRI to distinguish, according to their size, microadenomas (diameter less than 10 mm from macroadenomas (diameter greater than 10 mm pituitary. The risk of increasing the volume of the adenoma during pregnancy depends on the initial size of the tumor. This risk is evaluated at 2% for microadenoma and 15-35% for macroadenomas. However, the most severe complication during pregnancy remains paroxysmal acute growth or pituitary apoplexy by necrotic-haemorrhagic phenomena. The management is mainly based on prolactinoma on bromocryptin or cabergoline and sometimes surgery, urgently in the presence of a pituitary apoplexy or in the presence of an evolutionary macroadenoma.

  16. Magnetic resonance imaging of pituitary adenoma

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    Handa, Yuji; Hayashi, Minoru; Kubota, Toshihiko; Satoh, Kazufumi; Kobayashi, Hidenori; Kawano, Hirokazu; Kabuto, Masanori; Okumura, Ryousuke


    The magnetic resonance (MR) images of eight patients with pituitary macroadenoma, confirmed by means of CT, were evaluated retrospectively. The examinations were performed with a 0.35 T MR system using short repetition (TR) (T/sub 1/-weighted) and long TR (T/sub 2/-weighted) spin-echo sequences. T/sub 1/-weighted images were obtained on coronal, sagittal, or axial planes with all patients, while T/sub 2/-weighted images were routinely obtained on the axial plane with all patients and on the sagittal or coronal plane in some cases. Detailed information as to the size, configuration, and anatomical relationship, particularly to the optic tract, of the pituitary adenoma were well visualized on sagittal or coronal T/sub 1/-weighted images. The signal intensities from the tumor on T/sub 1/-weighted of T/sub 2/-weighted images were evaluated as iso-, hypo- or hyper-intense with respect to the cortical gray matter. The signal intensities from three non-functioning pituitary adenomas varied from low- to high-intense on the T/sub 1/- or T/sub 2/-weighted images. All the two growth-hormone-producing adenomas showed iso-intense signal intensities on both T/sub 1/- and T/sub 2/-weighted images. One of the two prolactine-producing adenomas were iso-intense on a T/sub 1/-weighted image and low-intense on a T/sub 2/-weighted image, while the other adenoma, when treated with bromocriptine, was iso-intense on both T/sub 1/- and T/sub 2/-weighted images. One adenocorticotropic hormone-producing adenoma was iso-intense on T/sub 1/-weighted and high-intense on T/sub 2/-weighted images. Although the signal intensities on the images, particularly the T/sub 2/-weighted images, were variable, regardless of the type of adenoma, it is presumed that the MR signal arising from a pituitary adenoma affected by the biological or pathological state of the tumor cells.

  17. Interactions of photoperiod and ectopic pituitary grafts on hypothalamic and pituitary function in male hamsters. (United States)

    Steger, R W; Matt, K S; Klemcke, H G; Bartke, A


    Exposure of adult male hamsters to short days (less than 12.5 light/day) leads to suppression of gonadal function which is secondary to reductions in gonadotropin and prolactin (PRL) secretion. PRL secretion is decreased in short days despite a reduction of dopaminergic (DA) input from the hypothalamus, suggesting that the pituitary may become more sensitive to the inhibitory effects of DA. Although hypothalamic DA metabolism is altered by short-day exposure, it is not known whether the DA system can respond to PRL feedback or whether these changes in DA or PRL levels are responsible for the observed changes in gonadotropin secretion. To address these questions, the effects of PRL-secreting ectopic pituitary grafts on hypothalamic catecholamine metabolism and the effects of experimental manipulations of catecholamine metabolism on PRL and gonadotropin secretion were evaluated in adult male hamsters exposed to a 14 h light: 10 h dark (14L:10D) or a 5L:19D photoperiod. Short-photoperiod exposure led to expected reductions in testes weight, plasma PRL levels, and in vitro PRL secretion, but circulating levels of luteinizing hormone or follicle-stimulating hormone were not affected. Norepinephrine and DA turnover in the median eminence and in the medial basal hypothalamus was also reduced in the 5L:19D as compared to the 14L:10D animals. Pituitary grafts elevated PRL levels and hypothalamic DA turnover in animals from either photoperiod, but in vitro PRL secretion was reduced only from the pituitaries of 14L:10D hamsters. Short-photoperiod exposure increased the ability of DA to suppress PRL secretion, and this effect could be reversed by the presence of an ectopic pituitary graft.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Expression of p53 protein in pituitary adenomas

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    Oliveira M.C.


    Full Text Available Inactivating mutations of TP53, a tumor suppressor gene, are associated with abnormal cell proliferation. Although p53 expression is common in many human malignancies, p53 protein has seldom been evaluated in pituitary tumors. When detected, the percentage of p53-positive cells is low, and, in general, it is exclusive for invasive lesions. The aim of the present study was to use immunohistochemistry to determine the presence of p53 protein in pituitary adenomas from tumor samples of 163 surgeries performed in 148 patients (40% male, 60% female. In 35% of the cases the adenoma was nonfunctional, while in the others it was associated with PRL, GH and/or ACTH endocrine hypersecretion syndrome. Macroadenomas were observed in 83.2% of the cases with available neuroimage evaluation, of which 28% invaded the cavernous, sphenoid and/or ethmoidal sinus, bone, third ventricle or subfrontal lobe. p53 protein was detected in 2/148 patients (1.3%. Immunohistochemistry was positive for PRL and GH in these cases. Due to the high percentage of invasive pituitary adenomas found in our study, the low frequency of p53 detection suggests that it is inadequate as a routine marker for aggressiveness and as a predictive factor of tumor behavior.

  19. Outcome of visual acuity after surgical removal of pituitary adenomas

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    Grković Desanka


    Full Text Available Introduction. Pituitary adenomas with suprasellar extension may produce anterior visual pathway compression, resulting in characteristic visual deficit. Surgical decompression of these structures prevents further visual deterioration and its postop­ erative recovery. Objective. The aim of this study was to investigate pre­ and postoperative visual acuity (VA in patients with pituitary ad­ enomas, and to detect the influence of prognostic factors, such as symptoms duration, degree of visual acuity reduction and tumor size in the assessment of the prognosis of postoperative visual function. Methods. We analyzed 40 consecutive patients who fulfilled three criteria: evidence of preoperative visual dysfunction, transsphenoidal or transfrontal tumor resection and hystologically verified pituitary adenoma. A visual examination was performed under standard conditions, pre and postoperatively (10 days, one month and six months after surgery. A paired t­test was used to assess the differences of pre­ and postoperative characteristics values, and the Chisquare test of independence in the assessment of the influence of prognostic factors. Results. Postoperative improvement of VA was seen in 84.61% patients (68% eyes. Eyes with preoperative mild and moderate degree of VA reduction showed improvement in 89.65% eyes in contrast to 22.60% eyes with preoperative severe reduction of VA, which was all statistically significant. Eyes in patients with tumor smaller than 20 mm had improvement of VA in 91.66% eyes, while eyes with tumor larger than 40 mm had improvement of VA in 61.11% eyes, which was statistically significant. When symptoms duration was below two years the improvement of VA was detected in 65.38% eyes as related to 50% eyes with symptoms duration exceeding two years, which was not statistically significant. Conclusion. Pituitary adenomas commonly cause visual impairment. Postoperatively the majority of patients show a distinct improvement of

  20. Dysregulated estrogen receptor signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis in mice.

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    Mary J Laws


    Full Text Available The etiology of ovarian epithelial cancer is poorly understood, mainly due to the lack of an appropriate experimental model for studying the onset and progression of this disease. We have created a mutant mouse model in which aberrant estrogen receptor alpha (ERα signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis. In these mice, termed ERαd/d, the ERα gene was conditionally deleted in the anterior pituitary, but remained intact in the hypothalamus and the ovary. The loss of negative-feedback regulation by estrogen (E at the level of the pituitary led to increased production of luteinizing hormone (LH by this tissue. Hyperstimulation of the ovarian cells by LH resulted in elevated steroidogenesis, producing high circulating levels of steroid hormones, including E. The ERαd/d mice exhibited formation of palpable ovarian epithelial tumors starting at 5 months of age with 100% penetrance. By 15 months of age, 80% of ERαd/d mice die. Besides proliferating epithelial cells, these tumors also contained an expanded population of luteinized stromal cells, which acquire the ability to express P450 aromatase and synthesize E locally. In response to the elevated levels of E, the ERα signaling was accentuated in the ovarian epithelial cells of ERαd/d mice, triggering increased ERα-dependent gene expression, abnormal cell proliferation, and tumorigenesis. Consistent with these findings, treatment of ERαd/d mice with letrozole, an aromatase inhibitor, markedly reduced circulating E and ovarian tumor volume. We have, therefore, developed a unique animal model, which serves as a useful tool for exploring the involvement of E-dependent signaling pathways in ovarian epithelial tumorigenesis.

  1. Dysregulated Estrogen Receptor Signaling in the Hypothalamic-Pituitary-Ovarian Axis Leads to Ovarian Epithelial Tumorigenesis in Mice (United States)

    Laws, Mary J.; Kannan, Athilakshmi; Pawar, Sandeep; Haschek, Wanda M.; Bagchi, Milan K.; Bagchi, Indrani C.


    The etiology of ovarian epithelial cancer is poorly understood, mainly due to the lack of an appropriate experimental model for studying the onset and progression of this disease. We have created a mutant mouse model in which aberrant estrogen receptor alpha (ERα) signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis. In these mice, termed ERαd/d, the ERα gene was conditionally deleted in the anterior pituitary, but remained intact in the hypothalamus and the ovary. The loss of negative-feedback regulation by estrogen (E) at the level of the pituitary led to increased production of luteinizing hormone (LH) by this tissue. Hyperstimulation of the ovarian cells by LH resulted in elevated steroidogenesis, producing high circulating levels of steroid hormones, including E. The ERαd/d mice exhibited formation of palpable ovarian epithelial tumors starting at 5 months of age with 100% penetrance. By 15 months of age, 80% of ERαd/d mice die. Besides proliferating epithelial cells, these tumors also contained an expanded population of luteinized stromal cells, which acquire the ability to express P450 aromatase and synthesize E locally. In response to the elevated levels of E, the ERα signaling was accentuated in the ovarian epithelial cells of ERαd/d mice, triggering increased ERα-dependent gene expression, abnormal cell proliferation, and tumorigenesis. Consistent with these findings, treatment of ERαd/d mice with letrozole, an aromatase inhibitor, markedly reduced circulating E and ovarian tumor volume. We have, therefore, developed a unique animal model, which serves as a useful tool for exploring the involvement of E-dependent signaling pathways in ovarian epithelial tumorigenesis. PMID:24603706

  2. Effect of aged garlic extract on immune responses to experimental fibrosarcoma tumor in BALB/c mice. (United States)

    Tabari, M Abouhosseini; Ebrahimpour, S


    Aged garlic extract (AGE) has many biological activities including radical scavenging, antioxidative and immunomodulative effects. In this research work, the antitumor and immunomodulatory effects of AGE against fibrosarcoma implanted tumor were studied. WEHI-164 fibrosarcoma cells were implanted subcutaneously on day 0 into the right flank of 40 BALB/c mice at age of 8 weeks. Mice were randomly categorized in two separate groups: First received AGE (100 mg/kg, IP), second group as the control group received phosphate buffered saline. Treatments were carried out 3 times/week. Tumor growth was measured and morbidity was recorded. Subpopulations of CD4+/CD8+ T cells were determined using flow cytometry. WEHI-164 cell specific cytotoxicity of splenocytes and in vitro production of interferon gamma (IFN-γ) and interleukin-4 cytokines were measured. The mice received AGE had significantly longer survival time compared with the control mice. The inhibitory effect on tumor growth was seen in AGE treated mice. The CD4+/CD8+ ratio and in vitro IFN-γ production of splenocytes were significantly increased in AGE group. WEHI-164 specific cytotoxicity of splenocytes from AGE mice was also significantly increased at 25:1 E: T ratio. Administration of AGE resulted in improved immune responses against experimentally implanted fibrosarcoma tumors in BALB/c mice. AGE showed significant effects on inhibition of tumor growth and longevity of survival times.

  3. Dietary mastic oil extracted from Pistacia lentiscus var. chia suppresses tumor growth in experimental colon cancer models. (United States)

    Spyridopoulou, Katerina; Tiptiri-Kourpeti, Angeliki; Lampri, Evangeli; Fitsiou, Eleni; Vasileiadis, Stavros; Vamvakias, Manolis; Bardouki, Haido; Goussia, Anna; Malamou-Mitsi, Vasiliki; Panayiotidis, Mihalis I; Galanis, Alex; Pappa, Aglaia; Chlichlia, Katerina


    Plant-derived bioactive compounds attract considerable interest as potential chemopreventive anticancer agents. We analyzed the volatile dietary phytochemicals (terpenes) present in mastic oil extracted from the resin of Pistacia lentiscus var. chia and comparatively investigated their effects on colon carcinoma proliferation, a) in vitro against colon cancer cell lines and b) in vivo on tumor growth in mice following oral administration. Mastic oil inhibited - more effectively than its major constituents- proliferation of colon cancer cells in vitro, attenuated migration and downregulated transcriptional expression of survivin (BIRC5a). When administered orally, mastic oil inhibited the growth of colon carcinoma tumors in mice. A reduced expression of Ki-67 and survivin in tumor tissues accompanied the observed effects. Notably, only mastic oil -which is comprised of 67.7% α-pinene and 18.8% myrcene- induced a statistically significant anti-tumor effect in mice but not α-pinene, myrcene or a combination thereof. Thus, mastic oil, as a combination of terpenes, exerts growth inhibitory effects against colon carcinoma, suggesting a nutraceutical potential in the fight against colon cancer. To our knowledge, this is the first report showing that orally administered mastic oil induces tumor-suppressing effects against experimental colon cancer.

  4. Hipoxia Tumoral – Metabonómica e Imagem Estudo Experimental


    Abrantes, Ana Margarida Coelho


    Tese de doutoramento em Ciências da Saúde, ramo de Ciências Biomédicas, apresentada à Faculdade de Medicina da Universidade de Coimbra Os tumores são organizações morfo-funcionais que, em geral, apresentam grande multiplicação celular. A elevada taxa de proliferação e o crescimento celular são características inerentes ao desenvolvimento de um tumor e que condicionam a resposta da célula tumoral no que diz respeito à sua capacidade de aumentar o aporte de oxigénio e de nutrientes. Como...

  5. Pituitary macroadenomas: reviews of 60 cases; Revisao de 60 casos de macroadenomas hipofisarios

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    Santos, Alair Augusto S.M.D. dos; Fontes, Cristina Asvolinsque P.; Magnago, Marcelo [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Inst. de Radiologia; Moreira, Denise Madeira [Universidade Federal, Rio de Janeiro, RJ (Brazil). Inst. de Radiologia; Andreiuolo, Pedro Angelo [Hospital Santa Cruz/Beneficencia Portuguesa, Niteroi, RJ (Brazil). Servico de Radiologia; Oliveira, Fernando Barros de; Teixeira, Ricardo Tostes D.; Correa, Saul Orlando C. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Inst. de Biofisica Carlos Chagas Filho. Curso de Pos-graduacao Medica


    We reviewed 60 cases of patients with pituitary macroadenomas who were submitted to magnetic resonance imaging evaluations at private institutions in Niteroi and Rio de Janeiro, Brazil. The aim of this study was to demonstrate the advantages of magnetic resonance imaging in the diagnosis and follow-up of these patients. Macroprolactinomas were the most prevalent tumors. We also observed four growth-hormone (GH) secreting macroadenomas with clinical signs of acromegaly, and one GH- and prolactin-secreting macroadenoma. Seven patients presented pituitary apoplexy and hyperintense signal on T1-W images before contrast medium (gadolinium) administration suggestive of intratumoral bleeding. The follow-up of 15 cases demonstrated a reduction in the size of the tumor after surgery, clinical treatment or radiotherapy. Magnetic resonance imaging is important for the study of pituitary macroadenomas, particularly before surgery, as it shows the involvement of adjacent structures, specially the cavernous sinus, optic chiasm and pituitary stalk compression. (author)

  6. In Vivo Imaging of Experimental Melanoma Tumors using the Novel Radiotracer 68Ga-NODAGA-Procainamide (PCA) (United States)

    Kertész, István; Vida, András; Nagy, Gábor; Emri, Miklós; Farkas, Antal; Kis, Adrienn; Angyal, János; Dénes, Noémi; Szabó, Judit P.; Kovács, Tünde; Bai, Péter; Trencsényi, György


    Purpose: The most aggressive form of skin cancer is the malignant melanoma. Because of its high metastatic potential the early detection of primary melanoma tumors and metastases using non-invasive PET imaging determines the outcome of the disease. Previous studies have already shown that benzamide derivatives, such as procainamide (PCA) specifically bind to melanin pigment. The aim of this study was to synthesize and investigate the melanin specificity of the novel 68Ga-labeled NODAGA-PCA molecule in vitro and in vivo using PET techniques. Methods: Procainamide (PCA) was conjugated with NODAGA chelator and was labeled with Ga-68 (68Ga-NODAGA-PCA). The melanin specificity of 68Ga-NODAGA-PCA was tested in vitro, ex vivo and in vivo using melanotic B16-F10 and amelanotic Melur melanoma cell lines. By subcutaneous and intravenous injection of melanoma cells tumor-bearing mice were prepared, on which biodistribution studies and small animal PET/CT scans were performed for 68Ga-NODAGA-PCA and 18FDG tracers. Results: 68Ga-NODAGA-PCA was produced with high specific activity (14.9±3.9 GBq/µmol) and with excellent radiochemical purity (98%<), at all cases. In vitro experiments showed that 68Ga-NODAGA-PCA uptake of B16-F10 cells was significantly (p≤0.01) higher than Melur cells. Ex vivo biodistribution and in vivo PET/CT studies using subcutaneous and metastatic tumor models showed significantly (p≤0.01) higher 68Ga-NODAGA-PCA uptake in B16-F10 primary tumors and lung metastases in comparison with amelanotic Melur tumors. In experiments where 18FDG and 68Ga-NODAGA-PCA uptake of B16-F10 tumors was compared, we found that the tumor-to-muscle (T/M) and tumor-to-lung (T/L) ratios were significantly (p≤0.05 and p≤0.01) higher using 68Ga-NODAGA-PCA than the 18FDG accumulation. Conclusion: Our novel radiotracer 68Ga-NODAGA-PCA showed specific binding to the melanin producing experimental melanoma tumors. Therefore, 68Ga-NODAGA-PCA is a suitable diagnostic radiotracer for

  7. In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features. (United States)

    Ibáñez-Costa, Alejandro; Gahete, Manuel D; Rivero-Cortés, Esther; Rincón-Fernández, David; Nelson, Richard; Beltrán, Manuel; de la Riva, Andrés; Japón, Miguel A; Venegas-Moreno, Eva; Gálvez, Ma Ángeles; García-Arnés, Juan A; Soto-Moreno, Alfonso; Morgan, Jennifer; Tsomaia, Natia; Culler, Michael D; Dieguez, Carlos; Castaño, Justo P; Luque, Raúl M


    Pituitary adenomas comprise a heterogeneous subset of pathologies causing serious comorbidities, which would benefit from identification of novel, common molecular/cellular biomarkers and therapeutic targets. The ghrelin system has been linked to development of certain endocrine-related cancers. Systematic analysis of the presence and functional implications of some components of the ghrelin system, including native ghrelin, receptors and the recently discovered splicing variant In1-ghrelin, in human normal pituitaries (n = 11) and pituitary adenomas (n = 169) revealed that expression pattern of ghrelin system suffers a clear alteration in pituitary adenomasas compared with normal pituitary, where In1-ghrelin is markedly overexpressed. Interestingly, in cultured pituitary adenoma cells In1-ghrelin treatment (acylated peptides at 100 nM; 24-72 h) increased GH and ACTH secretion, Ca(2+) and ERK1/2 signaling and cell viability, whereas In1-ghrelin silencing (using a specific siRNA; 100 nM) reduced cell viability. These results indicate that an alteration of the ghrelin system, specially its In1-ghrelin variant, could contribute to pathogenesis of different pituitary adenomas types, and suggest that this variant and its related ghrelin system could provide new tools to identify novel, more general diagnostic, prognostic and potential therapeutic targets in pituitary tumors.

  8. A FSH-Secreting Pituitary Macroadenoma Causing A Testosterone Deficiency Syndrome

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    Xiong Wang


    Full Text Available FSH-secreting pituitary adenomas can affect sexual and reproductive function. In this article, we have reported the case of a 32-year-old male with secondary infertility. The patient had sexual and reproductive disturbances. The test results of the blood samples indicated obviously decreased testosterone (T and estradiol (E2 levels. Based on previous hormonal results, the patient received pituitary stimulation and human chorionic gonadotropin (hCG tests. Both follicle stimulating hormone (FSH and luteinizing hormone (LH showed low response during the pituitary stimulation test. The results of the hCG test indicated that T/E2 could recover to a normal level. In addition, this patient was diagnosed with pituitary macroadenoma, which was supported by the pituitary MRI. The man’s sexual and reproductive functions recovered following surgery. The pathological results confirmed that the tumor tissue was an FSH-secreting pituitary adenoma by immunohistochemical staining. The purpose of this report was to review the relative literature and discuss the influence of FSH-secreting pituitary adenomas on hormones through the hypothalamus-pituitary-testis axis.

  9. In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features (United States)

    Ibáñez-Costa, Alejandro; Gahete, Manuel D.; Rivero-Cortés, Esther; Rincón-Fernández, David; Nelson, Richard; Beltrán, Manuel; de la Riva, Andrés; Japón, Miguel A.; Venegas-Moreno, Eva; Gálvez, Ma Ángeles; García-Arnés, Juan A.; Soto-Moreno, Alfonso; Morgan, Jennifer; Tsomaia, Natia; Culler, Michael D.; Dieguez, Carlos; Castaño, Justo P.; Luque, Raúl M.


    Pituitary adenomas comprise a heterogeneous subset of pathologies causing serious comorbidities, which would benefit from identification of novel, common molecular/cellular biomarkers and therapeutic targets. The ghrelin system has been linked to development of certain endocrine-related cancers. Systematic analysis of the presence and functional implications of some components of the ghrelin system, including native ghrelin, receptors and the recently discovered splicing variant In1-ghrelin, in human normal pituitaries (n = 11) and pituitary adenomas (n = 169) revealed that expression pattern of ghrelin system suffers a clear alteration in pituitary adenomasas comparedwith normal pituitary, where In1-ghrelin is markedly overexpressed. Interestingly, in cultured pituitary adenoma cells In1-ghrelin treatment (acylated peptides at 100 nM; 24–72 h) increased GH and ACTH secretion, Ca2+ and ERK1/2 signaling and cell viability, whereas In1-ghrelin silencing (using a specific siRNA; 100 nM) reduced cell viability. These results indicate that an alteration of the ghrelin system, specially its In1-ghrelin variant, could contribute to pathogenesis of different pituitary adenomas types, and suggest that this variant and its related ghrelin system could provide new tools to identify novel, more general diagnostic, prognostic and potential therapeutic targets in pituitary tumors. PMID:25737012

  10. Uneven Distribution of Regional Blood Supply Prompts the Cystic Change of Pituitary Adenoma. (United States)

    Zhang, Jianhe; Gu, Jianjun; Ma, Yiming; Huang, Yinxing; Wang, Jiaxing; Wu, Zhifeng; Zhong, Qun; Wang, Shousen


    Previous studies have suggested that the cystic change of pituitary adenoma might be related to the blood supply and metabolism of the tumor; however, the exact pathologic mechanism underlying the cystic change remains unknown. We aimed to assess the features of regional blood supply of pituitary adenoma and examine its relationship with the cystic change of pituitary adenoma. Patients (N = 79) with pituitary adenoma admitted to our hospital were divided into the parenchyma group (n = 40) or the cystic change group (n = 39). Dynamic contrast-enhanced magnetic resonance imaging of the pituitary adenoma was conducted for the parenchyma group and the steepest slopes (SSmax, reflecting regional blood supply) at different areas were calculated. The location of cystic change of the pituitary adenoma was recorded and analyzed for the cystic change group. The parenchyma group showed an upper SSmax of 2.52 ± 1.18, a lower SSmax of 2.89 ± 1.46, a left SSmax of 2.71 ± 1.31, and a right SSmax of 2.66 ± 1.29. The difference between the upper and lower SSmax was statistically significant (P supply is unevenly distributed in the parenchymal pituitary adenoma, with reduced blood supply in the upper than the lower region. Cystic change mainly occurs in the upper region of pituitary adenoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Isolated double pituitary adenomas: A silent corticotroph adenoma and a microprolactinoma. (United States)

    Eytan, Shira; Kim, Ki-Yoon; Bleich, David; Raghuwanshi, Maya; Eloy, Jean Anderson; Liu, James K


    We report a 27-year-old woman with amenorrhea and galactorrhea with mildly elevated serum prolactin levels. Her MRI demonstrated a cystic macroadenoma in the left aspect of the sella and a small microadenoma in the right aspect of the sella. Endoscopic transsphenoidal resection of the tumors revealed two histologically distinct tumors. The left tumor was consistent with a silent corticotroph macroadenoma and the right tumor was a prolactin producing microadenoma. Isolated double pituitary adenomas that are clearly separated by normal pituitary gland tissue are extremely rare. The incidence is approximately 0.37-2.6%. The coexistence of double adenomas can pose diagnostic and management challenges for the pituitary neuroendocrine team. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Dynamic gadolinium uptake in thermally treated canine brain tissue and experimental cerebral tumors. (United States)

    Kangasniemi, Marko; Stafford, R Jason; Price, Roger E; Jackson, Edward F; Hazle, John D


    Thermal coagulation of cerebral tumors induces reactive changes within adjacent brain tissue, which appear as Gd-DTPA enhancement in MR images. This makes assessment of therapeutic success difficult to establish radiographically because the reactive changes can mimic residual tumor. Dynamic Gd-DTPA uptake curves in reactive tissue and tumor were investigated to assess the utility of contrast enhanced (CE)-dynamic MRI to distinguish reactive changes from residual tumor in a canine model. Cerebral thermal necrosis was induced using a 980 nm laser in 11 dogs with intracerebral transmissible venereal tumors (TVTs). A fast spin-echo T1-weighted imaging sequence was used for CE-dynamic MRI. Gd-DTPA uptake data were acquired with 10-second temporal resolution and for untreated TVTs for reactive tissue using a sigmoidal-exponential model. Characteristic gadolinium uptake curves were measured and characterized for reactive brain tissue, and untreated and treated TVTs. Both early and delayed dynamic responses were significantly different in reactive brain tissue compared with TVT. Reactive thermal changes in otherwise normal brain tissue can be distinguished from residual tumor after cerebral thermal therapy using CE-dynamic MRI.

  13. Anterior Gray Matter Pituicytic Heterotopia with Monomorphic Anterior Pituitary Cells: A Variant of Nonsecretory Pituitary Adenoma Neuronal Choristoma? Report of a Rare Case and Review of the Literature. (United States)

    Yowtak, June; Sharma, Suash; Forseen, Scott E; Alleyne, Cargill H


    Mixed tumors of adenomatous and neuronal cells in the sellar region are an uncommon finding. The origins of these heterogeneous tumors are unknown, and management remains unsettled. We report a very rare case of anterior gray matter pituicytic heterotopia with monomorphic anterior pituitary cells that likely represents a variant of nonsecreting pituitary adenoma neuronal choristoma (PANCH) with no ganglion cells. We also review the current literature for the various clinical presentations of PANCH. A 49-year-old female complaining of headache, blurred vision, and hair loss was found to have a nonsecretory sellar mass with compression of the optic chiasm on magnetic resonance imaging (MRI). The mass was excised via a transsphenoidal procedure. Histological analysis of tissue sections revealed heterotopic gray matter with reactive gliosis without ganglion cells or Herring bodies. Only 1 smear exhibited characteristics of a pituitary adenoma. The overall findings were most consistent with a variant of PANCH. At a postoperative follow-up of 4.5 years, there was resolution of visual symptoms, and the residual sellar mass was stable on MRI. Neuronal choristoma is hypothesized to originate from embryonal pituitary or hypothalamus, or by differentiation from pituitary adenoma cells. Surgery is the cornerstone of management, and the clinical course appears to be similar to that of nonfunctioning pituitary adenoma in reported cases. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Convection-enhanced delivery of a hydrophilic nitrosourea ameliorates deficits and suppresses tumor growth in experimental spinal cord glioma models. (United States)

    Ogita, Shogo; Endo, Toshiki; Sugiyama, Shinichiro; Saito, Ryuta; Inoue, Tomoo; Sumiyoshi, Akira; Nonaka, Hiroi; Kawashima, Ryuta; Sonoda, Yukihiko; Tominaga, Teiji


    Convection-enhanced delivery (CED) is a technique allowing local infusion of therapeutic agents into the central nervous system, circumventing the blood-brain or spinal cord barrier. To evaluate the utility of nimustine hydrochloride (ACNU) CED in controlling tumor progression in an experimental spinal cord glioma model. Toxicity studies were performed in 42 rats following the administration of 4 μl of ACNU CED into the mid-thoracic spinal cord at concentrations ranging from 0.1 to 10 mg/ml. Behavioral analyses and histological evaluations were performed to assess ACNU toxicity in the spinal cord. A survival study was performed in 32 rats following the implantation of 9 L cells into the T8 spinal cord. Seven days after the implantation, rats were assigned to four groups: ACNU CED (0.25 mg/ml; n = 8); ACNU intravenous (i.v.) (0.4 mg; n = 8); saline CED (n = 8); saline i.v. (n = 8). Hind limb movements were evaluated daily in all rats for 21 days. Tumor sizes were measured histologically. The maximum tolerated ACNU concentration was 0.25 mg/ml. Preservation of hind limb motor function and tumor growth suppression was observed in the ACNU CED (0.25 mg/ml) and ACNU i.v. groups. Antitumor effects were more prominent in the ACNU CED group especially in behavioral analyses (P < 0.05; log-rank test). ACNU CED had efficacy in controlling tumor growth and preserving neurological function in an experimental spinal cord tumor model. ACNU CED can be a viable treatment option for spinal cord high-grade glioma.

  15. Pituitary adenomas: historical perspective, surgical management and future directions (United States)

    Theodros, Debebe; Patel, Mira; Ruzevick, Jacob; Lim, Michael; Bettegowda, Chetan


    Pituitary adenomas are among the most common central nervous system tumors. They represent a diverse group of neoplasms that may or may not secrete hormones based on their cell of origin. Epidemiologic studies have documented the incidence of pituitary adenomas within the general population to be as high as 16.7%. A growing body of work has helped to elucidate the pathogenesis of these tumors. Each subtype has been shown to demonstrate unique cellular changes potentially leading to tumorigenesis. Surgical advancements over several decades have included microsurgery and the employment of the endoscope for surgical resection. These advancements increase the likelihood of gross-total resection and have resulted in decreased patient morbidity. PMID:26497533

  16. Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary. (United States)

    Mathioudakis, Nestoras; Sundaresh, Ram; Larsen, Alexandra; Ruff, William; Schiller, Jennifer; Guerrero-Cázares, Hugo; Burger, Peter; Salvatori, Roberto; Quiñones-Hinojosa, Alfredo


    Recent studies suggest that adult pituitary stem cells may play a role in pituitary tumorigenesis. We sought to explore whether the Glial cell-line derived neurotrophic factor receptor alpha 2 (GFRα2), a recently described pituitary stem/progenitor marker, might be differentially expressed in pituitary adenomas versus normal pituitary. The expression of GFRα2 and other members of the GFR receptor family (GFRα1, α3, α4) were analyzed using RT-PCR, western blot, and immunohistochemistry in 39 pituitary adenomas, 14 normal pituitary glands obtained at autopsy, and cDNA from 3 normal pituitaries obtained commercially. GFRα2 mRNA was ~2.6 fold under-expressed in functioning adenomas (p adenomas (NFAs) (p pituitary. Among NFAs, GFRα2 was significantly over-expressed (~5-fold) in the gonadotropinoma subtype only (p adenomas by IHC and western blot. In normal pituitary, GFRα2 was localized in Rathke's remnant, the putative pituitary stem cell niche, and in corticotropes. Our results suggest that the pituitary stem cell marker GFRα2 is under-expressed in functioning adenomas and over-expressed in NFAs, specifically gonadotropinomas. Further studies are required to elucidate whether over-expression of GFRα2 in gonadotropinomas might play a role in pituitary tumorigenesis.

  17. Experimental radioimmunotherapy of a xenografted human colonic tumor (GW-39) producing carcinoembryonic antigen

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    Goldenberg, D.M.; Gaffar, S.A.; Bennett, S.J.; Beach, J.L.


    Experiments were undertaken to evaluate the antitumor effects of 131I-labeled goat antibody immunoglobulin G prepared against carcinoembryonic antigen in hamsters bearing the carcinoembryonic antigen-producing GW-39 human colonic carcinoma. At a single injection of 1 mCi 131I and higher, a marked growth inhibition of GW-39 tumors, as well as a considerable increase in the survival time of the tumor-bearing hamsters, could be achieved. At a dose of 1 mCi, the radioactive affinity-purified antibody appeared to be superior to radioactive normal goat immunoglobulin G in influencing tumor growth and survival time, but no significant difference could be seen at the higher dose of 2 mCi given. Radiobiological calculations indicated that the tumors received, at up to 20 days after therapy, 1325 rads for the specific antibody and only 411 rads for the normal immunoglobulin G preparation. These findings encourage the further evaluation of antibodies to tumor markers for isotopic cancer therapy.

  18. Modelo experimental de tumor na cavidade oral de ratos com carcinossarcoma de Walker 256 Experimental model of Walker 256 carcinosarcoma developed in the oral cavity of rats

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    Ana Paula Negreiros Nunes Alves


    Full Text Available OBJETIVO: Estabelecer um modelo experimental de desenvolvimento tumoral na cavidade oral de ratos, permitindo, assim, o estudo da osteólise induzida pelo tumor nos ossos do complexo maxilomandibular como também nas estruturas dentais, através da caracterização histomorfológica da reabsorção óssea e dentária. MÉTODOS: Uma suspensão de células tumorais (0,1mL do Carcinossarcoma de Walker 256, na concentração de 10(6 células/mL foi implantado na cavidade alveolar de ratos previamente aberta por exodontia. Os animais foram observados durante 12 (doze dias consecutivos para determinação da curva de peso corpóreo, sendo posteriormente sacrificados e as mandíbulas removidas para exames radiográfico e histológico. RESULTADOS: No exame radiográfico foi verificada área lítica, sem evidência de reparo, na região dos alvéolos. No exame microscópico foi identificada infiltração óssea, periférica e central, de pequenas células hipercromáticas e pleomórficas, com leve infiltrado inflamatório mononuclear associado e áreas de necrose. O índice de pega foi de 100%. CONCLUSÃO: O modelo animal de invasão óssea, do tumor de Walker na cavidade oral, possibilita a avaliação in vivo de drogas antitumorais e esquemas terapêuticos no tratamento do câncer bucal.PURPOSE: To estabilish an experimental model of tumor development in the oral cavity of rats, that would enable to study the tumor-induced autolysis in the maxillomandibular bone complex as well as of the dental structures, through histomorphological characterization of bone and dental resorption. METHODS: Walker 256 carcinossarcoma cell suspension (0,1 mL containing 10(6 cell/mL was implanted in the alveoli of first and second molars. The animals were observed during twelve consecutive days and the body weigth were determined. Later, the animals were sacrificed and their mandibles removed to radiographic and hystologic analysis. RESULTS: The radiographic image

  19. Mechanisms of tumor necrosis in photodynamic therapy with a chlorine photosensitizer: experimental studies (United States)

    Privalov, Valeriy A.; Lappa, Alexander V.; Bigbov, Elmir N.


    A photodynamic therapy experiment on 118 inbred white mice with transplanted Ehrlich's tumor (mouse mammary gland adenocarcinoma) is performed to reveal mechanisms of necrosis formation. In 7-10 days the tumor of 1-1.5 cm diameter is formed under skin at the injection point, and PDT procedure is applied. There were used a chlorine type photosensitizer RadachlorineTM and 662 nm wavelength diode laser. The drug is injected by intravenously at the dose of 40 mg/kg; the irradiation is executed in 2-2.5 hours at the surface dose of about 200 J/cm2. Each of the mice had a photochemical reaction in form of destructive changes at the irradiation region with subsequent development of dry coagulation necrosis. After rejection of the necrosis there occurred epithelization of defect tissues in a tumor place. Histological investigations were conducted in different follow-up periods, in 5 and 30 min, 1, 3, 6, and 12 hours, 1, 3, 7 and 28 days after irradiation. They included optical microscopy, immune marker analysis, morphometry with measurements of volume density of epithelium, tumor stroma and necroses, vascular bed. The investigations showed that an important role in damaging mechanisms of photodynamic action belongs to hypoxic injuries of tumor mediated by micro vascular disorders and blood circulatory disturbances. The injuries are formed in a few stages: microcirculation angiospasm causing vessel paresis, irreversible stases in capillaries, diapedetic hemorrhages, thromboses, and thrombovasculitis. It is marked mucoid swelling and fibrinoid necrosis of vascular tissue. Progressive vasculitises result in total vessel obliteration and tumor necrosis.

  20. Blocking Tumor Necrosis Factor α Enhances CD8 T-cell-Dependent Immunity in Experimental Melanoma. (United States)

    Bertrand, Florie; Rochotte, Julia; Colacios, Céline; Montfort, Anne; Tilkin-Mariamé, Anne-Françoise; Touriol, Christian; Rochaix, Philippe; Lajoie-Mazenc, Isabelle; Andrieu-Abadie, Nathalie; Levade, Thierry; Benoist, Hervé; Ségui, Bruno


    TNF plays a dual, still enigmatic role in melanoma, either acting as a cytotoxic cytokine or favoring a tumorigenic inflammatory microenvironment. Herein, the tumor growth of melanoma cell lines expressing major histocompatibility complex class I molecules at high levels (MHC-I(high)) was dramatically impaired in TNF-deficient mice, and this was associated with enhanced tumor-infiltrating CD8(+) T lymphocytes. Immunodepletion of CD8 T cells fully restored melanoma growth in TNF(-/-) mice. Systemic administration of Etanercept inhibited MHC-I(high) melanoma growth in immunocompetent but not in immunodeficient (IFNγ(-/-), nude, or CD8(-/-)) mice. MHC-I(high) melanoma growth was also reduced in mice lacking TNF-R1, but not TNF-R2. TNF(-/-) and TNF-R1(-/-) mice as well as Etanercept-treated WT mice displayed enhanced intratumor content of high endothelial venules surrounded by high CD8(+) T-cell density. Adoptive transfer of activated TNF-R1-deficient or -proficient CD8(+) T cells in CD8-deficient mice bearing B16K1 tumors demonstrated that TNF-R1 deficiency facilitates the accumulation of live CD8(+) T cells into the tumors. Moreover, in vitro experiments indicated that TNF triggered activated CD8(+) T cell death in a TNF-R1-dependent manner, likely limiting the accumulation of tumor-infiltrating CD8(+) T cells in TNF/TNF-R1-proficient animals. Collectively, our observations indicate that TNF-R1-dependent TNF signaling impairs tumor-infiltrating CD8(+) T-cell accumulation and may serve as a putative target to favor CD8(+) T-cell-dependent immune response in melanoma. ©2015 American Association for Cancer Research.


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    Gurudatta M, Deshmukh YA, Naikwadi A A


    Full Text Available Objective: To evaluate the anticancer effect of Carica papaya in DMBA induced mammary tumors in rats. Methods: Wistar rats were divided in to five groups (n=6, Group-I (Normal control administered vehicle olive oil, Group-II, Group-III ,Group-IV and V induced mammary tumors by administering single dose of DMBA (7,12 Dimethyl benz(Aanthracene orally 65 mg/kg. Group-III was administered aqueous leaf extract of Carica papaya (ALQECP in a dose of 200 mg/kg body wt for a period of 3 months, group-IV has given ALQECP 200 mg/kg body wt for a period of 21 days post 3 months of tumor induction, group-V rats were administered a small dose of Carica papaya extract intra tumor locally in the region of tumor. Results: Values of CA15-3 were increased in group-II rats (tumor control significantly, whereas in group-III (prevention group the levels of CA15-3 were found to be reduced substantially and the P value < 0.001. Similarly, CA-15-3 levels were reduced significantly in group-IV (treatment groupand P<0.005. The levels of LDH were seen to be increased in group-II, where as in group-III LDH levels were decreased and P<0.001.similarly group-IV LDH levels also reduced significantly but not to the level of group-III. Conclusion: Among the various markers for the detection of cancer antigen-15(CA15-3 and lactate dehydrogenase (LDH are important biochemical parameters that give a clear understanding of the progression and proliferation of cancer cells. In this study it was found that there is increase in the levels of markers such as CA15-3 and LDH and also the tumor volume in tumor control, these marker levels were decreased by the administration of aqueous leaf extract of Carica papaya in a dose of 200 mg/kg body wt. ALQECP not only prevented the progression of cancer growth but also has significant effect in reducing the both CA15-3 and LDH levels in treatment group.

  2. Aggressive Pituitary Adenomas: The Dark Side of the Moon. (United States)

    Priola, Stefano M; Esposito, Felice; Cannavò, Salvatore; Conti, Alfredo; Abbritti, Rosaria V; Barresi, Valeria; Baldari, Sergio; Ferraù, Francesco; Germanò, Antonino; Tomasello, Francesco; Angileri, Filippo F


    Although pituitary adenomas are considered benign lesions, a small group may show clinically aggressive behavior, sometimes independently from the classic markers of aggressiveness, including the Ki67 labeling index or p53 expression. We selected 7 patients harboring a pituitary tumor with clinical features of aggressiveness. Patients underwent a full preoperative and postoperative endocrinologic and neuroradiologic workup. Two were nonfunctioning, 2 prolactin-secreting, 2 adrenocorticotrophic hormone-secreting, and 1 a growth hormone-secreting adenoma. The 7 patients underwent a total of 17 surgical procedures. At the first surgical procedure, gross total removal was achieved in none of the patients, whereas subtotal removal (>90% of tumor removed) was achieved in 4/7 cases and partial removal (3%; this information was not available for 1 patient. Postoperatively, all patients underwent radiation therapy. Three patients received chemotherapy with temozolomide. Three patients underwent peptide receptor radionuclide therapy. To date, 1 patient has died of tumor progression, and 2 patients are in a poor general condition. The remaining 4 patients are in a fair/good condition, without any major complaints. The mean follow-up is 43.42 months. Aggressive pituitary adenomas represent a specific and still underestimated entity, often diagnosed late. Clinical and neuroradiologic rapid progression is often the only marker of aggressiveness. Surgical debulking remains the first therapeutic option. Multidisciplinary management is mandatory to offer these patients targeted therapeutic options. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Insulin-like growth factor-I gene therapy reverses morphologic changes and reduces hyperprolactinemia in experimental rat prolactinomas

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    Bracamonte Maria I


    Full Text Available Abstract Background The implementation of gene therapy for the treatment of pituitary tumors emerges as a promising complement to surgery and may have distinct advantages over radiotherapy for this type of tumors. Up to now, suicide gene therapy has been the main experimental approach explored to treat experimental pituitary tumors. In the present study we assessed the effectiveness of insulin-like growth factor I (IGF-I gene therapy for the treatment of estrogen-induced prolactinomas in rats. Results Female Sprague Dawley rats were subcutaneously implanted with silastic capsules filled with 17-β estradiol (E2 in order to induce pituitary prolactinomas. Blood samples were taken at regular intervals in order to measure serum prolactin (PRL. As expected, serum PRL increased progressively and 23 days after implanting the E2 capsules (Experimental day 0, circulating PRL had undergone a 3–4 fold increase. On Experimental day 0 part of the E2-implanted animals received a bilateral intrapituitary injection of either an adenoviral vector expressing the gene for rat IGF-I (RAd-IGFI, or a vector (RAd-GFP expressing the gene for green fluorescent protein (GFP. Seven days post vector injection all animals were sacrificed and their pituitaries morphometrically analyzed to evaluate changes in the lactotroph population. RAd-IGFI but not RAd-GFP, induced a significant fall in serum PRL. Furthermore, RAd-IGFI but not RAd-GFP significantly reversed the increase in lactotroph size (CS and volume density (VD induced by E2 treatment. Conclusion We conclude that IGF-I gene therapy constitutes a potentially useful intervention for the treatment of prolactinomas and that bioactive peptide gene delivery may open novel therapeutic avenues for the treatment of pituitary tumors.

  4. Expression of functional KISS1 and KISS1R system is altered in human pituitary adenomas: evidence for apoptotic action of kisspeptin-10. (United States)

    Martínez-Fuentes, Antonio J; Molina, Marcelo; Vázquez-Martínez, Rafael; Gahete, Manuel D; Jiménez-Reina, Luis; Moreno-Fernández, Jesús; Benito-López, Pedro; Quintero, Ana; de la Riva, Andrés; Diéguez, Carlos; Soto, Alfonso; Leal-Cerro, Alfonso; Resmini, Eugenia; Webb, Susan M; Zatelli, Maria C; degli Uberti, Ettore C; Malagón, María M; Luque, Raul M; Castaño, Justo P


    KISS1 was originally identified as a metastasis-suppressor gene able to inhibit tumor progression. KISS1 gene products, the kisspeptins, bind to a G-protein-coupled receptor (KISS1R, formerly GPR54), which is highly expressed in placenta, pituitary, and pancreas, whereas KISS1 mRNA is mainly expressed in placenta, hypothalamus, striatum, and pituitary. KISS1/KISS1R pituitary expression profile, coupled to their anti-tumoral capacities, led us to hypothesize that this system may be involved in the biology of pituitary tumors. To explore this notion, expression levels of KISS1R and KISS1 were evaluated in normal and adenomatous pituitaries. Additionally, functionality of this system was assessed by treating dispersed pituitary adenoma cells in primary culture with kisspeptin-10 and evaluating intracellular calcium kinetics and apoptotic rate. Both KISS1 and KISS1R were expressed in normal pituitary, whereas this simultaneous expression was frequently lost in pituitary tumors, where diverse patterns of KISS1/KISS1R expression were observed that differed among distinct types of pituitary adenomas. Measurement of calcium kinetics revealed that kisspeptin-10 elicits a remarkable increase in [Ca(2+)](i) in individual cells from four out of the five GH-producing adenomas studied, whereas cells derived from non-functioning pituitary adenomas (NFPA, n=45) did not respond. In contrast, kisspeptin-10 treatment increased the apoptotic rate in cells derived from both GH-producing and NFPA. These results provide primary evidence that KISS1 and KISS1R expression can be differentially lost in pituitary tumor subtypes, where this system can exert functional, proapoptotic actions, and thereby offer novel insights to investigate the biology and therapeutic options to treat these tumors.

  5. Primary pituitary tubercular abscess mimicking as pituitary adenoma

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    Rakesh Ranjan


    Full Text Available Tubercular abscess of the pituitary fossa is rare and may lead to diagnostic uncertainty in a patient with absence of tuberculosis elsewhere in the body. We present a rare case report of a young lady who presented with sellar and suprasellar cystic mass. She was diagnosed as a case of pituitary macroadenoma and was intraoperatively found to harbor pus in the lesion. She did not have any symptoms of infection. The case underlines the importance of considering such a possibility in the differential diagnosis of cystic sellar lesions and further diagnostic tests should be done for confirmation and treatment of this rare and potential life threatening illness.

  6. 99mTc(V)-DMSA. A useful radio isotopic material for the diagnosis of pituitary adenoma

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    Suzuki, Shinichi; Yamamura, Koji; Chang, Chia-Cheng; Kojima, Yasuhiro; Yamamoto, Isao; Ikegami, Tadashi [Yokohama City Univ., Kanagawa (Japan). School of Medicine


    We compared images of pituitary adenoma, parasellar tumors, and non-pituitary adenoma using the tumor-seeking agent technetium-99m-labeled pentavalent dimercaptosuccinic acid (99mTc(V)-DMSA) and evaluated the relationship between 99mTc(V)-DMSA uptake and pituitary hormone level. Fifteen patients with pituitary adenoma were studied: 3 non-functioning adenoma, 6 prolactinoma, 4 GH secreting adenoma, and 2 ACTH secreting adenoma. As a control group, we studied 6 patients without adenoma who had undergone a pathological examination. Planar and SPECT images were obtained 2-hours after intravenous injection of approximately 740 MBq 99mTc(V)-DMSA. Uptake ratios between normal background and tumor lesion were calculated. Three non-functioning adenoma (100%), five prolactinoma (83%), three GH secreting adenoma (75%) and no ACTH secreting adenoma (0%) significantly concentrated 99mTc(V)-DMSA. One of the non-adenomatous tumors, a Rathke's cleft cyst concentrated 99mTc(V)-DMSA in the pituitary while the others did not. The 99mTc(V)-DMSA scintigraphy showed an overall sensitivity of 73% (11/15) in detecting pituitary adenomas. Uptake ratios were higher in hormone-secreting adenoma than non-secreting adenoma. We were able to detect residual tumors and distinguish pituitary adenoma from surgical non-tumoral lesion with 99mTc(V)-DMSA. These results suggest that 99mTc(V)-DMSA imaging is useful in detecting pituitary adenoma and noninvasively differentiating tumor types in parasellar lesion. (author)

  7. Induced Pluripotent Stem Cells Reduce Progression of Experimental Chronic Kidney Disease but Develop Wilms’ Tumors

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    Heloisa Cristina Caldas


    Full Text Available The therapeutic effect of induced pluripotent stem cells (iPSs on the progression of chronic kidney disease (CKD has not yet been demonstrated. In this study, we sought to assess whether treatment with iPSs retards progression of CKD when compared with bone marrow mesenchymal stem cells (BMSCs. Untreated 5/6 nephrectomized rats were compared with CKD animals receiving BMSCs or iPSs. Renal function, histology, immunohistochemistry, and gene expression were studied. Implanted iPSs were tracked by the SRY gene expression analysis. Both treatments minimized elevation in serum creatinine, significantly improved clearance, and slowed down progression of disease. The proteinuria was reduced only in the iPS group. Both treatments reduced glomerulosclerosis, iPSs decreased macrophage infiltration, and TGF-β was reduced in kidneys from the BMSC group. Both types of treatments increased VEGF gene expression, TGF-β was upregulated only in the iPS group, and IL-10 had low expression in both groups. The SRY gene was found in 5/8 rats treated with iPSs. These 5 animals presented tumors with histology and cells highly staining positive for PCNA and Wilms’ tumor protein antibody characteristics of Wilms’ tumor. These results suggest that iPSs may be efficient to retard progression of CKD but carry the risk of Wilms’ tumor development.

  8. Experimental study of radiopharmaceuticals based on technetium-99m labeled derivative of glucose for tumor diagnosis (United States)

    Zeltchan, R.; Medvedeva, A.; Sinilkin, I.; Bragina, O.; Chernov, V.; Stasyuk, E.; Rogov, A.; Il'ina, E.; Larionova, L.; Skuridin, V.; Dergilev, A.


    Purpose: to study the potential utility of 1-thio-D-glucose labeled with 99mTc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of 99mTc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with 99mTc was added to the vials with 3 million cells and incubated for 30 minutes at room temperature. After centrifugation of the vials with cells, the supernatant was removed. Radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B 1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25MBq of 99mTc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 minutes. Results: when measuring the radioactivity of normal and malignant cells after incubation with 99mTc-1-thio-D- glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3±0.15MBq and 1.07±0.6MBq, respectively. All examined animals had increased accumulation of 99mTc-1-thio- D-glucose at the tumor site. The accumulation of 99mTc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that 99mTc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of 99mTc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

  9. Thyrotropin-producing pituitary adenoma simultaneously existing with Graves' disease: a case report. (United States)

    Arai, Nobuhiko; Inaba, Makoto; Ichijyo, Takamasa; Kagami, Hiroshi; Mine, Yutaka


    Thyrotropin-producing pituitary tumor is relatively rare. In particular, concurrent cases associated with Graves' disease are extremely rare and only nine cases have been reported so far. We describe a case of a thyrotropin-producing pituitary adenoma concomitant with Graves' disease, which was successfully treated. A 40-year-old Japanese woman presented with mild signs of hyperthyroidism. She had positive anti-thyroid-stimulating hormone receptor antibody, anti-thyroglobulin antibody, and anti-thyroid peroxidase antibody. Her levels of serum thyroid-stimulating hormone, which ranged from low to normal in the presence of high levels of serum free thyroid hormones, were considered to be close to a state of syndrome of inappropriate secretion of thyroid-stimulating hormone. Magnetic resonance imaging showed a macropituitary tumor. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease was suspected. Initial therapy included anti-thyroid medication, which was immediately discontinued due to worsening symptoms. Subsequently, surgical therapy for the pituitary tumor was conducted, and her levels of free thyroid hormones, including the thyroid-stimulating hormone, became normal. On postoperative examination, her anti-thyroid-stimulating hormone receptor antibody levels decreased, and the anti-thyroglobulin antibody became negative. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease is rarely reported. The diagnosis of this condition is complicated, and the appropriate treatment strategy has not been clearly established. This case suggests that physicians should consider the coexistence of thyrotropin-producing pituitary adenoma with Graves' disease in cases in which thyroid-stimulating hormone values range from low to normal in the presence of thyrotoxicosis, and the surgical treatment of thyrotropin-producing pituitary adenoma could be the first-line therapy in patients with both thyrotropin-producing pituitary adenoma

  10. Dendritic Cells in the Context of Human Tumors: Biology and Experimental Tools. (United States)

    Volovitz, Ilan; Melzer, Susanne; Amar, Sarah; Bocsi, József; Bloch, Merav; Efroni, Sol; Ram, Zvi; Tárnok, Attila


    Dendritic cells (DC) are the most potent and versatile antigen-presenting cells (APC) in the immune system. DC have an exceptional ability to comprehend the immune context of a captured antigen based on molecular signals identified from its vicinity. The analyzed information is then conveyed to other immune effector cells. Such capability enables DC to play a pivotal role in mediating either an immunogenic response or immune tolerance towards an acquired antigen. This review summarizes current knowledge on DC in the context of human tumors. It covers the basics of human DC biology, elaborating on the different markers, morphology and function of the different subsets of human DC. Human blood-borne DC are comprised of at least three subsets consisting of one plasmacytoid DC (pDC) and two to three myeloid DC (mDC) subsets. Some tissues have unique DC. Each subset has a different phenotype and function and may induce pro-tumoral or anti-tumoral effects. The review also discusses two methods fundamental to the research of DC on the single-cell level: multicolor flow cytometry (FCM) and image-based cytometry (IC). These methods, along with new genomics and proteomics tools, can provide high-resolution information on specific DC subsets and on immune and tumor cells with which they interact. The different layers of collected biological data may then be integrated using Immune-Cytomics modeling approaches. Such novel integrated approaches may help unravel the complex network of cellular interactions that DC carry out within tumors, and may help harness this complex immunological information into the development of more effective treatments for cancer.

  11. Different imaging characteristics of concurrent pituitary adenomas in a patient with Cushing's disease. (United States)

    Mehta, Gautam U; Montgomery, Blake K; Raghavan, Pooja; Sharma, Susmeeta; Nieman, Lynnette K; Patronas, Nicholas; Oldfield, Edward H; Chittiboina, Prashant


    We report a patient with Cushing's disease (CD) and two pituitary adenomas that demonstrated different imaging characteristics and therefore suggest an alternative imaging strategy for these patients. A 42-year-old woman presented with signs and symptoms of CD. Biochemical evaluation confirmed hypercortisolemia and suggested CD. On pituitary MRI with spoiled gradient recalled acquisition in the steady-state and T1-weighted spin echo protocols, a 5mm hypoenhancing region typical for a pituitary adenoma was identified on the left. However, after surgical resection the patient remained hypercortisolemic and pathology revealed a non-functional adenoma. At early repeat surgical exploration a 10mm adenoma was found in the right side of the gland. Postoperatively the patient became hypocortisolemic and pathology demonstrated an adrenocorticotropic hormone (ACTH)-staining adenoma. On review of the initial MRI this tumor corresponded to a region of contrast retention best visualized on delayed fluid attenuated inversion recovery (FLAIR) imaging. While the incidentaloma in this case demonstrated classical imaging characteristics of a pituitary adenoma the larger ACTH-secreting tumor was best appreciated by contrast retention. This suggests a role for delayed postcontrast FLAIR imaging in the preoperative evaluation of CD. ACTH-secreting tumors causing CD cause significant morbidity. Due to their small size, a pituitary adenoma is frequently not identified on imaging despite endocrinologic testing suggesting CD. Regardless of improvements in MRI, many tumors are only identified at surgical exploration. Published by Elsevier Ltd.

  12. Tumor Microenvironment In Experimental Models Of Human Cancer: Morphological Investigational Approaches

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    Lucia Minoli


    Discussion and conclusions. Due to the microenvironmental heterogeneity which influence tumor development and biological behavior, a sole quantification is unreliable for characterizing the TME. Considering that, morphological techniques proved to be a valuable approach, allowing the evaluation of the spatial distribution and mutual interaction between the different elements. Additional studies are needed for further investigate the biological significance of spatial distribution of the components of the TME.

  13. Endoscopic endonasal trans-sphenoid surgery of pituitary adenoma

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    Y R Yadav


    Full Text Available Endoscopic endonasal trans-sphenoid surgery (EETS is increasingly used for pituitary lesions. Pre-operative CT and MRI scans and peroperative endoscopic visualization can provide useful anatomical information. EETS is indicated in sellar, suprasellar, intraventricular, retro-infundibular, and invasive tumors. Recurrent and residual lesions, pituitary apoplexy and empty sella syndrome can be managed by EETS. Modern neuronavigation techniques, ultrasonic aspirators, ultrasonic bone curette can add to the safety. The binostril approach provides a wider working area. High definition camera is much superior to three-chip camera. Most of the recent reports favor EETS in terms of safety, quality of life and tumor resection, hospital stay, better endocrinological, and visual outcome as compared to the microscopic technique. Nasal symptoms, blood loss, operating time are less in EETS. Various naso-septal flaps and other techniques of CSF leak repair could help reduce complications. Complications can be further reduced after achieving the learning curve, good understanding of limitations with proper patient selection. Use of neuronavigation, proper post-operative care of endocrine function, establishing pituitary center of excellence and more focused residency and endoscopic fellowship training could improve results. The faster and safe transition from microscopic to EETS can be done by the team concept of neurosurgeon/otolaryngologist, attending hands on cadaveric dissection, practice on models, and observation of live surgeries. Conversion to a microscopic or endoscopic-assisted approach may be required in selected patients. Multi-modality treatment could be required in giant and invasive tumors. EETS appears to be a better surgical option in most pituitary adenoma.

  14. Endoscopic endonasal trans-sphenoid surgery of pituitary adenoma. (United States)

    Yadav, Yr; Sachdev, S; Parihar, V; Namdev, H; Bhatele, Pr


    Endoscopic endonasal trans-sphenoid surgery (EETS) is increasingly used for pituitary lesions. Pre-operative CT and MRI scans and peroperative endoscopic visualization can provide useful anatomical information. EETS is indicated in sellar, suprasellar, intraventricular, retro-infundibular, and invasive tumors. Recurrent and residual lesions, pituitary apoplexy and empty sella syndrome can be managed by EETS. Modern neuronavigation techniques, ultrasonic aspirators, ultrasonic bone curette can add to the safety. The binostril approach provides a wider working area. High definition camera is much superior to three-chip camera. Most of the recent reports favor EETS in terms of safety, quality of life and tumor resection, hospital stay, better endocrinological, and visual outcome as compared to the microscopic technique. Nasal symptoms, blood loss, operating time are less in EETS. Various naso-septal flaps and other techniques of CSF leak repair could help reduce complications. Complications can be further reduced after achieving the learning curve, good understanding of limitations with proper patient selection. Use of neuronavigation, proper post-operative care of endocrine function, establishing pituitary center of excellence and more focused residency and endoscopic fellowship training could improve results. The faster and safe transition from microscopic to EETS can be done by the team concept of neurosurgeon/otolaryngologist, attending hands on cadaveric dissection, practice on models, and observation of live surgeries. Conversion to a microscopic or endoscopic-assisted approach may be required in selected patients. Multi-modality treatment could be required in giant and invasive tumors. EETS appears to be a better surgical option in most pituitary adenoma.

  15. Pituitary aspergillosis abscess in an immunocompetent black ...

    African Journals Online (AJOL)

    Clinical Presentation An immunocompetent 26-year-old female patient showed up with amenorrhea-galactorrhea syndrome with infertility for several years. The CT Findings and hormonal studies strongly suggested pituitary adenoma or pituitary aspergillosis. Treatment The pituitary lesion was excised by a transsphenoidal ...

  16. Sellar tumors; Tumoren der Sellaregion

    Energy Technology Data Exchange (ETDEWEB)

    Weber, M.A.; Essig, M. [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Abt. Radiologie; Zoubaa, S. [GSF - Forschungszentrum fuer Gesundheit und Umwelt, Neuherberg, Muenchen (Germany). Abt. Neuropathologie; Politi, M.; Grunwald, I. [Universitaetsklinikum Saarland, Homburg (Germany). Klinik fuer Diagnostische und Interventionelle Neuroradiologie


    Because of the complex anatomy, examination of the sella turcica and hypophysis needs a dedicated MR sequence protocol. Not every sellar lesion is a pituitary adenoma. Thus, this review article summarizes the most frequently encountered intra-, supra-, and parasellar tumors and lesions. Differential diagnoses comprise besides adenoma among others craniopharyngioma, meningioma, glioma, germinoma, hamartoma, aneurysm, trigeminal schwannoma, pituitary carcinoma, chordoma, metastasis, infection, and empty sella. Characteristic imaging findings are presented and correlated to micro- and macro-pathology. (orig.)

  17. Differential effect of protein-bound polysaccharide (PSK) on survival of experimental murine tumors. (United States)

    Algarra, I; Collado, A; Garcia Lora, A; Garrido, F


    The effect of protein-bound polysaccharide (PSK) on the survival of BALB/c and C57BL/6 mice after intravenous injections of syngeneic murine sarcomas (GR9.B9 and Meth-A), LSTRA lymphoma and B16 melanoma cells was studied. Pretreatment of mice with PSK significantly increased survival after the injection of either type of sarcoma cells, although the effect was attenuated when high numbers of cells were injected. Survival was not modified significantly in LSTRA lymphoma or B16 melanoma. Mice pretreated with anti-asialo GMI serum showed significantly decreased survival from all tumors in comparison with untreated mice injected with tumors, regardless of cell dose used. We observed an inverse correlation between H-2 antigen expression and in vitro NK sensitivity of tumor cells from all lines except B16 melanoma cells. These results clearly suggest that pretreatment of mice with PSK prolongs survival and inhibits metastasis formation in mice injected with sarcoma cells, being this effect highly selective, since survival was not improved in mice injected with LSTRA lymphoma or B16 melanoma.

  18. The Characteristics of Incidental Pituitary Microadenomas in 120 Korean Forensic Autopsy Cases (United States)

    Kim, Jang-Hee; Seo, Jung-Seok; Lee, Bong-Woo; Lee, Sang-Young; Jeon, Seok-Hoon


    To investigate the characteristics of incidental pituitary microadenomas, we examined 120 pituitary glands from Korean forensic autopsy cases, from which eight tumors were identified (incidence 6.7%). The average age of the affected subjects was 50 yr (range: 33-96 yr) with a female predominance. The maximum diameters of the tumors ranged from 0.4 to 5.4 mm (mean: 2.8 mm). Immunohistochemical analysis of pituitary hormones revealed three growth hormone-secreting adenomas, one prolactin-producing adenoma, one gonadotropin-producing adenoma, one plurihormonal adenoma, and two null cell adenomas. MIB-1 staining for Ki-67 antigen showed no positive expression. The microvessel density (MVD) of the pituitary microadenomas ranged from 2.3 to 11.6% (mean: 5.3%) and was significantly lower than that of nonneoplastic pituitary glands (11.9-20.1%, mean: 14.8%). Our study provides reference data on incidental pituitary microadenomas in the Korean population. PMID:17923757

  19. Medical Classic. The functions of the pituitary body: Harvey Cushing. (United States)

    Cushing, H


    It may be said that the pituitary body is a double organ in the sense that the secretion of its anterior and solidly epithelial portion discharges into the blood sinuses which traverse this part of the gland; whereas the hyaline substance, apparently the product of secretion from the epithelial investment of the posterior lobe, enters the cerebrospinal space by way of channels in the pars nervosa. Though possessing a physiologically active principle, as shown by the results of injections, the secretion of the posterior lobe does not seem to be so vitally essential to physiological equilibrium as that of the anterior lobe, the total removal of which leads to death with a peculiar train of symptoms which set in at an early date in the adult and after a longer interval in younger animals. Alterations in the gland, which often ultimately assume the character of a malignant growth (adenoma) but which presumably, at least in their earlier stages, represent an hypertrophy, are common in clinical conditions of overgrowth (akromegaly and gigantism), and certain feeding experiments lend support to the view that these clinical states represent the consequences of hyperactivity of the pars anterior. Partial removals of the anterior lobe usually lead to obvious disturbances of metabolism accompanied oftentimes by adiposity and in the young by a persistence of infantilism, or in adults by a tendency top lose the secondary sexual characteristics already acquired. These experimental conditions are comparable to those which have been recognized clinically as accompaniments likewise of tumors in the hypophyseal region, which under these circumstances can therefore be interpreted as lesions which through pressure have led to lessened glandular activity. In view of the apparent interrelation of many of the glands of internal secretion it is quite probable that certain of the symptoms known to accompany hypophyseal disease may be consequent upon a secondary change in other glands which

  20. Pituitary function in human pseudocyesis. (United States)

    Forsbach, G; Güitron, A; Munoz, M; Bustos, H


    Two young women with clinically established pseudocyesis were studied by endometrial biopsy, basal hormonal serum levels and dynamic pituitary testing. Basal serum levels of PRL and TSH were in the normal range; estradiol - 17 beta, progesterone and FSH were in the follicular phase range, but LH was in the follicular phase range in one patient and in the climateric range in the other one. The histologic assessment of the endometrial biopsies disclosed a proliferative endometrium in both patients. A group of six patients with hypothalamic amenorrhea were subjected to dynamic pituitary testing to compare results with those obtained in the two patients with pseudocyesis. The dynamic pituitary response to GnRH, TRH and metoclopramide was normal in the two patients with pseudocyesis and in the group with hypothalamic amenorrhea; moreover, challenge with estradiol benzoate (EB) in the two patients with pseudocyesis disclosed a normal positive feedback of LH. These observations and the analysis of data already published suggest that the amenorrhea of pseudocyesis is associated neither with a persistent corpus luteum nor chronic hyperprolactinemia. We suggest that an abnormality in neurotransmitter pathways results in alterations of pituitary hormone secretion. However, additional patients must be studied to prove or disprove this hypothesis.

  1. Pituitary apoplexy masquerading as meningitis

    African Journals Online (AJOL)

    of pituitary apoplexy and often leads to a misdiagnosis of infectious meningoencephalitis. We present the case of a 52 year old male admitted with a diabetic ketoacidosis who subsequently developed a severe headache with features of meningism. Haematological tests revealed an elevated white cell count and C-reactive ...

  2. Computed tomography in pituitary abscess

    Energy Technology Data Exchange (ETDEWEB)

    Appel, W.; Scharphuis, T.; Distelmaier, P.


    This is a report on a rare case of a recurring abscess in the pituitary gland. Diagnosis was extremely difficult to establish preoperatively. This is demonstrated via various radiological methods. Anamnesis and clinical disease pattern are important assisting factors in diagnosis.

  3. Studies on prolactin-secreting cells in aging rats of different strains. I. Alterations in pituitary histology and serum prolactin levels as related to ageing.

    NARCIS (Netherlands)

    Putten, van L.J.A.; Zwieten, van M.J.; Mattheij, J.A.M.; Kemenade, J.A.M.


    Serum PRL levels and histologically tumor-free pituitary glands of 91 aging rats of the BN/BiRij strain, the WAG/Rij strain and their F1 hybrid were studied. In rats with pituitary glands without signs of hyperplasia, serum PRL levels were, in comparison to rats of 15-24 months, increased

  4. Ectopic Suprasellar Thyrotropin-Secreting Pituitary Adenoma: Case Report and Literature Review. (United States)

    Wang, Qing; Lu, Xiao-Jie; Sun, Jun; Wang, Jing; Huang, Ci You; Wu, Zhi Feng


    Ectopic thyroid-stimulating hormone (TSH)-secreting pituitary adenomas are rare and can often be misdiagnosed as primary hyperthyroidism. We present a case of an ectopic suprasellar TSH-secreting pituitary adenoma. A literature review of previously reported ectopic TSH-secreting and suprasellar pituitary adenomas is included to illustrate the clinical characteristics of this disease entity and the diversity of operative approaches to treating ectopic suprasellar pituitary adenomas. A 46-year-old man presented with typical clinical signs of hyperthyroidism and a history of progressive visual field impairment and vision loss. Laboratory investigations revealed that the patient had elevated levels of free thyroxine and free triiodothyronine and a normal level of TSH. Neuro-ophthalmologic examination showed right eye/left eye = 1.0/0.6 and left temporal hemianopia. Magnetic resonance imaging revealed a mass located in the suprasellar space. The patient underwent preoperative short-term octreotide treatment followed by gross total resection of the tumor via the extended endoscopic endonasal transtuberculum sellar approach. At 6-month follow-up evaluation, the patient's endocrinologic function tests met the criteria for cure, and magnetic resonance imaging revealed a normal pituitary gland and stalk with no tumor recurrence. Histologic diagnosis confirmed the presence of a TSH-secreting pituitary adenoma. To the best of our knowledge, this is the first reported case of an ectopic suprasellar TSH-secreting pituitary adenoma. Preoperative preparation and complete resection are the keys to a cure. The extended endoscopic endonasal transtuberculum sellar approach is an alternative minimally invasive method for the removal of an ectopic suprasellar pituitary adenoma. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Rapid Reticulin Fiber Staining Method is Helpful for the Diagnosis of Pituitary Adenoma in Frozen Section. (United States)

    Noh, Songmi; Kim, Sun Ho; Cho, Nam Hoon; Kim, Se Hoon


    Approximately 90% of neoplasms found in the sellar region are adenoma of the pituitary gland. The use of frozen sections for the diagnosis of pituitary adenomas has an accuracy of 90% and is useful in evaluating complete tumor removal. However, it is sometimes difficult to diagnose pituitary adenomas using frozen sections because of the small sample size and marked artifact, and the contiguity of the pituitary adenoma with normal pituitary gland tissue. In this study, we evaluated the use of our modified reticulin stain to make correct decision in frozen section with reduced stain time and investigated the objective diagnostic criteria of pituitary adenoma with reticulin stain. We used Gomori's silver impregnation methods to stain reticulin fibers in frozen pituitary gland sections of 36 samples from 24 patients. We modified the conventional staining method by reducing the overall staining time. We diagnosed pituitary lesion according to our interpretation criteria and compared the results to those of the conventional method and findings of hematoxylin and eosin-stained slides. Reticulin fiber staining of normal adenohypophysis outlines the supporting stroma around the blood vessels and shows regular of the gland meshwork interconnecting the capillaries. In contrast, reticulin fiber staining of the adenomatous tissue shows loss of meshwork or frequent fragmentation. Our modified reticulin stain is more rapid than the established method and shows similar levels of accuracy. Independent evaluation by two pathologists showed discrepancies in diagnosis in four out of 36 cases with modified reticulin stain. Our rapid modified reticulin staining method for frozen sections may be useful as a diagnostic tool for pituitary adenomas and can complement routine hematoxylin and eosin staining.

  6. Growth hormone is a cellular senescence target in pituitary and nonpituitary cells (United States)

    Chesnokova, Vera; Zhou, Cuiqi; Ben-Shlomo, Anat; Zonis, Svetlana; Tani, Yuji; Ren, Song-Guang; Melmed, Shlomo


    Premature proliferative arrest in benign or early-stage tumors induced by oncoproteins, chromosomal instability, or DNA damage is associated with p53/p21 activation, culminating in either senescence or apoptosis, depending on cell context. Growth hormone (GH) elicits direct peripheral metabolic actions as well as growth effects mediated by insulin-like growth factor 1 (IGF1). Locally produced peripheral tissue GH, in contrast to circulating pituitary-derived endocrine GH, has been proposed to be both proapoptotic and prooncogenic. Pituitary adenomas expressing and secreting GH are invariably benign and exhibit DNA damage and a senescent phenotype. We therefore tested effects of nutlin-induced p53-mediated senescence in rat and human pituitary cells. We show that DNA damage senescence induced by nutlin triggers the p53/p21 senescent pathway, with subsequent marked induction of intracellular pituitary GH in vitro. In contrast, GH is not induced in cells devoid of p53. Furthermore we show that p53 binds specific GH promoter motifs and enhances GH transcription and secretion in senescent pituitary adenoma cells and also in nonpituitary (human breast and colon) cells. In vivo, treatment with nutlin results in up-regulation of both p53 and GH in the pituitary gland, as well as increased GH expression in nonpituitary tissues (lung and liver). Intracrine GH acts in pituitary cells as an apoptosis switch for p53-mediated senescence, likely protecting the pituitary adenoma from progression to malignancy. Unlike in the pituitary, in nonpituitary cells GH exerts antiapoptotic properties. Thus, the results show that GH is a direct p53 transcriptional target and fulfills criteria as a p53 target gene. Induced GH is a readily measurable cell marker for p53-mediated cellular senescence. PMID:23940366

  7. Enhanced Performance of Brain Tumor Classification via Tumor Region Augmentation and Partition.

    Directory of Open Access Journals (Sweden)

    Jun Cheng

    Full Text Available Automatic classification of tissue types of region of interest (ROI plays an important role in computer-aided diagnosis. In the current study, we focus on the classification of three types of brain tumors (i.e., meningioma, glioma, and pituitary tumor in T1-weighted contrast-enhanced MRI (CE-MRI images. Spatial pyramid matching (SPM, which splits the image into increasingly fine rectangular subregions and computes histograms of local features from each subregion, exhibits excellent results for natural scene classification. However, this approach is not applicable for brain tumors, because of the great variations in tumor shape and size. In this paper, we propose a method to enhance the classification performance. First, the augmented tumor region via image dilation is used as the ROI instead of the original tumor region because tumor surrounding tissues can also offer important clues for tumor types. Second, the augmented tumor region is split into increasingly fine ring-form subregions. We evaluate the efficacy of the proposed method on a large dataset with three feature extraction methods, namely, intensity histogram, gray level co-occurrence matrix (GLCM, and bag-of-words (BoW model. Compared with using tumor region as ROI, using augmented tumor region as ROI improves the accuracies to 82.31% from 71.39%, 84.75% from 78.18%, and 88.19% from 83.54% for intensity histogram, GLCM, and BoW model, respectively. In addition to region augmentation, ring-form partition can further improve the accuracies up to 87.54%, 89.72%, and 91.28%. These experimental results demonstrate that the proposed method is feasible and effective for the classification of brain tumors in T1-weighted CE-MRI.

  8. Long-term outcomes of surgery and radiotherapy for secreting and non-secreting pituitary adenoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Young; Kim, Jin Hee; Oh, Young Kee; Kim, El [Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of)


    To investigate treatment outcome and long term complication after surgery and radiotherapy (RT) for pituitary adenoma. From 1990 to 2009, 73 patients with surgery and RT for pituitary adenoma were analyzed in this study. Median age was 51 years (range, 25 to 71 years). Median tumor size was 3 cm (range, 1 to 5 cm) with suprasellar (n = 21), cavernous sinus extension (n = 14) or both (n = 5). Hormone secreting tumor was diagnosed in 29 patients; 16 patients with prolactin, 12 patients with growth hormone, and 1 patient with adrenocorticotrophic hormone. Impairment of visual acuity or visual field was presented in 33 patients at first diagnosis. Most patients (n = 64) received RT as postoperative adjuvant setting. Median RT dose was 45 Gy (range, 45 to 59.4 Gy). Median follow-up duration was 8 years (range, 3 to 22 years). In secreting tumors, hormone normalization rate was 55% (16 of 29 patients). For 25 patients with evaluable visual field and visual acuity test, 21 patients (84%) showed improvement of visual disturbance after treatment. The 10-year tumor control rate for non-secreting and secreting adenoma was 100% and 58%, respectively (p < 0.001). Progression free survival rate at 10 years was 98%. Only 1 patient experienced endocrinological recurrence. Following surgery, 60% (n = 44) suffered from pituitary function deficit. Late complication associated with RT was only 1 patient, who developed cataract. Surgery and RT are very effective and safe in hormonal and tumor growth control for secreting and non-secreting pituitary adenoma.

  9. Pituitary Adenoma Recurrence Suspected on Central Hyperthyroidism Despite Empty Sella and Confirmed by 68Ga-DOTA-TOC PET/CT. (United States)

    Gauthé, Mathieu; Sarfati, Julie; Bourcigaux, Nathalie; Christin-Maitre, Sophie; Talbot, Jean-Noël; Montravers, Françoise


    Thyrotropin-secreting pituitary adenomas are very rare tumors, known to present overexpression of somatostatin receptor subtype 2 and which may consequently demonstrate abnormal uptake on Ga-DOTA-TOC PET/CT. A 67-year-old woman with a history of operated pituitary macroadenoma presented with symptoms of hyperthyroidism including a large goiter. Her serum thyroid hormone levels were in favor of central hyperthyroidism. Pituitary MRI depicted an empty sella but visualized an ambiguous lesion centered on the left sphenoidal sinus. Complementary Ga-DOTA-TOC PET/CT finally demonstrated intense uptake by the sphenoidal lesion, confirming recurrence of the pituitary adenoma.

  10. Photon spectrum and absorbed dose in brain tumor

    Energy Technology Data Exchange (ETDEWEB)

    Silva S, A. [General Electric Healthcare, Antonio Dovali Jaime 70, Torre A 3er. piso, Col. Santa Fe, 01210 Mexico D. F. (Mexico); Vega C, H. R. [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas, Zac. (Mexico); Rivera M, T. [IPN, Centro de Investigacion en Ciencia Aplicada y Tecnologia Avanzada, Av. Legaria No. 694, 11500 Mexico D. F. (Mexico)


    Using Monte Carlo methods a BOMAB phantom inside a treatment hall with a brain tumor nearby the pituitary gland was treated with photons produced by a Varian 6 MV linac. The photon spectrum and the absorbed dose were calculated in the tumor, pituitary gland and the head. The treatment beam was collimated to illuminate only the tumor volume; however photons were noticed in the gland. Photon fluence reaching the tumor is 78.1 times larger than the fluence in the pituitary gland, on the other hand the absorbed dose in the tumor is 188 times larger than the dose in the gland because photons that reach the pituitary gland are scattered, by the head and the tumor, through Compton effect. (Author)

  11. Clinical results of stereotactic helium-ion radiosurgery of the pituitary gland at Lawrence Berkeley Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Levy, R.P.; Fabrikant, J.I.; Lyman, J.T.; Frankel, K.A.; Phillips, M.H.; Lawrence, J.H.; Tobias, C.A.


    The first therapeutic clinical trial using accelerated heavy-charged particles in humans was performed for the treatment of various endocrine and metabolic disorders of the pituitary gland, and as suppressive therapy for adenohypophyseal hormone-responsive carcinomas and diabetic retinopathy. Since then, over 800 patients have received stereotactically-directed plateau-beam heavy-charged particle pituitary irradiation at this institution. In acromegaly, Cushing's disease, Nelson's syndrome and prolactin-secreting tumors, the therapeutic goal in the 433 patients treated has been to destroy or inhibit the growth of the pituitary tumor and control hormonal hypersecretion, while preserving a functional rim of tissue with normal hormone-secreting capacity, and minimizing neurologic injury. An additional group of 34 patients was treated for nonsecreting chromophobe adenomas. This paper discusses the methods and results of these treatments. 11 refs.

  12. Clinical results of stereotactic hellium-ion radiosurgery of the pituitary gland at Lawrence Berkeley Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Levy, R.P.; Fabrikant, J.I.; Lyman, J.T.; Frankel, K.A.; Phillips, M.H.; Lawrence, J.H.; Tobias, C.A.


    The first therapeutic clinical trial using accelerated heavy-charged particles in humans was performed at Lawrence Berkeley Laboratory (LBL) for the treatment of various endocrine and metabolic disorders of the pituitary gland, and as suppressive therapy for adenohypophyseal hormone-responsive carcinomas and diabetic retinopathy. In acromegaly, Cushing's disease, Nelson's syndrome and prolactin-secreting tumors, the therapeutic goal in the 433 patients treated has been to destroy or inhibit the growth of the pituitary tumor and control hormonal hypersecretion, while preserving a functional rim of tissue with normal hormone-secreting capacity, and minimizing neurologic injury. An additional group of 34 patients was treated for nonsecreting chromophobe adenomas. This paper discusses the methods and results of stereotactic helium-ion radiosurgery of the pituitary gland at Lawrence Berkeley Laboratory. 11 refs.

  13. A primary sellar neuroblastoma mimicking a pituitary adenoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Gun; Heo, Young Jin; Kim, Eun Kyoung; Baek, Jin Wook; Jeong, Hae Woong; Jung, Hyun Seok [Busan Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)


    Intracranial neuroblastomas are uncommon malignant tumors that usually arise in the supratentorial parenchymal or paraventricular location. A primary neuroblastoma arising in the sella turcica is extremely rare. We report a case of a 76-year-old man who presented with progressive bitemporal hemianopsia. His pituitary hormone levels were within the normal range, except for slightly increased prolactin. Pituitary magnetic resonance imaging revealed a solitary sellar mass with supra- and parasellar extension that mimicked a non-functioning pituitary adenoma or meningioma. The tumor was excised by transsphenoidal resection. Histopathologic analysis revealed small cells surrounded by a dense fibrillary stroma as well as strong expression of neural markers. Hence, the patient was diagnosed with sellar neuroblastoma. Prolactin levels normalized in the immediate postoperative period, although visual disturbances persisted. Herein, we describe the clinical manifestations, MRI characteristics, and histopathologic findings of this case.

  14. A patient with Cushing disease lateralizing a pituitary adenoma by inferior petrosal sinus sampling using desmopressin: a case report. (United States)

    Lim, Joo Hee; Kim, Soo Jung; Jung, Mo Kyung; Kim, Ki Eun; Kwon, Ah Reum; Chae, Hyun Wook; Kim, Duk Hee; Kim, Ho-Seong


    A 14-year-old girl was referred for evaluation of the etiology of Cushing syndrome. During the previous 2 years, she had experienced weight gain, secondary amenorrhea, growth retardation, and back pain. Random serum cortisol level, 24-hour urinary free cortisol excretion, and overnight and low-dose dexamethasone suppression tests suggested Cushing syndrome. Midnight adrenocorticotropic hormone (ACTH) level and high-dose dexamethasone suppression test confirmed Cushing disease. Pituitary magnetic resonance imaging was suspicious for microadenoma. To eliminate ectopic ACTH syndrome, and lateralize the pituitary tumor, inferior petrosal sinus sampling (IPSS) was performed by desmopressin use to stimulate ACTH. Finally, the patient was diagnosed with Cushing disease due to ACTH-secreting pituitary microadenoma, lateralized to the left side; subsequently underwent transsphenoidal surgery. Here we report a case of a 14-year-old girl diagnosed with Cushing disease with a pituitary tumor lateralized by IPSS using desmopressin, which is very rare in pediatric Cushing disease.

  15. Impact of subclinical haemorrhage on the pituitary gland in patients with pituitary adenomas. (United States)

    Kinoshita, Yasuyuki; Tominaga, Atsushi; Usui, Satoshi; Arita, Kazunori; Sugiyama, Kazuhiko; Kurisu, Kaoru


    Advanced magnetic resonance imaging (MRI) and optical instruments for surgery frequently demonstrate subclinical haemorrhage in pituitary adenomas; however, the effects of subclinical haemorrhage on pituitary glands remain unclear. We sought to clarify the pituitary function in patients with subclinical pituitary adenoma haemorrhage (SPAH). Between January 2006 and December 2012, we retrospectively reviewed 328 consecutive patients who underwent surgery for pituitary adenoma. SPAH was defined as an intratumoral haemorrhage based on both 3 tesla MRI and operative findings, with no clinical symptoms of acute pituitary adenoma apoplexy. The pituitary dysfunction assessed using pre- and postoperative provocative tests was investigated in patients categorized into three groups: nonapoplectic adenoma, adenoma with SPAH and adenoma with clinical apoplexy. The main outcome measure was the incidence of pituitary dysfunction. The overall incidence of nonapoplectic adenomas, adenomas with SPAH and adenomas with clinical apoplexy was 82·3%, 14·3% and 3·4%, respectively. Clinical pituitary apoplexy frequently occurred in male patients with large nonfunctioning adenomas, causing pituitary dysfunction. Contrastingly, the incidence of SPAH was significantly higher in the patients with prolactinoma (P = 0·0260), including those with relatively small adenomas (P = 0·0007). No medications, such as dopamine agonists or somatostatin analogues, were observed to affect the occurrence of SPAH. No deterioration of the pituitary function was observed in the SPAH patients in comparison with the patients with nonapoplectic adenoma, and the size of the haematoma occupying the pituitary adenoma did not exhibit any relationships with the deterioration of the pituitary function. Furthermore, SPAH caused no deterioration of the pituitary function after a surgery based on the postoperative provocation tests. Subclinical pituitary adenoma haemorrhage does not cause any added dysfunction in

  16. Apoplexy of a pituitary macroadenoma with reversible third, fourth and sixth cranial nerve palsies following administration of hypothalamic releasing hormones: MR features

    Energy Technology Data Exchange (ETDEWEB)

    Riedl, Michaela E-mail:; Clodi, Martin; Kotzmann, Harald; Hainfellner, Johann A.; Schima, Wolfgang; Reitner, Andreas; Czech, Thomas; Luger, Anton


    Pituitary apoplexy in patients with pituitary macroadenomas can occur either spontaneously or following various interventions. We present a case of a 71-year-old woman who developed third, fourth, and sixth cranial nerve palsies following administration of the four hypothalamic releasing hormones for routine preoperative testing of pituitary function. The MR examination showed interval tumor growth with impression of the floor of the third ventricle. There were also changes in signal intensity characteristics of the mass, suggestive of intratumoral bleeding. A transsphenoidal surgery with subtotal resection of the pituitary adenoma was performed. Microscopical examination revealed large areas of necrosis and blood surrounded by adenomatous tissue. Third, fourth, and sixth cranial nerve palsies completely resolved within 4 months. We conclude that MR imaging is useful in the demonstration of pituitary apoplexy following preoperative stimulation tests, but we suggest that these tests should be abandoned in patients with pituitary macroadenomas.

  17. Inhibition of Bladder Tumor Growth by Chitooligosaccharides in an Experimental Carcinogenesis Model

    Directory of Open Access Journals (Sweden)

    João C. Fernandes


    Full Text Available Urinary bladder cancer is one of the most common cancers worldwide, with the highest incidence in industrialized countries. Patients with cancer commonly use unconventional and complementary therapy including nutraceuticals. In this study we evaluated the efficacy of chitooligosaccharides (in orange juice in rat bladder cancer chemoprevention and as therapeutic agent, on a rat model of urinary bladder carcinogenesis induced with N-butyl-N-(4-hydroxybutyl nitrosamine. Results indicate that chitooligosaccharides may have a preventive effect on bladder cancer development and a curative effect upon established bladder tumors, dependent on the concentration ingested 500 mg/kg b.w., every three days, showed capacity to inhibit and prevent the proliferation of bladder cancer; however, this was associated with secondary effects such as hypercholesterolemia and hypertriglyceridemia. The use of lower doses (50 and 250 mg/kg b.w. showed only therapeutic effects. It is further suggested that this antitumor effect might be due to its expected anti-inflammatory action, as well as by mechanisms not directly dependent of COX-2 inhibition, such as cellular proliferation control and improvement in antioxidant profile.

  18. Tumor tracking based on correlation models in scanned ion beam therapy: an experimental study (United States)

    Seregni, M.; Kaderka, R.; Fattori, G.; Riboldi, M.; Pella, A.; Constantinescu, A.; Saito, N.; Durante, M.; Cerveri, P.; Bert, C.; Baroni, G.


    Accurate dose delivery to extra-cranial lesions requires tumor motion compensation. An effective compensation can be achieved by real-time tracking of the target position, either measured in fluoroscopy or estimated through correlation models as a function of external surrogate motion. In this work, we integrated two internal/external correlation models (a state space model and an artificial neural network-based model) into a custom infra-red optical tracking system (OTS). Dedicated experiments were designed and conducted at GSI (Helmholtzzentrum für Schwerionenforschung). A robotic breathing phantom was used to reproduce regular and irregular internal target motion as well as external thorax motion. The position of a set of markers placed on the phantom thorax was measured with the OTS and used by the correlation models to infer the internal target position in real-time. Finally, the estimated target position was provided as input for the dynamic steering of a carbon ion beam. Geometric results showed that the correlation models transversal (2D) targeting error was always lower than 1.3 mm (root mean square). A significant decrease of the dosimetric error with respect to the uncompensated irradiation was achieved in four out of six experiments, demonstrating that phase shifts are the most critical irregularity for external/internal correlation models.

  19. Effect of Preserving the Pituitary Stalk During Resection of Craniopharyngioma in Children on the Diabetes Insipidus and Relapse Rates and Long-Term Outcomes. (United States)

    Cheng, Jing; Fan, Yanqin; Cen, Bo


    The objective of this study was to investigate the effect of preserving an infiltrated pituitary stalk during the resection of craniopharyngioma of pituitary stalk origin on postoperative outcomes and thus provide a theoretical basis for microsurgical treatment and prognosis. We screened the clinical data of all 103 pediatric patients with craniopharyngioma undergoing surgical treatment at our department between January 2006 and January 2013 and conducted a retrospective analysis of 82 patients with craniopharyngioma originating in the pituitary stalk. The patients were followed up from 12 months to 8 years. We analyzed the effect of preserving the pituitary stalk on the early and persistent diabetes insipidus rates, postoperative relapse rate, and mortality. In the total resection group (n = 67), the early and persistent diabetes insipidus rates were significantly lower in the 46 patients (68.7%) with a pituitary stalk than in those whose pituitary stalk was removed (P  0.05). In the subtotal resection group (n = 15), a significant difference was observed in the early and persistent diabetes insipidus rates (P  0.05). For children with craniopharyngioma of pituitary stalk origin, preserving the pituitary stalk has a significant effect on the early and persistent diabetes insipidus rates. When intraoperative exploration showed excessive adhesion between the tumor and pituitary stalk, we opted to preserve the pituitary stalk, which significantly reduced the early and persistent postoperative diabetes insipidus rates, without significantly increasing the relapse or mortality rate.

  20. An experimental study on the change of the radiosensitivity of several tumor cell lines and primary cultured gingi cal fibrobrast

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sam Sun; You Dong Soo [Dept. of Oral and Maxillofacial Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)


    Radiation sensitivity data was generated for two human cancer cell lines (KB, RPMI 2650) and human primary gingival fibroblast was tested three times using a viable cell number counting with a hemocytometer, MTT (3-[4,5-dimethylthiazol 2-yl]-2,5-dipheny tetrazolium bromide) assay, and LDH (Lactate dehydrogenase) assay. Single irradiation of 2, 4, 6, 10, 15, 20 Gy were applied to the tumor cell lines and the primary cultured gingical fibroblast. The two fractions of 4 Gy an d 10 Gy were separated with a 4 hour time interval. The irradiation was done with 241.5 cGy/min dose rate using 137 Cs MK cell irradiator at room temperature. The obtained results were as followed : 1. There was significantly different viable cell numbers as the amount of radiation dose on the tested cells were cell number counted with a hemocytometer, In fractions, there were more viable cells remaining. 2. Phase-contrast microscopically, radiation-induced morphologic changes were pronounced on the tumor cells, however, almost no differences on the gingival fibroblast. 3. There was significantly different absorbance at 2 Gy on RPMI 2650, 4 Gy on KB and GF in MTT assay. In fractions, the absorbance was significantly higher on KB. 4. The level of extracellular LDH activity in the experimental group was significantly higher in the 2-4 Gy than the control group. 5. The total level of extracellular and intracellular LDH activity was decreased as increased amounts of radiation dose was applied.

  1. Significance of rat mammary tumors for human risk assessment. (United States)

    Russo, Jose


    We have previously indicated that the ideal animal tumor model should mimic the human disease. This means that the investigator should be able to ascertain the influence of host factors on the initiation of tumorigenesis, mimic the susceptibility of tumor response based on age and reproductive history, and determine the response of the tumors induced to chemotherapy. The utilization of experimental models of mammary carcinogenesis in risk assessment requires that the influence of ovarian, pituitary, and placental hormones, among others, as well as overall reproductive events are taken into consideration, since they are important modifiers of the susceptibility of the organ to neoplastic development. Several species, such as rodents, dogs, cats, and monkeys, have been evaluated for these purposes; however, none of them fulfills all the criteria specified previously. Rodents, however, are the most widely used models; therefore, this work will concentrate on discussing the rat rodent model of mammary carcinogenesis. © 2014 by The Author(s).

  2. LINAC-radiosurgery for nonsecreting pituitary adenomas. Long-term results

    Energy Technology Data Exchange (ETDEWEB)

    Runge, M.J.R.; Maarouf, M.; Hunsche, S.; Ruge, M.I.; El Majdoub, F.; Treuer, H.; Sturm, V. [Koeln Univ. (Germany). Dept. of Stereotaxy and Functional Neurosurgery; Kocher, M.; Mueller, R.P. [Koeln Univ. (Germany). Dept. of Radiation Oncology; Voges, J. [Magdeburg Univ. (Germany). Dept. of Stereotactic Neurosurgery


    Stereotactic linear accelerator-based radiosurgery (LINAC-RS) is increasingly used for microsurgically inaccessible or recurrent pituitary adenomas. This single-center study evaluates the long-term follow-up after LINAC-RS of nonsecreting pituitary adenomas (NSA). Patients and methods: Between 1992 and August 2008, 65 patients with NSA were treated. Patient treatment and follow-up were conducted according to a prospective protocol. Indications for LINAC-RS were (1) tumor recurrence or (2) residual tumor. Three patients were treated primarily. For analysis of prognostic factors, patients were grouped according to epidemiological or treatment-associated characteristics. Results: A total of 61 patients with a follow-up {>=} 12 months (median 83 months, range 15-186 months, longest follow-up of published radiosurgery series) were evaluated with regard to their clinical, radiological, and endocrinological course. The median tumor volume was 3.5 ml ({+-} 4.3 ml, range 0.3-17.3 ml) treated with a median surface and maximum dose of 13.0 Gy and 29.7 Gy, respectively. Local tumor control was achieved in 98%. One patient died of unrelated cause after 36 months and 1 patient developed a radiation-induced seizure disorder. Visual complications did not occur. In 37 of 41 patients (90.2%), pituitary function remained stable. Maximum dose to the pituitary {<=} 16 Gy and female gender were positive prognostic factors for the preservation of pituitary function. Conclusion: LINAC-RS is a minimally invasive, safe, and effective treatment for recurrent NSA or microsurgically inaccessible residual tumor. LINAC-RS yielded a high rate of local long-term tumor control with a small number of radiation-induced side effects. (orig.)

  3. Light bodies in human pituitary adenomas

    DEFF Research Database (Denmark)

    Holck, S; Wewer, U M; Albrechtsen, R


    Light bodies are large cytoplasmic granules originally described in the gonadotrophic cells of the rat pituitary gland. In order to determine whether similar bodies occur in the human anterior pituitary gland, 89 pituitary adenomas and periadenomatous tissue from 20 cases were examined...... cells in periadenomatous tissue from 20 cases. These results show that some human pituitary adenomas may contain light bodies identical to those seen in gonadotrophs of rat pituitary....... by transmission electron microscopy. Double membrane bound bodies with filamentous internal structure identical to rodent light bodies were identified in 10 hormone-producing adenomas: 5 PRL, 1 PRL-GH, 2 GH, and 2 ACTH-producing tumours. No light bodies were found in the remaining 79 tumours nor in the pituitary...

  4. [Transphenoidal endoscopic approaches for pituitary adenomas: a critical review of our experience]. (United States)

    Armengot, Miguel; Gallego, José María; Gómez, María José; Barcia, Juan Antonio; Basterra, Jorge; Barcia, Carlos


    The surgical approach to the pituitary fossae has evolved from transcranial to sublabial and transseptal microscopic ones, up to the current transsphenoidal endoscopic approach. To present our experience in the transnasal transsphenoidal approach for pituitary adenomas and the modifications introduced to improve tumoral resection and to lower iatrogenia. Over nine years, we operated on 37 patients with pituitary adenomas using the transsphenoidal endoscopic approach. We utilised optical lens of 0° (approach) and 30° (adenoma resection), optic navigator, surgical instruments for nasal endoscopic and pituitary surgery. During the neurosurgical step, the endoscope was fixed by an articulated arm. We acceded to the pituitary fossae by a bilateral sphenoidotomy. Sphenoid pneumatisation was sufficient in all the patients. The more common postoperative complications were diabetes insipidus and endocrinology deficiencies. Postoperative rhinoliquorrhea affected only one patient. No alterations of nasal fossae were observed. Mean patient hospitalisation was five days. Transsphenoidal endoscopic approach guided by navigator gives significant advantages: Shorter operating time and fewer complications, greater safety and preservation of the nasal passages. Resecting the sphenoidal rostrum and a fragment of adjacent nasal septum improves surgical instrument management into the pituitary fossae and therefore adenoma resection. Endoscope fixation stabilises the vision and allows the second surgeon to help more effectively. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  5. Dynamic computed tomography of the pituitary gland using a single slice scanner in dogs with pituitary-dependent hypercortisolism

    NARCIS (Netherlands)

    Del Magno, Sara; Grinwis, Guy C M; Voorhout, George; Meij, Björn P.

    Selective removal of the pituitary adenoma has not been advocated in dogs with pituitary-dependent hypercortisolism because the pituitary adenoma is usually not visualized on routine computed tomography (CT).Dynamic pituitary CT scanning is aimed at the detection of the pituitary flush and,

  6. Magnetic resonance characterization of tumor microvessels in experimental breast tumors using a slow clearance blood pool contrast agent (carboxymethyldextran-A2-Gd-DOTA) with histopathological correlation. (United States)

    Preda, Anda; Novikov, Viktor; Möglich, Martina; Floyd, Eugenia; Turetschek, Karl; Shames, David M; Roberts, Timothy P L; Corot, Claire; Carter, Wayne O; Brasch, Robert C


    Carboxymethyldextran (CMD)-A2-Gd-DOTA, a slow clearance blood pool contrast agent with a molecular weight of 52.1 kDa, designed to have intravascular residence for more than 1 h, was evaluated for its potential to characterize and differentiate the microvessels of malignant and benign breast tumors. Precontrast single-slice inversion-recovery snapshot FLASH and dynamic contrast-enhanced MRI using an axial T1-weighted three-dimensional spoiled gradient recalled sequence was performed in 30 Sprague-Dawley rats with chemically induced breast tumors. Endothelial transfer coefficient and fractional plasma volume of the breast tumors were estimated from MRI data acquired with CMD-A2-Gd-DOTA enhancement injected at a dose of 0.1 mmol Gd/kg body weight using a two-compartment bidirectional model of the tumor tissue. The correlation between MRI microvessel characteristics and histopathological tumor grade was determined using the Scarff-Bloom-Richardson method. Using CMD-A2-Gd-DOTA, no significant correlations were found between the MR-estimated endothelial transfer coefficient or plasma volumes with histological tumor grade. Analysis of CMD-A2-Gd-DOTA-enhanced MR kinetic data failed to demonstrate feasibility for the differentiation of benign from malignant tumors or for image-based tumor grading.

  7. Changes in the Structure of the Thymus under Conditions of Various Treatments for Experimental Mammary Tumor. (United States)

    Kazakov, O V; Kabakov, A V; Poveshchenko, A F; Ishchenko, I Yu; Poveshchenko, O V; Strunkin, D N; Raiter, T V; Michurina, S V; Konenkov, V I


    Morphological changes in the thymus of female Wistar rats with experimental mammary gland carcinomas were studied. After adjuvant therapy, the area of the cortical matter and density of parenchymal cells in the thymus decreased, while areas of the medulla, connective tissue, and content of immunoblasts and macrophages increased. In the thymuses of rats receiving exogenous DNA, morphological signs of activation of the lymphoid and epithelial components were found: areas of the cortex and medulla, glandular and connective tissue corresponded to the values in intact animals, the counts of lymphocytes in the central part of the cortical matter and of macrophages in all zones of the thymus increased, and lymphocyte migration from the thymus increased (in comparison with the chemotherapy group).

  8. Metastatic Mantle Cell Lymphoma to the Pituitary Gland: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Arthur Wang


    Full Text Available We present an unusual case of a metastatic mantle cell lymphoma (MCL to the pituitary gland. The patient had a known history of MCL for which she previously received chemotherapy. She presented with new-onset diplopia and confusion, and reported a history of progressive vision blurriness associated with headache, nausea, and vomiting. MRI of the brain showed an enhancing lesion within the sella turcica involving the cavernous sinuses bilaterally, extending into Meckel's cave on the left, and abutting the optic nerves bilaterally. Following surgical excision, histopathology revealed the tumor to be a MCL. Metastatic pituitary tumors are rare and have been estimated to make up 1% of tumors discovered in the sellar region. The two most common secondary metastatic lesions to the sella are breast and lung carcinoma followed by prostate, renal cell, and gastrointestinal carcinoma. Metastatic lymphoma to the pituitary gland is especially rare and is estimated to constitute 0.5% of all metastatic tumors to the sella turcica. To our knowledge, this is the first reported case of MCL metastasizing to the pituitary gland.

  9. Extended endoscopic endonasal surgery using three-dimensional endoscopy in the intra-operative MRI suite for supra-diaphragmatic ectopic pituitary adenoma. (United States)

    Fuminari, Komatsu; Hideki, Atsumi; Manabu, Osakabe; Mitsunori, Matsumae


    We describe a supra-diaphragmatic ectopic pituitary adenoma that was safely removed using the extended endoscopic endonasal approach, and discuss the value of three-dimensional (3D) endoscopy and intra-operative magnetic resonance imaging (MRI) to this type of procedure. A 61-year-old-man with bitemporal hemianopsia was referred to our hospital, where MRI revealed an enhanced suprasellar tumor compressing the optic chiasma. The tumor extended on the planum sphenoidale and partially encased the right internal carotid artery. An endocrinological assessment indicated normal pituitary function. The extended endoscopic endonasal approach was taken using a 3D endoscope in the intraoperative MRI suite. The tumor was located above the diaphragma sellae and separated from the normal pituitary gland. The pathological findings indicated non-functioning pituitary adenoma and thus the tumor was diagnosed as a supra-diaphragmatic ectopic pituitary adenoma. Intra-operative MRI provided useful information to minimize dural opening and the supra-diaphragmatic ectopic pituitary adenoma was removed from the complex neurovascular structure via the extended endoscopic endonasal approach under 3D endoscopic guidance in the intra-operative suite. Safe and effective removal of a supra-diaphragmatic ectopic pituitary adenoma was accomplished via the extended endoscopic endonasal approach with visual information provided by 3D endoscopy and intra-operative MRI.

  10. Computational and Experimental Evaluations of a Novel Thermo-Brachytherapy Seed for Treatment of Solid Tumors (United States)

    Warrell, Gregory R.

    Hyperthermia has long been known as a radiation therapy sensitizer of high potential; however successful delivery of this modality and integrating it with radiation have often proved technically difficult. We present the dual-modality thermobrachytherapy (TB) seed, based on the ubiquitous low dose-rate (LDR) brachytherapy permanent implant, as a simple and effective combination of hyperthermia and radiation therapy. Heat is generated from a ferromagnetic or ferrimagnetic core within the seed, which produces Joule heating by eddy currents. A strategically-selected Curie temperature provides thermal self-regulation. In order to obtain a uniform and sufficiently high temperature distribution, additional hyperthermia-only (HT-only) seeds are proposed to be used in vacant spots within the needles used to implant the TB seeds; this permits a high seed density without the use of additional needles. Experimental and computational studies were done both to optimize the design of the TB and HT-only seeds and to quantitatively assess their ability to heat and irradiate defined, patient-specific targets. Experiments were performed with seed-sized ferromagnetic samples in tissue-mimicking phantoms heated by an industrial induction heater. The magnetic and thermal properties of the seeds were studied computationally in the finite element analysis (FEA) solver COMSOL Multiphysics, modelling realistic patient-specific seed distributions. These distributions were derived from LDR permanent prostate implants previously conducted at our institution; various modifications of the seeds' design were studied. The calculated temperature distributions were analyzed by generating temperature-volume histograms, which were used to quantify coverage and temperature homogeneity for a range of blood perfusion rates, as well as for a range of seed Curie temperatures and thermal power production rates. The impact of the interseed attenuation and scatter (ISA) effect on radiation dose distributions

  11. Third Prize: Comparison of radical nephrectomy, laparoscopic microwave thermotherapy, cryotherapy, and radiofrequency ablation for destruction of experimental VX-2 renal tumors in rabbits. (United States)

    Eichel, Louis; Kim, Issac Y; Uribe, Carlos; Khonsari, Sephir; Basillote, Jay; Steward, Earl; Coad, James; Bischof, John; Rudie, Eric; Kluge, Stan; McDougall, Elspeth M; Clayman, Ralph V


    Currently available minimally invasive renal tumor-ablation procedures include cryotherapy, radiofrequency ablation, and microwave thermotherapy. In this study, we investigated the ability of these three approaches to destroy experimental renal tumors in rabbits. The mechanism of potential tumor metastasis was also explored. The VX-2 tumor line is an aggressive rabbit epidermoid tumor with a high metastatic potential. An initial experiment comparing cooled-tip microwave thermotherapy with cryotherapy and radical nephrectomy for treatment of small VX-2 tumors revealed that all microwave-treated rabbits had local recurrence and that several also had diffuse intraperitoneal carcinomatosis. In view of these results, a second experiment was performed in which 45 New Zealand White rabbits were implanted laparoscopically with VX-2 xenografts underneath the kidney capsule and divided into five groups of 9 each. The test groups were microwave thermotherapy with a 3.5-mm cooled-tip probe, microwave thermotherapy with a 3.5-mm noncooled- tip probe, radiofrequency ablation with a 1.5-mm cooled-tip probe, radiofrequency ablation with a 1.5- mm non-cooled tip probe, and cryotherapy with a 2.3-mm cryoprobe. The control groups were five rabbits that were not treated, five rabbits with tumors that had the tumor pierced with a probe but were untreated, and five rabbits that underwent nephrectomy after piercing of the tumor. Treatment was initiated 5 days after tumor implantation. One month later, all animals were euthanized and autopsied. At 5 days after tumor implantation, laparoscopic inspection revealed no visible peritoneal metastases. At 1 month, in the cooled and non-cooled microwave-thermotherapy groups, carcinomatosis occurred in five and six of nine animals, respectively. In comparison, carcinomatosis was detected in two of nine animals in the cryotherapy group at autopsy. With respect to cooled and non-cooled radiofrequency ablation, carcinomatosis was observed in four of

  12. Aryl‐hydrocarbon receptor activity modulates prolactin expression in the pituitary

    Energy Technology Data Exchange (ETDEWEB)

    Moran, Tyler B.; Brannick, Katherine E.; Raetzman, Lori T., E-mail:


    Pituitary tumors account for 15% of intracranial neoplasms, however the extent to which environmental toxicants contribute to the proliferation and hormone expression of pituitary cells is unknown. Aryl-hydrocarbon receptor (AhR) interacting protein (AIP) loss of function mutations cause somatotrope and lactotrope adenomas in humans. AIP sequesters AhR and inhibits its transcriptional function. Because of the link between AIP and pituitary tumors, we hypothesize that exposure to dioxins, potent exogenous ligands for AhR that are persistent in the environment, may predispose to pituitary dysfunction through activation of AhR. In the present study, we examined the effect of AhR activation on proliferation and endogenous pituitary hormone expression in the GH3 rat somatolactotrope tumor cell line and the effect of loss of AhR action in knockout mice. GH3 cells respond to nM doses of the reversible AhR agonist β-naphthoflavone with a robust induction of Cyp1a1. Although mRNA levels of the anti-proliferative signaling cytokine TGFbeta1 are suppressed upon β-naphthoflavone treatment, we did not observe an alteration in cell proliferation. AhR activation with β-naphthoflavone suppresses Ahr expression and impairs expression of prolactin (PRL), but not growth hormone (GH) mRNA in GH3 cells. In mice, loss of Ahr similarly leads to a reduction in Prl mRNA at P3, while Gh is unaffected. Additionally, there is a significant reduction in pituitary hormones Lhb and Fshb in the absence of Ahr. Overall, these results demonstrate that AhR is important for pituitary hormone expression and suggest that environmental dioxins can exert endocrine disrupting effects at the pituitary. -- Highlights: ► AhR signaling suppresses Prl mRNA expression. ► AhR signaling does not influence pituitary proliferation in culture. ► AhR is necessary for Prl, Lhb and Fshb expression at postnatal day 3.

  13. Pituitary disorders and their extra-pituitary implications : observations in patients with nonfunctioning pituitary macroadenoma and the IGSF1 deficiency syndrome

    NARCIS (Netherlands)

    Joustra, S.D.


    In this thesis, we explored pituitary functioning and extra-pituitary implications of two pituitary disorders in humans. In part A, we focused on the long-term consequences of the diagnosis and treatment of nonfunctioning pituitary macroadenoma (NFMA) on hypothalamic regulation of circadian

  14. Histopathological features of post-mortem pituitaries: A retrospective analysis

    Directory of Open Access Journals (Sweden)

    Francisco José Tortosa Vallecillos

    Full Text Available SUMMARY Objective: As a result of the use of neuroimaging techniques, silent pituitary lesions are diagnosed more and more frequently; however, there are few published post-mortem studies about this gland. Incidence data of pituitary lesions are rare and in Portugal they are outdated or even non-existent. The aim of this study is to determine the prevalence of normal patterns and incidental post-mortem pituitary pathology at Centro Hospitalar Lisboa Norte, analyzing the associations with clinical data and assessing the clinical relevance of the findings. Method: We reviewed retrospectively and histologically 167 pituitaries of a consecutive series of autopsies from the Department of Pathology of this centre. They were done between 2012 and 2014, and in all cases medical records were reviewed. The morphological patterns observed, were classified into three major groups: 1 Normal histological patterns and variants; 2 Infectious-inflammatory pathology, metabolic and vascular disorders; 3 Incidental primary proliferation and secondary to systemic diseases. Results: The subjects included in this study were of all age groups (from 1 day to 91 years old, 71 were female and 96 male. Fifty-seven of these glands didn’t show any alteration; 51 showed colloid cysts arising from Rathke cleft; 44 presented hyperplasia in adenohypophysis and we identified 20 adenomas in 19 glands (immunohistochemically, eight PRL-producing and five ACTH-producing tumors, ten of which associated with obesity, 11 to hypertension and six to diabetes mellitus. There were two cases with metastasis. Conclusion: Subclinical pathology in our country is similar to that seen in other parts of the world, but at older ages.

  15. Pituitary Gigantism: A Case Report

    Directory of Open Access Journals (Sweden)

    Rana Bhattacharjee


    Full Text Available Objective: To present a rare case of gigantism. Case Report: A 25-year-old lady presented with increased statural growth and enlarged body parts noticed since the age of 14 years, primary amenorrhea, and frontal headache for the last 2 years.She has also been suffering from non-inflammatory low back pain with progressive kyphosis and pain in the knees, ankles, and elbows for the last 5 years. There was no history of visual disturbance, vomiting, galactorrhoea, cold intolerance. She had no siblings. Family history was non-contributory.Blood pressure was normal. Height 221 cm, weight 138 kg,body mass index (BMI28. There was coarsening of facial features along with frontal bossing and prognathism, large hands and feet, and small goitre. Patient had severe kyphosis and osteoarthritis of knees. Confrontation perimetry suggested bitemporal hemianopia. Breast and pubic hair were of Tanner stage 1. Serum insulin like growth factor-1 (IGF1 was 703 ng/ml with all glucose suppressedgrowth hormone (GHvalues of >40 ng/ml. Prolactin was 174 ng/ml. Basal serum Lutenising Hormone (LH, follicle stimulating Hormone (FSH was low. Oral glucose tolerance test (OGTT, liver and renal function tests, basal cortisol and thyroid profile, Calcium, phosphorus and Intact Parathyroid hormone (iPTH were normal.Computed tomographyscan of brain showed large pituitary macroadenoma. Automated perimetry confirmed bitemporal hemianopia. A diagnosis of gigantism due to GH secreting pituitary macroadenoma with hypogonadotrophichypogonadism was made. Debulking pituitary surgery followed by somatostatin analogue therapy with gonadal steroid replacement had been planned, but the patient refused further treatment.

  16. Tumor microvasculature observed using different contrast agents: a comparison between Gd-DTPA-Albumin and B-22956/1 in an experimental model of mammary carcinoma. (United States)

    Boschi, Federico; Marzola, Pasquina; Sandri, Marco; Nicolato, Elena; Galiè, Mirco; Fiorini, Silvia; Merigo, Flavia; Lorusso, Vito; Chaabane, Linda; Sbarbati, Andrea


    The aim of this study was to compare a pure macromolecular contrast agent (Gd-DTPA-albumin) with a new protein-binding blood pool contrast agent (B22956/1) in terms of their capacity to investigate the microvasculature in an experimental model of mammary carcinoma. Tumors were induced by subcutaneous injection of 5 x 10(5) BB1 cells into the backs of 5-7 week-old female FVB/neuNT233 mice. The animals were observed using DCE-MRI when the longest diameter of the tumor was 10.2+/-2.0 mm. DCE-MRI experiments were carried out using B22956/1 and (24 h later) Gd-DTPA-albumin. DCE-MRI data showed that vasculature in the tumor rim was characterized by greater fractional plasma volume and transendothelial permeability than vasculature in the tumor core as measured by both contrast agents. Permeability to Gd-DTPA-albumin in the tumor core was hardly measurable while permeability to B22956/1 was substantial. Histologically the tumor core showed areas of well vascularized, viable tissue surrounded by necrotic regions. DCE-MRI experiments performed with B22956/1 are useful in the investigation of vasculature in those tumor regions that are characterized by low permeability to macromolecules.

  17. Current Trends in Pathogenesis, Diagnosis and Prognosis of Inactive Pituitary Adenomas

    Directory of Open Access Journals (Sweden)

    Z.Yu. Khalimova


    Full Text Available The paper presents an analysis of data from 138 sources in recent years. The study of factors of the development of inactive pituitary adenomas remains one of the most urgent problems of modern medicine. The development of various methods of instrumental and laboratory diagnostics of pituitary masses, as well as the achievement of genetics and molecular biology have significantly changed concepts of the etiology and pathogenesis and, consequently, the possibility of diagnosis, treatment and prevention of many diseases of the brain tumor.

  18. Shedding light on canine pituitary dwarfism

    NARCIS (Netherlands)

    Voorbij, A.M.W.Y.


    Pituitary dwarfism, associated with growth hormone deficiency, is an autosomal, recessively inherited disorder in shepherd dogs. Due to the serious nature of pituitary dwarfism and lack of efficient treatment, it is preferable to prevent dwarfs from being born by applying a correct breeding policy.

  19. Hypothalamic functions in patients with pituitary insufficiency

    NARCIS (Netherlands)

    Borgers, A.J.F.


    The main objective of this thesis is to increase our understanding of hypothalamic (dys)function in patients with pituitary insufficiency. This goal is driven by the clinical experience of persisting symptoms in patients adequately treated for pituitary insufficiency. We focus primarily on patients

  20. Expression of Eag1 K+ channel and ErbBs in human pituitary adenomas: cytoskeleton arrangement patterns in cultured cells. (United States)

    del Pliego, Margarita González; Aguirre-Benítez, Elsa; Paisano-Cerón, Karina; Valdovinos-Ramírez, Irene; Rangel-Morales, Carlos; Rodríguez-Mata, Verónica; Solano-Agama, Carmen; Martín-Tapia, Dolores; de la Vega, María Teresa; Saldoval-Balanzario, Miguel; Camacho, Javier; Mendoza-Garrido, María Eugenia


    Pituitary adenomas can invade surrounded tissue, but the mechanism remains elusive. Ether à go-go-1 (Eag1) potassium channel and epidermal growth factor receptors (ErbB1 and ErbB2) have been associated to invasive phenotypes or poor prognosis in cancer patients. However, cells arrange their cytoskeleton in order to acquire a successful migration pattern. We have studied ErbBs and Eag1 expression, and cytoskeleton arrangements in 11 human pituitary adenomas. Eag1, ErbB1 and ErbB2 expression were studied by immunochemistry in tissue and cultured cells. The cytoskeleton arrangement was analyzed in cultured cells by immunofluorescence. Normal pituitary tissue showed ErbB2 expression and Eag1 only in few cells. However, Eag1 and ErbB2 were expressed in all the tumors analyzed. ErbB1 expression was observed variable and did not show specificity for a tumor characteristic. Cultured cells from micro- and macro-adenomas clinically functional organize their cytoskeleton suggesting a mesenchymal pattern, and a round leucocyte/amoeboid pattern from invasive clinically silent adenoma. Pituitary tumors over-express EGF receptors and the ErbB2 repeated expression suggests is a characteristic of adenomas. Eag 1 was express, in different extent, and could be a therapeutic target. The cytoskeleton arrangements observed suggest that pituitary tumor cells acquire different patterns: mesenchymal, and leucocyte/amoeboid, the last observed in the invasive adenomas. Amoeboid migration pattern has been associated with high invasion capacity.

  1. Lack of Cell Proliferative and Tumorigenic Effects of 4-Hydroxyestradiol in the Anterior Pituitary of Rats: Role of Ultrarapid O-Methylation Catalyzed by Pituitary Membrane-Bound Catechol-O-Methyltransferase. (United States)

    Wang, Pan; Mills, Laura H; Song, Ji-Hoon; Yu, Jina; Zhu, Bao-Ting


    In animal models, estrogens are complete carcinogens in certain target sites. 4-Hydroxyestradiol (4-OH-E2), an endogenous metabolite of 17β-estradiol (E2), is known to have prominent estrogenic activity plus potential genotoxicity and mutagenicity. We report here our finding that 4-OH-E2 does not induce pituitary tumors in ACI female rats, whereas E2 produces 100% pituitary tumor incidence. To probe the mechanism, we conducted a short-term animal experiment to compare the proliferative effect of 4-OH-E2 in several organs. We found that, whereas 4-OH-E2 had little ability to stimulate pituitary cell proliferation in ovariectomized female rats, it strongly stimulates cell proliferation in certain brain regions of these animals. Further, when we used in vitro cultured rat pituitary tumor cells as models, we found that 4-OH-E2 has similar efficacy as E2 in stimulating cell proliferation, but its potency is approximately 3 orders of magnitude lower than that of E2. Moreover, we found that the pituitary tumor cells have the ability to selectively metabolize 4-OH-E2 (but not E2) with ultrahigh efficiency. Additional analysis revealed that the rat pituitary expresses a membrane-bound catechol-O-methyltransferase that has an ultralow Km value (in nM range) for catechol estrogens. On the basis of these observations, it is concluded that rapid metabolic disposition of 4-OH-E2 through enzymatic O-methylation in rat anterior pituitary cells largely contributes to its apparent lack of cell proliferative and tumorigenic effects in this target site.

  2. Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

    Energy Technology Data Exchange (ETDEWEB)

    D. W. Nigg


    We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

  3. Pituitary Involvement in Granulomatosis With Polyangiitis (United States)

    De Parisot, Audrey; Puéchal, Xavier; Langrand, Corinne; Raverot, Gerald; Gil, Helder; Perard, Laurent; Le Guenno, Guillaume; Berthier, Sabine; Tschirret, Olivier; Eschard, Jean Paul; Vinzio, Stephane; Guillevin, Loïc; Sève, Pascal


    Abstract Pituitary dysfunction is a rare manifestation of granulomatosis with polyangiitis (GPA) (Wegener). The main aim of this multicenter retrospective study was to describe the characteristics and outcomes of pituitary manifestations in patients with GPA included in the French Vasculitis Study Group database. Among the 819 GPA patients included in the database, 9 (1.1%) had pituitary involvement. The median age at diagnosis of GPA and pituitary involvement was 46 and 50.8 years, respectively. Pituitary involvement was present at onset of GPA in 1 case and occurred later in 8 patients after a median follow up of 58.5 months. When pituitary dysfunction occurred, 8 patients had active disease at other sites including ENT (n = 6), eye (n = 4), or central nervous system (n = 3) involvement. The most common hormonal dysfunctions were diabetes insipidus (n = 7) and hypogonadism (n = 7). Magnetic resonance imaging was abnormal in 7 patients. The most common lesions were an enlargement of the pituitary gland, thickening of the pituitary stalk, and loss of posterior hypersignal on T1-weighed images. All patients were treated with corticosteroid therapy and 8 patients received immunosuppressive agents for the pituitary involvement, including cyclophosphamide (n = 3), rituximab (n = 2), and methotrexate (n = 3). After a median follow-up of 9.2 years, GPA was in complete remission in 7 patients, but 8 patients were still under hormone replacement therapy. Among the 5 patients who had a subsequent MRI, 2 had complete resolution of pituitary lesions.By combining our study and the literature review, the frequency of hypogonadism and diabetes insipidus, among the patients with pituitary dysfunction, can be estimated at 78% and 71% respectively. Despite a high rate of systemic disease remission on maintenance therapy, 86% of the patients had persistent pituitary dysfunction. The patients who recovered from pituitary dysfunction had all been

  4. Concomitant Primary CNS Lymphoma and FSH-Pituitary Adenoma Arising Within the Sella. Entirely Coincidental? (United States)

    Ban, Vin Shen; Chaudhary, Bedansh Roy; Allinson, Kieren; Santarius, Thomas; Kirollos, Ramez Wadie


    Collision tumors are the simultaneous occurrence of more than one type of neoplasm within an anatomic space. In the pituitary sella, collision tumors are exceedingly rare, and not much is known about their etiology and prognosis. A 74-year-old man presented with a concomitant primary pituitary lymphoma (diffuse large B-cell non-Hodgkin's lymphoma; DLBCL) and follicle-stimulating hormone (FSH)-adenoma diagnosed histologically after clinical features of apoplexy prompted urgent surgical decompression and resection. Strong immunoreactivity for FSH by the lymphoma was evident. Full-body workup demonstrated no other source for the lymphoma. He subsequently underwent 4 cycles of chemotherapy and has been in remission for over 32 months. His ophthalmoplegia at presentation persisted with no further deficits. Four cases of collision tumors of primary pituitary lymphoma and adenoma have previously been reported. This case represents the first combination of an FSH-adenoma and a DLBCL in the literature. Prompt involvement of the hematology-oncology team contributed to the good outcome seen in this case. The putative role played by pituitary hormones in tumorigenesis is reviewed in this case report. The association is either a chance occurrence or due to the induction of lymphoma cell proliferation by the binding of FSH produced by the adenoma to the FSH receptors on the lymphoma cells.

  5. Posttransplantation lymphoproliferative disease involving the pituitary gland. (United States)

    Meriden, Zina; Bullock, Grant C; Bagg, Adam; Bonatti, Hugo; Cousar, John B; Lopes, M Beatriz; Robbins, Mark K; Cathro, Helen P


    Posttransplantation lymphoproliferative disorders (PTLD) are heterogeneous lesions with variable morphology, immunophenotype, and molecular characteristics. Multiple distinct primary lesions can occur in PTLD, rarely with both B-cell and T-cell characteristics. Lesions can involve both grafted organs and other sites; however, PTLD involving the pituitary gland has not been previously reported. We describe a patient who developed Epstein-Barr virus-negative PTLD 13 years posttransplantation involving the terminal ileum and pituitary, which was simultaneously involved by a pituitary adenoma. Immunohistochemistry of the pituitary lesion showed expression of CD79a, CD3, and CD7 with clonal rearrangements of both T-cell receptor gamma chain (TRG@) and immunoglobulin heavy chain (IGH@) genes. The terminal ileal lesion was immunophenotypically and molecularly distinct. This is the first report of pituitary PTLD and illustrates the potentially complex nature of PTLD. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Experimental study on differential diagnosis of tumor from inflammation by using /sup 125/I labeled Pisum sativum agglutinin

    Energy Technology Data Exchange (ETDEWEB)

    Kojima, Shuji; Jay, M.


    We have reported that Pisum sativum agglutinin (PSA), a plant lectin which recognizes mannosyl residues, accumulates markedly in Ehrlich solid tumor (EST) and suggested the possibility of applying PSA to tumor imaging radiopharmaceuticals. In the present work, an inflammation was induced by implantation of cotton thread in the left rear leg skeletal muscle of ddY mice and Ehrlich ascites tumor cells were inoculated into the right rear leg. /sup 67/Ga-citrate accumulated in the tumor tissue and the inflammatory lesion to almost equal extents. On the other hand, /sup 125/I-PSA preferentially accumulated in tumor tissues in mice bearing both tumor and inflammation. The results suggest that differential diagnosis of tumor from inflammation using radiolabeled PSA may be possible.

  7. The combination of IL-21 and IFN-alpha boosts STAT3 activation, cytotoxicity and experimental tumor therapy

    DEFF Research Database (Denmark)

    Eriksen, Karsten W; Søndergaard, Henrik; Woetmann, Anders


    such as IFN-alpha and IL-2 have multiple and severe side effects. Accordingly, they are generally used at sub-optimal doses, which limit their clinical efficacy. Here we hypothesized that a combination of IFN-alpha and IL-21, a novel cytokine of the IL-2 family with anti-cancer effects, will increase the anti-cancer...... efficacy at sub-optimal cytokine doses. We show that the combined stimulation of target-cells with IFN-alpha and IL-21 triggers an increased STAT3 activation whereas the activation of other STATs including STAT1/2 is unaffected. In parallel, the combined stimulation with IFN-alpha and IL-21 triggers...... a selective increase in MHC class I expression and NK- and CD8(+) T-cell-mediated cytotoxicity. In an experimental in vivo model of renal carcinoma, the combined treatment of IFN-alpha and IL-21 also produces a significant anti-cancer effect as judged by an inhibition of tumor growth and an increased survival...

  8. Combination use of lentinan with x-ray therapy in mouse experimental tumor system, (2). Combination effect on MM102 syngeneic tumor

    Energy Technology Data Exchange (ETDEWEB)

    Shiio, Tsuyoshi; Ohishi, Kazuo; Tsuchiya, Yoshiharu; Niitsu, Iwayasu; Hayashibara, Hiromi; Yoshihama, Takashi; Moriyuki, Hirobumi


    C3H/He mice transplanted syngeneic MM102 tumor subcutaneously in the footpad were used to study the timing of administration of lentinan when combined with local irradiation of X-ray. In combination with 1,000 rads irradiation, the administration of lentinan after X-ray was not effective. When lentinan was administered in combination with 2,000 to 3,000 rads irradiation, the growth of tumor was decreased significantly in comparison with the groups which received radiotherapy alone and those that received lentinan alone. The administration of lentinan before irradiation was effective at the same degree in the group that received lentinan after irradiation. Life prolongation effect was also observed in the group that received lentinan before and after irradiation, and 4 mice among 8 tested mice were survived at 70th day after tumor transplantation.

  9. Radioimmunotherapy with an antibody to HPV16 E6 oncoprotein is effective in experimental cervical tumor expressing low levels of E6 (United States)

    Jiang, Zewei; Wang, Xing Guo; Einstein, Mark H; Goldberg, Gary L; Casadevall, Arturo


    Purpose HPV16 is associated with ∼50% of all cervical cancers worldwide. The E6 and E7 genes of oncogenic HPV types, such as HPV16, are necessary for the HPV transforming function and tumorogenesis making them ideal targets for novel treatments. Radioimmunotherapy employs systemically administered radiolabeled monoclonal antibodies (mAbs) that bind to tumor-associated antigens. Previously we demonstrated in mice that radioimmunotherapy targeting viral antigens with mAb to HPV16 E6 suppressed CasKi cervical tumors expressing high levels of E6 (∼600 copies of HPV per cell). However, that study opened the question whether radioimmunotherapy can suppress the growth of cervical tumors with low E6 and E7 expression, such as may be seen in patients. Experimental Design We evaluated the expression of E6 in patients' tumors and in the SiHa cell line expressing low levels of E6 and E7 (1–2 copies of HPV per cell) and found them comparable. We initiated SiHa tumors in nude mice, radiolabeled C1P5 mAb to E6 with a beta-emitter 188-Rhenium (188Re) and treated tumor-bearing mice with: (1) 200 µCi 188Re-C1P5 alone; (2) proteasome inhibitor MG132 alone; (3) MG132 followed by 200 µCi 188Re-C1P5; (4) unlabeled C1P5; (5) 200 µCi 188Re-18B7 (isotype-matching control mAb); (6) no treatment. 188Re-C1P5 alone and in combination with MG-132 significantly retarded tumor growth compared to all control groups. Conclusions Our data demonstrate the possibility to suppress tumor growth by targeting viral antigens even in cervical tumors with low E6 expression and provide additional evidence for the potential usefulness of radioimmunotherapy targeting HPV-related antigens in the clinic. PMID:20861673

  10. Visual pathway impairment by pituitary adenomas: quantitative diagnostics by diffusion tensor imaging. (United States)

    Lilja, Ylva; Gustafsson, Oscar; Ljungberg, Maria; Starck, Göran; Lindblom, Bertil; Skoglund, Thomas; Bergquist, Henrik; Jakobsson, Karl-Erik; Nilsson, Daniel


    OBJECTIVE Despite ample experience in surgical treatment of pituitary adenomas, little is known about objective indices that may reveal risk of visual impairment caused by tumor growth that leads to compression of the anterior visual pathways. This study aimed to explore diffusion tensor imaging (DTI) as a means for objective assessment of injury to the anterior visual pathways caused by pituitary adenomas. METHODS Twenty-three patients with pituitary adenomas, scheduled for transsphenoidal tumor resection, and 20 healthy control subjects were included in the study. A minimum suprasellar tumor extension of Grade 2-4, according to the SIPAP (suprasellar, infrasellar, parasellar, anterior, and posterior) scale, was required for inclusion. Neuroophthalmological examinations, conventional MRI, and DTI were completed in all subjects and were repeated 6 months after surgery. Quantitative assessment of chiasmal lift, visual field defect (VFD), and DTI parameters from the optic tracts was performed. Linear correlations, group comparisons, and prediction models were done in controls and patients. RESULTS Both the degree of VFD and chiasmal lift were significantly correlated with the radial diffusivity (r = 0.55, p visual pathways that were compressed by pituitary adenomas. The correlation between radial diffusivity and visual impairment may reflect a gradual demyelination in the visual pathways caused by an increased tumor effect. The low level of axial diffusivity found in the patient group may represent early atrophy in the visual pathways, detectable on DTI but not by conventional methods. DTI may provide objective data, detect early signs of injury, and be an additional diagnostic tool for determining indication for surgery in cases of pituitary adenomas.

  11. Assessment of the extent of pituitary macroadenomas resection in immediate postoperative MRI. (United States)

    Taberner López, E; Vañó Molina, M; Calatayud Gregori, J; Jornet Sanz, M; Jornet Fayos, J; Pastor Del Campo, A; Caño Gómez, A; Mollá Olmos, E


    To evaluate if it is possible to determine the extent of pituitary macroadenomas resection in the immediate postoperative pituitary magnetic resonance imaging (MRI). MRI of patient with pituitary macroadenomas from January 2010 until October 2014 were reviewed. Those patients who had diagnostic MRI, immediate post-surgical MRI and at least one MRI control were included. We evaluate if the findings between the immediate postsurgical MRI and the subsequent MRI were concordant. Cases which didn't have evolutionary controls and those who were reoperation for recurrence were excluded. The degree of tumor resection was divided into groups: total resection, partial resection and doubtful. All MRI studies were performed on a1.5T machine following the same protocol sequences for all cases. One morphological part, a dynamic contrast iv and late contrast part. Of the 73 cases included, immediate postoperative pituitary MRI was interpreted as total resection in 38 cases and tumoral rest in 28 cases, uncertainty among rest or inflammatory changes in 7 cases. Follow- up MRI identified 41 cases total resection and tumoral rest in 32. Sensitivity and specificity of 0.78 and 0.82 and positive and negative predictive value (PPV and NPV) 0.89 and 0.89 respectively were calculated. Immediate post-surgery pituitary MRI is useful for assessing the degree of tumor resection and is a good predictor of the final degree of real resection compared with the following MRI studies. It allows us to decide the most appropriate treatment at an early stage. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Molecular Morphology of Pituitary Cells, from Conventional Immunohistochemistry to Fluorescein Imaging

    Directory of Open Access Journals (Sweden)

    R. Yoshiyuki Osamura


    Full Text Available In situ hybridization (ISH at the electron microscopic (EM level is essential for elucidating the intracellular distribution and role of mRNA in protein synthesis. EM-ISH is considered to be an important tool for clarifying the intracellular localization of mRNA and the exact site of pituitary hormone synthesis on the rough endoplasmic reticulum. A combined ISH and immunohistochemistry (IHC under EM (EM-ISH&IHC approach has sufficient ultrastructural resolution, and provides two-dimensional images of the subcellular localization of pituitary hormone and its mRNA in a pituitary cell. The advantages of semiconductor nanocrystals (quantum dots, Qdots and confocal laser scanning microscopy (CLSM enable us to obtain three-dimensional images of the subcellular localization of pituitary hormone and its mRNA. Both EM-ISH&IHC and ISH & IHC using Qdots and CLSM are useful for understanding the relationships between protein and mRNA simultaneously in two or three dimensions. CLSM observation of rab3B and SNARE proteins such as SNAP-25 and syntaxin has revealed that both rab3B and SNARE system proteins play important roles and work together as the exocytotic machinery in anterior pituitary cells. Another important issue is the intracellular transport and secretion of pituitary hormone. We have developed an experimental pituitary cell line, GH3 cell, which has growth hormone (GH linked to enhanced yellow fluorescein protein (EYFP. This stable GH3 cell secretes GH linked to EYFP upon stimulation by Ca2+ influx or Ca2+ release from storage. This GH3 cell line is useful for the real-time visualization of the intracellular transport and secretion of GH. These three methods from conventional immunohistochemistry and fluorescein imaging allow us to consecutively visualize the process of transcription, translation, transport and secretion of anterior pituitary hormone.

  13. Radiosurgery for pituitary adenomas: evaluation of its efficacy and safety

    Directory of Open Access Journals (Sweden)

    Canteras Miguel M


    Full Text Available Abstract Object To assess the effects of radiosurgery (RS on the radiological and hormonal control and its toxicity in the treatment of pituitary adenomas. Methods Retrospective analysis of 42 patients out of the first 48 consecutive patients with pituitary adenomas treated with RS between 1999 and 2008 with a 6 months minimum follow-up. RS was delivered with Gamma Knife as a primary or adjuvant treatment. There were 14 patients with non-secretory adenomas and, among functioning adenomas, 9 were prolactinomas, 9 were adrenocorticotropic hormone-secreting and 10 were growth hormone-secreting tumors. Hormonal control was defined as hormonal response (decline of more than 50% from the pre-RS levels and hormonal normalization. Radiological control was defined as stasis or shrinkage of the tumor. Hypopituitarism and visual deficit were the morbidity outcomes. Hypopituitarism was defined as the initiation of any hormone replacement therapy and visual deficit as loss of visual acuity or visual field after RS. Results The median follow-up was 42 months (6-109 months. The median dose was 12,5 Gy (9 - 15 Gy and 20 Gy (12 - 28 Gy for non-secretory and secretory adenomas, respectively. Tumor growth was controlled in 98% (41 in 42 of the cases and tumor shrinkage ocurred in 10% (4 in 42 of the cases. The 3-year actuarial rate of hormonal control and normalization were 62,4% and 37,6%, respectively, and the 5-year actuarial rate were 81,2% and 55,4%, respectively. The median latency period for hormonal control and normalization was, respectively, 15 and 18 months. On univariate analysis, there were no relationships between median dose or tumoral volume and hormonal control or normalization. There were no patients with visual deficit and 1 patient had hypopituitarism after RS. Conclusions RS is an effective and safe therapeutic option in the management of selected patients with pituitary adenomas. The short latency of the radiation response, the highly

  14. Clinical results of LINAC-based stereotactic radiosurgery for pituitary adenoma

    Energy Technology Data Exchange (ETDEWEB)

    Muramatsu, Julia; Yoshida, Masanori; Shioura, Hiroki; Kawamura, Yasutaka; Ito, Harumi; Takeuchi, Hiroaki; Kubota, Toshihiko [Fukui Medical Univ., Matsuoka (Japan); Maruyama, Ichiro [The Wakasa Wan Energy Research Center, Tsuruga, Fukui (Japan)


    We retrospectively evaluated our clinical results of stereotactic radiosurgery (SRS) for pituitary adenoma. Between 1995 and 2000, 13 patients were treated with SRS for pituitary adenoma. In all cases, the tumors had already been surgically resected. The adenomas were functional in 5 and non-functional in 8 patients. The median follow-up period was 30 months. SRS was performed with the use of a dedicated stereotactic 10-MV linear accelerator (LINAC). The median dose to the tumor margin was 15 Gy. The dose to the optic apparatus was limited to less than 8 Gy. MR images of 12 patients revealed tumor complete response (CR) in one case and partial response (PR) in 9 cases; in the remaining two patients, tumor size decreased by less than 50%. There was no recognizable regrowth of any of the tumors. In two of four GH-secreting adenomas, hormonal overproduction normalized, while the other two showed reduced hormonal production. One PRL-secreting adenoma did not respond. Reduction of visual acuity and field was seen in one patient. This patient also had a brain infarction. None of the patients developed brain radionecrosis or radiation-induced hypopituitarism. Although further studies based on greater numbers of cases and longer follow-up periods are needed, our results suggest that SRS seems to be a safe, effective treatment for pituitary adenoma. (author)

  15. Stem cells in the canine pituitary gland and in pituitary adenomas. (United States)

    van Rijn, Sarah J; Tryfonidou, Marianna A; Hanson, Jeanette M; Penning, Louis C; Meij, Björn P


    Cushing's disease (CD) or pituitary-dependent hypercortisolism is a common endocrinopathy in dogs, with an estimated prevalence of 1 or 2 in 1000 dogs per year. It is caused by an adrenocorticotropic hormone secreting adenoma in the pars distalis or pars intermedia of the pituitary gland. The pituitary gland is a small endocrine gland located in the pituitary fossa. In the postnatal individual, the hypothalamus-pituitary axis plays a central role in maintaining homeostatic functions, like control of metabolism, reproduction, and growth. Stem cells are suggested to play a role in the homeostatic adaptations of the adult pituitary gland, such as the rapid specific cell-type expansion in response to pregnancy or lactation. Several cell populations have been suggested as pituitary stem cells, such as Side Population cells and cells expressing Sox2 or Nestin. These cell populations are discussed in this review. Also, stem and progenitor cells are thought to play a role in pituitary tumorigenesis, such as the development of pituitary adenomas in dogs. There are limited reports on the role of stem cells in pituitary adenomas, especially in dogs. Further studies are needed to identify and characterize this cell population and to develop specific cell targeting therapeutic strategies as a new way of treating canine CD.

  16. Ectopic nasopharyngeal pituitary adenoma resected with endoscopic technique. (United States)

    Alexander, Alan A Z; Niktash, Nikta; Kardon, David E; Sadeghi, Nader


    We describe the case of an 80-year-old man with diabetes who presented with nonspecific dizziness. He was found on magnetic resonance imaging to have a 3.2-cm mass within the posterior and central aspect of the nasopharynx. Nasal endoscopy showed that the mass, which arose from the posterior edge of the nasal septum and was attached to the superior nasopharynx, was narrowing the patient's airway. Although initially the mass was suspected to be a minor salivary gland tumor, histopathologic analysis led to a diagnosis of pituitary adenoma. The ectopic tumor was removed via transnasal en bloc resection with partial adjacent septal resection. Final pathology confirmed the diagnosis. The patient had an uneventful recovery and no sequellae at 2-year follow-up.

  17. Landscape of Familial Isolated and Young-Onset Pituitary Adenomas: Prospective Diagnosis in AIP Mutation Carriers (United States)

    Hernández-Ramírez, Laura C.; Gabrovska, Plamena; Dénes, Judit; Stals, Karen; Trivellin, Giampaolo; Tilley, Daniel; Ferraù, Francesco; Evanson, Jane; Ellard, Sian; Grossman, Ashley B.; Roncaroli, Federico; Gadelha, Mônica R.


    Context: Familial isolated pituitary adenoma (FIPA) due to aryl hydrocarbon receptor interacting protein (AIP) gene mutations is an autosomal dominant disease with incomplete penetrance. Clinical screening of apparently unaffected AIP mutation (AIPmut) carriers could identify previously unrecognized disease. Objective: To determine the AIP mutational status of FIPA and young pituitary adenoma patients, analyzing their clinical characteristics, and to perform clinical screening of apparently unaffected AIPmut carrier family members. Design: This was an observational, longitudinal study conducted over 7 years. Setting: International collaborative study conducted at referral centers for pituitary diseases. Participants: FIPA families (n = 216) and sporadic young-onset (≤30 y) pituitary adenoma patients (n = 404) participated in the study. Interventions: We performed genetic screening of patients for AIPmuts, clinical assessment of their family members, and genetic screening for somatic GNAS1 mutations and the germline FGFR4 p.G388R variant. Main Outcome Measure(s): We assessed clinical disease in mutation carriers, comparison of characteristics of AIPmut positive and negative patients, results of GNAS1, and FGFR4 analysis. Results: Thirty-seven FIPA families and 34 sporadic patients had AIPmuts. Patients with truncating AIPmuts had a younger age at disease onset and diagnosis, compared with patients with nontruncating AIPmuts. Somatic GNAS1 mutations were absent in tumors from AIPmut-positive patients, and the studied FGFR4 variant did not modify the disease behavior or penetrance in AIPmut-positive individuals. A total of 164 AIPmut-positive unaffected family members were identified; pituitary disease was detected in 18 of those who underwent clinical screening. Conclusions: A quarter of the AIPmut carriers screened were diagnosed with pituitary disease, justifying this screening and suggesting a variable clinical course for AIPmut-positive pituitary adenomas. PMID

  18. Boron neutron capture therapy (BNCT) inhibits tumor development from precancerous tissue: an experimental study that supports a potential new application of BNCT. (United States)

    Monti Hughes, A; Heber, E M; Pozzi, E; Nigg, D W; Calzetta, O; Blaumann, H; Longhino, J; Nievas, S I; Aromando, R F; Itoiz, M E; Trivillin, V A; Schwint, A E


    We previously demonstrated the efficacy of boron neutron capture therapy (BNCT) mediated by boronophenylalanine (BPA), GB-10 (Na(2)(10)B(10)H(10)) and (GB-10+BPA) to control tumors, with no normal tissue radiotoxicity, in the hamster cheek pouch oral cancer model. Herein we developed a novel experimental model of field-cancerization and precancerous lesions (globally termed herein precancerous tissue) in the hamster cheek pouch to explore the long-term potential inhibitory effect of the same BNCT protocols on the development of second primary tumors from precancerous tissue. Clinically, second primary tumor recurrences occur in field-cancerized tissue, causing therapeutic failure. We performed boron biodistribution studies followed by in vivo BNCT studies, with 8 months follow-up. All 3 BNCT protocols induced a statistically significant reduction in tumor development from precancerous tissue, reaching a maximum inhibition of 77-100%. The inhibitory effect of BPA-BNCT and (GB-10+BPA)-BNCT persisted at 51% at the end of follow-up (8 months), whereas for GB-10-BNCT it faded after 2 months. Likewise, beam-only elicited a significant but transient reduction in tumor development. No normal tissue radiotoxicity was observed. At 8 months post-treatment with BPA-BNCT or (GB-10+BPA)-BNCT, the precancerous pouches that did not develop tumors had regained the macroscopic and histological appearance of normal (non-cancerized) pouches. A potential new clinical application of BNCT would lie in its capacity to inhibit local regional recurrences.

  19. Hypercortisolism due to a Pituitary Adenoma Associated with Beckwith-Wiedemann Syndrome. (United States)

    Brioude, Frederic; Nicolas, Carole; Marey, Isabelle; Gaillard, Stephan; Bernier, Michèle; Das Neves, Cristina; Le Bouc, Yves; Touraine, Philippe; Netchine, Irene


    Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome with an increased risk of cancer. Most BWS patients show a molecular defect in the 11p15 region that contains imprinted genes. BWS has been associated with malignant neoplasms during infancy. Descriptions of benign tumors, especially in adult patients, are rarer. We report the case of a BWS patient with pituitary adenoma caused by loss of methylation (LOM) at ICR2 (locus CDKN1C/KCNQ1OT1). The patient was referred to an endocrinology unit for suspicion of Cushing's disease due to a history of macroglossia and hemihyperplasia. Biological tests led to the diagnosis of ACTH-dependent hypercortisolism. MRI showed a microadenoma of the pituitary gland, confirming the diagnosis of Cushing's disease. DNA methylation analysis revealed LOM at ICR2 that was in a mosaic state in the patient's leukocytes, but was present in nearly all cells of the pituitary adenoma. The epigenetic defect was associated with a somatic USP8 mutation in the adenoma. Pituitary adenoma rarely occurs in patients with BWS. However, BWS should be considered in cases of pituitary adenoma with minor and/or major signs of BWS. The association between ICR2 LOM and USP8 mutation in the adenoma is questionable. © 2016 S. Karger AG, Basel.

  20. A pitfall in diagnosing Cushing's disease: ectopic ACTH-producing pituitary adenoma in the sphenoid sinus. (United States)

    Flitsch, J; Schmid, S M; Bernreuther, C; Winterberg, B; Ritter, M M; Lehnert, H; Burkhardt, T


    To show a rare case of Cushing's disease and possible cause of failed transsphenoidal surgery. We report on a 50-year-old woman suffering from ACTH-dependent Cushing's syndrome. Endocrinological work-up including low-dose/high-dose dexamethasone test (Liddle-test) and CRH test were clearly compatible with pituitary origin. Although an MRI showed no pituitary tumor, CRH-stimulated petrosal sinus sampling revealed a significant central-peripheral gradient in ACTH concentrations, rendering Cushing's disease very likely. The patient underwent transsphenoidal surgery with negative exploration of the pituitary gland. After intraoperative re-evaluation of the preoperative MRI, a "polyp" at the bottom of the sphenoid sinus was identified. The intraoperative microscopic aspect as well as instantaneous sections and cytology of a biopsy confirmed an adenoma, which was then removed. Histological analysis demonstrated an ACTH-producing pituitary adenoma adjacent to respiratory mucous membrane consisting of ciliated epithelium with submucous connective tissue. Postoperatively, ACTH concentrations were decreased and intermittent hydrocortisone substitution treatment was initiated. At the 3-month follow up, Cushing's stigmata were found to be alleviated and the hydrocortisone dosage could be reduced. Ectopic pituitary adenoma tissue causing Cushing's disease is extremely rare but a potential cause for surgical failure or re-evaluation.

  1. Segmentation of pituitary adenoma: a graph-based method vs. a balloon inflation method. (United States)

    Egger, Jan; Zukić, Dženan; Freisleben, Bernd; Kolb, Andreas; Nimsky, Christopher


    Among all abnormal growths inside the skull, the percentage of tumors in sellar region is approximately 10-15%, and the pituitary adenoma is the most common sellar lesion. A time-consuming process that can be shortened by using adequate algorithms is the manual segmentation of pituitary adenomas. In this contribution, two methods for pituitary adenoma segmentation in the human brain are presented and compared using magnetic resonance imaging (MRI) patient data from the clinical routine: Method A is a graph-based method that sets up a directed and weighted graph and performs a min-cut for optimal segmentation results: Method B is a balloon inflation method that uses balloon inflation forces to detect the pituitary adenoma boundaries. The ground truth of the pituitary adenoma boundaries - for the evaluation of the methods - are manually extracted by neurosurgeons. Comparison is done using the Dice Similarity Coefficient (DSC), a measure for spatial overlap of different segmentation results. The average DSC for all data sets is 77.5±4.5% for the graph-based method and 75.9±7.2% for the balloon inflation method showing no significant difference. The overall segmentation time of the implemented approaches was less than 4s - compared with a manual segmentation that took, on the average, 3.9±0.5min. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Dynamic {sup 11}C-methionine PET analysis has an additional value for differentiating malignant tumors from granulomas: an experimental study using small animal PET

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Songji; Zhao, Yan [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo (Japan); Hokkaido University, Department of Tracer Kinetics and Bioanalysis, Graduate School of Medicine, Sapporo (Japan); Kuge, Yuji; Hatano, Toshiyuki [Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan); Yi, Min; Kohanawa, Masashi [Hokkaido University, Department of Advanced Medicine, Graduate School of Medicine, Sapporo (Japan); Magota, Keiichi; Tamaki, Nagara [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo (Japan); Nishijima, Ken-ichi [Hokkaido University, Department of Molecular Imaging, Graduate School of Medicine, Sapporo (Japan)


    We evaluated whether the dynamic profile of L-{sup 11}C-methionine ({sup 11}C-MET) may have an additional value in differentiating malignant tumors from granulomas in experimental rat models by small animal positron emission tomography (PET). Rhodococcus aurantiacus and allogenic rat C6 glioma cells were inoculated, respectively, into the right and left calf muscles to generate a rat model bearing both granulomas and tumors (n = 6). Ten days after the inoculations, dynamic {sup 11}C-MET PET was performed by small animal PET up to 120 min after injection of {sup 11}C-MET. The next day, after overnight fasting, the rats were injected with {sup 18}F-2-deoxy-2-fluoro-D-glucose ({sup 18}F-FDG), and dynamic {sup 18}F-FDG PET was performed up to 180 min. The time-activity curves, static images, and mean standardized uptake value (SUV) in the lesions were calculated. {sup 11}C-MET uptake in the granuloma showed a slow exponential clearance after an initial distribution, while the uptake in the tumor gradually increased with time. The dynamic pattern of {sup 11}C-MET uptake in the granuloma was significantly different from that in the tumor (p < 0.001). In the static analysis of {sup 11}C-MET, visual assessment and SUV analysis could not differentiate the tumor from the granuloma in all cases, although the mean SUV in the granuloma (1.48 {+-} 0.09) was significantly lower than that in the tumor (1.72 {+-} 0.18, p < 0.01). The dynamic patterns, static images, and mean SUVs of {sup 18}F-FDG in the granuloma were similar to those in the tumor (p = NS). Dynamic {sup 11}C-MET PET has an additional value for differentiating malignant tumors from granulomatous lesions, which deserves further elucidation in clinical settings. (orig.)

  3. Radiotherapy for pituitary adenomas: long-term outcome and complications

    Energy Technology Data Exchange (ETDEWEB)

    Rim, Chai Hong; Yang, Dae Sik; Park, Young Je; Yoon, Won Sup; Lee, Jung AE; Kim, Chul Yong [Korea University Medical Center, Seoul (Korea, Republic of)


    To evaluate long-term local control rate and toxicity in patients treated with external beam radiotherapy (EBRT) for pituitary adenomas. We retrospectively reviewed the medical records of 60 patients treated with EBRT for pituitary adenoma at Korea University Medical Center from 1996 and 2006. Thirty-fi ve patients had hormone secreting tumors, 25 patients had non-secreting tumors. Fifty-seven patients had received postoperative radiotherapy (RT), and 3 had received RT alone. Median total dose was 54 Gy (range, 36 to 61.2 Gy). The definition of tumor progression were as follows: evidence of tumor progression on computed tomography or magnetic resonance imaging, worsening of clinical sign requiring additional operation or others, rising serum hormone level against a previously stable or falling value, and failure of controlling serum hormone level so that the hormone level had been far from optimal range until last follow-up. Age, sex, hormone secretion, tumor extension, tumor size, and radiation dose were analyzed for prognostic significance in tumor control. Median follow-up was 5.7 years (range, 2 to 14.4 years). The 10-year actuarial local control rates for non-secreting and secreting adenomas were 96% and 66%, respectively. In univariate analysis, hormone secretion was significant prognostic factor (p = 0.042) and cavernous sinus extension was marginally significant factor (p = 0.054) for adverse local control. All other factors were not significant. In multivariate analysis, hormone secretion and gender were significant. Fifty-three patients had mass-effect symptoms (headache, dizziness, visual disturbance, hypopituitarism, loss of consciousness, and cranial nerve palsy). A total of 17 of 23 patients with headache and 27 of 34 patients with visual impairment were improved. Twenty-seven patients experienced symptoms of endocrine hypersecretion (galactorrhea, amenorrhea, irregular menstruation, decreased libido, gynecomastia, acromegaly, and Cushing

  4. Research in radiobiology: Final report of work in progress in immunobiology of experimental host-tumor relationships

    Energy Technology Data Exchange (ETDEWEB)


    Our work on the immunobiology of tumors induced in normal mice by non-ionizing radiation and chemical carcinogens has previously demonstrated a correlation between MHC molecule expression and the immunogenicity of tumors in a transplanted syngeneic host. Such that immunogenic or regressive tumors were found to demonstrate higher constitutive or inducible levels of MHC expression, while most virulent, aggressive tumors exhibited a low level of MHC Class I expression. We attributed much of the control of MHC molecule expression by antigen-bearing tumors and normal cells to the immunological status of the host since the host must provide the appropriate stimulus to enhance MHC antigen expression by the invading tumor. Our results with UVR-induced tumors suggested that a significant role is played by the T-cell lymphokine, {gamma}-interferon ({gamma}IFN), in the modulation of MHC molecule expression in vivo. Virulent tumors, induced by boneseeking radionuclides, may be refractory to {gamma}IFN stimulation of MHC molecule expression. It is also possible that certain tumors might be fully responsive to the Class I modulatory influences by {gamma}IFN, but exhibit a reduced capacity to stimulate the synthesis of this lymphokine by host T cells. We present experiments designed to : Describe the virulence, latency period, and transplantation characteristics of {sup 238}PU, {sup 24l}Am, and {sup 228}Th tumors arising as osteogenic sarcomas and hepatic carcinomas, to determine the relationship between inducible expression of MHC Class I molecules by {gamma}IFN and in vivo immunogenicity of these radioisotype-induced tumors, and to elucidate any molecular mechanisms responsible for a lack of responsiveness to a {gamma}IFN failure by the host to induce host {gamma}IFN production.

  5. Research in radiobiology: Final report of work in progress in immunobiology of experimental host-tumor relationships

    Energy Technology Data Exchange (ETDEWEB)


    Our work on the immunobiology of tumors induced in normal mice by non-ionizing radiation and chemical carcinogens has previously demonstrated a correlation between MHC molecule expression and the immunogenicity of tumors in a transplanted syngeneic host. Such that immunogenic or regressive tumors were found to demonstrate higher constitutive or inducible levels of MHC expression, while most virulent, aggressive tumors exhibited a low level of MHC Class I expression. We attributed much of the control of MHC molecule expression by antigen-bearing tumors and normal cells to the immunological status of the host since the host must provide the appropriate stimulus to enhance MHC antigen expression by the invading tumor. Our results with UVR-induced tumors suggested that a significant role is played by the T-cell lymphokine, [gamma]-interferon ([gamma]IFN), in the modulation of MHC molecule expression in vivo. Virulent tumors, induced by boneseeking radionuclides, may be refractory to [gamma]IFN stimulation of MHC molecule expression. It is also possible that certain tumors might be fully responsive to the Class I modulatory influences by [gamma]IFN, but exhibit a reduced capacity to stimulate the synthesis of this lymphokine by host T cells. We present experiments designed to : Describe the virulence, latency period, and transplantation characteristics of [sup 238]PU, [sup 24l]Am, and [sup 228]Th tumors arising as osteogenic sarcomas and hepatic carcinomas, to determine the relationship between inducible expression of MHC Class I molecules by [gamma]IFN and in vivo immunogenicity of these radioisotype-induced tumors, and to elucidate any molecular mechanisms responsible for a lack of responsiveness to a [gamma]IFN failure by the host to induce host [gamma]IFN production.

  6. Endoscopic endonasal transsphenoidal surgery for invasive pituitary adenoma. (United States)

    Zhang, Xiang; Fei, Zhou; Zhang, Wei; Zhang, Jian-ning; Liu, Wei-ping; Fu, Luo-an; Cao, Wei-dong; Jiang, Xiao-fan; Song, Shao-jun


    Invasive pituitary adenomas (IPA) involving the skull base extend from the sella region, and invade surrounding structures. In the present study, we reviewed the therapeutic efficacy in a group of patients with IPA treated with endoscopic endonasal transsphenoidal surgery. Data from 78 IPA patients at our hospital were retrospectively reviewed. The diagnostic modalities, surgical techniques, and outcomes were reviewed. Diagnosis was confirmed by endocrinological profile and CT or MRI in all patients. Surgery was performed via an endoscopic endonasal transsphenoidal approach. Thirty-five patients (44.9%) had hormonally active tumors, and 43 (55.1%) had nonfunctioning tumors. Complete removal of the tumor was achieved in 62 patients (79.5%) and subtotal removal in 12 (15.4%); partial removal was achieved in the remaining four patients (5.1%) who had fibrous or dumbbell-shaped adenomas. The mean follow-up was 43.2 months in 65 patients and the clinical symptoms in all patients improved to varying degrees. In 52 patients, the tumors completely disappeared on follow-up imaging. Visual symptoms improved in 96.4% of the patients who had presented with visual impairment. These surgical results show that endoscopic endonasal transsphenoidal surgery for resection of IPA has advantages. We suggest that the endoscopic endonasal transsphenoidal surgery method is a safe, minimally invasive and efficient surgical technique for removal of IPA, providing good visualization of the operative field, generally complete tumor removal, short procedure duration, and minimal postoperative complications.

  7. Magnetic resonance imaging of hypothalamus hypophysis axis lesions; Relationship between posterior pituitary function and posterior bright spot

    Energy Technology Data Exchange (ETDEWEB)

    Shiina, Takeki; Uno, Kimiichi; Arimizu, Noboru; Yoshida, Sho (Chiba Univ. (Japan). School of Medicine); Yamada, Kenichi


    Magnetic resonance imaging (MRI) using a 0.5T superconductive machine was performed to the thirty three cases with a variety of the sellar and parasellar tumors and with dysfunction of the hypothalamus-hypophysis axis. Posterior pituitary bright spot (PBS) on T1 weighted image was evaluated with the pituitary hormonal function. These cases were 12 cases of post-treated tumors including pituitary adenoma (9 patients), suprasellar germinoma (2 patients) and craniopharyngioma (one patient), and non-tumorous conditions including 15 cases of central diabetes insipidus (DI), Syndrome of inappropriate secretion of ADH (SIADH) (one patient), Sheehan's syndrome (3 patients) and anorexia nervosa (2 patients). Pituitary bright spot was not seen in all 19 cases with overt DI. On the other hand, PBS was not seen in 9 cases without overt DI. Three cases of these 9 cases showing Sheehan's syndrome with insufficient antidiuretic hormone (ADH) secretion was considered as the state of subclinical DI. Posterior bright spot was not seen in all 13 cases of empty sella including partial empty sella. The results suggested that disappearance of PBS represents abnormality or loss of posterior pituitary function and also it was considered to be closely related to the empty sella. (author).

  8. Combination use of lentinan with x-ray therapy in mouse experimental tumor system, (3). Combination effect on the metastatic tumors

    Energy Technology Data Exchange (ETDEWEB)

    Shiio, Tsuyoshi; Ohishi, Kazuo; Niitsu, Iwayasu; Hayashibara, Hiromi; Tsuchiya, Yoshiharu; Yoshihama, Takashi; Moriyuki, Hirobumi


    Combination effect of lentinan with X-ray irradiation on the metastatic mouse tumors, L1210, KLN205 and Lewis lung carcinoma were studied. Combination use of lentinan with X-ray therapy prolonged the life of BDF/sub 1/ mice bearing L1210 leukemia in the suitable combination conditions. Combination effects of lentinan with X-ray therapy were also observed on the suppression of the growth of KLN205 squamus cell carcinoma and on the suppression of the metastasis of Lewis lung carcinoma. Especially, in the case that lentinan was administered before or after X-ray local irradiation in the pulmorary metastasis system of Lewis lung carcinoma, a marked suppressin of pulmonary metastasis was observed and 2 to 4 mice among 8 tested mice were tumor free.

  9. Inflammatory Pseudotumor of the Pituitary Gland Mimicking a Pituitary Adenoma: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Da Mi; Yu, In Kyu [Dept. of Radiology, Eulji University Hospital, Daejeon (Korea, Republic of); Kim, Han Kyu [Dept. of Neurosurgery, Eulji University Hospital, Daejeon (Korea, Republic of); Son Hyun Jin [Dept. of Pathology, Eulji University Hospital, Daejeon (Korea, Republic of)


    A 38-year-old man was admitted to our hospital with diplopia. The patient had a relatively well-defined pituitary mass with high cellularity as well as weaker enhancement on imaging modalities including computed tomography (CT) and magnetic resonance imaging (MRI), than a typical pituitary adenoma. The distinction between a pseudotumor and an invasive neoplasm is very difficult before biopsy. In this case report, we discuss the characteristic imaging features of a fibrosing inflammatory pseudotumor of the pituitary gland

  10. Effect of polychromatic visible light on proliferation of tumor cells under conditions in vitro and in vivo—after implantation to experimental animals (United States)

    Knyazev, N. A.; Samoilova, K. A.; Filatova, N. A.; Galaktionova, A. A.


    -irradiated animals. Moreover, there was recorded a decrease of incidence of the tumor development—by 16-24%, downregulation of the tumor growth rate—on average, by 40% and an increase of survival of the animals (by 20%). Thus, for the first time, an antitumor effect of polychromatic visible light has been shown at its application on the body surface of experimental animals.

  11. Prolactinomas, Cushing's disease and acromegaly: debating the role of medical therapy for secretory pituitary adenomas

    Directory of Open Access Journals (Sweden)

    Bonert Vivien S


    Full Text Available Abstract Pituitary adenomas are associated with a variety of clinical manifestations resulting from excessive hormone secretion and tumor mass effects, and require a multidisciplinary management approach. This article discusses the treatment modalities for the management of patients with a prolactinoma, Cushing's disease and acromegaly, and summarizes the options for medical therapy in these patients. First-line treatment of prolactinomas is pharmacotherapy with dopamine agonists; recent reports of cardiac valve abnormalities associated with this class of medication in Parkinson's disease has prompted study in hyperprolactinemic populations. Patients with resistance to dopamine agonists may require other treatment. First-line treatment of Cushing's disease is pituitary surgery by a surgeon with experience in this condition. Current medical options for Cushing's disease block adrenal cortisol production, but do not treat the underlying disease. Pituitary-directed medical therapies are now being explored. In several small studies, the dopamine agonist cabergoline normalized urinary free cortisol in some patients. The multi-receptor targeted somatostatin analogue pasireotide (SOM230 shows promise as a pituitary-directed medical therapy in Cushing's disease; further studies will determine its efficacy and safety. Radiation therapy, with medical adrenal blockade while awaiting the effects of radiation, and bilateral adrenalectomy remain standard treatment options for patients not cured with pituitary surgery. In patients with acromegaly, surgery remains the first-line treatment option when the tumor is likely to be completely resected, or for debulking, especially when the tumor is compressing neurovisual structures. Primary therapy with somatostatin analogues has been used in some patients with large extrasellar tumors not amenable to surgical cure, patients at high surgical risk and patients who decline surgery. Pegvisomant is indicated in patients

  12. MASEP gamma knife radiosurgery for secretory pituitary adenomas: experience in 347 consecutive cases

    Directory of Open Access Journals (Sweden)

    Yuan Shubin


    Full Text Available Abstract Background Secretory pituitary adenomas are very common brain tumors. Historically, the treatment armamentarium for secretory pituitary adenomas included neurosurgery, medical management, and fractionated radiotherapy. In recent years, MASEP gamma knife radiosurgery (MASEP GKRS has emerged as an important treatment modality in the management of secretory pituitary adenomas. The goal of this research is to define accurately the efficacy, safety, complications, and role of MASEP GKRS for treatment of secretory pituitary adenomas. Methods Between 1997 and 2007 a total of 347 patients with secretory pituitary adenomas treated with MASEP GKRS and with at least 60 months of follow-up data were identified. In 47 of these patients some form of prior treatment such as transsphenoidal resection, or craniotomy and resection had been conducted. The others were deemed ineligible for microsurgery because of body health or private choice, and MASEP GKRS served as the primary treatment modality. Endocrinological, ophthalmological, and neuroradiological responses were evaluated. Results MASEP GKRS was tolerated well in these patients under the follow-up period ranged from 60 to 90 months; acute radioreaction was rare and 17 patients had transient headaches with no clinical significance. Late radioreaction was noted in 1 patient and consisted of consistent headache. Of the 68 patients with adrenocorticotropic hormone-secreting(ACTH adenomas, 89.7% showed tumor volume decrease or remain unchanged and 27.9% experienced normalization of hormone level. Of the 176 patients with prolactinomas, 23.3% had normalization of hormone level and 90.3% showed tumor volume decrease or remain unchanged. Of the 103 patients with growth hormone-secreting(GH adenomas, 95.1% experienced tumor volume decrease or remain unchanged and 36.9% showed normalization of hormone level. Conclusion MASEP GKRS is safe and effective in treating secretory pituitary adenomas. None of the

  13. PET/MR imaging in the diagnosis of hormone-producing pituitary micro-adenoma: a prospective pilot study. (United States)

    Wang, Hao; Hou, Bo; Lu, Lin; Feng, Ming; Zang, Jie; Yao, Shaobo; Feng, Feng; Wang, Renzhi; Li, Fang; Zhu, Zhaohui


    Purpose: This study was designed to evaluate positron emission tomography/magnetic resonance (PET/MR), using 18F-FDG and 68Ga-DOTATATE as tracers, in the detection of hormone-producing pituitary micro-adenoma, where diagnosis is difficult using magnetic resonance imaging (MRI) alone. Methods: A total of 37 patients with elevated hormone levels were recruited, including 19 patients with undiagnosable primary pituitary tumors and 18 patients with suspected recurrent pituitary adenomas (PAs). Patients underwent 18F-FDG PET/MR and 68Ga-DOTATATE PET/MR within one week. Finally, 27 patients underwent transsphenoidal adenomectomy within two weeks, 3 patients underwent sella region radiotherapy, 1 patient underwent somatostatin therapy, and the other 6 patients had a clinical follow-up. The image characteristics and uptake levels were correlated with the surgical findings and pathological results. Receiver-operating-characteristic (ROC) curve analysis was performed to determine an optimal cutoff pituitary to differentiate pituitary adenoma from normal pituitary tissue. The area under the ROC curve was calculated to compare the diagnostic performance. Results: The PET/MR images were in diagnostic quality without obvious image artifacts. The high contrast of PET imaging provided complementary information to the fine anatomy display of MRI. Increased 18F-FDG uptake was clearly observed in the all patients, whereas enhanced MRI enhanced MRI using 0.05 mmol/kg Gadopentetate dimeglumine had suspicious findings only in 47% primary and 39% recurrent PAs patients, which were 37% and 50%, respectively when using 0.1 mmol/kg Gadopentetate dimeglumine. The maximum standardized uptake values (SUVmax) of 18F-FDG activity (6.8 ± 3.7) in 16 primary pituitary adenomas who underwent transsphenoidal adenomectomy, was significantly higher than that of the rest of the normal pituitary gland (3.2 ± 1.1, P adenoma showed moderate 68Ga-DOTATATE uptake (3.8 ± 2.6), but generally lower than that

  14. Clinical Interrogation for Unveiling an Isolated Hypophysitis Mimicking Pituitary Adenoma. (United States)

    Lee, Seungjoo; Choi, Jun Ho; Kim, Chang Jin; Kim, Jeong Hoon


    Hypophysitis is a rare disease entity mimicking a pituitary adenoma. Despite crucial disease involving a pituitary gland which is a main component of the hormonal axis, there have been minimal researches regarding the hypophysitis. In this study, we described the constellation of the preoperative findings including clinical, radiologic, and endocrinologic features, as well as postoperative outcomes of the hypophysitis. The authors reviewed the data retrospectively of a total of 2814 patients who underwent microsurgery at our institution to treat a pituitary mass lesion. Among them, the patients proven as hypophysitis in histologic examination were enrolled, followed by stratification into tumor-associated hypophysitis and isolated hypophysitis depending on the existence of associated tumor lesion. As a result, a total 21 cases were enrolled consisting of the 13 cases of tumor-associated and the 8 cases of isolated hypophysitis. In this study, the isolated hypophysitis was focused on the analysis. All patients with isolated hypophysitis were evaluated the clinical, radiologic, and endocrinologic tests preoperatively. After microsurgery, all patients had a minimum follow up of 6 months (6∼72 months). The clinical symptoms, endocrinologic tests, and brain MRI were checked at every 6 months during first 2 year, since then, at every 12 months. Among 2814 cases of pituitary mass lesion underwent microsurgery, the hypophysitis were found 21 cases (0.74 %). The 13 cases were the tumor-associated hypophysitis, consisting of rathke's cleft cyst (7 cases), craniopharyngioma (3 cases), pituitary adenoma (2 cases), and germinoma (1 case). The 8 cases were the isolated hypophysitis including lymphocytic (4 cases), granulomatous (3 cases), and IgG4-related (1 case) hypophysitis. The patients presented a wide range of clinical symptoms from general weakness to panhypopituitarism. In addition, the most remarkable radiologic features of the isolated hypophysitis were infundibular

  15. Prenatal expression of interleukin 1beta and interleukin 6 in the rat pituitary gland. (United States)

    Moro, J A; Carretero, J; Alonso, M I; Martín, C; Gato, A; Mano, A de la


    It is known that interleukin 1beta (IL-1beta) and interleukin 6 (IL-6) are expressed post-natally in normal and tumoral cells in the anterior pituitary, and that they play a role in both the liberation of different hormones and in the growth, proliferation and tumor formation of the pituitary gland. However, their expression and role during embryonic and fetal development remain unknown. We have performed an immunocytochemistry study of prenatal expression and distribution of IL-1beta and IL-6 in isolated embryonic rat Rathke's pouch prior to birth, more specifically between 13.5 and 19.5 days p.c. Western-blot analysis carried out on 19.5-day p.c. embryos showed positive immunolabelling for IL-1beta and IL-6. These interleukins were initially expressed simultaneously in the rostral and ventral portions of Rathke's pouch in 15.5-day p.c. embryos, and this expression progressed caudodorsally in later developmental stages, extending to most of the hypophysis before birth. The number of cells expressing these interleukins increased throughout this period: 48.22% of anterior pituitary cells expressed IL-6 in 19.5-day embryos, whilst IL-1beta was positive in 39.8% of the cells. Moreover, we have demonstrated that some adenohypophyseal cells co-express both interleukins. Such findings represent the first step towards an understanding of the physiological role of these interleukins in anterior pituitary development.

  16. Anesthesia and Intensive care implications for pituitary surgery: Recent trends and advancements

    Directory of Open Access Journals (Sweden)

    Sukhminder Jit Singh Bajwa


    Full Text Available The advancements in neuro-endocrine surgical interventions have been well supported by similar advancements in anesthesiology and intensive care. Surgery of the pituitary tumor poses unique challenges to the anesthesiologists and the intensivists as it involves the principles and practices of both endocrine and neurosurgical management. A multidisciplinary approach involving the endocrine surgeon, neurosurgeon, anesthesiologist, endocrinologist and intensivist is mandatory for a successful surgical outcome. The focus of pre-anesthetic checkup is mainly directed at the endocrinological manifestations of pituitary hypo or hyper-secretion as it secretes a variety of essential hormones, and also any pathological state that can cause imbalance of pituitary secretions. The pathophysiological aspects associated with pituitary tumors mandate a thorough airway, cardiovascular, neurologic and endocrinological assessment. A meticulous preoperative preparation and definite plans for the intra-operative period are the important clinical components of the anesthetic strategy. Various anesthetic modalities and drugs can be useful to provide a smooth intra-operative period by countering any complication and thus providing an uneventful recovery period.

  17. Metastases from a pituitary adenoma: MRI

    Energy Technology Data Exchange (ETDEWEB)

    Boucaud, L. de; Dousset, V.; Viaud, B.; Caille, J.M. [Service de Neuroradiologie, CHU Pellegrin, Bordeaux (France); Caillaud, P.; Guerin, J. [Service de Neurochirurgie, CHU Pellegrin, Bordeaux (France)


    Few cases of pituitary adenoma with metastases have been reported. We report a case with histologically benign intracranial and cauda equina metastases. We compare it to the others in the literature. (orig.)

  18. Glioblastoma after radiotherapy for pituitary adenoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Young; Park, Kyung Ran; KIm, Jun Joo; Lee, Chong In; Kim, Myung Soon; Jung, Soon Hee [Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of)


    A 39-year-old woman developed a glioblastoma about 7 years and 10 months after local radiotherapy (45 Gy) for pituitary adenoma. Clinical and histopathological details are presented, and previously reported cases of radiation-induced glioma are reviewed.

  19. Pituitary diseases : long-term clinical consequences

    NARCIS (Netherlands)

    Klaauw, Agatha Apolonia van der


    This thesis describes various studies during the long-term follow-up of patients after treatment for pituitary diseases. The focus of this thesis is acromegaly, growth hormone deficiency, sleep and quality of life. Various aspects are described.

  20. Caveolin-1 sensitizes rat pituitary adenoma GH3 cells to bromocriptine induced apoptosis

    Directory of Open Access Journals (Sweden)

    Huang Mu-Chiou


    Full Text Available Abstract Background Prolactinoma is the most frequent pituitary tumor in humans. The dopamine D2 receptor agonist bromocriptine has been widely used clinically to treat human breast tumor and prolactinoma through inhibition of hyperprolactinemia and induction of tumor cell apoptosis, respectively, but the molecular mechanism of bromocriptine induction of pituitary tumor apoptosis remains unclear. Caveolin-1 is a membrane-anchored protein enriched on caveolae, inverted flask-shaped invaginations on plasma membranes where signal transduction molecules are concentrated. Currently, caveolin-1 is thought to be a negative regulator of cellular proliferation and an enhancer of apoptosis by blocking signal transduction between cell surface membrane receptors and intracellular signaling protein cascades. Rat pituitary adenoma GH3 cells, which express endogenous caveolin-1, exhibit increased apoptosis and shrinkage after exposure to bromocriptine. Hence, the GH3 cell line is an ideal model for studying the molecular action of bromocriptine on prolactinoma. Results The expression of endogenous caveolin-1 in GH3 cells was elevated after bromocriptine treatment. Transiently expressed mouse recombinant caveolin-1 induced apoptosis in GH3 cells by enhancing the activity of caspase 8. Significantly, caveolin-1 induction of GH3 cell apoptosis was sensitized by the administration of bromocriptine. Phosphorylation of caveolin-1 at tyrosine 14 was enhanced after bromocriptine treatment, suggesting that bromocriptine-induced phosphorylation of caveolin-1 may contribute to sensitization of apoptosis in GH3 cells exposed to bromocriptine. Conclusion Our results reveal that caveolin-1 increases sensitivity for apoptosis induction in pituitary adenoma GH3 cells and may contribute to tumor shrinkage after clinical bromocriptine treatment.

  1. Visual Outcomes after Endoscopic Pituitary Surgery in Patients Presenting with Preoperative Visual Deficits. (United States)

    Fredes, Felipe; Undurraga, Gabriel; Rojas, Pablo; Constanzo, Felipe; Lazcano, Carolina; Pinto, Jaime; Schmidt, Thomas


    Introduction  Pituitary adenomas represent 15% of primary brain tumors. Visual disturbance is a common clinical manifestation of these neoplasms due, among other factors, to local mass effect on the optic system. Objective  To evaluate changes of the visual fields in patients undergoing endoscopic endonasal approach (EEA) for pituitary adenomas and to find predictive factors for successful visual field outcome. Material and Methods  This is a cross-sectional study. A review was conducted of medical records of consecutive patients with tumors of the sellar region undergoing EEA between January 2008 and December 2012 at the Skull Base Unit of Guillermo Grant Benavente Hospital, University of Concepción, Concepción, Chile, and who had undergone pre- and postoperative visual field evaluation. Results  A total of 35 patients, with a mean age of 50.2 years, fulfilled the inclusion criteria. All patients had objective visual field disturbances before the surgery. Following surgery, 25 patients (71.4%) had favorable outcomes, whereas 8 (22.8%) had no change and 2 (5.8%) had an unfavorable outcome. Complete tumor removal was associated with a better visual outcome than those obtained after a subtotal removal. Discussion  The EEA for pituitary tumors is particularly effective for visual field disturbances, with reported improvement rates ranging from 50 to 90%. Our series show similar results, with a 71.4% improvement of visual field disturbances. Conclusion  This study adds further evidence to the current belief that EEA for pituitary adenomas is a safe and effective technique to improve visual field alterations. Complete removal of the tumor during surgery seems to be a predictive factor for a good visual outcome.

  2. Experimental ex-vivo validation of PMMA-based bone cements loaded with magnetic nanoparticles enabling hyperthermia of metastatic bone tumors (United States)

    Harabech, Mariem; Kiselovs, Normunds Rungevics; Maenhoudt, Wim; Crevecoeur, Guillaume; Van Roost, Dirk; Dupré, Luc


    Percutaneous vertebroplasty comprises the injection of Polymethylmethacrylate (PMMA) bone cement into vertebrae and can be used for the treatment of compression fractures of vertebrae. Metastatic bone tumors can cause such compression fractures but are not treated when injecting PMMA-based bone cement. Hyperthermia of tumors can on the other hand be attained by placing magnetic nanoparticles (MNPs) in an alternating magnetic field (AMF). Loading the PMMA-based bone cement with MNPs could both serve vertebra stabilization and metastatic bone tumor hyperthermia when subjecting this PMMA-MNP to an AMF. A dedicated pancake coil is designed with a self-inductance of 10 μH in series with a capacitance of 0.1 μF that acts as resonant inductor-capacitor circuit to generate the AMF. The thermal rise is appraised in beef vertebra placed at 10 cm from the AMF generating circuit using optical temperatures sensors, i.e. in the center of the PMMA-MNP bone cement, which is located in the vicinity of metastatic bone tumors in clinical applications; and in the spine, which needs to be safeguarded to high temperature exposures. Results show a temperature rise of about 7 °C in PMMA-MNP whereas the temperature rise in the spine remains limited to 1 °C. Moreover, multicycles heating of PMMA-MNP is experimentally verified, validating the technical feasibility of having PMMA-MNP as basic component for percutaneous vertebroplasty combined with hyperthermia treatment of metastatic bone tumors.

  3. Incidence of Diabetes Insipidus in Postoperative Period among the Patients Undergoing Pituitary Tumour Surgery. (United States)

    Kadir, M L; Islam, M T; Hossain, M M; Sultana, S; Nasrin, R; Hossain, M M


    Post operative complications after pituitary tumour surgery vary according to procedure. There are several surgical procedures being done such as transcranial, transsphenoidal microsurgical and transsphenoidal endoscopic approaches. One of the commonest complications is diabetes insipidus (DI). Our main objective was to find out the incidence of diabetes insipidus in post operative period among patients undergoing surgical intervention for pituitary tumour in our institute. The presence of diabetes insipidus in the postoperative period was established by measuring serum Na+ concentration, hourly urine output and urinary specific gravity to find out the incidence of diabetes insipidus in postoperative period in relation to age, gender, tumour diameter, function of tumour (i.e., either hormone secreting or not) and operative procedure used for surgical resection of pituitary tumor. As it is the most common postoperative complication so, in this study we tried to find out how many of the patients develop diabetes insipidus in postoperative period following surgical resection of pituitary tumour. This cross sectional type of observational study was carried out in the department of Neurosurgery, BSMMU from May 2014 to October 2015 on 33 consecutive patients who underwent surgical intervention for pituitary tumour for the first time. Data was collected by using a data collection sheet. The incidence of diabetes insipidus was found 23.1% of patients in diabetes insipidus (p=0.073). Regarding tumour size 30.8% and 69.2% of patients developed diabetes insipidus having tumour diameter diabetes insipidus who was operated by transsphenoidal endoscopic approach, 23.1% and 7.7% of patients developed diabetes insipidus who underwent pituitary tumour resection through transsphenoidal microscopic approach and transcranial microscopic approach respectively (p=0.432). 17.6% of patients develop DI having functioning pituitary macroadenoma and 62.5% of patients develop DI having

  4. Resistance of novel mouse strains different in MHC class I and the NKC domain to the development of experimental tumors

    National Research Council Canada - National Science Library

    Fišerová, Anna; Richter, Jan; Čapková, Katarína; Bieblová, Jana; Mikyšková, Romana; Reiniš, Milan; Indrová, Marie


    ... (3-methycholanthrene-induced tumor) syngeneic to Balb/c. Furthermore, we induced colorectal carcinoma by azoxymethane-DSS treatment to test the susceptibility to chemically-induced primary cancer...

  5. siRNA-mediated silencing of bFGF gene inhibits the proliferation, migration, and invasion of human pituitary adenoma cells. (United States)

    Zhou, Kai; Fan, Yan-Dong; Duysenbi, Serick; Wu, Peng-Fei; Feng, Zhao-Hai; Qian, Zheng; Zhang, Ting-Rong


    Human pituitary adenoma is one of the most common intracranial tumors with an incidence as high as 16.7%. Recent evidence has hinted a relationship between growth factors of pituitary or hypothalamic origin and proliferation of human pituitary adenoma cells. This study explores the effects of small interfering RNA-mediated silencing of basic fibroblast growth factor gene on the proliferation, migration, and invasion of human pituitary adenoma cells. Human pituitary adenoma tissues were collected to obtain human pituitary adenoma cells. The basic fibroblast growth factor silencing interference plasmid was constructed, and the human pituitary adenoma cells were transfected and assigned as basic fibroblast growth factor-small interfering RNA, negative control-small interfering RNA, and blank groups. The quantitative real-time polymerase chain reaction and Western blotting were carried out to detect the expression of basic fibroblast growth factor, pituitary tumor transforming gene, vascular endothelial growth factor, cluster of differentiation 147, and matrix metalloproteinase 9. Cell Counting Kit-8 assay was conducted to observe cell proliferation at 0, 24, 48, and 72 h. Flow cytometry was used to determine cell cycle. Transwell and scratch test were applied to detect the invasion and migration of pituitary adenoma cells. Protein kinase C activity was detected. In comparison with the blank group, the basic fibroblast growth factor-small interfering RNA group showed reduced messenger RNA and protein expression of basic fibroblast growth factor, reduced cell viability at 24, 48, and 72 h, increased cells in G0/G1 stage, declined cells in S and G2/M stages, decreased number of cell migration, shortened migrating distance, reduced protein kinase C activity, and decreased expression of pituitary tumor transforming gene, vascular endothelial growth factor, cluster of differentiation 147, and matrix metalloproteinase 9. However, the negative control-small interfering

  6. Using Positron Emission Tomography with [18F]FDG to Predict Tumor Behavior in Experimental Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Bryan M. Burt


    Full Text Available This study investigates the relationship between FDG uptake as determined by positron emission tomography (PET imaging and rates of tumor growth, cellular GLUT1 transporter density, and the activities of hexokinase and glucose-6-phosphatase in a solid tumor implant model. Five different human colorectal xenografts of different growth properties were implanted in athymic rats and evaluated by dynamic 18F-FDG-PET. The phosphorylating and dephosphorylating activities of the key glycolytic enzymes, hexokinase and glucose-6-phosphatase, were measured in these tumor types by spectrophotometric assays and the expression of GLUT1 glucose transporter protein was determined by immunohistochemistry. Correlations among FDG accumulation, hexokinase activity, and tumor doubling time are reported in these colon xenografts. The results indicate that the activity of tumor hexokinase may be a marker of tumor growth rate that can be determined by 18F-FDG-PET imaging. PET scanning may not only be a useful tool for staging patients for extent of disease, but may provide important prognostic information concerning the proliferative rates of malignancies.

  7. Gender-related differences in prolactin secretion in pituitary prolactinomas

    Energy Technology Data Exchange (ETDEWEB)

    Nishioka, H.; Haraoka, J.; Akada, K.; Azuma, S. [Department of Neurosurgery, Tokyo Medical University (Japan)


    In pituitary prolactinomas, serum prolactin (PRL) levels usually parallel the tumor size. We conducted a retrospective study to determine differences in PRL production between men and women with prolactinomas. A total of 51 patients, 16 men and 35 women, was studied. We investigated clinical, endocrinological, radiological and histological findings, and estimated the tumor volume (TV) by high-resolution magnetic resonance imaging (MRI). Correlation between PRL level and TV was low in men (R=0.458), in contrast to women (R=0.953), c. Men with prolactinomas showed predominance of large tumors (P=0.0009) with high PRL levels (P=0.0009) and had greater tendencies for cyst formation (P=0.0047). Large prolactinomas tended to be accompanied by cyst(s) (P=0.0051) and hemorrhage (P=0.0015), both of which were associated with reduced PRL secretion (P=0.0004 and P<0.0001, respectively). When the volume of the cysts and hemorrhage was subtracted from the total TV, correlation between PRL level and TV became greater (R=0.905) with no gender difference. Histological examination demonstrated a sparsely granulated type of lactotroph adenoma with occasional fibrosis, particularly in tumors with hemorrhage and cysts. Although a significant discrepancy between PRL level and TV may exist in prolactinomas when intratumoral hemorrhage and/or cysts are present, there is no essential difference in PRL secretion between the sexes. (orig.)

  8. Total resection of a solitary fibrous tumor of the sellar diaphragm: A case report




    The present study reports the case of a patient with a vision impairment in the right eye. Head computed tomography revealed a round, hyperdense mass in the sellar and suprasellar regions. Pituitary gland magnetic resonance imaging (MRI) revealed isointensity on T1- and T2-weighted imaging. Tumor-enhanced scanning showed heterogeneous contrast enhancement. The initial diagnosis was that of meningioma or pituitary tumor. A total tumor resection was performed using a right pterional approach un...

  9. Surgical treatment of pituitary adenomas using low-field intraoperative magnetic resonance imaging. (United States)

    Tabakow, Paweł; Czyz, Margin; Jarmundowicz, Włodzimierz; Lechowicz-Głogowska, Ewa


    Intraoperative magnetic resonance imaging (iMRI) is a new technique for imaging of the brain and is used with increasing frequency during neurosurgical operations, enabling the surgeon to make decisions based on real-time images. This paper presents the technique for the surgical treatment of pituitary adenomas using low-field iMRI, evaluates the safety of iMRI usage in pituitary surgery and examines the influence of iMRI on the extent of tumor removal. From October 2008 to December 2010, 18 patients were treated for pituitary adenomas using the low-field iMRI system Polestar N20. The procedures were conducted via the transsphenoidal approach, using the microscopic technique in 15 cases and endoscopically in three cases. The patients' mean age was 56 +/- 15 years; their mean American Society of Anesthesiologists (ASA) score was 2; 67% of them were male. Most of the patients were operated on for macroadenomas, 83% of which were hormonally inactive. The analysis concerned the technical aspects of iMRI usage, such as preparation and surgery time and the quality of the iMRI-scans performed. The safety of iMRI and its influence on decisions regarding further tumor resection. The operations on pituitary adenomas using iMRI were safe. Only two hemorrhagic complications were noted, and they were not related to iMRI usage. The mean preparation and surgery times were 109 +/- 37 minutes and 238 +/- 188 minutes, respectively. The iMRI images of sella turcica were of satisfactory quality in 16 patients. In 50% of the cases, iMRI conducted when the surgeon believed that the desired extent of tumor resection had been attained showed that there were still tumor remnants to be resected. In 67% of these cases, continued tumor removal lead to achievement of the desired degree of resection. Low-field iMRI-guided operations on pituitary tumors are safe and feasible, and they ensure an increased radicality of tumor resection.

  10. Hypothalamic Pituitary Adrenal Axis Functioning in Reactive and Proactive Aggression in Children (United States)

    Lopez-Duran, Nestor L.; Olson, Sheryl L.; Hajal, Nastassia J.; Felt, Barbara T.; Vazquez, Delia M.


    The purpose of this study was to examine the association between hypothalamic-pituitary-adrenal axis (HPA-axis) reactivity and proactive and reactive aggression in pre-pubertal children. After a 30-min controlled base line period, 73 7-year-old children (40 males and 33 females) were randomly assigned to one of two experimental tasks designed to…

  11. Stem cells in the canine pituitary gland and in pituitary adenomas

    NARCIS (Netherlands)

    van Rijn, Sarah J|info:eu-repo/dai/nl/392860163; Tryfonidou, Marianna A|info:eu-repo/dai/nl/24306599X; Hanson, Jeanette M; Penning, Louis C|info:eu-repo/dai/nl/110369181; Meij, Björn P|info:eu-repo/dai/nl/164045805


    Cushing's disease (CD) or pituitary-dependent hypercortisolism is a common endocrinopathy in dogs, with an estimated prevalence of 1 or 2 in 1000 dogs per year. It is caused by an adrenocorticotropic hormone secreting adenoma in the pars distalis or pars intermedia of the pituitary gland. The

  12. Fractionated stereotactic radiosurgery using the Novalis system for the management of pituitary adenomas close to the optic apparatus. (United States)

    Liao, Huang-I; Wang, Chun-Chieh; Wei, Kuo-Cheng; Chang, Cheng-Nen; Hsu, Yung-Hsin; Lee, Shih-Tseng; Huang, Yin-Cheng; Chen, Hsien-Chih; Hsu, Peng-Wei


    Radiosurgery has been proven to be an effective treatment for residual or recurrent pituitary adenomas after surgery. However, it causes severe complications when the optic apparatus is irradiated over the tolerance dose. In this study, we analyzed the feasibility of fractionated stereotactic radiosurgery to treat pituitary tumors close to the optic apparatus. Thirty-four patients from June 2006 to June 2011 with recurrent or residual pituitary adenomas close to (stereotactic radiosurgery. Three fractions with a total dose of 2100 cGy were applied to the tumors. Imaging, examination of vision, and estimation of hormone level were regularly performed before and after radiosurgery. The mean tumor volume before fractioned stereotactic radiosurgery was 5.06±3.08 cm3 (range: 0.82-12.69 cm3). After a mean follow up of 36.8±15.7 months (range: 16-72 months), tumor size was reduced in seven (20.6%) patients and remained the same in the other 27 (79.4%) patients. Vision was improved in one patient and remained stable in the rest. Only one patient developed transient post-treatment diplopia. This study suggests that fractionated stereotactic radiosurgery is safe for treating pituitary adenomas close to the optic apparatus. Studies with more patients and longer follow-up are required to draw definite conclusions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Сatamnesis of organic hallucinosis case at pituitary macroadenoma

    Directory of Open Access Journals (Sweden)

    Yur’yeva L.N.


    Full Text Available The article describes a one-year follow-up study of the clinical case of organic hallucinosis that we have described in the previous article in the patient with pituitary macroadenoma. At primary admission to the hospital (one year earlier the likelihood of permanent or recurrent nature of hallucinosis and absolutely poor prognosis for recovery and life without removal of the tumor was pointed out to the patient and his family. However, the patient and his relatives flatly refused to undergo neurosurgical intervention. The article describes the dynamics of psychopathological and somatic statuses of the patient during his readmission to a psychiatric hospital. The exciting cause of death on the 25th day of hospital stay was phenomenon of cerebral edema. By results of post-mortem studies the underlying cause of death was small cell chromophobe pituitary adenoma. There was a complete accuracy between clinical and post-mortem diagnosis. Absolutely unfavorable prognosis made before has been confirmed. The conclusion about the need of psychoeducational interventions with this contingent of patients and their relatives for prevention of an adverse disease outcome is made.

  14. Melanotroph pituitary adenoma in a cat with diabetes mellitus. (United States)

    Meij, B P; van der Vlugt-Meijer, R H; van den Ingh, T S G A M; Flik, G; Rijnberk, A


    A 13-year-old male, castrated, crossbred cat was referred for insulin-resistant diabetes mellitus. The cat had a ravenous appetite and a dull coat. Basal urinary corticoid/creatinine ratios were normal. In the low-dose dexamethasone suppression test there was no suppression of the (nonelevated) plasma cortisol concentration, whereas the (nonelevated) plasma adrenocorticotropic hormone (ACTH) concentration declined to low values. Basal plasma alpha-melanocyte-stimulating hormone (alpha-MSH) concentrations were highly elevated (> 1,500 ng/liter). Computed tomography revealed a pituitary tumor originating from the pars intermedia (PI). After microsurgical transsphenoidal hypophysectomy, the clinical signs resolved and the cat no longer required insulin administration. Microscopic examination of the surgical specimen revealed a pituitary adenoma originating from the PI with infiltration into the neural lobe. The adenoma immunostained intensely positive for alpha-MSH and only weakly for ACTH. It is concluded that the ACTH-independent cortisol production was probably due to the (weak) glucocorticorticotropic effects of the extremely high plasma concentration of alpha-MSH and related peptides.

  15. Two forensic autopsy cases of death from unexpected lesions of the pituitary gland. (United States)

    Suzuki, Hideto; Hayashi, Kino; Fukunaga, Tatsushige


    Herein, we report the findings of 2 forensic autopsy cases, in which unexpected pituitary lesions were the underlying cause of death. Case 1: A 56-year-old woman was found dead at her home during a cold winter spell. Macroscopic autopsy findings included a difference in the color of blood that filled her left and right cardiac chambers (deep red and dark red, respectively), collapse of both lungs, atrophy of the thyroid gland, and a large tumor arising from the sella turcica. Microscopic examination revealed a pituitary adenoma along with extensive bleeding. The cause of death was considered to be hypothermia, resulting from dysregulation of thermogenesis due to the pituitary adenoma. Case 2: An 86-year-old man with a history of pollakiuria was found dead in a bathtub, with his face and chest submerged in bathwater and his legs positioned outside the bathtub. The macroscopic findings of the autopsy included hyper-inflated lungs, fluid collection in the thoracic cavity, and aspiration of gastric contents in the bronchi. The atherosclerotic changes of the man's coronary and cerebral arteries were considered mild for his age. Microscopic examination showed a marked infiltration of lymphocytes and plasma cells in the posterior pituitary gland, as well as in the liver, pancreas, and submandibular gland. Considering the results of the autopsy and the findings from the investigation conducted at the death scene, we concluded that the man probably lost consciousness following a neurally mediated syncope, which was induced by diabetes insipidus (lymphocytic hypophysitis). After losing consciousness, the man likely fell in the filled bathtub and then drowned. These 2 cases highlight the need for a thorough post-mortem investigation, including a microscopic examination of the pituitary gland. In addition, forensic pathologists should carefully study the pituitary gland in cases where the cause of death is thought to be related to dysfunction of thermoregulation or

  16. Boron neutron capture therapy (BNCT) inhibits tumor development from precancerous tissue: An experimental study that supports a potential new application of BNCT

    Energy Technology Data Exchange (ETDEWEB)

    Monti Hughes, A.; Heber, E.M. [Department of Radiobiology, National Atomic Energy Commission (CNEA), Buenos Aires (Argentina); Pozzi, E. [Department of Radiobiology, National Atomic Energy Commission (CNEA), Buenos Aires (Argentina); Department of Research and Production Reactors, Ezeiza Atomic Center, CNEA, Buenos Aires (Argentina); Nigg, D.W. [Idaho National Laboratory, Idaho Falls, Idaho (United States); Calzetta, O.; Blaumann, H.; Longhino, J. [Department of Nuclear Engineering, Bariloche Atomic Center, CNEA, Rio Negro (Argentina); Nievas, S.I. [Department of Chemistry, CNEA, Buenos Aires (Argentina); Aromando, R.F. [Department of Oral Pathology, Faculty of Dentistry, University of Buenos Aires, Buenos Aires (Argentina); Itoiz, M.E. [Department of Radiobiology, National Atomic Energy Commission (CNEA), Buenos Aires (Argentina); Department of Oral Pathology, Faculty of Dentistry, University of Buenos Aires, Buenos Aires (Argentina); Trivillin, V.A. [Department of Radiobiology, National Atomic Energy Commission (CNEA), Buenos Aires (Argentina); Schwint, A.E. [Department of Radiobiology, National Atomic Energy Commission (CNEA), Buenos Aires (Argentina)], E-mail:


    We previously demonstrated the efficacy of boron neutron capture therapy (BNCT) mediated by boronophenylalanine (BPA), GB-10 (Na{sub 2}{sup 10}B{sub 10}H{sub 10}) and (GB-10+BPA) to control tumors, with no normal tissue radiotoxicity, in the hamster cheek pouch oral cancer model. Herein we developed a novel experimental model of field-cancerization and precancerous lesions (globally termed herein precancerous tissue) in the hamster cheek pouch to explore the long-term potential inhibitory effect of the same BNCT protocols on the development of second primary tumors from precancerous tissue. Clinically, second primary tumor recurrences occur in field-cancerized tissue, causing therapeutic failure. We performed boron biodistribution studies followed by in vivo BNCT studies, with 8 months follow-up. All 3 BNCT protocols induced a statistically significant reduction in tumor development from precancerous tissue, reaching a maximum inhibition of 77-100%. The inhibitory effect of BPA-BNCT and (GB-10+BPA)-BNCT persisted at 51% at the end of follow-up (8 months), whereas for GB-10-BNCT it faded after 2 months. Likewise, beam-only elicited a significant but transient reduction in tumor development. No normal tissue radiotoxicity was observed. At 8 months post-treatment with BPA-BNCT or (GB-10+BPA)-BNCT, the precancerous pouches that did not develop tumors had regained the macroscopic and histological appearance of normal (non-cancerized) pouches. A potential new clinical application of BNCT would lie in its capacity to inhibit local regional recurrences.

  17. The role of flow cytometry in the study of cell growth in the rat anterior pituitary gland

    Directory of Open Access Journals (Sweden)

    M Vitale


    Full Text Available Flow cytometry is a suitable technique for studying in vivo and in vitro the cell cycle kinetics of different animal and human tissues, both in normal and tumoral conditions. The rat anterior pituitary gland is a model to investigate cell growth and replication of differentiated, neuroendocrine cells, and we report current evidence on its cell cycle kinetics as well as on the role played by flow cytometry in this type of study. The proliferation potential of normal anterior pituitary cells is related to a number of different conditions, including heterogeneity of cell types, age and sex of donors, and circadian influences. In addition, the trend of cell proliferation in both in vivo and in vitro studies is similar, suggesting that cultured anterior pituitary elements may, at least in parts, retain growth features analogous to those of the intact gland. Sorting of selective cell types and analysis of the relation between proliferating anterior pituitary cells and the light-dark cycle have shown that flow cytometry may be useful to investigate the replication process of the gland. By using a combination of flow cytometry, light microscopic immunocytochemistry and morphometry, we have reported a peculiar trend of proliferation in prima- ry monolayer cultures of rat anterior pituitary gland, characterized by a non-linear reduction in their proliferation rate with advancing age, primarily dependent on a reduced transition of cells from the G0/G1- to the early S-phase pool. These studies indicate that flow cytometry offers insights into cell cycle check points of anterior pituitary cells, and suggest that it might be applied to the study of growth of selective pituitary elements, both in normal and tumoral conditions.

  18. The FGFR4-G388R polymorphism promotes mitochondrial STAT3 serine phosphorylation to facilitate pituitary growth hormone cell tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Toru Tateno


    Full Text Available Pituitary tumors are common intracranial neoplasms, yet few germline abnormalities have been implicated in their pathogenesis. Here we show that a single nucleotide germline polymorphism (SNP substituting an arginine (R for glycine (G in the FGFR4 transmembrane domain can alter pituitary cell growth and hormone production. Compared with FGFR4-G388 mammosomatotroph cells that support prolactin (PRL production, FGFR4-R388 cells express predominantly growth hormone (GH. Growth promoting effects of FGFR4-R388 as evidenced by enhanced colony formation was ascribed to Src activation and mitochondrial serine phosphorylation of STAT3 (pS-STAT3. In contrast, diminished pY-STAT3 mediated by FGFR4-R388 relieved GH inhibition leading to hormone excess. Using a knock-in mouse model, we demonstrate the ability of FGFR4-R385 to promote GH pituitary tumorigenesis. In patients with acromegaly, pituitary tumor size correlated with hormone excess in the presence of the FGFR4-R388 but not the FGFR4-G388 allele. Our findings establish a new role for the FGFR4-G388R polymorphism in pituitary oncogenesis, providing a rationale for targeting Src and STAT3 in the personalized treatment of associated disorders.

  19. The FGFR4-G388R Polymorphism Promotes Mitochondrial STAT3 Serine Phosphorylation to Facilitate Pituitary Growth Hormone Cell Tumorigenesis (United States)

    Tateno, Toru; Asa, Sylvia L.; Zheng, Lei; Mayr, Thomas; Ullrich, Axel; Ezzat, Shereen


    Pituitary tumors are common intracranial neoplasms, yet few germline abnormalities have been implicated in their pathogenesis. Here we show that a single nucleotide germline polymorphism (SNP) substituting an arginine (R) for glycine (G) in the FGFR4 transmembrane domain can alter pituitary cell growth and hormone production. Compared with FGFR4-G388 mammosomatotroph cells that support prolactin (PRL) production, FGFR4-R388 cells express predominantly growth hormone (GH). Growth promoting effects of FGFR4-R388 as evidenced by enhanced colony formation was ascribed to Src activation and mitochondrial serine phosphorylation of STAT3 (pS-STAT3). In contrast, diminished pY-STAT3 mediated by FGFR4-R388 relieved GH inhibition leading to hormone excess. Using a knock-in mouse model, we demonstrate the ability of FGFR4-R385 to promote GH pituitary tumorigenesis. In patients with acromegaly, pituitary tumor size correlated with hormone excess in the presence of the FGFR4-R388 but not the FGFR4-G388 allele. Our findings establish a new role for the FGFR4-G388R polymorphism in pituitary oncogenesis, providing a rationale for targeting Src and STAT3 in the personalized treatment of associated disorders. PMID:22174695

  20. Magnetic thermotherapy of breast tumors: an experimental therapeutic approach; Magnetische Thermotherapie von Tumoren der Brust: ein experimenteller Therapieansatz

    Energy Technology Data Exchange (ETDEWEB)

    Hilger, I.; Kaiser, W.A. [Inst. fuer Diagnostische und Interventionelle Radiologie des Klinikums der Friedrich-Schiller-Univ. Jena (Germany); Andrae, W.; Hergt, R.; Hiergeist, R. [Inst. fuer Physikalische Hochtechnologie e.V., Jena (Germany)


    The therapeutic strategy for breast cancer is changing, especially for early tumor stages with good prognosis. One potential minimally invasive therapy modality consists in the accumulation of a well-tolerated magnetic material (iron oxides, particularly magnetite) in the target tissue. By applying an alternating magnetic field, energy is selectively absorbed and induces harmful heating of the tumor. The present review deals with the essential conditions and parameters as studied in vitro and in vivo in animal experiments. Extrapolations to the clinical situation are discussed, in particular, the heating potential of the magnetic material, the selection of the magnetic field parameters, the occurrence of eddy currents, the generation of localized heating spots and the expected temperature rises and their effects on the tumor area. (orig.)

  1. SU11248 inhibits tumor growth and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model. (United States)

    Murray, Lesley J; Abrams, Tinya J; Long, Kelly R; Ngai, Theresa J; Olson, Lisa M; Hong, Weiru; Keast, Paul K; Brassard, Jacqueline A; O'Farrell, Anne Marie; Cherrington, Julie M; Pryer, Nancy K


    The aim of the study was to investigate inhibitory effects of the receptor tyrosine kinase (RTK) inhibitor SU11248 against CSF-1R and osteoclast (OC) formation. We developed an in vivo model of breast cancer metastasis to evaluate efficacy of SU11248 against tumor growth and tumor-induced osteolysis in bone. The in vitro effects of SU11248 on CSF-1R phosphorylation, OC formation and function were evaluated. Effects on 435/HAL-Luc tumor growth in bone were monitored by in vivo bioluminescence imaging (BLI), and inhibition of osteolysis was evaluated by measurement of serum pyridinoline (PYD) concentration and histology. Phosphorylation of the receptor for M-CSF (CSF-1R) expressed by NIH3T3 cells was inhibited by SU11248 with an IC50 of 50-100 nM, consistent with CSF-1R belonging to the class III split kinase domain RTK family. The early M-CSF-dependent phase of in vitro murine OC development and function were inhibited by SU11248 at 10-100 nM. In vivo inhibition of osteolysis was confirmed by significant lowering of serum PYD levels following SU11248 treatment of tumor-bearing mice (P = 0.047). Using BLI, SU11248 treatment at 40 mg/kg/day for 21 days showed 64% inhibition of tumor growth in bone (P = 0.006), and at 80 mg/kg/day showed 89% inhibition (P = 0.001). Collectively, these data suggest that SU11248 may be an effective and tolerated therapy to inhibit growth of breast cancer bone metastases, with the additional advantage of inhibiting tumor-associated osteolysis.

  2. Hypothalamic, pituitary and thyroid dysfunction after radiotherapy to the head and neck

    Energy Technology Data Exchange (ETDEWEB)

    Samaan, N.A.; Vieto, R.; Schultz, P.N.; Maor, M.; Meoz, R.T.; Sampiere, V.A.; Cangir, A.; Ried, H.L.; Jesse, R.H. Jr.


    One hundred-ten patients who had nasopharyngeal cancer and paranasal sinus tumors and were free of the primary disease were studied one to 26 years following radiotherapy. There were 70 males and 40 females ranging in age from 4 to 75 years, with a mean age of 36.5 years. During therapy both the hypothalamus and the anterior pituitary gland were in the field of irradiation. The radiation dose to the hypothalamus and the anterior pituitary gland was estimated to be 400 to 7500 rad with a median dose of 5618 rad to the anterior pituitary gland and a median dose of 5000 rad to the hypothalamus. We found evidence of endocrine deficiencies in 91 of the 110 patients studied. Seventy-six patients showed evidence of one or more hypothalamic lesions and 43 patients showed evidence of primary pituitary deficiency. Forty of the 66 patients who received radiotherapy to the neck for treatment or prevention of lymph node metastasis showed evidence of primary hypothyroidism. The range of the dose to the thyroid area was 3000 to 8800 rad with a median of 5000 rad. One young adult woman who developed galactorrhea and amenorrhea 2 years following radiotherapy showed a high serum prolactin level, but had normal anterior pituitary function and sella turcica. She regained her menses and had a normal pregnancy and delivery following bromocriptine therapy. These results indicate that endocrine deficiencies after radiotherapy for tumors of the head and neck are common and should be detected early and treated. Long-term follow-up of these patients is indicated since complications may appear after the completion of radiotherapy.

  3. ACTH response to desmopressin in a patient with acromegaly; expression of corticotropin-releasing factor, urocortins and vasopressin V1b receptor in GH-producing pituitary adenoma. (United States)

    Arihara, Zenei; Sakurai, Kanako; Osaki, Yoshinori; Fukazawa, Hiroshi; Yamada, Shozo; Inoshita, Naoko; Murakami, Osamu; Ohba, Koji; Takahashi, Kazuhiro


    GH-producing pituitary adenomas frequently co-produce other certain anterior pituitary hormones, such as prolactin (PRL). In contrast, GH-producing adenomas which express all of corticotropin-releasing factor (CRF), urocorin1 (Ucn1) and urocortin3 (Ucn3) have not been reported. A 39-year-old woman was admitted for evaluation of the pituitary tumor. The diagnosis of acromegaly was confirmed by elevated serum GH and IGF-I levels, and the absence of GH suppression by oral glucose tolerance test. ACTH response to desmopressin (DDAVP) was observed (plasma ACTH levels increased from 13.9 to 50.4 pg/ml at 90 min). Although it is known that ACTH response to DDAVP is considerably useful for the diagnosis of ACTH-dependent Cushing's syndrome, the diagnosis of Cushing's disease was not supported by the criteria. The patient underwent transsphenoidal resection of the pituitary tumor. Immunohistological examination confirmed a GH- and PRL-producing adenoma, whereas ACTH was negative. ACTH response to DDAVP disappeared after tumor removal. To determine the cause of preoperative ACTH response to DDAVP, we examined expression of CRF family peptides and vasopressin V1b receptor in the pituitary adenoma by immunohistochemistry. Immunohistochemistry revealed positive immunostaining for CRF, Ucn1, Ucn3 and vasopressin V1b receptor in the adenoma. These observations raised the possibility that DDAVP caused an ACTH response, perhaps via the paracrine effects of tumor-derived CRF and Ucn1. When ACTH response to DDAVP is observed in patients with pituitary tumor, not only the direct effect of DDAVP on ACTH secretion, but also a possible involvement of CRF and/or urocortins expressed in the pituitary adenoma, should be considered.

  4. Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer. (United States)

    Molinari, Ana J; Pozzi, Emiliano C C; Monti Hughes, Andrea; Heber, Elisa M; Garabalino, Marcela A; Thorp, Silvia I; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Trivillin, Verónica A; Schwint, Amanda E


    We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer. Blood vessel normalization was induced by two doses of thalidomide in tumor-bearing hamsters on 2 consecutive days. All studies in thalidomide-treated animals were performed 48 h after the first dose of thalidomide, previously established as the window of normalization. Biodistribution studies were performed with BPA at a dose of 15.5 mg (10)B/kg in thalidomide-treated (Th+) and untreated (Th-) tumor-bearing hamsters. The effect of blood vessel normalization prior to BPA administration on the efficacy of BNCT was assessed in in vivo BNCT studies at the RA-3 Nuclear Reactor in tumor-bearing hamsters. Group I was treated with BPA-BNCT after treatment with thalidomide (Th+ BPA-BNCT). Group II was treated with BPA-BNCT alone (Th- BPA-BNCT). Group III was treated with the beam only after treatment with thalidomide (Th+ BO), and Group IV was treated with the beam only (Th- BO). Groups I and II were given the same dose of BPA (15.5 mg (10)B/kg), and all groups (I-IV) were exposed to the same neutron fluence. Two additional groups were treated with the beam only at a higher dose to exacerbate mucositis in precancerous tissue and to explore the potential direct protective effect of thalidomide on radiation-induced mucositis in a scenario of more severe toxicity, i.e. Group V (Th+ hdBO) and Group

  5. Lymphocytic hypophysitis masquerading as pituitary adenoma

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    Rajneesh Mittal


    Full Text Available Introduction: Pituitary hypophysitis (PH is characterized by pituitary infiltration of lymphocytes, macrophages, and plasma cells that could lead to loss of pituitary function. Hypophysitis may be autoimmune or secondary to systemic diseases or infections. Based on the histopathological findings PH is classified into lymphocytic, granulomatous, xanthomatous, mixed forms (lymphogranulomatous, xanthogranulomatous, necrotizing and Immunoglobulin- G4 (IgG4 plasmacytic types. Objective: To report a case of lymphocytic hypophysitis (LH. Case Report: A 15-year-old girl presented with history of headache, amenorrhea, and history of polyuria for past 4 months. Initial evaluation had suppressed follicular stimulating hormone (<0.01 mIU/ml, high prolactin levels (110.85 ng/ml and diabetes insipidus (DI. Magnetic resonance imaging of sella was suggestive of pituitary macroadenoma with partial compression over optic chiasma. Patient underwent surgical decompression. Yellowish firm tissue was evacuated and xanthochromic fluid was aspirated. Histopathology was suggestive of LH. She resumed her cycles postoperatively after 4 months, prolactin levels normalized, however, she continues to have DI and is on desmopressin spray. This case has been presented here for its rare presentation in an adolescent girl because it is mostly seen in young females and postpartum period and its unique presentation as an expanding pituitary mass with optic chiasma compression. Conclusion: Definitive diagnosis of LH is based on histopathological evaluation. Therapeutic approach should be based on the grade of suspicion and clinical manifestations of LH.

  6. A potential inhibitory role for the new truncated variant of somatostatin receptor 5, sst5TMD4, in pituitary adenomas poorly responsive to somatostatin analogs. (United States)

    Durán-Prado, Mario; Saveanu, Alexandru; Luque, Raul M; Gahete, Manuel D; Gracia-Navarro, Francisco; Jaquet, Philippe; Dufour, Henry; Malagón, María M; Culler, Michael D; Barlier, Anne; Castaño, Justo P


    Somatostatin (SST) receptors, specially sst2 and sst5, provide a valuable target to inhibit excessive hormone release and cell growth in pituitary tumors by using SST analogs (SSAs). Unfortunately, an appreciable proportion of tumors fail to respond to SSA despite expressing high levels of one or more ssts. Recently we identified two novel truncated sst5 variants, sst5TMD5, and sst5TMD4, absent in normal pituitary but expressed in pituitary tumors. We aimed at exploring the potential role of sst5TMD5 and sst5TMD4 in the poor response of some tumors to SSA in vivo and in vitro. Specifically, 25 somatotropinomas showing different responses to octreotide in vivo and sst2 (BIM-23197)- and sst5(BIM-23268)-selective compounds in vitro were screened for sst5TMD5/sst5TMD4 expression by real-time PCR. Relationships between ssts expression and in vivo and in vitro secretory response of the corresponding pituitary samples were assessed. sst5TMD5 was absent in all samples analyzed. sst5TMD4 was found in 85% of tumors, and its expression was positively correlated to that of sst5 (R(2) = 0.79, P < 0.001). Expression of sst5TMD4 was negatively correlated with the ability of octreotide to reduce GH levels in vivo and partially negatively correlated with inhibition of GH secretion by an sst5 selective agonist (BIM-23268) in vitro. These results indicate that sst5TMD4 is related to the reduced ability of octreotide at normalizing hormone secretion in poorly responsive tumors in vivo. Further studies will help to evaluate the potential use of sst5TMD4 expression in surgically removed pituitary adenomas as a predictor of the subsequent response of different pituitary tumors to SSA therapy.

  7. Chronically stimulated mouse invariant NKT cell lines have a preserved capacity to enhance protection against experimental tumor metastases.

    NARCIS (Netherlands)

    Molling, J.W.; Moreno, M.; Groot, J. de; Vliet, H.J. van der; Blomberg, B.M.E. von; Eertwegh, A.J. van den; Scheper, R.J.; Bontkes, H.J.


    In pre-clinical models, CD1d restricted invariant Natural Killer T (iNKT) cells play a pivotal role in natural anti-tumor immune responses, mainly by trans-activating cells of both the innate and adaptive arms via swift and potent cytokine secretion. We have previously reported that patients with a

  8. Ectopic sphenoid sinus pituitary adenoma (ESSPA) with normal anterior pituitary gland: a clinicopathologic and immunophenotypic study of 32 cases with a comprehensive review of the english literature. (United States)

    Thompson, Lester D R; Seethala, Raja R; Müller, Susan


    Ectopic sphenoid sinus pituitary adenoma (ESSPA) may arise from a remnant of Rathke's pouch. These tumors are frequently misdiagnosed as other neuroendocrine or epithelial neoplasms which may develop in this site (olfactory neuroblastoma, neuroendocrine carcinoma, sinonasal undifferentiated carcinoma, paraganglioma, melanoma). Thirty-two patients with ESSPA identified in patients with normal pituitary glands (intact sella turcica) were retrospectively retrieved from the consultation files of the authors' institutions. Clinical records were reviewed with follow-up obtained. An immunohistochemical panel was performed on available material. Sixteen males and 16 females, aged 2-84 years (mean, 57.1 years), presented with chronic sinusitis, headache, obstructive symptoms, and visual field defects, although several were asymptomatic (n = 6). By definition, the tumors were centered within the sphenoid sinus and demonstrated, by imaging studies or intraoperative examination, a normal sella turcica without a concurrent pituitary adenoma. A subset of tumors showed extension into the nasal cavity (n = 5) or nasopharynx (n = 9). Mean tumor size was 3.4 cm. The majority of tumors were beneath an intact respiratory epithelium (n = 22), arranged in many different patterns (solid, packets, organoid, pseudorosette-rosette, pseudopapillary, single file, glandular, trabecular, insular). Bone involvement was frequently seen (n = 21). Secretions were present (n = 16). Necrosis was noted in 8 tumors. The tumors showed a variable cellularity, with polygonal, plasmacytoid, granular, and oncocytic tumor cells. Severe pleomorphism was uncommon (n = 5). A delicate, salt-and-pepper chromatin distribution was seen. In addition, there were intranuclear cytoplasmic inclusions (n = 25) and multinucleated tumor cells (n = 18). Mitotic figures were infrequent, with a mean of 1 per 10 HPFs and a pituitary hormones included 48% reactive for 2 or more hormones (plurihormonal), and

  9. A GRFa2/Prop1/stem (GPS) cell niche in the pituitary. (United States)

    Garcia-Lavandeira, Montse; Quereda, Víctor; Flores, Ignacio; Saez, Carmen; Diaz-Rodriguez, Esther; Japon, Miguel A; Ryan, Aymee K; Blasco, Maria A; Dieguez, Carlos; Malumbres, Marcos; Alvarez, Clara V


    The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem) cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the physiological expansion of the pituitary gland throughout life as well as

  10. A GRFa2/Prop1/stem (GPS cell niche in the pituitary.

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    Montse Garcia-Lavandeira

    Full Text Available BACKGROUND: The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. PRINCIPAL FINDINGS: We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. SIGNIFICANCE: Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the

  11. A case of pituitary abscess presenting without a source of infection or prior pituitary pathology

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    Derick Adams


    Full Text Available Pituitary abscess is a relatively uncommon cause of pituitary hormone deficiencies and/or a suprasellar mass. Risk factors for pituitary abscess include prior surgery, irradiation and/or pathology of the suprasellar region as well as underlying infections. We present the case of a 22-year-old female presenting with a spontaneous pituitary abscess in the absence of risk factors described previously. Her initial presentation included headache, bitemporal hemianopia, polyuria, polydipsia and amenorrhoea. Magnetic resonance imaging (MRI of her pituitary showed a suprasellar mass. As the patient did not have any risk factors for pituitary abscess or symptoms of infection, the diagnosis was not suspected preoperatively. She underwent transsphenoidal resection and purulent material was seen intraoperatively. Culture of the surgical specimen showed two species of alpha hemolytic Streptococcus, Staphylococcus capitis and Prevotella melaninogenica. Urine and blood cultures, dental radiographs and transthoracic echocardiogram failed to show any source of infection that could have caused the pituitary abscess. The patient was treated with 6 weeks of oral metronidazole and intravenous vancomycin. After 6 weeks of transsphenoidal resection and just after completion of antibiotic therapy, her headache and bitemporal hemianopsia resolved. However, nocturia and polydipsia from central diabetes insipidus and amenorrhoea from hypogonadotrophic hypogonadism persisted.

  12. Role of PROPELLER diffusion-weighted imaging and apparent diffusion coefficient in the evaluation of pituitary adenomas

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    Mahmoud, Omar M. [Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551 (Japan); Department of Radiology, South Egypt Cancer Institute, Assiut University, Assiut 71515 (Egypt); Tominaga, Atsushi [Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551 (Japan); Amatya, Vishwa Jeet [Department of Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551 (Japan); Ohtaki, Megu [Department of Environmetrics and Biometrics, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8551 (Japan); Sugiyama, Kazuhiko; Sakoguchi, Tetsuhiko; Kinoshita, Yasuyuki [Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551 (Japan); Takeshima, Yukio [Department of Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551 (Japan); Abe, Nobukazu; Akiyama, Yuji [Department of Clinical Radiology, Hiroshima University Hospital, Hiroshima 734-8551 (Japan); El-Ghoriany, Ahmad I. [Department of Neurosurgery, Faculty of Medicine, Assiut University, Assiut 71515 (Egypt); Alla, Abdel Karim H. Abd; El-Sharkawy, Mostafa A.M. [Department of Radiology, Faculty of Medicine, Assiut University, Assiut 71515 (Egypt); Arita, Kazunori [Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima (Japan); Kurisu, Kaoru [Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551 (Japan); Yamasaki, Fumiyuki, E-mail: [Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551 (Japan)


    Objective: The relationship between tumor consistency and apparent diffusion coefficient (ADC) values is controversial. We evaluated the role of the ADC using an advanced diffusion-weighted imaging (DWI) technique. We employed periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) DWI acquired on a 3-T magnetic resonance imaging (MRI) scanner to assess the consistency of pituitary adenomas and examined the relationship between the ADC and the hormone secretion status of the tumors and their MIB-1 labeling index (MIB-1 LI). Materials and methods: The study protocol was approved by our institutional review board. We retrospectively studied 24 operated patients with pituitary adenomas who had undergone PROPELLER DWI on a 3-T MRI scanner. Conventional MRI findings were expressed as the ratio of the signal intensity (SI) in the lesions to the SI of the normal white matter and the degree of contrast enhancement. Minimum-, mean-, and maximum ADC (ADC{sub min}, ADC{sub mean}, ADC{sub max}) values were calculated. The consistency of the tumors was determined by neurosurgeons. All surgical specimens were submitted for histological study to calculate the MIB-1 LI and the percent collagen content. Preoperative MRI-, intraoperative-, and histological findings were analyzed by a statistician. Results: Our study included 15 soft-, 5 fibrous-, and 4 hard tumors. Tumor consistency was strongly associated with the percent collagen content. However, neither the tumor consistency nor the percent collagen content was correlated with MRI findings or ADC values. The SI of growth hormone-producing adenomas on T2-WI was lower than of the other pituitary adenomas studied (p < 0.01); no other significant difference was found in the ADC or on conventional MRI between pituitary adenomas with different secretory functions. The MIB-1 LI of pituitary adenomas was not correlated with their appearance on conventional MRI or their ADC values. Conclusion: Using the

  13. Abscess Formation in a Nonfunctioning Pituitary Adenoma. (United States)

    Safaee, Michael M; Blevins, Lewis; Liverman, Christopher S; Theodosopoulos, Philip V


    Pituitary abscesses are rare clinical entities that can occur in the setting of a normal gland or underlying disease, including adenoma, craniopharyngioma, or Rathke cleft cyst. Although once believed to be indolent, when these secondary abscesses occur in the setting of an adenoma, they can be associated with significant clinical morbidity. Most patients present with visual disturbances or headache without fever or meningitis. We present the case of a 63-year-old woman with remote history of Staphylococcus osteomyelitis who presented with 1 week of diplopia, partial left third nerve palsy, and bitemporal hemianopsia who was found to have a pituitary abscess in the setting of an adenoma. She underwent drainage of the abscess and resection of her adenoma followed by complete resolution of her symptoms. This case highlights the need for prompt treatment of pituitary abscesses, with the possibility of excellent neurologic recovery. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Contrast-enhanced near-infrared laser mammography with a prototype breast scanner: feasibility study with tissue phantoms and preliminary results of imaging experimental tumors. (United States)

    Boehm, T; Hochmuth, A; Malich, A; Reichenbach, J R; Fleck, M; Kaiser, W A


    Near-infrared (NIR) optical mammography without contrast has a low specificity. The application of optical contrast medium may improve the performance. The concentration-dependent detectability of a new NIR contrast medium was determined with a prototype optical breast scanner. In vivo imaging of experimental tumors was performed. The NIR contrast agent NIR96010 is a newly synthesized, hydrophilic contrast agent for NIR mammography. A concentration-dependent contrast resolution was determined for tissue phantoms consisting of whole milk powder and gelatin. A central part of the phantoms measuring 2 x 2 cm2 without contrast was replaced with phantom material containing 1 micromol/L to 25 nmol/L NIR96010. The composite phantoms were measured with a prototype NIR breast scanner with lasers of lambda1 = 785 nm and lambda2 = 850 nm wavelength. Intensity profiles and standard deviations of the transmission signal in areas with and without contrast were determined by linear fit procedures. Signal-to-noise ratios and spatial resolution as a function of contrast concentration were determined. Near-infrared imaging of five tumor-bearing SCID mice (MX1 breast adenocarcinoma, tumor diameter 5-10 mm) was performed before and after intravenous application of 2 micromol/kg NIR96010. Spectrometry showed an absorption maximum of the contrast agent at 755 nm. No spectral shifts occurred in protein-containing solution. Signal-to-noise ratio in the transmission intensity profiles ranged from 1.1 at 25 nmol/L contrast to 28 at 1 micromol/L. At concentrations <40 nmol/L, no differentiation from the background was possible. The transitional area between the contrast-free edge of the phantom and the central contrast-containing part appeared in the profiles as a steep increase with a width of 4.2 +/- 1.8 mm. The experimental tumors were detectable in nonenhanced images as well as contrast-enhanced images, with better delineation after contrast administration. In postcontrast absorption

  15. MR guided thermal therapy of pancreatic tumors with endoluminal, intraluminal and interstitial catheter-based ultrasound devices: preliminary theoretical and experimental investigations (United States)

    Prakash, Punit; Salgaonkar, Vasant A.; Scott, Serena J.; Jones, Peter; Hensley, Daniel; Holbrook, Andrew; Plata, Juan; Sommer, Graham; Diederich, Chris J.


    Image-guided thermal interventions have been proposed for potential palliative and curative treatments of pancreatic tumors. Catheter-based ultrasound devices offer the potential for temporal and 3D spatial control of the energy deposition profile. The objective of this study was to apply theoretical and experimental techniques to investigate the feasibility of endogastric, intraluminal and transgastric catheter-based ultrasound for MR guided thermal therapy of pancreatic tumors. The transgastric approach involves insertion of a catheter-based ultrasound applicator (array of 1.5 mm OD x 10 mm transducers, 360° or sectored 180°, ~7 MHz frequency, 13-14G cooling catheter) directly into the pancreas, either endoscopically or via image-guided percutaneous placement. An intraluminal applicator, of a more flexible but similar construct, was considered for endoscopic insertion directly into the pancreatic or biliary duct. An endoluminal approach was devised based on an ultrasound transducer assembly (tubular, planar, curvilinear) enclosed in a cooling balloon which is endoscopically positioned within the stomach or duodenum, adjacent to pancreatic targets from within the GI tract. A 3D acoustic bio-thermal model was implemented to calculate acoustic energy distributions and used a FEM solver to determine the transient temperature and thermal dose profiles in tissue during heating. These models were used to determine transducer parameters and delivery strategies and to study the feasibility of ablating 1-3 cm diameter tumors located 2-10 mm deep in the pancreas, while thermally sparing the stomach wall. Heterogeneous acoustic and thermal properties were incorporated, including approximations for tumor desmoplasia and dynamic changes during heating. A series of anatomic models based on imaging scans of representative patients were used to investigate the three approaches. Proof of concept (POC) endogastric and transgastric applicators were fabricated and experimentally

  16. CT finding of ectopic pituitary adenoma: Case report and review of literature. (United States)

    Wu, Xiaofeng; Wen, Ming


    Ectopic pituitary adenoma was first described by Erdheim in 1909, about 100 cases have been reported in literature, to the best of our knowledge, an ectopic pituitary adenoma located in the parapharyngeal space has not been reported thus far. A 59-year-old woman presenting with a neck lump, which was painlessness and growing, was without any neurological disorders or endocrine disorders. Auxiliary examinations included ultrasound, electronic nasopharyngolaryngoscopy, endocrine assessment, CT, and CT angiography. A CT scan showed a soft tissue density mass with clear boundary involving the carotid sheath area. The contrast-enhanced CT scan showed heterogeneous density. Tissues around the mass were pushed and displaced. CT angiography showed the mass was hypervascular and supported by the right internal carotid artery and branches of the external carotid artery. The tumor underwent a total removal and was confirmed as an adenoma with pituitary cells by histopathologic examinations, and postoperative recovery went well. It is rarely seen that a pituitary adenoma is ectopic to the parapharyngeal space. Diagnosis is difficult and mainly depends on the postoperative pathological examination. © 2015 Wiley Periodicals, Inc.

  17. Clinical implications of rhinosinusitis detected by preoperative computed tomography for endoscopic endonasal transsphenoidal pituitary surgery. (United States)

    Min, Jin-Young; Chung, Seung-Kyu; Kim, Hyo Yeol; Kong, Doo-Sik; Dhong, Hun-Jong


    Rhinosinusitis detected by preoperative osteomeatal unit computed tomography (OMU CT) may not increase the incidence of postoperative central nervous system (CNS) infections. To evaluate the safety of endoscopic endonasal transsphenoidal pituitary surgery in patients who had rhinosinusitis detected by preoperative OMU CT. A total of 107 patients who underwent endoscopic endonasal transsphenoidal pituitary surgery were enrolled. The presence of rhinosinusitis and the location of involved sinuses were assessed by preoperative OMU CT. The extent of pituitary tumors was assessed by preoperative sellar MRI. The occurrence of intraoperative cerebrospinal fluid (CSF) leakage and postoperative central nervous system (CNS) complications were analyzed using the medical records. The correlations between these variables and postoperative CNS complications were examined. After pituitary surgery, postoperative CNS complications occurred in four patients (3.7%). Twenty-eight patients (26.2%) had findings of rhinosinusitis on preoperative OMU CT. Of the 28 patients, 8 had rhinosinusitis in the anterior sinuses and 20 in the posterior sinuses. Intraoperative CSF leakage occurred in eight patients (7.5%). The occurrence of intraoperative CSF leakage showed a significant correlation with the incidence of postoperative CNS complications (p = 0.003) but not with the presence of rhinosinusitis (p = 0.134). Although not statistically significant, patients with rhinosinusitis in the posterior ethmoidal and/or sphenoidal sinuses tended to have higher incidences of postoperative CNS complications (p = 0.057).


    Directory of Open Access Journals (Sweden)

    Mani Ram


    Full Text Available INTRODUCTION Between September 2013 and October 2014, we conducted a retrospective analysis to assess the complications related to endoscopic pituitary surgery in a series of 50 patients. We analysed the complications in preoperative, postoperative and endocrinological categories. We had a follow up of 1-2 years. Endonasal endoscopic transsphenoidal surgery (ETSS is an effective option for pituitary tumors. Complications do occur, but they can be reduced with experience & expertise and there is a steep learning curve. It demands a multidisciplinary approach.

  19. Radiation therapy in the multimodal treatment approach of pituitary adenoma

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    Becker, G. [Klinik am Eichert, Goeppingen (Germany). Dept. of Radiooncology and Radiation Therapy; Radiooncologic Univ. Clinic, Tuebingen (Germany); Kocher, M.; Mueller, R.P. [Koeln Univ. (Germany). Clinic of Radiation Therapy; Kortmann, R.D.; Paulsen, F.; Jeremic, B.; Bamberg, M. [Radiooncologic Univ. Clinic, Tuebingen (Germany)


    In this paper, literature will be reviewed to assess the role of modern radiotherapy and radiosurgery in the management of pituitary adenomas. Material and Methods: Nowadays, magnetic resonance imaging for the definition of the target volume and a real three-dimensional (3-D) treatment planning with field conformation and the possibility for non-coplanar irradiation has to be recommended. Most groups irradiate these benign tumors with single doses of 1.8-2.0 Gy up to a total dose of 45 Gy or 50.4 Gy in extensive parasellar adenomas. Adenomas are mostly small, well circumscribed lesions, and have, therefore, attracted the use of stereotactically guided high-precision irradiation techniques which allow extreme focussing and provide steep dose gradients with selective treatment of the target and optimal protection of the surrounding brain tissue. Results: Radiation therapy controls tumor growth in 80-98% of patients with non-secreting adenomas and 67-89% for endocrine active tumors. Reviewing the recent literature including endocrine active and non-secreting adenomas, irradiated postoperatively or in case of recurrence the 5-, 10- and 15-year local control rates amount 92%, 89% and 79%. In cases of microprolactinoma primary therapy consists of dopamine agonists. Irradiation should be preferred in patients with macroprolactinomas, when drug therapy and/or surgery failed or for patients medically unsuitable for surgery. Reduction and control of prolactin secretion can be achieved in 44-70% of patients. After radiotherapy in acromegaly patients somatomedin-C and growth hormone concentrations decrease to normal levels in 70-90%, with a decrease rate of 10-30% per year. Hypercortisolism is controlled in 50-83% of adults and 80% of children with Cushing's disease, generally in less than 9 months. Hypopituitarism is the most common side effect of pituitary irradiation with an incidence of 13-56%. Long-term overall risk for brain necrosis in a total of 1,388 analyzed

  20. [Cushing's disease caused by pituitary macroadenoma]. (United States)

    Rubatino, Antônio C; Pereira, Rodrigo Ferreira; Benchimol, Isaac; Laun, Ingeborg Christa


    Cushing's syndrome comprises the symptoms and signs associated with prolonged exposure to inappropriately elevated levels of free plasma glucocorticoids. When iatrogenic causes are excluded, the commonest cause of Cushing's syndrome is Cushing's disease, accounting for approximately 70% of cases. We present the case of a 20-year-old male patient with central obesity, moon face and purple-red striae, whose diagnostic investigation shows a pituitary macroadenoma. The patient was submitted to transsphenoidal hypophysectomy, but developed early recurrence. He was submitted to a second transsphenoidal intervention followed by pituitary radiation. Presently, the patient is in clinical and laboratory remission.

  1. Tumor-targeting Salmonella typhimurium A1-R prevents experimental human breast cancer bone metastasis in nude mice


    Miwa, Shinji; Yano, Shuya; Zhang, Yong; Matsumoto,Yasunori; Uehara, Fuminari; Yamamoto, Mako; Hiroshima, Yukihiko; Kimura, Hiroaki; Hayashi, Katsuhiro; Yamamoto, Norio; Bouvet, Michael; Tsuchiya, Hiroyuki; Hoffman, Robert M.; Zhao, Ming


    Bone metastasis is a lethal and morbid late stage of breast cancer that is currently treatment resistant. More effective mouse models and treatment are necessary. High bone-metastatic variants of human breast cancer cells were selected in nude mice by cardiac injection. After cardiac injection of a high bone-metastatic variant of breast cancer, all untreated mice had bone metastases compared to only 20% with parental cells. Treatment with tumor-targeting Salmonella typhimurium A1-R completely...

  2. Feasibility and utility of telephone-based psychological support for people with brain tumor: A single-case experimental study

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    Stephanie eJones


    Full Text Available Rates of psychological distress are high following diagnosis and treatment of brain tumor. There can be multiple barriers to accessing psychological support, including physical and cognitive impairments and geographical limitations. Tele-based support could provide an effective and more flexible option for delivering psychological interventions. The present study aimed to investigate the feasibility and utility of a telephone-based psychotherapy intervention for people with brain tumor. A single-case multiple-baseline design was employed with a 4-7 week baseline phase, 10-week treatment phase and 5-week maintenance phase including a booster session. Four participants with a benign or malignant brain tumor (3 males & 1 female; aged 34 to 49 years, received 10 sessions of tele-based therapy and a booster session at four weeks post-treatment. Levels of depression, anxiety, and illness cognitions were monitored on a weekly basis throughout each phase whilst measures of quality of life, stress and self-concept were administered at the start and end of each phase. Weekly measures were analysed using a combination of both visual analysis and Tau-U statistics. Of the four participants, two of them demonstrated significant gains in mental health (depression and/or anxiety and a significant decrease in their levels of helplessness (p<.05. The other two participants did not show gains in mental health or change in illness cognitions. All participants reported improvement in quality of life post-treatment. The results of the study provide preliminary support concerning the feasibility and utility of tele-based therapy for some people with brain tumor. Further research examining factors influencing the outcomes of tele-based psychological support is needed.

  3. MR findings in three pituitary abscesses. Case reports

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    Kashiwagi, N. [Kansai Rosai Hospital, Amagasaki-city Hyogo (Japan). Dept. of Radiology; Fujita, N.; Hirabuki, N.; Tanaka, H.; Nakamura, H. [Osaka Univ. Medical School (Japan). Dept. of Radiology; Sato, T. [Tonyonaka Municipal Hospital, Osaka (Japan). Dept. of Radiology; Sato, M. [Tonyonaka Municipal Hospital, Osaka (Japan). Dept. of Neurosurgery


    We present MR findings in 3 surgically proved cases of pituitary abscess. All lesions were seen as a sellar cystic mass with a thin rim of enhancement. In addition, the pituitary stalk was thickened in 2 cases in which central diabetes insipidus developed. These findings may be suggestive of pituitary abscess. (orig.)

  4. Diagnostic imaging of the pituitary gland in dogs

    NARCIS (Netherlands)

    Vlugt-Meijer, R.H. van der


    Pituitary-dependent hyperadrenocorticism (PDH) is a frequently encountered endocrinopathy in dogs. Transsphenoidal hypophysectomy is an effective treatment of PDH in dogs. However, for pituitary surgery to be successful information about the size of the pituitary gland and the exact location of the

  5. Pituitary Metastases. Metastases de la Glande Pituitaire (English ...

    African Journals Online (AJOL)

    Introduction Metastatic disease of the pituitary is an uncommon clinical problem, although autopsy findings on patients who die of disseminated carcinoma suggest that it occurs more frequently than is clinically evident. Pituitary metastases are often difficult to distinguish from pituitary adenomas both clinically and ...

  6. Value of pituitary MRI in children with short stat

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    Huan ZHOU


    Full Text Available Objective To explore the value of pituitary MRI in diagnosis of etiology and prognosis in children with short stature. Methods The MRI data of 130 children with short stature admitted from Jan. to Dec. 2012 were retrospectively analyzed. Of the 130 children, 79 were males and 51 were females, aged 3 to 18 years with mean of 9.8 years. Results Of the 130 children, 82 cases (63.1% were shown to have normal pituitary morphology and signal manifestation, and in 48 cases (36.9% pituitary morphology and signal manifestation were abnormal, and among them pituitary dysplasia was found in 30 cases, deficiency of bright signals in posterior pituitary lobe was found in 4 cases, in whom pituitary stalk deficiency was found in 2 cases. Pituitary microadenoma was found in 3 cases, and pituitary cystic lesions were found in 6 cases. Suprasellar cistern hernia was found in 4 cases, and empty sella was found in one case. The height of pituitary glands was 3.00-7.00mm in children with normal pituitary morphology and signal manifestation. Conclusion MRI pituitary examination can clearly display the anatomy and the signal of the pituitary gland, therefore MR imaging is of important value in the diagnosis of the etiology diagnosis, treatment, and prognosis of children with short stature. It should be the preferred examination. DOI: 10.11855/j.issn.0577-7402.2013.11.008

  7. Focused ultrasound delivery of Raman nanoparticles across the blood-brain barrier: Potential for targeting experimental brain tumors (United States)

    Diaz, Roberto Jose; McVeigh, Patrick Z.; O’Reilly, Meaghan A.; Burrell, Kelly; Bebenek, Matthew; Smith, Christian; Etame, Arnold; Zadeh, Gelareh; Hynynen, Kullervo; Wilson, Brian C.; Rutka, James T.


    Spectral mapping of nanoparticles with surface enhanced Raman scattering (SERS) capability in the near-infrared range is an emerging molecular imaging technique. We used magnetic resonance image-guided transcranial focused ultrasound (TcMRgFUS) to reversibly disrupt the blood-brain barrier (BBB) adjacent to brain tumor margins in rats. Glioma cells were found to internalize SERS capable nanoparticles of 50 nm or 120 nm physical diameter. Surface coating with anti-epidermal growth factor receptor antibody or non-specific human immunoglobulin G, resulted in enhanced cell uptake of nanoparticles in-vitro compared to nanoparticles with methyl terminated 12-unit polyethylene glycol surface. BBB disruption permitted the delivery of SERS capable spherical 50 or 120 nm gold nanoparticles to the tumor margins. Thus, nanoparticles with SERS imaging capability can be delivered across the BBB non-invasively using TcMRgFUS and have the potential to be used as optical tracking agents at the invasive front of malignant brain tumors. PMID:24374363

  8. Iodine-125 Seeds Strand for Treatment of Tumor Thrombus in Inferior Vena Cava: An Experimental Study in a Rabbit Model

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    Zhang, Wen, E-mail:; Yan, Zhiping, E-mail:; Luo, Jianjun, E-mail:; Fang, Zhuting, E-mail:; Wu, Linlin, E-mail:; Liu, QingXin, E-mail:; Qu, Xudong, E-mail:; Liu, Lingxiao, E-mail:; Wang, Jianhua, E-mail: [Fudan University, Department of Interventional Radiology, Zhongshan Hospital (China)


    Objective: The purpose of this study was to establish an animal model of implanted inferior vena cava tumor thrombus (IVCTT) and to evaluate the effect of linear iodine-125 seeds strand in treating implanted IVCTT. Methods: Tumor cell line VX{sub 2} was inoculated subcutaneously into New Zealand rabbit to develop the parent tumor. The tumor strip was inoculated into inferior vena cava (IVC) to establish the IVCTT model. The IVCTT was confirmed by multidetector computed tomography (MDCT) after 2 weeks. Twelve rabbits with IVCTT were randomly divided into two groups. Treatment group (group T; n = 6) underwent Iodine-125 seeds brachytherapy, and the control group (group C; n = 6) underwent blank seeds strand. The blood laboratory examination (including blood routine examination, hepatic and renal function), body weight, survival time, and IVCTT volume by MDCT were monitored. All rabbits were dissected postmortem, and the therapeutic effects were evaluated on the basis of histopathology. The proliferating cell nuclear antigen index (PI) and apoptosis index (AI) of IVCTT were compared between two groups. T test, Wilcoxon rank test, and Kaplan-Meier survival curve analysis were used. Results: The success rate of establishing IVCTT was 100 %. The body weight loss and cachexia of rabbits in group C appeared earlier than in group T. Body weight in the third week, the mean survival time, PI, AI in groups T and C were 2.23 {+-} 0.12 kg, 57.83 {+-} 8.68 days, (16.73 {+-} 5.18 %), (29.47 {+-} 7.18 %), and 2.03 {+-} 0.13 kg, 43.67 {+-} 5.28 days, (63.01 {+-} 2.01 %), (6.02 {+-} 2.93 %), respectively. There were statistically significant differences between group T and group C (P < 0.05). The IVCTT volume of group T was remarkably smaller than that of group C. Conclusions: Injecting and suspensory fixing VX2 tumor strip into IVC is a reliable method to establish IVCTT animal model. The linear Iodine-125 seeds strand brachytherapy was a safe and effective method for treating IVCTT

  9. Differential response of two somatolactin genes to zinc or estrogen in pituitary of Cyprinus carpio. (United States)

    Valenzuela, G E; Perez, A; Navarro, M; Romero, A; Figueroa, J; Kausel, G


    Environmental changes affect gene expression that we addressed in the pituitary, a central regulatory organ at the interface between the central nervous system and the endocrine system. With the aim to reveal effects of changes in the aquatic environment on the expression of hypothalamo-hypophyseal factors, we characterized somatolactin (SL) in Cyprinus carpio. SL, a fish specific pituitary hormone belonging to the prolactin (PRL) superfamily, is involved in background adaptation, osmoregulation, reproduction and fatty acid metabolism. Two sl genes, α and β, were discovered in carp and transcripts of both were detected in pituitaries. Clearly, expression of slα and slβ was modulated significantly in pituitary of male adult carp in response to treatment with ZnCl2 (Zn), but only slβ responded to 17β-estrogen (E2), relative to control carp as shown by RT-qPCR analyses. Furthermore, the amount of mRNA of related factors was assessed revealing variable effects on prl, growth hormone (gh), and factors involved in sl regulation: the pituitary transcription factor pit1 and hypothalamic pituitary adenylase cyclase activating peptide (pacap). In parallel, the physiological response of the experimental animals to Zn or E2 was confirmed by showing a significant increase of metallothionein (mt) or vitellogenin (vg) gene expression in liver, classical sentinels for exposure to heavy metal or estrogens. These data suggest that the sl genes seem to be involved in the response to Zn, as well as to estrogen, and could contribute to evaluate biological relevant changes in the aquatic environment. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Giovanni Verga (1879-1923), author of a pioneering treatise on pituitary surgery: the foundations of this new field in Europe in the early 1900s. (United States)

    Pascual, José M; Mongardi, Lorenzo; Prieto, Ruth; Castro-Dufourny, Inés; Rosdolsky, María; Strauss, Sewan; Carrasco, Rodrigo; Winter, Eduard; Mazzarello, Paolo


    The field of pituitary surgery was born in the first decade of the twentieth century in Europe, and it evolved rapidly with the development of numerous innovative surgical techniques by some of the founding fathers of neurosurgery. This study investigates the pioneering Italian treatise on pituitary surgery, La Patologia Chirurgica dell'Ipofisi (Surgical Pathology of the Hypophysis), published in 1911 by Giovanni Verga (1879-1923), a surgeon from Pavía and one of Golgi's disciples. This little-known monograph compiles the earliest experience on pituitary surgery through the analysis of the first 50 procedures performed between 1903 and 1911. We conducted a biographical survey of Giovanni Verga and the motivations for his work on pituitary surgery. In addition, a systematic analysis of all original reports and historical documents about these pituitary procedures referenced in Verga's treatise was carried out. Verga's treatise provides a summary of the techniques employed and surgical outcomes for the first 50 attempted procedures of pituitary tumor removal. This monograph is the only scientific source that includes a complete account of the series of 10 pituitary tumors operated on by Sir Victor Horsley in the 1900s. Three major types of surgery were employed: (i) palliative procedures of craniectomy (n = 6); (ii) transcranial approaches to the pituitary gland, either subfrontal or subtemporal (n = 13); and (iii) transphenoidal routes to expose the sella turcica, either using an upper transnasal-transethmoidal approach (n = 19) or a lower sublabial/endonasal-transeptal one (n = 12). An operative mortality rate of 36% (n = 17) was observed in these early series. The pathological nature of the tumors operated on was available in 42 cases. There were 28 adenomas and 15 craniopharyngiomas. Sir Victor Horsley (1857-1916) and the Viennese surgeons Anton von Eiselsberg (1860-1939) and Oskar Hirsch (1877-1965) were the leading European figures in the development

  11. [Pituitary functional recovery and hormone replacement therapy of patients with pituitary adenoma surgery]. (United States)

    Fu, Xiao-Hong; Xue, Xin-Cheng; Zhou, Pei-Zhi; Yin, Sen-Lin; Jiang, Shu


    To study the pituitary functional recovery of patients with pituitary adenoma surgery and to identify appropriate dosages of hormone replacement for those patients. Serum hormone levels of 187 patients with pituitary adenoma were detected before and after surgery. The lowest serum hormone levels were detected on the 3rd day after surgery (P pituitary adenoma experienced hypopituitarism shortly after surgery, especially for the elderly who recovered more slowly. Low dosage of hormone replacement therapy based on their symptoms can help the patients reach a stable level of hormone within three months. As a result, the 90th day after surgery can be regarded as a cut-off time for measuring functional recovery of glandula pituitaria.

  12. [Rol of pituitary tumour-transforming gene (PTTG) in the pituitary adenomas]. (United States)

    Sánchez-Ortiga, Ruth; Sánchez Tejada, Laura; Peiró Cabrera, Gloria; Moreno-Pérez, Oscar; Arias Mendoza, Nieves; Aranda López, F Ignacio; Picó Alfonso, Antonio


    The pathogenesis of pituitary tumours is far to be understood. Pituitary transforming tumour gene (PTTG), a gen that induces aneuploidy, genetic instability, cellular proliferation and to stimulate angiogenesis, has been involved in neoplasic transformation and shown overexpressed in many neoplasm as lung, breast, endometrium, thyroid and colon malignant tumours. On the other hand, PTTG has been inconsistently studied in pituitary tumours. The majority of studies have been performed in animals and there is a great variability in the methods used in its determination. The goal of this review is to resume the role of PTTG in tumourogenesis and critically to revise the studies published in humans in order to advance in the knowledge of the pathogenesis of pituitary adenomas and to find clinical useful predictors of the behavior of these tumours. Copyright 2010 Sociedad Española de Endocrinología y Nutrición. Published by Elsevier Espana. All rights reserved.

  13. Cold inducible RNA binding protein upregulation in pituitary corticotroph adenoma induces corticotroph cell proliferation via Erk signaling pathway (United States)

    Fu, Wei; Tang, Hao; Chen, Xiao; Zhao, Yao; Zheng, Lili; Pan, Sijian; Wang, Weiqing; Bian, Liuguan; Sun, Qingfang


    Cushing's disease is caused by pituitary corticotroph adenoma, and the pathogenesis of it has remained obscure. Here, we showed that cold inducible RNA binding protein (CIRP) was markedly elevated in corticotroph tumors. Forced overexpression of CIRP in murine AtT20 pituitary corticotroph cell line increased corticotroph precursor hormone proopiomelanocortin (POMC) transcription, ACTH secretion and cellular proliferation. In vivo, CIRP overexpression promotes murine corticotroph tumor growth and enhances ACTH production. Mechanistically, we show that CIRP could promote AtT20 cells proliferation by inducing cyclinD1 and decreasing p27 expression via Erk1/2 signaling pathway. Clinically, CIRP overexpression is significantly correlated with Cushing's disease recurrence. CIRP appears to play a critical tumorigenesis function in Cushing's disease and its expression might be a useful biomarker for tumor recurrence. PMID:26824322

  14. Ectopic Cushing and other paraneoplastic syndromes in thoracic neuroendocrine tumors. (United States)

    Ferone, Diego; Albertelli, Manuela


    Overproduction of corticotropin by the pituitary gland or extrapituitary tumors leads to hypercortisolism or Cushing syndrome. Diagnosis of suspected Cushing syndrome involves 3 major steps: confirmation of hypercortisolism, differentiation between corticotropin-independent and corticotropin-dependent causes of Cushing syndrome, and distinction between pituitary and ectopic corticotropin production. A definitive diagnosis of ectopic corticotropin secretion requires stringent criteria, including reversal of the clinical picture after resection of the tumor and/or demonstration of corticotropin immunohistochemical staining within the tumor tissue. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Ceacam1 separates graft-versus-host-disease from graft-versus-tumor activity after experimental allogeneic bone marrow transplantation.

    Directory of Open Access Journals (Sweden)

    Sydney X Lu

    Full Text Available Allogeneic bone marrow transplantation (allo-BMT is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT activity are limited by graft-versus-host-disease (GVHD. Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1 is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT in mouse models. In vivo, Ceacam1(-/- T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi, CD62L(lo. Additionally, Ceacam1(-/- CD8 T cells had greater expression of the gut-trafficking integrin α(4β(7, though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(-/- recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(-/- mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+ lymphoma model was improved in animals receiving Ceacam1(-/- vs. control T cells.We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the

  16. Impaired Pituitary Axes Following Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Robert A. Scranton


    Full Text Available Pituitary dysfunction following traumatic brain injury (TBI is significant and rarely considered by clinicians. This topic has received much more attention in the last decade. The incidence of post TBI anterior pituitary dysfunction is around 30% acutely, and declines to around 20% by one year. Growth hormone and gonadotrophic hormones are the most common deficiencies seen after traumatic brain injury, but also the most likely to spontaneously recover. The majority of deficiencies present within the first year, but extreme delayed presentation has been reported. Information on posterior pituitary dysfunction is less reliable ranging from 3%–40% incidence but prospective data suggests a rate around 5%. The mechanism, risk factors, natural history, and long-term effect of treatment are poorly defined in the literature and limited by a lack of standardization. Post TBI pituitary dysfunction is an entity to recognize with significant clinical relevance. Secondary hypoadrenalism, hypothyroidism and central diabetes insipidus should be treated acutely while deficiencies in growth and gonadotrophic hormones should be initially observed.

  17. Pituitary and mammary growth hormone in dogs

    NARCIS (Netherlands)

    Bhatti, Sofie Fatima Mareyam


    Several pathological (e.g. obesity and chronic hypercortisolism) and non-pathological (e.g. ageing) states in humans are characterized by a reduction in pituitary growth hormone (GH) secretion. Chronic hypercortisolism in humans is also associated with an impaired GH response to various stimuli.


    African Journals Online (AJOL)

    iMac User


    Mar 3, 2008 ... diagnosis of vertebrobasilar insufficiency. Head CT however did not reveal any haemorrhage and a lumbar tap performed about twelve hours after initial occurrence of symptoms failed to reveal xanthochromia. Brain MRI scan showed a hyperintense area in the posterior pituitary with decreased signals on.

  19. [TSH secreting adenoma of pituitary gland (TSHom) - rare cause of hyperthyroidism in pregnancy]. (United States)

    Bolz, M; Körber, S; Schober, H-C


    A 28 year-old woman in her first pregnancy was referred to the department of obstetrics and gynecology at 24 weeks of gestation because of pregnancy-induced hypertension. Thyroid stimulating hormone (TSH), free T3 and free T4 were elevated. Antibody screening did not show antithyroid peroxidase (anti-TPO) antibodies and TSH receptor antibodies. Clinical findings were suspicious of TSH secreting pituitary tumour (TSH-om) or thyroid hormone resistance (RTH). In absence of clinical sings of elevated intracranial pressure magnetic resonance imaging (MR) was discussed but not carried out and planned after delivery. A visual-field defect was ruled out by orbital field evaluation. Treatment with 3 × 50 mg propylthiouracil daily was initiated. However, normal fT3/fT4 titers could not be achieved. Serum levels were in the high normal ranges and TSH remained increased. The clinical situation of the patient improved resulting in a normal delivery at term. The healthy newborn was breast feed and MR imaging of the mother revealed a 5×8 mm tumor of the pituitary gland. In pregnant women with pregnancy-induced hypertension thyroid diseases have to be ruled out. Rare causes of hyperthyreoidism are TSH secreting pituitary tumors or thyroid hormone resistance (RTH). Treatment of choice for hyperthyreoidism in pregnancy is propylthiouracil. Normal vaginal delivery and breast feeding are possible. Following delivery it is mandatory to determine an individual treatment strategy. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Long-Term Effect of Cranial Radiotherapy on Pituitary-Hypothalamus Area in Childhood Acute Lymphoblastic Leukemia Survivors. (United States)

    Follin, Cecilia; Erfurth, Eva Marie


    Survival rates of childhood cancer have improved markedly, and today more than 80 % of those diagnosed with a pediatric malignancy will become 5-year survivors. Nevertheless, survivors exposed to cranial radiotherapy (CRT) are at particularly high risk for long-term morbidity, such as endocrine insufficiencies, metabolic complications, and cardiovascular morbidity. Deficiencies of one or more anterior pituitary hormones have been described following therapeutic CRT for primary brain tumors, nasopharyngeal tumors, and following prophylactic CRT for childhood acute lymphoblastic leukemia (ALL). Studies have consistently shown a strong correlation between the total radiation dose and the development of pituitary deficits. Further, age at treatment and also time since treatment has strong implications on pituitary hormone deficiencies. There is evidence that the hypothalamus is more radiosensitive than the pituitary and is damaged by lower doses of CRT. With doses of CRT hypothalamus and this usually causes isolated GH deficiency (GHD). Higher doses (>50 Gy) may produce direct anterior pituitary damage, which contributes to multiple pituitary deficiencies. The large group of ALL survivors treated with CRT in the 70-80-ties has now reached adulthood, and these survivors were treated mainly with 24 Gy, and the vast majority of these patients suffer from GHD. Further, after long-term follow-up, insufficiencies in prolactin (PRL) and thyroid stimulating hormone (TSH) have also been reported and a proportion of these patients were also adrenocoticotrophic hormone (ACTH) deficient. CRT to the hypothalamus causes neuroendocrine dysfunction, which means that the choice of GH test is crucial for the diagnosis of GHD.

  1. Perillyl Alcohol Protects against Fe-NTA-Induced Nephrotoxicity and Early Tumor Promotional Events in Rat Experimental Model

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    Tamanna Jahangir


    Full Text Available Plants have been widely used as protective agents against a wide variety of processes and compounds that damage tissues via free radical mechanisms. Perillyl alcohol (PA is a naturally occurring monoterpene found in the essential oils of numerous species of plants including mints, cherries and celery seeds. This monocyclic monoterpene has shown antioxidant and therapeutic activity in various studies against various xenobiotics. In this study, we have analyzed the effects of PA against single intraperitoneal dose of ferric nitrilotriacetate (Fe-NTA (9 mg iron per kg body weight-induced nephrotoxicity and early tumor promotional events. The pretreatment of Fe-NTA-treated rats with 0.5% per kg body weight dose and 1% per kg body weight dose of PA for seven consecutive days significantly reversed the Fe-NTA-induced malondialdehyde formation, xanthine oxidase activity (P < 0.001, ornithine decarboxylase activity (P < 0.001 and 3[H]thymidine incorporation in renal DNA (P < 0.001 with simultaneous significant depletion in serum toxicity markers blood urea nitrogen and creatinine (P < 0.001. Significant restoration at both the doses was recorded in depleted renal glutathione content, and its dependent enzymes with prophylactic treatment of PA. Present results suggest that PA potentially attenuates against Fe-NTA-induced oxidative damage and tumor promotional events that preclude its development as a future drug to avert the free radical-induced toxicity.

  2. Fat-suppressed dynamic MR imaging for the postoperative evaluation of pituitary adenomas

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    Akada, Kiyohiro [Tokyo Medical Coll. (Japan)


    The usefulness of the early post operative evaluation of pituitary adenomas with fat-suppressed MR imaging was studied. Thirty patients with pituitary adenoma, who underwent trans-sphenoidal surgery were analyzed. These include 22 with macroadenoma (3 recurrent cases) and 8 with microadenoma (2 recurrent cases). In all cases after adenoma resection, fat tissue was placed into the sella turcica to prevent postoperative cerebro-spinal fluid leakage and infections. T1-weighted and Gd DTPA-enhanced MR images were obtained using a 1.5-T superconductive MRI system (Shimadzu Co., Ltd.) by a standard technique and also by a fat suppression technique (chemical shift selective presaturation: CHESS) after surgery. It was difficult to discriminate between hematoma, fat tissue and pituitary posterior lobe on T1-weighted images within 1 month after surgery because of high-signal intensity. However, these regions could be distinguished one another by the CHESS technique. Normal pituitary anterior lobe could be identified in 86% of macroadenoma cases using Gd CHESS dynamic study, whereas it was identified only in 23% by standard technique. Normal anterior lobe was identified in 100% of microadenoma cases using Gd CHESS dynamic study. The residual tumors were found to invade into the supra sella or cavernous sinus, and these lesions could be distinguished from the surrounding tissue by the CHESS dynamic study in 83%, whereas only 33% could be distinguished by the standard technique. Although the fat tissue showed a time-sequence decrease in volume, high-signal intensity sometimes lasted long in association with degenerative granulation. In conclusion, CHESS dynamic MR Imaging study is useful for detection of the normal pituitary lobe and residual adenomas after trans-sphenoidal surgery. (author)

  3. Transsphenoidal Posterior Pituitary Lobe Biopsy in Patients with Neurohypophysial Lesions. (United States)

    Kinoshita, Yasuyuki; Yamasaki, Fumiyuki; Tominaga, Atsushi; Usui, Satoshi; Arita, Kazunori; Sakoguchi, Tetsuhiko; Sugiyama, Kazuhiko; Kurisu, Kaoru


    The differential diagnosis of neurohypophysial lesions is difficult, and surgical biopsies are indispensable in the histologic diagnosis of some patients. Although pituitary stalk biopsies are uniformly performed, there is a considerable risk that they will result in impaired hormonal secretion. We attempt to clarify the usefulness and safety of posterior pituitary lobe biopsy by transsphenoidal surgery (TSS). The cases of 11 consecutive patients who underwent posterior pituitary lobe biopsies by TSS were retrospectively studied. Patients with cystic sellar lesions were excluded. We examined the clinical findings, endocrinologic data, magnetic resonance imaging findings, and histologic diagnoses of the patients. The locations of neurohypophysial lesions and the histologic diagnoses by posterior pituitary lobe biopsies were examined. The major preoperative clinical symptoms were diabetes insipidus (DI) (90.9%), followed by anterior pituitary lobe dysfunction (hypopituitarism) (54.5%). In all the patients, the lesions occupied the pituitary stalk and the posterior pituitary lobe, and the bright spot, which would indicate a normal posterior pituitary gland, disappeared on T1-weighted imaging. The posterior pituitary lobe specimens could be histologically diagnosed in all these cases. DI persisted in 10 patients with preoperative DI after the biopsy, whereas the 1 patient without preoperative DI did not suffer from DI after the biopsy. A posterior pituitary lobe biopsy by TSS may be an alternative to pituitary stalk biopsy in patients with neurohypophysial lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Pituitary dysfunction in granulomatosis with polyangiitis. (United States)

    Esposito, Daniela; Trimpou, Penelope; Giugliano, Dario; Dehlin, Mats; Ragnarsson, Oskar


    Granulomatosis with polyangiitis (GPA) is a multisystem disease, characterized by necrotizing small-vessel vasculitis, which mainly affects the respiratory tract and the kidneys. Pituitary involvement in GPA is rare, present in about 1% of all cases of GPA. To date, only case reports or small case series have been published. Herein we report clinical features, imaging findings, treatment and outcomes in three patients with GPA-related pituitary dysfunction (PD). A retrospective analysis of three cases of GPA-related PD was conducted, followed by systematic review of the English medical literature using PubMed. The three cases include three women aged between 32 and 37 years. PD was the presenting feature in one and two developed PD in the course of the disease. All patients had a pituitary lesion on MRI. Conventional treatment with high doses of glucocorticoids and cyclophosphamide led to resolution or improvement of the MRI abnormalities, whereas it was not effective in restoring PD. A systematic review identified 51 additional patients, showing that GPA can lead to partial or global PD, either at onset or, during the course of the disease. Secondary hypogonadism is the predominant manifestation, followed by diabetes insipidus (DI). Sellar mass with central cystic lesion is the most frequent radiological finding. GPA should be carefully considered in patients with a sellar mass and unusual clinical presentation with DI and systemic disease. Although conventional induction-remission treatment improves systemic symptoms and radiological pituitary abnormalities, hormonal deficiencies persist in most of the patients. Therefore, follow-up should include both imaging and pituitary function assessment.

  5. Genes regulating hypothalamic and pituitary development. (United States)

    Parks, J S; Adess, M E; Brown, M R


    Several pituitary transcription factors have been identified in the last 3 years. They offer new insights into the processes that direct organogenesis, cell commitment, proliferation and differentiated function. All are DNA-binding proteins, but they have ties to different families of homeodomain proteins. They differ in their distribution and in the timing of their appearance and extinction. The Rathke's pouch homeobox protein (Rpx) has a paired-like homeodomain. In mice, it appears on embryonic day 8.5 (day e8.5) and is gone by day e14.5. Its targets for activation are unknown. Pituitary OTX has a tryptophan--phenylalanine--lysine motif in its homeodomain. It appears early and persists. It shows independent activation of the alpha-glycoprotein subunit (alpha-GSU) and pro-opiomelanocortin genes and co-operates with Pit-1 in activation of the growth hormone and prolactin genes. Pituitary Lim (P-Lim) protein also acts independently on the alpha-GSU gene, and acts in concert with Pit-1 to activate other genes. A fourth protein, termed the 'Prophet of Pit-1', or Prop-1, is the recently discovered cause of Ames dwarfism in mice. This paired-like protein is necessary for the subsequent expression of Pit-1 in somatotrophs, lactotrophs and thyrotrophs. Any or all of the newly discovered pituitary genes are candidates for mutations causing hypopituitarism in humans. As several are expressed transiently in tissues other than the pituitary during organogenesis, the phenotypes produced by mutations in these genes may prove to be complex.

  6. A dynamic Gli code interprets Hh signals to regulate induction, patterning, and endocrine cell specification in the zebrafish pituitary. (United States)

    Devine, Christine A; Sbrogna, Jennifer L; Guner, Burcu; Osgood, Marcey; Shen, Meng-Chieh; Karlstrom, Rolf O


    Hedgehog (Hh) signaling is necessary for the induction and functional patterning of the pituitary placode, however the mechanisms by which Hh signals are interpreted by placodal cells are unknown. Here we show distinct temporal requirements for Hh signaling in endocrine cell differentiation and describe a dynamic Gli transcriptional response code that interprets these Hh signals within the developing adenohypophysis. Gli1 is required for the differentiation of selected endocrine cell types and acts as the major activator of Hh-mediated pituitary induction, while Gli2a and Gli2b contribute more minor activator functions. Intriguingly, this Gli response code changes as development proceeds. Gli1 continues to be required for the activation of the Hh response anteriorly in the pars distalis. In contrast, Gli2b is required to repress Hh target gene expression posteriorly in the pars intermedia. Consistent with these changing roles, gli1, gli2a, and gli2b, but not gli3, are expressed in pituitary precursor cells at the anterior neural ridge. Later in development, gli1 expression is maintained throughout the adenohypophysis while gli2a and gli2b expression are restricted to the pars intermedia. Given the link between Hh signaling and pituitary adenomas in humans, our data suggest misregulation of Gli function may contribute to these common pituitary tumors.

  7. A case of Anterior Pituitary Failure Associated with Ectopic Neurohypophysis

    Directory of Open Access Journals (Sweden)

    Eren Gürkan


    Full Text Available Ectopic neurohypophysis is an anomaly of the pituitary gland. This syndrome is characterized by ectopic neurohypophysis hyperintense signal on magnetic resonance imaging (MRI. Absence of pituitary stalk visibility and anterior hypophysis hypoplasia may also present. Sensitivity of MRI for pituitary stalk is increased by gadolinium injection. Visibility of the pituitary stalk is related to isolated growth hormone (GH deficiency. In patients with no visible pituitary stalk on MRI after gadolinium injection, GH deficiency is expected during first years of life. Then anterior pituitary failure usually occurs on second and third decade of life. In this repor, we present a case of ectopic neurohypophysis in which the diagnosis of late-diagnosed anterior pituitary function failure was established at advanced age. Turk Jem 2012; 16: 49-51

  8. The effect of clomethiazole on plasma concentrations of interleukin-6, -8, -1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation.

    LENUS (Irish Health Repository)

    Harmon, D


    Clomethiazole (CMZ), a neuroprotective drug, has antiinflammatory actions. We investigated the effects of CMZ administration on plasma concentrations of interleukin (IL)-6, IL-8, IL-1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation. Five healthy volunteers each donated 500 mL of blood, which was subsequently divided into equal portions. Identical extracorporeal circuits were simultaneously primed with donated blood (250 mL) and circulated for 2 h at 37 degrees C. CMZ was added to 1 of the circuits of each pair to achieve a total plasma concentration of 40 micro mol\\/L. Blood samples were withdrawn at (i) donation, (ii) immediately after addition of CMZ, and at (iii) 30, 60, 90, and 120 min after commencing circulation. Plasma concentrations of IL-6, IL-8, and tumor necrosis factor-alpha were less in the CMZ group compared with control after 60 min of circulation (2.2 [0.3] versus 3.2 [0.4], 14.9 [4.8] versus 21.9 [18.4], 63.3 [43.5] versus 132.2 [118.9] pg\\/mL, respectively, P < 0.05). After 120 min of circulation, neutrophils from CMZ-treated circuits showed significantly less CD18 expression compared with control (237.5 [97.4] versus 280.5 [111.5], P = 0.03). The addition of CMZ to experimental extracorporeal circuits decreases the inflammatory response. This effect may be of clinical benefit by decreasing inflammatory-mediated neurological injury during cardiopulmonary bypass. IMPLICATIONS: Enhancement of gamma-aminobutyric acid(A)-mediated effects by clomethiazole (CMZ) and associated neuroprotection has been established in animal models of cerebral ischemia. In an ex vivo study, we demonstrated antiinflammatory activity of CMZ in experimental extracorporeal circulation. This represents a potential neuroprotective mechanism of CMZ in patients undergoing coronary artery bypass surgery.

  9. Increased pulmonary secretion of tumor necrosis factor-alpha in calves experimentally infected with bovine respiratory syncytial virus

    DEFF Research Database (Denmark)

    Rontved, C. M.; Tjørnehøj, Kirsten; Viuff, B.


    Bovine respiratory syncytial virus (BRSV) is an important cause of respiratory disease among calves in the Danish cattle industry. An experimental BRSV infection model was used to study the pathogenesis of the disease in calves. Broncho alveolar lung lavage (BAL) was performed on 28 Jersey calves...

  10. Time course of apoptotic tumor response after a single dose of chemotherapy: comparison with 99mTc-annexin V uptake and histologic findings in an experimental model. (United States)

    Takei, Toshiki; Kuge, Yuji; Zhao, Songji; Sato, Masayuki; Strauss, H William; Blankenberg, Francis G; Tait, Jonathan F; Tamaki, Nagara


    In tumors the process of apoptosis occurs over an interval of time after chemotherapy. To determine the best timing for detecting apoptosis in vivo with (99m)Tc-annexin V after chemotherapy, we examined the changes in (99m)Tc-annexin V accumulation over time in comparison with those of caspase-3 and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) expression level after cyclophosphamide treatment in an experimental model. Hydrazinonicotinamide (HYNIC)-annexin V was labeled with (99m)Tc ((99m)Tc-annexin V). Rats were inoculated with allogenic hepatoma cells (KDH-8) into the left calf muscle. Eleven days after the inoculation, the rats were randomly divided into the group receiving a single dose of cyclophosphamide (150 mg/kg intraperitoneally) and the control group. (99m)Tc-Annexin V (18.5 MBq [0.5 mCi] per rat) was injected intravenously in the rats 4, 12, and 20 h after the treatment and also to the control rats (n = 5 in each group). Radioactivity in tissues was determined 6 h after (99m)Tc-annexin V injection. Immunostaining of caspase-3 and TUNEL were performed to detect apoptosis, and the rates of positively stained cells were calculated. (99m)Tc-Annexin V accumulation in tumors significantly increased at 20 h (0.077 +/- 0.007 [%ID/g] x kg, where %ID/g = percentage injected dose per gram) but not at 4 or 12 h (0.048 +/- 0.008 and 0.052 +/- 0.014 [%ID/g] x kg, respectively) after cyclophosphamide treatment. (99m)Tc-Annexin V accumulation in tumors and the rate of apoptotic cells determined by caspase-3 immunostaining and TUNEL were significantly higher in treated rats 20 h after cyclophosphamide treatment as compared with control rats. The effective detection of apoptotic tumor response with (99m)Tc-annexin V required 20 h after cyclophosphamide treatment in an experimental model. The present results provide an important basis for determining the best timing of annexin V imaging after the start of chemotherapy

  11. Cavernous sinus invasion by pituitary macroadenomas: neuroradiological, clinical and surgical correlation

    Directory of Open Access Journals (Sweden)



    Full Text Available The classical imaging gold-standard for this diagnosis is the presence of tumor lateral to the carotid artery. Seventeen patients with pituitary macroadenomas with intraoperative confirmation of cavernous sinus invasion were studied with MRI. Only 8 patients had tumor lateral to the carotid artery; 13 had tumor within the carotid syphon and all lacked the ring enhancement of the medial wall of the cavernous sinus. In 10 patients, widening of the posterior double leaflets of the cavernous sinus could be. All patients were operated by the transesphenoidal route. Only one patient was cured by surgery alone. Only 3 patients disclosing the above mentioned MRI features were identified in a series of 250 patients and did not have cavernous sinus invasion. The present criteria proved to be useful in the pre-operative diagnosis of cavenous sinus invasion and patients' counselling. Pre-operative diagnosis of cavernous sinus invasion of pituitary tumors has a great impact in the management of such patients.

  12. Evaluation of Fine Feeding System and Angioarchitecture of Giant Pituitary Adenoma--Implications for Establishment of Surgical Strategy. (United States)

    Ogawa, Yoshikazu; Sato, Kenichi; Matsumoto, Yasushi; Tominaga, Teiji


    Giant pituitary adenomas carry higher surgical risks despite recent advances in microsurgical and/or endoscopic surgery, and postoperative acute catastrophic changes without major vessel disturbance are still extremely difficult to predict, may manifest as postoperative pituitary apoplexy, and are associated with poor outcomes. Eight males and 4 females aged 31-72 years (mean 50.7 years) with giant pituitary adenomas underwent preoperative investigation of fine angioarchitecture using C-arm cone-beam computed tomography with a flat-panel detector. Angiographical findings were used to decide the surgical routes and compared with clinical outcome. Feeding arteries were verified in 10 of 12 patients, whereas no feeding arteries were evident in 2 patients. The patients were divided into the faint tumor staining group and the significant staining group, which was reconfirmed by region of interest analysis. The former group had faint supply from the ipsilateral superior hypophyseal arteries and meningohypophyseal trunk, and the latter group had significant supply from the meningohypophyseal and inferolateral trunks, which passed centrifugally from the inferoposterior pole of the tumor. All patients were treated through the extended transsphenoidal approach. Intraoperative bleeding was significantly greater in the latter group (P = 0.013). All patients had improvement of neurologic deficit and were released from the intensive care unit within a few days. Major blood supply of giant pituitary adenomas originates from branches of the infraclinoidal portion of the internal carotid artery, different from the normal anterior pituitary gland. Surgical route should depend on not only tumor shape and extension but also feeding systems. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Silibinin modulates caudal-type homeobox transcription factor (CDX2), an intestine specific tumor suppressor to abrogate colon cancer in experimental rats. (United States)

    Sangeetha, N; Nalini, N


    To authenticate the colon cancer preventive potential of silibinin, the efficacy of silibinin needs to be tested by evaluating an organ-specific biomarker. The aim of this study was to evaluate the impact of silibinin on the colonic expression of the caudal-type homeobox transcription factor (CDX2) an intestine specific tumor suppressor gene and its downstream targets in the colon of rats challenged with 1,2 dimethyl hydrazine (DMH). Rats of groups 1 and 2 were treated as control and silibinin control. Rats under groups 3 and 4 were given DMH (20 mg/kg body weight (b.w.) subcutaneously) once a week for 15 consecutive weeks from the 4th week of the experimental period. In addition, group 4 rats alone were treated with silibinin (50 mg/kg b.w. per os) everyday throughout the study period of 32 weeks. Histological investigation and messenger RNA and protein expression studies were performed in the colonic tissues of experimental rats. Findings of the study revealed that DMH administration significantly decreased the expression of CDX2 and Guanylyl cyclase C (GCC) in the colon of experimental rats. Further the decreased levels of CDX2 protein, colonic mucin content, and increased number of mast cells in the colon of DMH alone-administered rats reflects the onset of carcinogenesis. The pathological changes caused due to CDX2 suppression were attenuated by silibinin supplementation. © The Author(s) 2014.

  14. Cryptococcal meningitis after transnasal transsphenoidal pituitary microsurgery of ACTH-secreting pituitary adenoma: A case report. (United States)

    Liu, Yang; Feng, Ming; Yao, Yong; Deng, Kan; Bao, Xinjie; Liu, Xiaohai; Wang, Renzhi


    Microbial infection should be regarded in the differential diagnosis of neurosurgical complications after transnasal transsphenoidal pituitary microsurgery, albeit cryptococcal meningitis is rare. This article will discuss the risk factors of cryptococcal meningitis in patients underwent transnasal transsphenoidal pituitary microsurgery, and summary the potential origins of infection. Here, we report a case of 37-year-old male who had cryptococcal meningitis after transnasal transsphenoidal pituitary microsurgery of a relapsing ACTH-secreting pituitary adenoma. Standard therapy for Cryptococcus neoformans (fluconazole [400 mg per day] and flucytosine) was administered and followed by maintenance dose. The patient had been on treatment for one and a half years during follow-up and reported neurologically well with repeated negative cerebrospinal fluid (CSF) culture until sudden death of heart arrest. C neoformans can be a possible cause of meningitis in immunocompetent patients after transnasal transsphenoidal pituitary microsurgery. Risk factors, such as pre-existed pulmonary infection and Cushing-associated hypercortisolemia, should be stressed. Promising preventive measures may include preoperative routine sputum smear and India-ink stain for screening, preoperative treatment of cryptococcal pneumonia, postoperative antibiotic management, and a more secure skull base reconstruction. Radiation and pharmaceutical treatment may be alternative for recurrent Cushing disease.

  15. Melatonin and hypothalamic-pituitary-gonadal axis. (United States)

    Shi, L; Li, N; Bo, L; Xu, Z


    Melatonin (N-acetyl-5-methoxy-tryptamine), a principal product of the pineal gland, is produced mainly during the dark phase of the circadian cycle. This hormone plays a crucial role in the regulation of circadian and seasonal changes in various aspects of physiology and neuroendocrine functions. In mammals, melatonin can influence sexual maturation and reproductive functions via activation of its receptors and binding sites in the hypothalamic-pituitary-gonadal (HPG) axis. This review summarizes current knowledge of melatonin on the hypothalamus, pituitary gland, and gonads. We also review recent progress in clinical applications of melatonin or potentials of using melatonin, as a reducer of oxidative stress, to improve reproductive functions for the diseases such as women infertility.

  16. Increased severity of experimental autoimmune encephalomyelitis, chronic macrophage/microglial reactivity, and demyelination in transgenic mice producing tumor necrosis factor-alpha in the central nervous system

    DEFF Research Database (Denmark)

    Taupin, V; Renno, T; Bourbonnière, L


    Tumor necrosis factor-alpha (TNF-alpha) is an inflammatory cytokine implicated in a number of autoimmune diseases. Apoptotic cell death is induced by TNF-alpha in vitro, and has been suggested as one cause of autoimmune pathology, including autoimmune demyelinating diseases where oligodendrocytes...... and showed no spontaneous pathology, but they developed experimental autoimmune encephalomyelitis (EAE) with greater severity than nontransgenic controls when immunized with MBP in adjuvant. Unlike nontransgenic controls, EAE then progressed to a nonabating demyelinating disease. Macrophage....../microglial reactivity was evident in demyelinating lesions in spinal cord, but T cells were not detected during chronic disease. The participation of TNF-alpha in the demyelinating process is thus more probably due to the perpetuation of macrophage/microglial activation than to direct cytotoxicity of myelin...

  17. Pituitary apoplexy presenting as myocardial infarction

    Directory of Open Access Journals (Sweden)

    Vishal Gupta


    Full Text Available We describe a male patient who presented with sudden onset severe headache and right sided ptosis that was diagnosed to be secondary to pituitary apoplexy on the background of diabetes mellitus. This was complicated by left ventricular failure and acute coronary syndrome. The case highlights the importance of considering hypocortisolism/hypopituitarism as an important and rare precipitant of an acute coronary event as occurred in the case.

  18. Adjuvant or radical fractionated stereotactic radiotherapy for patients with pituitary functional and nonfunctional macroadenoma

    Directory of Open Access Journals (Sweden)

    Weber Damien C


    Full Text Available Abstract Purpose To evaluate the efficacy and toxicity of stereotactic fractionated radiotherapy (SFRT for patients with pituitary macroadenoma (PMA. Methods and Materials Between March 2000 and March 2009, 27 patients (male to female ratio, 1.25 with PMA underwent SFRT (median dose, 50.4 Gy. Mean age of the patients was 56.5 years (range, 20.3 - 77.4. In all but one patient, SFRT was administered for salvage treatment after surgical resection (transphenoidal resection in 23, transphenoidal resection followed by craniotomy in 2 and multiple transphenoidal resections in another patient. In 10 (37% patients, the PMAs were functional (3 ACTH-secreting, 3 prolactinomas, 2 growth hormone-secreting and 2 multiple hormone-secretion. Three (11.1% and 9 (33.3% patients had PMA abutting and compressing the optic chiasm, respectively. Mean tumor volume was 2.9 ± 4.6 cm3. Eighteen (66.7% patients had hypopituitarism prior to SFRT. The mean follow-up period after SFRT was 72.4 ± 37.2 months. Results Tumor size decreased for 6 (22.2% patients and remained unchanged for 19 (70.4% other patients. Two (7.4% patients had tumor growth inside the prescribed treatment volume. The estimated 5-year tumor growth control was 95.5% after SFRT. Biochemical remission occurred in 3 (30% patients with functional PMA. Two patients with normal anterior pituitary function before SFRT developed new deficits 25 and 65 months after treatment. The 5-year survival without new anterior pituitary deficit was thus 95.8%. Five patients with visual field defect had improved visual function and 1 patient with no visual defect prior to SFRT, but an optic chiasm abutting tumor, had a decline in visual function. The estimated 5-year vision and pituitary function preservation rates were 93.2% and 95.8%, respectively. Conclusions SFRT is a safe and effective treatment for patients with PMA, although longer follow-up is needed to evaluate long-term outcomes. In this study, approximately 1

  19. Pituitary transplantation: Part 1. Successful reconstitution of pituitary-dependent hormone levels. (United States)

    Tulipan, N B; Zacur, H A; Allen, G S


    Neonatal or adult pituitary glands were transplanted to the median eminence of adult rats of the same or a histoincompatible inbred strain. The hormonal status of 39 transplanted rats and of control animals was evaluated by serial determination of serum prolactin and thyroxine. Grafts of neonatal tissue to adults of the same strain resulted in normal postoperative hormone levels. This indicates not only that pituitary grafts had survived, but also that the transplants were under hypothalamic control. Grafts of adult tissue were less successful. The prolactin value was lower, but still within the normal range, whereas the thyroxine value was lower than normal, suggesting that viable pituitary tissue had survived but was not under hypothalamic control. Transplantation across a histocompatibility barrier was uniformly unsuccessful. Postoperative prolactin levels were low and thyroxine levels were not significantly different from those in hypophysectomized controls.

  20. Rare case of Cushing's disease due to double ACTH-producing adenomas, one located in the pituitary gland and one into the stalk. (United States)

    Mendola, Marco; Dolci, Alessia; Piscopello, Lanfranco; Tomei, Giustino; Bauer, Dario; Corbetta, Sabrina; Ambrosi, Bruno


    We describe a patient affected by Cushing's disease due to the presence of double pituitary adenomas, one located within the anterior pituitary and the other in the infundibulum associated with a remnant of Rakthe's pouch. Cure was achieved only after the infundibulum lesion was surgically removed. A 38-year-old female presented with unexplained weight gain, hirsutism, amenorrhea, asthenia, recurrent cutaneous micotic infections and alopecia. Hormonal studies indicated Cushing's disease and MRI showed an enlarged pituitary gland with a marked and homogeneous enhancement after injection of gadolinium and an enlarged infundibulum with a maximum diameter of 8 mm. As a venous sampling of the inferior petrosal sinus after 10 μg iv desmopressin stimulation revealed a central to peripheral ACTH ratio consistent with a pituitary ACTH-secreting tumor, transphenoidal explorative surgery was performed and a 4-mm pituitary adenoma immunopositive for ACTH was disclosed and removed. Since postoperative hormonal evaluation showed persistent hypercortisolism, confirmed by dynamic tests, the patient again underwent surgery by transcranial access and the infundibulum mass was removed. Histology and immunochemistry were consistent with an ACTH-secreting adenoma. A few months after the second operation, cushingoid features were significantly reverted and symptoms improved. Although Cushing's patients bearing multiple adenomas have already been documented, the presence of two adenomas both immunohistochemically positive for ACTH is a very rare cause of Cushing's disease and this is the first report of a case of double ACTH-producing adenomas, one located in the pituitary gland and one attached to the stalk.

  1. Infundibulo-hypophysitis-like radiological image in a patient with pituitary infiltration of a diffuse large B-cell non-Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    A León-Suárez


    Full Text Available Non-Hodgkin lymphoma (NHL is a hematological tumor caused by abnormal lymphoid proliferation. NHL can arise in any part of the body, including central nervous system (CNS. However, pituitary involvement is a quite rare presentation. The diffuse large B-cell lymphoma (DLBCL is the most common subtype when pituitary is infiltrated. Here, we report a case of pituitary infiltration of NHL DLBCL type in a woman with hypopituitarism and an infundibulum-hypophysitis-like image on magnetic resonance imaging (MRI. A female aged 64 years, complained of dyspepsia, fatigue, weight loss and urine volume increment with thirst. Endoscopy and gastric biopsy confirmed diffuse large B-cell lymphoma. Treatment with chemotherapy using R-CHOP was initiated. During her hospitalization, hypotension and polyuria were confirmed. Hormonal evaluation was compatible with central diabetes insipidus and hypopituitarism. Simple T1 sequence of MRI showed thickening of the infundibular stalk with homogeneous enhancement. After lumbar puncture analysis, CNS infiltration was confirmed showing positive atypical lymphocytes. Pituitary and infundibular stalk size normalized after R-CHOP chemotherapy treatment. In conclusion, pituitary infiltration of NHL with infundibular-hypophysitis-like image on MRI is a rare finding. Clinical picture included hypopituitarism and central diabetes insipidus. Diagnosis should be suspected after biochemical analysis and MRI results. Treatment consists of chemotherapy against NHL and hormonal replacement for pituitary dysfunction.

  2. A high-throughput analysis of the IDH1(R132H) protein expression in pituitary adenomas

    DEFF Research Database (Denmark)

    Casar-Borota, Olivera; Øystese, Kristin Astrid Berland; Sundström, Magnus


    PURPOSE: Inactivating mutations of isocitrate dehydrogenase (IDH) 1 and 2, mitochondrial enzymes participating in the Krebs tricarboxylic acid cycle play a role in the tumorigenesis of gliomas and also less frequently in acute myeloid leukemia and other malignancies. Inhibitors of mutant IDH1...... and IDH2 may potentially be effective in the treatment of the IDH mutation driven tumors. Mutations in the succinate dehydrogenase, the other enzyme complex participating in the Krebs cycle and electron transfer of oxidative phosphorylation occur in the paragangliomas, gastrointestinal stromal tumors......, and occasionally in the pituitary adenomas. We aimed to determine whether the IDH1(R132H) mutation, the most frequent IDH mutation in human malignancies, occurs in pituitary adenomas. METHODS: We performed immunohistochemical analysis by using a monoclonal anti-IDH1(R132H) antibody on the tissue microarrays...

  3. Effect of titanium dental implants on proton therapy delivered for head tumors: experimental validation using an anthropomorphic head phantom (United States)

    Oancea, C.; Shipulin, K.; Mytsin, G.; Molokanov, A.; Niculae, D.; Ambrožová, I.; Davídková, M.


    A dosimetric experiment was performed at the Medico-Technical Complex in the Joint Institute for Nuclear Research, Dubna, to investigate the effects of metallic dental implants in the treatment of head and neck tumours with proton therapy. The goal of the study was to evaluate the 2D dose distributions of different clinical treatment plans measured in an anthropomorphic phantom, and compare them to predictions from a treatment planning system. The anthropomorphic phantom was sliced into horizontal segments. Two grade 4 Titanium implants were inserted between 2 slices, corresponding to a maxillary area. GafChromic EBT2 films were placed between the segments containing the implants to measure the 2D delivered dose. Two different targets were designed: the first target includes the dental implants in the isocentre, and in the second target, the proton beam is delivered through the implants, which are located at the entrance region of the Bragg curve. The experimental results were compared to the treatment plans made using our custom 3D Treatment Planning System, named RayTreat. To quantitatively determine differences in the isodose distributions (measured and calculated), the gamma index (3 mm, 3%) was calculated for each target for the matrix value in the region of high isodose (> 90%): for the experimental setup, which includes the implants in the SOBP region, the result obtained was 84.3%. When the implants were localised in the entrance region of the Bragg curve, the result obtained was 86.4%. In conclusion, the uncertainties introduced by the clinically planned dose distribution are beyond reasonable limits. The linear energy transfer spectra in close proximity to the implants were investigated using solid state nuclear track detectors (TED). Scattered particles outside the target were detected.

  4. Plurihormonal cells of normal anterior pituitary: Facts and conclusions


    Mitrofanova, Lubov B; Konovalov, Petr V.; Krylova, Julia S.; Polyakova, Victoria O.; Igor M. Kvetnoy


    Introduction plurihormonality of pituitary adenomas is an ability of adenoma cells to produce more than one hormone. After the immunohistochemical analysis had become a routine part of the morphological study, a great number of adenomas appeared to be multihormonal in actual practice. We hypothesize that the same cells of a normal pituitary gland releases several hormones simultaneously. Objective To analyse a possible co-expression of hormones by the cells of the normal anterior pituitary of...

  5. 3D Volumetric Measurements of GH Secreting Adenomas Correlate with Baseline Pituitary Function, Initial Surgery Success Rate, and Disease Control. (United States)

    Tirosh, Amit; Papadakis, Georgios Z; Chittiboina, Prashant; Lyssikatos, Charalampos; Belyavskaya, Elena; Keil, Meg; Lodish, Maya B; Stratakis, Constantine A


    There is scarce data on the clinical utility of volume measurement for growth hormone (GH)-secreting pituitary adenomas. The current study objective was to assess the association between pituitary adenoma volumes and baseline endocrine evaluation, initial surgical success rate, and disease control among patients with acromegaly. A retrospective cohort study was conducted at a clinical research center including patients with acromegaly due to GH-secreting pituitary adenomas. Baseline hormonal evaluation and adenoma characteristics according to MRI were collected. Volumetric measurements of pituitary adenomas were performed using a semi-automated lesion segmentation and tumor-volume assessment tools. Rates of post-operative medical treatment, radiation therapy, and re-operation were gathered from the patients' medical records. Twenty seven patients (11 females) were included, median age 21.0 years (interquartile range 29 years, range 3-61 years). Patients harboring adenomas with a volume <2 000 mm 3 had higher chance to achieve disease remission [94.1% (n=16) vs. 50.0% (n=4), p<0.05]. Adenoma volumes positively correlated with baseline plasma GH levels before and after oral glucose administration, and with plasma IGF-I and PRL levels. Adenoma volume had negative correlation with morning plasma cortisol levels. Finally, patients harboring larger adenomas required 2nd surgery and/or medical treatment more often compared with subjects with smaller adenomas. Accurate 3D volume measurement of GH-secreting pituitary adenomas may be used for the prediction of initial surgery success and for disease control rates among patients with a GH-secreting pituitary adenomas and performs better than standard size assessments. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Plurihormonality of pituitary adenomas in light of immunohistochemical studies. (United States)

    Pawlikowski, Marek; Kunert-Radek, Jolanta; Radek, Maciej


    Plurihormonality of pituitary adenomas can be defined as the ability of an adenoma to express more than one pituitary hormone. The application of immunohistochemistry to diagnose surgically removed pituitary tumours revealed that a great number of pituitary adenomas are in fact plurihormonal. However, data on the incidence and the clinical relevance of the pituitary adenoma plurihormonality are still scarce and controversial. Hundred fifty-five pituitary adenomas, surgically removed, were studied immunohistochemically with the antibodies against pituitary hormones or their subunits. Additionally, 40 adenomas were immunostained with Ki-67 antibody to evaluate the proliferative potential. According to the World Health Organization (WHO) recommendations, we did not consider tumours expressing both FSH and LH (gonadotropinomas) or somatoprolactinomas expressing both GH and prolactin as plurihormonal. Even with this limitation, plurihormonality was found to be a frequent finding in both hormonally active and clinically non-functioning pituitary adenomas. It was shown that over one-third (36.1%) of the investigated adenomas expressed more than one hormone. Plurihormonality, especially that which is connected with co-expression of ACTH, seems to be more frequent in the recurrent tumours. Plurihormonal adenomas also possess higher Ki-67 indices, as compared to monohormonal tumours. Plurihormonality is a frequent phenomenon in both hormonally active and clinically non-functioning pituitary adenomas. It also seems to predict a higher risk of tumour recurrence. (Pol J Endocrinol 2010; 61 (1): 63-66).

  7. Volume of the adrenal and pituitary glands in depression

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Willer, Inge Stoel; Knorr, Ulla


    Numerous studies have shown that the hypothalamic-pituitary-adrenal (HPA) axis is hyperactive in some depressed patients. It is unclear whether such hyperactivity results in changed volumes of the adrenal glands, pituitary gland and hypothalamus. We systematically reviewed all controlled studies...... on the adrenal or pituitary glands or hypothalamus volume in unipolar depressive disorder published in PubMed 1966 to December 2009. We identified three studies that investigated the volume of the adrenal glands and eight studies that examined the volume of the pituitary gland, but no studies on hypothalamus...

  8. Predictive value of PWI for blood supply and T1-spin echo MRI for consistency of pituitary adenoma

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Zengyi; He, Wenqiang; Zhao, Yao; Zhang, Qilin; Li, Shiqi; Wang, Yongfei [Fudan University, Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Shanghai (China); Shanghai Pituitary Tumor Center, Shanghai (China); Yuan, Jie; Wu, Yue; Yao, Zhenwei [Fudan University, Department of Radiology, Huashan Hospital, Shanghai Medical College, Shanghai (China); Chen, Hong [Fudan University, Department of Neuropathology, Huashan Hospital, Shanghai Medical College, Shanghai (China)


    It is a common view that consistency and blood supply of pituitary adenoma (PA) can influence the surgical effect. The aim of this study was to determine whether MRI signal intensity (SI) was correlated to the consistency or blood supply of pituitary macroadenoma. Forty eight pituitary macroadenoma patients were underwent preoperative MRI, including precontrast and contrast-enhanced (CE) T1-spin echo (T1-SE) imaging, CE-sampling perfection with application-optimized contrasts by using different flip angle evolutions (SPACE) imaging, and perfusion-weighted imaging (PWI). The tumor consistency and blood supply were determined by neurosurgeons. The expression of collagen IV and MIB-1 was detected with immunohistology. The correlation of the relative SI (rSI) values (tumor to normal frontal white matter SI) and PWI data to the tumor consistency, blood supply, and the expression level of collagen IV and MIB-1 was statistically studied by Kruskal-Wallis rank test (K-W test). A significant correlation was observed between the tumor consistency and the rSI on precontrast T1-SE imaging (P = 0.004) but not on CE T1-SE and CE SPACE imaging. The expression of collagen IV was also significantly associated with rSI on T1-SE imaging (P = 0.010). The blood supply was correlated with the relative CBV (rCBV) (P = 0.030). In addition, the expression of MIB-1 was correlated with rSI of CE T1-SE imaging (P = 0.007). Our results suggest that T1-SE imaging may be a simple and useful method for predicting consistency of PA. CBV value can provide helpful information for assessing the blood supply of pituitary macroadenoma. (orig.)

  9. Predictive value of PWI for blood supply and T1-spin echo MRI for consistency of pituitary adenoma. (United States)

    Ma, Zengyi; He, Wenqiang; Zhao, Yao; Yuan, Jie; Zhang, Qilin; Wu, Yue; Chen, Hong; Yao, Zhenwei; Li, Shiqi; Wang, Yongfei


    It is a common view that consistency and blood supply of pituitary adenoma (PA) can influence the surgical effect. The aim of this study was to determine whether MRI signal intensity (SI) was correlated to the consistency or blood supply of pituitary macroadenoma. Forty eight pituitary macroadenoma patients were underwent preoperative MRI, including precontrast and contrast-enhanced (CE) T1-spin echo (T1-SE) imaging, CE-sampling perfection with application-optimized contrasts by using different flip angle evolutions (SPACE) imaging, and perfusion-weighted imaging (PWI). The tumor consistency and blood supply were determined by neurosurgeons. The expression of collagen IV and MIB-1 was detected with immunohistology. The correlation of the relative SI (rSI) values (tumor to normal frontal white matter SI) and PWI data to the tumor consistency, blood supply, and the expression level of collagen IV and MIB-1 was statistically studied by Kruskal-Wallis rank test (K-W test). A significant correlation was observed between the tumor consistency and the rSI on precontrast T1-SE imaging (P = 0.004) but not on CE T1-SE and CE SPACE imaging. The expression of collagen IV was also significantly associated with rSI on T1-SE imaging (P = 0.010). The blood supply was correlated with the relative CBV (rCBV) (P = 0.030). In addition, the expression of MIB-1 was correlated with rSI of CE T1-SE imaging (P = 0.007). Our results suggest that T1-SE imaging may be a simple and useful method for predicting consistency of PA. CBV value can provide helpful information for assessing the blood supply of pituitary macroadenoma.

  10. [Effect of coenzyme Q10 on the expression of tumor necrosis factor-α and interleukin-10 in gingival tissue of experimental periodontitis in rats]. (United States)

    Jin, Hui-jiao; Xue, Yi; Chen, Guang; Wu, Zhong-yin


    To investigate the effect of coenzyme Q10 on the levels of tumor necrosis factor-α(TNF-α) and interleukin-10 (IL-10) in gingival tissue of experimental periodontitis in rats. A total of 48 healthy Wistar rats were divided into 3 groups of 16 randomly, normal group, coenzyme Q10 treatment group (Q10 group) and periodontitis group.Normal group was fed with normal diet and water. Periodontitis models were established in other two groups.Q10 group received coenzyme Q10 for 12 weeks and periodontitis group was fed with the same dose of normal saline.Four rats in each group were sacrified before administration and 4, 8 and 12 weeks after administration. Gingival tissue samples from mandiblar first permanent molar were taken. The levels of TNF-α and IL-10 were detected by immunohistochemistry. The expression of TNF-α in periodontitis group [54.9% (52.9%, 57.3%)] was significantly higher than that in Q10 group [15.1% (12.7%, 17.5%)] at 12 weeks (P Q10 group [38.9% (38.0%, 40.4%)] (P Q10 group at 12th weeks (P Q10 group (P Coenzyme Q10 inhibits the expression of TNF-α and promotes the expression of IL-10 in periodontal tissues of experimental periodontitis rats. Coenzyme Q10 may play a role in treating periodontitis.

  11. Clinical Characteristics and Treatment Outcome of 485 Patients with Nonfunctioning Pituitary Macroadenomas

    Directory of Open Access Journals (Sweden)

    Guadalupe Vargas


    Full Text Available Background. Nonfunctioning pituitary adenomas (NFPAs are the most common benign lesions of the pituitary gland. Objective. To describe our experience with the management of NFPA. Study Design and Methods. Retrospective evaluation of NFPA patients managed between 2008 and 2013. We analyzed data regarding clinical presentation, imaging diagnosis, hormonal status, surgical, radiotherapeutic, and pharmacological treatment, and outcome. Results. 485 patients (54% men, mean age 53±14 years were followed for a median of 6.5 years. Visual field abnormalities and headaches were the presenting complaints in 87% and 66%, respectively. The diagnosis of NFPA was made incidentally in 6.2%, and 8% presented with clinical evidence of apoplexy. All patients harbored macroadenomas, with a median volume of 10306 mm3; 57.9% had supra- or parasellar invasion and 19.6% had tumors larger than 4 cm. Central hypothyroidism, hypogonadism, and hypocortisolism were present in 47.2%, 35.9%, and 27.4%, respectively. Surgical resection was performed at least once in 85.7%. Tumor persistence was documented in 27% and was related to the size and invasiveness of the lesion. In selected cases, radiotherapy proved to be effective in controlling or preventing tumor growth. Conclusions. The diagnosis and treatment of NFPA are complex and require a multidisciplinary approach.

  12. Bone tumor (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects passed down ...

  13. Unsuspected meningioma in a patient with pituitary gigantism. Case report with autopsy findings

    Energy Technology Data Exchange (ETDEWEB)

    Stock, J.M.; Ghatak, N.R.; Oppenheimer, J.H.


    A unique example of a clinically unsuspected large parasellar meningioma is described in a 36-yr-old pituitary giant who had been treated initially with conventional irradiation, subsequently by surgical excision of an acidophil adenoma, and ultimately with medroxyprogesterone acetate (MPA) prior to his demise. The patient died of increased intracranial pressure resulting from a combined mass effect of the meningioma and recurrent tumor. The relationship between radiation and the development of the meningioma is discussed, as well as the fine ultrastructure of a highly functioning acidophil adenoma.

  14. Harvey Cushing and pituitary Case Number 3 (Mary D.): the origin of this most baffling problem in neurosurgery. (United States)

    Pascual, José María; Prieto, Ruth


    From the very beginning of his career, Harvey Williams Cushing (1869-1939) harbored a deep interest in a complex group of neoplasms that usually developed at the infundibulum. These were initially known as "interpeduncular" or "suprasellar" cysts. Cushing introduced the term "craniopharyngioma" for these lesions, which he believed represented one of the most baffling problems faced by neurosurgeons. The patient who most influenced Cushing's thinking was a 16-year-old seamstress named "Mary D.," whom he attended in December 1901, exactly the same month that Alfred Fröhlich published his seminal article describing an adiposogenital syndrome in a young boy with a pituitary cyst. Both Cushing's and Fröhlich's patients showed similar symptoms caused by the same type of tumor. Notably, Cushing and Fröhlich had met one another and became good friends in Liverpool the summer before these events took place. Their fortunate relationship led Cushing to realize that Fröhlich's syndrome represented a state of hypopituitarism and provided a useful method of diagnosing interpeduncular cysts. It is noteworthy that Cushing's very first neurosurgical procedure on a pituitary tumor was performed in the case of Mary D.'s "interpeduncular cyst," on February 21, 1902. Cushing failed to remove this lesion, which was later found during the patient's autopsy. This case was documented as Pituitary Case Number 3 in Cushing's masterpiece, The Pituitary Body and Its Disorders, published in 1912. This tumor was considered "a teratoma"; however, multiple sources of evidence suggest that this lesion actually corresponded to an adamantinomatous craniopharyngioma. Unfortunately, the pathological specimens of this lesion were misplaced, and this prompted Cushing's decision to retain all specimens and documents of the cases he would operate on throughout his career. Accordingly, Mary D.'s case crystallized the genesis of the Cushing Brain Tumor Registry, one of Cushing's major legacies to


    Jiang, Kan; Kwak, Hyeongil; Tosato, Giovanna


    Although Vascular Endothelial Growth Factor (VEGF)-targeted therapies have shown efficacy in the treatment of certain advanced cancers, benefits to patients have been modest, which is attributed to tumor resistance to VEGF neutralization. Recent efforts to identify new targets to inhibit tumor angiogenesis have identified Bv8 (prokineticin 2), a myeloid cell-derived protein that promotes endothelial cell growth and tumor angiogenesis, but many mechanistic aspects of the pro-tumorigenic function of Bv8 are unclear. Here we demonstrate that CD11b+, Ly6C+, Ly6G+ granulocytes are the predominant cell source of Bv8 expression in bone marrow, spleen and in tumor tissues. Using granulocyte-deficient Growth factor independence-1 (Gfi1)-null mutant mice and normal littermates, we found that EL4 lymphoma tumors grow significantly larger in the granulocyte and Bv8-deficient mutant mice in comparison to the normal mice that display abundant tumor-associated granulocytes and Bv8 expression. Conversely, Lewis lung carcinoma (LLC-1) tumors grew to a significantly greater size in the normal mice in comparison to the Gfi1-null mice, but normal granulocyte tumor infiltration was modest. Quantitative analysis of tissue vascularization showed that EL4 and LLC-1 tumors from normal and Gfi1-mutant mice are similarly vascularized. These results confirm the critical contribution of the tumor microenvironment in determining the rate of tumor progression independently of tumor angiogenesis, and reveal some of the complexities of granulocyte and Bv8 functions in modulating tumor growth.

  16. Mutation and genomic amplification of the PIK3CA proto-oncogene in pituitary adenomas

    Energy Technology Data Exchange (ETDEWEB)

    Murat, C.B.; Braga, P.B.S.; Fortes, M.A.H.Z. [Laboratório de Endocrinologia Celular e Molecular (LIM-25), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Bronstein, M.D. [Unidade de Neuroendocrinologia, Serviço de Endocrinologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Corrêa-Giannella, M.L.C.; Giorgi, R.R. [Laboratório de Endocrinologia Celular e Molecular (LIM-25), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)


    The tumorigenesis of pituitary adenomas is poorly understood. Mutations of the PIK3CA proto-oncogene, which encodes the p110-α catalytic subunit of PI3K, have been reported in various types of human cancers regarding the role of the gene in cell proliferation and survival through activation of the PI3K/Akt signaling pathway. Only one Chinese study described somatic mutations and amplification of the PIK3CA gene in a large series of pituitary adenomas. The aim of the present study was to determine genetic alterations of PIK3CA in a second series that consisted of 33 pituitary adenomas of different subtypes diagnosed by immunohistochemistry: 6 adrenocorticotropic hormone-secreting microadenomas, 5 growth hormone-secreting macroadenomas, 7 prolactin-secreting macroadenomas, and 15 nonfunctioning macroadenomas. Direct sequencing of exons 9 and 20 assessed by qPCR was employed to investigate the presence of mutations and genomic amplification defined as a copy number ≥4. Previously identified PIK3CA mutations (exon 20) were detected in four cases (12.1%). Interestingly, the Chinese study reported mutations only in invasive tumors, while we found a PIK3CA mutation in one noninvasive corticotroph microadenoma. PIK3CA amplification was observed in 21.2% (7/33) of the cases. This study demonstrates the presence of somatic mutations and amplifications of the PIK3CA gene in a second series of pituitary adenomas, corroborating the previously described involvement of the PI3K/Akt signaling pathway in the tumorigenic process of this gland.

  17. Prospective trial of a short hospital stay protocol after endoscopic endonasal pituitary adenoma surgery. (United States)

    Thomas, Jonathan G; Gadgil, Nisha; Samson, Susan L; Takashima, Masayoshi; Yoshor, Daniel


    Patients typically remain hospitalized for several days after transsphenoidal surgery for pituitary adenoma resection for reasons including pain control, serial neurological assessments, surveillance for cerebrospinal fluid leak, and management of endocrine issues. We sought to determine whether an evidence-based perioperative care protocol combined with an endoscopic approach could lead to routine and safe discharge on postoperative day 1. Our multidisciplinary pituitary group prospectively implemented a perioperative care protocol that emphasizes patient education, early mobilization, and scheduled inpatient and outpatient endocrine assessments on 50 consecutive patients who underwent surgical resection of a pituitary adenoma (82% macroadenomas, 2.1 ± 0.8 cm, maximum 4.5 cm, 18% microadenomas). Endoscopic endonasal surgery characterized by aggressive tumor resection and avoidance of nasal packing and lumbar drains was used in all cases. Lengths of stay, readmissions, and postoperative outcomes were analyzed. Using the short-stay protocol, 92% (46 of 50) of patients were successfully discharged on postoperative day 1. The average length of stay for all patients was 1.16 ± 0.55 days (range 1 to 4). Postoperative diabetes insipidus occurred in 16% of patients (8 of 50), was effectively managed on an outpatient basis, and did not delay discharge. Readmission was required in 2 patients, in both cases for delayed presentation of a cerebrospinal fluid leak. A short-stay protocol allows for an overnight hospital stay for patients after pituitary surgery, with a low rate of complications or readmission. This study offers evidence-based guidelines that may be used to avoid complications and facilitate early discharge after transsphenoidal surgery. Published by Elsevier Inc.

  18. Immediate recovery of pituitary function after transsphenoidal resection of pituitary macroadenomas. (United States)

    Arafah, B M; Kailani, S H; Nekl, K E; Gold, R S; Selman, W R


    Mild hyperprolactinemia frequently accompanies the hypopituitarism associated with pituitary macroadenomas not secreting PRL. Because of this association, hypopituitarism was postulated to be due to compression of portal vessels. We postulate that resumption of hypothalamic control over pituitary function occurs immediately after adenomectomy. To test this hypothesis, we examined pituitary function before and after transsphenoidal adenomectomy in 26 ACTH-deficient patients and 23 subjects with normal adrenal and thyroidal functions (control group). Glucocorticoids, given only to ACTH-deficient subjects, were withdrawn 36 h after surgery. ACTH, cortisol, and PRL levels were measured twice daily in all patients. Both ACTH and PRL levels increased hours after surgery in controls and returned to baseline over 4 days. In all hypopituitary subjects, PRL levels decreased by 50% within hours of adenomectomy and remained so until discharge. ACTH levels, measured simultaneously, increased within hours in 17 of 26 hypopituitary patients, all of whom recovered normal adrenal function before discharge. Nine additional patients had low ACTH levels and required cortisol replacement. The reciprocal changes in PRL and ACTH levels measured simultaneously, hours after surgery, support the hypothesis that hypopituitarism is reversible and largely caused by compression of the protal vessels and the resulting interruption of delivery of hypothalamic hormones. The persistence of hypopituitarism in some patients suggests that ischemic necrosis of the anterior pituitary could limit recovery.

  19. Pituitary adenylate cyclase activating polypeptide and migraine

    DEFF Research Database (Denmark)

    Zagami, Alessandro S; Edvinsson, Lars; Goadsby, Peter J


    Pituitary adenylate cyclase activating peptide (PACAP) is found in human trigeminocervical complex and can trigger migraine. PACAP levels were measured using a sensitive radioimmunoassay. Stimulation of the superior sagittal sinus (SSS) in cat elevated PACAP levels in cranial blood. Patients...... with moderate or severe migraine headache had elevated PACAP in the external jugular vein during headache (n = 15), that was reduced 1 h after treatment with sumatriptan 6 mg (n = 11), and further reduced interictally (n = 9). The data suggest PACAP, or its receptors, are a promising target for migraine...

  20. Steroidogenic Factor 1, Pit-1, and Adrenocorticotropic Hormone: A Rational Starting Place for the Immunohistochemical Characterization of Pituitary Adenoma. (United States)

    McDonald, William C; Banerji, Nilanjana; McDonald, Kelsey N; Ho, Bridget; Macias, Virgilia; Kajdacsy-Balla, Andre


    -Pituitary adenoma classification is complex, and diagnostic strategies vary greatly from laboratory to laboratory. No optimal diagnostic algorithm has been defined. -To develop a panel of immunohistochemical (IHC) stains that provides the optimal combination of cost, accuracy, and ease of use. -We examined 136 pituitary adenomas with stains of steroidogenic factor 1 (SF-1), Pit-1, anterior pituitary hormones, cytokeratin CAM5.2, and α subunit of human chorionic gonadotropin. Immunohistochemical staining was scored using the Allred system. Adenomas were assigned to a gold standard class based on IHC results and available clinical and serologic information. Correlation and cluster analyses were used to develop an algorithm for parsimoniously classifying adenomas. -The algorithm entailed a 1- or 2-step process: (1) a screening step consisting of IHC stains for SF-1, Pit-1, and adrenocorticotropic hormone; and (2) when screening IHC pattern and clinical history were not clearly gonadotrophic (SF-1 positive only), corticotrophic (adrenocorticotropic hormone positive only), or IHC null cell (negative-screening IHC), we subsequently used IHC for prolactin, growth hormone, thyroid-stimulating hormone, and cytokeratin CAM5.2. -Comparison between diagnoses generated by our algorithm and the gold standard diagnoses showed excellent agreement. When compared with a commonly used panel using 6 IHC for anterior pituitary hormones plus IHC for a low-molecular-weight cytokeratin in certain tumors, our algorithm uses approximately one-third fewer IHC stains and detects gonadotroph adenomas with greater sensitivity.

  1. Coexistence of GH-Producing Pituitary Macroadenoma and Meningioma in a Patient with Multiple Endocrine Neoplasia Type 1 with Hyperglycemia and Ketosis as First Clinical Sign

    Directory of Open Access Journals (Sweden)

    A. Herrero-Ruiz


    Full Text Available We present the clinical case of a patient who was admitted with an onset of diabetes mellitus (DM with associated ketosis and whose clinical, hormonal, and radiological evolution revealed the presence of primary hyperparathyroidism, pancreatic neuroendocrine tumor, and GH-producing pituitary macroadenoma in the context of multiple endocrine neoplasia type 1 (MEN1. DM is relatively common in cases of acromegaly, but it is not generally associated with ketosis. Simultaneously, the patient presented a meningioma, which is associated with pituitary macroadenoma only in extremely rare cases.

  2. Pituitary Volume Prospectively Predicts Internalizing Symptoms in Adolescence (United States)

    Zipursky, Amy R.; Whittle, Sarah; Yucel, Murat; Lorenzetti, Valentina; Wood, Stephen J.; Lubman, Dan I.; Simmons, Julian G.; Allen, Nicholas B.


    Background: Early adolescence is a critical time for the development of both internalizing and externalizing disorders. We aimed to investigate whether pituitary volume, an index of hypothalamic-pituitary-adrenal (HPA) axis function, represents a vulnerability factor for the emergence of internalizing and externalizing symptoms during adolescence…

  3. Morphologic changes in the anterior pituitary gland of male wistar ...

    African Journals Online (AJOL)

    Background: Mixed Palm oil diets have been reported to alter the morphology of testes, which is related to the pituitary-testicular axis. Aims: To determine the morphologic changes of the anterior pituitary gland following high consumption of mixed palm oil diets. Methods: Twelve (12) albino wistar rats were divided into three ...

  4. Pituitary Adenoma Misdiagnosed as Glaucoma in an Adult Nigerian ...

    African Journals Online (AJOL)

    is most commonly associated with glaucoma, pathologic cupping of the disc in some cases of pituitary adenoma has been reported in the literature.[2-4]. We add to the literature the case of a pale and pathologically cupped disc in a Nigerian male with pituitary adenoma misdiagnosed and treated for glaucoma with resultant.

  5. Mechanism of neuroadenolysis of the pituitary for cancer pain control

    NARCIS (Netherlands)

    Trouwborst, A.; Yanagida, H.; Erdmann, W.; Kok, A.


    Studied whether neuronal activity of the pituitary gland, as related to the primary somatosensory cortex, may be involved in the pain perception pathway influenced by neuroadenolysis of the pituitary. EEG and tooth-pulp EPs (TPEPs) were examined in 3 rhesus monkeys (Macaca mulatta). Findings

  6. Case Report: The ectopic posterior pituitary gland | Mahomed ...

    African Journals Online (AJOL)

    An ectopic posterior pituitary gland is a rare condition and may present with an empty pituitary fossa, hypoplasia or absence of the infundibular stalk and resultant short stature due to growth hormone deficiency. The location of the ectopic lobe can vary, but it is most commonly situated along the median eminence in the floor ...

  7. Benign intracranial hypertension after pituitary surgery for Cushing's disease.


    Parfitt, V.J.; Dearlove, J C; Savage, D; Griffith, H. B.; Hartog, M


    An 11 year old girl underwent successful transsphenoidal pituitary adenomectomy for pituitary-dependent Cushing's syndrome. Three months after operation, just after stopping glucocorticoid replacement therapy, she developed benign intracranial hypertension. This resolved when exogenous glucocorticoids were restarted but occurred again when they were later stopped. On restarting glucocorticoids again, this second episode of intracranial hypertension resolved. This complication may have been du...

  8. Hyperprolactinemia associated to calcification of the pituitary stalk: case report

    Directory of Open Access Journals (Sweden)



    Full Text Available In this work, the authors report the case of a female patient with 24 years of age with hyperprolactinemia, who presented a pituitary stalk calcification as seen by CT scan. Once other possible etiologies were excluded, we concluded that the calcification was probably related to hyperprolactinemia caused by interruption of the input of dopamine to the pituitary gland.

  9. Lineage-Specific Restraint of Pituitary Gonadotroph Cell Adenoma Growth (United States)

    Chesnokova, Vera; Zonis, Svetlana; Zhou, Cuiqi; Ben-Shlomo, Anat; Wawrowsky, Kolja; Toledano, Yoel; Tong, Yunguang; Kovacs, Kalman; Scheithauer, Bernd; Melmed, Shlomo


    Although pituitary adenomas are usually benign, unique trophic mechanisms restraining cell proliferation are unclear. As GH-secreting adenomas are associated with p53/p21-dependent senescence, we tested mechanisms constraining non-functioning pituitary adenoma growth. Thirty six gonadotroph-derived non-functioning pituitary adenomas all exhibited DNA damage, but undetectable p21 expression. However, these adenomas all expressed p16, and >90% abundantly expressed cytoplasmic clusterin associated with induction of the Cdk inhibitor p15 in 70% of gonadotroph and in 26% of somatotroph lineage adenomas (p = 0.006). Murine LβT2 and αT3 gonadotroph pituitary cells, and αGSU.PTTG transgenic mice with targeted gonadotroph cell adenomas also abundantly expressed clusterin and exhibited features of oncogene-induced senescence as evidenced by C/EBPβ and C/EBPδ induction. In turn, C/EBPs activated the clusterin promoter ∼5 fold, and elevated clusterin subsequently elicited p15 and p16 expression, acting to arrest murine gonadotroph cell proliferation. In contrast, specific clusterin suppression by RNAis enhanced gonadotroph proliferation. FOXL2, a tissue-specific gonadotroph lineage factor, also induced the clusterin promoter ∼3 fold in αT3 pituitary cells. As nine of 12 pituitary carcinomas were devoid of clusterin expression, this protein may limit proliferation of benign adenomatous pituitary cells. These results point to lineage-specific pathways restricting uncontrolled murine and human pituitary gonadotroph adenoma cell growth. PMID:21464964

  10. Effects of endocrine disrupting heavy metals on pituitary and ...

    African Journals Online (AJOL)

    Association of hypogonadism and visceral obesity (VO) was recently demonstrated in male auto-mechanics occupationally exposed to endocrine disruptors (ED)-lead, cadmium, mercury and arsenic, known to alter the hypothalamic-pituitary-testicular axis. The effects of exposure to these EDs on pituitary and gonadal ...

  11. Proliferaton index in pituitary adenomas from a black African ...

    African Journals Online (AJOL)

    Background: The WHO has recognized a variant of pituitary adenomas with potential aggressive behaviour which have been termed atypical pituitary adenomas. This group of tumours are recognized by their mitotic rate of more than >3%, p53 expression and invasion of surrounding structures. There has however been no ...

  12. Proliferaton index in pituitary adenomas from a black African ...

    African Journals Online (AJOL)

    Ayodeji Salami


    Dec 31, 2016 ... Background: The WHO has recognized a variant of pituitary adenomas with potential aggressive beha- viour which have been termed atypical pituitary adenomas. This group of tumours are recognized by their mitotic rate of more than >3%, p53 expression and invasion of surrounding structures. There has.

  13. Calcitonin serum levels in different pituitary diseases. A preliminary report. (United States)

    Ziliotto, D; Luisetto, G; Cecchini, M; Gastaldo, M; Francia, G; Padovan, L; Heynen, G


    The calcitonin (CT) concentration has been determined in the serum of 17 patients with different pituitary diseases. More or less elevated levels were found in 7 of them. No definite correlation has been observed between the immunoreactive CT and the different pituitary hormones.

  14. Volume of the adrenal and pituitary glands in depression

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Willer, Inge Stoel; Knorr, Ulla


    Numerous studies have shown that the hypothalamic-pituitary-adrenal (HPA) axis is hyperactive in some depressed patients. It is unclear whether such hyperactivity results in changed volumes of the adrenal glands, pituitary gland and hypothalamus. We systematically reviewed all controlled studies...... on the adrenal or pituitary glands or hypothalamus volume in unipolar depressive disorder published in PubMed 1966 to December 2009. We identified three studies that investigated the volume of the adrenal glands and eight studies that examined the volume of the pituitary gland, but no studies on hypothalamus...... in enlarged adrenal and pituitary glands and it is suggested that prospective studies should be conducted with scanning during successive depressive episodes and periods of remission....

  15. Growth hormone receptor expression and function in pituitary adenomas

    DEFF Research Database (Denmark)

    Clausen, Lene R; Kristiansen, Mikkel T; Rasmussen, Lars M