Science.gov

Sample records for non-functioning pituitary adenomas

  1. Clinical Concerns about Recurrence of Non-Functioning Pituitary Adenoma

    PubMed Central

    Lee, Min Ho; Lee, Ju Hee; Seol, Ho Jun; Lee, Jung-Il; Kim, Jong Hyun; Kong, Doo-Sik

    2016-01-01

    Background Non-functioning pituitary adenomas (NFPA) are clinically challenging because they present at a late stage with local mass effects or hypopituitarism. Surgery for non-functioning pituitary adenoma requires a special strategic approach for both minimal morbidity and radical resection. However, the clinical predictive factors associated with recurrence are limited. Here, we investigated optimal treatment of non-functioning pituitary adenoma. Methods We enrolled 289 patients who presented with non-functioning pituitary adenoma between January 2000 and January 2012 and who had received follow-up for at least one year for this retrospective study. Of these patients, 152 were male and 137 were female, with a median age of 51 years (range 15.79 years) and a median follow-up of four years (range 1.12.6 years). Characteristics of patients and tumors were reviewed with electronic medical records and radiologic images, retrospectively. Results Of the tumors, 193 were gross-totally resected, 53 were near-totally resected, and 43 were sub-totally resected. The extent of resection and adjuvant radiotherapy were both statistically significant prognostic factors of recurrence. Immunohistochemistry of tumor specimens did not yield consistent results. Conclusion With a high rate of recurrence, NFPA should be closely followed-up over a long-term period. Improvement of surgical techniques with advanced surgical equipment and adjuvant radiosurgery would lead to reduce the recurrence rate and improve patients' outcome. PMID:27195254

  2. Non-functioning pituitary adenoma: immunohistochemical analysis of 85 cases.

    PubMed

    Mahta, Ali; Haghpanah, Vahid; Lashkari, Anahita; Heshmat, Ramin; Larijani, Bagher; Tavangar, Seyed Mohammad

    2007-01-01

    Pituitary adenomas without clinically active hypersecretion are summarized under the term non-functioning pituitary adenoma (NFPA). Since there are no specific serum markers, the differential diagnosis and treatment imply special difficulties. By using immunohistochemical methods we will have new insight into the nature and pathogenesis of these tumours. Ki-67 is a nuclear antigen detected by the monoclonal antibody MIB-1 and its labelling index (LI) is considered a marker of normal and abnormal cell proliferation. The aim of this study was to investigate the possible role of immunohistochemistry and MIB1-LI determination in NFPAs to predict tumoural behaviour and better management. In this clinicopathological study, 85 cases of NFPAs were analysed immunohistochemically. MIB1-LI was also determined in studied cases. Clinical presentation, treatment and follow-up data were also reviewed and the correlation between clinical and pathologic findings was established. Eighteen adenomas (21.2%) were immunoreactive to one or two adenohypophysial hormones of which 4 GH positive adenomas had aggressive behaviour (2 significant juxtasellar extensions and 2 recurrences). MIB-1 LI was more than 5% in only 5 cases including 2 invasive adenomas but with no evidence of recurrence. No significant statistical difference between clinical presentations in immunoreactive and non-immunoreactive NFPAs was observed except for unilateral temporal hemianopia which was more common in immunoreactive adenomas (P=0.022). NFPAs comprise several pathologically different types of tumours, some of which are potentially hormone producing, but some defects in hormone secretion or production of biologically inactive or insufficient amount of hormone may be the culprit in the lack of evidence of rising serum hormone levels. MIB-1 LI may be indicative of invasiveness but not a predictor of recurrence. Silent somatotropinomas may have more aggressive behaviour in comparison with other NFPAs.

  3. Microarray Technology Reveals Potentially Novel Genes and Pathways Involved in Non-Functioning Pituitary Adenomas

    PubMed Central

    Qiao, X; Wang, H; Wang, X; Zhao, B; Liu, J

    2016-01-01

    Abstract Microarray data of non-functioning pituitary adenomas (NFPAs) were analyzed to disclose novel genes and pathways involved in NFPA tumorigenesis. Raw microarray data were downloaded from Gene Expression Omnibus. Data pre-treatment and differential analysis were conducted using packages in R. Functional and pathway enrichment analyses were performed using package GOs-tats. A protein-protein interaction (PPI) network was constructed using server STRING and Cytoscape. Known genes involved in pituitary adenomas (PAs), were obtained from the Comparative Toxicogenomics Database. A total of 604 differentially expressed genes (DEGs) were identifed between NFPAs and controls, including 177 up- and 427 down-regulated genes. Jak-STAT and p53 signaling pathways were significantly enriched by DEGs. The PPI network of DEGs was constructed, containing 99 up- and 288 down-regulated known disease genes (e.g. EGFR and ESR1) as well as 16 up- and 17 down-regulated potential novel NFPAs-related genes (e.g. COL4A5, LHX3, MSN, and GHSR). Genes like COL4A5, LHX3, MSN, and GHSR and pathways such as p53 signaling and Jak-STAT signaling, might participate in NFPA development. Although further validations are required, these findings might provide guidance for future basic and therapy researches. PMID:28289583

  4. Prevalence of gsp oncogene in somatotropinomas and clinically non-functioning pituitary adenomas: our experience.

    PubMed

    Taboada, Giselle Fernandes; Tabet, Ana Lúcia Osório; Naves, Luciana A; de Carvalho, Denise Pires; Gadelha, Mônica Roberto

    2009-01-01

    The purpose of the present study is to evaluate the prevalence of the gsp oncogene in Brazilian patients harboring somatotropinomas and non-functioning pituitary adenomas (NFPA). Patients and methods Deoxyribonucleic acid was extracted from 54 somatotropinomas and 14 NFPA. Exons 8 and 9 (including codons 201 and 227, respectively) of the GNAS gene were amplified by polymerase chain reaction (PCR). The PCR products were then purified and sequenced using the same primers. Results The gsp oncogene was found in nine tumors (eight somatotropinomas). The prevalence among somatotropinomas was 15% and among NFPA was 7%. The mutation was found in codon 201 in eight tumors and in codon 227 in one tumor (a somatotropinoma). No differences were found in age, sex, GH, and IGF-I levels or tumor volume at diagnosis between gsp+ and gsp- patients. Conclusion We found a lower than expected prevalence of gsp mutations in somatotropinomas and a similar prevalence in NFPA compared to previous studies from other countries.

  5. ZAC1 and SSTR2 Are Downregulated in Non-Functioning Pituitary Adenomas but Not in somatotropinomas

    PubMed Central

    Colli, Leandro Machado; Kasuki, Leandro; Marques, Nelma Veronica; Moraes, Aline Barbosa; Gasparetto, Emerson L.; Takiya, Christina Maeda; Castro, Margaret; Gadelha, Mônica Roberto

    2013-01-01

    Introduction There are few data regarding ZAC1 expression in clinically non-functioning pituitary adenomas (NFPA). Because somatotropinomas and NFPA behave differently with respect to tumor shrinkage during somatostatin analogs (SA) therapy, we sought to compare the ZAC1 and somatostatin receptor (sstr) types 1, 2, 3 and 5 mRNA expression in these two pituitary adenoma subtypes and in normal human pituitaries. Methods ZAC1 and SSTR mRNA expression levels were evaluated using real-time RT-PCR (TaqMan) in 20 NFPA and compared with the expression levels in 23 somatotropinomas and five normal pituitaries. The NFPA invasiveness was evaluated using magnetic resonance imaging with Hardy’s modified criteria. Ki-67 and p53 were evaluated using immunohistochemistry. Results A total of 20 patients with NFPA [6 males, median age 56 years (range: 30-78)], 23 with acromegaly [12 males, median age 43 years (range: 24–57)] and five normal pituitaries [4 males, median age 48 years (range: 36–54)] were included. Four of the patients (20%) had Hardy’s grade 2 tumors; all of the others had Hardy’s grade 3 tumors. The Ki-67 median expression was 2.35 (range: 0.2–9.23), and only four of the tumors (20%) were positive for p53. The ZAC1 mRNA expression was significantly lower in NFPA than in somatotropinomas and in normal pituitaries (p<0.001 for both), as well as the SSTR2 (p=0.001 and 0.01, respectively). The SSTR3 expression was higher in the NFPA than in the somatotropinomas and in the normal pituitaries (p=0.03 and 0.02, respectively). No correlation was found between the ZAC1 mRNA expression and the tumor invasiveness, Ki-67 and p53. Conclusion ZAC1 and SSTR2 are underexpressed and SSTR3 is overexpressed in NFPA compared to those in somatotropinomas and in normal pituitaries, which might explain the lack of tumor shrinkage that is observed in response to commercially available SA therapy in patients with NFPA. PMID:24098585

  6. SNPs in the aryl hydrocarbon receptor-interacting protein gene associated with sporadic non-functioning pituitary adenoma

    PubMed Central

    HU, YESHUAI; YANG, JUN; CHANG, YONGKAI; MA, SHUNCHANG; QI, JIANFA

    2016-01-01

    Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene have previously been associated with a predisposition to pituitary adenomas. However, to the best of our knowledge, mutations in AIP that relate specifically to sporadic non-functioning pituitary adenomas (NFPAs) have yet to be reported. Therefore, the present study aimed to identify single nucleotide polymorphisms (SNPs) in the AIP gene that may be associated with NFPAs. Peripheral blood samples and the entire coding sequence of the AIP gene from 56 patients with NFPAs and 56 controls were analyzed in triplicate. Of the 56 patients with NFPAs, 9 patients (16.1%) were identified as harboring five different SNPs, although no germline mutations in the AIP gene were detected in any of the patients. Three different SNPs (7051C>T, 8012G>C and 8020G>C) were identified in exons 4 and 6 in 3 different patients (each in 1 patient). Two different SNPs (7318C>A and 7886A>G) were identified in exons 5 and 6, respectively, in 6 different patients (each in 3 patients). No SNPs or germline mutations in the AIP gene were identified in the controls. The results of the present study suggested that mutations in the AIP gene might not have an important role in the tumorigenesis of NFPAs. However, further studies are required in order to investigate potential molecular and genetic mechanisms that may underlie the involvement of AIP in NFPA. PMID:26998050

  7. Therapeutic Strategy for Cavernous Sinus-Invading Non-Functioning Pituitary Adenomas Based on the Modified Knosp Grading System

    PubMed Central

    Hwang, Juyoung; Seol, Ho Jun; Nam, Do-Hyun; Lee, Jung-Il

    2016-01-01

    Background Non-functioning pituitary adenomas (NFPA) invading into the cavernous sinus are surgically challenging. To decrease recurrence rate, surgeon makes a strong endeavor to resect tumor gross totally. However, gross total resection (GTR) is difficult to achieve with cavernous sinus invasion. Recently, a new classification system for cavernous invasion of pituitary adenomas was suggested. The aim of this study is to validate this new classification system and to identify limitations and considerations in designing treatment strategies for patients with NFPA involving the cavernous sinus. Methods Between January 2000 and January 2012, 275 patients who underwent operation for NFPA were enrolled in the study. Median age was 50 years (15–79 years). There were 145 males and 130 females. The median follow-up duration was 4 years (range 1–12.5 years). Results Related to extent of tumor removal, GTR was obtained in 184 patients (66.9%), near total resection (NTR) was obtained in 45 patients (16.3%), and sub-total resection (STR) was obtained in 46 patients (16.7%) of a total 275 patients. There were statistically significant differences between the extent of resection and the new Knosp classification (p<0.001). In the high-grade group of the new Knosp classification, there was no difference in recurrence between patients who underwent GTR or NTR only and those who underwent STR with adjuvant radiation therapy (p=0.515). Conclusion In case of high risk of surgical complications, STR with adjuvant radiation therapy can be considered as an alternative strategy for safe treatment of cavernous-invading adenomas. PMID:27867914

  8. TSH secreting pituitary adenoma.

    PubMed

    Jha, S; Kumar, S

    2009-07-01

    Thyrotropin (TSH) secreting pituitary adenomas are a very rare cause of hyperthyroidism. They typically present with signs and symptoms of hyperthyroidism and rarely can be asymptomatic. TSH secreting tumors account for 1 percent of all pituitary adenoma. They are a rare cause of thyrotoxicosis in which adenomas completely or partially lose feedback regulation of thyroid hormones and lead to sustained stimulation of thyroid gland. The most definitive treatment of thyrotropin (TSH)-secreting pituitary adenomas is transsphenoidal removal of tumor after restoring euthyroidism. We report a case of pituitary adenoma associated with elevated serum free thyroid hormones and non-suppressed TSH levels.

  9. Single-Cell Phenotypic Characterization of Human Pituitary GHomas and Non-Functioning Adenomas Based on Hormone Content and Calcium Responses to Hypothalamic Releasing Hormones.

    PubMed

    Senovilla, Laura; Núñez, Lucía; de Campos, José María; de Luis, Daniel A; Romero, Enrique; García-Sancho, Javier; Villalobos, Carlos

    2015-01-01

    Human pituitary tumors are generally benign adenomas causing considerable morbidity due to excess hormone secretion, hypopituitarism, and other tumor mass effects. Pituitary tumors are highly heterogeneous and difficult to type, often containing mixed cell phenotypes. We have used calcium imaging followed by multiple immunocytochemistry to type growth hormone secreting (GHomas) and non-functioning pituitary adenomas (NFPAs). Individual cells were typed for stored hormones and calcium responses to classic hypothalamic releasing hormones (HRHs). We found that GHomas contained growth hormone cells either lacking responses to HRHs or responding to all four HRHs. However, most GHoma cells were polyhormonal cells responsive to both thyrotropin-releasing hormone (TRH) and GH-releasing hormone. NFPAs were also highly heterogeneous. Some of them contained ACTH cells lacking responses to HRHs or polyhormonal gonadotropes responsive to LHRH and TRH. However, most NFPAs were made of cells storing no hormone and responded only to TRH. These results may provide new insights on the ontogeny of GHomas and NFPAs.

  10. Single-Cell Phenotypic Characterization of Human Pituitary GHomas and Non-Functioning Adenomas Based on Hormone Content and Calcium Responses to Hypothalamic Releasing Hormones

    PubMed Central

    Senovilla, Laura; Núñez, Lucía; de Campos, José María; de Luis, Daniel A.; Romero, Enrique; García-Sancho, Javier; Villalobos, Carlos

    2015-01-01

    Human pituitary tumors are generally benign adenomas causing considerable morbidity due to excess hormone secretion, hypopituitarism, and other tumor mass effects. Pituitary tumors are highly heterogeneous and difficult to type, often containing mixed cell phenotypes. We have used calcium imaging followed by multiple immunocytochemistry to type growth hormone secreting (GHomas) and non-functioning pituitary adenomas (NFPAs). Individual cells were typed for stored hormones and calcium responses to classic hypothalamic releasing hormones (HRHs). We found that GHomas contained growth hormone cells either lacking responses to HRHs or responding to all four HRHs. However, most GHoma cells were polyhormonal cells responsive to both thyrotropin-releasing hormone (TRH) and GH-releasing hormone. NFPAs were also highly heterogeneous. Some of them contained ACTH cells lacking responses to HRHs or polyhormonal gonadotropes responsive to LHRH and TRH. However, most NFPAs were made of cells storing no hormone and responded only to TRH. These results may provide new insights on the ontogeny of GHomas and NFPAs. PMID:26106585

  11. Non-functioning pituitary tumors: 2012 update.

    PubMed

    Cámara Gómez, Rosa

    2014-03-01

    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.

  12. [Treatment of pituitary adenomas].

    PubMed

    Mezosi, Emese; Nemes, Orsolya

    2009-09-27

    According to epidemiological studies, the prevalence of pituitary adenomas is 16.5% and the majority of them are "incidentalomas". The symptoms of pituitary disorders are often non-specific; disturbances of pituitary function, compression symptoms, hypophysis apoplexy or accidental findings may help the diagnosis. The hormonal evaluation of pituitary adenomas is different from the algorithm used in the disorders of peripheral endocrine organs. The first-line therapy of prolactinomas are the dopamine agonists, and the aims of the treatment are to normalize the prolactin level, restore fertility in child-bearing age, decrease tumor mass, save or improve the residual pituitary function and inhibit the relapse of the disease. The available dopamine agonists in Hungary are bromocriptine and quinagolide. In case of tumors with good therapeutic response, medical therapy can be withdrawn after 3-5 years; hyperprolactinemia will not recur in 2/3 of these patients. Neurosurgery is the primary therapy of GH-, ACTH-, TSH-producing and inactive adenomas. In the last decades, significant improvement has been reached in surgical procedures, resulting in low mortality rates. Acromegalic patients with unresectable tumors have a great benefit from somatostatin analog treatment. The growth hormone receptor antagonist pegvisomant is the newest modality for the treatment of acromegaly. The medical therapy of Cushing's disease is still based on the inhibition of steroid production. A new, promising somatostatin analog, pasireotide is evaluated in clinical trials. The rare TSH-producing tumor can respond to both dopamine agonist and somatostatin analog therapy. The application of conventional radiotherapy has decreased; radiotherapy is mainly used in the treatment of invasive, incurable or malignant tumors. Further studies are needed to elucidate the exact role of radiosurgery and fractionated stereotaxic irradiation in the treatment of pituitary tumors.

  13. Increased β‑catenin and c-myc expression predict aggressive growth of non-functioning pituitary adenomas: An assessment using a tissue microarray-based approach.

    PubMed

    Liu, Chunhui; Wu, Youtu; Yu, Shengyuan; Bai, Jiwei; Li, Chuzhong; Wu, Dan; Zhang, Yazhuo

    2017-04-01

    Non-functional pituitary adenomas (NFPAs) account for 80% of pituitary adenomas with the majority of these exhibiting recurrences post-surgery. Overexpression of β-catenin and c‑myc is common in numerous invasive tumors. The present study sought to investigate the correlation of β‑catenin and c‑myc expression levels with aggressive growth and recurrence of NFPAs, using immunohistochemical examination of tissue microarrays. Tissue microarrays comprised 212 NFPAs specimens and 10 healthy specimens as controls. NFPAs were categorized as non‑aggressive or aggressive. Immunohistochemical examination was performed to determine the expression of β‑catenin and c‑myc. Correlation of the expression levels of β‑catenin and c‑myc with clinicopathological parameters, including aggressiveness and recurrence, were assessed by univariate, multivariate and logistic regression analysis. Increased expression of β‑catenin and c‑myc was detected in the majority of aggressive NFPAs specimens (71.1 and 88.7%, respectively). There was a significant positive correlation between β‑catenin and c‑myc expression and aggressiveness [P=0.001, Odds Ratio (OR)=4.011; P<0.001, OR=30.833]. Only β‑catenin expression demonstrated a significant correlation with recurrence in NFPAs (P=0.021, OR=2.571). β‑catenin and c‑myc were demonstrated to be potential biomarkers for aggressive NFPAs and in the future, β-catenin may serve as a marker for aggressive behavior and recurrence in NFPAs.

  14. Self-perception of cognitive function among patients with active acromegaly, controlled acromegaly, and non-functional pituitary adenoma: a pilot study.

    PubMed

    Yedinak, Chris G; Fleseriu, Maria

    2014-08-01

    Pituitary adenomas (PAs) represent 15 % of all brain tumors. One-sixth of these are reported to cause acromegaly via excess growth hormone secretion. These tumors have been associated with multiple comorbidities, including neuropsychiatric and cognitive dysfunction. We aimed to assess patient perception of cognitive deficits and the relationship of cognitive changes to active acromegaly (AA) versus controlled acromegaly (CA) versus non-functional PAs (NFPA). A modified FACT-Cog survey was used, which focused on the prevalence and severity of perceived dysfunction in five areas of cognitive function: ability to learn, concentration/distractibility, mental agility, memory and recall, and verbal recall. Patient perception of current health and health change over the previous 12 months was also assessed. The overall perceived prevalence and severity of cognitive dysfunction were the highest among NFPA groups, particularly in the areas of mental agility, verbal recall, and memory/recall. Patients with AA reported greater prevalence and severity of dysfunction with respect to concentration/distractibility and ability to learn. Patients with AA reported the best overall current health, though patients with CA reported the greatest improvement in health over the previous year. These findings may indicate that PAs can affect cognitive function regardless of whether excess growth hormone is present. Acromegaly and NFPA patients perceive specific areas of cognitive dysfunction that may require further evaluation and treatment. Further research may be useful regarding patient quality of life, patient functionality during normal daily activities, and perceived dysfunction despite biological disease control.

  15. Pituitary lymphoma developing within pituitary adenoma.

    PubMed

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

    2012-06-01

    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.

  16. The prevalence of hyperprolactinemia in non-functioning pituitary macroadenomas

    PubMed Central

    Zhang, Fangfang; Huang, Yinxing; Ding, Chenyu; Huang, Guoliang; Wang, Shousen

    2015-01-01

    Objective: The prevalence of hyperprolactinemia in non-functioning pituitary macroadenomas (NFPMAs) is not well known, and hyperprolactinemia caused by a NFPMA is currently associated with diagnostic uncertainty. Thus, the aim of this study was to evaluate the prevalence of hyperprolactinemia in NFPMAs. Methods: A meta-analysis of all existing articles in PubMed was conducted. The search string was designed as “(non-functioning pituitary tumor OR non-functioning pituitary tumor OR non-functioning pituitary macroadenomas OR non-functioning pituitary macroadenomas OR non-functioning pituitary adenomas OR non-functioning pituitary adenomas) and hyperprolactinemia”. References of the articles found were also reviewed. Study selection and data extraction were performed independently by two reviewers. Data were analyzed with STATA 11.0 software (StataCorp LP, USA). The fixed effects model was used to evaluate these studies. Results: The search identified 57 published studies, seven of which were accepted for the final meta-analysis. The authors found an overall estimated 40.2% prevalence of (95% CI, 36.6%-43.7%) hyperprolactinemia in NFPMAs. Conclusions: Given the high frequency of hyperprolactinemia in NFPMAs, a diagnosis of NFPMA or prolactinoma should be made more carefully. PMID:26770524

  17. [Thyrotropin-secreting pituitary adenomas].

    PubMed

    Caron, Philippe

    2009-01-01

    TSH-secreting pituitary adenomas represent 0.5 to 1% of all pituitary adenomas. They are recognized with increasing frequency due to the measurement of TSH level in patients with hyperthyroidism, the ultra sensitive TSH assays and the improvement in pituitary imaging. Patients present mild or moderate signs of hyperthyroidism. Hormonal evaluation shows increased free thyroid hormone concentration with detectable, normal or increased serum TSH level, raising the differential diagnosis with pituitary resistance to thyroid hormone syndrome. Magnetic resonance imaging reveals pituitary adenomas in most patients. Transphenoidal surgery remains the treatment of choice in patients with TSH-secreting pituitary microadenomas, while long-acting somatostatin analogs seem to be an alternative medical treatment to surgery in patients with macroadenomas or invasive pituitary tumors.

  18. Contemporary issues in the evaluation and management of pituitary adenomas.

    PubMed

    Pekic, S; Stojanovic, M; Popovic, V

    2015-12-01

    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

  19. Overexpression of the Notch3 receptor in non-functioning pituitary tumours.

    PubMed

    Miao, Zengli; Miao, Yifeng; Lin, Yuchang; Lu, Xiaojie

    2012-01-01

    Human non-functioning pituitary adenomas cause hypopituitarism or the compression of adjacent structures. At present, there is no available medical treatment for these tumours. The Notch3 pathway has an important role in the progression of non-functioning pituitary adenomas. We found, using reverse transcriptase-polymerase chain reaction, that Notch3 mRNA was significantly upregulated in clinically non-functioning pituitary adenomas, and, using Western blotting, that Notch3 protein was expressed at a higher level in non-functioning pituitary adenomas than in normal human pituitary tissue. In addition, using immunohistochemistry, we observed that Notch3 is highly expressed in the cytoplasm of adenoma cells compared to normal pituitary cells. These results suggest that the overexpression of Notch3 mRNA and protein by non-functioning pituitary adenomas may facilitate the growth of these tumours. Our results provide the first comprehensive analysis of Notch3 mRNA and protein overexpression in non-functioning pituitary tumours. This study provides new insights into the pathogenesis of human non-functioning pituitary adenomas and implicates the Notch3 pathway as a molecular therapeutic target for their treatment.

  20. Discrimination of prolactinoma from hyperprolactinemic non-functioning adenoma.

    PubMed

    Hong, Jae Won; Lee, Mi Kyung; Kim, Sun Ho; Lee, Eun Jig

    2010-02-01

    The objective of this study was to evaluate characteristics that discriminate prolactinoma from non-functioning pituitary macroadenoma with hyperprolactinemia. We included 117 patients with hyperprolactinemic pituitary macroadenomas. Patients were divided into three groups according to treatment outcomes and pathologic results: (A) prolactinoma that responded to dopamine agonist (DA) treatment (PRDA); (B) prolactinoma requiring surgical treatment (PRS); and (C) non-functioning pituitary adenoma with hyperprolactinemia (NFPAH). Old age, low serum prolactin levels, and extrasellar extension were associated with NFPAH. Most patients with NFPAH had serum prolactin levels less than 100 ng/ml. Visual defects and GH deficiency were more common in patients with NFPAH compared with patients with PRS and PRDA, without difference of tumor size. Galactorrhea and amenorrhea were less frequent in patients with NFPAH than in patients with PRS and PRDA. Post-operative remission of hyperprolactinemia was achieved in 100% of patients with NFPAH and in 72.5% of patients with PRS. DA administration was required in 25.5% of patients with PRS; however, no patients with NFPAH required DA administration. In conclusion, old age, extrasellar tumor extension with relatively low prolactin levels, visual defect, and GH deficiency were considered suggestive of non-functioning pituitary adenoma rather than prolactinoma in hyperprolactinemic pituitary macroadenoma.

  1. Transcranial surgery for pituitary adenomas.

    PubMed

    Youssef, A Samy; Agazzi, Siviero; van Loveren, Harry R

    2005-07-01

    Although the transsphenoidal approach is the preferred approach to the vast majority of pituitary tumors with or without suprasellar extension, the transcranial approach remains a vital part of the neurosurgical armamentarium for 1 to 4% of these tumors. The transcranial approach is effective when resection becomes necessary for a portion of a pituitary macroadenoma that is judged to be inaccessible from the transsphenoidal route because of isolation by a narrow waist at the diaphragma sellae, containment within the cavernous sinus lateral to the carotid artery, projection anteriorly onto the planum sphenoidale, or projection laterally into the middle fossa. The application of a transcranial approach in these circumstances may still be mitigated by response to prolactin inhibition of prolactinomas, the frequent lack of necessity to remove asymptomatic nonsecretory adenomas from the cavernous sinus, and the lack of evidence that sustained chemical cures can be reliably achieved by removal of secretory adenomas (adrenocorticotropic hormone, growth hormone) from the cavernous sinus. Cranial base surgical techniques have refined the surgical approach to pituitary adenomas but have had less effect on actual surgical indications than anticipated. Because application of the transcranial approach to pituitary adenomas is and should be rare in clinical practice, it is useful to standardize the technique to a default mode with which the surgical team is most experienced and, therefore, most comfortable. Our default mode for transcranial pituitary surgery is the frontotemporal-orbitozygomatic approach.

  2. Fibrosarcoma complicating irradiated pituitary adenoma

    SciTech Connect

    Shi, T.; Farrell, M.A.; Kaufmann, J.C.

    1984-09-01

    Eight years after radiation therapy (5000 rads of 60Co) for a pituitary adenoma, a patient developed a sellar fibrosarcoma. The tumor had an aggressive growth pattern: it infiltrated the optic nerve, sphenoidal air sinus, hypothalamus, and both cavernous sinuses, where compression of the left internal carotid artery resulted in a massive hemispheric infarction. Surgery was ineffective in arresting rapid growth of the lesion; death occurring 5 months after onset of symptoms.

  3. Phospho-histone H3 (pHH3) immuno-reactivity as a prognostic marker in non-functioning pituitary adenomas

    PubMed Central

    Hightower, Erica; Cabanillas, Maria E.; Fuller, Greg N.; McCutcheon, Ian E.; Hess, Kenneth R.; Shah, Komal; Waguespack, Steven G.; Corley, Lynda J.

    2013-01-01

    Nonfunctioning pituitary adenomas (NFPA) are typically benign neoplasms that can cause significant morbidity through local mass effects. MIB-1/Ki-67 and p53 immuno-reactivity are used to predict aggressive behavior but have known limitations. No marker to date is widely used to reliably predict tumor progression. Phospho-histone H3 (pHH3) is a protein phosphorylated during chromatin condensation in mitosis, and thus anti-pHH3 immunocyto-chemistry is able to assess mitotic activity. Study objectives were to determine the relationship among pHH3, MIB-1/Ki-67, and p53 in NFPA, and to evaluate the relationship between these indices and time to progression (TTP). Seventy-six patients with NFPA operated on by a single neuro-surgeon at University of Texas M. D. Anderson Cancer Center from 1992 to 2006 were identified from a database and met all criteria for inclusion in this clinicopathology study. PHH3, MIB-1/Ki-67, and p53 immuno-reactivity was evaluated in each case. Retrospective review was used to determine TTP. With 282 person-years of follow-up, 19 progression events were observed. A correlation was found between MIB-1/Ki-67 and p53 immuno-reactivity (r = 0.25, p = 0.031). PHH3 did not correlate with either. When markers were dichotomized at the median, only MIB-1/Ki-67 correlated with TPP (log rank p = 0.018). Rank correlation analysis confirmed a significant inverse correlation between both MIB-1/Ki-67 (Dxy = −0.33, p = 0.036) and p53 (Dxy = −0.40, 0.016) immuno-reactivity and TTP. Our results support previous data suggesting that MIB-1/Ki-67 and p53 have clinical utility as prognostic markers for tumor progression. PHH3 did not prove to be associated with TTP in this retrospective study limited by few progression events. PMID:22120760

  4. Novel Genetic Causes of Pituitary Adenomas.

    PubMed

    Caimari, Francisca; Korbonits, Márta

    2016-10-15

    Recently, a number of novel genetic alterations have been identified that predispose individuals to pituitary adenomas. Clinically relevant pituitary adenomas are relatively common, present in 0.1% of the general population. They are mostly benign monoclonal neoplasms that arise from any of the five hormone-secreting cell types of the anterior lobe of the pituitary gland, and cause disease due to hormonal alterations and local space-occupying effects. The pathomechanism of pituitary adenomas includes alterations in cell-cycle regulation and growth factor signaling, which are mostly due to epigenetic changes; somatic and especially germline mutations occur more rarely. A significant proportion of growth hormone- and adrenocorticotrophin-secreting adenomas have activating somatic mutations in the GNAS and USP8 genes, respectively. Rarely, germline mutations predispose to pituitary tumorigenesis, often in a familial setting. Classical tumor predisposition syndromes include multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4) syndromes, Carney complex, and McCune-Albright syndrome. Pituitary tumors have also been described in association with neurofibromatosis type 1, DICER1 syndrome, and SDHx mutations. Pituitary adenomas with no other associated tumors have been described as familial isolated pituitary adenomas. Patients with AIP or GPR101 mutations often present with pituitary gigantism either in a familial or simplex setting. GNAS and GPR101 mutations that arise in early embryonic age can lead to somatic mosaicism involving the pituitary gland and resulting in growth hormone excess. Senescence has been suggested as the key mechanism protecting pituitary adenomas turning malignant in the overwhelming majority of cases. Here we briefly summarize the genetic background of pituitary adenomas, with an emphasis on the recent developments in this field. Clin Cancer Res; 22(20); 5030-42. ©2016 AACR SEE ALL ARTICLES IN THIS CCR FOCUS SECTION, "ENDOCRINE CANCERS

  5. Association of craniopharyngioma and pituitary adenoma.

    PubMed

    Guaraldi, Federica; Prencipe, Nunzia; di Giacomo, Valentina; Scanarini, Massimo; Gasco, Valentina; Gardiman, Marina Paola; Berton, Alessandro M; Ghigo, Ezio; Grottoli, Silvia

    2013-08-01

    Intracranial tumors of different histologic types infrequently affect patients with pituitary adenomas and no history of head irradiation. The association with craniopharyngioma is extremely rare. Aims of this paper are: (1) to provide a critical literature review of typical features of pituitary adenoma presenting in association with craniopharyngioma; (2) to describe the first documented (clinically, biochemically, histologically, and radiologically) case of aggressive, suprasellar papillary craniopharyngioma presenting with amenorrhea, progressive reduction of visual field, and severe headache in a 38-year-old woman, a decade after surgical cure for microprolactinoma associated with empty sella, during which she had carried two pregnancies; and (3) to discuss common etiopathogenetic mechanisms, in relation to the management of these lesions. Systematic literature search for English literature focusing on the association of craniopharyngioma and pituitary adenoma was performed using PubMed database. Additional relevant articles from references lists were also included. Clinical, laboratory, and radiological examinations performed in our patient for the two brain lesions at diagnosis and follow up were collected. Literature search retrieved nine articles. Typically, craniopharyngioma were of adamantinomatous type, occurred simultaneously to pituitary adenoma, presented with headache and visual loss, and affected men. No case of clearly documented metachronous lesion affecting a woman after pregnancy had been described before. Although very rare and with uncertain etiopathogenesis, second tumors (i.e., craniopharyngioma) should be considered in patients with a history of pituitary adenoma, presenting with suggestive signs and symptoms, even after a long disease-free period, in order to provide proper and prompt treatment.

  6. RT-01FRACTIONATED STEREOTACTIC RADIOTHERAPY FOR PITUITARY ADENOMA WITH NOVALIS

    PubMed Central

    Arakawa, Yoshiki; Mizowaki, Takashi; Ogura, Kengo; Sakanaka, Katsuyuki; Hojo, Masato; Hiraoka, Masahiro; Miyamoto, Susumu; Murata, Daiki

    2014-01-01

    BACKGROUND: Radiation therapy is an available treatment modality for pituitary adenoma. In particular, it is effective for the case unable to be removed with surgery or repeating recurrence. However, hypopituitarism and optic nerve injury associated with radiation therapy become a problem. Novalis® (Brain Lab) is an equipment of radiation to establish the detailed irradiation area, fractionated stereotactic radiotherapy (fSRT) and intensity-modulated radiation therapy (IMRT). Retrospectively, we review local control and morbidity following fSRT with Novalis in pituitary adenoma. PATIENTS AND METHODS: Between 2007 and 2012, 29 patients with pituitary adenoma (9 functioning, 20 non-functioning) received fSRT with Novalis in our institute. Total radiation dose was 50.4-54Gy (1.8 Gy per fraction) and prescribed to the gross target volume + 2 mm. The effectiveness of fSRT was evaluated by tumor volume and clinical symptoms on pre- fSRT, and every 1-year. RESULTS: The median follow-up time was 59.1 months (20 to 83 months). Tumor regrowth was observed in 2 cases. Progression free survival rate was 93%. New visual field deficit was observed in 1 case, and new pituitary dysfunction were not observed in all patients. CONCLUSION: fSRT with Novalis is safe and effective in the treatment for pituitary adenoma. Although follow-up time is short, any problematic complications were not observed. In the future, fSRT is expected to make for safe and effective treatment in pituitary adenoma impossible to cure surgically.

  7. Clinical analysis of infarction in pituitary adenoma

    PubMed Central

    Xiao, Deyong; Wang, Shousen; Huang, Yinxing; Zhao, Lin; Wei, Liangfeng; Ding, Chenyu

    2015-01-01

    Objectives: This study is to summarize the clinical manifestations, imaging findings, treatment and prognosis of pituitary apoplexy caused by ischemic infarction. Methods: From January 2010 to March 2014, 412 patients with pituitary adenoma were admitted in the Department of Neurosurgery at Fuzhou General Hospital, with 9 cases being diagnosed with ischemic infarction stroke. Imaging examinations were performed, including computed tomography and magnetic resonance imaging. Pituitary adenomas were evaluated according to suprasellar, infrasellar, parasellar, anterior and posterior classification. Hematoxylin and eosin staining and immunohistochemical staining were used for identifying pituitary adenoma. Results: Tumor height was 1.3-3.3 cm, with an average of 2.27 cm. Eight patients had typical clinical stroke symptoms. Preoperatively, high blood growth hormone concentration was presented in 6 cases, full hypopituitarism in 2 cases, dysfunction of corticosteroids and gonads in 4 cases, and single gonadal dysfunction in 2 cases. Ring enhancement was presented in 8 cases on constructed computed tomography or magnetic resonance images, and sellar settlement in 7 cases. Eight patients were conducted with transsphenoidal resection, and secondary transsphenoidal after craniotomy in 1 case. During surgery, poor tumor blood supply was found in 7 cases, cheese-like or tofu-like necrotic tissues in 5 cases, and few dark blood clots in 2 cases. Conclusions: Pituitary ischemic infarction stroke is clinically rare, but can be correctly diagnosed before surgery by imaging examinations. The pathological characteristics of the tumor are necrosis and fibrosis, which are easy for resection. Therefore, pituitary adenoma usually has good prognosis. PMID:26221291

  8. Pituitary tumours: TSH-secreting adenomas.

    PubMed

    Beck-Peccoz, Paolo; Persani, Luca; Mannavola, Deborah; Campi, Irene

    2009-10-01

    Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism and account for less than 2% of all pituitary adenomas. In the last years, the diagnosis has been facilitated by the routine use of ultra-sensitive TSH immunometric assays. Failure to recognise the presence of a TSHoma may result in dramatic consequences, such as improper thyroid ablation that may cause the pituitary tumour volume to further expand. The diagnosis mainly rests on dynamic testing, such as T3 suppression tests and TRH, which are useful in differentiating TSHomas from the syndromes of thyroid hormone resistance. The first therapeutical approach to TSHomas is the pituitary neurosurgery. The medical treatment of TSHomas mainly rests on the administration of somatostatin analogues, such as octreotide and lanreotide, which are effective in reducing TSH secretion in more than 90% of patients with consequent normalisation of FT4 and FT3 levels and restoration of the euthyroid state.

  9. Preoperative volume determination for pituitary adenoma

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

    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.

  10. Fractionated proton beam irradiation of pituitary adenomas

    SciTech Connect

    Ronson, Brian B.; Schulte, Reinhard W.; Han, Khanh P.; Loredo, Lilia N.; Slater, James M.; Slater, Jerry D. . E-mail: jdslater@dominion.llumc.edu

    2006-02-01

    Purpose: Various radiation techniques and modalities have been used to treat pituitary adenomas. This report details our experience with proton treatment of these tumors. Methods and Materials: Forty-seven patients with pituitary adenomas treated with protons, who had at least 6 months of follow-up, were included in this analysis. Forty-two patients underwent a prior surgical resection; 5 were treated with primary radiation. Approximately half the tumors were functional. The median dose was 54 cobalt-gray equivalent. Results: Tumor stabilization occurred in all 41 patients available for follow-up imaging; 10 patients had no residual tumor, and 3 had greater than 50% reduction in tumor size. Seventeen patients with functional adenomas had normalized or decreased hormone levels; progression occurred in 3 patients. Six patients have died; 2 deaths were attributed to functional progression. Complications included temporal lobe necrosis in 1 patient, new significant visual deficits in 3 patients, and incident hypopituitarism in 11 patients. Conclusion: Fractionated conformal proton-beam irradiation achieved effective radiologic, endocrinological, and symptomatic control of pituitary adenomas. Significant morbidity was uncommon, with the exception of postradiation hypopituitarism, which we attribute in part to concomitant risk factors for hypopituitarism present in our patient population.

  11. Radiolabelled spiroperidol: Possible pituitary adenoma imaging agent

    SciTech Connect

    Otto, C.A.; Marshall, J.C.; Lloyd, R.V.; Sherman, P.S.; Wieland, D.M.

    1984-01-01

    Prolactin-secreting pituitary adenomas are the most common type of pituitary tumors. Detection currently depends on physical symptoms, elevated serum prolactin levels and CT scans. An imaging agent which specifically localized in prolactinomas based on some functional characteristic of the tumor would be of considerable clinical value not only for early detection but also for monitoring of therapy. Tritiated spiroperidol (/sup 3/H-Sp) was selected for evaluation based on 1) the presence of D-2 receptors in normal anterior pituitary and adenoma tissue and 2) the high affinity of spiroperidol for D-2 receptors. Recent data have established that implantation of diethylstilbestrol (DES) in Fischer F344 rats induced prolactin-secreting tumors in the pituitary. /sup 3/HSp was evaluated in pituitary tissue of both control and DES-treated rats. /sup 3/HSp concentration in normal female anterior pituitary tissue was found to be about 0.27% kg dose/g from 5 min to 4hrs. This value was about 10 times levels in cortex, cerebellum and striatum. In DES-treated rats the % kg dose/g values remained approximately the same. A 5-fold increase in serum prolactin was associated with a 6-fold increase in both pituitary weight and % dose/organ. The data suggests that although total pituitary weight has increased due to tumor growth (reflected in increased values for % dose/organ), the relative number of receptors per g of tissue has remained constant. This result is in agreement with observations of others on D-2 receptor concentration in prolactinomas.

  12. Pituitary Adenoma Volumetry with 3D Slicer

    PubMed Central

    Nimsky, Christopher; Kikinis, Ron

    2012-01-01

    In this study, we present pituitary adenoma volumetry using the free and open source medical image computing platform for biomedical research: (3D) Slicer. Volumetric changes in cerebral pathologies like pituitary adenomas are a critical factor in treatment decisions by physicians and in general the volume is acquired manually. Therefore, manual slice-by-slice segmentations in magnetic resonance imaging (MRI) data, which have been obtained at regular intervals, are performed. In contrast to this manual time consuming slice-by-slice segmentation process Slicer is an alternative which can be significantly faster and less user intensive. In this contribution, we compare pure manual segmentations of ten pituitary adenomas with semi-automatic segmentations under Slicer. Thus, physicians drew the boundaries completely manually on a slice-by-slice basis and performed a Slicer-enhanced segmentation using the competitive region-growing based module of Slicer named GrowCut. Results showed that the time and user effort required for GrowCut-based segmentations were on average about thirty percent less than the pure manual segmentations. Furthermore, we calculated the Dice Similarity Coefficient (DSC) between the manual and the Slicer-based segmentations to proof that the two are comparable yielding an average DSC of 81.97±3.39%. PMID:23240062

  13. Different imaging characteristics of concurrent pituitary adenomas in a patient with Cushing's disease.

    PubMed

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

    2015-05-01

    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.

  14. Co-occurrence of Pituitary Adenoma with Suprasellar and Olfactory Groove Meningiomas

    PubMed Central

    Lim, Kai-Zheong; Goldschlager, Tony; Chandra, Ronil V.; Hall, Jonathan; Uren, Brent; Pullar, Michael

    2016-01-01

    Introduction: The co-existence of pituitary adenoma and meningioma is extremely rare. It is even rarer in patients with no previous known risk factors for either tumour. Here, we present a case of synchronous non-functioning pituitary adenoma with suprasellar and olfactory groove meningiomas in a patient without previous irradiation. Methods: The tumours were diagnosed on MRI in the 65-year-old patient who presented with patchy visual deficits. The decision was made to undergo surgery for resection of the suprasellar meningioma and the pituitary adenoma, leaving the small olfactory groove meningioma intact. Extended endoscopic transsphenoidal surgery was performed. Results: Macroscopic clearance was achieved for pituitary macroadenoma and suprasellar meningioma. Postoperatively, visual field tsting and pituitary axis hormonal levels were normal. The pituitary macroadenoma was confirmed to be a non-functioning pituitary adenoma. The meningioma was diagnosed to be of WHO grade 1. Conclusion: The rationale for choosing such management option, including its risks and benefits in this challenging patient is discussed. PMID:27872697

  15. Non-functioning adrenal adenomas discovered incidentally on computed tomography

    SciTech Connect

    Mitnick, J.S.; Bosniak, M.A.; Megibow, A.J.; Naidich, D.P.

    1983-08-01

    Eighteen patients with unilateral non-metastatic non-functioning adrenal masses were studied with computed tomography (CT). Pathological examination in cases revealed benign adrenal adenomas. The others were followed up with serial CT scans and found to show no change in tumor size over a period of six months to three years. On the basis of these findings, the authors suggest certain criteria of a benign adrenal mass, including (a) diameter less than 5 cm, (b) smooth contour, (c) well-defined margin, and (d) no change in size on follow-up. Serial CT scanning can be used as an alternative to surgery in the management of many of these patients.

  16. Prolactin-secreting pituitary adenomas: CT appearance in diffuse invasion

    SciTech Connect

    Virapongse, C.; Bhimani, S.; Sarwar, M.; Greenberg, A.; Jung, K.

    1984-08-01

    The authors describe 2 diffusely invasive prolactin-secreting pituitary adenomas which produced marked destruction of the base of the skull thought to be diagnostic of chordoma on computed tomography (CT). Failure to recognize this pattern led to biopsy, which was diagnostic. The authors emphasize the need to recognize this rare growth pattern of diffusely invasive pituitary adenoma on CT.

  17. Promoter CpG methylation of multiple genes in pituitary adenomas: frequent involvement of caspase-8.

    PubMed

    Bello, M Josefa; De Campos, Jose M; Isla, Alberto; Casartelli, Cacilda; Rey, Juan A

    2006-02-01

    The epigenetic changes in pituitary adenomas were identified by evaluating the methylation status of nine genes (RB1, p14(ARF), p16(INK4a), p73, TIMP-3, MGMT, DAPK, THBS1 and caspase-8) in a series of 35 tumours using methylation-specific PCR analysis plus sequencing. The series included non-functional adenomas (n=23), prolactinomas (n=6), prolactinoma plus thyroid-stimulating hormone adenoma (n=1), growth hormone adenomas (n=4), and adrenocorticotropic adenoma (n=1). All of the tumours had methylation of at least one of these genes and 40% of samples (14 of 35) displayed concurrent methylation of at least three genes. The frequencies of aberrant methylation were: 20% for RB1, 17% for p14(ARF), 34% for p16(INK4a), 29% for p73, 11% for TIMP-3, 23% for MGMT, 6% for DAPK, 43% for THBS1 and 54% for caspase-8. No aberrant methylation was observed in two non-malignant pituitary samples from healthy controls. Although some differences in the frequency of gene methylation between functional and non-functional adenomas were detected, these differences did not reach statistical significance. Our results suggest that promoter methylation is a frequent event in pituitary adenoma tumourigenesis, a process in which inactivation of apoptosis-related genes (DAPK, caspase-8) might play a key role.

  18. Human Pituitary Adenoma Proteomics: New Progresses and Perspectives

    PubMed Central

    Zhan, Xianquan; Wang, Xiaowei; Cheng, Tingting

    2016-01-01

    Pituitary adenoma (PA) is a common intracranial neoplasm that impacts on human health through interfering hypothalamus–pituitary–target organ axis systems. The development of proteomics gives great promises in the clarification of molecular mechanisms of a PA and discovery of effective biomarkers for prediction, prevention, early-stage diagnosis, and treatment for a PA. A great progress in the field of PA proteomics has been made in the past 10 years, including (i) the use of laser-capture microdissection, (ii) proteomics analyses of functional PAs (such as prolactinoma), invasive and non-invasive non-functional pituitary adenomas (NFPAs), protein post-translational modifications such as phosphorylation and tyrosine nitration, NFPA heterogeneity, and hormone isoforms, (iii) the use of protein antibody array, (iv) serum proteomics and peptidomics, (v) the integration of proteomics and other omics data, and (vi) the proposal of multi-parameter systematic strategy for a PA. This review will summarize these progresses of proteomics in PAs, point out the existing drawbacks, propose the future research directions, and address the clinical relevance of PA proteomics data, in order to achieve our long-term goal that is use of proteomics to clarify molecular mechanisms, construct molecular networks, and discover effective biomarkers. PMID:27303365

  19. Nonfunctioning giant pituitary adenomas: Invasiveness and recurrence

    PubMed Central

    Landeiro, José Alberto; Fonseca, Elissa Oliveira; Monnerat, Andrea Lima Cruz; Taboada, Giselle Fernandes; Cabral, Gustavo Augusto Porto Sereno; Antunes, Felippe

    2015-01-01

    Background: We report our surgical series of 35 patients with giant nonfunctioning pituitary adenomas (GNFPA). We analyzed the rule of Ki-67 antigen expression in predicting recurrence. Methods: Thirty-five patients were operated between 2000 and 2010. Suprassellar extension of the tumors were classified according to Hardy and Mohr based on magnetic resonance (MR) studies. Pituitary endocrine function and MR scans were assessed preoperatively and at 1, 6, and 12 months postoperatively. Immunohistochemical studies were based in regard to the expression of the proliferative Ki-67 index and the hormonal receptor for luteinizing hormone, follicle stimulating hormone, growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, and prolactin. Tumors specimens were obtained from 35 patients with GNFPA. Endoscopic transsphenoidal surgery was the approach of choice. Results: Thirty-five patients were submitted to 49 surgeries, 44 (89.8%) were transsphenoidal and 5 (10.2%) were transcranial. The most frequent preoperative complaints were visual acuity impairment and visual field defect in 25 (71.2%) and 23 (65.7%) cases, respectively. Improvement of visual acuitiy and visual field deficit after surgery was seen in 20 (80%) and 17 (73.9%) patients, respectively. Endocrinological deficits were encountered in 20 patients (57.1%). After surgery, 18 patients (51.4%) required hormonal replacement. Three patients had visual symptoms related to pituitary apoplexy and recovered after surgery. The Ki-67 labeling index (LI) ranged from <1% to 4.8%. The rate of recurrence in tumors with Ki-67 <3% was 7.7% (2 patients), Ki-67 >3% was present in 5 patients and the recurrence committed 3 patients. Conclusion: In our series, regardless the improvement of visual function and compressing symptoms, 5 patients with expression of Ki-67 LI more than 3% experienced a recurrence. PMID:26674325

  20. Thyrotropin secreting pituitary adenoma accompanying a silent somatotropinoma.

    PubMed

    Berker, Dilek; Isik, Serhat; Aydin, Yusuf; Tutuncu, Yasemin; Akdemir, Gokhan; Ozcan, Hatice Nursun; Guler, Serdar

    2011-01-01

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

  1. Localization of carboxyl ester lipase in human pituitary gland and pituitary adenomas.

    PubMed

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

    2010-10-01

    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.

  2. Etiology, prognosis, and management of secondary pituitary abscesses forming in underlying pituitary adenomas.

    PubMed

    Awad, Ahmed J; Rowland, Nathan Christopher; Mian, Matthew; Hiniker, Annie; Tate, Matthew; Aghi, Manish Kumar

    2014-05-01

    Pituitary abscesses occurring in pre-existing pituitary pathology like Rathke's cleft cyst or adenomas (secondary pituitary abscesses) are rare and of unclear etiology. While surgery and antibiotics have been effective in some cases reported to date, leading to the suggestion that secondary pituitary abscesses are mostly indolent, we investigated the hypothesis that infected adenomas, given their propensity to invade the paranasal sinuses and subarachnoid space, could carry a worse prognosis than uninfected adenomas or secondary abscesses forming in other pituitary pathologies. We identified infected adenomas from our center through retrospective review. Given the rarity of this diagnosis at any single center, we also reviewed published cases of secondary pituitary abscesses occurring in pituitary adenomas to look for common features. Twenty-three cases (19 from the literature and four from our center) of infected adenomas were identified. The mean age at presentation was 46 years, with 65 % male. The most common presenting symptoms were visual disturbances (83 %) and headache (65 %), followed by infectious signs like fever (39 %) and meningitis (26 %). The sphenoidal sinus was the most common site of extrasellar invasion. While good outcome occurred in 74 % of patients, and most achieved vision improvement, the mortality was 26 %. Patients with infected pituitary adenomas commonly present with visual disturbances and headache, with symptoms of infection also occurring. Surgery and antibiotics are indicated for these lesions. While the infection is more indolent than other intracranial abscesses, it is associated with high mortality even after prompt operation and antibiotic treatment.

  3. Postirradiation sarcomatous transformation of a pituitary adenoma: a combined pituitary tumor. Case report

    SciTech Connect

    Pieterse, S.; Dinning, T.A.; Blumbergs, P.C.

    1982-02-01

    A case is reported in which a fibrosarcoma developed 20 years after irradiation of a pituitary chromophobe adenoma. This rare lesion, like most of the other documented postirradiation pituitary sarcomas, was a combination of fibrosarcoma and pituitary adenoma. These lesions tend to behave in a characteristic fashion, with onset after a long latent interval following irradiation, growth to a large size, and failure to metastasize.

  4. Radiation therapy in the management of pituitary adenomas.

    PubMed

    Pashtan, Itai; Oh, Kevin S; Loeffler, Jay S

    2014-01-01

    Radiation therapy in the form of fractionated treatment or radiosurgery has an important role in the management of pituitary adenomas. Radiation is a reliable way of gaining local control for radiographically progressing pituitary adenomas. For functioning adenomas that are biochemically recurrent or persistent, radiation therapy is less consistent in offering biochemical normalization and often requires a latency period of years or decades. The decision of when to use radiation therapy is a delicate balance between its benefits and late sequelae, especially in the context of benign disease. Recent technological advances in radiation oncology hold the potential to minimize dose to uninvolved normal tissue and therefore reduce the risk of toxicity.

  5. Immunohistochemical detection of human natural killer cell like immunoreactivity in human pituitary adenomas, using monoclonal antibody NK-1.

    PubMed

    Sanno, N; Itoh, J; Teramoto, A; Itoh, Y; Hori, S; Osamura, R Y

    1997-10-01

    Natural killer (NK) cells are specialized lymphocytes which are characterized as non-T and non-B cells, as they lack classic T and B cell surface markers. Recently, NK like immunoreactivity has been identified in endocrine and neuronal tissues as well as in the tumors derived from the neuroectoderm and neuroendocrine system. We examined the expression of NK-1 like immunoreactivity in 6 normal pituitary glands and in 55 cases of neoplastic pituitaries (16 growth hormone (GH) producing adenomas, 14 prolactin (PRL) producing adenomas, 4 thyrotropin (TSH) producing adenomas, 5 adrenocortocitropin (ACTH) producing adenomas and 16 non-functioning adenomas) immunohistochemically. The expression of the S-100 protein, which is a marker for folliclo-stellate (FS) cells, which have been reported to secrete cytokines as immuno-endocrine modulators, were also examined. In normal pituitary glands, NK-1 was detected in all 6 tissues in the cytoplasm of about 5-10% of the anterior pituitary cells. By serial sectioning and double immunostaining, NK-1 immunopositivity was frequently found to be localized in ACTH cells. The colocalization with other anterior pituitary hormones such as GH. PRL, the beta-subunit of luteinizing hormone (LH beta), follicle stimulating hormone (FSH beta). TSH beta and alpha-subunit of glycoprotein (alpha SU) was not observed. The S-100 immunopositive FS cells, which were scattered among hormone producing cells, were closely associated with NK-1 immunoreactive cells in the normal pituitaries. Among the 55 cases of pituitary adenomas, NK-1 was present in all the types of pituitary tumors, and a total of 33 (60.0%) contained NK-1 positive tumor cells. The frequency of NK-1 immunoreactivity in the individual adenoma types was; 14 of 16 GH producing adenomas (87.5%), 7 of 14 PRL producing adenomas (50%). 3 of 4 TSH producing adenomas (75%), 3 of 5 ACTH producing adenomas (60%), and 5 of 16 nonfunctioning adenomas (31.3%). By double immunostaining, NK-1 was

  6. Identification of a subtype-specific ENC1 gene related to invasiveness in human pituitary null cell adenoma and oncocytomas.

    PubMed

    Feng, Jie; Hong, Lichuan; Wu, Yonggang; Li, Chuzhong; Wan, Hong; Li, Guilin; Sun, Yilin; Yu, Shenyuan; Chittiboina, Prashant; Montgomery, Blake; Zhuang, Zhengping; Zhang, Yazhuo

    2014-09-01

    Non-functioning pituitary adenomas (NFPAs) may be locally invasive. Surgery is a treatment option, but unlike the case for functional pituitary adenomas, there are almost no drug treatments available for NFPAs. Markers of invasiveness are needed to guide therapeutic decision-making and identify potential adjuvant drugs. Owing to the highly heterogeneous nature of NFPAs, little is known regarding the subtype-specific gene expression profiles associated with invasiveness. To identify important biomarkers of invasiveness, we selected 23 null cell adenomas and 20 oncocytomas. These tumors were classified as invasive or non-invasive adenomas based on magnetic resonance imaging, pathology slides and surgical findings. Firstly, we observed that there were significant differences in expression between invasive (n = 3) and non-invasive (n = 4) adenomas by gene expression microarray. A total of 1,188 genes were differentially expressed in the invasive and non-invasive adenomas. Among these 1,188 genes, 578 were upregulated and 610 were downregulated in invasive adenomas. Secondly, the expression of ENC1, which displayed the significant alterations, was further confirmed by qRT-PCR and Western blot analysis in all 43 tumor samples and three normal pituitary glands. Low levels of ENC1 were found in tumor samples, while high levels were detected in normal pituitary glands. Interestingly, the ENC1 expression level was low in invasive null cell adenomas compared with non-invasive adenomas, but this relationship was not observed in invasive oncocytomas. Immunohistochemistry also demonstrated that the staining of ENC1 was different between invasive and non-invasive null cell adenomas. In addition, bioinformatics studies, including gene ontology and protein interaction analyses, were also performed to better understand the critical role of ENC1 in the development and progression of null cell adenomas and oncocytomas. Consequently, ENC1 may be an important biomarker for null cell

  7. Familial pituitary adenomas - who should be tested for AIP mutations?

    PubMed

    Korbonits, Márta; Storr, Helen; Kumar, Ajith V

    2012-09-01

    Familial Isolated Pituitary Adenomas (FIPA), an autosomal dominant disease with low penetrance is being increasingly recognized. FIPA families can be divided into two distinct groups based on genetic and phenotypic features. Patients with mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are characterized by young-onset somatotroph or lactotroph macroadenomas, while in the other, larger group of FIPA patients with typically adult-onset disease and more varied adenoma types, no causative gene(s) has been identified. Young-onset macroadenoma patients can also be identified with germline AIP mutation without an apparent family history. Further data and longer follow-up are necessary to establish formal guidelines, but the current data suggest genetic screening of the AIP gene in patients with a pituitary adenoma and no other associated features who have (i) a family history of pituitary adenoma, (ii) childhood-onset pituitary adenoma or (iii) a pituitary somatotroph or lactotroph macroadenoma diagnosed before the age of 30 years.

  8. From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal.

    PubMed

    Asa, S L; Casar-Borota, O; Chanson, P; Delgrange, E; Earls, P; Ezzat, S; Grossman, A; Ikeda, H; Inoshita, N; Karavitaki, N; Korbonits, M; Laws, E R; Lopes, M B; Maartens, N; McCutcheon, I E; Mete, O; Nishioka, H; Raverot, G; Roncaroli, F; Saeger, W; Syro, L V; Vasiljevic, A; Villa, C; Wierinckx, A; Trouillas, J

    2017-04-01

    The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients.

  9. Familial isolated pituitary adenomas (FIPA) and the pituitary adenoma predisposition due to mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene.

    PubMed

    Beckers, Albert; Aaltonen, Lauri A; Daly, Adrian F; Karhu, Auli

    2013-04-01

    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

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

    PubMed Central

    Aaltonen, Lauri A.; Daly, Adrian F.

    2013-01-01

    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

  11. Isolated double pituitary adenomas: A silent corticotroph adenoma and a microprolactinoma.

    PubMed

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

    2015-10-01

    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.

  12. Gigantism caused by growth hormone secreting pituitary adenoma.

    PubMed

    Rhee, Noorisaem; Jeong, Kumi; Yang, Eun Mi; Kim, Chan Jong

    2014-06-01

    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. [Intrasellar small TSH secreting pituitary adenomas, 2 case reports].

    PubMed

    Ogawa, Yoshikazu; Tominaga, Teiji; Ikeda, Hidetoshi

    2007-07-01

    Thyroid-stimulating hormone (TSH)-secreting pituitary adenoma accounts for 1% of pituitary adenoma and often manifests as invasive macroadenoma. If the TSH value is not high enough to cause clinical symptoms presenting as inappropriate secretion of TSH, the tumor may be missed or misdiagnosed as Graves disease. Some of these patients receive inadequate treatment with the antithyroid agent, radioiodine treatment, and thyroidectomy. This tumor is also known as a tough and firm tumor because of the significant interstitial fibrosis. We report two cases of TSH-secreting pituitary adenomas which were comparatively small. Although a tough and difficult operation was expected, actual tumor dissection was easy and gross total removal was achieved within less than 3 hours. We discuss the relationship between the intraoperative findings and histopathology, as well as the ultrastructure and endocrinology.

  14. The trans-sphenoidal resection of pituitary adenomas in elderly patients and surgical risk.

    PubMed

    Locatelli, M; Bertani, G; Carrabba, G; Rampini, P; Zavanone, M; Caroli, M; Sala, E; Ferrante, E; Gaini, S M; Spada, A; Mantovani, G; Lania, A

    2013-06-01

    In western countries, the process of "ageing of the population" is increasingly forcing clinical medicine to find answers for pathologies affecting the elder segments of our community. In this respect, pituitary adenomas often raise difficult questions on surgical indications, since little is known about postoperative morbidity and mortality in elderly patients. The transsphenoidal endonasal approach (TNS), which is considered the gold standard for surgical resection of the majority of functioning and non-functioning pituitary adenomas, is supposed to be a low morbidity and mortality procedure in adult patients. However, only a few contradicting data are available in the literature about elderly patients. In this paper we retrospectively analyze a cohort of 43 consecutive patients aged more than 65 years, operated on for pituitary adenomas at our Institution in the years 1998-2007. These patients were treated by transsphenoidal endonasal approach (TNS) for resection of non-functioning pituitary adenomas (n = 31), GH-secreting adenomas (n = 4) and ACTH-secreting adenomas (n = 8). Clinical records reported a macroadenoma with tumour-related mass symptoms in about 80 % of patients; single or multiple pituitary deficits were present in 44 % of patients. Regarding comorbidities, cardiac disease was the most frequently observed (86 %); assessment of anaesthesiological risk indicated a moderate to severe ASA score in most patients, 11 % showing a 4-5 score. On the basis of current criteria, our retrospective analysis revealed that cure was achieved in 54 % of patients. The outcome was similar to that observed in the general population of patients undergoing transphenoidal surgery in our centre, without differences in the rate of surgical and endocrinological cure, minor and major surgical complications and hospitalization duration. In particular, no significant anaesthesiological complications were observed and no patient developed either permanent diabetes

  15. Stem cells in the canine pituitary gland and in pituitary adenomas.

    PubMed

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

    2013-12-01

    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. Gene expression profiling analysis of MENX-associated rat pituitary adenomas contributes to understand molecular mechanisms of human pituitary adenomas

    PubMed Central

    ZHANG, HONGZHI; XU, CHUAN; SUN, NINGYANG; ZHOU, YINTING; YU, XIAOFEI; YAN, XUE; ZHANG, QIUJUAN

    2016-01-01

    The present study aimed to screen potential genes associated with pituitary adenomas to obtain further understanding with regard to the pathogenesis of pituitary adenomas. The microarray GSE23207 dataset, containing 16 pituitary adenoma samples from multiple endocrine neoplasia syndrome-associated rats and 5 normal pituitary tissue samples, was downloaded from Gene Expression Omnibus. The Linear Models for Microarray Data package was used to identify the differentially-expressed genes (DEGs) with the cut-off criteria of a |log2fold change (FC)|>1 and adjusted P-values of <0.05. The potential functions of the DEGs were predicted by functional and pathway enrichment analysis with the Database for Annotation, Visualization and Integrated Discovery. Furthermore, the interaction associations of the up- and downregulated DEGs obtained from the Search Tool for the Retrieval of Interacting Genes database were respectively revealed by the protein-protein interaction networks visualized with Cytoscape. A total of 391 upregulated and 238 downregulated DEGs in were screened in the pituitary adenoma samples. The upregulated DEGs with a higher degree in the protein-protein interaction network (e.g., CCNA2, CCNB1 and CDC20) were significantly involved in cell cycle and cell division. Notably, PTTG1 was enriched in every functional term. These DEGs interacted with each other. The downregulated DEGs (e.g., GABRA1, GABRA4 and GABRB1) also interacted with each other, and were relevant to neuroactive ligand-receptor interaction; the DEG POU1F1, interacting with POMC, was correlated with the development of the pituitary gland, adenohypophysis and endocrine system. Certain DEGs, including CCNB1, CCNA2, CDC20, GABRA1, GABRA4, GABRB1, POU1F1 and POMC, and particularly PTTG1, were shown to be closely involved in the pathogenesis of pituitary adenomas. PMID:26870179

  17. Assessment of Mitotic Activity in Pituitary Adenomas and Carcinomas.

    PubMed

    Thapar, Kamal; Yamada, Yukio; Scheithauer, Bernd; Kovacs, Kalman; Yamada, Shozo; Stefaneanu, Lucia

    1996-01-01

    Assessment of mitotic activity represents one of the oldest and most routinely used histopathologic methods of evaluating the biological aggressiveness of human tumors. In the case of pituitary tumors, however, the relevance of this approach as a means of gauging tumor behavior remains ill-defined. In this article, the relationship between the mitotic index and biological aggressiveness of pituitary tumors was evaluated in a series of 54 pituitary adenomas and 6 primary pituitary carcinomas. All tumors were fully classified by immunohistochemistry and electron microscopy; adenomas were further stratified on the basis of their invasion status, the latter being defined as gross, operatively, or radiologically apparent infiltration of dura or bone. Mitotic figures were present in 11 tumors, 10 being either invasive adenomas or pituitary carcinomas. A significant association between the presence of mitotic figures and tumor behavior was noted, as evidenced by progressive increments in the proportion of cases expressing mitotic figures in the categories of noninvasive adenoma, invasive adenoma, and pituitary carcinoma (3.9, 21.4, and 66.7%, respectively; Fisher's exact test, two-tailed, p < 0.001). The mitotic index, however, appeared to be a less informative parameter, being extremely low in all cases (mean = 0.016% +/- 0.005 [+/- SEMI). Although the mean mitotic index in pituitary carcinomas (0.09% +/- 0.035) was significantly higher than the mean mitotic index of either noninvasive adenomas (0.002% +/- 0.002) or invasive adenomas (0.013% +/- 0.005), no practical threshold value capable of distinguishing these three groups was evident. Comparison of the mitotic index with Ki-67 derived growth fractions in these tumors revealed a significant but weak linear correlation (r = 0.41, p < 0.01). These data suggest that when, mitotic figures are present, they do provide some indication of the behavior and invasive potential of pituitary tumors. For routine diagnostic

  18. Familial isolated pituitary adenomas experience at a single center: clinical importance of AIP mutation screening.

    PubMed

    Pinho, Leandro Kasuki Jomori de; Vieira Neto, Leonardo; Wildemberg, Luiz Eduardo Armondi; Moraes, Aline Barbosa; Takiya, Christina M; Frohman, Lawrence A; Korbonits, Márta; Gadelha, Mônica R

    2010-11-01

    We present four FIPA kindred discussing clinical and molecular data and emphasizing the differences regarding AIP status, as well as the importance of genetic screening. Family 1 consists of five patients harboring somatotropinomas with germline E24X mutation in AIP. In one of the patients, acromegaly was diagnosed through active screening, being cured by surgery. Families 2 and 3 are composed of two patients with non-functioning pituitary adenomas. Family 4 comprises patients harboring a prolactinoma and a somatotropinoma. No mutations in AIP were found in these families. No patient in Family 1 was controlled with octreotide treatment, while the acromegalic patient in Family 4 was controlled with octreotide LAR. In conclusion, FIPA is a heterogeneous condition, which may be associated with AIP mutation. Genomic and clinical screening is recommended in families with two or more members harboring pituitary adenomas, allowing early diagnosis and better outcome.

  19. MMP-14 and TGFβ-1 methylation in pituitary adenomas

    PubMed Central

    Ruskyte, Kornelija; Liutkevicienė, Rasa; Vilkeviciute, Alvita; Vaitkiene, Paulina; Valiulytė, Indre; Glebauskiene, Brigita; Kriauciuniene, Loresa; Zaliuniene, Dalia

    2016-01-01

    Pituitary adenoma (PA) is one of the most common abnormalities in the sellar region. Despite the fact that PA is a benign monoclonal neoplasm, it can cause serious complications, including ophthalmological, neurological and endocrinological abnormalities. Currently, the causes that increase the progression of tumors are unknown. Epigenetic silencing of the matrix metalloproteinase-14 (MMP-14) and transforming growth factor beta-1 (TGFβ-1) genes may be associated with the development of PA, since these genes are important in the processes of tumor metastasis and angiogenesis. The purpose of the present study was to determine if the methylation status of the MMP-14 and TGFβ-1 promoters is associated with PA development. In the present study, 120 tissue samples of PA were used. The methylation status of the MMP-14 and TGFβ-1 promoters was investigated by methylation specific-polymerase chain reaction. Statistical analysis was conducted to investigate the associations between the methylation status, age and gender of PA patients, PA tumoral activity, recurrence and invasiveness. The MMP-14 gene was methylated in 30.00% (17/56 functioning and 19/64 non-functioning) of patients with PA, while the TGFβ-1 gene was methylated in 13.33% (9/56 functioning and 7/64 non-functioning) of patients with PA. It was also observed that promoter methylation of MMP-14 correlated with the male gender (58.8 vs. 35.7%, P=0.022), while unmethylated (non-silenced) MMP-14 correlated with the female gender (64.3 vs. 41.7%, P=0.027). Associations between the promoter methylation status of the MMP-14 and TGFβ-1 genes and PA functioning or recurrence were not identified. The present study reveals that silencing of the MMP-14 gene correlates with patients' gender. However, MMP-14 and TGFβ-1 promoter methylation cannot be considered as a prognostic marker in PAs. PMID:27698891

  20. Genetics Home Reference: familial isolated pituitary adenoma

    MedlinePlus

    ... adenoma predisposition due to mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. Endocr Rev. 2013 ... AB, Korbonits M. The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic ...

  1. Whole-exome sequencing identifies variants in invasive pituitary adenomas

    PubMed Central

    Lan, Xiaolei; Gao, Hua; Wang, Fei; Feng, Jie; Bai, Jiwei; Zhao, Peng; Cao, Lei; Gui, Songbai; Gong, Lei; Zhang, Yazhuo

    2016-01-01

    Pituitary adenomas exhibit a wide range of behaviors. The prediction of invasion or malignant behavior in pituitary adenomas remains challenging. The objective of the present study was to identify the genetic abnormalities associated with invasion in sporadic pituitary adenomas. In the present study, the exomes of six invasive pituitary adenomas (IPA) and six non-invasive pituitary adenomas (nIPA) were sequenced by whole-exome sequencing. Variants were confirmed by dideoxynucleotide sequencing, and candidate driver genes were assessed in an additional 28 pituitary adenomas. A total of 15 identified variants were mainly associated with angiogenesis, metabolism, cell cycle phase, cellular component organization, cytoskeleton and biogenesis immune at a cellular level, including 13 variants that occurred as single nucleotide variants and 2 that comprised of insertions. The messenger RNA (mRNA) levels of diffuse panbronchiolitis critical region 1 (DPCR1), KIAA0226, myxovirus (influenza virus) resistance, proline-rich protein BstNI subfamily 3, PR domain containing 2, with ZNF domain, RIZ1 (PRDM2), PR domain containing 8 (PRDM8), SPANX family member N2 (SPANXN2), TRIO and F-actin binding protein and zinc finger protein 717 in IPA specimens were 50% decreased compared with nIPA specimens. In particular, DPCR1, PRDM2, PRDM8 and SPANXN2 mRNA levels in IPA specimens were approximately four-fold lower compared with nIPA specimens (P=0.003, 0.007, 0.009 and 0.004, respectively). By contrast, the mRNA levels of dentin sialophospho protein, EGF like domain, multiple 7 (EGFL7), low density lipoprotein receptor-related protein 1B and dynein, axonemal, assembly factor 1 (LRRC50) were increased in IPA compared with nIPA specimens (P=0.041, 0.037, 0.022 and 0.013, respectively). Furthermore, decreased PRDM2 expression was associated with tumor recurrence. The findings of the present study indicate that DPCR1, EGFL7, the PRDM family and LRRC50 in pituitary adenomas are modifiers of

  2. Pituitary null cell adenoma in a domestic llama (Lama glama).

    PubMed

    Chalkley, M D; Kiupel, M; Draper, A C E

    2014-07-01

    Pituitary gland neoplasia has been reported rarely in camelids. A 12-year-old neutered male llama (Lama glama) presented with lethargy, inappetence and neurological signs. On physical examination, the llama was mentally dull and exhibited compulsive pacing and circling to the left. Complete blood count and serum biochemistry revealed haemoconcentration, mild hypophosphataemia, hyperglycaemia, hypercreatininaemia and hyperalbuminaemia. Humane destruction was elected due to rapid clinical deterioration and poor prognosis. Post-mortem examination revealed a pituitary macroadenoma and bilateral internal hydrocephalus. Microscopically, the pituitary tumour was composed of neoplastic chromophobic pituitary cells. Ultrastructural studies revealed similar neoplastic cells to those previously described in human null cell adenomas. Immunohistochemically, the neoplastic cells were strongly immunoreactive for neuroendocrine markers (synaptophysin and chromogranin A), but did not exhibit immunoreactivity for epithelial, mesenchymal, neuronal and all major pituitary hormone markers (adrenocorticotropic hormone, follicle stimulating hormone, growth hormone, luteinizing hormone, melanocyte-stimulating hormone, prolactin and thyroid stimulating hormone), consistent with the diagnosis of a pituitary null cell adenoma. This is the first report of pituitary neoplasia in a llama.

  3. Molecular screening of pituitary adenomas for gene mutations and rearrangements

    SciTech Connect

    Herman, V.; Drazin, N.Z.; Gonskey, R.; Melmed, S. )

    1993-07-01

    Although pituitary tumors arise as benign monoclonal neoplasms, genetic alterations have not readily been identified in these adenomas. The authors studied restriction fragment abnormalities involving the GH gene locus, and mutations in the p53 and H-, K-, and N-ras genes in 22 human GH cell adenomas. Twenty two nonsecretory adenomas were also examined for p53 and ras gene mutations. Seven prolactinoma DNA samples were tested for deletions in the multiple endocrine neoplasia-1 (MEN-1) locus, as well as for rearrangements in the hst gene, a member of the fibroblast growth factor family. In DNA from GH-cell adenomas, identical GH restriction patterns were detected in both pituitary and lymphocyte DNA in all patients and in one patient with a mixed GH-TSH cell adenoma. Using polymerase chain reaction (PCR)-single stranded conformation polymorphism analysis, no mutations were detected in exons 5, 6, 7 and 8 of the p53 gene in GH cell adenomas nor in 22 nonsecretory adenomas. Codons 12/13 and 61 of H-ras, K-ras, and N-ras genes were also intact on GH cell adenomas and in nonsecretory adenomas. Site-specific probes for chromosome 11q13 including, PYGM, D11S146, and INT2 were used in 7 sporadic PRL-secreting adenomas to detect deletions of the MEN-1 locus on chromosome 11. One patient was identified with a loss of 11p, and the remaining 6 patients did not demonstrate loss of heterozygosity in the pituitary 11q13 locus, compared to lymphocyte DNA. None of these patients demonstrated hst gene rearrangements which also maps to this locus. These results show that p53 and ras gene mutations are not common events in the pathogenesis of acromegaly and nonsecretory tumors. Although hst gene rearrangements and deletions of 11q13 are not associated with sporadic PRl-cell adenoma formation, a single patient was detected with a partial loss of chromosome 11, including the putative MEN-1 site. 31 refs., 5 figs., 2 tabs.

  4. Concurrent somatotroph and plurihormonal pituitary adenomas in a cat.

    PubMed

    Sharman, Mellora; FitzGerald, Louise; Kiupel, Matti

    2013-10-01

    An 8-year-old, male neutered, domestic longhair cat was referred for investigation of insulin-resistant diabetes mellitus. Routine haematology, serum biochemistry, urinalysis (including culture), total T4 and urine creatinine:cortisol ratio were unremarkable, but markedly increased insulin-like growth factor-1 concentration was identified and a pituitary mass was subsequently documented. The cat was treated conservatively with the dopamine agonist L-deprenyl and was re-presented 16 months later for worsening polyuria, polydipsia, polyphagia, marked lumbar muscle atrophy, development of a pendulous abdomen and marked thinning of the abdominal skin. Hyperadrenocorticism was diagnosed based on abdominal ultrasonography, dexamethasone suppression testing and endogenous adrenocorticotropic hormone (ACTH). The cat was treated with trilostane (30 mg q24h PO) and showed some clinical improvement, but developed an opportunistic fungal infection and skin fragility syndrome 4.5 months after commencing treatment, and was euthanased. A double-pituitary adenoma comprising a discrete somatotroph adenoma and a separate plurihormonal adenoma (positive immunoreactivity for ACTH, melanocyte-stimulating hormone and follicle-stimulating hormone) was identified on post-mortem examination. These two pituitary adenomas were suspected to have arisen as independent neoplastic entities with the plurihormonal tumour either being clinically silent at the initial presentation or having developed over the subsequent 16 months.

  5. Expression of Neuropeptide Y and Its Relationship with Molecular and Morphological Changes in Human Pituitary Adenomas.

    PubMed

    Jia, Ruichao; Li, Mu; Chang, Binge; Chen, Laichao; Ma, Jingjian

    2015-12-01

    The purpose of this study was to explore the role of neuropeptide Y (NPY) on molecular and histological changes in human pituitary adenomas. The localization of NPY and its expression at the protein, messenger RNA (mRNA), and receptor levels were investigated here in different subcategories of pituitary adenomas. Immunohistochemical staining was performed in all cases to assess expression of NPY. Reverse transcription-polymerase chain reaction (RT-PCR) was used to study the mRNA expression of NPY. NPY subcellular localization was observed using immunoelectron microscopy in cytoplasm, rough endoplasmic reticulum, and cell matrix in four of the six cases of pituitary adenoma. NPY protein expression was observed in 59.6% of 57 cases of pituitary adenoma and in 2 cases of pituitary hyperplasia. mRNA expression of NPY was observed in all 57 cases of pituitary adenoma and in 2 cases of pituitary hyperplasia. Significantly different levels of expression were observed across different subcategories of pituitary adenoma. mRNA expression of Y1R and Y2R was observed across all subcategories of pituitary adenomas, and a positive correlation was observed between NPY and Y2R. In conclusion, evidence is provided here for the expression of NPY and its receptors, Y1R and Y2R, in human pituitary adenoma, and the levels of expression were found to differ across different subcategories. Differences in expression of Y2R in human pituitary adenomas were found to have remarkable statistical significance.

  6. Expression of cell growth negative regulators MEG3 and GADD45γ is lost in most sporadic human pituitary adenomas.

    PubMed

    Mezzomo, Lisiane Cervieri; Gonzales, Paulo Henrique; Pesce, Frederico Giacomoni; Kretzmann Filho, Nélson; Ferreira, Nelson Pires; Oliveira, Miriam Costa; Kohek, Maria Beatriz Fonte

    2012-09-01

    We aimed at the evaluation of MEG3 and GADD45γ expression in sporadic functioning and clinically non-functioning human pituitary adenomas, morphologically characterized by immunohistochemistry analysis and their association with clinical features. Thirty eight patients who had undergone hypophysectomy at São José Hospital of Irmandade Santa Casa de Misericórdia in Porto Alegre, Brazil, were included in this study. We evaluated tumor-type specific MEG3 and GADD45γ expression by qRT-PCR in the pituitary adenomas, and its association with clinical features, as age, gender and tumor size, obtained from medical records. The patients consisted of 21 males and 17 females and the mean age was 47 ± 14 (mean ± SD), ranging from 18 to 73 years-old. Of these 14 were clinically non-functioning, 10 GH-secreting, 9 PRL-secreting, and 5 ACTH-secreting pituitary adenomas. All samples were macroadenomas, except four ACTH-secreting tumors, which were microadenomas. In summary, MEG3 and GADD45γ expression was significantly lost in most clinically non-functioning adenomas (78 and 92%, respectively). Other assessed pituitary tumor phenotypes expressed both genes at significantly different levels, and, in some cases, with overexpression. There was no significant association between gene expression and the analyzed clinical features. Our results confirm the previous report, which indicated that MEG3 and GADD45γ expression is lost in the majority of human pituitary tumors, mainly in clinically-nonfunctioning adenomas. Functioning tumors had differences of relative expression levels. The two groups of tumors are probably genetically different and may have a different natural history.

  7. Occult invasive pituitary adenoma predisposing to fatal bacterial meningitis.

    PubMed

    Laszewski, M J; Moore, S A

    1990-01-01

    Pituitary adenomata are benign neoplasms which usually grow slowly and present with manifestations relating to an associated endocrinopathy or visual disturbance. Rarely these neoplasms will demonstrate a more aggressive behavior with extracranial extension and symptoms of upper airway obstruction or anosmia. Several reported cases suggest that although these neoplasms behave aggressively the overall survival and prognosis for these patients remains good. We present the clinical and postmortem findings of an occult invasive pituitary adenoma leading to the development of bacterial meningitis, coma and death. This communication stresses the necessity for the early diagnosis and treatment of the invasive adenomata to prevent the development of potentially fatal infectious sequelae.

  8. Pituitary adenomas: historical perspective, surgical management and future directions

    PubMed Central

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

    2016-01-01

    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

  9. Long-Term Outcomes of Radiotherapy for Pituitary Adenomas

    SciTech Connect

    Snead, Felicia E. Amdur, Robert J. M.D.; Morris, Christopher G. M.S.; Mendenhall, William M.

    2008-07-15

    Purpose: To evaluate long-term local control and toxicity for pituitary adenomas treated with fractionated radiotherapy (RT). Methods and Materials: The records of 100 patients with pituitary adenomas treated between 1983 and 2003 were retrospectively reviewed. Thirty-one patients had hormone-secreting tumors; 69 patients were treated with surgery and postoperative RT. Median follow-up was 6.7 years (range, 0.6-20.2 years) for all patients and 6.2 years (range, 2-20.2 years) for living patients. The mean dose delivered was 45 Gy (range, 43-50.4 Gy). Results: The 10-year actuarial local control rates for nonsecreting and secreting adenomas were 98% and 73%, respectively (p 0.0015). Actuarial 10-year cause-specific survival (CSS) rates were 95% and 88%, and overall survival rates were 66% and 79% for nonsecreting and secreting adenomas, respectively. Involvement of the sphenoid sinus was found to be significantly associated with decreased 10-year CSS (p = 0.0453). When compared with the two- or three-field techniques, stereotactic RT was associated with improved CSS (p = 0.0775). CSS was not significantly associated with hormone excretion, extent of surgery, or whether RT was administrated postoperatively or for salvage after a postsurgical recurrence. New cases of hypopituitarism occurred in 35 patients. One patient experienced vision loss, and one patient developed a post-treatment glioma. Conclusions: This is one of the most mature series in the literature that documents excellent results with fractionated RT for pituitary adenoma. We recommend 45 Gy at 1.8 Gy per fraction using stereotactic noncoplanar fields.

  10. Clinicopathologic analysis of pituitary adenoma: a single institute experience.

    PubMed

    Cho, Hwa Jin; Kim, Hanna; Kwak, Yoon Jin; Seo, Jeong Wook; Paek, Sun Ha; Sohn, Chul-Ho; Yun, Jung Min; Kim, Da Seu Ran; Kang, Peter; Park, Peom; Park, Sung-Hye

    2014-03-01

    Pituitary adenoma (PA) is a common benign neuroendocrine tumor; however, the incidence and proportion of hormone-producing PAs in Korean patients remain unknown. Authors analyzed 506 surgically resected and pathologically proven pituitary lesions of the Seoul National University Hospital from 2006 to 2011. The lesions were categorized as: PAs (n = 422, 83.4%), Rathke's cleft cysts (RCCs) (n = 54, 10.6%), inflammatory lesions (n = 8, 1.6%), meningiomas (n = 4), craniopharyngiomas (n = 4), granular cell tumors (n = 1), metastatic renal cell carcinomas (n = 2), germinomas (n = 1), ependymomas (n = 1), and unsatisfactory specimens (n = 9, 1.8%). PAs were slightly more prevalent in women (M: F = 1:1.17) with a mean age of 48.8 yr (9-80 yr). Immunohistochemical analysis revealed that prolactin-producing PAs (16.6%) and growth hormone-producing adenomas (9.2%) were the most common functional PAs. Plurihormonal PAs and nonfunctioning (null cell) adenomas were found in 14.9% and 42.4% of patients with PAs, respectively. The recurrence rate of PAs was 11.1%, but nearly 0% for the remaining benign lesions such as RCCs. 25.4% of patients with PAs were treated by gamma-knife after surgery due to residual tumors or regrowth of residual tumor. In conclusion, the pituitary lesions and the proportions of hormone-producing PAs in Korean patients are similar to those of previous reports except nonfunctioning (null cell) PAs, which are unusually frequent.

  11. Isolated double adrenocorticotropic hormone-secreting pituitary adenomas: A case report and review of the literature

    PubMed Central

    PU, JIUJUN; WANG, ZHIMING; ZHOU, HUI; ZHONG, AILING; JIN, KAI; RUAN, LUNLIANG; YANG, GANG

    2016-01-01

    Only a few cases of double or multiple pituitary adenomas have previously been reported in the literature; however, isolated double adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are even more rare. The present study reports a rare case of a 50-year-old female patient who presented with typical clinical features of Cushing's disease and was diagnosed with isolated double ACTH-secreting pituitary adenomas. Endocrinological examination revealed an ACTH-producing pituitary adenoma, and preoperative magnetic resonance imaging (MRI) demonstrated a microadenoma with a lower intensity on the right side of the pituitary gland. The patient underwent endoscopic endonasal transsphenoidal surgery, which revealed another pituitary tumor in the left side of the pituitary gland. The two, clearly separated, pituitary adenomas identified in the same gland were completely resected. Immunohistochemistry and pathology revealed that the clearly separated double pituitary adenomas were positive for ACTH, thyroid-stimulating, growth and prolactin hormones. Postoperatively, the levels of ACTH and cortisol hormone decreased rapidly. The case reported in the present study is considerably rare, due to the presence of a second pituitary adenoma in the same gland, which was not detected by preoperative MRI scan, but was noticed during surgery. Intraoperative evaluation may be important in the identification of double or multiple pituitary adenomas. PMID:27347184

  12. Isolated double adrenocorticotropic hormone-secreting pituitary adenomas: A case report and review of the literature.

    PubMed

    Pu, Jiujun; Wang, Zhiming; Zhou, Hui; Zhong, Ailing; Jin, Kai; Ruan, Lunliang; Yang, Gang

    2016-07-01

    Only a few cases of double or multiple pituitary adenomas have previously been reported in the literature; however, isolated double adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are even more rare. The present study reports a rare case of a 50-year-old female patient who presented with typical clinical features of Cushing's disease and was diagnosed with isolated double ACTH-secreting pituitary adenomas. Endocrinological examination revealed an ACTH-producing pituitary adenoma, and preoperative magnetic resonance imaging (MRI) demonstrated a microadenoma with a lower intensity on the right side of the pituitary gland. The patient underwent endoscopic endonasal transsphenoidal surgery, which revealed another pituitary tumor in the left side of the pituitary gland. The two, clearly separated, pituitary adenomas identified in the same gland were completely resected. Immunohistochemistry and pathology revealed that the clearly separated double pituitary adenomas were positive for ACTH, thyroid-stimulating, growth and prolactin hormones. Postoperatively, the levels of ACTH and cortisol hormone decreased rapidly. The case reported in the present study is considerably rare, due to the presence of a second pituitary adenoma in the same gland, which was not detected by preoperative MRI scan, but was noticed during surgery. Intraoperative evaluation may be important in the identification of double or multiple pituitary adenomas.

  13. MRI appearances of an ectopic pituitary adenoma: case report and review of the literature.

    PubMed

    Slonim, S M; Haykal, H A; Cushing, G W; Freidberg, S R; Lee, A K

    1993-01-01

    MR images of an ectopic pituitary adenoma have been published in only a single case, a suprasellar mass. We present a patient with Cushing's disease in whom MRI revealed a pituitary adenoma within the sphenoid sinus. Radiologic characteristics of ectopic pituitary adenomas are reviewed, with emphasis on MRI, which demonstrates a soft tissue mass, isointense with gray matter on T1-weighted images, which enhances in a heterogeneous manner.

  14. Familial isolated pituitary adenomas (FIPA) and mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene.

    PubMed

    Daly, Adrian F; Beckers, Albert

    2015-03-01

    The most frequent conditions that are associated with inherited/familial pituitary adenomas are familial isolated pituitary adenoma (FIPA) and multiple endocrine neoplasia type 1 (MEN1), which together account for up to 5% of pituitary adenomas. One important genetic cause of FIPA are inactivating mutations or deletions in the aryl hydrocarbon receptor interacting protein (AIP) gene. FIPA is the most frequent clinical presentation of AIP mutations. This article traces the current state of knowledge regarding the clinical features of FIPA and the particular genetic, pathologic, and clinical characteristics of pituitary adenomas due to AIP mutations.

  15. Mutation analysis of inhibitory guanine nucleotide binding protein alpha (GNAI) loci in young and familial pituitary adenomas.

    PubMed

    Demir, Hande; Donner, Iikki; Kivipelto, Leena; Kuismin, Outi; Schalin-Jäntti, Camilla; De Menis, Ernesto; Karhu, Auli

    2014-01-01

    Pituitary adenomas are neoplasms of the anterior pituitary lobe and account for 15-20% of all intracranial tumors. Although most pituitary tumors are benign they can cause severe symptoms related to tumor size as well as hypopituitarism and/or hypersecretion of one or more pituitary hormones. Most pituitary adenomas are sporadic, but it has been estimated that 5% of patients have a familial background. Germline mutations of the tumor suppressor gene aryl hydrocarbon receptor-interacting protein (AIP) predispose to hereditary pituitary neoplasia. Recently, it has been demonstrated that AIP mutations predispose to pituitary tumorigenesis through defective inhibitory GTP binding protein (Gαi) signaling. This finding prompted us to examine whether germline loss-of-function mutations in inhibitory guanine nucleotide (GTP) binding protein alpha (GNAI) loci are involved in genetic predisposition of pituitary tumors. To our knowledge, this is the first time GNAI genes are sequenced in order to examine the occurrence of inactivating germline mutations. Thus far, only somatic gain-of-function hot-spot mutations have been studied in these loci. Here, we have analyzed the coding regions of GNAI1, GNAI2, and GNAI3 in a set of young sporadic somatotropinoma patients (n = 32; mean age of diagnosis 32 years) and familial index cases (n = 14), thus in patients with a disease phenotype similar to that observed in AIP mutation carriers. In addition, expression of Gαi proteins was studied in human growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH)-secreting and non-functional pituitary tumors. No pathogenic germline mutations affecting the Gαi proteins were detected. The result suggests that loss-of-function mutations of GNAI loci are rare or nonexistent in familial pituitary adenomas.

  16. Secondary abscess formation in pituitary adenoma after tooth extraction. Case report.

    PubMed

    Kroppenstedt, S N; Liebig, T; Mueller, W; Gräf, K J; Lanksch, W R; Unterberg, A W

    2001-02-01

    The presence of an abscess in a pituitary tumor is a very rare finding. The authors report the case of a 69-year-old man with a pituitary adenoma confirmed by neuroimaging results, in whom a high fever, meningismus, and left-sided ophthalmoplegia developed 4 days after tooth extraction. The results of serial cranial magnetic resonance imaging were highly indicative of an abscess formation within the pituitary adenoma. During surgery the tumor was approached transsphenoidally and removed. Histological examination confirmed the presence of an abscess formation within the pituitary adenoma. It is most likely that the tooth extraction caused a bacteremia, which led to an inflammation with abscess formation within the pituitary adenoma. The authors conclude that invasive dental procedures should be avoided before planned resection of a pituitary adenoma.

  17. The AIP (aryl hydrocarbon receptor-interacting protein) gene and its relation to the pathogenesis of pituitary adenomas.

    PubMed

    Lloyd, Catrin; Grossman, Ashley

    2014-08-01

    Pituitary adenomas are monoclonal neoplasms that may secrete excessive quantities of their endogenous hormones, or may not be associated with any obvious syndrome, in which case they are known as non-functioning pituitary adenomas. Around 2 % have been said to occur in a familial setting, in the absence of any other tumor, now described as familial isolated pituitary adenomas (FIPA). Some 15-30 % of such families harbor inactivating germ-line mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene, along with 20 % of pediatric seemingly sporadic cases. AIP mutants are referred to as having pituitary adenoma predisposition, and present with early onset, aggressive macroadenomas, most of which secrete somatotropin. Evidence from transfection studies implies that AIP acts as a tumor suppressor; although whether this is mediated through an interaction with the aryl hydrocarbon receptor, phosphodiesterases, or with cell cycle regulators such as survivin or RET remains controversial. However, at present an interaction with the cyclic AMP pathway seems most plausible. Recently, evidence has shown that AIP may act at the cell surface, causing changes in integrin function. The presence of AIP mutations in a significant proportion of FIPA families as well as in apparently sporadic cases, particularly in young patients, suggests a need to screen such patients for AIP mutations to enable better clinical management. However, the absence of AIP mutations in over half of such cases highlights the need to search for further gene mutations.

  18. Peroxisome proliferator-activated receptor gamma in the human pituitary gland: expression and splicing pattern in adenomas versus normal pituitary.

    PubMed

    Occhi, G; Albiger, N; Berlucchi, S; Gardiman, M; Scanarini, M; Scienza, R; Fassina, A; Mantero, F; Scaroni, C

    2007-07-01

    Pituitary adenomas are slow-growing tumours arising within the pituitary gland. If secreting, they give rise to well-known syndromes such as Cushing's disease or acromegaly; when hormonally inactive, they come to clinical attention often with local mass effects or pituitary deficiency. Peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor with a key role in fat and glucose metabolism, but also involved in several neoplasia, has recently been detected in pituitary adenomas. In the present study, we evaluated the occurrence and splicing profile of PPARgamma in 43 cases of pituitary adenoma of different subtypes and compared it to 12 normal pituitary glands. By real-time polymerase chain reaction, PPARgamma was expressed as much in adrenocorticotrophic hormone (ACTH)-secreting and ACTH-silent adenomas as in controls, with a moderate underexpression in somatotrophinomas and prolactinomas and overexpression in 54% of nonfunctioning pituitary adenomas (NFPA). There was no apparent qualitative change in the splicing profile of pathological pituitary glands, nor was the presence of specific isoforms with dominant negative effects against PPARgamma detected. Western blotting revealed similar expression levels in the different subgroups of pituitary adenomas and normal glands. Immunohistochemistry confirmed PPARgamma expression in approximately one-half of analysed samples. The intra- and intergroup differences observed in pituitary adenomas may represent new elements in the process of understanding the different clinical responses of Cushing's and Nelson patients to PPARgamma-ligand treatment. Moreover, the higher level of PPARgamma expression detected in the NFPA subgroup may suggest its possible role as a molecular target in these pituitary adenomas, paving the way for investigations on the effectiveness of treatment with thiazolidinediones in such patients.

  19. ESR1 and its antagonist fulvestrant in pituitary adenomas.

    PubMed

    Gao, Hua; Xue, Yake; Cao, Lei; Liu, Qian; Liu, Chunhui; Shan, Xiaosong; Wang, Hongyun; Gu, Yi; Zhang, Yazhuo

    2017-03-05

    Estrogen has a key role in the pathogenesis of pituitary adenomas (PAs). The study was to evaluate the estrogen receptor alpha (ESR1) level in 289 PAs cases, its association with clinicopathologic features and serving as a target of cancer treatment. In this study, the ESR1 level was evaluated by tissue microarray (TMA). The effect of fulvestrant was determined by an animal model of prolactinoma established by subcutaneous injection of 17β-estradiol in F344 rats. The volume and weight of the pituitary were assessed in the different groups. The effects of fulvestrant on cell proliferation and cell invasion were explored in the pituitary adenoma cell lines GH3 and JT1-1. The ESR1-positive cells rates of 191/289 cases were more than 50%. And ESR1 high level cases (age≥50) were 103/133, and 88/156 in cases (age<50) (X(2) = 14.17, p = 0.0001). The average weight of the pituitary gland in F344 rat tumor model induced by 17-β-estradiol was 38.6 ± 11.2 mg, almost 6 times higher than control group (6.2 ± 1.7 mg). Fulvestrant significantly reduced the weight of the pituitary and its inhibition rate was 68.4 ± 8.3%. TUNEL assay and Western blotting showed that fulvestrant induced apoptotic cell death in vivo and in vitro. PTEN/MAPK signaling pathways were activated in response to fulvestrant treatment in GH3 cells. U0126 partly rescued cell viability of GH3 cells after fulvestrant exposure. ESR1 can be a potential target for PAs, especially for elder GHomas and NFPAs. Fulvestrant may be a new choice for the treatment of PAs.

  20. Temozolomide therapy in patients with aggressive pituitary adenomas or carcinomas.

    PubMed

    Losa, Marco; Bogazzi, Fausto; Cannavo, Salvo; Ceccato, Filippo; Curtò, Lorenzo; De Marinis, Laura; Iacovazzo, Donato; Lombardi, Giuseppe; Mantovani, Giovanna; Mazza, Elena; Minniti, Giuseppe; Nizzoli, Maurizio; Reni, Michele; Scaroni, Carla

    2016-02-01

    Temozolomide is effective in some patients with progressive pituitary adenoma or carcinoma. We report a survey study of Italian patients treated with Temozolomide because of aggressive pituitary adenoma or carcinoma resistant to standard therapies. Italian endocrinologists were surveyed and asked to participate into the study. A questionnaire was sent to all those who agreed and had used Temozolomide in at least one patient with pituitary tumor. Database was closed in December 2013. A literature review was also performed. Thirty-one patients were included into the analysis. Mean age at start of Temozolomide treatment was 58.3 ± 1.9 years (± standard error). Six of the 31 (19.4%) Italian patients had a pituitary carcinoma. Twenty-five patients (80.6%) had disease control during Temozolomide treatment, while 6 patients (19.4%) had disease progression. Median follow-up after beginning Temozolomide was 43 months. Thirteen patients had tumor growth after stopping Temozolomide. The 2-year progression-free survival was 47.7% (95% CI 29.5-65.9%), while the 2-year disease control duration was 59.1% (95% CI 39.1-79.1%). Eleven patients died of progressive disease and other two patients of unrelated causes. The 2-year and 4-year overall survival rates were 83.9% (95% CI 70.7-97.1%) and 59.6% (95% CI 40.0-79.2%), respectively. Temozolomide is an additional effective therapeutic option for the treatment of aggressive pituitary tumors. The drug is well tolerated and causes few severe adverse effects. Recurrence of the tumor can occur after an initial positive response and usually portends a grim outcome.

  1. PPAR-γ receptor ligands: novel therapy for pituitary adenomas

    PubMed Central

    Heaney, Anthony P.; Fernando, Manory; Melmed, Shlomo

    2003-01-01

    Pituitary tumors cause considerable morbidity due to local invasion, hypopituitarism, or hormone hypersecretion. In many cases, no suitable drug therapies are available, and surgical excision is currently the only effective treatment. We show here abundant expression of nuclear hormone receptor PPAR-γ in all of 39 human pituitary tumors. PPAR-γ activating thiazolidinediones (TZDs) rosiglitazone and troglitazone induced G0-G1 cell-cycle arrest and apoptosis in human, rat somatolactotroph, and murine gonadotroph pituitary tumor cells, and suppressed in vitro hormone secretion. In vivo development and growth of murine somatolactotroph and gonadotroph tumors, generated by subcutaneous injection of prolactin-secreting (PRL-secreting) and growth hormone–secreting (GH-secreting) GH3 cells, luteinizing hormone–secreting (LH-secreting) LβT2 cells, and α-T3 cells, was markedly suppressed in rosiglitazone-treated mice, and serum GH, PRL, and LH levels were attenuated in all treated animals (P < 0.009). These results demonstrate that PPAR-γ is an important molecular target in pituitary adenoma cells and PPAR-γ ligands inhibit tumor cell growth and GH, PRL, and LH secretion in vitro and in vivo. TZDs are proposed as novel oral medications for managing pituitary tumors. PMID:12727930

  2. Hyponatremia and pituitary adenoma: think twice about the etiopathogenesis.

    PubMed

    Zogheri, A; Di Mambro, A; Mannelli, M; Serio, M; Forti, G; Peri, A

    2006-09-01

    Pituitary adenomas may be the cause of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), although few cases have so far been reported. We described a case of hypotonic hyponatremia in a 76-yr-old man with a pituitary macroadenoma. He had a recent history of two syncopal attacks which had occurred in the last two months. Baseline assessment demonstrated a sodium serum level of 114 mEq/l. Clinically, the patient appeared euvolemic. Thyroid and adrenal function testing did not show any abnormality. Plasma and urinary osmolality (238 and 186 mOsm/kg, respectively) were in agreement with the diagnosis of SIADH. Accordingly, 3% hypertonic saline solution was started, followed by water intake restriction when natremia reached 126 mEq/l. A computed tomography (CT) scan of the chest revealed the presence of a 2-cm lesion in the azygos-esophageal recess. Because the nature of the lesion appeared uncertain, antibiotic therapy was initiated. After one month, a new CT scan did not show any evidence of the mediastinic mass. Sodium serum level was within the normal range (141 mEq/l) and remained stable thereafter, without fluid restriction. This case very well demonstrates that, in the presence of hyponatremia due to SIADH, more frequently associated co-morbidities (ie mediastinic diseases) have to be searched, even in the presence of a possible, yet rare, cause of this syndrome (ie pituitary adenoma).

  3. Thyrotropin-secreting pituitary adenomas: epidemiology, diagnosis, and management.

    PubMed

    Amlashi, Fatemeh G; Tritos, Nicholas A

    2016-06-01

    Inappropriate secretion of TSH was first described in 1960 in a patient with evidence of hyperthyroidism and expanded sella on imaging. It was later found that a type of pituitary adenoma that secretes TSH (thyrotropinoma) was the underlying cause. The objective of the present review article is to summarize data on the epidemiology, pathogenesis, diagnosis, and management of thyrotropinomas. The prevalence of thyrotropinomas is lower than that of other pituitary adenomas. Early diagnosis is now possible thanks to the availability of magnetic resonance imaging and sensitive laboratory assays. As a corollary, many patients now present earlier in the course of their disease and have smaller tumors at the time of diagnosis. Treatment also has evolved over time. Transsphenoidal surgery is still considered definitive therapy. Meanwhile, radiation therapy, including radiosurgery, is effective in achieving tumor control in the majority of patients. In the past, radiation therapy was used as second line treatment in patients with residual or recurrent tumor after surgery. However, the availability of somatostatin analogs, which can lead to normalization of thyroid function as well as shrink these tumors, has led to an increase in the role of medical therapy in patients who are not in remission after pituitary surgery. In addition, dopamine agonists have shown some efficacy in the management of these tumors. Better understanding of the molecular pathogenesis of thyrotropinomas may lead to rationally designed therapies for patients with thyrotropinomas.

  4. Extended endoscopic endonasal surgery using three-dimensional endoscopy in the intra-operative MRI suite for supra-diaphragmatic ectopic pituitary adenoma.

    PubMed

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

    2015-01-01

    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.

  5. Increased serum interleukin-22 levels in patients with PRL-secreting and non-functioning pituitary macroadenomas.

    PubMed

    Cannavo, S; Ferrau, F; Cotta, O R; Saitta, S; Barresi, V; Cristani, M T; Saija, A; Ruggeri, R M; Trimarchi, F; Gangemi, S

    2014-02-01

    Cytokines' involvement in tumorigenesis has been hypothesized. Interleukin-22 (IL-22) is implicated in proliferative and anti-apoptotic pathways via its receptor IL-22R. Its role in pituitary adenomas has never been investigated. Twenty-seven patients with pituitary macroadenomas (PA, 21 males, mean age 53.8 ± 14.4 years) and 30 healthy controls (19 males, mean age 50.4 ± 8.4 years) were enrolled. Out of 27 PA patients, 17 had a non-functioning tumour (NFPA) and 10 a PRL-secreting adenoma (PRL-oma). Serum IL-22 levels were measured in both patients and controls. Immunohistochemical (IHC) tumoral IL-22R expression was evaluated in 10 patients with NFPA and 4 with PRL-oma. IL-22 levels were significantly higher in PA patients than in controls [32.47 (11.29-70.12) vs. 5.58 (0.19-21.46) pg/mL, p < 0.0001] but did not correlate with tumor maximum diameter and were not associated to pituitary function impairment. PRL-oma patients had significantly higher IL-22 levels than NFPA patients [37.18 (14.82-70.12) vs. 21.29 (11.29-56) pg/mL, p = 0.039]. IHC revealed a strong IL-22R staining in 100 % of PRL-omas and 60 % of NFPAs. We provide the first evidence of increased serum IL-22 levels in patients with pituitary macroadenoma, especially in PRL-omas, regardless of tumor size and/or degree of pituitary function impairment. We also demonstrated the expression of IL22R in all PRL-omas and in 60 % of NFPAs.

  6. Hyperplasia-adenoma sequence in pituitary tumorigenesis related to aryl hydrocarbon receptor interacting protein gene mutation.

    PubMed

    Villa, Chiara; Lagonigro, Maria Stefania; Magri, Flavia; Koziak, Maria; Jaffrain-Rea, Marie-Lise; Brauner, Raja; Bouligand, Jerome; Junier, Marie Pierre; Di Rocco, Federico; Sainte-Rose, Christian; Beckers, Albert; Roux, François Xavier; Daly, Adrian F; Chiovato, Luca

    2011-06-01

    Mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene are associated with pituitary adenomas that usually occur as familial isolated pituitary adenomas (FIPA). Detailed pathological and tumor genetic data on AIP mutation-related pituitary adenomas are not sufficient. Non-identical twin females presented as adolescents to the emergency department with severe progressive headache caused by large pituitary macroadenomas require emergency neurosurgery; one patient had incipient pituitary apoplexy. Post-surgically, the patients were found to have silent somatotrope adenomas on pathological examination. Furthermore, the light microscopic, immunohistochemical, and electron microscopic studies demonstrated tumors of virtually identical characteristics. The adenomas were accompanied by multiple areas of pituitary hyperplasia, which stained positively for GH, indicating somatotrope hyperplasia. Genetic analyses of the FIPA kindred revealed a novel E216X mutation of the AIP gene, which was present in both the affected patients and the unaffected father. Molecular analysis of surgical specimens revealed loss of heterozygosity (LOH) in the adenoma but showed that LOH was not present in the hyperplastic pituitary tissue from either patient. AIP immunostaining confirmed normal staining in the hyperplastic tissue and decreased staining in the adenoma in the tumors from both patients. These results demonstrate that patients with AIP germline mutation can present with silent somatotrope pituitary adenomas. The finding of somatotrope hyperplasia unaccompanied by AIP LOH suggests that LOH at the AIP locus might be a late event in a potential progression from hyperplastic to adenomatous tissue.

  7. Spontaneous pituitary adenoma occurring after resection of a Rathke's cleft cyst.

    PubMed

    Chaudhry, Nauman S; Raber, Michael R; Cote, David J; Laws, Edward R

    2016-11-01

    Rathke's cleft cysts (RCC) are benign cystic lesions that originate from remnants of the epithelial lining of Rathke's pouch. RCC are known rarely to occur together with a concomitant pituitary adenoma. Here, we report a patient with a pituitary adenoma arising in the same location as a previously-resected RCC, 3 years post-operatively, and review the literature of "collision" sellar lesions. Consecutive transsphenoidal operations from a single-center between 2008 and 2016 were reviewed to identify patients with pituitary adenoma arising after surgical resection of RCC, and a systematic search of the literature was also performed to identify such patient reports, as well as reports of concomitant pituitary adenoma and RCC. Of 837 transsphenoidal operations from our own experience, one patient with pituitary adenoma occurring after RCC resection was identified and is reported here. A systematic review of the literature resulted in identification of 34 patients with concomitant RCC and pituitary adenoma and no incidents of pituitary adenoma occurring after resection of RCC. Concomitant occurrence of RCC and pituitary adenoma was more commonly diagnosed in women (61%), at a median age of diagnosis of 44 years. The RCC histological analysis in these patients consistently described ciliated columnar or cuboidal epithelium. Although rare, the presence of a new, pathologically-distinct lesions in the sella after prior surgical treatment, is possible. During post-operative monitoring, physicians should consider that what appears as a "recurrent" lesion may actually be growth of a new and entirely different lesion.

  8. [Rol of pituitary tumour-transforming gene (PTTG) in the pituitary adenomas].

    PubMed

    Sánchez-Ortiga, Ruth; Sánchez Tejada, Laura; Peiró Cabrera, Gloria; Moreno-Pérez, Oscar; Arias Mendoza, Nieves; Aranda López, F Ignacio; Picó Alfonso, Antonio

    2010-01-01

    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.

  9. Progress in the Diagnosis and Classification of Pituitary Adenomas

    PubMed Central

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

    2015-01-01

    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. Progress in the Diagnosis and Classification of Pituitary Adenomas.

    PubMed

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

    2015-01-01

    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.

  11. Combined anterior pituitary function test using CRH, GRH, LH-RH, TRH and vasopressin in patients with non-functioning pituitary tumors.

    PubMed

    Hashimoto, K; Makino, S; Hirasawa, R; Takao, T; Kageyama, J; Ogasa, T; Ota, Z

    1990-06-01

    We examined 8 normal subjects and 16 patients with non-functioning pituitary tumors with a combined anterior pituitary test to evaluate the clinical usefulness of the test. Diagnoses included 9 of chromophobe adenoma, 3 of craniopharyngioma, 2 of Rathke's cleft cyst, and 1 each of intrasellar cyst and tuberculum sella meningioma. All subjects received hypothalamic releasing hormones: 1 micrograms/kg corticotropin releasing hormone (CRH), 1 micrograms/kg growth hormone releasing hormone (GRH), 500 micrograms thyrotropin-releasing hormone (TRH), 100 micrograms luteinizing hormone releasing hormone (LH-RH), and a relatively small dose (5 mU/kg) of lysine vasopressin (LVP). In the normal subjects, the addition of LVP potentiated the secretion of adenocorticotropic hormone (ACTH) induced by CRH, but had no significant effect on the secretion of other anterior pituitary hormones. In the combined test with 5 releasing hormones, the plasma ACTH and cortisol responses were not impaired in the majority of the patients before pituitary surgery. Serum thyroid-stimulating hormone (TSH), prolactin (PRL) and follicle-stimulating hormone (FSH) responses were not impaired in 82%, 70% and 67% of the patients, respectively, while the serum LH and GH responses were impaired in 67% and 73% of the patients, respectively. Following pituitary surgery, responses of these hormones to combined testing were similarly impaired in more than 75% of the patients. These results indicate that plasma ACTH, cortisol and serum TSH responses are fairly good before pituitary surgery but are impaired significantly after surgery. No subjects experienced any serious adverse effects related to the testing. These results suggest that combined testing with hypothalamic hormones is a convenient and useful method for evaluating pituitary function.

  12. Cushing's disease due to mixed pituitary adenoma-gangliocytoma of the posterior pituitary gland presenting with Aspergillus sp. sinus infection.

    PubMed

    Bridenstine, Mark; Kerr, Janice M; Lillehei, Kevin O; Kleinschmidt-DeMasters, Bette K

    2013-01-01

    Gangliocytic lesions of the pituitary gland producing Cushing's disease are extremely rare entities that may exist with or without a pituitary adenoma. The latter have been designated mixed pituitary adenoma-gangliocytomas, the majority of which produce growth hormone, not adrenocorticotropin (ACTH), and are localized to the anterior gland. We now report an immunocompetent woman with hypercortisolism who presented with an intranasal aspergilloma eroding the bony sellar floor. The fungal ball was contiguous with, and extended into, a large neurohypophyseal-centered mass. Transsphenoidal resection revealed a gangliocytic lesion of the posterior gland with small clusters of intimately admixed ACTH-immunoreactive adenoma cells as the cause of her Cushing's disease. Rare transitional sizes and shapes of cells coupled with immunohistochemical findings supported interpretation as advanced neuronal metaplasia within an ACTH adenoma. This mixed ACTH adenoma-gangliocytoma is the first example to present clinically with an opportunistic infection.

  13. Effects of cabergoline in a pituitary adenoma secreting follicle-stimulating hormone.

    PubMed Central

    Leese, G.; Jeffreys, R.; Vora, J.

    1997-01-01

    A patient with a pituitary adenoma secreting follicle-stimulating hormone with co-existent primary hyperaldosteronism is described. After his second transsphenoidal surgery, the patient developed a Staphylococcus aureus pituitary abscess. Symptoms improved after abscess drainage. Subsequent cabergoline therapy arrested the deterioration of symptoms. and decreased serum follicle-stimulating hormone concentrations. Cabergoline may be a useful treatment for aggressively growing non-prolactin-secreting pituitary adenomas. PMID:9307745

  14. hpttg is over-expressed in pituitary adenomas and other primary epithelial neoplasias.

    PubMed

    Sáez, C; Japón, M A; Ramos-Morales, F; Romero, F; Segura, D I; Tortolero, M; Pintor-Toro, J A

    1999-09-23

    The role of oncogenes in pituitary tumorigenesis remains elusive since few genetic changes have been identified so far in pituitary tumors. Pituitary tumor-transforming gene (pttg) has been recently cloned from rat GH4 pituitary tumor cells. We have previously isolated and characterized hpttg from human thymus. In the present study, we analyse the expression of hpttg mRNA in a series of human pituitary adenomas. We show that hpttg is highly expressed in the majority of pituitary adenomas while only very low levels of mRNA can be detected in normal pituitary gland by Northern blot analysis. hPTTG protein was immunolocalized mainly in the cytoplasm of adenoma cells. Other common extra-cranial malignant tumors were also analysed by immunohistochemistry. Interestingly, strong hPTTG immunoreactivity was detected in most adenocarcinomas of mammary and pulmonary origins.

  15. Expression of Cold-Inducible RNA-Binding Protein (CIRP) in Pituitary Adenoma and its Relationships with Tumor Recurrence

    PubMed Central

    Wang, Mingguang; Zhang, Huan; Heng, Xueyuan; Pang, Qi; Sun, Aigang

    2015-01-01

    Background The aim of this study was to detect the expression of cold-inducible RNA-binding protein in pituitary adenoma and to determine its effects on tumor recurrence. Material/Methods We collected a total of 60 post-op samples collected from pituitary adenoma patients (including 20 cases of invasive pituitary adenoma, 20 cases of non-invasive adenoma, and 20 cases of non-invasive recurrent adenoma) admitted in our hospital. Both protein and mRNA levels of CIRP in 3 types of pituitary adenoma samples were quantified by Western blotting and real-time PCR, respectively. Results Western blotting revealed significantly elevated CIRP expression levels in invasive pituitary adenoma compared to non-invasive tumors, with statistical significance (p<0.05). Recurrent pituitary adenoma expressed significantly higher CIRP levels compared to non-recurrent tumors (p<0.05). Real-time PCR for CIRP mRNA obtained consistent results: transcript levels were significantly higher in invasive pituitary adenoma compared to non-invasive adenoma (p<0.05); recurrent adenoma also had significantly higher CIRP mRNA levels compared to non-recurrent tumors (p<0.05). Among all 3 types of pituitary adenoma, recurrent tumors had the highest levels of CIRP mRNA and protein. Conclusions The expression of CIRP in pituitary adenoma is closely related with tumor proliferation and invasion, and its significantly elevated expression level indicates post-op recurrence. PMID:25934796

  16. Persistence of intrasellar trigeminal artery and simultaneous pituitary adenoma: description of two cases and their importance for the differential diagnosis of sellar lesions.

    PubMed

    Machado, Marcio Carlos; Kodaira, Sergio; Musolino, Nina Rosa Castro

    2014-08-01

    Persistent trigeminal artery (PTA) is the most frequent embryonic communication between the carotid and vertebrobasilar systems. However, hormonal changes or the association of PTA with other sellar lesions, such as pituitary adenomas, are extremely rare. The aim of the present study was to report two patients with intrasellar PTA and simultaneous pituitary adenoma in order to emphasize the importance of differential diagnoses for sellar lesions. Case 1. A female patient, 41 years old, was admitted with a history of chronic headache (> 20 years). Pituitary magnetic resonance imaging (MRI) showed a rounded lesion in the left portion of the pituitary gland suggestive of adenoma (most likely clinically non-functioning adenoma). In addition to this lesion, the MRI demonstrated ecstasy of the right internal carotid artery and imaging suggestive of an intrasellar artery that was subsequently confirmed by an angio-MRI of the cerebral vessels as PTA. Case 2. A female patient, 42 years old, was admitted with a history of amenorrhea and galactorrhea in 1994. Laboratorial investigation revealed hyperprolactinemia. Pituitary MRI showed a small hyposignal area in the anterior portion of pituitary gland suggestive of a microadenoma initiated by a dopaminergic agonist. Upon follow-up, aside from the first lesion, the MRI showed a well delineated rounded lesion inside the pituitary gland, similar to a vessel. Angio-MRI confirmed a left primitive PTA. Failure to recognize these anomalous vessels within the sella might lead to serious complications during transsphenoidal surgery. Therefore, although their occurrence is uncommon, a working knowledge of vascular lesions in the sella turcica or pituitary gland is important for the differential diagnosis of pituitary lesions, especially pituitary adenomas.

  17. Geometric survey on magnetic resonance imaging of growth hormone producing pituitary adenoma.

    PubMed

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

    2014-04-01

    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.

  18. CDK5 and Its Activator P35 in Normal Pituitary and in Pituitary Adenomas: Relationship to VEGF Expression

    PubMed Central

    Xie, Weiyan; Wang, Hongyun; He, Yue; Li, Dan; Gong, Lei; Zhang, Yazhuo

    2014-01-01

    Pituitary tumors are monoclonal adenomas that account for about 10-15% of intracranial tumors. Cyclin-dependent kinase 5 (CDK5) regulates the activities of various proteins and cellular processes in the nervous system, but its potential roles in pituitary adenomas are poorly understood. The kinase activity of CDK5 requires association with an activating protein, p35 (also known as CDK5 activator 1, p35). Here, we show that functional CDK5, associated with p35, is present in normal human pituitary and in pituitary tumors. Furthermore, p35 mRNA and protein levels were higher in pituitary adenomas than in the normal glands, suggesting that CDK5 activity might be upregulated in pituitary tumors. Inhibition of CDK5 activity in rat pituitary cells, reduced the expression of vascular endothelial growth factor (VEGF), a protein that regulates vasculogenesis and angiogenesis. Our results suggest that increased CDK5-mediated VEGF expression might play a crucial role in the development of pituitary adenomas, and that roscovitine and other CDK5 inhibitors could be useful as anticancer agents. PMID:24550687

  19. The Coexistence of Rathke Cleft Cyst and Pituitary Adenoma.

    PubMed

    Gao, Mingtong; An, Yanyan; Huang, Zhihong; Niu, Jianyi; Yuan, Xunhui; Bai, Yun'an; Guo, Liemei

    2016-03-01

    Both of Pituitary adenoma (PA) and Rathke cleft cyst (RCC) are the most common and benign sellar lesions. Generally, the origin of RCC is considered to be derived from remnants of Rathke punch, while PA is formed by proliferation of the anterior wall of Rathke pouch. Although they have a possibility to share a common embryological origin, the coexistence of PA and RCC is extremely rare. Here, the authors report a 50-year-old male patient who was found to have a large cystic sellar lesion, and surgical resection revealed components of a RCC coexisting with a PA. This collision reminded us of the possibility of RCC coexisting with PA. Furthermore, a clinicopathologic relation of them were reviewed and investigated.

  20. Immunohistochemical detection of angiotensin receptors AT1 and AT2 in normal rat pituitary gland, estrogen-induced rat pituitary tumor and human pituitary adenomas.

    PubMed

    Pawlikowski, Marek

    2006-01-01

    Male rat pituitary glands, diethylstilbestrol (DES)-induced rat pituitary tumors and 12 human pituitary adenomas were immunostained with antibodies raised against AT1 and AT2 angiotensin receptor proteins. Positive immunostaining of AT1 was observed in a subpopulation of anterior and intermediate pituitary lobe cells as well as in some nerve endings of the neurohypophysis. In the DES-induced rat pituiary tumors, the subpopulation of AT1-immunnopositive cells was smaller than in the non-tumoral anterior pituitary. In human pituitary adenomas, weak AT1 immunostaining was found in 5 tumors. In the remaining adenomas, the AT1 immunostaining was trace (doubtful) or absent. The AT1 immunostaining in the peritumoral non-neoplastic pituitary tissue was stronger than that observed in the tumors. The normal rat pituitaries and rat tumors did not show immunostaining with anti-AT2 antibody. In human pituitary adenomas, the tumoral cells were AT2- negative but moderate to strong AT2 immunostaining was observed in intratumoral blood vessel walls. The data suggest that the experimental (in rat) and spontaneous (in man) pituitary tumorigenesis is associated with the down-regulation of AT1 receptors. The expression of AT2 receptors, in turn, may be connected with the process of tumoral neo-angiogenesis.

  1. Stereotactic Irradiation of GH-Secreting Pituitary Adenomas

    PubMed Central

    Minniti, G.; Scaringi, C.; Amelio, D.; Maurizi Enrici, R.

    2012-01-01

    Radiotherapy (RT) is often employed in patients with acromegaly refractory to medical and/or surgical interventions in order to prevent tumour regrowth and normalize elevated GH and IGF-I levels. It achieves tumour control and hormone normalization up to 90% and 70% of patients at 10–15 years. Despite the excellent tumour control, conventional RT is associated with a potential risk of developing late toxicity, especially hypopituitarism, and its role in the management of patients with GH-secreting pituitary adenomas remains a matter of debate. Stereotactic techniques have been developed with the aim to deliver more localized irradiation and minimize the long-term consequences of treatment, while improving its efficacy. Stereotactic irradiation can be given in a single dose as stereotactic radiosurgery (SRS) or in multiple doses as fractionated stereotactic radiotherapy (FSRT). We have reviewed the recent published literature on stereotactic techniques for GH-secreting pituitary tumors with the aim to define the efficacy and potential adverse effects of each of these techniques. PMID:22518123

  2. Incidence of cerebral infarction after radiotherapy for pituitary adenoma

    SciTech Connect

    Flickinger, J.C.; Nelson, P.B.; Taylor, F.H.; Robinson, A.

    1989-06-15

    The incidence of cerebral infarction was studied in 156 patients irradiated for treatment of pituitary adenomas. Seven patients experienced strokes at intervals of 3.2 to 14.6 years after irradiation. The observed incidence was not significantly greater than the expected value of 3.5 strokes (P = 0.078). Six strokes occurred in patients receiving equivalent doses (ED) of 1070 ret or more (observed to expected ratio 3.87, significantly elevated; P less than 0.001). Univariate log-rank analysis showed that the risk of stroke was significantly higher (P = 0.010) in patients receiving an ED of 1070 ret or more (4180 cGy/22 fractions) than those receiving lower doses. Multivariate analysis, however, demonstrated that the increased risk of stroke was associated only with increasing age (P less than 0.0001), not ED (P = 0.148). Due to these inconsistent statistical results, no definitive conclusions could be reached about the relationship between radiation dose to the pituitary and subsequent cerebral infarction.

  3. Transsphenoidal approach for pituitary adenomas in patients with McCune-Albright syndrome.

    PubMed

    Dou, Wanchen; Di, Xiao; Wang, Renzhi; Zhu, Huijuan; Yao, Yong; Deng, Kan; Feng, Ming; Li, Guilin; Wei, Junji

    2013-06-01

    The feasibility of transsphenoidal approach under a guidance of neuronavigation was explored to remove pituitary adenomas for patients with McCune-Albright syndrome (MAS). From August, 2008 to July, 2010, there were 5 patients diagnosed with MAS associated with a pituitary adenoma in our department of Peking Union Medical College Hospital. All the patients underwent transsphenoidal surgery for the removal of pituitary adenomas with the assistant of neuronavigation and all the procedures went uneventfully. Four of the five patients have got cured radiologically by imaging and 3 of them have got cured based on endocrinological criteria. Transsphenoidal approach under the neuronavigational guidance is a safe and effective management for the MAS patients with pituitary adenomas.

  4. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms.

    PubMed

    Mooney, Michael A; Simon, Elias D; Little, Andrew S

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment.

  5. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms

    PubMed Central

    Mooney, Michael A.; Simon, Elias D.; Little, Andrew S.

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment. PMID:27517036

  6. BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas.

    PubMed

    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

    2017-02-09

    Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D2 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/D2 compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D2 expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760.

  7. BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas

    PubMed Central

    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.

    2017-01-01

    Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D2 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 (Ca2+ 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 Ca2+ concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca2+ concentration, hormone secretion/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca2+ signaling and/or hormone secretion, which was associated with the relative somatostatin/dopamine-receptors levels, especially sst5 and sst5TMD4. The chimeric sst2/sst5/D2 compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D2 expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760. PMID:28181484

  8. [AIP mutations in familial and sporadic pituitary adenomas: local experience and review of the literature].

    PubMed

    Fajardo-Montañana, Carmen; Daly, Adrian F; Riesgo-Suárez, Pedro; Gómez-Vela, José; Tichomirowa, María A; Camara-Gómez, Rosa; Beckers, Albert

    2009-01-01

    Clinically relevant pituitary adenomas occur 3-5 times more frequently than previously thought. The majority are isolated cases, but their presentation can be familial in the setting of known syndromes such as multiple endocrine neoplasia (MEN)-1 and Carney complex. When 2 or more cases of pituitary adenomas occur in the same family in the absence of the above-mentioned syndromes, a diagnosis of FIPA (familial isolated pituitary adenomas) is made, which accounts for 1-2% of all pituitary adenomas. Mutations of the gene AIP (aryl hydrocarbon receptor-interacting protein) may account for 15% of FIPA families (50% of familial acromegaly), and as such the genetic causes continue to be studied. Also mutations in AIP can be detected in sporadic adenomas among young populations (< 30 years of age). We describe the characteristics of FIPA, detailing the study of a spanish family, in this case AIP mutation negative. Also, the reported findings in sporadic adenomas in the young population are detailed, accompanied by the description of a 19- year old patient with an intronic AIP mutation. Multicenter studies have provided understanding of aspects such as mutations in AIP; however, further studies are necessary to identify other genes involved in FIPA and sporadic pituitary adenomas occurring at a young age.

  9. Different imaging characteristics of concurrent pituitary adenomas in a patient with Cushing’s disease

    PubMed Central

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

    2015-01-01

    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 5 mm hypoenhancing region typical for a pituitary adenoma was identified on the left. However, after surgical resection the patient remained hypercortisolemic and pathology revealed a nonfunctional adenoma. At early repeat surgical exploration a 10 mm 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. PMID:25827866

  10. Epistaxis and pituitary apoplexy due to ruptured internal carotid artery aneurysm embedded within pituitary adenoma

    PubMed Central

    Peng, Zesheng; Tian, Daofeng; Wang, Hongliu; Kong, Derek Kai; Zhang, Shenqi; Liu, Baohui; Deng, Gang; Xu, Zhou; Wu, Liquan; Ji, Baowei; Wang, Long; Cai, Qiang; Li, Mingchang; Wang, Junmin; Zhang, Aimin; Chen, Qianxue

    2015-01-01

    Epistaxis due to ruptured internal carotid artery (ICA) aneurysm embedded within a pituitary adenoma (PA) has seldom been reported in the literature. Here we want to elaborate the incidence, mechanisms, clinical manifestations, and treatment strategy for this condition. The first survived case of a patient with epistaxis and pituitary apoplexy due to ruptured aneurysm embedded within PA was reported and the literature was reviewed. A 53-year-old male patient presented to our institution with sudden onset epistaxis and progressive vision loss. Neurological examination revealed bilateral ptosis and dilated unresponsive pupils. A CT scan showed a large mass in the pituitary fossa with bony erosion. MRI revealed a large pituitary tumor and abnormal signal intensity in the tumor. No aneurysm was noted during the pre-operative MR angiography. Abundant arterial bleeding suddenly occurred during urgent transsphenoidal surgery. Digital subtraction angiography confirmed the presence of a 14 mm unexpected saccular aneurysm of right ICA in the cavernous sinus with the dome protruding into the sella turcica. Balloon test occlusion of the right ICA was undertaken and permanent occlusion was performed. The patient recovered well and received bromocriptine and thyroid hormone replacement therapy during the follow-up period. At 14-month followup, the patient had no neurological deficits, no features of ischaemia relating to the right ICA therapeutic occlusion. Our case indicated that epistaxis and pituitary apoplexy could be due to the rupture of an ICA aneurysm embedded in a PA. Clinical suspicion should remain high when evaluating any case of epistaxis and pituitary apoplexy. Optimal treatment should take into consideration individual features of the tumor, aneurysm, and patient. Making the correct diagnosis as well as identifying an appropriate management strategy is critical in the care of such patients. PMID:26823732

  11. Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations

    PubMed Central

    Georgitsi, Marianthi; Raitila, Anniina; Karhu, Auli; Tuppurainen, Karoliina; Mäkinen, Markus J.; Vierimaa, Outi; Paschke, Ralf; Saeger, Wolfgang; van der Luijt, Rob B.; Sane, Timo; Robledo, Mercedes; De Menis, Ernesto; Weil, Robert J.; Wasik, Anna; Zielinski, Grzegorz; Lucewicz, Olga; Lubinski, Jan; Launonen, Virpi; Vahteristo, Pia; Aaltonen, Lauri A.

    2007-01-01

    Pituitary adenomas are common neoplasms of the anterior pituitary gland. Germ-line mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene cause pituitary adenoma predisposition (PAP), a recent discovery based on genetic studies in Northern Finland. In this population, a founder mutation explained a significant proportion of all acromegaly cases. Typically, PAP patients were of a young age at diagnosis but did not display a strong family history of pituitary adenomas. To evaluate the role of AIP in pituitary adenoma susceptibility in other populations and to gain insight into patient selection for molecular screening of the condition, we investigated the possible contribution of AIP mutations in pituitary tumorigenesis in patients from Europe and the United States. A total of 460 patients were investigated by AIP sequencing: young acromegaly patients, unselected acromegaly patients, unselected pituitary adenoma patients, and endocrine neoplasia-predisposition patients who were negative for MEN1 mutations. Nine AIP mutations were identified. Because many of the patients displayed no family history of pituitary adenomas, detection of the condition appears challenging. Feasibility of AIP immunohistochemistry (IHC) as a prescreening tool was tested in 50 adenomas: 12 AIP mutation-positive versus 38 mutation-negative pituitary tumors. AIP IHC staining levels proved to be a useful predictor of AIP status, with 75% sensitivity and 95% specificity for germ-line mutations. AIP contributes to PAP in all studied populations. AIP IHC, followed by genetic counseling and possible AIP mutation analysis in IHC-negative cases, a procedure similar to the diagnostics of the Lynch syndrome, appears feasible in identification of PAP. PMID:17360484

  12. MALDI mass spectrometry imaging analysis of pituitary adenomas for near-real-time tumor delineation

    PubMed Central

    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.

    2015-01-01

    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

  13. Successful Management of a Giant Pituitary Lactosomatotroph Adenoma Only with Cabergoline

    PubMed Central

    Bozkirli, Emre; Bakiner, Okan; Ersozlu Bozkirli, Emine Duygu; Ertorer, Eda; Bascil Tutuncu, Neslihan; Guvener Demirag, Nilgun

    2013-01-01

    Although advances in endocrinologic and neuroradiologic research allow easier recognition of pituitary adenomas, giant pituitary tumours are relatively rare. In the literature, the term “giant” is generally used when a pituitary tumour becomes larger than 4 cm in diameter. Cabergoline is a potent and long-acting inhibitor of prolactin secretion, which exhibits high specificity and affinity for dopamine D2 receptor. Herein, we report a 46-year-old woman with a giant lactosomatotroph pituitary adenoma, sized 6 × 5 × 5.5 cm, who is treated successfully only with cabergoline. The patient showed dramatic response to cabergoline treatment by means of clinical, biochemical and radiological imaging findings. Cabergoline seems to be safe and effective in the treatment of prolactin and growth hormone cosecreting pituitary adenomas as well as prolactinomas. However, surgical or more aggressive approach must be considered where indicated. PMID:23762662

  14. [Somatotropic pituitary adenoma with lesions of the oculomotor nerve in a cat].

    PubMed

    Allgoewer, I; Grevel, V; Philipp, K; Schmidt, P; Brunnberg, L

    1998-07-01

    A case of a 6.5-year-old castrated male European Shorthair Cat with an unilateral lesion of the oculomotor nerve is described. Nuclear magnetic resonance imaging revealed a mass in the area of the pituitary gland which could be identified as a somatotrope adenoma by immunochemistry. Unlike the feline somatotrope adenoma cases described in the literature this cat showed clinically no acromegalic features or hyperglycemia. An oculomotor nerve lesion in conjunction with a feline somatotropic pituitary adenoma has also not been described before.

  15. In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features.

    PubMed

    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

    2015-03-04

    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.

  16. In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features

    PubMed Central

    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.

    2015-01-01

    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

  17. Rapid Reticulin Fiber Staining Method is Helpful for the Diagnosis of Pituitary Adenoma in Frozen Section.

    PubMed

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

    2015-05-01

    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.

  18. Sphenoid sinus ectopic pituitary adenomas: CT and MRI findings

    PubMed Central

    Yang, B T; Chong, V F H; Wang, Z C; Xian, J F; Chen, Q H

    2010-01-01

    Ectopic pituitary adenomas (EPAs) are rare lesions. The purpose of this study was to describe the CT and MRI features of sphenoid sinus EPAs. Eight patients with histology-proven EPAs in the sphenoid sinus, all of whom underwent CT and MRI, were reviewed retrospectively. The following imaging features were analysed: (i) size, (ii) margin, (iii) CT attenuation characteristics and (iv) MRI signal intensity. In addition, the involvement of adjacent structures and the time–intensity curve (TIC) of dynamic contrast-enhanced (DCE) MRI were analysed. All EPAs had well-defined margins and showed no relationship to the intrasellar pituitary gland. The mean size was 28 mm (range, 20–46 mm). On non-enhanced CT, the lesions appeared isodense to grey matter in 7 (88%) patients and hypodense in 1 (12%) patient. Only two patients underwent post-contrast CT, and they showed moderate enhancement. On T1 weighted images, EPAs appeared isointense in 6 (75%) patients and hypointense in 2 (25%). On T2 weighted images, the lesions appeared hyperintense in 2 (25%) patients and isointense in 6 (75%). EPAs showed mild to moderate heterogeneous contrast enhancement and exhibited a cribriform-like appearance. Two patients underwent DCE MRI; the TIC showed a rapidly enhancing and slow washout pattern. The following features were also seen: an empty sella, bone changes and involvement of the cavernous sinus (5 patients; 62.5%). In conclusion, a high index of suspicion for EPA and a familiarity with the imaging findings may help to diagnose this rare entity accurately. PMID:19651706

  19. Differentiation of human pituitary adenomas determines the pattern of chromogranin/secretogranin messenger ribonucleic acid expression.

    PubMed

    Jin, L; Chandler, W F; Smart, J B; England, B G; Lloyd, R V

    1993-03-01

    The distribution of chromogranin/secretogranin (Cg/Sg) mRNAs, determined by Northern and in situ hybridization, was analyzed in 14 cultured pituitary adenomas characterized by immunohistochemistry and hormone secretion in a defined medium in vitro. There were 5 functional GH adenomas, 1 silent GH adenoma, 7 null cell adenomas, and 1 oncocytoma. The null cell adenomas, oncocytoma, and silent GH adenomas were also analyzed by electron microscopy. Most null cell adenomas and the oncocytoma secreted FSH and LH into the culture medium. GH adenomas, which are examples of well differentiated tumors based on morphological examination, expressed significantly more SgIII mRNA compared to the null cell adenomas and oncocytoma (70 +/- 6% vs. 22 +/- 5%; P < 0.001). GH adenomas also expressed significantly less CgA mRNA compared to the less well differentiated null cell adenomas and oncocytoma (27 +/- 6% vs. 67 +/- 4%; P < 0.001), which could be considered less well differentiated based on ultrastructural morphological features. After treatment with phorbol 12-myristate 13-acetate (10(-7) M) for 7 days, there was an increase in the mRNA for CgB and SgII mRNAs in GH and null cell tumors, while dexamethasone treatment for 7 days increased CgA mRNA in GH and null cell adenomas. GnRH treatment for 7 days increased CgB mRNA in null cell adenomas. Phorbol 12-myristate 13-acetate also decreased the percentage of immunoreactive GH cells and GHm RNA, determined by in situ and Northern hybridization analyses. These results indicate that pituitary adenomas have a distinct pattern of Cg/Sg mRNA expression, which appears to be related to the degree of morphological differentiation of these neoplasms, and suggest that the effects of secretagogues on various Cg/Sg mRNA levels may be related to the stimulation of hormone secretion.

  20. Thyrotoxic periodic paralysis as the first manifestation of a thyrotropin-secreting pituitary adenoma.

    PubMed

    Pappa, Theodora; Papanastasiou, Labrini; Markou, Athina; Androulakis, Ioannis; Kontogeorgos, George; Seretis, Andreas; Piaditis, George

    2010-01-01

    Thyrotoxic Periodic Paralysis (TPP) is a rare manifestation of hyperthyroidism characterized by muscle weakness and hypokalemia. Thyroid-Stimulating Hormone (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism. Even more rare is the occurrence of TPP as the first manifestation of a TSH-secreting pituitary adenoma. We report a 31-year-old Asian male patient suffering from TPP caused by a TSH-secreting adenoma, who was evaluated for persistent episodes of muscle paralysis. Laboratory investigation revealed hypokalemia as well as elevated levels of both thyroid hormones and TSH. The Magnetic Resonance Imaging (MRI) of the pituitary gland revealed a microadenoma, thus suggesting the presence of a TSH-secreting adenoma. The patient underwent transphenoidal resection and the pathological investigation confirmed the diagnosis of TSH-secreting pituitary adenoma. After the adenomectomy and the restoration of euthyroidism, the patient did not experience any episode of hypokalemic paralysis or weakness. Despite its rarity, TSH-secreting pituitary adenoma should be included in the differential diagnosis of TPP.

  1. Human pituitary adenomas show no loss of heterozygosity at the retinoblastoma gene locus

    SciTech Connect

    Zhu, J.; Leon, S.P.; Beggs, A.H.; Busque, L.; Gilliland, D.G.; Black, P.M.

    1994-04-01

    The retinoblastoma tumor suppressor gene (RB1) is inactivated in hereditary and sporadic forms of retinoblastoma as well as in a number of other sporadic tumors. The majority of human pituitary tumors have been shown to be monoclonal neoplasms, suggesting that 1 or more somatic mutations are involved in the clonal expansion of a single progenitor cell. Recently, a high percentage of transgenic mice containing a disrupted RB1 allele have been shown to develop pituitary tumors. To investigate whether RB1 inactivation contributes to the development of human pituitary adenomas, the authors searched for loss of heterozygosity (LOH) within the RB1 gene locus in a variety of human pituitary adenomas. They screened 34 adenomas for LOH using a polymerase chain reaction (PCR)-based microsatellite polymorphic marker at the RB1 gene locus. In addition, a variable number of tandem repeat markers from within the RB1 gene was also used to search for LOH in 14 tumors. They found no LOH or microsatellite instability at the RB1 locus in any of the informative cases (30 of 34). Additionally, they showed that 4 representative adenomas from female patients are monoclonal in origin using a PCR-based clonality analysis assay. They conclude that the RB1 gene shows no LOH in a variety of human pituitary adenomas and that PCR-based microsatellite markers can serve as a useful tool for LOH analysis in human pituitary tumors. 42 refs., 3 figs., 1 tab.

  2. Metalloproteinases ADAM12 and MMP-14 are associated with cavernous sinus invasion in pituitary adenomas.

    PubMed

    Wang, Junwen; Voellger, Benjamin; Benzel, Julia; Schlomann, Uwe; Nimsky, Christopher; Bartsch, Jörg W; Carl, Barbara

    2016-09-15

    Invasion of tumor cells critically depends on cell-cell or cell-extracellular matrix interactions. Enzymes capable of modulating these interactions belong to the proteinase families of ADAM (a disintegrin and metalloprotease) and MMP (matrix metalloprotease) proteins. Our objective is to examine their expression levels and evaluate the relationship between expression levels and cavernous sinus invasion in pituitary adenomas. Tissue samples from 35 patients with pituitary adenomas were analyzed. Quantitative real-time polymerase chain reaction (qPCR) was employed to assess mRNA expression levels for ADAM and MMP genes. Protein levels were examined using immunohistochemistry and Western Blot. Correlation analyses between expression levels and clinical parameters were performed. By silencing ADAM12 and MMP-14 with siRNA in a mouse pituitary adenoma cell line (TtT/GF), their cellular effects were investigated. In our study, nine women and 26 men were included, with a mean age of 53.1 years (range 15-84 years) at the time of surgery. There were 19 cases with cavernous sinus invasion. The proteins ADAM12 and MMP-14 were significantly up-regulated in invasive adenomas compared to noninvasive adenomas. Both human isoforms of ADAM12 (ADAM12L and ADAM12s) were involved in tumor invasion; moreover, ADAM12L was found to correlate positively with Ki-67 proliferation index in pituitary adenomas. In TtT/GF pituitary adenoma cells, silencing of ADAM12 and MMP-14 significantly inhibited cell invasion and migration, respectively, whereas only silencing of ADAM12 suppressed cell proliferation. We conclude that ADAM12 and MMP-14 are associated with cavernous sinus invasion in pituitary adenomas, which qualifies these proteins in diagnosis and therapy.

  3. Somatostatin and dopamine receptor regulation of pituitary somatotroph adenomas.

    PubMed

    Ben-Shlomo, Anat; Liu, Ning-Ai; Melmed, Shlomo

    2017-02-01

    Somatostatin and dopamine receptors are expressed in normal and tumoral somatotroph cells. Upon receptor stimulation, somatostatin and the somatostatin receptor ligands octreotide, lanreotide, and pasireotide, and to a lesser extent, dopamine and the dopamine analogs bromocriptine and cabergoline, suppress growth hormone (GH) secretion from a GH-secreting pituitary somatotroph adenoma. Somatostatin and dopamine receptors are Gαi-protein coupled that inhibit adenylate cyclase activity and cAMP production and reduce intracellular calcium concentration and calcium flux oscillations. Although their main action on somatotroph cells is acute inhibition of GH secretion, they also may inhibit GH production and possibly somatotroph proliferation. These receptors have been reported to create complexes that exhibit functions distinct from that of receptor monomers. Somatostatin suppression of GH is mediated mainly by somatostatin receptor subtype 2 and to a lesser extent by SST5. Human somatostatin receptor subtype 5 has also been shown to harbor mutations associated with GH levels, somatotroph tumor behavior, and somatostatin receptor ligand (SRL) responsiveness. Reviewing current knowledge of somatostatin and dopamine receptor expression and signaling in normal and tumoral somatotroph cells offers insights into mechanisms underlying SRL and dopamine agonist effectiveness in patients with acromegaly.

  4. Imaging of Resected Nonfunctioning Pituitary Adenomas: The Cost of Surveillance

    PubMed Central

    Kistka, Heather M.; Kasl, Rebecca A.; Nayeri, Arash; Utz, Andrea L.; Weaver, Kyle D.; Chambless, Lola B.

    2015-01-01

    Objectives To determine the cost of annual magnetic resonance imaging (MRI) surveillance after resection of nonfunctioning pituitary adenomas (NFPAs) and its effectiveness in reducing visual compromise due to tumor recurrence. Design Retrospective case series. Setting Vanderbilt University Medical Center (2003–2011). Participants A total of 120 patients underwent primary transsphenoidal resection and surveillance of NFPAs between 2003 and 2011. Main Outcome Measures Time from initial surgery to most recent imaging or progression. Surveillance MRI costs according to Centers for Medicare and Medicaid database and visual field deficits. Results Patients received 382 surveillance scans at a total cost of $218,477.30. The median follow-up was 47 months (interquartile range [IQR]: 26–76), and the median interval between scans was 357 days (IQR: 225–434). Overall, 50 scans (13%) revealed tumor growth. The cost per scan revealing growth was $4,369.55. The cost to identify 19 patients (16%) with clinically significant growth was $11,498.80 per patient. A total of 5 of 19 patients (26%) experienced new visual deficits prior to intervention. Patients with visual decline tended to have longer scan intervals than those with preserved vision (mean: 239 versus 794 days; p = 0.0584). No patient with annual surveillance imaging experienced visual decline. Conclusions Annual MRI scans are a sensitive and cost-conscious method to identify NFPA recurrence prior to visual decline. PMID:26401475

  5. Non-functioning parathyroid adenoma: a rare differential diagnosis for vocal-cord paralysis

    PubMed Central

    Kamali, D; Sharpe, A; Nagarajan, S; Elsaify, W

    2016-01-01

    Introduction Adenomas of the parathyroid gland typically present with symptoms of hyperparathyroidism, manifested by fatigue, bone pain, abdominal pain, weakness, dyspepsia, nephrolithiasis and skeletal bone disease. Here, we describe, for the first time, a case of a non-functioning benign tumour of the parathyroid gland presenting as vocal-cord paralysis. Case History A 49-year-old male presented with a 10-week history of dysphonia and the feeling of having ‘something stuck in my throat’. History-taking elicited no other associated symptoms. Flexible nasal endoscopy demonstrated paralysis of the left vocal cord. Computed tomography of the neck revealed a cystic lesion, 18mm in diameter adjacent to the oesophagus. After more rigorous tests, a neck exploration, left hemithyroidectomy, excision of the left paratracheal mass and level-VI neck dissection was undertaken, without incident to the patient or surgical team. Histology was consistent with a parathyroid adenoma. Conclusions This case emphasises the importance of including adenomatous disease of the parathyroid gland in the differential diagnosis despite normal parathyroid status as a cause of vocal cord palsy. PMID:27055408

  6. LRRC4 haplotypes are associated with pituitary adenoma in a Chinese population.

    PubMed

    Xiao, Lan; Tu, Chaofeng; Chen, Shuai; Yu, Zhibin; Lei, Qianqian; Wang, Zeyou; Xu, Gang; Wu, Minghua; Li, Guiyuan

    2014-04-01

    Pituitary adenoma results from accumulation of multiple genetic and/or epigenetic aberrations such as GNAS, MEN1, CNC, and FIPA. LRRC4 is relatively tissue-specific expressed gene in the normal brain and downregulated expression in glioma (87.5%), meningioma (80.9%), and pituitary adenoma (85.5%). It has been suggested that the aberrant expression of LRRC4 contributes to tumorigenesis in glioma. However, little is known yet about association between LRRC4 and risk of pituitary adenoma. In this study, we genotyped three LRRC4 haplotype-tagging SNPs (htSNP) by direct sequencing in case-control studies, which included 183 Han Chinese patients diagnosed with pituitary adenoma and 183 age-, gender-matched, and geographically matched Han Chinese controls. Haplotypes were reconstructed according to the genotyping data and linkage disequilibrium status of the htSNP. We observed statistically significant differences regarding the genotype TT + CT of rs6944446 in the NCA. Haplotype AC of rs3823994-rs6944446 is suggested to have a protective effect in the development of pituitary adenoma (OR 0.339; 95% CI 0.123-0.934). However, haplotype GT of rs3808058-rs6944446 (OR 1.575; 95% CI 1.048-2.368) and AGT of rs3823994-rs6944446-rs3808058 (OR 1.673; 95% CI 1.056-2.651) might be a risk factor for pituitary adenoma development. In a brief, the results support the hypothesis that polymorphisms or haplotypes in the LRRC4 may have important research significance and could be used to predict the risk of pituitary adenoma.

  7. Angiogenesis in Pituitary Adenomas: Human Studies and New Mutant Mouse Models

    PubMed Central

    Cristina, Carolina; Demarchi, Gianina; Lopez Vicchi, Felicitas; Perez Millan, Maria Ines; Perrone, Sofia; Ornstein, Ana Maria; Berner, Silvia Inés; Becu-Villalobos, Damasia

    2014-01-01

    The role of angiogenesis in pituitary tumor development has been questioned, as pituitary tumors have been usually found to be less vascularized than the normal pituitary tissue. Nevertheless, a significantly higher degree of vasculature has been shown in invasive or macropituitary prolactinomas when compared to noninvasive and microprolactinomas. Many growth factors and their receptors are involved in pituitary tumor development. For example, VEGF, FGF-2, FGFR1, and PTTG, which give a particular vascular phenotype, are modified in human and experimental pituitary adenomas of different histotypes. In particular, vascular endothelial growth factor, VEGF, the central mediator of angiogenesis in endocrine glands, was encountered in experimental and human pituitary tumors at different levels of expression and, in particular, was higher in dopamine agonist resistant prolactinomas. Furthermore, several anti-VEGF techniques lowered tumor burden in human and experimental pituitary adenomas. Therefore, even though the role of angiogenesis in pituitary adenomas is contentious, VEGF, making permeable pituitary endothelia, might contribute to adequate temporal vascular supply and mechanisms other than endothelial cell proliferation. The study of angiogenic factor expression in aggressive prolactinomas with resistance to dopamine agonists will yield important data in the search of therapeutical alternatives. PMID:25505910

  8. Angiogenesis in pituitary adenomas: human studies and new mutant mouse models.

    PubMed

    Cristina, Carolina; Luque, Guillermina María; Demarchi, Gianina; Lopez Vicchi, Felicitas; Zubeldia-Brenner, Lautaro; Perez Millan, Maria Ines; Perrone, Sofia; Ornstein, Ana Maria; Lacau-Mengido, Isabel M; Berner, Silvia Inés; Becu-Villalobos, Damasia

    2014-01-01

    The role of angiogenesis in pituitary tumor development has been questioned, as pituitary tumors have been usually found to be less vascularized than the normal pituitary tissue. Nevertheless, a significantly higher degree of vasculature has been shown in invasive or macropituitary prolactinomas when compared to noninvasive and microprolactinomas. Many growth factors and their receptors are involved in pituitary tumor development. For example, VEGF, FGF-2, FGFR1, and PTTG, which give a particular vascular phenotype, are modified in human and experimental pituitary adenomas of different histotypes. In particular, vascular endothelial growth factor, VEGF, the central mediator of angiogenesis in endocrine glands, was encountered in experimental and human pituitary tumors at different levels of expression and, in particular, was higher in dopamine agonist resistant prolactinomas. Furthermore, several anti-VEGF techniques lowered tumor burden in human and experimental pituitary adenomas. Therefore, even though the role of angiogenesis in pituitary adenomas is contentious, VEGF, making permeable pituitary endothelia, might contribute to adequate temporal vascular supply and mechanisms other than endothelial cell proliferation. The study of angiogenic factor expression in aggressive prolactinomas with resistance to dopamine agonists will yield important data in the search of therapeutical alternatives.

  9. ICA Occlusion by an ACTH-secreting pituitary adenoma post-TSS and irradiation

    PubMed Central

    El-Zammar, Diala; Akagami, Ryojo

    2011-01-01

    Occlusion of intracranial arteries by a pituitary adenoma with ensuing infarction is a rare occurrence. In this case study, we show the instance of a pituitary macroadenoma and apoplexy causing mechanical obstruction of the internal carotid artery with consequent infarction following transphenoidal surgery (TSS) and radiation therapy in a patient with Cushing's disease. We report a 44-year-old woman presented with amenorrhea and headaches. Necessary investigations, resection by TSS, and microscopic examination revealed an adenocorticotropin (ACTH)-secreting pituitary macroadenoma. The pituitary tumour recurred in subsequent years, resulting in the development of Cushing's disease and syndrome. Despite two more transphenoidal surgeries, radiotherapy, and medical suppressive therapy, the pituitary adenoma continued to enlarge, and the hypercortisolemia and Cushingoid symptoms persisted. A craniotomy was arranged as the next step in the treatment strategy. Only hours prior to the scheduled surgery, the patient developed left-sided hemiplegia, was diagnosed with acute occlusion of the right ICA and underwent an emergency bifrontal craniotomy with evacuation of the tumour and decompression. Pathological examination revealed evidence of apoplexy in the ACTH-secreting pituitary adenoma. This case demonstrates the vast scope of complications that can arise from pituitary adenomas despite combination therapy and forewarns clinicians to be prepared to manage these infrequent but conceivable occurrences. PMID:22399870

  10. Acromegaly in a patient with normal pituitary gland and somatotropic adenoma located in the sphenoid sinus.

    PubMed

    Kurowska, Maria; Tarach, Jerzy S; Zgliczyński, Wojciech; Malicka, Joanna; Zieliński, Grzegorz; Janczarek, Marzena

    2008-01-01

    Ectopic acromegaly is a very rare clinical entity occurring in less than 1% of acromegalic patients. In most cases it is caused by GHRH or rarely GH-secreting neoplasms. Even rarer are ectopic pituitary adenomas located in the sphenoid sinus or nasopharynx that originate from pituitary remnants in the craniopharyngeal duct. This dissertation presents the difficulties in visualizing GH-secreting adenoma located in the sphenoid sinus. A 55-year-old man had somatic features of acromegaly for several years. MRI imaging revealed a slightly asymmetric pituitary gland (14 yen 4 mm) without focal lesions. Simultaneously, a spherical mass, 10 mm in diameter, corresponding with ectopic microadenoma was demonstrated on the upper wall of the sphenoid sinus. The serum GH level was 4.3 mg/l, IGF-1 = 615 mg/l, and a lack of GH suppression with oral glucose was proven. After preliminary treatment with a long-acting somatostatin analogue, transsphenoidal pituitary tumour removal was performed. Histopathological, electron microscopical and immunohistochemical analysis revealed densely granulated somatotropic pituitary adenoma: GH(+), PRL(-), ACTH(-), TSH(-), FSH(-), LH(-), MIB1 < 1%, SSTR3(+) and SSTR5(+). Post-surgical evaluation showed normal pituitary MRI scans, GH and IGF-1 levels 0.18 mug/l and 140 mg/l, respectively, as well as normal GH suppression with oral glucose. The careful analysis of possible pituitary embryonic malformations points out their significance for proper localization of extrapituitary adenomas.

  11. STAT3 upregulation in pituitary somatotroph adenomas induces growth hormone hypersecretion.

    PubMed

    Zhou, Cuiqi; Jiao, Yonghui; Wang, Renzhi; Ren, Song-Guang; Wawrowsky, Kolja; Melmed, Shlomo

    2015-04-01

    Pituitary somatotroph adenomas result in dysregulated growth hormone (GH) hypersecretion and acromegaly; however, regulatory mechanisms that promote GH hypersecretion remain elusive. Here, we provide evidence that STAT3 directly induces somatotroph tumor cell GH. Evaluation of pituitary tumors revealed that STAT3 expression was enhanced in human GH-secreting adenomas compared with that in nonsecreting pituitary tumors. Moreover, STAT3 and GH expression were concordant in a somatotroph adenoma tissue array. Promoter and expression analysis in a GH-secreting rat cell line (GH3) revealed that STAT3 specifically binds the Gh promoter and induces transcription. Stable expression of STAT3 in GH3 cells induced expression of endogenous GH, and expression of a constitutively active STAT3 further enhanced GH production. Conversely, expression of dominant-negative STAT3 abrogated GH expression. In primary human somatotroph adenoma-derived cell cultures, STAT3 suppression with the specific inhibitor S3I-201 attenuated GH transcription and reduced GH secretion in the majority of derivative cultures. In addition, S3I-201 attenuated somatotroph tumor growth and GH secretion in a rat xenograft model. GH induced STAT3 phosphorylation and nuclear translocation, indicating a positive feedback loop between STAT3 and GH in somatotroph tumor cells. Together, these results indicate that adenoma GH hypersecretion is the result of STAT3-dependent GH induction, which in turn promotes STAT3 expression, and suggest STAT3 as a potential therapeutic target for pituitary somatotroph adenomas.

  12. Segmentation of pituitary adenoma: a graph-based method vs. a balloon inflation method.

    PubMed

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

    2013-06-01

    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.

  13. Thyrotropin-secreting pituitary adenomas: biological and molecular features, diagnosis and therapy.

    PubMed

    Losa, M; Fortunato, M; Molteni, L; Peretti, E; Mortini, P

    2008-12-01

    Central hyperthyroidism due to a thyrotropin (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism, representing 0.5-1.0% of all pituitary adenomas. The etiopathogenesis of TSH-secreting-adenomas is unknown and no definite role for various oncogenes has been proven. Patients with TSH-secreting adenoma usually present with signs and symptoms of hyperthyroidism milder than those in patients with hyperthyroidism of thyroid origin, in addition to symptoms secondary to mass effects of the pituitary tumour. Mixed pituitary tumours co-secrete growth hormone and prolactin. The characteristic biochemical abnormalities are normal or high serum TSH concentrations in the presence of elevated total and/or free thyroid hormones concentrations. Measurement of markers of peripheral thyroid hormone action and dynamic tests may aid in the differential diagnosis with the syndrome of resistance to thyroid hormone. Neuroimaging is fundamental to visualize the pituitary tumor. Therapy of TSH-secreting adenomas can be accomplished by surgery, radiation therapies, and medical treatment with somatostatin analogs or dopamine agonists. Nowadays, and in contrast with the first reports on this rare disease, most patients are well controlled by current therapies.

  14. Relationship between RSUME and HIF-1α/VEGF-A with invasion of pituitary adenoma.

    PubMed

    He, Wei; Huang, Ling; Shen, Xiaoli; Yang, Yanlin; Wang, Dapeng; Yang, Yue; Zhu, Xingen

    2017-03-01

    The RWD-containing sumoylation enhancer (RSUME) can stabilize hypoxia-inducible factor-1α (HIF-1α) which promotes vascular endothelial growth factor-A (VEGF-A) expression. RSUME plays an important role in promoting the invasion of pituitary adenoma. In this study, we compared the mRNA and protein levels of RSUME, HIF-1α, and VEGF-A in pituitary adenoma tissue and analyzed the correlation. We found that the expression levels of RSUME, HIF-1α, and VEGF-A in invasive pituitary adenoma were significantly higher than in noninvasive pituitary adenoma. Moreover, a positive correlation was found between RSUME and HIF-1α/VEGF pathways. RSUME and HIF-1α were treated with hypoxia-mimicking CoCl2 and transfected into AtT-20 and GT1.1 cell lines to determine the relationship between them. It was found that RSUME effects post-transcriptional expression of HIF-1α regulated VEGF-A secretion. Reducing RSUME expression using siRNA transfection resulted in a decrease of the invasion inhibition rate of AtT-20 cells, as determined using Transwell and MTT assays. Together, we found that RSUME silencing can inhibit the invasion of pituitary adenoma cells.

  15. [Primary Pituitary Malignant Lymphoma that was Difficult to Differentiate from Nonfunctioning Pituitary Adenoma:A Case Report].

    PubMed

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

    2016-09-01

    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.

  16. Expression and mutation analysis of Tpit in the canine pituitary gland and corticotroph adenomas.

    PubMed

    Hanson, J M; Mol, J A; Leegwater, P A J; Bilodeau, S; Drouin, J; Meij, B P

    2008-04-01

    Pituitary-dependent hyperadrenocorticism (PDH) in dogs is caused by a pituitary corticotroph adenoma. Although PDH is a common disorder in dogs, little is known about the underlying pathogenesis. In the pituitary glands of humans and mice, the pro-opiomelanocortin (POMC)-expressing cell lineages, the corticotrophs and melanotrophs, have a specific marker in common, the T-box transcription factor Tpit (Tbx19), which is obligate for POMC expression. Tpit also regulates the late differentiation of the corticotrophs and melanotrophs, and therefore may contribute to the pathogenesis of the corticotroph adenomas. The aim of this study was to perform an expression and mutation analysis of Tpit in the normal canine pituitary and in corticotroph adenomas. The distribution of the Tpit protein in the pituitary gland was studied with immunohistochemistry and the expression of the gene with RT-PCR. The coding region of Tpit cDNA from 14 dogs with PDH was screened for mutations. Tpit was expressed in corticotroph and melanotroph cells of the normal and adenomatous canine pituitary, and remained present in non-adenomatous corticotrophs of pituitaries from PDH dogs. No tumor-specific mutation in the Tpit cDNA from the corticotroph adenomas was found. However, a missense polymorphism in the highly conserved DNA-binding domain, the T-box, was discovered in one dog. It is concluded that Tpit can be used as a reliable marker for the corticotroph and melanotroph cells in the canine pituitary tissue and that mutations in the Tpit gene are unlikely to play a major role in the pathogenesis of canine corticotroph adenomas.

  17. Gamma Knife radiosurgery in pituitary adenomas: Why, who, and how to treat?

    PubMed

    Castinetti, Frederic; Brue, Thierry

    2010-08-01

    Pituitary adenomas are benign tumors that can be either secreting (acromegaly, Cushing's disease, prolactinomas) or non-secreting. Transsphenoidal neurosurgery is the gold standard treatment; however, it is not always effective. Gamma Knife radiosurgery is a specific modality of stereotactic radiosurgery, a precise radiation technique. Several studies reported the efficacy and low risk of adverse effects induced by this technique: in secreting pituitary adenomas, hypersecretion is controlled in about 50% of cases and tumor volume is stabilized or decreased in 80-90% of cases, making Gamma Knife a valuable adjunctive or first-line treatment. As hormone levels decrease progressively, the main drawback is the longer time to remission (12-60 months), requiring an additional treatment during this period. Hypopituitarism is the main side effect, observed in 20-40% cases. Gamma Knife is thus useful in the therapeutic algorithms of pituitary adenomas in well-defined indications, mainly low secreting small lesions well identified on magnetic resonance imaging (MRI).

  18. Immunohistochemical Expression of p16 and p21 in Pituitary Tissue Adjacent to Pituitary Adenoma versus Pituitary Tissue Obtained at Autopsy: Is There a Difference?

    PubMed

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

    2015-05-01

    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.

  19. Lack of Ubiquitin Specific Protease 8 (USP8) Mutations in Canine Corticotroph Pituitary Adenomas

    PubMed Central

    Sbiera, Silviu; Tryfonidou, Marianna A.; Weigand, Isabel; Grinwis, Guy C. M.; Broeckx, Bart; Herterich, Sabine; Allolio, Bruno; Deutschbein, Timo

    2016-01-01

    Purpose Cushing’s disease (CD), also known as pituitary-dependent hyperadrenocorticism, is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary tumours. Affected humans and dogs have similar clinical manifestations, however, the incidence of the canine disease is thousand-fold higher. This makes the dog an obvious model for studying the pathogenesis of pituitary-dependent hyperadrenocorticism. Despite certain similarities identified at the molecular level, the question still remains whether the two species have a shared oncogenetic background. Recently, hotspot recurrent mutations in the gene encoding for ubiquitin specific protease 8 (USP8) have been identified as the main driver behind the formation of ACTH-secreting pituitary adenomas in humans. In this study, we aimed to verify whether USP8 mutations also play a role in the development of such tumours in dogs. Methods Presence of USP8 mutations was analysed by Sanger and PCR-cloning sequencing in 38 canine ACTH-secreting adenomas. Furthermore, the role of USP8 and EGFR protein expression was assessed by immunohistochemistry in a subset of 25 adenomas. Results None of the analysed canine ACTH-secreting adenomas presented mutations in the USP8 gene. In a subset of these adenomas, however, we observed an increased nuclear expression of USP8, a phenotype characteristic for the USP8 mutated human tumours, that correlated with smaller tumour size but elevated ACTH production in those tumours. Conclusions Canine ACTH-secreting pituitary adenomas lack mutations in the USP8 gene suggesting a different genetic background of pituitary tumourigenesis in dogs. However, elevated nuclear USP8 protein expression in a subset of tumours was associated with a similar phenotype as in their human counterparts, indicating a possible end-point convergence of the different genetic backgrounds in the two species. In order to establish the dog as a useful animal model for the study of CD, further comprehensive studies are

  20. Cystic mammary adenocarcinoma associated with a prolactin-secreting pituitary adenoma in a New Zealand white rabbit (Oryctolagus cuniculus).

    PubMed

    Sikoski, Paul; Trybus, James; Cline, J Mark; Muhammad, F Salih; Eckhoff, Andrew; Tan, Josh; Lockard, Mandy; Jolley, Tammy; Britt, Susan; Kock, Nancy D

    2008-06-01

    Pituitary adenoma in a rabbitA 44-mo-old, female, nulliparous New Zealand White Rabbit (Oryctolagus cuniculus) presented with bilaterally diffusely enlarged mammary glands with enlarged, discolored teats that exuded brown, mucoid discharge. The complete blood count and serum chemistry panels were within normal limits, bacteria were not isolated from a culture of the discharge, and the clinical signs did not resolve with antibiotic treatment. Computed tomography and serum prolactin levels supported the diagnosis of mammary gland dysplasia, possibly due to a prolactin-secreting pituitary adenoma. Histologic evaluation confirmed the presence of a pituitary adenoma, mammary hyperplasia, dysplasia, and cystic mammary adenocarcinoma. Immunohistochemical staining confirmed the presence of abundant prolactin secreting cells in the pituitary adenoma. This is the second report of hyperprolactinemia with mammary dysplasia in rabbits, and the first report of cystic mammary adenocarcinoma associated with a prolactin-secreting pituitary adenoma in a rabbit.

  1. Ectopic pituitary adenoma of the clivus presenting with apoplexy: case report and review of the literature.

    PubMed

    Mudd, Pamela A; Hohensee, Samantha; Lillehei, Kevin O; Kingdom, Todd T; Kleinschmidt-Demasters, Bette K

    2012-01-01

    Ectopic pituitary adenomas usually occur within sphenoid sinus or nasopharynx, and seldom within the clivus. There is only a single reported example of ectopic adenoma with clinical apoplexy, albeit not from clivus. We report a 78-year-old male with known prostate carcinoma admitted with acute onset of blurred vision, suggestive of apoplexy. Work-up revealed unilateral cranial nerve VI palsy and neuroimaging showed a mass confined to the clivus; sellar region was normal. Preoperative considerations included chordoma, chondrosarcoma, or metastatic prostate carcinoma to bone. Resection was via endoscopic transsphenoidal approach to the clivus. An ectopic null cell pituitary adenoma with bland infarction was identified as the cause of the patient's clinical apoplexy. No antecedent precipitating factors for apoplexy were present; specifically the patient had not received leuprolide preoperatively, a known precipitant of pituitary apoplexy in prostate cancer patients who receive drug. We review the literature on ectopic clival pituitary adenomas, apoplexy in ectopic adenomas, and the link between apoplexy and leuprolide usage.

  2. Comprehensive review of stereotactic radiosurgery for medically and surgically refractory pituitary adenomas

    PubMed Central

    Kim, Won; Clelland, Claire; Yang, Isaac; Pouratian, Nader

    2012-01-01

    Despite advances in surgical techniques and medical therapies, a significant proportion of pituitary adenomas remain endocrinologically active, demonstrate persistent radiographic disease, or recur when followed for long periods of time. While surgical intervention remains the first-line therapy, stereotactic radiosurgery is increasingly recognized as a viable treatment option for these often challenging tumors. In this review, we comprehensively review the literature to evaluate both endocrinologic and radiographic outcomes of radiosurgical management of pituitary adenomas. The literature clearly supports the use of radiosurgery, with endocrinologic remission rates and time to remission varying by tumor type [prolactinoma: 20–30%, growth hormone secreting adenomas: ~50%, adrenocorticotrophic hormone (ACTH)-secreting adenomas: 40–65%] and radiographic control rates almost universally greater than 90% with long-term follow-up. We stratify the outcomes by tumor type, review the importance of prognostic factors (particularly, pre-treatment endocrinologic function and tumor size), and discuss the complications of treatment (with special attention to endocrinopathy and visual complications). We conclude that the literature supports the use of radiosurgery for treatment-refractory pituitary adenomas, providing the patient with a minimally invasive, safe, and effective treatment option for an otherwise resistant tumor. As such, we provide literature-based treatment considerations, including radiosurgical dose, endocrinologic, radiographic, and medical considerations for each adenoma type. PMID:22826820

  3. Fibrosarcoma after high energy radiation therapy for pituitary adenoma

    SciTech Connect

    Martin, W.H.; Cail, W.S.; Morris, J.L.; Constable, W.C.

    1980-11-01

    Pituitary sarcoma is a rare late complication of radiotherapy for pituitary tumors. Although early case reports involved multiple courses of relatively low-energy radiation therapy, pituitary sarcoma has been seen with single courses of high-energy x-ray or heavy particle radiotherapy. This report describes a fibrosarcoma of the pituitary occurring 5 years after 4,500 rad (45 Gy) of x-irradiation delivered in 20 treatments over 3 weeks by an 8 MeV linear accelerator.

  4. Expression and Clinical Significance of miR-26a and Pleomorphic Adenoma Gene 1 (PLAG1) in Invasive Pituitary Adenoma

    PubMed Central

    Yu, ChuanTing; Li, JiXia; Sun, FengNan; Cui, JinPeng; Fang, HuaLi; Sui, GuoLang

    2016-01-01

    Background Although pituitary adenoma is a malignant tumor, it can present as invasive growth in some cases. MicroRNA (miR)-26a has been found to be abnormally highly expressed in pituitary adenoma, indicating possible involvement in pathogenesis. As a known target gene of miR-26a, PLAG1 has abnormally low expression in pituitary adenoma. The correlation between miR-26a or PLAG1 expressional abnormality and occurrence of pituitary adenoma is still unknown, as is its association with invasiveness of pituitary adenoma. Material/Methods Pituitary adenoma tissues, including both invasive and non-invasive subtypes, were collected from our Neurosurgery Department, in parallel with normal pituitary tissues from postmortem autopsy. qRT-PCR was used to detect mRNA expression of miR-26a and PLAG1, while Western blotting was used to test PLAG1 protein expression. The correlation between miR-26a and PLAG1, and with pathological features, were analyzed. ROC analysis revealed the utility of miR-26a and PLAG1 in differential diagnosis of invasive/non-invasive pituitary tumors and in analyzing their effects on patient prognosis. Results MiR-26a was remarkably upregulated in pituitary tumors, while PLAG1 was downregulated, especially in invasive pituitary tumors. miR-26a and PLAG1 had higher diagnostic values for differentiating between invasive and non-invasive pituitary tumors (AUC=0.889 and 0.818, respectively). Those patients with miR-26 overexpression and PLAG1 downregulation had unfavorable prognosis. miR-26 and PLAG1 are independent factors affecting patient diagnosis. Conclusions MiR-26a can facilitate occurrence of pituitary tumor and invasiveness, probably via inhibiting PLAG1 expression. PMID:28012286

  5. Heterogeneous Genetic Background of the Association of Pheochromocytoma/Paraganglioma and Pituitary Adenoma: Results From a Large Patient Cohort

    PubMed Central

    Dénes, Judit; Swords, Francesca; Rattenberry, Eleanor; Stals, Karen; Owens, Martina; Cranston, Treena; Xekouki, Paraskevi; Moran, Linda; Kumar, Ajith; Wassif, Christopher; Fersht, Naomi; Baldeweg, Stephanie E.; Morris, Damian; Lightman, Stafford; Agha, Amar; Rees, Aled; Grieve, Joan; Powell, Michael; Boguszewski, Cesar Luiz; Dutta, Pinaki; Thakker, Rajesh V.; Srirangalingam, Umasuthan; Thompson, Chris J.; Druce, Maralyn; Higham, Claire; Davis, Julian; Eeles, Rosalind; Stevenson, Mark; O'Sullivan, Brendan; Taniere, Phillipe; Skordilis, Kassiani; Gabrovska, Plamena; Barlier, Anne; Webb, Susan M.; Aulinas, Anna; Drake, William M.; Bevan, John S.; Preda, Cristina; Dalantaeva, Nadezhda; Ribeiro-Oliveira, Antônio; Garcia, Isabel Tena; Yordanova, Galina; Iotova, Violeta; Evanson, Jane; Grossman, Ashley B.; Trouillas, Jacqueline; Ellard, Sian; Stratakis, Constantine A.; Maher, Eamonn R.; Roncaroli, Federico

    2015-01-01

    Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence. Objective: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL. Design: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples. Setting: The study was conducted at university hospitals. Patients: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study. Outcome: Outcomes included genetic screening and clinical characteristics. Results: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context. Conclusions: Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma. PMID:25494863

  6. Outcomes of Proton Therapy for Patients With Functional Pituitary Adenomas

    SciTech Connect

    Wattson, Daniel A.; Tanguturi, Shyam K.; Spiegel, Daphna Y.; Niemierko, Andrzej; Biller, Beverly M.K.; Nachtigall, Lisa B.; Bussière, Marc R.; Swearingen, Brooke; Chapman, Paul H.; Loeffler, Jay S.; Shih, Helen A.

    2014-11-01

    Purpose/Objective(s): This study evaluated the efficacy and toxicity of proton therapy for functional pituitary adenomas (FPAs). Methods and Materials: We analyzed 165 patients with FPAs who were treated at a single institution with proton therapy between 1992 and 2012 and had at least 6 months of follow-up. All but 3 patients underwent prior resection, and 14 received prior photon irradiation. Proton stereotactic radiosurgery was used for 92% of patients, with a median dose of 20 Gy(RBE). The remainder received fractionated stereotactic proton therapy. Time to biochemical complete response (CR, defined as ≥3 months of normal laboratory values with no medical treatment), local control, and adverse effects are reported. Results: With a median follow-up time of 4.3 years (range, 0.5-20.6 years) for 144 evaluable patients, the actuarial 3-year CR rate and the median time to CR were 54% and 32 months among 74 patients with Cushing disease (CD), 63% and 27 months among 8 patients with Nelson syndrome (NS), 26% and 62 months among 50 patients with acromegaly, and 22% and 60 months among 9 patients with prolactinomas, respectively. One of 3 patients with thyroid stimulating hormone—secreting tumors achieved CR. Actuarial time to CR was significantly shorter for corticotroph FPAs (CD/NS) compared with other subtypes (P=.001). At a median imaging follow-up time of 43 months, tumor control was 98% among 140 patients. The actuarial 3-year and 5-year rates of development of new hypopituitarism were 45% and 62%, and the median time to deficiency was 40 months. Larger radiosurgery target volume as a continuous variable was a significant predictor of hypopituitarism (adjusted hazard ratio 1.3, P=.004). Four patients had new-onset postradiosurgery seizures suspected to be related to generously defined target volumes. There were no radiation-induced tumors. Conclusions: Proton irradiation is an effective treatment for FPAs, and hypopituitarism remains the primary

  7. Role of a p53 polymorphism in the development of nonfunctional pituitary adenomas.

    PubMed

    Yagnik, Garima; Jahangiri, Arman; Chen, Rebecca; Wagner, Jeffrey R; Aghi, Manish K

    2017-02-16

    Non-functional pituitary adenomas (NFPAs) are among the commonest intracranial neoplasms. While histologically benign, NFPAs sometimes become large enough to limit therapeutic options and reduce quality of life. Investigations of the molecular etiology of NFPAs have failed to identify prevalent genetic changes and, while a role for p53 has been suggested, TP53 gene alterations have yet to be described in NFPAs. We found that the polymorphism rs1042522:C > G in codon 72 of exon 4 of the TP53 gene, whose C variant produces a proline and is more common in most ethnicities, has a G variant producing an arginine in 79.8% of NFPAs (n = 42; p < 1.411 × 10(-18) vs. 1000 Genomes database), causing patients to present a decade earlier with symptomatic NFPAs. In cultured NFPA cells, transfection with the rs1042522 G variant versus the C variant reduced expression of cell arrest gene p21 and increased proliferation. These findings suggest that this TP53 polymorphism influences NFPA growth.

  8. Landscape of Familial Isolated and Young-Onset Pituitary Adenomas: Prospective Diagnosis in AIP Mutation Carriers

    PubMed Central

    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.

    2015-01-01

    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

  9. Pathological study of thyrotropin-secreting pituitary adenoma: plurihormonality and medical treatment.

    PubMed

    Teramoto, Akira; Sanno, Naoko; Tahara, Shigeyuki; Osamura, Yoshiyuki R

    2004-08-01

    Thyrotropin (TSH)-secreting adenomas are rare and, as most adenomas are large, invasive and difficult to cure by surgery only, many require additional medical treatment. Many TSH-secreting adenomas cosecrete growth hormone (GH) and/or prolactin (PRL). We evaluated the relationship between pathology and the effect of dopamine agonist bromocriptine and somatostatin analogue octreotide in 20 operated patients with TSH-secreting adenomas. The four men and 16 women ranged in age from 23 to 62 years; three had clinically overt acromegaly; two manifested galactorrhea-amenorrhea. Endocrinologically, elevated serum GH, and/or IGF-1 were observed in six patients and elevated serum PRL was observed in eight. Immunohistochemically, 16 of the 20 adenomas were positive for GH and/or PRL (GH-positive, n=13; PRL-positive, n=9). Pituitary-specific transcription factor Pit-1 was demonstrated in the nuclei of all adenoma cells. Octreotide tests showed suppression of serum TSH (<50%) in ten of 14 patients. Preoperative octreotide treatment effectively reduced serum TSH and tumor size in two patients. Electron micrographs of octreotide-treated TSH-secreting adenomas showed shrinkage of the cytoplasm and diffuse distribution of secretory granules. Our study suggests that cosecretion of GH and/or PRL from TSH-secreting adenoma has no correlation with response of tumor cells to medical treatment.

  10. Expression and significance of E-cadherin and β-catenins in pituitary adenoma.

    PubMed

    Zhou, Kaiyu; Jin, Hanghuang; Luo, Yongkang

    2013-08-01

    This study used immunohistochemical methods for detecting the expression of E-cadherin and β-catenin in pituitary adenoma. Specimens were collected from 91 cases. EnVision was used for immunohistochemical staining. The results were graded depending on the staining intensity and range. Associations between E-cadherin and β-catenin expression and tumor subtype, invasiveness, and postoperative recurrence were investigated. There was a significant downregulation of E-cadherin and β-catenin in growth hormone (GH)-type tumors when compared with prolactin-type tumors (u(c) = 2.693 and 2.109, respectively; P < .05). E-cadherin and β-catenin were downregulated in invasive pituitary adenomas (u(c) = 3.563 and 4.166, respectively; P < .05) and in clinically recurring pituitary adenomas (u(c) = 2.871 and 3.866, respectively; P < .05). There was no difference in the percentage of invasive prolactin and GH secreting tumors (28.57% and 22.86%, respectively; P > .05). The expression of E-cadherin and β-catenin in pituitary adenoma was significantly downregulated and related to subtype, invasiveness, and postoperative recurrence.

  11. Radiation-induced meningioma after treatment for pituitary adenoma: Case report and literature review

    SciTech Connect

    Partington, M.D.; Davis, D.H. )

    1990-02-01

    Radiation-induced meningiomas are becoming increasingly well-recognized. We report a case of a 35-year-old man who developed a suprasellar meningioma 9 years after receiving a radiation dose of 4480 cGy for a pituitary adenoma. The literature is also reviewed. 10 references.

  12. MASEP gamma knife radiosurgery for secretory pituitary adenomas: experience in 347 consecutive cases

    PubMed Central

    Wan, Heng; Chihiro, Ohye; Yuan, Shubin

    2009-01-01

    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 patients in our study

  13. Somatomammotrophic cells in GH-secreting and PRL-secreting human pituitary adenomas.

    PubMed

    Bassetti, M; Brina, M; Spada, A; Giannattasio, G

    1989-11-01

    A morphological study has been carried out on 20 GH-secreting adenomas removed from acromegalic normoprolactinemic patients, on 29 PRL-secreting adenomas removed from hyperprolactinemic patients without signs of acromegaly and on one normal human anterior pituitary gland collected at autopsy. The protein A-gold immunoelectron microscopic technique has been utilized in order to verify the presence of mixed cells producing both GH and PRL (somatomammotrophs) in these pituitary tissues. In the normal pituitary a considerable number of somatomammotrophs (15-20%) was found, thus supporting the idea that these cells are normal components of the human anterior pituitary gland. In 10 GH-secreting adenomas and in 10 PRL-secreting adenomas somatomammotrophs were present in a variable number (from 4 to 20% of the whole cell population in GH adenomas and from 1 to 47% in PRL tumors). It can be concluded therefore that these cells, largely present in all GH/PRL-secreting adenomas, can also be found in GH-secreting and PRL-secreting tumors without clinical evidence of a mixed secretion. Adenomatous somatomammotrophs displayed ultrastructural features of adenomatous somatotrophs and mammotrophs (prominent Golgi complexes, abundant rough endoplasmic reticulum, irregular nuclei). The size and the number of granules were variable. In some cells GH and PRL were stored in distinct secretory granules, in others in mixed granules or both in mixed and distinct granules, thus suggesting that in adenomatous somatomammotrophs the efficiency of the mechanisms of sorting of the two hormones varies from one cell to another.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. The expression of AIP-related molecules in elucidation of cellular pathways in pituitary adenomas.

    PubMed

    Heliövaara, Elina; Raitila, Anniina; Launonen, Virpi; Paetau, Anders; Arola, Johanna; Lehtonen, Heli; Sane, Timo; Weil, Robert J; Vierimaa, Outi; Salmela, Pasi; Tuppurainen, Karoliina; Mäkinen, Markus; Aaltonen, Lauri A; Karhu, Auli

    2009-12-01

    Germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene predispose to the development of pituitary adenomas. Here, we characterized AIP mutation positive (AIPmut+) and AIP mutation negative (AIPmut-) pituitary adenomas by immunohistochemistry. The expressions of the AIP-related proteins aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), cyclin-dependent kinase inhibitor 1B encoding p27(Kip1), and hypoxia-inducible factor 1-alpha were examined in 14 AIPmut+ and 53 AIPmut- pituitary adenomas to detect possible expression differences. In addition, the expression of CD34, an endothelial and hematopoietic stem cell marker, was analyzed. We found ARNT to be less frequently expressed in AIPmut+ pituitary adenomas (P = 0.001), suggesting that AIP regulates the ARNT levels. AIP small interfering RNA-treated HeLa, HEK293, or Aip-null mouse embryonic fibroblast cells did not show lowered expression of ARNT. Instead, in the pituitary adenoma cell line GH3, Aip silencing caused a partial reduction of Arnt and a clear increase in cell proliferation. We also observed a trend for increased expression of nuclear AHR in AIPmut+ samples, although the difference was not statistically significant (P = 0.06). The expressions of p27(Kip1), hypoxia-inducible factor 1-alpha, or CD34 did not differ between tumor types. The present study shows that the expression of ARNT protein is significantly reduced in AIPmut+ tumors. We suggest that the down-regulation of ARNT may be connected to an imbalance in AHR/ARNT complex formation arising from aberrant cAMP signaling.

  15. Transformation of a Microprolactinoma into a Mixed Growth Hormone and Prolactin-Secreting Pituitary Adenoma

    PubMed Central

    Dessimoz, Cédric; Browaeys, Patrick; Maeder, Philippe; Lhermitte, Benoît; Pitteloud, Nelly; Momjian, Shahan; Pralong, François P.

    2012-01-01

    Combined prolactin (PRL) and growth hormone (GH) secretion by a single pituitary tumor can occur in approximately 5% of cases. However, in all previously reported patients, combined secretion of both hormones was present at the time of diagnosis. Here we describe a patient initially diagnosed with a pure prolactin-secreting microadenoma, who experienced the progressive apparition of symptomatic autonomous GH secretion while on intermittent long term dopamine agonist therapy. She was operated on, and immunohistochemical analysis of tumor tissue confirmed the diagnosis of pituitary adenoma with uniform co-staining of all cells for both GH and PRL. This patient represents the first documented occurrence of asynchronous development of combined GH and PRL secretion in a pituitary adenoma. Although pathogenic mechanisms implicated remain largely speculative, it emphasizes the need for long term hormonal follow up of patients harboring prolactinomas. PMID:22654846

  16. Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant Temozolomide Chemotherapy: A Review

    PubMed Central

    Cruz, Aurora S; Benkers, Tara; Rostad, Steven; Broyles, Frances Broyles; Yuen, Kevin; Mayberg, Marc

    2016-01-01

    Most prolactin-secreting pituitary adenomas demonstrate slow growth and are effectively managed with medical/surgical therapy. Rarely, these tumors can behave aggressively with rapid growth and invasion of local tissues, and are refractory to medical, surgical, or radio-surgical therapies. We report a case of a prolactin-secreting adenoma in a young woman, which became progressively aggressive and refractory to usual treatment modalities, but responded to treatment with the chemotherapeutic agent temozolomide. In addition, we review the literature for treatment of refractory adenomas with temozolomide. The clinical and pathologic characteristics of aggressive prolactin-secreting adenomas are reviewed, as well as their response to dopamine agonists, surgery, radiotherapy, and chemotherapy. PMID:27489751

  17. Clinical and morphological features of undifferentiated monomorphous GH/TSH-secreting pituitary adenoma.

    PubMed

    Skorić, T; Korsić, M; Zarković, K; Plavsić, V; Besenski, N; Breskovac, L; Giljević, Z; Paladino, J

    1999-06-01

    A 41-year-old male presented with progressive visual defects, acromegaly and hyperthyroidism. After clinical evaluation a giant GH/TSH-secreting pituitary adenoma was diagnosed. Administration of the somatostatin analog octreotide at doses of 150 microg s.c. per day inhibited the secretion of both GH and TSH. A three-week treatment with octreotide prior to surgery led to slight visual improvement and CT scan showed some new necrotic areas within the tumor mass. Transcranial surgery was performed. By immunohistochemical analyses of the adenoma tissue GH, prolactin and beta-chorionic gonadotropin were detected; TSH was negative. Electron microscopy revealed an undifferentiated, monomorphous adenoma with morphological features of an acidophil stem cell adenoma such as the presence of misplaced exocytoses, fibrous bodies and mitochondrial gigantism. However, the tumor cells contained small secretory granules (up to 250 nm) accumulated along the cell membrane characteristic of thyrotrope cells. Furthermore, some adenoma cells were fusiform with long cytoplasmic processes resembling thyrotropes. Two months after the operation CT scan revealed a large residual tumor. Serum GH and TSH levels had increased again and the TSH level was even higher than before the treatment. The patient died suddenly, most probably of lethal arrhythmia. Specimens of the adenoma tissue obtained at autopsy confirmed the previous findings with the exception of positive immunostaining for TSH which was found in less than 1% of the adenoma cells. This undifferentiated, monomorphous GH/TSH-secreting pituitary adenoma represents an entity that is unusual both in its ultrastructural features and clinical manifestations suggesting a cytogenesis from an early, undifferentiated stem cell.

  18. Concomitant Graves hyperthyroidism with thyrotrophin-secreting pituitary adenoma.

    PubMed

    Lee, Ming-Tsang; Wang, Chih-Yuan

    2010-04-01

    The relationship of autoimmune thyroid disease and TSH-producing pituitary tumor is rarely found. We report two patients with hyperthyroidism, a 27-year-old man and a 28-year-old woman, who were diagnosed with Graves hyperthyroidism with elevated free thyroxine (FT4), suppressed TSH and positive thyrotropin receptor autoantibodies. After treatment with antithyroid drugs, FT4 did not return to normal, and serum TSH levels were found to be above-normal range. Pituitary tumors were subsequently found via pituitary magnetic resonance imaging (MRI). We suggest that Graves hyperthyroidism concomitant with TSH-producing pituitary tumor be kept in mind, as it may confuse the therapeutic course of hyperthyroidism and make it more complicated.

  19. Functional Outcome Changes in Surgery for Pituitary Adenomas After Intraoperative Occurrence of the Trigeminocardiac Reflex

    PubMed Central

    Chowdhury, T.; Nöthen, C.; Filis, A.; Sandu, N.; Buchfelder, M.; Schaller, Bernhard

    2015-01-01

    Abstract Trigeminocardiac reflex (TCR) represents now a nearly ubiquitary phenomenon in skull base surgery. Functional relevance of the intrainterventional TCR occurrence is hitherto only proven for vestibular schwannoma. In a retrospective observational study, 19 out of 338 (8%) enrolled adult patients demonstrated a TCR during transsphenoidal/transcranial surgery for pituitary adenomas. The 2 subgroups (TCR vs non-TCR) had similar patient's characteristics, risk factors, and histology. Preoperatively, there was a similar distribution of normal pituitary function in the TCR and non-TCR subgroups. In this TCR subgroup, there was a significant decrease of that normal pituitary function after operation (37%) compared to the non-TCR group (60%) (P < 0.03). The TCR subgroup therefore demonstrated a 3.15 times (95%CI 1.15–8.68) higher risk for non-normalizing of postoperative pituitary function compared with the non-TCR subgroup (P < 0.03). It is presented, for the first time, an impact of TCR on the functional hormonal outcome after pituitary surgery and strongly underline again the importance of the TCR in clinical daily practice. As a consequence, TCR should be considered as a negative prognostic factor of hormonal normalization after surgery for pituitary adenomas that should be included into routine practice. PMID:26376385

  20. Expression of leukemia inhibitory factor and leukemia inhibitory factor receptor in the canine pituitary gland and corticotrope adenomas.

    PubMed

    Hanson, J M; Mol, J A; Meij, B P

    2010-05-01

    Leukemia inhibitory factor (LIF) is a pleiotropic cytokine of the IL-6 family that activates the hypothalamic-pituitary-adrenal axis and promotes corticotrope cell differentiation during development. The aim of this study was to investigate the expression of LIF and its receptor (LIFR) in the canine pituitary gland and in corticotrope adenomas, and to perform a mutation analysis of LIFR. Using immunohistochemistry, immunofluorescence, and quantitative expression analysis, LIF and LIFR expression were studied in pituitary glands of control dogs and in specimens of corticotrope adenoma tissue collected through hypophysectomy in dogs with pituitary-dependent hypercortisolism (PDH, Cushing's disease). Using sequence analysis, cDNA was screened for mutations in the LIFR. In the control pituitary tissues and corticotrope adenomas, there was a low magnitude of LIF expression. The LIFR, however, was highly expressed and co-localized with ACTH(1-24) expression. Cytoplasmatic immunoreactivity of LIFR was preserved in corticotrope adenomas and adjacent nontumorous cells of pars intermedia. No mutation was found on mutation analysis of the complete LIFR cDNA. Surprisingly, nuclear to perinuclear immunoreactivity for LIFR was present in nontumorous pituitary cells of the pars distalis in 10 of 12 tissue specimens from PDH dogs. These data show that LIFR is highly co-expressed with adrenocorticotropic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) in the canine pituitary gland and in corticotrope adenomas. Nuclear immunoreactivity for LIFR in nontumorous cells of the pars distalis may indicate the presence of a corticotrope adenoma.

  1. In vivo measurement of dopamine receptors in pituitary adenomas using positron emission tomography.

    PubMed

    Muhr, C; Bergström, M; Lundberg, P O; Bergström, K; Långström, B

    1986-01-01

    Patients with pituitary adenomas were examined with positron emission tomography (PET) with the administration of the 11C-labelled dopamine-D2 antagonists N-methylspiperone and raclopride. The studies were repeated after protection of the D2-receptors with Haloperidol to enable a separation of specific and unspecific receptor binding. The receptor binding was evaluated by visual inspection and with the application of a kinetic model. The results showed marked specific dopamine-D2 receptor binding in the prolactinomas and minimal or no such binding in the hormonally inactive adenomas. The two tracers 11C-raclopride and 11C-N-methylspiperone showed qualitatively the same result although raclopride resulted in a higher tumor to normal brain ratio. In conclusion, PET is a valuable complement to other radiologic techniques like computed tomography and magnetic resonance imaging in the evaluation of pituitary adenomas. An assessment of the dopamine-D2 receptors in the adenomas has a direct influence on the choice of treatment because adenomas with high amounts of receptors are in most cases effectively treated with dopamine agonists like bromocriptine.

  2. McCune-Albright syndrome: surgical and therapeutic challenges in GH-secreting pituitary adenomas.

    PubMed

    Madsen, Helen; Borges, Manuel Thomas; Kerr, Janice M; Lillehei, Kevin O; Kleinschmidt-Demasters, B K

    2011-08-01

    McCune-Albright syndrome (MAS) is a postzygotic (non-germline) disorder characterized by polyostotic fibrous dysplasia, cafe-au-lait macules and hypersecretory endocrinopathies. A significant percentage of MAS patients have pituitary adenomas that are either growth hormone (GH) or mixed GH/prolactin (PRL)-producing. Surgical excision may be challenging-or even impossible-due to the associated severe fibrous dysplasia of the skull base. Treatment relies on an interdisciplinary, multi-modal approach from endocrinologists, neurosurgeons and radiation oncologists. We present two cases of women with MAS and GH-secreting pituitary adenomas, encountered in our 30-year experience with pituitary diseases. The first patient successfully underwent transsphenoidal surgical resection for a pituitary microadenoma in 1997 (at age 18) and again in 2009 for recurrent disease, with a significant reduction in IGF-1 level. Immunohistochemistry (IHC) and electron microscopy (EM), performed on both specimens, showed a mammosomatotroph adenoma with GH, PRL, alpha subunit (+) IHC, with increased fibrous bodies developing over the 13-year interval. Focal hyperplasia could be discerned. EM in 1997 showed an admixture of mammosomatotrophs, mature lactotrophs and somatotrophs, with a bimodal population identified in 2009. The second MAS patient had long-standing polyostotic fibrous dysplasia, but was only recently diagnosed with GH excess and a pituitary adenoma, at the age of 29 years. Surgical resection was not advised in this patient because of the massive obstructive skull-base fibrous dysplasia. Medical therapy was initiated with somatostatin analogues, although responses in both patients have been suboptimal to date. We review the literature on GH excess in MAS to highlight its surgical and medical challenges.

  3. Cystic Mammary Adenocarcinoma Associated with a Prolactin-secreting Pituitary Adenoma in a New Zealand White Rabbit (Oryctolagus cuniculus)

    PubMed Central

    Sikoski, Paul; Trybus, James; Cline, J Mark; Muhammad, F Salih; Eckhoff, Andrew; Tan, Josh; Lockard, Mandy; Jolley, Tammy; Britt, Susan; Kock, Nancy D

    2008-01-01

    A 44-mo-old, female, nulliparous New Zealand White Rabbit (Oryctolagus cuniculus) presented with bilaterally diffusely enlarged mammary glands with enlarged, discolored teats that exuded brown, mucoid discharge. The complete blood count and serum chemistry panels were within normal limits, bacteria were not isolated from a culture of the discharge, and the clinical signs did not resolve with antibiotic treatment. Computed tomography and serum prolactin levels supported the diagnosis of mammary gland dysplasia, possibly due to a prolactin-secreting pituitary adenoma. Histologic evaluation confirmed the presence of a pituitary adenoma, mammary hyperplasia, dysplasia, and cystic mammary adenocarcinoma. Immunohistochemical staining confirmed the presence of abundant prolactin secreting cells in the pituitary adenoma. This is the second report of hyperprolactinemia with mammary dysplasia in rabbits, and the first report of cystic mammary adenocarcinoma associated with a prolactin-secreting pituitary adenoma in a rabbit. PMID:18589874

  4. Matrix metalloproteinase-9 and -2 and tissue inhibitor of matrix metalloproteinase-2 in invasive pituitary adenomas

    PubMed Central

    Liu, Hong-Yan; Gu, Wei-Jun; Wang, Cheng-Zhi; Ji, Xiao-Jian; Mu, Yi-Ming

    2016-01-01

    Abstract The extracellular matrix is important for tumor invasion and metastasis. Normal function of the extracellular matrix depends on the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The objective of this meta-analysis was to assess the relationship between expression of MMP-9, MMP-2, and TIMP-2 and invasion of pituitary adenomas. We searched Pubmed, Embase, and the Chinese Biomedical Database up to October 2015. RevMan 5.1 software (Cochrane Collaboration, Copenhagen, Denmark) was used for statistical analysis. We calculated the standardized mean difference (SMD) for data expressed as mean ± standard deviation because of the difference in the detection method. Twenty-four studies (1320 patients) were included. MMP-9 expression was higher in the patients with invasive pituitary adenomas (IPAs) than patients with noninvasive pituitary adenomas (NIPAs) with detection methods of IHC [odds ratio (OR) = 5.48, 95% confidence interval (CI) = 2.61–11.50, P < 0.00001), and reverse transcriptase-polymerase chain reaction (SMD = 2.28, 95% CI = 0.91–3.64, P = 0.001). MMP-2 expression was also increased in patients with IPAs at the protein level (OR = 3.58, 95% CI = 1.63–7.87, P = 0.001), and RNA level (SMD = 3.91, 95% CI = 1.52–6.29, P = 0.001). Meta-analysis showed that there was no difference in TIMP-2 expression between invasive and NIPAs at the protein level (OR = 0.38, 95% CI = 0.06–2.26, P = 0.29). MMP-9 expression in prolactinomas and nonfunctioning pituitary adenomas was also no difference (OR = 1.03, 95% CI = 0.48–2.20, P = 0.95). The results indicated that MMP-9 and -2 may be correlated with invasiveness of pituitary adenomas, although their relationship with functional status of pituitary adenomas is still not clear. TIMP-2 expression in IPAs needs to be investigated further. PMID:27310993

  5. Pituitary apoplexy

    PubMed Central

    Ranabir, Salam; Baruah, Manash P.

    2011-01-01

    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. PMID:22029023

  6. TSH-secreting pituitary adenomas: follow-up of 11 cases and review of the literature.

    PubMed

    Ness-Abramof, Rosane; Ishay, Avraham; Harel, Gideon; Sylvetzky, Noa; Baron, Elzbieta; Greenman, Yona; Shimon, Ilan

    2007-01-01

    Thyrotropin (TSH)-secreting pituitary adenomas account for less than 1% of all pituitary tumors. In the last two decades, their clinical management has changed markedly due to technological advances that made earlier diagnosis possible and the introduction of somatostatin analog therapy. We retrieved the data of 11 patients in Israel diagnosed with TSH-secreting pituitary tumors since 1989. There were six men and five women of mean age 44.8 +/- 19.5 years (range 18-80 years). All had elevated thyroxine and triidothyronine levels with nonsuppressed TSH and imaging evidence of a pituitary tumor. In three patients the tumor co-secreted growth hormone. Ten patients had macroadenomas (> or =10 mm) and one patient had a microadenoma (<10 mm). Nine patients underwent surgery, and all had postoperative evidence of residual tumor. Ten patients received long-term somatostatin analog therapy (9 postoperatively, 1 primarily), which controlled the hyperthyroidism in all of them. In addition, three patients showed tumor shrinkage and seven, stabilization of tumor growth.In conclusion, in patients with TSH-secreting pituitary adenomas, somatostatin therapy appears to be highly effective in treating hyperthyroidism and in halting tumor growth or promoting tumor shrinkage.

  7. A pituitary carcinoma secreting TSH and prolactin: a non-secreting adenoma gone awry.

    PubMed

    Brown, Rebecca L; Muzzafar, Tariq; Wollman, Robert; Weiss, Roy E

    2006-05-01

    To our knowledge, only one case of a TSH-secreting carcinoma has previously been reported. We describe here a second patient with a pituitary carcinoma producing TSH and prolactin (PRL). A 37-year-old male underwent a left frontotemporal craniotomy in 1996 for a sellar mass. Except for mildly increased PRL and elevated alpha-subunit, hormone evaluation was normal. Pathologic examination revealed a chromophobe adenoma with increased mitotic forms. The patient completed a course of external beam radiation to the pituitary and was prescribed l-thyroxine, bromocriptine, and hydrocortisone. He was lost to follow-up but did well for 6 years, until 2002, when he presented with TSH-dependent thyrotoxicosis and hyperprolactinemia. The patient was started on bromocriptine and propylthiouracil and was, again, lost to follow-up. In 2004, 9 years after his initial presentation, he presented after falling. Magnetic resonance imaging showed two brain masses with associated midline shift. Emergent resection of the larger mass revealed a pituitary cancer with positive staining for PRL, but not for TSH. Nine months later, the patient underwent further debulking of metastatic disease. Although development of a carcinoma from a pituitary adenoma is very rare (<0.5%), macroadenomas that become hormonally active should be suspect for transformation into pituitary cancer.

  8. Interesting coincidence of atypical TSH-secreting pituitary adenoma and chronic lymphocytic leukemia.

    PubMed

    Bolanowski, Marek; Zieliński, Grzegorz; Jawiarczyk-Przybyłowska, Aleksandra; Maksymowicz, Maria; Potoczek, Stanisław; Syrycka, Joanna; Podgórski, Jan K

    2014-01-01

    Thyrotropin-secreting adenomas (TSH-oma) are very rare pituitary tumours. They are macroadenomas usually presenting with signs and symptoms of hyperthyroidism, and mass effects. They can co-secrete other hormones such as growth hormone or prolactin. Different malignancies, including haematological ones, are reported in patients with pituitary diseases. Chronic lymphocytic leukemia (CLL) occurs mostly in older patients, more often in males. CLL is associated with increased risk of second malignancies such as other blood neoplasms, skin and solid tumours. We present a successful neurosurgical outcome in a patient with an interesting coincidence of atypical TSH-oma and asymptomatic CLL.

  9. [Thyrotropin secreting pituitary adenoma in a child: case report and literature review].

    PubMed

    Mazerkina, N A; Trunin, Iu Iu; Gorelyshev, S K; Golovanov, A V; Kadasev, B A; Shishkina, L V; Rotin, D A; Karmanov, M E; Orlova, E M

    2012-01-01

    We present a case of 11-year old boy with Type 1 Autoimmune Polyglandular Syndrome and thyrotropin secreting pituitary adenoma, which was diagnosed by elevated TSH and thyroid hormones levels and MRI signs of pituitary tumor and without clinical symptoms of hyperthyroidism. He underwent partial resection of the tumor via transnasal approach and subsequent radiation therapy. Consequently 1 year after XRT patient developed growth hormone deficiency, 3.5 years later patient became euthyroid, and 5.5 years after treatment - hypothyroid. This is the first described case of coexistence of this 2 rare endocrine diseases in the same patient.

  10. [Inappropriate TSH: from common etiologies to the rare TSH secreting pituitary adenoma].

    PubMed

    Portmann, L; Gomez, F; Flattet, A

    2012-11-14

    Dealing with a patient with hyperthyroidism and goiter, the association of high values of free T4 or free T3 with a normal TSH, may suggest the presence of errors in the measurement as well as the possibility of a TSH secreting pituitary adenoma. However, a very similar clinical picture may occur in the syndrome of resistance to thyroid hormone. The differential diagnosis is made by history and appropriate laboratory tests before considering pituitary imaging. The sole measurement of TSH cannot allow the diagnosis of a TSH secreting adenoma, of which the work-up and treatment are discussed. A similar situation may occur in laboratory medicine, where the doctor has to be puzzled by a inappropriate level of TSH with a high free T4, requiring the establishment of an etiology with a logical approach considering the most frequent causes.

  11. Radiotherapy of nonfunctional adenomas of the pituitary gland. Results with long-term follow-up

    SciTech Connect

    Flickinger, J.C.; Nelson, P.B.; Martinez, A.J.; Deutsch, M.; Taylor, F.

    1989-06-15

    A total of 112 patients with the diagnosis of nonfunctional pituitary adenoma received radiation therapy at the University of Pittsburgh between 1964 and 1987. Postoperative radiation therapy was administered in 87 patients. Actuarial progression-free survival (tumor control) at 5, 10, 15, and 20 years was 97%, 89%, 87%, and 76%, respectively. Radiation prescribed to the 95% isodose ranged from 35.72 Gy to 62.32 Gy. Multivariate analysis showed decreased tumor control to be significantly associated with increasing field size (P = .036). No improvement in tumor control could be detected with increasing total radiation dose or nominal standard dose (NSD). One patient developed optic neuropathy and another developed a glioblastoma after doses in both patients of 4750 cGy in 25 fractions. External beam radiotherapy for nonfunctional pituitary adenomas was found to be effective and safe when doses less than 4750 cGy in 25 fractions were used.

  12. Economic impact of CT scanning on the evaluation of pituitary adenomas

    SciTech Connect

    Newton, D.R.; Witz, S.; Norman, D.; Newton, T.H.

    1983-03-01

    The medical and financial records of three cohorts of 20 consecutive patients with pituitary adenomas surgically treated in 1976, 1978, and 1980 were evaluated to assess the impact of changing technology on the cost of preoperative diagnostic evaluation. The average preoperative length of hospital stay decreased from 6.8 days in 1976 to 1.9 days in 1980. The average diagnostic radiologic charge adjusted to 1980 dollars decreased from $1,747 in 1976 to $585 in 1980, while the radiologic bill as a percentage of the total hospital bill changed from 17.3% in 1976 to 11.9% in 1980. The decline in cost parameters coincided with the dramatic increase in the use of cranial computed tomography and the sharp reduction in the use of angiography and pneumoencephalography. These findings suggest that computed tomography is a highly efficacious technique for the evaluation of patients with suspected pituitary adenoma, resulting in significant savings in the costs of diagnostic evaluation.

  13. PET as a tool in the clinical evaluation of pituitary adenomas

    SciTech Connect

    Bergstroem, M.M.; Muhr, C.; Lundberg, P.O.; Langstroem B4 )

    1991-04-01

    Positron emission tomography (PET) was used in over 400 examinations in patients with pituitary adenoma. It was demonstrated that PET with carbon-11-methionine can give valuable complementary information in the diagnosis of this tumor due to PET's ability to adequately depict viable tumor tissue in contrast to fibrosis, cysts and necrosis. Furthermore, PET with dopamine D2 receptor ligands can characterize the degree of receptor binding and thus give information as to the prerequisites for dopamine agonist treatment. Most important is the very high sensitivity given by PET with carbon-11-methionine in the evaluation of treatment effects. It is concluded that when properly used PET can be fully justified in the clinical handling of patients with pituitary adenomas and other intracranial tumors.

  14. Bone morphogenetic protein 4 and bone morphogenetic protein receptor expression in the pituitary gland of adult dogs in healthy condition and with ACTH-secreting pituitary adenoma.

    PubMed

    Sato, A; Ochi, H; Harada, Y; Yogo, T; Kanno, N; Hara, Y

    2017-01-01

    The purpose of this study was to investigate the expression of bone morphogenetic protein 4 (BMP4) and its receptors, bone morphogenetic protein receptor I (BMPRI) and BMPRII, in the pituitary gland of healthy adult dogs and in those with ACTH-secreting pituitary adenoma. Quantitative polymerase chain reaction analysis showed that the BMP4 messenger RNA expression level in the ACTH-secreting pituitary adenoma samples was significantly lower than that in the normal pituitary gland samples (P = 0.03). However, there were no statistically significant differences between samples with respect to the messenger RNA expression levels of the receptors BMPRIA, BMPRIB, and BMPRII. Double-immunofluorescence analysis of the normal canine pituitary showed that BMP4 was localized in the thyrotroph (51.3 ± 7.3%) and not the corticotroph cells. By contrast, BMPRII was widely expressed in the thyrotroph (19.9 ± 5.2%) and somatotroph cells (94.7 ± 3.6%) but not in the corticotroph cells (P < 0.001, thyrotroph cells vs somatotroph cells). Similarly, in ACTH-secreting pituitary adenoma, BMP4 and BMPRII were not expressed in the corticotroph cells. Moreover, the percentage of BMP4-positive cells was also significantly reduced in the thyrotroph cells of the surrounding normal pituitary tissue obtained from the resected ACTH-secreting pituitary adenoma (8.3 ± 7.9%) compared with that in normal canine pituitary (P < 0.001). BMP4 has been reported to be expressed in corticotroph cells in the human pituitary gland. Therefore, the results of this study reveal a difference in the cellular pattern of BMP4-positive staining in the pituitary gland between humans and dogs and further revealed the pattern of BMPRII-positive staining in the dog pituitary gland. These species-specific differences regarding BMP4 should be considered when using dogs as an animal model for Cushing's disease.

  15. Decreased expression of APAF-1 and increased expression of cathepsin B in invasive pituitary adenoma

    PubMed Central

    Tanase, Cristiana; Albulescu, Radu; Codrici, Elena; Calenic, Bogdan; Popescu, Ionela Daniela; Mihai, Simona; Necula, Laura; Cruceru, Maria Linda; Hinescu, Mihail Eugen

    2015-01-01

    Purpose Apoptotic protease-activating factor-1 (APAF-1) and cathepsin B are important functional proteins in apoptosis; the former is involved in the intrinsic (mitochondrial) pathway, while the latter is associated with both intrinsic and extrinsic pathways. Changes in the expression of apoptosome-related proteins could be useful indicators of tumor development since a priori defects in the mitochondrial pathway might facilitate the inception and progression of human neoplasms. Our aim was to evaluate the profiles of APAF-1 and cathepsin B in relation with other molecules involved in apoptosis/proliferation and to correlate them with the aggressive behavior of invasive pituitary adenomas. Materials and methods APAF-1 and cathepsin B were assessed in tissue samples from 30 patients with pituitary adenomas, of which 16 were functional adenomas and 22 were invasive adenomas. Results A positive relationship between high proliferation and invasiveness was observed in invasive pituitary adenomas when compared to their noninvasive counterparts (Ki-67 labeling index – 4.72% versus 1.75%). Decreased expression of APAF-1 was recorded in most of the invasive adenomas with a high proliferation index, while the cathepsin B level was elevated in this group. We have noticed a negative correlation between the low level of APAF-1 and invasiveness (63.63%; P<0.01); at the same time, a positive correlation between cathepsin B expression and invasiveness (59.09%; P<0.01) was found. In all, 81.25% out of the total APAF-1-positive samples were cathepsin B negative (P<0.01); 76.92% out of the total cathepsin B-positive samples were APAF-1-negative (P<0.01). These results were reinforced by an apoptosis protein array examination, which showed inhibition of the extrinsic apoptotic pathway in an invasive pituitary adenoma. Conclusion A bidirectional–inverted relationship between APAF-1 and cathepsin B expressions was noticed. One might hypothesize that shifting the balance between

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

    PubMed Central

    Kim, Mi Young; Kim, Jin Hee; Oh, Young Kee; Kim, El

    2016-01-01

    Purpose: To investigate treatment outcome and long term complication after surgery and radiotherapy (RT) for pituitary adenoma. Materials and Methods: 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). Results: 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. Conclusion: Surgery and RT are very effective and safe in hormonal and tumor growth control for secreting and non-secreting pituitary adenoma. PMID:27306775

  17. Ectopic Pituitary Adenomas Presenting as Sphenoid or Clival Lesions: Case Series and Management Recommendations.

    PubMed

    Tajudeen, Bobby A; Kuan, Edward C; Adappa, Nithin D; Han, Joseph K; Chandra, Rakesh K; Palmer, James N; Kennedy, David W; Wang, Marilene B; Suh, Jeffrey D

    2017-04-01

    Background An ectopic pituitary adenoma presenting as a clival or sphenoid mass is a rare clinical occurrence that may mislead the clinician and result in unnecessary interventions or potential medicolegal consequences. Here, we present one of the largest multi-institutional case series and review the literature with an emphasis on radiological findings and critical preoperative workup. Methods Retrospective chart review. Results Nine patients were identified with ectopic pituitary adenomas of the sphenoid or clivus. There were four females and five males. Median age was 60 years old (range, 36-73 years). The most common presenting symptom was headache (56%). Five (56%) patients presented with a mass arising from the clivus while four (44%) presented with a mass in the sphenoid. Six (67%) patients demonstrated biochemical evidence of hypersecretion on full endocrinology panel. All masses showed evidence of enhancement with gadolinium with a propensity for adjacent bone involvement. Lesions also had a predilection for growth toward the cavernous sinus, carotid artery, or sellar floor. Surgical intervention was performed in eight patients (89%). In eight patients (89%), tumors demonstrated immunoreactivity to prolactin. Conclusions Pituitary adenomas can rarely present as an isolated sphenoid or clival mass. Lesions displayed similar magnetic resonance imaging findings with an erosive growth pattern toward the sellar floor, cavernous sinus, or adjacent carotid artery. Patients with clival or parasellar lesions with comparable features should have a preoperative workup which includes prolactin level and alert the physician to consider an ectopic pituitary adenoma in the differential to prevent unnecessary surgery and potential complications.

  18. Cushing's disease due to a giant pituitary adenoma in early infancy: CT and MRI features.

    PubMed

    Maeder, P; Gudinchet, F; Rillet, B; Theintz, G; Meuli, R

    1996-01-01

    We report the case of a 12-month-old girl presenting with diabetes insipidus and Cushing s disease. Brain magnetic resonance imaging (MRI) demonstrated a large tumour arising from the sella turcica, extending up to the foramen of Monro and invading the cavernous sinuses. Surgery was performed to remove the suprasellar part of the tumour, and histology revealed an adrenocorticotrophin (ACTH) secreting pituitary adenoma. This entity is very rare in this age group and the MRI features have not previously been described.

  19. Endoscopic versus microscopic transsphenoidal pituitary adenoma surgery: a meta-analysis

    PubMed Central

    2014-01-01

    Background Endoscopic transsphenoidal surgery has gradually come to be regarded as a preferred option in the treatment of pituitary adenomas because of its advantages of improved visualization and its minimal invasiveness. The aim of this study was to compare and evaluate the outcomes and complications of endoscopic and microscopic transsphenoidal surgery in the treatment of pituitary adenomas. Methods We performed a systematic literature search of MEDLINE, EMBASE, the Cochrane Library and the Web of Science between January 1992 and May 2013. Studies with consecutive patients that explicitly and fully compared endoscopic and microscopic approaches in the treatment of pituitary adenomas were included. Results A total of 15 studies (n = 1,014 patients) met the inclusion criteria among 487 studies that involved endoscopic surgery and 527 studies that dealt with microscopic surgery. The rate of gross tumor removal was higher in the endoscopic group than in the microscopic group. The post-operative rates of septal perforation were less frequent in patients who underwent endoscopic surgery. There was no significant difference between the two techniques in the incidence rates of meningitis, diabetes insipidus, cerebrospinal fluid leak, epistaxis or hypopituitarism. The post-operative hospital stay was significantly shorter for the endoscopic surgery group compared with the microscopic surgery group (P < 0.05). There was no significant difference in the length of the operation (P > 0.05). Conclusions The present study indicates that the endoscopic transsphenoidal approach is safer and more effective than microscopic surgery in the treatment of pituitary adenomas. PMID:24721812

  20. Combining Cadherin Expression with Molecular Markers Discriminates Invasiveness in Growth Hormone and Prolactin Pituitary Adenomas.

    PubMed

    Chauvet, N; Romanò, N; Meunier, A-C; Galibert, E; Fontanaud, P; Mathieu, M-N; Osterstock, G; Osterstock, P; Baccino, E; Rigau, V; Loiseau, H; Bouillot-Eimer, S; Barlier, A; Mollard, P; Coutry, N

    2016-02-01

    Although growth hormone (GH)- and prolactin (PRL)-secreting pituitary adenomas are considered benign, in many patients, tumour growth and/or invasion constitute a particular challenge. In other tumours, progression relies in part on dysfunction of intercellular adhesion mediated by the large family of cadherins. In the present study, we have explored the contribution of cadherins in GH and PRL adenoma pathogenesis, and evaluated whether this class of adherence molecules was related to tumour invasiveness. We have first established, by quantitative polymerase chain reaction and immunohistochemistry, the expression profile of classical cadherins in the normal human pituitary gland. We show that the cadherin repertoire is restricted and cell-type specific. Somatotrophs and lactotrophs express mainly E-cadherin and cadherin 18, whereas N-cadherin is present in the other endocrine cell types. This repertoire undergoes major differential modification in GH and PRL tumours: E-cadherin is significantly reduced in invasive GH adenomas, and this loss is associated with a cytoplasmic relocalisation of cadherin 18 and catenins. In invasive prolactinomas, E-cadherin distribution is altered and is accompanied by a mislocalisation of cadherin 18, β-catenin and p120 catenin. Strikingly, de novo expression of N-cadherin is present in a subset of adenomas and cells exhibit a mesenchymal phenotype exclusively in invasive tumours. Binary tree analysis, performed by combining the cadherin repertoire with the expression of a subset of known molecular markers, shows that cadherin/catenin complexes play a significant role in discrimination of tumour invasion.

  1. Human kallikrein 10 expression in surgically removed human pituitary corticotroph adenomas: an immunohistochemical study.

    PubMed

    Di Meo, Ashley; Rotondo, Fabio; Kovacs, Kalman; Cusimano, Michael D; Syro, Luis V; Di Ieva, Antonio; Diamandis, Eleftheros P; Yousef, George M

    2015-07-01

    Human kallikrein 10 (hk10), a secreted serine protease, was reported to function as a tumor suppressor. hK10 immunoexpression has been demonstrated in lactrotrophs and corticotrophs of the nontumorous human adenohypophysis. In the present study, for the first time we report hK10 immunoexpression in various surgically removed corticotroph adenoma subtypes. Specimens were fixed in formalin and embedded in paraffin. Immunostaining was performed using the streptavidin-biotin-peroxidase complex method with an hK10-specific rabbit polyclonal antibody. Results showed that the endocrinologically active adrenocorticotropic hormone (ACTH)-producing pituitary tumors and the silent subtypes were immunopositve for hK10. Intensity of staining varied between the different subtypes. Intensity was lowest in the silent subtypes (silent corticotroph subtypes 1 and 2) compared with nontumorous human adenohypophysial corticotrophs, whereas the endocrinologically active subtypes (ACTH-secreting adenomas, corticotroph carcinomas, Crooke cell adenomas, Crooke cell carcinomas), showed the highest hK10 immunoexpression. Immunopositivity in the nuclei of the ACTH-secreting adenomas and carcinomas, as well as dual cytoplasmic and nuclear localization of hK10 in some of the secreting tumor types was an intriguing finding. Immunoexpression of hK10 in the ACTH-secreting tumors as well as in the Crooke cell tumors was significantly increased when compared with the nonfunctioning tumors and in the corticotrophs of nontumorous pituitaries.

  2. Intensity-modulated radiotherapy for pituitary adenomas: The preliminary report of Cleveland Clinic experience

    SciTech Connect

    Mackley, Heath B. . E-mail: hmackley@alumni.upenn.edu; Reddy, Chandana A. M.S.; Lee, S.-Y.; Harnisch, Gayle A.; Mayberg, Marc R.; Hamrahian, Amir H.; Suh, John H.

    2007-01-01

    Purpose: Intensity-modulated radiotherapy (IMRT) is being increasingly used for the treatment of pituitary adenomas. However, there have been few published data on the short- and long-term outcomes of this treatment. This is the initial report of Cleveland Clinic's experience. Methods and Materials: Between February 1998 and December 2003, 34 patients with pituitary adenomas were treated with IMRT. A retrospective chart review was conducted for data analysis. Results: With a median follow-up of 42.5 months, the treatment has proven to be well tolerated, with performance status remaining stable in 90% of patients. Radiographic local control was 89%, and among patients with secretory tumors, 100% had a biochemical response. Only 1 patient required salvage surgery for progressive disease, giving a clinical progression free survival of 97%. The only patient who received more than 46 Gy experienced optic neuropathy 8 months after radiation. Smaller tumor volume significantly correlated with subjective improvements in nonvisual neurologic complaints (p = 0.03), and larger tumor volume significantly correlated with subjective worsening of visual symptoms (p = 0.05). New hormonal supplementation was required for 40% of patients. Younger patients were significantly more likely to require hormonal supplementation (p 0.03). Conclusions: Intensity-modulated radiation therapy is a safe and effective treatment for pituitary adenomas over the short term. Longer follow-up is necessary to determine if IMRT confers any advantage with respect to either tumor control or toxicity over conventional radiation modalities.

  3. Prediction of adrenocortical insufficiency after pituitary adenoma surgery using postoperative basal cortisol levels.

    PubMed

    Hána, V; JeŽková, J; Kosák, M; Kršek, M; Marek, J; Netuka, D; Hill, M; Hána, V

    2015-01-01

    Our aim was to analyze the correlation of early postoperative cortisol levels in patients after transsphenoidal pituitary adenoma surgery compared to the standard dose ACTH test and Insulin tolerance test (ITT) several months later. We retrospectively reviewed data from 94 patients operated for pituitary adenoma in years 2009-2012. The comparison of day 7 (median) postoperative basal cortisol levels and 3.6 months (median) after pituitary adenoma surgery stimulation test - standard dose 250 microg 1-24ACTH test in 83 patients or ITT in 11 patients were performed. All 16 patients with early postoperative cortisol levels >500 nmol/l proved a sufficient response in the stimulation tests. At basal cortisol levels of 370-500 nmol/l the sufficient response was found in 96 % (27/28) of patients. In the postoperative basal cortisol levels 200-370 nmol/l we found a preserved corticotroph axis later on in 88 % (28/32) of cases. Patients with basal cortisol levels 100-200 nmol/l had a maintained corticotroph axis function in 8/11 cases - 73 %. All patients with an early postoperative basal cortisol level above 500 nmol/l proved in the stimulation tests a preserved corticotroph axis function. The interval 370-500 nmol/l showed a minimal risk of postoperative adrenal insufficiency.

  4. Cushing Disease After Treatment of Nonfunctional Pituitary Adenoma: A Case Report and Literature Review.

    PubMed

    Fang, Hongjuan; Tian, Rui; Wu, Huanwen; Xu, Jian; Fan, Hong; Zhou, Jian; Zhong, Liyong

    2015-12-01

    We describe a very rare case of nonfunctional pituitary adenoma (NFPA) that exhibited corticotrophic activity after resection and radiotherapy. The possible mechanisms of the transformation from NFPA to Cushing disease (CD) are discussed.A 43-year-old man presented with impaired vision, bilateral frontal headaches, and hyposexuality. He had no symptoms suggestive of hypercortisolism, and 8 am plasma cortisol concentration was 67.88 ng/mL. Brain imaging revealed a 15 × 15 × 21-mm sellar mass suggestive of a macroadenoma. The tumor was resected by transsphenoidal surgery and identified by immunohistochemical analysis as a chromophobic adenoma that did not stain for pituitary hormones. The patient was treated with prednisone and levothyroxine replacement therapy. After a third recurrence, the patient presented with clinical features and physical signs of Cushing syndrome. Plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations were elevated, and there was a loss of circadian rhythms. Inferior petrosal sinus sampling after desmopressin showed the central-peripheral ACTH ratio was greater than 3:1. A repeat transsphenoidal resection was undertaken. Immunohistochemistry revealed ACTH positivity. Three months following surgery, imaging showed little residual tumor, but plasma ACTH remained elevated. He was referred for postoperative Gamma Knife radiotherapy.The immunological activity and biological features of the hormones secreted from a pituitary adenoma vary with time. Because long-term outcomes are unpredictable, postoperative follow-up is essential to detect postoperative transformation from NFPA to CD.

  5. Parasellar Extension Grades and Surgical Extent in Endoscopic Endonasal Transsphenoidal Surgery for Pituitary Adenomas : A Single Surgeon's Consecutive Series with the Aspects of Reliability and Clinical Validity

    PubMed Central

    Lee, Sang-Hyo; Park, Jae-Sung; Lee, Song; Kim, Sung-Won

    2016-01-01

    Objective The inter-rater reliability of the modified Knosp's classification was measured before the analysis. The clinical validity of the parasellar extension grading system was evaluated by investigating the extents of resection and complication rates among the grades in the endoscopic endonasal transsphenoidal surgery (EETS) for pituitary adenomas. Methods From November 2008 to August 2015, of the 286 patients who underwent EETS by the senior author, 208 were pituitary adenoma cases (146 non-functioning pituitary adenomas, 10 adrenocorticotropic hormone-secreting adenomas, 31 growth hormone-secreting adenomas, 17 prolactin-secreting adenomas, and 4 thyroid-stimulating hormone-secreting adenomas; 23 microadenomas, 174 macroadenomas, and 11 giant adenomas). Two neurosurgeons and a neuroradiologist independently measured the degree of parasellar extension on the preoperative sellar MRI according to the modified Knosp's classification. Inter-rater reliability was statistically assessed by measuring the intraclass correlation coefficient. The extents of resection were evaluated by comparison of the pre- and post-operative MR images; the neurovascular complications were assessed by reviewing the patients' medical records. The extent of resection was measured in each parasellar extension grade; thereafter, their statistical differences were calculated. Results The intraclass correlation coefficient value of reliability across the three raters amounted to 0.862. The gross total removal (GTR) rates achieved in each grade were 70.0, 69.8, 62.9, 21.4, 37.5, and 4.3% in Grades 0, 1, 2, 3A, 3B, and 4, respectively. A significant difference in the extent of resection was observed only between Grades 2 and 3A. In addition, significantly higher complication rates were observed in the groups above Grade 3A. Conclusion Although the modified Knosp's classification system appears to be complex, its inter-rater reliability proves to be excellent. Regarding the clinical validity of

  6. Pituitary Adenoma and Hyperprolactinemia Accompanied by Idiopathic Granulomatous Mastitis

    PubMed Central

    Destek, Sebahattin; Ahioglu, Serkan; Serin, Kursat Rahmi

    2017-01-01

    Idiopathic granulomatous mastitis (IGM) is a rare chronic inflammatory disease of the breast, and its etiology remains not fully elucidated. IGM is observed more often in patients with autoimmune disease. Hyperprolactinemia is observed during pregnancy, lactation, and a history of oral contraceptive use. A 39-year-old patient with no history of oral contraceptive use presented with complaints such as redness, pain, and swelling in her left breast. Ultrasound and magnetic resonance imaging (MRI) revealed a suspicious inflamed mass lesion. Core biopsy was performed to exclude breast cancer and to further diagnose. The breast abscess was drained and steroids were given for treatment. In order to monitor any progression during the three months of treatment, hormone levels were routinely examined. Prolactin level was above the reference range, and pituitary MRI revealed a pituitary prolactinoma. After treatment with prolactin inhibitors, IGM also improved with hyperprolactinemia. This report emphasizes attention to hyperprolactinemia in cases of IGM diagnosis and treatment. PMID:28321344

  7. Biopsy proven pituitary sarcoidosis presenting as a possible adenoma.

    PubMed

    Prayson, Richard A

    2016-12-01

    Sarcoidosis is a well-recognized systemic granulomatous process which involves the central nervous system in 5-15% of patients. One of the more frequent sites of central nervous system involvement is the pituitary and hypothalamic region. Involvement of the sellar region by sarcoidosis is overall an infrequent occurrence, comprising less than 1% of all intrasellar lesions. Patients typically present with an infiltrative lesion on imaging studies and clinically with symptoms related to diabetes insipidus or hyperprolactinemia. This report describes a 38-year-old woman who initially presented with a variety of symptoms including headaches, light sensitivity, nausea and vomiting, acute visual changes, cold intolerance, amenorrhea, decreased libido, fatigue and galactorrhea. She had an elevated serum prolactin level and evidence of oligoclonal bands in the cerebrospinal fluid. Imaging studies discovered a 1.8cm mass involving the pituitary gland and compressing the optic chiasm. The lesion was excised and microscopically was marked by a chronic inflammatory cell infiltrate and scattered nonnecrotizing granulomas. Stains and microbiologic cultures failed to demonstrate microorganisms. There was no evidence of other organ involvement on postoperative imaging. She was treated with prednisone with improvement of symptoms and subsequently required methotrexate to treat left eye pain and blurred vision, 29months after her surgery. Achieving treatment control in patients with pituitary and hypothalamic improvement in sarcoidosis still remains a challenge.

  8. Emerging Targets in Pituitary Adenomas: Role of the CXCL12/CXCR4-R7 System

    PubMed Central

    Thellung, Stefano; Würth, Roberto; Gatto, Federico; Corsaro, Alessandro; Villa, Valentina; Nizzari, Mario; Albertelli, Manuela; Ferone, Diego; Florio, Tullio

    2014-01-01

    Chemokines are chemotactic regulators of immune surveillance in physiological and pathological conditions such as inflammation, infection, and cancer. Several chemokines and cognate receptors are constitutively expressed in the central nervous system, not only in glial and endothelial cells but also in neurons, controlling neurogenesis, neurite outgrowth, and axonal guidance during development. In particular, the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, form a functional network that controls plasticity in different brain areas, influencing neurotransmission, neuromodulation, and cell migration, and the dysregulation of this chemokinergic axis is involved in several neurodegenerative, neuroinflammatory, and malignant diseases. CXCR4 primarily mediates the transduction of proliferative signals, while CXCR7 seems to be mainly responsible for scavenging CXCL12. Importantly, the multiple intracellular signalling generated by CXCL12 interaction with its receptors influences hypothalamic modulation of neuroendocrine functions, although a direct modulation of pituitary functioning via autocrine/paracrine mechanisms was also reported. Both CXCL12 and CXCR4 are constitutively overexpressed in pituitary adenomas and their signalling induces cell survival and proliferation, as well as hormonal hypersecretion. In this review we focus on the physiological and pathological functions of immune-related cyto- and chemokines, mainly focusing on the CXCL12/CXCR4-7 axis, and their role in pituitary tumorigenesis. Accordingly, we discuss the potential targeting of CXCR4 as novel pharmacological approach for pituitary adenomas. PMID:25484899

  9. Visual pathway impairment by pituitary adenomas: quantitative diagnostics by diffusion tensor imaging.

    PubMed

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

    2016-11-25

    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 < 0.05 and r = 0.48, p < 0.05, respectively) and the fractional anisotropy (r = -0.58, p < 0.05 and r = -0.47, p < 0.05, respectively) but not with the axial diffusivity. The axial diffusivity differed significantly between controls and patients with VFD, both before and after surgery (p < 0.05); however, no difference was found between patients with and without VFD. Based on the axial diffusivity and fractional anisotropy, a prediction model classified all patients with VFD correctly (sensitivity 1.0), 9 of 12 patients without VFD correctly (sensitivity 0.75), and 17 of 20 controls as controls (specificity 0.85). CONCLUSIONS DTI could detect pathology and degree of injury in the anterior visual pathways that were compressed by pituitary adenomas. The correlation

  10. Concurrent production of adrenocorticotropin and prolactin from two distinct cell lines in a single pituitary adenoma: a detailed immunohistochemical analysis.

    PubMed

    Sherry, S H; Guay, A T; Lee, A K; Hedley Whyte, E T; Federman, M; Freidberg, S R; Woolf, P D

    1982-11-01

    A pituitary tumor from a patient with severe Cushing's disease and marked hyperprolactinemia was extensively studied by immunohistochemical techniques. Tissues from two separate areas of the adenoma were found to contain similar cell proportions of PRL as well as ACTH and related peptides (beta-lipotropin, beta-endorphin, and alpha MSH). The tumor was composed of approximately 70% immunoreactive PRL cells and 5% ACTH-containing cells. Double immunostaining revealed that PRL or ACTH and related peptides were found in two distinct populations of tumor cells. These results document for the first time inappropriate synthesis and secretion of an unusual combination of pituitary hormones from a mixed pituitary adenoma.

  11. Pituitary adenoma apoplexy with initial presentation mimicking bacterial meningoencephalitis: a case report.

    PubMed

    Huang, Wen-Yi; Chien, Yu-Yi; Wu, Chia-Lun; Weng, Wei-Chieh; Peng, Tsung-I; Chen, Hsien-Chih

    2009-05-01

    Pituitary apoplexy is a rare but life-threatening disorder. Clinical presentation of this condition includes severe headache, impaired consciousness, fever, visual disturbance, and variable ocular paresis. Signs of meningeal irritation are very rare. However, if present and associated with headache, fever, and pleocytosis, meningeal irritation may lead to misinterpretation as infectious meningoencephalitis. To the best of our knowledge, pituitary apoplexy with an initial presentation mimicking infectious meningoencephalitis had rarely been reported in the literature. Here, we report a 57-year-old man who had acute severe headache, high fever, neck stiffness, disturbance in consciousness, and left ocular paresis. Laboratory data showed leukocytosis, an elevated C-reactive protein level, and neutrophilic pleocytosis in the cerebrospinal fluid. Because bacterial meningoencephalitis was suspected, empiric antibiotic therapy was administered but in vain. Further examinations indicated a diagnosis of pituitary adenoma with apoplexy. After the immediate administration of intravenous corticosteroid supplement and surgical decompression, the patient recovered.

  12. Somatostatin receptor subtypes mRNA in TSH-secreting pituitary adenomas: a case showing a dramatic reduction in tumor size during short octreotide treatment.

    PubMed

    Horiguchi, Kazuhiko; Yamada, Masanobu; Umezawa, Ryohei; Satoh, Teturo; Hashimoto, Koshi; Tosaka, Masahiko; Yamada, Shozo; Mori, Masatomo

    2007-06-01

    TSH-secreting adenoma is a rare pituitary adenoma, and the expression levels of the specific subtypes of somatostatin receptors (sstr) mRNAs have remained obscure. To determine the quantitative expression of the sstr1-5 mRNAs in TSH-secreting adenomas that may be related to the efficacy of treatment with a somatostatin analogue, expression of the sstr1-5 mRNAs was examined and compared in TSH-secreting adenomas and other pituitary adenomas. The pituitary adenomas were obtained at transsphenoidal surgery from 4 cases of TSH-secreting adenoma, including 1 patient showing a significant shrinkage of the tumor size after only 10 days of octreotide treatment, 2 patients without tumor size reduction and 1 patient without treatment, and 5 GH-secreting adenomas, 6 prolactinomas, 5 nonfunctioning adenomas, 4 ACTH-secreting adenomas and normal pituitaries at autopsy from 4 normal subjects. In comparison to the normal pituitary, sstr2A>sstr1>sstr5>sstr3 mRNAs were expressed in the TSH-secreting adenomas examined. No expression of sstr2B or sstr4 mRNA was observed. The expression level of sstr2 mRNA was significantly higher than those in normal pituitary, prolactinomas, ACTH-secreting and nonfunctioning pituitary adenomas. The patient with marked shrinkage of the tumor showed the highest expression of both sstr2 and sstr5 mRNAs among all the cases of pituitary adenoma. A TSH-secreting tumor without shrinkage showed a similar expression level of sstr2 mRNA. These findings demonstrated that TSH-secreting adenomas express sstr1, 2A, 3 and 5 mRNAs, predominantly sstr2A, and in addition to the expression of sstr2 mRNA, the expression level of sstr5 mRNA may be a factor affecting the tumor shrinkage by somatostatin analogues against TSH-secreting adenomas.

  13. Effect of miR-106b on Invasiveness of Pituitary Adenoma via PTEN-PI3K/AKT

    PubMed Central

    Zheng, Zhiming; Zhang, Yongchao; Zhang, Zhen; Yang, Yihang; Song, Tao

    2017-01-01

    Background Pituitary adenomas are mostly benign tumors, although certain cases have invasiveness, which might be related with high expression of miR-106b. The PTEN-PI3K/AKT signal pathway is known to be related with cell migration and invasion. Among these, PTEN is the target gene for miR-106b. Whether miR-106b affects invasiveness of pituitary adenoma via PTEN-PI3K/AKT is unclear. Material/Methods Both invasive and non-invasive pituitary adenoma tissue samples were collected from our Neurosurgery Department, in parallel with brain tissues after head contusion surgery. Pituitary adenoma cell line HP75 was cultured in vitro and divided into NC and miR-106b inhibitor groups for measuring cell cycle/proliferation. Malignant growth of cells was measured by agarose gel clonal assay, while cell migration and invasion were reflected by starch assay and Transwell assay, respectively. The expression of PTEN, PI3K/AKT, and MMP-9 was measured. Results MiR-106b was significantly up-regulated in pituitary adenoma but PTEN was down-regulated, especially in invasive tumors. The inhibition of miR-106b remarkably suppressed proliferation and anchorage-independent growth of HP75 cells, with major arrest of cell cycles. The inhibition of miR-106b significantly depressed starch healing and invasive potency of cells. A negative targeted regulation existed between miR-106b and PTEN, as the inhibition of miR-106b significantly enhanced PTEN expression, affecting the activity of downstream PI3K/AKT signaling pathway, thus affecting migration and invasion of pituitary adenoma. Conclusions MiR-106b can affect migration and invasion of pituitary adenoma cells via regulating PTEN and further activity of the PI3K/AKT signaling pathway and MMP-9 expression. PMID:28288092

  14. Lower prolactin levels during cabergoline treatment are associated to tumor shrinkage in prolactin secreting pituitary adenoma.

    PubMed

    Lombardi, M; Lupi, I; Cosottini, M; Rossi, G; Manetti, L; Raffaelli, V; Sardella, C; Martino, E; Bogazzi, F

    2014-12-01

    Dopamine agonists are considered as the first line therapy in prolactin (PRL) secreting pituitary adenomas inducing a normalization of serum PRL and reduction of tumor size. It is known that serum PRL levels, obtained during treatment, are a predictor of tumor shrinkage. Whether PRL suppression below the lower limit of the normal range is related to a greater chance of tumor shrinkage than just its normalization has not been established. This retrospective cohort study was carried out in a tertiary center. Clinical records of 151 patients with PRL-secreting pituitary adenomas (73 micro-, 78 macroadenomas) treated with cabergoline for at least 24 months were analyzed. The adenoma size was analyzed by MRI before and after 24 months of treatment. PRL levels were evaluated every 6 months, assigning a score at each time point (PRL 0 = suppressed; 1 = normal; 2 = above normal). The total score, after 24 months of treatment, was expressed as the sum of the score at each time point and ranged between 0 and 8. A tumor shrinkage was observed in 102/151 patients (67.5%) and it was significantly associated to a lower PRL total score (p = 0.021, OR = 0.85, CI = 0.73-0.97), being significantly more frequent in patients with suppressed PRL than in those with normal PRL (p = 0.045, OR = 0.42, CI = 0.18-0.98) at 24 months. Cabergoline therapy with the goal of achieving PRL levels below the lower limit of normal range can increase the chance to obtain tumor shrinkage of PRL-secreting pituitary adenomas.

  15. Three-dimensional Alginate-bead Culture of Human Pituitary Adenoma Cells.

    PubMed

    Avila-Rodríguez, Dulce; Paisano-Cerón, Karina; Valdovinos-Ramírez, Irene; Solano-Agama, Carmen; Ortiz-Plata, Alma; Mendoza-Garrido, María E

    2016-02-18

    A three-dimensional culture method is described in which primary pituitary adenoma cells are grown in alginate beads. Alginate is a polymer derived from brown sea algae. Briefly, the tumor tissue is cut into small pieces and submitted to an enzymatic digestion with collagenase and trypsin. Next, a cell suspension is obtained. The tumor cell suspension is mixed with 1.2% sodium alginate and dropped into a CaCl2 solution, and the alginate/cell suspension is gelled on contact with the CaCl2 to form spherical beads. The cells embedded in the alginate beads are supplied with nutrients provided by the culture media enriched with 20% FBS. Three-dimensional culture in alginate beads maintains the viability of adenoma cells for long periods of time, up to four months. Moreover, the cells can be liberated from the alginate by washing the beads with sodium citrate and seeded on glass coverslips for further immunocytochemical analyses. The use of a cell culture model allows for the fixation and visualization of the actin cytoskeleton with minimal disorganization. In summary, alginate beads provide a reliable culture system for the maintenance of pituitary adenoma cells.

  16. Hormones and the bone marrow: panhypopituitarism and pancytopenia in a man with a pituitary adenoma.

    PubMed

    Lang, Dianna; Mead, Jennifer S; Sykes, David B

    2015-05-01

    In rare cases, pancytopenia results from hormonal deficiencies that arise in the setting of panhypopituitarism. Here we describe the unusual case of a 60-year-old man who presented with progressive fatigue and polyuria, and whose laboratory workup revealed a deficiency of the five hormones associated with the action of the anterior pituitary (thyroid hormone, testosterone, cortisol, prolactin, and insulin-like growth factor-1). Imaging of the pituitary demonstrated a cystic mass consistent with a pituitary adenoma replacing much of the normal pituitary tissue. His symptoms and hematologic abnormalities rapidly resolved with prednisone and levothyroxine supplementation. While the majority of reported cases of panhypopituitarism with bone marrow suppression are the result of peripartum sepsis or hemorrhage leading to pituitary gland necrosis (Sheehan's syndrome), it is also important to consider the diagnosis of hypopituitarism in patients with hypothyroidism, low cortisol levels, and pancytopenia. The causal relationship between pancytopenia and panhypopituitarism is not well understood, though it does reinforce the important influence of these endocrine hormones on the health of the bone marrow.

  17. Thyroid storm induced by TSH-secreting pituitary adenoma: a case report.

    PubMed

    Fujio, Shingo; Ashari; Habu, Mika; Yamahata, Hitoshi; Moinuddin, F M; Bohara, Manoj; Arimura, Hiroshi; Nishijima, Yui; Arita, Kazunori

    2014-01-01

    Thyroid stimulating hormone-secreting pituitary adenomas (TSHomas) are uncommon tumors of the anterior pituitary gland. Patients with TSHomas may present with hyperthyroidism, but the incidence of thyroid storm due to TSHomas has yet to be determined. We report a rare case of thyroid storm caused by TSHoma in a 54-year-old woman. Preoperatively she had symptoms of excessive sweating and palpitation. Blood tests showed inappropriate secretion of TSH with blood TSH 6.86 μ U/mL, fT3 19.8 pg/mL, and fT4 5.95 ng/dL. Magnetic resonance imaging (MRI) revealed a pituitary tumor with maximum diameter of 13 mm that was extirpated through transsphenoidal route. After operation the patient was stuporous and thyroid storm occurred presenting with hyperthermia, hypertension, and tachycardia. It was well managed with nicardipine, midazolam, steroids, and potassium iodide. Immunohistochemical staining of tumor specimen was positive for TSH and growth hormone (GH). One year after operation, fT3 and fT4 levels were still high. As her tumor was diagnosed to be GH- and TSH-producing adenoma, octreotide injection therapy was started, which normalized thyroid hormone levels. This is the second reported case with thyroid storm due to TSHoma and emphasizes the importance of strategies with interdisciplinary cooperation for prevention of such emergency conditions.

  18. Vascular endothelial growth inhibitor (VEGI) is an independent indicator for invasion in human pituitary adenomas.

    PubMed

    Jia, Wang; Sander, Andrew J; Jia, Guijun; Ni, Ming; Liu, Xiao; Lu, Runchun; Jiang, Wen G

    2013-09-01

    Pituitary ademonas are benign tumours from the pituitary gland but may have an invasive and destructive growth pattern. There is little understanding of the growth and progression control of pituitary tumours. In the present study, we investigated the expression of vascular endothelial growth inhibitor (VEGI), a vascular endothelial growth and apoptosis regulator and VEGI receptor Death Receptor-3 (DR3), in clinical pituitary tumours. Pituitary tumours from 95 patients were included in the study. Fresh pituitary tumours were obtained immediately after surgery and processed for histological and molecular-based analyses. Histopathological and clinical information including tumour size, tumour invasion and endocrine status were analyzed against the gene transcript expression of VEGI, DR3 and VEGF. VEGI and VEGF family and VEGF receptors were quantitatively determined for their gene transcript expression. The expression levels of VEGI were significantly lower in pituitary tumours which invaded the sella floor, and with suprasellar extension than in non-invasive tumours (p=0.0073). VEGI levels were also negatively correlated with cavernous sinus invasion stage (p<0.0001), in that a high level of VEGI was associated with low tumour grade. Multivariate analysis indicated that VEGI is an independent factor predictive of invasion (p=0.05). It was further demonstrated that the relationship between VEGI and pituitary tumour invasion were independent of the expression of VEGF and its receptors. Low levels of VEGI transcripts were associated with the intratumoural haemorrhage (p=0.05). Out of all the pituitary tumours, 59 were non-functional. Out of the functional tumours, it was found that follicle stimulating hormone (FSH)-expressing and gonadotrophic tumours tended to have markedly low levels of VEGI transcripts, compared with non-functional tumours (p=0.0026 and p=0.003, respectively). The opposite was seen with thyroid-stimulating hormone (TSH)-secreting tumours. Levels of

  19. In vitro impact of pegvisomant on growth hormone-secreting pituitary adenoma cells

    PubMed Central

    Cuny, Thomas; Zeiller, Caroline; Bidlingmaier, Martin; Défilles, Céline; Roche, Catherine; Blanchard, Marie-Pierre; Theodoropoulou, Marily; Graillon, Thomas; Pertuit, Morgane; Figarella-Branger, Dominique; Enjalbert, Alain; Brue, Thierry

    2016-01-01

    Pegvisomant (PEG), an antagonist of growth hormone (GH)-receptor (GHR), normalizes insulin-like growth factor 1 (IGF1) oversecretion in most acromegalic patients unresponsive to somatostatin analogs (SSAs) and/or uncontrolled by transsphenoidal surgery. The residual GH-secreting tumor is therefore exposed to the action of circulating PEG. However, the biological effect of PEG at the pituitary level remains unknown. To assess the impact of PEG in vitro on the hormonal secretion (GH and prolactin (PRL)), proliferation and cellular viability of eight human GH-secreting tumors in primary cultures and of the rat somatolactotroph cell line GH4C1. We found that the mRNA expression levels of GHR were characterized in 31 human GH-secreting adenomas (0.086 copy/copy β-Gus) and the GHR was identified by immunocytochemistry staining. In 5/8 adenomas, a dose-dependent inhibition of GH secretion was observed under PEG with a maximum of 38.2±17% at 1μg/mL (P<0.0001 vs control). A dose-dependent inhibition of PRL secretion occurred in three mixed GH/PRL adenomas under PEG with a maximum of 52.8±11.5% at 10μg/mL (P<0.0001 vs control). No impact on proliferation of either human primary tumors or GH4C1 cell line was observed. We conclude that PEG inhibits the secretion of GH and PRL in primary cultures of human GH(/PRL)-secreting pituitary adenomas without effect on cell viability or cell proliferation. PMID:27267119

  20. A Rapid Biochemical and Radiological Response to the Concomitant Therapy with Temozolomide and Radiotherapy in an Aggressive ACTH Pituitary Adenoma.

    PubMed

    Misir Krpan, Ana; Dusek, Tina; Rakusic, Zoran; Solak, Mirsala; Kraljevic, Ivana; Bisof, Vesna; Ozretic, David; Kastelan, Darko

    2017-01-01

    Background and Importance. In the last eight years temozolomide (TMZ) has been used as the last-line treatment modality for aggressive pituitary tumors to be applied after the failure of surgery, medical therapy, and radiotherapy. The objective was to achieve a rapid control of tumor growth and hormone normalization with concurrent chemoradiotherapy in a patient with very aggressive ACTH pituitary adenoma. Clinical Presentation. We describe a patient with an aggressive ACTH-producing adenoma treated with concurrent temozolomide and radiotherapy. The patient suffered from an aggressive ACTH adenoma resistant to surgical and medical treatment. After two months of concurrent temozolomide and radiotherapy, cortisol normalization and significant tumor shrinkage were observed. After 22 months of follow-up, there is still no evidence of tumor recurrence. Conclusion. Concurrent treatment with temozolomide and irradiation appears to be highly effective in the achievement of the tumor volume control as well as in the control of ACTH secretion in aggressive ACTH adenoma.

  1. A Rapid Biochemical and Radiological Response to the Concomitant Therapy with Temozolomide and Radiotherapy in an Aggressive ACTH Pituitary Adenoma

    PubMed Central

    2017-01-01

    Background and Importance. In the last eight years temozolomide (TMZ) has been used as the last-line treatment modality for aggressive pituitary tumors to be applied after the failure of surgery, medical therapy, and radiotherapy. The objective was to achieve a rapid control of tumor growth and hormone normalization with concurrent chemoradiotherapy in a patient with very aggressive ACTH pituitary adenoma. Clinical Presentation. We describe a patient with an aggressive ACTH-producing adenoma treated with concurrent temozolomide and radiotherapy. The patient suffered from an aggressive ACTH adenoma resistant to surgical and medical treatment. After two months of concurrent temozolomide and radiotherapy, cortisol normalization and significant tumor shrinkage were observed. After 22 months of follow-up, there is still no evidence of tumor recurrence. Conclusion. Concurrent treatment with temozolomide and irradiation appears to be highly effective in the achievement of the tumor volume control as well as in the control of ACTH secretion in aggressive ACTH adenoma. PMID:28357143

  2. Rapid decrease in amino acid metabolism in prolactin-secreting pituitary adenomas after bromocriptine treatment: a PET study

    SciTech Connect

    Bergstroem, M.M.; Muhr, C.; Lundberg, P.O.; Bergstroem, K.G.; Gee, A.D.; Fasth, K.J.; Langstroem B5

    1987-09-01

    Four patients with prolactin-secreting pituitary adenomas were examined with positron emission tomography using L-(/sup 11/C)methionine to monitor the effect of dopamine agonist treatment on the amino acid metabolism in the tumors. Within the first few hours after intramuscular injection of bromocriptine retard (50 mg) the amino acid metabolism decreased by 40%. Two of the patients were reexamined 7 and 9 days later and showed a 70% reduction in the metabolism of the adenomas. This metabolic effect was later accompanied by significant tumor shrinkage in all adenomas. It is suggested that bromocriptine has a general and rapid effect on the protein synthesis of the prolactin-secreting pituitary adenoma cells.

  3. Thyroid-stimulating hormone-secreting ectopic pituitary adenoma of the nasopharynx.

    PubMed

    Nishiike, Suetaka; Tatsumi, Ke-ita; Shikina, Takashi; Masumura, Chisako; Inohara, Hidenori

    2014-12-01

    Thyroid-stimulating hormone-secreting ectopic pituitary adenoma of the nasopharynx is highly unusual, with only three reported cases in the world literature. We describe the clinical presentation and radiologic findings in one patient with such rare lesions. A 46-year-old male with typical symptoms of Grave's disease was found to have a mass on magnetic resonance imaging. An otolaryngologic examination revealed a nasopharyngeal mass lesion, which was endoscopically resected. The results of immunohistochemical staining for thyroid-stimulating hormone were positive. After the resection, the patient's TSH was within normal limits. The clinical significance of the case and a brief literature review are presented.

  4. Preoperative Extrapontine Myelinolysis with Good Outcome in a Patient with Pituitary Adenoma

    PubMed Central

    Zhou, Ying; Zhu, Yicheng; Wang, Wenze

    2016-01-01

    Few preoperative extrapontine myelinolysis (EPM) cases with pituitary adenoma have been reported. No such case had long follow-up to see the outcome of EPM. We reported a 38-year-old man complaining of nausea, malaise and transient loss of consciousness who was found to have severe hyponatremia. Neurologic deficits including altered mental status, behavioral disturbances, dysarthria and dysphagia developed despite slow correction of hyponatremia. Endocrine and imaging studies revealed hypopituitarism, nonfunctional pituitary macroadenoma and extrapontine myelinolysis. Transsphenoidal surgery was performed after three weeks of supportive therapy, when neurological symptoms improved significantly. The patient recovered function completely 3 months after surgery. Our case indicates that outcome of EPM can be good even with prolonged periods of severe neurologic impairment. PMID:26962424

  5. Quantitative evaluation of vision-related and health-related quality of life after endoscopic transsphenoidal surgery for pituitary adenoma.

    PubMed

    Wolf, Amparo; Coros, Alexandra; Bierer, Joel; Goncalves, Sandy; Cooper, Paul; Van Uum, Stan; Lee, Donald H; Proulx, Alain; Nicolle, David; Fraser, J Alexander; Rotenberg, Brian W; Duggal, Neil

    2016-10-07

    OBJECTIVE Endoscopic resection of pituitary adenomas has been reported to improve vision function in up to 80%-90% of patients with visual impairment due to these adenomas. It is unclear how these reported rates translate into improvement in visual outcomes and general health as perceived by the patients. The authors evaluated self-assessed health-related quality of life (HR-QOL) and vision-related QOL (VR-QOL) in patients before and after endoscopic resection of pituitary adenomas. METHODS The authors prospectively collected data from 50 patients who underwent endoscopic resection of pituitary adenomas. This cohort included 32 patients (64%) with visual impairment preoperatively. Twenty-seven patients (54%) had pituitary dysfunction, including 17 (34%) with hormone-producing tumors. Patients completed the National Eye Institute Visual Functioning Questionnaire and the 36-Item Short Form Health Survey preoperatively and 6 weeks and 6 months after surgery. RESULTS Patients with preoperative visual impairment reported a significant impact of this condition on VR-QOL preoperatively, including general vision, near activities, and peripheral vision; they also noted vision-specific impacts on mental health, role difficulties, dependency, and driving. After endoscopic resection of adenomas, patients reported improvement across all these categories 6 weeks postoperatively, and this improvement was maintained by 6 months postoperatively. Patients with preoperative pituitary dysfunction, including hormone-producing tumors, perceived their general health and physical function as poorer, with some of these patients reporting improvement in perceived general health after the endoscopic surgery. All patients noted that their ability to work or perform activities of daily living was transiently reduced 6 weeks postoperatively, followed by significant improvement by 6 months after the surgery. CONCLUSIONS Both VR-QOL and patient's perceptions of their ability to do work and

  6. Prolactinomas, Cushing's disease and acromegaly: debating the role of medical therapy for secretory pituitary adenomas

    PubMed Central

    2010-01-01

    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 who have not responded to

  7. Endoscopic approach to a collision tumor of growth hormone-secreting adenoma and gangliocytoma in the pituitary gland.

    PubMed

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

    2014-07-01

    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.

  8. EZH2 is highly expressed in pituitary adenomas and associated with proliferation.

    PubMed

    Schult, David; Hölsken, Annett; Siegel, Sonja; Buchfelder, Michael; Fahlbusch, Rudolf; Kreitschmann-Andermahr, Ilonka; Buslei, Rolf

    2015-11-23

    Enhancer of zeste homolog 2 (EZH2) is a core epigenetic regulator, playing a crucial role in cell cycle regulation. The protein is known to be associated with proliferation and worse outcome in several tumor entities. In this study, we immunohistochemically investigated the expression pattern of EZH2 in a large cohort of pituitary tumors. These results were correlated with clinical features and double immunofluorescence stainings (DIS) were conducted to evaluate co-expression of EZH2 and proliferation marker Ki-67. Furthermore, we analyzed the effect of EZH2 inhibition on cell proliferation in vitro using the pituitary cell line AtT-20. While in the normal anterior pituitary EZH2 was almost absent, the cohort of tumors showed enhanced expression levels (p ≤ 0.0005). This was positively associated with Ki-67 indices (r = 0.834, p ≤ 0.0005) and DIF confirmed a predominant co-expression of both markers. In vitro experiments revealed a significant (p ≤ 0.05) decrease of tumor cell proliferation using the EZH2 inhibitor GSK126. Our results further support that epigenetic events are involved in the pathogenesis and biology of pituitary adenomas (PA). Therefore, EZH2 may function as a new potential target for therapeutic interventions in PA.

  9. [Clinical and morphological characteristics, diagnostic criteria, and outcomes of surgical treatment of TSH-secreting pituitary adenomas].

    PubMed

    Astaf'eva, L I; Kadashev, B A; Shishkina, L V; Kalinin, P L; Fomichev, D V; Kutin, M A; Aref'eva, I A; Dzeranova, L K; Sidneva, Yu G; Klochkova, I S; Rotin, D L

    2016-01-01

    Thyrotropinomas (TSH-secreting tumors) are a rare type of pituitary adenomas, which account for about 0.5-2.0% of all pituitary tumors. The criterion of thyrotropinoma is visualization of the tumor in the presence of a normal or elevated level of the thyroid-stimulating hormone (TSH) in the blood and elevated concentrations of free T4 (fT4) and free T3 (fT3).

  10. The anterolateral approach for the transcranial resection of pituitary adenomas: technical note.

    PubMed

    Agazzi, Siviero; Youssef, Ashraf Sami; van Loveren, Harry R

    2010-05-01

    We sought to quantify the mean surface area of the exposed diaphragma sellae and the mean sellar volume in the subfrontal and anterolateral approaches to pituitary adenomas and to detail our expansion of the superficial and deep window in the anterolateral approach. We performed a retrospective data analysis and cadaveric study in a clinical and skull base laboratory. We studied eight patients who had anterolateral approach for transcranial resection of pituitary macroadenoma and seven cadaveric specimens. Main outcome measures were degree of tumor resection, cerebrospinal fluid (CSF) leak, cranial nerve outcome, and quantification of the exposed sella via the anterior (subfrontal) and anterolateral approach. We observed complete resection in one; visual outcome: stable in three, improved in four, worsened in one; CSF leakage in two; transient CN III palsy in three; mean surface area (mm(2)) of exposed diaphragma sellae,115.3 (subfrontal approach) versus 94.7 (anterolateral approach; p = 0.1); mean sellar volume (mm(3)) exposed, 224.8 (subfrontal approach) versus 569.3 (anterolateral approach; p < 0.0001). Our technical note supports the increased exposure of sellar volume via the anterolateral approach. Despite the relatively high complication rate, complex cranial surgeons should maintain the skills and knowledge of transcranial approaches. Indeed, the rapid expansion of transsphenoidal techniques will continue to decrease the number of cases but will also continue to increase the complexity of those adenomas that are referred for transcranial resection.

  11. The role of stereotactic radiosurgery in the multimodal management of growth hormone-secreting pituitary adenomas.

    PubMed

    Stapleton, Christopher J; Liu, Charles Y; Weiss, Martin H

    2010-10-01

    Growth hormone (GH)-secreting pituitary adenomas represent a common source of GH excess in patients with acromegaly. Whereas surgical extirpation of the culprit lesion is considered first-line treatment, as many as 19% of patients develop recurrent symptoms due to regrowth of previously resected adenomatous tissue or to continued growth of the surgically inaccessible tumor. Although medical therapies that suppress GH production can be effective in the management of primary and recurrent acromegaly, these therapies are not curative, and lifelong treatment is required for hormonal control. Stereotactic radiosurgery has emerged as an effective adjunctive treatment modality, and is an appealing alternative to conventional fractionated radiation therapy. The authors reviewed the growing body of literature concerning the role of radiosurgical procedures in the treatment armamentarium of acromegaly, and identified more than 1350 patients across 45 case series. In this review, the authors report that radiosurgery offers true hormonal normalization in 17% to 82% of patients and tumor growth control in 37% to 100% of cases across all series, while minimizing adverse complications. As a result, stereotactic radiosurgery represents a safe and effective treatment option in the multimodal management of primary or recurrent acromegaly secondary to GH-secreting pituitary adenomas.

  12. Temozolomide and pasireotide treatment for aggressive pituitary adenoma: expertise at a tertiary care center.

    PubMed

    Ceccato, Filippo; Lombardi, Giuseppe; Manara, Renzo; Emanuelli, Enzo; Denaro, Luca; Milanese, Laura; Gardiman, Marina Paola; Bertorelle, Roberta; Scanarini, Massimo; D'Avella, Domenico; Occhi, Gianluca; Boscaro, Marco; Zagonel, Vittorina; Scaroni, Carla

    2015-03-01

    Aggressive pituitary adenomas (PAs) are clinically challenging for endocrinologists and neurosurgeons due to their locally invasive nature and resistance to standard treatment (surgery, medical or radiotherapy). Two pituitary-directed drugs have recently been proposed: temozolomide (TMZ) for aggressive PA, and pasireotide for ACTH-secreting PA. We describe the experience of our multidisciplinary team of endocrinologists, neurosurgeons, neuroradiologists, oncologists, otolaryngologists and pathologists with TMZ and pasireotide treatment for aggressive PAs in terms of their radiological shrinkage and genetic features. We considered five patients with aggressive PA, three of them non-secreting (two ACTH-silent and one becoming ACTH secreting), and two secreting (one GH and one ACTH). TMZ was administrated orally at 150-200 mg/m(2) daily for 5 days every 28 days to all 5 patients, and 2 of them also received pasireotide 600-900 µg bid sc. We assessed the MRI at the baseline and during TMZ or pasireotide treatment. We also checked for MGMT promoter methylation and IDH, BRAF and kRAS mutations. Considering TMZ, two patients showed PA progression, one stable disease and two achieved radiological and clinical response. Pasireotide was effective in reducing hypercortisolism and mass volume, combined with TMZ in one case. Both treatments were generally well tolerated; one patient developed a grade 2 TMZ-induced thrombocytopenia. None of patients developed hypopituitarism while taking TMZ or pasireotide treatment. No genetic anomalies were identified in the adenoma tissue. TMZ and pasireotide may be important therapies for aggressive PA, alone or in combination.

  13. Pituitary gland metastasis from renal cell carcinoma presented as a non-functioning macroadenoma.

    PubMed

    Kramer, Caroline Kaercher; Ferreira, Nélson; Silveiro, Sandra Pinho; Gross, Jorge Luiz; Dora, José Miguel; Azevedo, Mirela Jobim de

    2010-01-01

    Metastatic tumors involving the pituitary gland are an uncommon finding and occur in up to 1% of all pituitary tumor resections. A 74-year-old man had progressive vision deterioration, over the 30 days prior to consultation. He did not complain of headache or polyuria, but referred to intestinal constipation. Five years ago, he underwent a right radical nephrectomy for renal cell carcinoma, followed by chemotherapy and radiotherapy for lung and parotid metastases. On ophthalmologic examination, there was a left abducens nerve palsy and bitemporal hemianopia. Magnetic resonance imaging demonstrated a sellar mass with suprasellar cistern extension compressing the optic chiasm. Endocrinological evaluation revealed central adrenal and gonadal insufficiencies. The patient underwent a transsphenoidal tumor resection that revealed renal cell carcinoma. This case illustrates that metastatic pituitary lesions can mimic typical symptoms and signs of pituitary macroadenoma. Furthermore, clinical diabetes insipidus, a common finding of pituitary metastases, can be absent.

  14. Clinical factors involved in the recurrence of pituitary adenomas after surgical remission: a structured review and meta-analysis.

    PubMed

    Roelfsema, Ferdinand; Biermasz, Nienke R; Pereira, Alberto M

    2012-03-01

    To study the currently available data of recurrence rates of functioning and nonfunctioning pituitary adenomas following surgical cure and to analyze associated predisposing factors, which are not well established. A systematic literature search was conducted using Medline, Embase, Web of Science and the Cochran Library for studies reporting data on recurrence of pituitary adenoma after surgery, in nonfunctioning adenoma (NF), prolactinoma (PRL) acromegaly (ACRO) and Cushing's disease (CUSH). Of 557 initially retrieved potential relevant studies 143 were selected. Recurrence in NFA was defined as reappearance of tumor on MRI or CT. Increase of hormone levels above normal limits as set by the authors after initial remission was used to indicate recurrence in the functioning tumor types. Remission percentage was lowest in NFA compared with other tumor types (P < 0.001). Surgery-related hypopituitarism was more frequent in CUSH than in the other tumors (P < 0.001). Recurrence, expressed as percentage of the cured population or as ratio of recurrence and total patient years of follow-up was highest in PRL (P < 0.001). The remission percentage did not improve over 3 decades of publications, but there was a modest decrease in recurrence rate (P = 0.04). Recurrences peaked between 1 and 5 years after surgery. Most of the studies with a sufficient number of recurrences did not apply multivariate statistics, and mentioned at best associated factors. Age, gender, tumor size and invasion were generally unrelated to recurrence. For functioning adenomas a low postoperative hormone concentration was a prognostically favorable factor. In NFA no specific factor predicted recurrence. Recurrence rate differs between pituitary adenomas, being highest in patients with prolactinoma, with the highest incidence of recurrence between 1 and 5 years after surgery in all adenomas. Patients with NFA have a lower chance of remission than patients with functioning adenomas. The postoperative

  15. Gamma Knife Radiosurgery for Patients With Nonfunctioning Pituitary Adenomas: Results From a 15-Year Experience

    SciTech Connect

    Pollock, Bruce E. Cochran, Joseph; Natt, Neena; Brown, Paul D.; Erickson, Dana; Link, Michael J.; Garces, Yolanda I.; Foote, Robert L.; Stafford, Scott L.; Schomberg, Paula J.

    2008-04-01

    Purpose: To evaluate the efficacy and complications of stereotactic radiosurgery for patients with nonfunctioning pituitary adenomas (NFA). Methods and Materials: This was a retrospective review of 62 patients with NFA undergoing radiosurgery between 1992 and 2004, of whom 59 (95%) underwent prior tumor resection. The median treatment volume was 4.0 cm{sup 3} (range, 0.8-12.9). The median treatment dose to the tumor margin was 16 Gy (range, 11-20). The median maximum point dose to the optic apparatus was 9.5 Gy (range, 5.0-12.6). The median follow-up period after radiosurgery was 64 months (range, 23-161). Results: Tumor size decreased for 37 patients (60%) and remained unchanged for 23 patients (37%). Two patients (3%) had tumor growth outside the prescribed treatment volume and required additional treatment (fractionated radiation therapy, n = 1; repeat radiosurgery, n 1). Tumor growth control was 95% at 3 and 7 years after radiosurgery. Eleven (27%) of 41 patients with normal (n = 30) or partial (n = 11) anterior pituitary function before radiosurgery developed new deficits at a median of 24 months after radiosurgery. The risk of developing new anterior pituitary deficits at 5 years was 32%. The 5-year risk of developing new anterior pituitary deficits was 18% for patients with a tumor volume of {<=}4.0 cm{sup 3} compared with 58% for patients with a tumor volume >4.0 cm{sup 3} (risk ratio 4.5; 95% confidence interval = 1.3-14.9, p = 0.02). No patient had a decline in visual function. Conclusions: Stereotactic radiosurgery is effective in the management of patients with residual or recurrent NFA, although longer follow-up is needed to evaluate long-term outcomes. The primary complication is hypopituitarism, and the risk of developing new anterior pituitary deficits correlates with the size of the irradiated tumor.

  16. Effects of preoperative bromocriptine treatment on prolactin-secreting pituitary adenoma surgery

    PubMed Central

    CAO, YINGXIAO; WANG, FENGJU; LIU, ZHENBO; JIAO, BAOHUA

    2016-01-01

    Pituitary adenomas are benign intracranial endocrine tumors, accounting for ~10% of intracranial tumors. The aim of the present study was to analyze the effects of preoperative treatment with bromocriptine on the surgical treatment and postoperative complications of prolactin-secreting pituitary adenomas (prolactinomas). Data from 102 patients whose prolactinomas were surgically treated between March 2006 and March 2010 were retrospectively reviewed in the present study. The study group included 54 patients who had been treated preoperatively with bromocriptine. The patients were examined by magnetic resonance imaging (MRI) of the head and coronal computed tomography (CT) scanning, after which the pathological diagnosis of prolactinoma was confirmed. A total of 64 patients underwent total resection surgery through the nose and sphenoid sinus, and 25 patients underwent subtotal resection surgery or excision of a large portion of the tumor, leaving only a small quantity of residual tumor or tumor capsule. Patients were followed up for 1–9 months using MRI and measurements of serum prolactin levels. Seven patients were lost to follow-up. The results of the present study demonstrated that patients who were treated with large doses of bromocriptine or used bromocriptine chronically suffered from an increased rate of surgical difficulties and postoperative complications, as compared with the patents who had not been pre-treated with bromocriptine. In conclusion, oral administration of bromocriptine is important in the treatment of prolactinoma tumors. However, large doses or long-term use of bromocriptine may increase difficulties in surgery or postoperative complications, and reduce its ability to treat prolactinonas, as it can lead to hardening of the tumor tissue and capsules, and aggravate pituitary stalk adhesions. PMID:27168837

  17. Intraoperative magnetic resonance imaging during surgery for pituitary adenomas: pros and cons.

    PubMed

    Buchfelder, Michael; Schlaffer, Sven-Martin

    2012-12-01

    Surgery for pituitary adenomas still remains a mainstay in their treatment, despite all advances in sophisticated medical treatments and radiotherapy. Total tumor excision is often attempted, but there are limitations in the intraoperative assessment of the radicalism of tumor resection by the neurosurgeon. Standard postoperative imaging is usually performed with a few months delay from the surgical intervention. The purpose of this report is to review briefly the facilities and kinds of intraoperative magnetic resonance imaging for all physician and surgeons involved in the management of pituitary adenomas on the basis of current literature. To date, there are several low- and high-field magnetic resonance imaging systems available for intraoperative use and depiction of the extent of tumor removal during surgery. Recovery of vision and the morphological result of surgery can be largely predicted from the intraoperative images. A variety of studies document that depiction of residual tumor allows targeted attack of the remnant and extent the resection. Intraoperative magnetic resonance imaging offers an immediate feedback to the surgeon and is a perfect quality control for pituitary surgery. It is also used as a basis of datasets for intraoperative navigation which is particularly useful in any kind of anatomical variations and repeat operations in which primary surgery has distorted the normal anatomy. However, setting up the technology is expensive and some systems even require extensive remodeling of the operation theatre. Intraoperative imaging prolongs the operation, but may also depict evolving problems, such as hematomas in the tumor cavity. There are several artifacts in intraoperative MR images possible that must be considered. The procedures are not associated with an increased complication rate.

  18. Plurihormonal pituitary adenoma with concomitant adrenocorticotropic hormone (ACTH) and growth hormone (GH) secretion: a report of two cases and review of the literature.

    PubMed

    Rasul, Fahid Tariq; Jaunmuktane, Zane; Khan, Akbar Ali; Phadke, Rahul; Powell, Michael

    2014-01-01

    Plurihormonal pituitary adenomas are tumours that show immunoreactivity for more than one hormone that cannot be explained by normal adenohypophysial cytodifferentiation. The most common combinations in these adenomas include growth hormone (GH), prolactin (PRL) and one or more glycoprotein hormone sub-units (β-TSH, β-FSH, β-LH and αSU). The authors report two cases of a plurihormonal pituitary adenoma expressing the rare combination of ACTH and GH. They both underwent successful transphenoidal hypophysectomy (TSH). Long-term post-operative follow-up revealed no evidence of tumour recurrence. Due to the multiple secretions and plurihormonal characteristics clinical diagnosis of composite pituitary adenomas can be difficult. The authors discuss the diagnosis and management of composite pituitary adenomas and review the literature regarding this rare phenomenon.

  19. HIF-1α Inhibition Sensitized Pituitary Adenoma Cells to Temozolomide by Regulating Presenilin 1 Expression and Autophagy.

    PubMed

    Kun, Zhang; Yuling, Yang; Dongchun, Wang; Bingbing, Xie; Xiaoli, Li; Bin, Xu

    2016-12-01

    Pituitary adenomas usually develop temozolomide resistance, which could compromise the anticancer effects of temozolomide. Suppression of hypoxia-inducible factor 1α has been shown to sensitize glioblastoma cells to temozolomide treatment according to previous reports. However, whether and how the suppression of hypoxia-inducible factor 1α could sensitize pituitary adenomas to temozolomide treatment are still poorly understood. In the present study, using hypoxia-inducible factor 1α knockdown strategy, we demonstrated for the first time that hypoxia-inducible factor 1α knockdown could inhibit temozolomide-induced autophagy in rat pituitary adenoma GH3 cells and thus increase antitumor efficacy of temozolomide. Furthermore, we found hypoxia-inducible factor 1α knockdown could block autophagy process through neutralizing lysosomal pH value but not inhibiting autophagy induction. Finally, we found hypoxia-inducible factor 1α could regulate lysosomal pH value through regulating full length presenilin 1 expression, and exogenous reexpression of presenilin 1could restore lysosome acidic levels. Our data indicated hypoxia-inducible factor 1α knockdown could be a potential approach to improve the efficacy of temozolomide therapy for pituitary adenomas.

  20. [Congestive heart failure caused by the thyroid stimulating hormone(TSH) secreting pituitary adenoma: report of two cases].

    PubMed

    Fujita, K; Yanaka, K; Tomono, Y; Kamezaki, T; Kujiraoka, Y; Nose, T

    2001-08-01

    A 42-year-old man and a 31-year-old man with congestive heart failure caused by the thyroid stimulating hormone(TSH) secreting pituitary adenoma were reported. Heart failure was improved after transsphenoidal resection of the pituitary adenoma in each patient. The syndrome of inappropriate secretion of TSH causes hyperthyroidism. Thyroid hormone acts directly on cardiac muscle to increase the stroke volume. Hyperthyroidism itself reduces the peripheral vascular resistance and an elevated basal metabolism which is the basic physiologic change in hyperthyroidism dilates small vessels and reduces vascular resistance. The reduced vascular resistance contributes to increase stroke volume. Thyroid hormone also acts directly on the cardiac pacemakers to be apt to cause tachycardiac atrial fibrillation. These mechanical changes in hyperthyroidism increase not only the cardiac output but also the venous return. The increased blood volume and the shortened ventricular filling time due to tachycardia result in congestive heart failure. TSH secreting pituitary adenoma is a rare tumor, however heart failure is common disease. TSH secreting pituitary adenoma should be taken into consideration in patients with heart failure. The presented cases were very enlightening to understand the relation between brain tumor and heart disease.

  1. Interrater and intrarater reliability of the Knosp scale for pituitary adenoma grading.

    PubMed

    Mooney, Michael A; Hardesty, Douglas A; Sheehy, John P; Bird, Robert; Chapple, Kristina; White, William L; Little, Andrew S

    2016-07-01

    OBJECTIVE The goal of this study was to determine the interrater and intrarater reliability of the Knosp grading scale for predicting pituitary adenoma cavernous sinus (CS) involvement. METHODS Six independent raters (3 neurosurgery residents, 2 pituitary surgeons, and 1 neuroradiologist) participated in the study. Each rater scored 50 unique pituitary MRI scans (with contrast) of biopsy-proven pituitary adenoma. Reliabilities for the full scale were determined 3 ways: 1) using all 50 scans, 2) using scans with midrange scores versus end scores, and 3) using a dichotomized scale that reflects common clinical practice. The performance of resident raters was compared with that of faculty raters to assess the influence of training level on reliability. RESULTS Overall, the interrater reliability of the Knosp scale was "strong" (0.73, 95% CI 0.56-0.84). However, the percent agreement for all 6 reviewers was only 10% (26% for faculty members, 30% for residents). The reliability of the middle scores (i.e., average rated Knosp Grades 1 and 2) was "very weak" (0.18, 95% CI -0.27 to 0.56) and the percent agreement for all reviewers was only 5%. When the scale was dichotomized into tumors unlikely to have intraoperative CS involvement (Grades 0, 1, and 2) and those likely to have CS involvement (Grades 3 and 4), the reliability was "strong" (0.60, 95% CI 0.39-0.75) and the percent agreement for all raters improved to 60%. There was no significant difference in reliability between residents and faculty (residents 0.72, 95% CI 0.55-0.83 vs faculty 0.73, 95% CI 0.56-0.84). Intrarater reliability was moderate to strong and increased with the level of experience. CONCLUSIONS Although these findings suggest that the Knosp grading scale has acceptable interrater reliability overall, it raises important questions about the "very weak" reliability of the scale's middle grades. By dichotomizing the scale into clinically useful groups, the authors were able to address the poor

  2. An R201H activating mutation of the GNAS1 (Gsα) gene in a corticotroph pituitary adenoma

    PubMed Central

    Riminucci, M; Collins, M T; Lala, R; Corsi, A; Matarazzo, P; Gehron Robey, P; Bianco, P

    2002-01-01

    In the pituitary gland, activating mutations of the GNAS1 (Gsα) gene at Gln227 have been identified in adrenocorticotrophin secreting, growth hormone secreting, and prolactin secreting adenomas. To date, mutations at the codon encoding R201, typically underlying the McCune-Albright syndrome and isolated fibrous dysplasia of bone, have been demonstrated only in growth hormone secreting pituitary adenomas. In this study, a polymerase chain reaction amplified target sequence in exon 8 of the GNAS1 gene was sequenced, identifying the first R201 mutation seen in an isolated basophilic adenoma which generated Cushing's disease in a child. This case adds Cushing's disease to the range of human diseases caused by R201 mutations of the GNAS1 gene. PMID:11836449

  3. Elevation of growth hormone-releasing hormone receptor messenger ribonucleic acid expression in growth hormone-secreting pituitary adenoma with Gsalpha protein mutation.

    PubMed

    Sakai, Naoyuki; Kim, Kyongsong; Sanno, Naoko; Yoshida, Daizo; Teramoto, Akira; Shibasaki, Tamotsu

    2008-01-01

    Growth hormone-releasing hormone (GHRH) stimulates not only the synthesis and secretion of GH but also the proliferation of normal somatotrophs. The expression of GHRH receptor (GHRHR) is regulated by GHRH, both of which are known to be expressed in human GH-secreting pituitary adenoma cells. Somatic mutations in the subunit of Gsalpha protein (gsp), lead to the constitutive activation of adenylyl cyclase in pituitary adenomas that secrete GH. It has not been examined how gsp mutations influence GHRHR expression in GH-secreting adenomas. We therefore analyzed the expression levels of GHRHR messenger ribonucleic acid (mRNA) in GH-secreting pituitary adenomas focusing on a gsp mutation. Furthermore, we investigated the effect of GHRH on the expression of GHRHR mRNA in primary cultures of GH-secreting pituitary adenoma cells. GHRHR mRNA expression levels were significantly elevated in gsp mutation-positive GH-secreting adenomas compared with those in gsp mutation-negative ones. In primary-cultured GH-secreting adenoma cells, the increase of GH secretion in response to GHRH was shown in both gsp mutation-positive and -negative adenoma cells with a significantly higher response in the latter adenoma cells. GHRH increased GHRHR mRNA expression level in gsp mutation-negative adenoma cells while it was not influenced by GHRH in gsp mutation-positive adenoma cells. These results suggest that gsp mutations up-regulate GHRHR mRNA expression in GH-secreting pituitary adenoma cells, and that gsp mutations desensitize the adenoma cells to GHRH in terms of their GHRHR mRNA expression probably because of their saturation of GHRH signaling.

  4. Pituitary Adenoma With Paraganglioma/Pheochromocytoma (3PAs) and Succinate Dehydrogenase Defects in Humans and Mice

    PubMed Central

    Xekouki, Paraskevi; Szarek, Eva; Bullova, Petra; Giubellino, Alessio; Quezado, Martha; Mastroyannis, Spyridon A.; Mastorakos, Panagiotis; Wassif, Christopher A.; Raygada, Margarita; Rentia, Nadia; Dye, Louis; Cougnoux, Antony; Koziol, Deloris; Sierra, Maria de La Luz; Lyssikatos, Charalampos; Belyavskaya, Elena; Malchoff, Carl; Moline, Jessica; Eng, Charis; Maher, Louis James; Pacak, Karel; Lodish, Maya

    2015-01-01

    Context: Germline mutations in genes coding succinate dehydrogenase (SDH) subunits A, B, C, and D have been identified in familial paragangliomas (PGLs)/pheochromocytomas (PHEOs) and other tumors. We described a GH-secreting pituitary adenoma (PA) caused by SDHD mutation in a patient with familial PGLs. Additional patients with PAs and SDHx defects have since been reported. Design: We studied 168 patients with unselected sporadic PA and with the association of PAs, PGLs, and/or pheochromocytomas, a condition we named the 3P association (3PAs) for SDHx germline mutations. We also studied the pituitary gland and hormonal profile of Sdhb+/− mice and their wild-type littermates at different ages. Results: No SDHx mutations were detected among sporadic PA, whereas three of four familial cases were positive for a mutation (75%). Most of the SDHx-deficient PAs were either prolactinomas or somatotropinomas. Pituitaries of Sdhb+/− mice older than 12 months had an increased number mainly of prolactin-secreting cells and several ultrastructural abnormalities such as intranuclear inclusions, altered chromatin nuclear pattern, and abnormal mitochondria. Igf-1 levels of mutant mice tended to be higher across age groups, whereas Prl and Gh levels varied according to age and sex. Conclusion: The present study confirms the existence of a new association that we termed 3PAs. It is due mostly to germline SDHx defects, although sporadic cases of 3PAs without SDHx defects also exist. Using Sdhb+/− mice, we provide evidence that pituitary hyperplasia in SDHx-deficient cells may be the initial abnormality in the cascade of events leading to PA formation. PMID:25695889

  5. Neurocysticercosis, meningioma, and silent corticotroph pituitary adenoma in a 61-year-old woman.

    PubMed

    Ramirez, Maria Del Pilar; Restrepo, Juan E; Syro, Luis V; Rotondo, Fabio; Londoño, Francisco J; Penagos, Luis C; Uribe, Humberto; Horvath, Eva; Kovacs, Kalman

    2012-01-01

    We report here the case of a 61-year-old woman who presented with hydrocephalus and cystic and solid lesions in sella turcica, suprasellar areas, and third ventricle. After ventriculoperitoneal shunt she developed cognitive changes and the cystic lesions enlarged. Magnetic resonance imaging (MRI) demonstrated multiple cysts and a solid lesion in the sella and around the anterior clinoid process. With diagnosis of neurocysticercosis she underwent craniotomy. Pathologic examination documented two different lesions: viable and dead cysticerci with inflaming infiltration and a left anterior clinoidal meningioma. At the second surgery, six weeks later via transnasal transsphenoidal approach a silent corticotroph pituitary adenoma was removed which was studied by histology, immunohistochemistry, and electron microscopy. To our knowledge, the occurrence of these three different lesions in the sellar area was not described before.

  6. Neurocysticercosis, Meningioma, and Silent Corticotroph Pituitary Adenoma in a 61-Year-Old Woman

    PubMed Central

    Ramirez, Maria del Pilar; Restrepo, Juan E.; Syro, Luis V.; Rotondo, Fabio; Londoño, Francisco J.; Penagos, Luis C.; Uribe, Humberto; Horvath, Eva; Kovacs, Kalman

    2012-01-01

    We report here the case of a 61-year-old woman who presented with hydrocephalus and cystic and solid lesions in sella turcica, suprasellar areas, and third ventricle. After ventriculoperitoneal shunt she developed cognitive changes and the cystic lesions enlarged. Magnetic resonance imaging (MRI) demonstrated multiple cysts and a solid lesion in the sella and around the anterior clinoid process. With diagnosis of neurocysticercosis she underwent craniotomy. Pathologic examination documented two different lesions: viable and dead cysticerci with inflaming infiltration and a left anterior clinoidal meningioma. At the second surgery, six weeks later via transnasal transsphenoidal approach a silent corticotroph pituitary adenoma was removed which was studied by histology, immunohistochemistry, and electron microscopy. To our knowledge, the occurrence of these three different lesions in the sellar area was not described before. PMID:23346440

  7. Archetype based patient data modeling to support treatment of pituitary adenomas.

    PubMed

    Chalopin, Claire; Lindner, Dirk; Kropf, Stefan; Denecke, Kerstin

    2015-01-01

    The treatment of patients with pituitary adenoma requires the assessment of various patient data by the clinician. Because of their heterogeneity, they are stored in different sub-information systems, limiting a fast and easy access. The objective of this paper is to apply and test the tools provided by the openEHR Foundation to model the patient data relevant for diagnosis and treatment of the disease with the future intention to implement a centralised standard-based information platform. This platform should support the clinician in the treatment of the disease and improve the information exchange with other healthcare institutions. Some results of the domain modeling, so far obtained, are presented, and the advantages of openEHR emphasized. The free tools and the large database of existing structured and standard archetypes facilitated the modeling task. The separation of the domain modeling from the application development will support the next step of development of the information platform.

  8. Pituitary adenoma with seizures: PET demonstration of reduced glucose utilization in the medial temporal lobe

    SciTech Connect

    Bairamian, D.; Di Chiro, G.; Blume, H.; Ehrenberg, B.

    1986-05-01

    A patient with a benign chromophobe adenoma, who had incomplete surgical removal followed by radiotherapy, continued to have epileptic seizures up to two or three times a day. She was studied with positron emission tomography using /sup 18/F-2-deoxyglucose (FDG). This technique showed a high level of glucose utilization in the area of the operated tumor but also clear reduction of glucose utilization in the left medial temporal region adjacent to the sella and the scar tissue from the neoplasm. This area of reduced glucose utilization corresponded well to the same finding observed in other patients with complex partial epilepsy. A left temporal anterior lobectomy was carried out followed by improved control of the epilepsy. Positron emission tomography using FDG, together with electrophysiological examinations, may assist in the management of epilepsy related to pituitary tumors.

  9. AIP mutation identified in a patient with acromegaly caused by pituitary somatotroph adenoma with neuronal choristoma.

    PubMed

    Nishizawa, H; Fukuoka, H; Iguchi, G; Inoshita, N; Yamada, S; Takahashi, Y

    2013-05-01

    Pituitary adenoma with neuronal choristoma (PANCH) is a rare condition that includes ganglion cells and GH-producing tumor that is characterized by sparsely granulated somatotroph cell type. However, the pathophysiology of this condition remains to be elucidated. We report a case of 46-year-old woman with acromegaly caused by PANCH. The patient had a large and invasive macroadenoma that was resistant to preoperative therapy with somatostatin analogue (SSA) and dopamine agonist. Histological examination showed typical diffuse, chromophobe-type adenoma containing ganglion cells, and sparsely granulated somatotroph cell type, which were consistent with PANCH. Genetic analysis showed heterozygous germline missense mutation in the AIP gene that results in Y261X amino acid substitution. The clinical characteristics of acromegaly associated with AIP mutations are reportedly macroadenomas with tumor extension and invasion, lower decreases in GH and IGF-I and less tumor shrinkage with SSA treatment, and sparsely granulated somatotroph cell type, which are comparable with those observed in PANCH. Taken together, the mutation in AIP gene may explain the clinical characteristics and pathogenesis of PANCH.

  10. A Case of a TSH-secreting Pituitary Adenoma Associated with Evans' Syndrome.

    PubMed

    Yasuda, Atsushi; Seki, Toshiro; Oki, Masayuki; Takagi, Atsushi; Inomoto, Chie; Nakamura, Naoya; Atsumi, Hideki; Baba, Tanefumi; Matsumae, Mitsunori; Sasaki, Noriko; Suzuki, Yasuo; Fukagawa, Masafumi

    2015-06-20

    We present a case of a TSH-secreting pituitary adenoma (TSHoma) associated with Evans' syndrome. A 30-year-old woman was referred to our hospital due to purpura and ecchymoses on her limb and body and epistaxis. Evans' syndrome was diagnosed based on idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia. She had a history of malocclusion and thyroid gland enlargement 4 years prior to admission. Endocrinological tests and magnetic resonance imaging also revealed that this patient had hyperthyroidism due to the TSHoma and that this adenoma concomitantly secreted GH. Recently, several cases of Evans' syndrome were associated with hyperthyroidism caused by autoimmune thyroid disease, such as Graves' disease, suggesting that these 2 conditions may have a common immunological basis. To the best of our knowledge, there is no case report of Evans' syndrome associated with hyperthyroidism due to TSHoma. Our report suggests that the excess of thyroid hormone itself promotes autoimmunity in Evans' syndrome. Thus, early treatment for hyperthyroidism is necessary in TSHomas because of the possibility that thyroid hormone normalization may prevent the development of Evans' syndrome.

  11. Long-term results of radiotherapy in the treatment of pituitary adenomas in children and adolescents

    SciTech Connect

    Grigsby, P.W.; Thomas, P.R.; Simpson, J.R.; Fineberg, B.B.

    1988-12-01

    A retrospective review was performed of 11 children and adolescents (less than 19 years of age) with diagnosed pituitary adenomas. The patients were treated with subtotal resection and postoperative irradiation (S + R) or with irradiation alone (RT) at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, Washington University Medical Center, from January 1958 through December 1982. Patient conditions at diagnosis were acromegaly in one, Nelson's syndrome in one, prolactinoma in three, chromophobe adenoma in three, and Cushing's disease in three. Median follow-up was 15.6 years (range 6.3-29.5 years). Only two patients have had failure: one at 8.6 years and the other at 20.7 years following treatment. All four patients with visual field (VF) defects at diagnosis underwent S + R, with only one developing recurrent disease. The remaining seven patients, who did not have VF defects, received RT only, and there has been one failure in this group. None have suffered long-term visual complications. All have been able to continue school and/or work. Three of eight females have borne children. Hypopituitarism requiring medication occurred in all who received S + R and in four of seven who received RT only.

  12. Loss of heterozygosity at the SS receptor type 5 locus in human GH- and TSH-secreting pituitary adenomas.

    PubMed

    Filopanti, M; Ballarè, E; Lania, A G; Bondioni, S; Verga, U; Locatelli, M; Zavanone, L M; Losa, M; Gelmini, S; Peri, A; Orlando, C; Beck-Peccoz, P; Spada, A

    2004-11-01

    SS receptor types 2 and 5 (sst2 and sst5) are involved in the control of secretion and proliferation of normal and tumoral somatotrophs and thyrotrophs. The mechanisms leading to reduced responsiveness to SS analogues in patients with pituitary tumors are poorly understood. The aim of the study was to verify the possible loss of heterozygosity (LOH) at the sst5 gene locus in somatotroph and thyrotroph adenomas by screening leukocyte and tumor DNA for two single nucleotide polymorphisms, i.e. C1004T leading to P335L change and T-461C in the 5'-upstream region. Among the 13 informative samples, 1 GH- and 1 TSH-secreting adenoma showed LOH at sst5 gene locus with the retention of Leu335 variant. By analyzing other polymorphic markers spanning from telomere to 16p13.3-13.2 boundaries, DNA deletion of at least 1 megabase was found in both tumors. LOH in thyrotroph adenoma was associated with unusual tumor aggressiveness that required a second surgery and resistance to SS analogs, while no obvious phenotype was identified in the case of the somatotroph adenoma. In conclusions, LOH at the sst5 gene locus is a rare phenomenon, occurring in about 10% of pituitary tumors, that seems to be associated with an aggressive phenotype, at least in thyrotroph adenomas. Further studies are required to confirm this association and to identify the genes, in addition to sst5, lost in these tumors.

  13. Clusterin expression in non-neoplastic adenohypophyses and pituitary adenomas: cytoplasmic clusterin localization in adenohypophysis is related to aging.

    PubMed

    Ekici, A Işin Doğan; Eren, Bülent; Türkmen, Nursel; Comunoğlu, Nil; Fedakar, Recep

    2008-01-01

    Clusterin is a circulating multifunctional glycoprotein produced in several kinds of epithelial and neuronal cells. Clusterin is upregulated during different physiological and pathological states, such as senescence, type-2 diabetes mellitus, Alzheimer disease, and in various neoplasms. Herein, we investigated the immunohistochemical expression of clusterin in non-neoplastic adenohypophysis of human autopsy subjects and pituitary adenomas. We also investigated the association of clusterin increase with age in adenohypophysis of autopsy subjects. Immunohistochemically, clusterin was found positive in the cytoplasm of all adenoma cases, and in the cytoplasm of parenchymal cells, stellate cells, mixed cell follicles and in colloidal material inside of the follicles of non-neoplastic adenohypophysis as well. Clusterin expression in pituitary adenomas was found significantly higher than in non-neoplastic adenohypophyses. In addition, in non-neoplastic adenohypophysis, a significant increase in clusterin expression levels between young (or=61 years) subjects (p < 0.00001, analysis of variance [ANOVA]) was found. In addition to clusterin accumulation, presence of calcification (p < 0.045, ANOVA) and presence of large follicles with colloid accumulation (p < 0.004, ANOVA) were also statistically significant factors related to aging in non-neoplastic adenohypophysis. In conclusion, the present study demonstrated that clusterin expression was found in non-neoplastic adenohypophysis and in upregulated amounts in pituitary adenomas. This study also demonstrated that in non-neoplastic adenohypophyses, increase of clusterin positive cells; histopathological findings of calcification or presence colloidal material accumulation in large follicles were associated with age. To our knowledge, immunohistochemical localization of clusterin in pituitary adenomas was not reported previously.

  14. Long-Term Outcomes of Fractionated Stereotactic Radiation Therapy for Pituitary Adenomas at the BC Cancer Agency

    SciTech Connect

    Kim, Julian O.; Ma, Roy; Akagami, Ryojo; McKenzie, Michael; Johnson, Michelle; Gete, Ermias; Nichol, Alan

    2013-11-01

    Purpose: To assess the long-term disease control and toxicity outcomes of fractionated stereotactic radiation therapy (FSRT) in patients with pituitary adenomas treated at the BC Cancer Agency. Methods and Materials: To ensure a minimum of 5 years of clinical follow-up, this study identified a cohort of 76 patients treated consecutively with FSRT between 1998 and 2007 for pituitary adenomas: 71% (54/76) had nonfunctioning and 29% (22/76) had functioning adenomas (15 adrenocorticotrophic hormone-secreting, 5 growth hormone-secreting, and 2 prolactin-secreting). Surgery was used before FSRT in 96% (73/76) of patients. A median isocenter dose of 50.4 Gy was delivered in 28 fractions, with 100% of the planning target volume covered by the 90% isodose. Patients were followed up clinically by endocrinologists, ophthalmologists, and radiation oncologists. Serial magnetic resonance imaging was used to assess tumor response. Results: With a median follow-up time of 6.8 years (range, 0.6 - 13.1 years), the 7-year progression-free survival was 97.1% and disease-specific survival was 100%. Of the 2 patients with tumor progression, both had disease control after salvage surgery. Of the 22 patients with functioning adenomas, 50% (11/22) had complete and 9% (2/22) had partial responses after FSRT. Of the patients with normal pituitary function at baseline, 48% (14/29) experienced 1 or more hormone deficiencies after FSRT. Although 79% (60/76) of optic chiasms were at least partially within the planning target volumes, no patient experienced radiation-induced optic neuropathy. No patient experienced radionecrosis. No secondary malignancy occurred during follow-up. Conclusion: In this study of long-term follow-up of patients treated for pituitary adenomas, FSRT was safe and effective.

  15. Fractionated stereotactic radiosurgery using the Novalis system for the management of pituitary adenomas close to the optic apparatus.

    PubMed

    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

    2014-01-01

    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 (<3 mm) the optic apparatus were treated with fractionated 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.

  16. [A Case of an Adrenocorticotropic Hormone-Producing Pituitary Adenoma Removed via Electromagnetic-Guided Neuroendoscopy].

    PubMed

    Tomita, Yusuke; Kurozumi, Kazuhiko; Terasaka, Tomohiro; Inagaki, Kenichi; Otsuka, Fumio; Date, Isao

    2016-06-01

    The use of navigation systems is safe and reliable for neurological surgery. We performed endoscopic transsphenoidal surgery to totally resect an adrenocorticotropic hormone (ACTH)-producing pituitary adenoma associated with oculomotor nerve palsy. A 70-year-old woman developed right ptosis 4 months before admission. She developed anisocoria 2 months later and was referred to the department of neurology from clinic. Brain magnetic resonance imaging(MRI)showed an intrasellar tumor that partially invaded the right cavernous sinus, and she was then referred to our department. She exhibited a round face ("moon face") and central obesity. Laboratory test results showed a high urinary cortisol level and high serum ACTH level, and neither the serum cortisol nor ACTH level was suppressed by a low-dose dexamethasone test. We performed transsphenoidal surgery using high-dimensional endoscopy under electromagnetic navigation. The tumor invading the cavernous sinus was visualized via endoscopy and confirmed on navigation using a flexible needle probe. Postoperative MRI showed total removal of the tumor, and the serum ACTH level recovered to the normal range. The patient's right oculomotor palsy resolved within 1 week postoperatively. In summary, electromagnetic navigation was useful for total resection of a pituitary tumor invading the cavernous sinus, contributing to normalization of the ACTH level and improvement in neurological symptoms.

  17. Loss of heterozygosity of the MEN1 gene in a large series of TSH-secreting pituitary adenomas.

    PubMed

    Asteria, C; Anagni, M; Persani, L; Beck-Peccoz, P

    2001-11-01

    Thyrotropin-secreting pituitary adenomas (TSH-omas) are rare tumors (0.5% of all pituitary adenomas) showing an invasive behavior and usually sporadic, although a few cases are associated with multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant inherited syndrome. This disorder is linked to loss of heterozygosity (LOH) on 11q13 and inactivating mutations of MEN1 gene, which is located in the same chromosomal region. As other types of anterior pituitary adenomas, TSH-omas are the result of a monoclonal outgrowth where the intrinsic genetic defects involving oncogenes or tumor suppressor genes occur in a progenitor cell. However, so far no activating mutations of particular oncogenes or inactivating mutations of tumor suppressor genes have been identified. Starting from the observation that 3-30% of sporadic pituitary adenomas show LOH on 11q13, and that allelic losses on the long arms of chromosome 11, beside 10 and 13, are significantly associated with the transition from the non-invasive to the invasive phenotype, we decided to investigate LOH on 11q13 and mutations of menin in a large series of TSH-omas. Thirteen tumors were evaluated. DNA was extracted from tumors by standard methods and genomic DNA from peripheral blood leukocytes was used as control. LOH was screened by using 3 polymorphic markers on 11q13: D11S956, PYGM, INT-2. In 3 out of 15 cases we could demonstrate LOH on 11q13, but none of the tumors showed menin mutation after sequence analysis. These data strongly suggest that menin does not play a causative role in the development of TSH-omas, and are in agreement with other studies demonstrating a limited role of menin in pituitary sporadic tumorigenesis.

  18. Takotsubo cardiomyopathy in a patient with pituitary adenoma and secondary adrenal insufficiency

    PubMed Central

    Singh, Georgene; Manickam, Ari; Sethuraman, Manikandan; Rathod, Ramesh Chandra

    2015-01-01

    We describe a case of Takotsubo cardiomyopathy in a case of pituitary macroadenoma in acute adrenal crisis. A 48-year-old man presented with acute onset altered sensorium, vomiting, and gasping. On admission, he was unresponsive and hemodynamically unstable. He was intubated and ventilated and resuscitated with fluids and inotropes. The biochemical evaluation revealed hyponatremia, hyperkalemia, and hypocortisolism. Hyponatremia was corrected with 3% hypertonic saline. Contrast enhanced computed tomography (CT) scan of the brain revealed a sellar-suprasellar mass with hypothalamic extension with no evidence of pituitary apoplexy. A diagnosis of invasive pituitary adenoma with the Addisonian crisis was made and steroid replacement was initiated. Despite volume resuscitation, he had persistent refractory hypotension, recurrent ventricular tachycardia, and metabolic acidosis. Electrocardiogram (ECG) showed ST elevation and T-wave inversion in lateral leads; cardiac-enzymes were increased suggestive of acute coronary syndrome. Transthoracic echocardiography showed severe regional wall motion abnormalities (RWMAs) involving left anterior descending territory and low ejection fraction (EF). Coronary angiogram revealed normal coronaries, apical ballooning, and severe left ventricular dysfunction, consistent with a diagnosis of Takotsubo's cardiomyopathy. Patient was managed with angiotensin-converting enzyme inhibitors and B-blockers. He improved over few days and recovered completely. At discharge, ECG changes and RWMA resolved and EF normalized to 56%. In patients with Addisonian Crisis with persistent hypotension refractory to optimal resuscitation, possibility of Takotsubo's cardiomyopathy should be considered. Early recognition of association of Takotsubos cardiomyopathy in neurological conditions, prompt resuscitation, and supportive care are essential to ensure favorable outcomes in this potentially lethal condition. PMID:26816449

  19. Effect of surgery and radiotherapy on visual and endocrine function in nonfunctioning pituitary adenomas.

    PubMed

    Colao, A; Cerbone, G; Cappabianca, P; Ferone, D; Alfieri, A; Di Salle, F; Faggiano, A; Merola, B; de Divitiis, E; Lombardi, G

    1998-05-01

    The effect of surgery alone or followed by radiotherapy in recovering visual abnormalities, debulking tumor mass and restoring hormone impairments was evaluated in 84 patients with clinical nonfunctioning pituitary adenomas (NFPA) subjected to 1-10 yr follow-up. All patients underwent surgery via transsphenoidal (in 69) or transcranic-pterional approach (in 15). Radiotherapy was performed after surgery in 59 of 72 patients with incomplete tumor removal. The assessment of pituitary function was performed in all patients before and every 1-2 yr after surgery and/or radiotherapy. Radiological and ophthalmologic assessment was performed before and 3, 6 and 12 months after surgery, then yearly. At diagnosis, headache and visual disturbances occurred in 63 and 58 patients, respectively, while deficiency of GH, TSH, ACTH, FSH, LH and ADH was documented in 55, 7, 19 47 and 6 patients, respectively. After surgery, gonadal function recovered in 12 women, visual disturbances improved in 43 patients (15 regained normal vision), pituitary function improved in 8 of 62 patients, worsened in 34 patients. At MRI, complete tumor removal was documented in 12 of 84 patients. After surgery alone, tumor regrowth was observed in 7 patients between 3-7 yr. After radiotherapy, vision improved in 9, remained unchanged in 49 and worsened in 1 of 59 patients. After radiotherapy, tumor regrowth was documented in 9 patients between 2-12 yr and the prevalence of hypopituitarism raised from 28.8% to 92% after 1 and 10 yr. In conclusion, surgery alone is effective only in a minority of patients (14.3%) and radiotherapy causes hypopituitarism in rather the totality of patients after 10 yr. The prevalence of tumor regrowth was similar in irradiated ones (15%) and non irradiated patients (28%; chi(2), p = 0.4). Therefore, a careful radiological followup is suggested after surgery so that radiotherapy can be performed promptly on the basis of clinical data, tumor regrowth and/or invasiveness

  20. Disappearance of pituitary macro adenoma with combination of ketoconazole and cabergoline treatment: an unusual case of Cushing’s syndrome with interesting findings

    PubMed Central

    Ahmed, Asma; Furqan, Saira; Islam, Najmul

    2012-01-01

    Cushing syndrome is associated with significant morbidity and mortality if left untreated because of associated metabolic and cardiovascular complications. An extremely ill patient with Cushing’s syndrome caused by adrenocorticotropic hormone producing pituitary macro adenoma responded dramatically to ketoconazole and cabergoline treatment. His 4 month long medical treatment resulted in improvement of hypercotisolism clinically and biochemically and in complete disappearance of pituitary macro adenoma without any surgical intervention. PMID:22761217

  1. A case of growth-hormone staining pituitary adenoma with renal cyst and hepatic cyst: are they related manifestations of a single disease?

    PubMed

    Ma, Jun; Liu, Pinan

    2014-01-01

    Growth-hormone staining pituitary adenoma is a popular disease of the central nervous system. We noticed some patients have accompanying cystic disorders. Several cases of concomitant growth-hormone (GH)-staining pituitary adenoma and other cystic changes have been reported but with no further investigation. We report a case of adult growth-hormone staining pituitary adenoma with accompanying polycystic changes of multiple systems, as well as hypertension and nephrolithiasis. Preoperative clinical assessment revealed intrasellar tumor, multinodular thyroid disorder, renal cysts, and hepatic cysts, with increased serum growth-hormone level and normal thyroid hormone level. The total tumor resection was performed via endoscopic transsphenoidal approach. The pathologic analysis reported growth-hormone staining pituitary adenoma. The postoperative course was uneventful. The endocrine testing was normal soon after the operation and the patient remained well for a follow-up period of eight months. This is the fifth report about simultaneous growth-hormone staining pituitary adenoma and polycystic changes of the kidneys and the liver. With review of the literature we speculate that the abnormal growth hormone secretion of the pituitary adenoma may arouse sequential cystic changes of multiple systems through some IGF-I involved pathways.

  2. Gene and protein expression in pituitary corticotroph adenomas: a systematic review of the literature.

    PubMed

    Seltzer, Justin; Ashton, Charles E; Scotton, Thomas C; Pangal, Dhiraj; Carmichael, John D; Zada, Gabriel

    2015-02-01

    OBJECT Functional corticotroph pituitary adenomas (PAs) secrete adrenocorticotropic hormone (ACTH) and are the cause of Cushing's disease, which accounts for 70% of all cases of Cushing's syndrome. Current classification systems for PAs rely primarily on laboratory hormone findings, tumor size and morphology, invasiveness, and immunohistochemical findings. Likewise, drug development for functional ACTH-secreting PAs (ACTH-PAs) is limited and has focused largely on blocking the production or downstream effects of excess cortisol. The authors aimed to summarize the findings from previous studies that explored gene and protein expression of ACTH-PAs to prioritize potential genetic and protein targets for improved molecular diagnosis and treatment of Cushing's disease. METHODS A systematic literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A PubMed search of select medical subject heading (MeSH) terms was performed to identify all studies that reported gene- and protein-expression findings in ACTH-PAs from January 1, 1990, to August 24, 2014, the day the search was performed. The inclusion criteria were studies on functional ACTH-PAs compared with normal pituitary glands, on human PA tissue only, with any method of analysis, and published in the English language. Studies using anything other than resected PA tissue, those that compared other adenoma types, those without baseline expression data, or those in which any pretreatment was delivered before analysis were excluded. RESULTS The primary search returned 1371 abstracts, of which 307 were found to be relevant. Of those, 178 were selected for secondary full-text analysis. Of these, 64 articles met the inclusion criteria and an additional 4 studies were identified from outside the search for a total of 68 included studies. Compared with the normal pituitary gland, significant gene overexpression in 43 genes and 22 proteins was reported

  3. Nasal Lobular Capillary Hemangioma as a Complication after an Endoscopic Transsphenoidal Gonadotrophin-Producing Pituitary Adenoma Resection.

    PubMed

    Forte, Dalila; Irañeta, Amets Sagarribay; Nabais, Anabela; Figueiredo, António; Mafra, Manuela; Gonçalves, Victor

    2017-01-01

    Background Lobular capillary hemangioma is a rare benign tumor, most frequently located in the head or neck region, the nasal cavity being uncommonly affected. Its etiopathogenesis is not fully established, although traumatic and hormonal factors have been implied. Case Description A 50-year-old female patient underwent an uneventful endoscopic transsphenoidal removal of a pituitary cystic macroadenoma at our institution. Nasal packing was used in postoperative hemostasis. Histopathology was compatible with a gonadotrophin-producing adenoma. One month after the surgery, the patient presented with frequent episodes of epistaxis and a progressively growing nasal mass, which was removed endoscopically. Its pathological examination confirmed a lobular capillary hemangioma. Conclusions The authors present a clinical case combining two possible predisposing factors to the development of a nasal lobular capillary hemangioma: local traumatic injury through surgery and postoperative nasal packing and hormonal influence. This lesion is a rare complication of endoscopic transsphenoidal resections of pituitary adenomas.

  4. Nasal Lobular Capillary Hemangioma as a Complication after an Endoscopic Transsphenoidal Gonadotrophin-Producing Pituitary Adenoma Resection

    PubMed Central

    Forte, Dalila; Irañeta, Amets Sagarribay; Nabais, Anabela; Figueiredo, António; Mafra, Manuela; Gonçalves, Victor

    2017-01-01

    Background Lobular capillary hemangioma is a rare benign tumor, most frequently located in the head or neck region, the nasal cavity being uncommonly affected. Its etiopathogenesis is not fully established, although traumatic and hormonal factors have been implied. Case Description A 50-year-old female patient underwent an uneventful endoscopic transsphenoidal removal of a pituitary cystic macroadenoma at our institution. Nasal packing was used in postoperative hemostasis. Histopathology was compatible with a gonadotrophin-producing adenoma. One month after the surgery, the patient presented with frequent episodes of epistaxis and a progressively growing nasal mass, which was removed endoscopically. Its pathological examination confirmed a lobular capillary hemangioma. Conclusions The authors present a clinical case combining two possible predisposing factors to the development of a nasal lobular capillary hemangioma: local traumatic injury through surgery and postoperative nasal packing and hormonal influence. This lesion is a rare complication of endoscopic transsphenoidal resections of pituitary adenomas. PMID:28326242

  5. 5-ALA Fluorescence in Native Pituitary Adenoma Cell Lines: Resection Control and Basis for Photodynamic Therapy (PDT)?

    PubMed Central

    Poeschke, Stephan; Greve, Burkhard; Prevedello, Daniel; Santacroce, Antonio; Stummer, Walter; Senner, Volker

    2016-01-01

    Objective: Pituitary adenomas (PA), especially invasive ones, are often not completely resectable. Usage of 5-aminolevulinic acid (5-ALA) for fluorescence guided surgery could improve the rate of total resection and, additionally, open the doors for photodynamic therapy (PDT) in case of unresectable or partially resected PAs. The aim of this study was to investigate the uptake of 5-ALA and the effect of 5-ALA based PDT in cell lines. Methods: GH3 and AtT-20 cell lines were incubated with different concentrations of 5-ALA, protoporphyrin IX (PPIX) fluorescence was measured by flow cytometry and fluorescencespectrometry. WST-1 assays were performed to determine the surviving fraction of cells after PDT. PPIX fluorescence intensities and PDT effect of the pituitary adenoma cells were compared to U373MG, a well-known glioblastoma cell line. Results: Both cell lines showed a 5-ALA dependent intracellular PPIX fluorescence. Significant differences after 24hrs of incubation were observed in AtT-20 cells in comparison to GH3. Regardless of the incubation or metabolism time, there was a proliferation inhibiting effect after PDT, with no statistical significance. Conclusion: Since GH3 cells showed a heterogenous uptake of 5-ALA in the flow cytometry profile, but not constantly high concentrations they might have a 5-ALA efflux mechanism, which still needs to be determined. In the case of AtT-20, the cells might need a longer time for the uptake due to their size or slow metabolism. We showed that the different cell lines have different uptake and metabolism mechanisms, which needs to be further investigated. The general uptake of 5-ALA allows the possibility of resection control and PDT for pituitary adenomas. But, the role of PDT for unresectable pituitary adenomas deserves further investigations. PMID:27583461

  6. Incidence, Causative Mechanisms, and Anatomic Localization of Stroke in Pituitary Adenoma Patients Treated With Postoperative Radiation Therapy Versus Surgery Alone

    SciTech Connect

    Sattler, Margriet G.A.; Vroomen, Patrick C.; Sluiter, Wim J.; Schers, Henk J.; Berg, Gerrit van den; Langendijk, Johannes A.; Wolffenbuttel, Bruce H.R.; Bergh, Alphons C.M. van den; Beek, André P. van

    2013-09-01

    Purpose: To assess and compare the incidence of stroke and stroke subtype in pituitary adenoma patients treated with postoperative radiation therapy (RT) and surgery alone. Methods and Materials: A cohort of 462 pituitary adenoma patients treated between 1959 and 2008 at the University Medical Center Groningen in The Netherlands was studied. Radiation therapy was administered in 236 patients. The TOAST (Trial of ORG 10172 in Acute Stroke Treatment) and the Oxfordshire Community Stroke Project classification methods were used to determine causative mechanism and anatomic localization of stroke. Stroke incidences in patients treated with RT were compared with that observed after surgery alone. Risk factors for stroke incidence were studied by log–rank test, without and with stratification for other significant risk factors. In addition, the stroke incidence was compared with the incidence rate in the general Dutch population. Results: Thirteen RT patients were diagnosed with stroke, compared with 12 surgery-alone patients. The relative risk (RR) for stroke in patients treated with postoperative RT was not significantly different compared with surgery-alone patients (univariate RR 0.62, 95% confidence interval [CI] 0.28-1.35, P=.23). Stroke risk factors were coronary or peripheral artery disease (univariate and multivariate RR 10.4, 95% CI 4.7-22.8, P<.001) and hypertension (univariate RR 3.9, 95% CI 1.6-9.8, P=.002). There was no difference in TOAST and Oxfordshire classification of stroke. In this pituitary adenoma cohort 25 strokes were observed, compared with 16.91 expected (standard incidence ratio 1.48, 95% CI 1.00-1.96, P=.049). Conclusions: In pituitary adenoma patients, an increased incidence of stroke was observed compared with the general population. However, postoperative RT was not associated with an increased incidence of stroke or differences in causative mechanism or anatomic localization of stroke compared with surgery alone. The primary stroke risk

  7. The Clinical Outcome of Hypofractionated Stereotactic Radiotherapy With CyberKnife Robotic Radiosurgery for Perioptic Pituitary Adenoma.

    PubMed

    Puataweepong, Putipun; Dhanachai, Mantana; Hansasuta, Ake; Dangprasert, Somjai; Swangsilpa, Thiti; Sitathanee, Chomporn; Jiarpinitnun, Chuleeporn; Vitoonpanich, Patamintita; Yongvithisatid, Pornpan

    2016-12-01

    Stereotactic radiation technique including single fraction radiosurgery and conventional fractionated stereotactic radiotherapy is widely reported as an effective treatment of pituitary adenomas. Because of the restricted radiation tolerance dose of the optic pathway, single fraction radiosurgery has been accepted for small tumor located far away from the optic apparatus, while fractionated stereotactic radiotherapy may be suitable for larger tumor located close to the optic pathway. More recently, hypofractionated stereotactic radiotherapy has become an alternative treatment option that provides high rate of tumor control and visual preservation for the perioptic lesions within 2 to 3 mm of the optic pathway. The objective of the study was to analyze the clinical outcomes of perioptic pituitary adenomas treated with hypofractionated stereotactic radiotherapy. From 2009 to 2012, 40 patients with perioptic pituitary adenoma were treated with CyberKnife robotic radiosurgery. The median tumor volume was 3.35 cm(3) (range, 0.82-25.86 cm(3)). The median prescribed dose was 25 Gy (range, 20-28 Gy) in 5 fractions (range, 3-5). After the median follow-up time of 38.5 months (range, 14-71 months), 1 (2.5%) patient with prolactinoma had tumor enlargement, 31 (77.5%) were stable, and the remaining 8 (20%) tumors were smaller in size. No patient's vision deteriorated after hypofractionated stereotactic radiotherapy. Hormone normalization was observed in 7 (54%) of 13 patients. No newly developed hypopituitarism was detected in our study. These data confirmed that hypofractionated stereotactic radiotherapy achieved high rates of tumor control and visual preservation. Because of the shorter duration of treatment, it may be preferable to use hypofractionated stereotactic radiotherapy over fractionated stereotactic radiotherapy for selected pituitary adenomas immediately adjacent to the optic apparatus.

  8. Proopiomelanocortin, glucocorticoid, and CRH receptor expression in human ACTH-secreting pituitary adenomas.

    PubMed

    Cassarino, Maria Francesca; Sesta, Antonella; Pagliardini, Luca; Losa, Marco; Lasio, Giovanni; Cavagnini, Francesco; Pecori Giraldi, Francesca

    2017-03-01

    ACTH-secreting pituitary tumors are by definition partially autonomous, i.e., secrete ACTH independent of physiological control. However, only few, small-sized studies on proopiomelanocortin (POMC) and its regulation by corticotropin-releasing hormone (CRH) or glucocorticoids are available. Objective of the present study was to report on constitutive and CRH- and dexamethasone-regulated POMC, CRH (CRH-R1), and glucocorticoid receptor (NR3C1) gene expression in a large series of human corticotrope adenomas. Fifty-three ACTH-secreting adenomas were incubated with 10 nM CRH or 10 nM dexamethasone for 24 h. POMC, CRH-R1, NR3C1, and its alpha and beta isoforms were quantified and medium ACTH measured. Constitutive POMC expression proved extremely variable, with macroadenomas exhibiting higher levels than microadenomas. POMC increased during CRH in most specimens; conversely, changes induced by dexamethasone were varied, ranging from decrease to paradoxical increase. No correlation between POMC and ACTH was detected in any experimental condition. CRH-R1 expression was not linked to the response to CRH while NR3C1 was expressed at greater levels in specimens who failed to inhibit during dexamethasone; glucocorticoid receptor α was the more abundant isoform and subject to down-regulation by dexamethasone. Our results demonstrate a considerable variability in POMC expression among tumors and no correlation between POMC and ACTH, suggesting that POMC peptide processing/transport plays a major role in modulating ACTH secretion. Further, CRH-R1 and NR3C1 expression were not linked to the expected ligand-induced outcome, indicating that receptor signaling rather than abundance determines corticotrope responses. Our findings pave the way to new avenues of research into Cushing's disease pathophysiology.

  9. TSH-secreting adenomas: rare pituitary tumors with multifaceted clinical and biological features.

    PubMed

    Foppiani, L; Del Monte, P; Ruelle, A; Bandelloni, R; Quilici, P; Bernasconi, D

    2007-01-01

    TSH-secreting pituitary adenomas (TSH-omas) are a rare cause of hyperthyroidism in clinical practice. As their diagnosis is often delayed, these tumors are mostly diagnosed as macroadenomas, preventing an effective and radical cure and leading to serious local and systemic comorbidities. In addition to neurosurgery, medical therapy with the effective and tolerable SS analogs is a fundamental tool for the treatment of TSHomas. We report 3 cases of TSH-macroadenomas which displayed different clinical presentations. All patients showed increased free-thyroid hormone levels with inappropriately normal (2 patients) or high (1 patient) TSH levels. Magnetic resonance imaging (MRI)/computed tomography (CT) evidenced a pituitary macroadenoma and octreoscan was positive in all patients. In the 2 patients who underwent neurosurgery, hormonal hypersecretion by the tumor normalized. Histology showed nuclear pleomorphism and fibrosis, whereas immunohistochemistry showed positivity for TSH and, in a lesser amount, for FSH. In one of these patient (case 1), however, the presence of a tumor remnant inside the left cavernous sinus prompted us, in accordance with the patient, to start therapy with octreotide- long-acting release. As the third patient had a cardiac comorbidity which contraindicated neurosurgery, he underwent satisfactory treatment with long-acting SS analogs alone which normalized thyroid hormone levels. In this case, previous treatment with amiodarone confused and delayed the correct diagnosis of TSH-oma. As a result of improved laboratory and morphological techniques, TSH-omas should currently be diagnosed in early stages, thus enabling most patients to be managed satisfactorily through a combined approach.

  10. Does MMP-9 Gene Polymorphism Play a Role in Pituitary Adenoma Development?

    PubMed Central

    Liutkeviciene, Rasa; Kriauciuniene, Loresa; Jakstiene, Silvija; Tamosiunas, Abdonas; Vaitkiene, Paulina

    2017-01-01

    Purpose. To determine if the MMP-9 genotype has an influence on development of pituitary adenoma (PA). Methodology. The study enrolled n = 86 patients with PA and n = 526 healthy controls (reference group). The genotyping of MMP-9 was carried out using the real-time polymerase chain reaction method. Results. Our data demonstrated that the MMP-9 (–1562) C/C genotype was more frequent in PA group than in healthy controls (81.4% versus 64.6%, p = 0.002); C/C genotype was more frequently present in PA females compared to healthy control females, 81.5% versus 64.6%, p = 0.018, as well. MMP-9 (–1562) C/C genotype was frequently observed for all subgroups: noninvasive and invasive, nonrecurrence, and inactive PA compared to healthy controls: 81.8% versus 64.6%, p = 0.021; 81.0% versus 64.6%, p = 0.041; 81.8% versus 64.6%, p = 0.005; 100.0% versus 64.6%, p < 0.001, respectively. MMP-9 (–1562) C/C genotype was more frequent in inactive PA compared to active PA: 100.0% versus 71.4%; p < 0.001. Conclusion. MMP-9 (–1562) C/C genotype plays a role in nonrecurrence, inactive, and invasive as well as in nonivasive PA development. PMID:28194042

  11. Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families.

    PubMed

    Igreja, Susana; Chahal, Harvinder S; King, Peter; Bolger, Graeme B; Srirangalingam, Umasuthan; Guasti, Leonardo; Chapple, J Paul; Trivellin, Giampaolo; Gueorguiev, Maria; Guegan, Katie; Stals, Karen; Khoo, Bernard; Kumar, Ajith V; Ellard, Sian; Grossman, Ashley B; Korbonits, Márta

    2010-08-01

    Familial isolated pituitary adenoma (FIPA) is an autosomal dominant condition with variable genetic background and incomplete penetrance. Germline mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene have been reported in 15-40% of FIPA patients. Limited data are available on the functional consequences of the mutations or regarding the regulation of the AIP gene. We describe a large cohort of FIPA families and characterize missense and silent mutations using minigene constructs, luciferase and beta-galactosidase assays, as well as in silico predictions. Patients with AIP mutations had a lower mean age at diagnosis (23.6+/-11.2 years) than AIP mutation-negative patients (40.4+/-14.5 years). A promoter mutation showed reduced in vitro activity corresponding to lower mRNA expression in patient samples. Stimulation of the protein kinase A-pathway positively regulates the AIP promoter. Silent mutations led to abnormal splicing resulting in truncated protein or reduced AIP expression. A two-hybrid assay of protein-protein interaction of all missense variants showed variable disruption of AIP-phosphodiesterase-4A5 binding. In summary, exonic, promoter, splice-site, and large deletion mutations in AIP are implicated in 31% of families in our FIPA cohort. Functional characterization of AIP changes is important to identify the functional impact of gene sequence variants.

  12. Short-term preoperative octreotide treatment for TSH-secreting pituitary adenoma.

    PubMed

    Fukuhara, Noriaki; Horiguchi, Kentaro; Nishioka, Hiroshi; Suzuki, Hisanori; Takeshita, Akira; Takeuchi, Yasuhiro; Inoshita, Naoko; Yamada, Shozo

    2015-01-01

    Preoperative control of hyperthyroidism in patients with TSH-secreting pituitary adenomas (TSHoma) may avoid perioperative thyroid storm. Perioperative administration of octreotide may control hyperthyroidism, as well as shrink tumor size. The effects of preoperative octreotide treatment were assessed in a large number of patients with TSHomas. Of 81 patients who underwent surgery for TSHoma at Toranomon Hospital between January 2001 and May 2013, 44 received preoperative short-term octreotide. After excluding one patient because of side effects, 19 received octreotide as a subcutaneous injection, and 24 as a long-acting release (LAR) injection. Median duration between initiation of octreotide treatment and surgery was 33.5 days. Octreotide normalized free T4 in 36 of 43 patients (84%) and shrank tumors in 23 of 38 (61%). Length of octreotide treatment did not differ significantly in patients with and without hormonal normalization (p=0.09) and with and without tumor shrinkage (p=0.84). Serum TSH and free T4 concentrations, duration of treatment, incidence of growth hormone (GH) co-secretion, results of octreotide loading tests, form of administration (subcutaneous injection or LAR), tumor volume, and tumor consistency did not differ significantly in patients with and without hormonal normalization and with and without tumor shrinkage. Short-term preoperative octreotide administration was highly effective for TSHoma shrinkage and normalization of excess hormone concentrations, with tolerable side effects.

  13. Characterization of Aryl Hydrocarbon Receptor Interacting Protein (AIP) Mutations in Familial Isolated Pituitary Adenoma Families

    PubMed Central

    Igreja, Susana; Chahal, Harvinder S; King, Peter; Bolger, Graeme B; Srirangalingam, Umasuthan; Guasti, Leonardo; Chapple, J Paul; Trivellin, Giampaolo; Gueorguiev, Maria; Guegan, Katie; Stals, Karen; Khoo, Bernard; Kumar, Ajith V; Ellard, Sian; Grossman, Ashley B; Korbonits, Márta

    2010-01-01

    Familial isolated pituitary adenoma (FIPA) is an autosomal dominant condition with variable genetic background and incomplete penetrance. Germline mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene have been reported in 15–40% of FIPA patients. Limited data are available on the functional consequences of the mutations or regarding the regulation of the AIP gene. We describe a large cohort of FIPA families and characterize missense and silent mutations using minigene constructs, luciferase and β-galactosidase assays, as well as in silico predictions. Patients with AIP mutations had a lower mean age at diagnosis (23.6±11.2 years) than AIP mutation-negative patients (40.4±14.5 years). A promoter mutation showed reduced in vitro activity corresponding to lower mRNA expression in patient samples. Stimulation of the protein kinase A-pathway positively regulates the AIP promoter. Silent mutations led to abnormal splicing resulting in truncated protein or reduced AIP expression. A two-hybrid assay of protein–protein interaction of all missense variants showed variable disruption of AIP-phosphodiesterase-4A5 binding. In summary, exonic, promoter, splice-site, and large deletion mutations in AIP are implicated in 31% of families in our FIPA cohort. Functional characterization of AIP changes is important to identify the functional impact of gene sequence variants. Hum Mutat 31:1–11, 2010. © 2010 Wiley-Liss, Inc. PMID:20506337

  14. Body Image Disturbance in Acromegaly Patients Compared to Nonfunctioning Pituitary Adenoma Patients and Controls

    PubMed Central

    Conaglen, Helen M.; de Jong, Dennis; Crawford, Veronica; Elston, Marianne S.; Conaglen, John V.

    2015-01-01

    Purpose. Excess growth hormone secretion in adults results in acromegaly, a condition in which multiple physical changes occur including bony and soft tissue overgrowth. Over time these changes can markedly alter a person's appearance. The aim of this study was to compare body image disturbance in patients with acromegaly to those with nonfunctioning pituitary adenomas (NFAs) and controls and assess the impact of obesity in these groups. Methods. A cross-sectional survey including quality of life, body image disturbance, anxiety and depression measures, growth hormone, and BMI measurement was carried out. Results. The groups did not differ with respect to body image disturbance. However separate analysis of obese participants demonstrated relationships between mood scales, body image disturbance, and pain issues, particularly for acromegaly patients. Conclusions. While the primary hypothesis that acromegaly might be associated with body image disturbance was not borne out, we have shown that obesity together with acromegaly and NFA can be associated with body image issues, suggesting that BMI rather than primary diagnosis might better indicate whether patients might experience body image disturbance problems. PMID:26078758

  15. Somatotroph Pituitary Adenoma with Acromegaly and Autosomal Dominant Polycystic Kidney Disease – SSTR5 polymorphism and PKD1 mutation

    PubMed Central

    Syro, Luis V.; Sundsbak, Jamie L.; Scheithauer, Bernd W.; Toledo, Rodrigo A.; Camargo, Mauricio; Heyer, Christina M.; Sekiya, Tomoko; Uribe, Humberto; Escobar, Jorge I.; Vasquez, Martin; Rotondo, Fabio; Toledo, Sergio P. A.; Kovacs, Kalman; Horvath, Eva; Babovic-Vuksanovic, Dusica; Harris, Peter C.

    2014-01-01

    A 39-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) presented with acromegaly and a pituitary macroadenoma. There was a family history of this renal disorder. She had undergone surgery for pituitary adenoma 6 years prior. Physical examination disclosed bitemporal hemianopsia and elevation of both basal growth hormone (GH) 106 ng/mL (normal 0–5) and insulin-like growth factor (IGF-1) 811 ng/mL (normal 48–255) blood levels. A magnetic resonance imaging scan disclosed a 3.0 cm sellar and suprasellar mass with both optic chiasm compression and left cavernous sinus invasion. Histologic, immunohistochemical and ultrastructural studies of the lesion disclosed a sparsely granulated somatotroph adenoma. Standard chromosome analysis on the blood sample showed no abnormality. Sequence analysis of the coding regions of PKD1 and PKD2 employing DNA from both peripheral leukocytes and the tumor revealed the most common PKD1 mutation, 5014_5015delAG. Analysis of the entire SSTR5 gene disclosed the variant c.143C>A (p.L48M, rs4988483) change in the heterozygous state in both blood and tumor, while no pathogenic mutations were noted in the MEN1, AIP, p27Kip1 and SSTR2 genes. To our knowledge, this is the fourth reported case of a GH-producing pituitary adenoma associated with ADPKD, but the first subject to extensive morphological, ultrastructural, cytogenetic and molecular studies. The question arises whether the physical proximity of the PKD1 and SSTR5 genes on chromosome 16 indicates a causal relationship between ADPKD and the somatotroph adenoma. PMID:21744088

  16. Somatotroph pituitary adenoma with acromegaly and autosomal dominant polycystic kidney disease: SSTR5 polymorphism and PKD1 mutation.

    PubMed

    Syro, Luis V; Sundsbak, Jamie L; Scheithauer, Bernd W; Toledo, Rodrigo A; Camargo, Mauricio; Heyer, Christina M; Sekiya, Tomoko; Uribe, Humberto; Escobar, Jorge I; Vasquez, Martin; Rotondo, Fabio; Toledo, Sergio P A; Kovacs, Kalman; Horvath, Eva; Babovic-Vuksanovic, Dusica; Harris, Peter C

    2012-09-01

    A 39-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) presented with acromegaly and a pituitary macroadenoma. There was a family history of this renal disorder. She had undergone surgery for pituitary adenoma 6 years prior. Physical examination disclosed bitemporal hemianopsia and elevation of both basal growth hormone (GH) 106 ng/mL (normal 0-5) and insulin-like growth factor (IGF-1) 811 ng/mL (normal 48-255) blood levels. A magnetic resonance imaging scan disclosed a 3.0 cm sellar and suprasellar mass with both optic chiasm compression and left cavernous sinus invasion. Pathologic, cytogenetic, molecular and in silico analysis was undertaken. Histologic, immunohistochemical and ultrastructural studies of the lesion disclosed a sparsely granulated somatotroph adenoma. Standard chromosome analysis on the blood sample showed no abnormality. Sequence analysis of the coding regions of PKD1 and PKD2 employing DNA from both peripheral leukocytes and the tumor revealed the most common PKD1 mutation, 5014_5015delAG. Analysis of the entire SSTR5 gene disclosed the variant c.142C>A (p.L48M, rs4988483) in the heterozygous state in both blood and tumor, while no pathogenic mutations were noted in the MEN1, AIP, p27Kip1 and SSTR2 genes. To our knowledge, this is the fourth reported case of a GH-producing pituitary adenoma associated with ADPKD, but the first subjected to extensive morphological, ultrastructural, cytogenetic and molecular studies. The physical proximity of the PKD1 and SSTR5 genes on chromosome 16 suggests a causal relationship between ADPKD and somatotroph adenoma.

  17. The Molecular Registry of Pituitary Adenomas (REMAH): A bet of Spanish Endocrinology for the future of individualized medicine and translational research.

    PubMed

    Luque, Raúl M; Ibáñez-Costa, Alejandro; Sánchez-Tejada, Laura; Rivero-Cortés, Esther; Robledo, Mercedes; Madrazo-Atutxa, Ainara; Mora, Mireia; Álvarez, Clara V; Lucas-Morante, Tomás; Álvarez-Escolá, Cristina; Fajardo, Carmen; Castaño, Luis; Gaztambide, Sonia; Venegas-Moreno, Eva; Soto-Moreno, Alfonso; Gálvez, María Ángeles; Salvador, Javier; Valassi, Elena; Webb, Susan M; Picó, Antonio; Puig-Domingo, Manel; Gilabert, Montserrat; Bernabéu, Ignacio; Marazuela, Mónica; Leal-Cerro, Alfonso; Castaño, Justo P

    2016-01-01

    Pituitary adenomas are uncommon, difficult to diagnose tumors whose heterogeneity and low incidence complicate large-scale studies. The Molecular Registry of Pituitary Adenomas (REMAH) was promoted by the Andalusian Society of Endocrinology and Nutrition (SAEN) in 2008 as a cooperative clinical-basic multicenter strategy aimed at improving diagnosis and treatment of pituitary adenomas by combining clinical, pathological, and molecular information. In 2010, the Spanish Society of Endocrinology and Nutrition (SEEN) extended this project to national level and established 6 nodes with common protocols and methods for sample and clinical data collection, molecular analysis, and data recording in a common registry (www.remahnacional.com). The registry combines clinical data with molecular phenotyping of the resected pituitary adenoma using quantitative real-time PCR of expression of 26 genes: Pituitary hormones (GH-PRL-LH-FSH-PRL-ACTH-CGA), receptors (somatostatin, dopamine, GHRH, GnRH, CRH, arginine-vasopressin, ghrelin), other markers (Ki67, PTTG1), and control genes. Until 2015, molecular information has been collected from 704 adenomas, out of 1179 patients registered. This strategy allows for comparative and relational analysis between the molecular profile of the different types of adenoma and the clinical phenotype of patients, which may provide a better understanding of the condition and potentially help in treatment selection. The REMAH is therefore a unique multicenter, interdisciplinary network founded on a shared database that provides a far-reaching translational approach for management of pituitary adenomas, and paves the way for the conduct of combined clinical-basic innovative studies on large patient samples.

  18. Demographic study of pituitary adenomas undergone trans-sphenoidal surgery in Loghman Hakim Hospital, Tehran, Iran 2001–2013

    PubMed Central

    Zerehpoosh, Farahnaz Bidari; Sabeti, Shahram; Sharifi, Guive; Shakeri, Hania; Alipour, Setareh; Arman, Farid

    2015-01-01

    Background: Pituitary adenomas (PAs) are abnormal benign tumors that develop in the pituitary gland. This study aimed to assess the prevalence of different types of PAs with an indication for trans-sphenoidal surgery in a well-defined population referred to Loghman Hakim Hospital during 2001–2013. Subjects and Methods: In this retrospective study, the prevalence rate and symptoms associated with pituitary mass and hormone excess in operated patients were investigated. The diagnosis was verified after retrieval of clinical, hormonal, radiological, and pathological data. Demographic data were collected in all cases. Descriptive analysis, t-test, one-way analysis of variance and Fischer exacts test were used. Results: A total of 278 patients with PAs who underwent surgical interventions were evaluated. Most of the patients were aged 40–50 years with an average of 41 ± 14. The most prominent complaint was pressure effect, which was detected in 153 cases (55.2%). At the second place, hormonal disorders were observed in 125 cases (44.8%). Type of pituitary tumors were: Prolactinomas (29.1%), growth hormone (GH)-producing tumors (25%), nonfunctioning PAs (28.4%), adrenocorticotropic hormone (ACTH)-producing tumors (2.1%), thyroid stimulating hormone (TSH)-producing tumors (0.7%), GH/prolactin (13.6%), GH/ACTH (0.3%), and TSH/ACTH (0.3%). Fifty-seven patients presented with recurrent adenomas. Pituitary apoplexy was found in 11 patients. One case of Sheehan syndrome was recorded among these. The correlations between clinical symptoms and patients, age and sex were not significant. Conclusion: The overview of demographic characteristics in Iranian patients with PAs with surgical indication has been discussed in the present investigation. The prevalence of different types of PAs and the most common clinical symptoms have been demonstrated. PMID:26693430

  19. A novel truncating AIP mutation, p.W279*, in a familial isolated pituitary adenoma (FIPA) kindred.

    PubMed

    Cansu, Güven Barış; Taşkıran, Bengür; Trivellin, Giampaolo; Faucz, Fabio R; Stratakis, Constantine A

    2016-07-01

    Familial isolated pituitary adenomas (FIPA) constitute 2-3% of pituitary tumours. AIP is the most commonly mutated gene in FIPA. We herein report a novel germline mutation of the AIP gene in a family with FIPA. We present two patients, a father and his 12-year-old daughter, diagnosed clinically and using laboratory measures with acromegaly-gigantism. Both underwent transsphenoidal hypophyseal surgery for macroadenomas. We initially detected a novel heterozygous germline AIP mutation, c.836G>A (p.W279*), in the father's DNA. We then found the same mutation in his affected daughter. Pituitary adenomas associated with AIP mutations mostly present as FIPA (68%) at an early age (78% occur at <30 years old). They are often growth hormone (GH) - or prolactin - secreting macroadenomas (88%) that have already extended beyond the sella at the time of diagnosis. Acromegalic cases are resistant to somatostatin analogues and multimodal management is frequently essential to control the disease. Our patients had normalized GH/IGF-1 values soon after surgery, although enough time may not have elapsed to reach final cure. While penetrance of the disease can be as low as 10% in FIPA, especially children and young patients with somatotropinoma and prolactinoma should be surveyed for inactivating mutations or deletions in AIP. Determining the causative mutations may be of assistance in early diagnosis, treatment success, and genetic counseling.

  20. Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and Its Molecular Link to Patient Osteoporosis

    PubMed Central

    Wang, Renzhi; Yang, Yakun; Sheng, Miaomiao; Bu, Dechao; Huang, Fengming; Liu, Xiaohai; Zhou, Cuiqi; Dai, Congxin; Sun, Bowen; Zhu, Jindong; Qiao, Yi; Yao, Yong; Zhu, Huijuan; Lu, Lin; Pan, Hui; Feng, Ming; Deng, Kan; Xing, Bing; Lian, Wei; Zhao, Yi; Jiang, Chengyu

    2016-01-01

    Adrenocorticotrophin (ACTH)-secreting pituitary adenoma, also known as Cushing disease (CD), is rare and causes metabolic syndrome, cardiovascular disease and osteoporosis due to hypercortisolism. However, the molecular pathogenesis of CD is still unclear because of a lack of human cell lines and animal models. Here, we study 106 clinical characteristics and gene expression changes from 118 patients, the largest cohort of CD in a single-center. RNA deep sequencing is used to examine genotypic changes in nine paired female ACTH-secreting pituitary adenomas and adjacent nontumorous pituitary tissues (ANPT). We develop a novel analysis linking disease clinical characteristics and whole transcriptomic changes, using Pearson Correlation Coefficient to discover a molecular network mechanism. We report that osteoporosis is distinguished from the phenotype and genotype analysis. A cluster of genes involved in osteoporosis is identified using Pearson correlation coefficient analysis. Most of the genes are reported in the bone related literature, confirming the feasibility of phenotype-genotype association analysis, which could be used in the analysis of almost all diseases. Secreted phosphoprotein 1 (SPP1), collagen type I α 1 chain (COL1A1), 5′-nucleotidase ecto (NT5E), HtrA serine peptidase 1 (HTRA1) and angiopoietin 1 (ANGPT1) and their signalling pathways are shown to be involved in osteoporosis in CD patients. Our discoveries provide a molecular link for osteoporosis in CD patients, and may open new potential avenues for osteoporosis intervention and treatment. PMID:27690016

  1. Mice with inactivation of aryl hydrocarbon receptor-interacting protein (Aip) display complete penetrance of pituitary adenomas with aberrant ARNT expression.

    PubMed

    Raitila, Anniina; Lehtonen, Heli J; Arola, Johanna; Heliövaara, Elina; Ahlsten, Manuel; Georgitsi, Marianthi; Jalanko, Anu; Paetau, Anders; Aaltonen, Lauri A; Karhu, Auli

    2010-10-01

    Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene have been shown to predispose to pituitary adenoma predisposition, a condition characterized by growth hormone (GH)-secreting pituitary tumors. To study AIP-mediated tumorigenesis, we generated an Aip mouse model. Heterozygous mice developed normally but were prone to pituitary adenomas, in particular to those secreting GH. A complete loss of AIP was detected in these lesions, and full penetrance was reached at the age of 15 months. No excess of any other tumor type was found. Ki-67 analysis indicated that Aip-deficient tumors have higher proliferation rates compared with Aip-proficient tumors, suggesting a more aggressive disease. Similar to human AIP-deficient pituitary adenomas, immunohistochemical studies showed that expression of aryl hydrocarbon receptor nuclear translocator 1 or 2 (ARNT or ARNT2) protein was lost in the mouse tumors, suggesting that mechanisms of AIP-related tumorigenesis involve aberrant ARNT function. The Aip(+/-) mouse appears to be an excellent model for the respective human disease phenotype. This model constitutes a tool to further study AIP-associated pituitary tumorigenesis and may be potentially valuable in efforts to develop therapeutic strategies to treat pituitary adenomas.

  2. Genetic analysis in a patient presenting with meningioma and familial isolated pituitary adenoma (FIPA) reveals selective involvement of the R81X mutation of the AIP gene in the pathogenesis of the pituitary tumor.

    PubMed

    Guaraldi, Federica; Corazzini, Valentina; Gallia, Gary L; Grottoli, Silvia; Stals, Karen; Dalantaeva, Nadezhda; Frohman, Lawrence A; Korbonits, Márta; Salvatori, Roberto

    2012-12-01

    Familial isolated pituitary adenoma (FIPA), defined as the occurrence of at least two cases of pituitary adenoma in a family that does not exhibit features of syndromic diseases, such as Carney complex or Multiple Endocrine Neoplasia type 1 or 4, is a rare autosomal dominant disease with low penetrance. About 20 % of the families with FIPA harbor inactivating mutation in aryl hydrocarbon receptor-interacting protein gene (AIP) associated with loss of heterozygosity of the same genetic locus (11q13) in the tumor. Rarely different types of extra-pituitary tumors have been described in the setting of AIP mutation-positive FIPA. We present the case of a patient who was diagnosed with acromegaly due to the AIP mutation c.241C>T (p.R81X) at the age of 34 years, and treated by transsphenoidal surgery. At the age of 43 years she was diagnosed with a meningioma, and at age 46 had recurrence of the somatotropinoma. Genetic studies demonstrated loss of the normal allele (by sequencing and microsatellite analysis) in DNA from the pituitary adenoma but not from the meningioma, suggesting a selective involvement of AIP mutation in the pathogenesis of the pituitary adenoma, and a casual association with the meningioma. Further investigations are required to define the exact role of AIP in non-pituitary tumorigenesis.

  3. Percutaneous transluminal angioplasty in a patient with internal carotid artery stenosis following gamma knife radiosurgery for recurrent pituitary adenoma

    PubMed Central

    Ito, Hidemichi; Onodera, Hidetaka; Sase, Taigen; Uchida, Masashi; Morishima, Hiroyuki; Oshio, Kotaro; Shuto, Takashi; Tanaka, Yuichiro

    2015-01-01

    Background: Intracranial vascular complications following radiosurgery are extremely rare. Case Description: We report a case of stenosis in the internal carotid artery 5 years after gamma knife radiosurgery for a recurrent pituitary adenoma. Percutaneous transluminal angioplasty was performed successfully with anatomical and functional improvement. Conclusion: These results suggested the importance of monitoring for arterial stenosis in the long-term follow-up. Moreover, this is the first case of endovascular treatment as an effective therapy for intracranial arterial stenosis due to radiotherapy. PMID:26069850

  4. Increased expression of programmed death ligand 1 (PD-L1) in human pituitary tumors

    PubMed Central

    Greenwald, Noah F.; Du, Ziming; Agar, Nathalie Y. R.; Kaiser, Ursula B.; Woodmansee, Whitney W.; Reardon, David A.; Freeman, Gordon J.; Fecci, Peter E.; Laws, Edward R.; Santagata, Sandro; Dunn, Gavin P.; Dunn, Ian F.

    2016-01-01

    Purpose Subsets of pituitary tumors exhibit an aggressive clinical courses and recur despite surgery, radiation, and chemotherapy. Because modulation of the immune response through inhibition of T-cell checkpoints has led to durable clinical responses in multiple malignancies, we explored whether pituitary adenomas express immune-related biomarkers that could suggest suitability for immunotherapy. Specifically, programmed death ligand 1 (PD-L1) has emerged as a potential biomarker whose expression may portend more favorable responses to immune checkpoint blockade therapies. We thus investigated the expression of PD-L1 in pituitary adenomas. Methods PD-L1 RNA and protein expression were evaluated in 48 pituitary tumors, including functioning and non-functioning adenomas as well as atypical and recurrent tumors. Tumor infiltrating lymphocyte populations were also assessed by immunohistochemistry. Results Pituitary tumors express variable levels of PD-L1 transcript and protein. PD-L1 RNA and protein expression were significantly increased in functioning (growth hormone and prolactin-expressing) pituitary adenomas compared to non-functioning (null cell and silent gonadotroph) adenomas. Moreover, primary pituitary adenomas harbored higher levels of PD-L1 mRNA compared to recurrent tumors. Tumor infiltrating lymphocytes were observed in all pituitary tumors and were positively correlated with increased PD-L1 expression, particularly in the functional subtypes. Conclusions Human pituitary adenomas harbor PD-L1 across subtypes, with significantly higher expression in functioning adenomas compared to non-functioning adenomas. This expression is accompanied by the presence of tumor infiltrating lymphocytes. These findings suggest the existence of an immune response to pituitary tumors and raise the possibility of considering checkpoint blockade immunotherapy in cases refractory to conventional management. PMID:27655724

  5. AIP mutations impair AhR signaling in pituitary adenoma patients fibroblasts and in GH3 cells.

    PubMed

    Lecoq, Anne-Lise; Viengchareun, Say; Hage, Mirella; Bouligand, Jérôme; Young, Jacques; Boutron, Audrey; Zizzari, Philippe; Lombès, Marc; Chanson, Philippe; Kamenický, Peter

    2016-05-01

    Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene predispose humans to pituitary adenomas through unknown molecular mechanisms. The best-known interacting partner of AIP is the aryl hydrocarbon receptor (AhR), a transcription factor that mediates the effects of xenobiotics implicated in carcinogenesis. As 75% of AIP mutations disrupt the physical and/or functional interaction with AhR, we postulated that the tumorigenic potential of AIP mutations might result from altered AhR signaling. We evaluated the impact of AIP mutations on the AhR signaling pathway, first in fibroblasts from AIP-mutated patients with pituitary adenomas, by comparison with fibroblasts from healthy subjects, then in transfected pituitary GH3 cells. The AIP protein level in mutated fibroblasts was about half of that in cells from healthy subjects, but AhR expression was unaffected. Gene expression analyses showed significant modifications in the expression of the AhR target genes CYP1B1 and AHRR in AIP-mutated fibroblasts, both before and after stimulation with the endogenous AhR ligand kynurenine. Kynurenine increased Cyp1b1 expression to a greater extent in GH3 cells overexpressing wild type compared with cells expressing mutant AIP Knockdown of endogenous Aip in these cells attenuated Cyp1b1 induction by the AhR ligand. Both mutant AIP expression and knockdown of endogenous Aip affected the kynurenine-dependent GH secretion of GH3 cells. This study of human fibroblasts bearing endogenous heterozygous AIP mutations and transfected pituitary GH3 cells shows that AIP mutations affect the AIP protein level and alter AhR transcriptional activity in a gene- and tissue-dependent manner.

  6. Ectopic ACTH-secreting pituitary adenoma of the sphenoid sinus: case report of endoscopic endonasal resection and systematic review of the literature.

    PubMed

    Seltzer, Justin; Lucas, Joshua; Commins, Deborah; Lerner, Olga; Lerner, Alexander; Carmichael, John D; Zada, Gabriel

    2015-02-01

    Ectopic pituitary adenomas are exceedingly rare entities that are often misdiagnosed. The resulting delay in diagnosis may be particularly concerning in the case of Cushing syndrome caused by an ectopic adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. Although the total resection of ectopic adenomas results in rapid and durable remission, persistent Cushing syndrome is often associated with permanently damaging invasive procedures and significantly higher risk of mortality. The authors report the case of a 48-year-old man with ACTH-dependent Cushing syndrome. On the morning before surgery, his serum cortisol measured 51 μg/dl, his ACTH level was 195.7 pg/ml, and his urinary free cortisol level was 2109 μg/day. Serum cortisol was not suppressed with the administration of high-dose dexamethasone. Imaging showed separate masses in both the sphenoid sinus and the pituitary gland, complicating the diagnostic process and requiring pathological assessment of both masses. No other abnormalities were found on thoracic, abdominal, or pelvic scans. Gross-total resection of both lesions was accomplished via an endoscopic endonasal transsphenoidal approach. Pathology confirmed an ectopic ACTH pituitary adenoma of the sphenoid sinus and a Crooke hyaline change of the pituitary gland. The patient achieved stable hormonal remission without significant postoperative complications, returned to full activity within 3 months, and remained disease free nearly 1 year after tumor resection. In a systematic literature review, the authors identified 41 cases of ectopic ACTH-secreting pituitary adenomas, including 18 arising in the sphenoid sinus without direct involvement of the sella. Including the case described here, the total number of ectopic ACTH pituitary adenomas arising in the sphenoid sinus was 19, and the total number of ectopic ACTH pituitary adenomas without regard to location was 42. For the 19 patients with adenomas found in the sphenoid sinus, ages ranged

  7. Effect of Treatment Modality on the Hypothalamic–Pituitary Function of Patients Treated with Radiation Therapy for Pituitary Adenomas: Hypothalamic Dose and Endocrine Outcomes

    PubMed Central

    Elson, Andrew; Bovi, Joseph; Kaur, Kawaljeet; Maas, Diana; Sinson, Grant; Schultz, Chris

    2014-01-01

    Background: Both fractionated external beam radiotherapy and single fraction radiosurgery for pituitary adenomas are associated with the risk of hypothalamic–pituitary (HP) axis dysfunction. Objective: To analyze the effect of treatment modality (Linac, TomoTherapy, or gamma knife) on hypothalamic dose and correlate these with HP-axis deficits after radiotherapy. Methods: Radiation plans of patients treated post-operatively for pituitary adenomas using Linac-based 3D-conformal radiotherapy (CRT) (n = 11), TomoTherapy-based intensity modulated radiation therapy (IMRT) (n = 10), or gamma knife stereotactic radiosurgery (n = 12) were retrospectively reviewed. Dose to the hypothalamus was analyzed and post-radiotherapy hormone function including growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, prolactin, and gonadotropins (follicle stimulating hormone/luteinizing hormone) were assessed. Results: Post-radiation, 13 of 27 (48%) patients eligible for analysis developed at least one new hormone deficit, of which 8 of 11 (72%) occurred in the Linac group, 4 of 8 (50%) occurred in the TomoTherapy group, and 1 of 8 (12.5%) occurred in the gamma knife group. Compared with fractionated techniques, gamma knife showed improved hypothalamic sparing for DMax Hypo and V12Gy. For fractionated modalities, TomoTherapy showed improved dosimetric characteristics over Linac-based treatment with hypothalamic DMean (44.8 vs. 26.8 Gy p = 0.02), DMax (49.8 vs. 39.1 Gy p = 0.04), and V12Gy (100 vs. 76% p = 0.004). Conclusion: Maximal dosimetric avoidance of the hypothalamus was achieved using gamma knife-based radiosurgery followed by TomoTherapy-based IMRT, and Linac-based 3D conformal radiation therapy, respectively. PMID:24782984

  8. Pituitary apoplexy: pathophysiology, diagnosis and management.

    PubMed

    Glezer, Andrea; Bronstein, Marcello D

    2015-06-01

    Pituitary apoplexy is characterized by sudden increase in pituitary gland volume secondary to ischemia and/or necrosis, usually in a pituitary adenoma. Most cases occur during the 5th decade of life, predominantly in males and in previously unknown clinically non-functioning pituitary adenomas. There are some predisposing factors as arterial hypertension, anticoagulant therapy and major surgery. Clinical picture comprises headache, visual impairment, cranial nerve palsies and hypopituitarism. Most cases improve with both surgical and expectant management and the best approach in the acute phase is still controversial. Surgery, usually by transsphenoidal route, is indicated if consciousness and/or vision are impaired, despite glucocorticoid replacement and electrolyte support. Pituitary function is impaired in most patients before apoplexy and ACTH deficiency is common, which makes glucocorticoid replacement needed in most cases. Pituitary deficiencies, once established, usually do not recover, regardless the treatment. Sellar imaging and endocrinological function must be periodic reevaluated.

  9. Successful management of a pregnant woman with a TSH secreting pituitary adenoma with surgical and medical therapy.

    PubMed

    Chaiamnuay, Sumapa; Moster, Mark; Katz, M Richard; Kim, Young Nam

    2003-09-01

    We described a 39-yr-old asian female who was initially diagnosed with prolactinoma and presented with increase nervousness and weight loss. Laboratory evaluation revealed an inappropriately normal TSH level with elevated free T4, total T3, alpha-subunit and prolactin level. The alpha-subunit/TSH molar ratio was 4. MRI showed a macroadenoma extending to the suprasellar cistern. Treatment was begun with propylthiouracil and bromocriptine. After 5 months of therapy, she became pregnant. At 27 weeks of gestation, she developed headache and decreased visual acuity in her left eye. MRI showed a slightly increase in tumor size compressing the optic chaiasm. Transphenoid macroadenectomy was performed with immediate relief of the visual field abnormality. At 39 weeks gestation a baby with no malformations was delivered. This is the second case report of TSH secreting pituitary adenoma which was exarcerbated during pregnancy. In contrast to the first case, our case was managed with both surgical and medical approach. The judicious use of both medical and surgical therapy can result in a successful outcome to mother and fetus in a patient with TSH secreting pituitary adenoma.

  10. Altered Vision-Related Resting-State Activity in Pituitary Adenoma Patients with Visual Damage

    PubMed Central

    Qian, Haiyan; Wang, Xingchao; Wang, Zhongyan; Wang, Zhenmin; Liu, Pinan

    2016-01-01

    Objective To investigate changes of vision-related resting-state activity in pituitary adenoma (PA) patients with visual damage through comparison to healthy controls (HCs). Methods 25 PA patients with visual damage and 25 age- and sex-matched corrected-to-normal-vision HCs underwent a complete neuro-ophthalmologic evaluation, including automated perimetry, fundus examinations, and a magnetic resonance imaging (MRI) protocol, including structural and resting-state fMRI (RS-fMRI) sequences. The regional homogeneity (ReHo) of the vision-related cortex and the functional connectivity (FC) of 6 seeds within the visual cortex (the primary visual cortex (V1), the secondary visual cortex (V2), and the middle temporal visual cortex (MT+)) were evaluated. Two-sample t-tests were conducted to identify the differences between the two groups. Results Compared with the HCs, the PA group exhibited reduced ReHo in the bilateral V1, V2, V3, fusiform, MT+, BA37, thalamus, postcentral gyrus and left precentral gyrus and increased ReHo in the precuneus, prefrontal cortex, posterior cingulate cortex (PCC), anterior cingulate cortex (ACC), insula, supramarginal gyrus (SMG), and putamen. Compared with the HCs, V1, V2, and MT+ in the PAs exhibited decreased FC with the V1, V2, MT+, fusiform, BA37, and increased FC primarily in the bilateral temporal lobe (especially BA20,21,22), prefrontal cortex, PCC, insular, angular gyrus, ACC, pre-SMA, SMG, hippocampal formation, caudate and putamen. It is worth mentioning that compared with HCs, V1 in PAs exhibited decreased or similar FC with the thalamus, whereas V2 and MT+ exhibited increased FCs with the thalamus, especially pulvinar. Conclusions In our study, we identified significant neural reorganization in the vision-related cortex of PA patients with visual damage compared with HCs. Most subareas within the visual cortex exhibited remarkable neural dysfunction. Some subareas, including the MT+ and V2, exhibited enhanced FC with the thalamic

  11. Tumor-specific downregulation and methylation of the CDH13 (H-cadherin) and CDH1 (E-cadherin) genes correlate with aggressiveness of human pituitary adenomas.

    PubMed

    Qian, Zhi Rong; Sano, Toshiaki; Yoshimoto, Katsuhiko; Asa, Sylvia L; Yamada, Shozo; Mizusawa, Noriko; Kudo, Eiji

    2007-12-01

    The gene products of CDH13 and CDH1, H-cadherin and E-cadherin, respectively, play a key role in cell-cell adhesion. Inactivation of the cadherin-mediated cell adhesion system caused by aberrant methylation is a common finding in human cancers, indicating that the CDH13 and CDH1 function as tumor suppressor and invasion suppressor genes. In this study, we analyzed the expression of H-cadherin mRNA and E-cadherin protein in 5 normal pituitary tissues and 69 primary pituitary adenomas including all major types by quantitative real-time RT-PCR (qRT-PCR) and immunohistochemistry, respectively. Reduced expression of H-cadherin was detected in 54% (28/52) of pituitary tumors and was significantly associated with tumor aggressiveness (P<0.05). E-cadherin expression was lost in 30% (21 of 69) and significantly reduced in 32% (22 of 69) of tumors. E-cadherin expression was significantly lower in grade II, III, and IV than in grade I adenomas (P=0.015, P=0.029, and P=0.01, respectively). Using methylation-specific PCR (MSP), promoter hypermethylation of CDH13 and CDH1 was detected in 30 and 36% of 69 adenomas, respectively, but not in 5 normal pituitary tissues. Methylation of CDH13 was observed more frequently in invasive adenomas (42%) than in non-invasive adenomas (19%) (P<0.05) and methylation of CDH1 was more frequent in grade IV adenomas compared with grade I adenomas (P<0.05). Methylation of either CDH13 or CDH1 was identified in 35 cases (51%) and was more frequent in grade IV invasive adenomas than in grade I non-invasive adenomas (P<0.05 and P<0.05, respectively). Downregulation of expression was correlated with promoter hypermethylation in CDH13 and CDH1. In conclusion, the tumor-specific downregulation of expression and methylation of CDH13 and CDH1, alone or in combination, may be involved in the development and invasive growth of pituitary adenomas.

  12. The expression profile of Dopamine D2 receptor, MGMT and VEGF in different histological subtypes of pituitary adenomas: a study of 197 cases and indications for the medical therapy

    PubMed Central

    2014-01-01

    Background To study the expression of D2R, MGMT and VEGF for clinical significance in pituitary adenomas, and to predict the potential curative medical therapy of dopamine agonists, temozolomide and bevacizumab on pituitary adenomas. Methods Immunohistochemistry and western blot were performed to detect the expression of expression of D2R, MGMT and VEGF in pituitary adenoma tissue samples. The ratio of high expression of D2R, MGMT or VEGF in different subtypes of PA was compared by the use of chi-squared tests. The relationships between D2R, MGMT and VEGF expression were assessed by the Spearman rank correlation test. The association between their expression and clinical parameters was analyzed using a chi-squared test, or Fisher's exact probability test when appropriate. Results The data showed that in 197 different histological subtypes of pituitary adenomas (PAs), 64.9% of them were D2R high expression, 86.3% were MGMT low expression and 58.9% were VEGF high expression. D2R high expression existed more frequently in PRL- and GH- secreting PAs. MGMT low expression existed in all PA subtypes. VEGF high expression existed more frequently in PRL, ACTH, FSH secreting and non-functioning PAs. The data of western blot also support the results. Spearman's rank correlation analysis showed that expression of MGMT was positively associated with D2R (r = 0.154, P = 0.031) and VEGF (r = 0.161, P = 0.024) in PAs, but no correlation was showed between D2R and VEGF expression (r = −0.025, P = 0.725 > 0.05). The association between their expression and clinical parameters was analyzed using a chi-squared test, or Fisher's exact probability test when appropriate, but the result showed no significant association. Conclusions PRL-and GH-secreting PAs exist high expression of D2R, responding to dopamine agonists; Most PAs exist low expression of MGMT and high expression of VEGF, TMZ or bevacizumab treatment could be applied under the premise of

  13. Amino acid distribution and metabolism in pituitary adenomas using positron emission tomography with D-(/sup 11/C)methionine and L-(/sup 11/C)methionine

    SciTech Connect

    Bergstroem, M.M.; Muhr, C.; Lundberg, P.O.; Bergstroem, K.L.; Lundqvist, H.; Antoni, G.; Fasth, K.J.; Langstroem B3

    1987-05-01

    Four patients with hormonally inactive pituitary adenomas were examined with positron emission tomography (PET) after injection, during different examinations, of L-(methyl-/sup 11/C)methionine and D-(methyl-/sup 11/C)methionine, respectively. After the rapid distribution phase, the enantiomer L-(/sup 11/C)methionine, which is metabolically active, showed a considerable continuous irreversible trapping attributed to amino acid metabolism. The stereoisomer D-(/sup 11/C)methionine, which does not participate in protein synthesis, showed a rapid distribution within the whole adenoma tissue, with a distribution space on the order of 100%. A minimal irreversible trapping was observed which could be explained by technical factors. It is concluded that PET using the two enantiomers allows a separation of passive distribution and metabolism, and that L-(/sup 11/C)methionine can be used for in vivo quantitative studies of amino acid metabolism of pituitary adenomas.

  14. 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.

    PubMed

    Thompson, Lester D R; Seethala, Raja R; Müller, Susan

    2012-03-01

    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 <1% proliferation index (Ki-67). There was a vascularized to sclerotic or calcified

  15. Increased micronucleus, nucleoplasmic bridge, nuclear bud frequency and oxidative DNA damage associated with prolactin levels and pituitary adenoma diameters in patients with prolactinoma.

    PubMed

    Bitgen, N; Donmez-Altuntas, H; Bayram, F; Cakir, I; Hamurcu, Z; Diri, H; Baskol, G; Senol, S; Durak, A C

    2016-01-01

    Prolactinoma is the most common pituitary tumor. Most pituitary tumors are benign, but they often are clinically significant. We investigated cytokinesis-block micronucleus cytome (CBMN cyt) assay parameters and oxidative DNA damage in patients with prolactinoma to assess the relations among age, prolactin level, pituitary adenoma diameter and 8-hydroxy-2'-deoxyguanosine (8-OHdG) level in patients with prolactinoma. We investigated 27 patients diagnosed with prolactinoma and 20 age- and sex-matched healthy controls. We measured CBMN cyt parameters and plasma 8-OHdG levels in peripheral blood lymphocytes of patients with prolactinoma and controls. The frequencies of micronucleus (MN), nucleoplasmic bridge, nuclear bud, apoptotic and necrotic cells, and plasma 8-OHdG levels in patients with prolactinoma were significantly greater than controls. MN frequency was correlated positively with age, prolactin levels and pituitary adenoma diameters in patients with prolactinoma. The increased chromosomal and oxidative DNA damage, and the positive correlation between MN frequency, prolactin levels and pituitary adenoma diameters may be associated with increased risk of cancer in patients with prolactinoma, because increased MN frequency is a predictor of cancer risk.

  16. In vivo detection of somatostatin receptors in patients with functionless pituitary adenomas by means of a radioiodinated analog of somatostatin ((123I)SDZ 204-090)

    SciTech Connect

    Faglia, G.; Bazzoni, N.; Spada, A.; Arosio, M.; Ambrosi, B.; Spinelli, F.; Sara, R.; Bonino, C.; Lunghi, F. )

    1991-10-01

    The recent availability of a Tyr3-substituted octreotide (SDZ 204-090) for radioiodination has allowed somatostatin (SRIH) receptor binding to be studied in vivo, and receptor-positive tumors of different origins to be visualized with a gamma-camera. This prompted us to investigate whether this compound could be used for external imaging of functionless pituitary adenomas displaying SRIH receptors. Eight patients with functionless pituitary adenomas, three patients with acromegaly, and three with macroprolactinoma were injected iv with 123I-labeled Tyr3-octreotide and then scanned with a gamma-camera. Positive scans were obtained in the three acromegalics and in two of the eight patients with functionless pituitary tumors. The patients with macroprolactinoma had negative scans. The diagnosis of functionless pituitary adenomas was confirmed by light and electron microscopic examination as well as immunocytochemical studies. In vitro binding of (125I)Tyr11-SRIH to cell membranes was evaluated in four functionless and three GH-secreting adenomas removed from seven of the patients. All of the GH-secreting as well as one of the four functionless adenomas had high affinity SRIH-binding sites, without differences in number or affinity, whereas SRIH-binding sites were not detected in the others. Positive scans were observed only in patients bearing tumors with high affinity SRIH-binding sites. In conclusion, (123I)Tyr3-octreotide appears to be a promising tool for singling out, in vivo, patients with functionless pituitary tumors displaying SRIH receptors who might potentially benefit from octreotide treatment.

  17. Pituitary gland involvement by a gamma delta hepatosplenic lymphoma, a mimicker of pituitary adenoma: report of a rare case.

    PubMed

    Jain, D; Sharma, M C; Sarkar, C; Suri, V; Garg, A; Mahapatra, A K; Kumar, L

    2008-06-01

    The authors report an unusual case of hepatosplenic T-cell lymphoma in a 41-year-old male patient. He presented initially with low grade fever, hepatosplenomegaly and pancytopenia. Splenectomy was done which showed infiltration of red pulp by monomorphic lymphocytes. Liver was also infiltrated with similar cells. A provisional diagnosis of hairy cell leukemia was made. Subsequently, after 6 months he was found to have a sellar mass, which on microscopy revealed lymphoma cells. These cells were positive for leukocyte common antigen and T-cell markers. Finally, based on overall clinical, histomorphological and immunophenotypic features, a diagnosis of hepatosplenic T-cell lymphoma, possibly gamma delta type, involving pituitary gland was established. On follow up, this patient showed evidence of bone marrow involvement and died after 1.5-year of diagnosis. This case highlights the involvement of rare site by a rare lymphoma and should be kept in mind in the differential diagnoses of pituitary tumors.

  18. Pilot Study on Early Postoperative Discharge in Pituitary Adenoma Patients: Effect of Socioeconomic Factors and Benefit of Specialized Pituitary Centers.

    PubMed

    Sarkiss, Christopher A; Lee, James; Papin, Joseph A; Geer, Eliza B; Banik, Rudrani; Rucker, Janet C; Oudheusden, Barbara; Govindaraj, Satish; Shrivastava, Raj K

    2015-08-01

    Introduction Pituitary neoplasms are benign entities that require distinct diagnostic and treatment considerations. Recent advances in endoscopic transsphenoidal surgery have resulted in shorter lengths of stay (LOS). We implemented a postoperative day (POD) 1 discharge paradigm involving a multidisciplinary approach and detailed preoperative evaluation and review of both medical and socioeconomic factors. Methods The experience of a single neurosurgeon/ears, nose, throat (ENT) team was reviewed, generating a preliminary retrospective database of the first 30 patients who underwent resection of pituitary lesions under the POD 1 discharge paradigm. We assessed multiple axes from their preoperative, in-house, and postoperative care. Results There were 14 men and 16 women with an average age of 53.8 years (range: 27-76 years). There were 22 nonsecretory and 8 secretory tumors with average size of 2.80 cm (range: 1.3-5.0 cm). All 30 patients underwent preoperative ENT evaluation. Average LOS was 1.5 ± 0.7 days. A total of 18 of 30 patients were discharged on POD 1. The insurance status included 15 with public insurance such as emergency Medicaid and 15 with private insurance. Four patients had transient diabetes insipidus (DI); none had permanent DI. Overall, 28 of 30 patients received postoperative steroids. Factors that contributed to LOS > 1 day included public insurance status, two or more medical comorbidities, diabetes mellitus, transient panhypopituitarism, and DI. Conclusion The implementation of a POD 1 discharge plan for pituitary tumors is feasible and safe for elective patients. This implementation requires the establishment of a dedicated Pituitary Center model with experienced team members. The consistent limitation to early discharge was socioeconomic status. Efforts that incorporate the analysis of social disposition parameters with proper management of clinical sequelae are crucial to the maintenance of ideal LOS and optimal patient

  19. Ectopic acromegaly due to a GH-secreting pituitary adenoma in the sphenoid sinus: a case report and review of the literature

    PubMed Central

    2013-01-01

    Background In more than 98% of cases, acromegaly is due to a GH-secreting pituitary adenoma. The term “ectopic acromegaly” includes neuroendocrine tumors secreting GH releasing hormone (GHRH), usually located in the lungs, thymus and endocrine pancreas. Considerably less frequent are cases of ectopic acromegaly due to GH-secreting tumors located out of the pituitary fossa; except for one isolated case of a well-documented GH-secreting lymphoma, the majority of these lesions are located in the sphenoid sinus. Case presentation We present the case of a 45 year old woman with acromegaly whose MRI showed an empty sella without evidence of a pituitary adenoma but revealed a large mass within the sphenoid sinus. She underwent transsphenoidal surgery and the excised sphenoid sinus mass, proved to be a GH-secreting adenoma; the sellar floor was intact and no other lesions were found in the pituitary fossa. She required postoperative treatment with somatostatin analogs and cabergoline for clinical and biochemical control. Conclusions This case highlights the importance of carefully evaluating the structures surrounding the sellar area when a pituitary adenoma is not found with currently available imaging techniques. The finding of an intact sellar floor and duramater lead us to conclude that the patient’s tumor originated de novo from embryological pituitary remnants. Upon a careful review of the literature and a critical evaluation of our case we found neither clinical nor biochemical features that would distinguish an ectopic from the more common eutopically located somatotrophinoma. PMID:24119925

  20. [Prognostic implications of folliculo-stellate cells in pituitary adenomas: relationship with tumoral behavior].

    PubMed

    Tortosa, F; Pires, M; Ortiz, S

    2016-10-01

    Introduccion. A pesar del progreso en la comprension de su patogenia, no se ha encontrado ningun marcador predictivo independiente del comportamiento agresivo de los adenomas hipofisarios que facilite el tratamiento y seguimiento de pacientes afectados. Objetivo. Analizar la expresion de celulas foliculo-estrelladas, mediante inmunomarcacion con proteina S-100, en una serie de pacientes con adenomas hipofisarios seguidos durante al menos siete años. Pacientes y metodos. Estudio retrospectivo de 51 pacientes diagnosticados de adenoma hipofisario entre 2006 y 2008, segun los criterios vigentes de la Organizacion Mundial de la Salud. Se evaluo inmunohistoquimicamente la expresion de S-100 en celulas foliculo-estrelladas, y se correlaciono con parametros clinicorradiologicos e histopatologicos del tumor y la progresion/recurrencia postoperatoria. Resultados. De 51 tumores, 40 se clasificaron como adenomas hipofisarios tipicos y 11 como atipicos. La mayoria de los tipicos mostro celulas foliculo-estrelladas positivas para S-100 (media: 3,93%); los atipicos tenian pocas o ninguna celula S-100 positivas (media: 0,83%). No hubo diferencias significativas en la expresion de S-100 con respecto a la edad o sexo del paciente, tamaño, invasividad o recidiva tumoral posquirurgica. Conclusiones. En el grupo de estudio, a excepcion de los adenomas no funcionantes inmunopositivos para prolactina, con la media mas baja y mas alta de todos los subtipos en ambos grupos (tipicos, 0,25%, frente a atipicos, 9,24%; p = 0,0028), el factor predictivo de agresividad tumoral para los adenomas hipofisarios no esta representado por un bajo valor de S-100 en las celulas foliculo-estrelladas, lo que no permite seleccionar a pacientes para un tratamiento postoperatorio intensivo.

  1. A pleiomorphic GH pituitary adenoma from a Carney complex patient displays universal allelic loss at the protein kinase A regulatory subunit 1A (PRKARIA) locus

    PubMed Central

    Bossis, I; Voutetakis, A; Matyakhina, L; Pack, S; Abu-Asab, M; Bourdeau, I; Griffin, K; Courcoutsakis, N; Stergiopoulos, S; Batista, D; Tsokos, M; Stratakis, C

    2004-01-01

    Carney complex (CNC) is a familial multiple endocrine neoplasia syndrome associated with GH-producing pituitary tumours and transmitted as an autosomal dominant trait. Mutations of the PRKAR1A gene are responsible for approximately half the known CNC cases but have never found in sporadic pituitary tumours. Pituitary tissue was obtained from an acromegalic CNC patient heterozygote for a common (PRKARIA)i-inactivating mutation. Both immunohistochemistry and electron microscopy showed a highly pleiomorphic pituitary adenoma. The cell culture population appeared morphologically heterogeneous and remained so after more than 30 passages. The mixture was comprised of cells strongly immunostained for GH, spindle-shaped myofibroblast-like cells, and cuboid cells with large axonal projections (negative for GH). The population appeared to have both epithelial and mesenchymal cells. Both at baseline and at passage 30, cytogenetic analysis indicated the presence of normal 46, XY diploid karyotype, whereas losses of the PRKARIAi locus were demonstrated in more than 98% of the cells by fluorescent in situ hybridisation, supporting this gene's involvement in pituitary tumorigenesis. Allelic loss may have occurred in a single precursor cell type that differentiated and clonally expanded into several phenotypes. Epithelial-to-mesenchymal transition may also occur in CNC-associated pleiomorphic pituitary adenomas. PMID:15286154

  2. The Influence of Pituitary Adenoma Size on Vision and Visual Outcomes after Trans-Sphenoidal Adenectomy: A Report of 78 Cases

    PubMed Central

    Ho, Ren-Wen; Huang, Hsiu-Mei

    2015-01-01

    Objective The aims of this study were to investigate the quantitative relationship between pituitary macroadenoma size and degree of visual impairment, and assess visual improvement after surgical resection of the tumor. Methods The medical records of patients with pituitary adenoma, who had undergone trans-sphenoidal adenectomy between January 2009 and January 2011, were reviewed. Patients underwent an ocular examination and brain MRI before and after surgery. The visual impairment score (VIS) was derived by combining the scores of best-corrected visual acuity and visual field. The relationship between VIS and tumor size/tumor type/position of the optic chiasm was assessed. Results Seventy-eight patients were included (41 male, 37 female). Thirty-two (41%) patients experienced blurred vision or visual field defect as an initial symptom. Receiver operating characteristic curve analysis showed that tumors <2.2 cm tended to cause minimal or no visual impairment. Statistical analysis showed that 1) poor preoperative vision is related to tumor size, displacement of the optic chiasm in the sagittal view on MRI and optic atrophy, and 2) poorer visual prognosis is associated with greater preoperative VIS. In multivariate analysis the only factor significantly related to VIS improvement was increasing pituitary adenoma size, which predicted decreased improvement. Conclusion Results from this study show that pituitary adenomas larger than 2 cm cause defects in vision while adenomas 2 cm or smaller do not cause significant visual impairment. Patients with a large macroadenoma or giant adenoma should undergo surgical resection as soon as possible to prevent permanent visual loss. PMID:25674340

  3. Familial isolated pituitary adenoma caused by a Aip gene mutation not described before in a family context.

    PubMed

    García-Arnés, J A; González-Molero, I; Oriola, J; Mazuecos, N; Luque, R; Castaño, J; Arraez, M A

    2013-12-01

    The cause of familial isolated pituitary adenomas (FIPA) remains unknown in a high percentage of cases, but the AIP gene plays an important role in the etiology. The aim of the study is to describe a family with FIPA syndrome and the results of genomic studies. A 16-year-old man had a giant prolactinoma resistant tomedical treatment with delayed growth and pubertal development. His mother had been previously diagnosed with a nonfunctioning pituitary macroadenoma. Transsphenoidal endoscopic resection was performed and a genetic study revealed a heterozygous mutation in exon 6: 974G>A (p.Arg325Gln). Because the AIP gene is a tumor suppressor gene, we searched for loss of heterozygosity within the AIP gene by amplifying exon 6 from tumor tissue of the patient. In the electropherogram, only the A allele was amplified (hemizygous state), indicating loss of the normal allele. We report a Spanish family with FIPA in whom a mutation in the AIP gene previously unreported in a familiar context was identified.

  4. Cyclin-dependent kinase inhibitor 1B (CDKN1B) gene variants in AIP mutation-negative familial isolated pituitary adenoma kindreds.

    PubMed

    Tichomirowa, Maria A; Lee, Misu; Barlier, Anne; Daly, Adrian F; Marinoni, Ilaria; Jaffrain-Rea, Marie-Lise; Naves, Luciana A; Rodien, Patrice; Rohmer, Vincent; Faucz, Fabio Rueda; Caron, Philippe; Estour, Bruno; Lecomte, Pierre; Borson-Chazot, Françoise; Penfornis, Alfred; Yaneva, Maria; Guitelman, Mirtha; Castermans, Emily; Verhaege, Catherine; Wémeau, Jean-Louis; Tabarin, Antoine; Fajardo Montañana, Carmen; Delemer, Brigitte; Kerlan, Veronique; Sadoul, Jean-Louis; Cortet Rudelli, Christine; Archambeaud, Françoise; Zacharieva, Sabine; Theodoropoulou, Marily; Brue, Thierry; Enjalbert, Alain; Bours, Vincent; Pellegata, Natalia S; Beckers, Albert

    2012-06-01

    Familial isolated pituitary adenoma (FIPA) occurs in families and is unrelated to multiple endocrine neoplasia type 1 and Carney complex. Mutations in AIP account only for 15-25% of FIPA families. CDKN1B mutations cause MEN4 in which affected patients can suffer from pituitary adenomas. With this study, we wanted to assess whether mutations in CDKN1B occur among a large cohort of AIP mutation-negative FIPA kindreds. Eighty-eight AIP mutation-negative FIPA families were studied and 124 affected subjects underwent sequencing of CDKN1B. Functional analysis of putative CDKN1B mutations was performed using in silico and in vitro approaches. Germline CDKN1B analysis revealed two nucleotide changes: c.286A>C (p.K96Q) and c.356T>C (p.I119T). In vitro, the K96Q change decreased p27 affinity for Grb2 but did not segregate with pituitary adenoma in the FIPA kindred. The I119T substitution occurred in a female patient with acromegaly. p27(I119T) shows an abnormal migration pattern by SDS-PAGE. Three variants (p.S56T, p.T142T, and c.605+36C>T) are likely nonpathogenic because In vitro effects were not seen. In conclusion, two patients had germline sequence changes in CDKN1B, which led to functional alterations in the encoded p27 proteins in vitro. Such rare CDKN1B variants may contribute to the development of pituitary adenomas, but their low incidence and lack of clear segregation with affected patients make CDKN1B sequencing unlikely to be of use in routine genetic investigation of FIPA kindreds. However, further characterization of the role of CDKN1B in pituitary tumorigenesis in these and other cases could help clarify the clinicopathological profile of MEN4.

  5. What Happens After Treatment for Pituitary Tumors?

    MedlinePlus

    ... adenomas. If you had a functional (hormone-making) pituitary adenoma, hormone measurements can often be done within days ... risk. Occasionally, people with large or fast-growing pituitary adenomas may be disabled or have their lives shortened ...

  6. The Application of a New Maximum Color Contrast Sensitivity Test to the Early Prediction of Chiasma Damage in Cases of Pituitary Adenoma: The Pilot Study

    PubMed Central

    Liutkeviciene, Rasa; Glebauskiene, Brigita; Zaliuniene, Dalia; Kriauciuniene, Loresa; Bernotas, Giedrimantas; Tamasauskas, Arimantas

    2016-01-01

    Purpose Our objective was to estimate the maximum color contrast sensitivity (MCCS) thresholds in individuals with chiasma opticum damage. Methods The pilot study tested 41 people with pituitary adenoma (PA) and 100 age- and gender-matched controls. Patients were divided into two groups according to PA size, PA ≤1 cm or PA >1 cm. A new MCCS test program was used for color discrimination. Results The mean total error score (TES) of MCCS was 1.8 in the PA ≤1 cm group (standard deviation [SD], 0.38), 3.5 in the PA >1 cm group (SD, 0.96), and 1.4 in the control group (SD, 0.31; p < 0.001). There was a positive correlation between tumor size and MCCS result (r = 0.648, p < 0.01). In the group that had PA-producing hormones, the TES was 2.5 (SD, 1.09), compared to 4.2 value in the non-functioning PA group of patients that did not have clinically significant hormone excess (SD, 3.16; p < 0.01). In patients with normal visual acuity (VA) or visual field MCCS, the TES was 3.3 (SD, 1.8), while that in patients with VA <0.00 was 4.6 (SD, 2.9). Conclusions Results of the MCCS test TES were 1.9 times better in patients with PA ≤1 cm compared to patients with PA >1 cm (p < 0.01). In PA patients with normal VA, the TES was 2.35 times worse than that of healthy persons (p < 0.01). PMID:27478357

  7. Correlation of scintigraphic results using 123I-methoxybenzamide with hormone levels and tumor size response to quinagolide in patients with pituitary adenomas.

    PubMed

    Ferone, D; Lastoria, S; Colao, A; Varrella, P; Cerbone, G; Acampa, W; Merola, B; Salvatore, M; Lombardi, G

    1998-01-01

    The efficacy of dopaminergic agents in the medical treatment of pituitary adenomas is well known. Quinagolide is a nonergot derivative dopamine agonist, which binds dopamine D2 receptors with high affinity. The treatment with this drug is reported to suppress hormone levels and to cause tumor shrinkage in prolactinomas and in a few GH-secreting pituitary adenomas. In clinically nonfunctioning pituitary adenomas (NFPA), the efficacy of quinagolide treatment is controversial. The scintigraphy of the pituitary region using 123I-methoxybenzamide (123I-IBZM) allows us to visualize in vivo the expression of dopamine D2 receptors on pituitary tumors. In this study, the pituitary scintigraphy with 123I-IBZM was performed in 14 patients with macroadenoma before starting a long-term treatment with quinagolide: 6 NFPA with high circulating alpha-subunit levels, 4 PRL-secreting, and 4 GH-secreting adenomas. A 3-point score was used to grade the ligand accumulation within the pituitary adenomas: 0 = negative, 1 = moderate uptake (equal to that recorded in the cerebral cortex), and 2 = intense uptake (equal to that recorded in the basal nuclei). The treatment with quinagolide was carried out at the dose of 0.3-0.6 mg/day for 6-12 months. Clinical, biochemical and hormonal assessment was repeated monthly during the first 3 months, then quarterly. Sellar magnetic resonance imaging was performed before and after 6 and 12 months of quinagolide treatment, to evaluate tumor shrinkage (> 25% of baseline size). In all 14 patients, a significant positive correlation was found between the degree of 123I-IBZM uptake and the clinical response to quinagolide treatment (r = 0.90; P < 0.001). In particular, the normalization of serum alpha-subunit and PRL levels, respectively, was achieved in 3 patients with NFPA and in 2 patients with prolactinoma, who showed intense 123I-IBZM uptake in the pituitary region. In 4 of these 5 patients with positive scan, a significant tumor shrinkage occurred

  8. Benign pituitary adenoma associated with hyperostosis of the spenoid bone and monocular blindness. Case report.

    PubMed

    Milas, R W; Sugar, O; Dobben, G

    1977-01-01

    The authors describe a case of benign chromophobe adenoma associated with hyperostosis of the lesser wing of the sphenoid bone and monocular blindness in a 38-year-old woman. The endocrinological and radiological evaluations were all suggestive of a meningioma. The diagnosis was established by biopsy of the tumor mass. After orbital decompression and removal of the tumor, the patient was treated with radiation therapy. Her postoperative course was uneventful, and her visual defects remained fixed.

  9. Immediate postoperative radiotherapy in residual nonfunctioning pituitary adenoma: Beneficial effect on local control without additional negative impact on pituitary function and life expectancy

    SciTech Connect

    Bergh, Alfons C.M. van den . E-mail: a.c.m.van.den.bergh@rt.umcg.nl; Berg, Gerrit van den; Schoorl, Michiel A.; Sluiter, Wim J.; Vliet, Anton M. van der; Hoving, Eelco W.; Szabo, Ben G.; Langendijk, Johannes A.; Wolffenbuttel, Bruce H.R.; Dullaart, Robin P.F.

    2007-03-01

    Purpose: To demonstrate the benefit of immediate postoperative radiotherapy in residual nonfunctioning pituitary adenoma (NFA) in perspective to the need for hormonal substitution and life expectancy. Methods and Materials: Retrospective cohort analysis of 122 patients, operated for NFA between 1979 and 1998. Recurrence was defined as regrowth on computed tomography or magnetic resonance imaging. The occurrence of hormonal deficiencies was defined as the starting date of hormonal substitution therapy. Results: Seventy-six patients had residual NFA after surgery and received immediate postoperative radiotherapy (Group 1); three patients developed a recurrence, resulting in a 95% local control rate at 10 years. Twenty-eight patients had residual NFA after surgery, but were followed by a wait-and-see policy (Group 2). Sixteen developed a recurrence, resulting in a local control rate of 49% at 5 years and 22% at 10 years (p < 0.001 compared with Group 1). There were no differences between Group 1 and 2 regarding the need for substitution with thyroid hormone, glucocorticoids, and sex hormones before first surgery, directly after surgery and at end of follow-up. There were no differences in hormone substitution free survival between Group 1 and Group 2 during the study period after first surgery. Life expectancy was similar in Group 1 and 2, and their median life expectancy did not differ from median life expectancy in the general population. Conclusions: Immediate postoperative radiotherapy provides a marked improvement of local control among patients with residual NFA compared with surgery alone, without an additional deleterious effect on pituitary function and life expectancy.

  10. Genetic disruption of dopamine production results in pituitary adenomas and severe prolactinemia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dopamine release from tuberoinfundibular dopamine neurons into the median eminence activates dopamine-D2 receptors in the pituitary gland where it inhibits lactotroph function. We have previously described genetic dopamine-deficient mouse models which lack the ability to synthesize dopamine. Because...

  11. Role of mTOR Inhibitors in Growth Hormone-Producing Pituitary Adenomas Harboring Different FGFR4 Genotypes.

    PubMed

    Jalali, Shahrzad; Monsalves, Eric; Tateno, Toru; Zadeh, Gelareh

    2016-09-01

    Pituitary adenomas (PAs) are common intracranial lesions. Available medical therapies are limited in PAs, and therefore, it is essential to identify treatments that control PA growth when surgery is not an option. Fibroblast growth factor 4 is implicated in PA pathogenesis; therefore, in this study, we used an isogenic mammosomatotroph cell line (GH4C1) harboring different fibroblast growth factor receptor (FGFR)-4 genotypes to establish and characterize intracranial xenograft mouse models that can be used for preclinical drug testing. We show that proliferating GH4C1 tumors have an average latency of 3 weeks to form. Histological analysis revealed that prototypic FGFR4 (G388) tumors express increased prolactin and less GH, whereas tumors possessing the polymorphic variant of FGFR4 (R388) express increased GH relative to prolactin. All tumors show abundant mammalian target of rapamycin (mTOR) signaling as confirmed using phosphorylated (p)-S6 and p-4E-binding protein 1 as downstream regulators of this pathway. We subsequently demonstrate that the mTOR inhibitor RAD001 decreases tumor growth rate and reduces p-S6 but not p-4E-binding protein 1 activation, regardless of FGFR4 status. More importantly, GH activity was significantly reduced after mTOR inhibition in the R388 polymorphic variant tumors. This reduction was also associated with a concomitant reduction in serum IGF-1 levels in the R388 group. In summary, we demonstrate that the GH4C1 FGFR polymorphic xenograft is a useful model for examining PAs. Furthermore, we show that RAD001 can efficiently reduce tumor growth rate by a reduction in mTOR signaling and more importantly results in control of GH expression and IGF-1 secretion, providing further support for using mTOR inhibitors in PA patients, in particular GH-producing adenomas.

  12. Dopamine receptors in pituitary adenomas: PET visualization with 11C-N-methylspiperone

    SciTech Connect

    Muhr, C.; Bergstroem, M.L.; Lundberg, P.O.; Bergstroem, K.H.; Hartvig, P.; Lundqvist, H.; Antoni, G.; Langstroem B2

    1986-03-01

    Two patients with pituitary tumors were examined with positron emission tomography (PET) after intravenous administration of 11C-N-methylspiperone. In repeat studies the patients were given 1 mg of intravenous haloperidol prior to the administration of the radioligand to block the dopamine receptors. High uptakes of the radiolabeled ligand were seen in one of the tumors. With haloperidol pretreatment the uptake was lower, probably mainly showing the remaining unspecific binding. The most marked uptake and the largest effect of haloperidol pretreatment was seen in a patient with a hormonally active prolactinoma. Dopamine receptor binding in pituitary tumors can be demonstrated in vivo with PET, and quantification of this binding is possible using a compartmental model. This technique may be useful in improving our understanding of the variable response to medical treatment of prolactinomas with dopamine agonists as well as in the prediction of the effect of such treatment.

  13. Null cell adenomas of the pituitary gland: an institutional review of their clinical imaging and behavioral characteristics.

    PubMed

    Balogun, James A; Monsalves, Eric; Juraschka, Kyle; Parvez, Kashif; Kucharczyk, Walter; Mete, Ozgur; Gentili, Fred; Zadeh, Gelareh

    2015-03-01

    The aim of the study was to establish if the null cell adenoma (NCA) forms a distinct subgroup with unique clinicopathological characteristics within the nonfunctioning pituitary adenoma group particularly in relation to the silent gonadotroph adenomas (SGAs). We identified 31 patients with the pathological diagnosis of NCA verified by routine histology and immunohistochemistry with distinct differentiation from SGAs by an established negative testing for SF-1 at the Toronto Western Hospital between December 2004 and August 2010. We reviewed their demographic data, clinical features, magnetic resonance imaging, and the histologic variables: MIB-1, FGFR4, and P27. We compared these to 63 SGAs identified within the same period. All the NCAs were macroadenomas with diameter ranging from 15-57 mm and tumor volumes between 1.95-53.5 mm(3). Preoperative cavernous sinus tumor growth was able to predict the presence of a residual after surgery (p = 0.023). Furthermore, preoperative cavernous sinus extension (p = 0.002) and negative P27 expression (p = 0.035) were able to independently predict the subsequent growth of the postoperative tumor residual. Comparing the NCA to SGA, we found that MIB-1 was higher in NCA (mean ± SD = 3.43 ± 2.76 %) compared to SGAs (mean ± SD = 2.49 ± 1.41 %) (p = 0.044). The preoperative and postoperative tumor volume doubling times (TVDTs) displayed a negative correlation in the SGA (r = -0.855, p = 0.002) while in the NCA, a positive correlation was evident (r = 0.718, p = 0.029). Our study suggests that the NCAs are a distinct group with differing behavioral characteristics from the SGAs. It also appears that the finding of cavernous sinus extension on preoperative imaging and a negative P27 expression on immunohistochemistry in NCAs may be valuable tools in predicting residual tumor growth which may impact on postoperative care.

  14. TSH-secreting pituitary adenomas treated by gamma knife radiosurgery: our case experience and a review of the literature.

    PubMed

    Mouslech, Zadalla; Somali, Maria; Sakali, Anastasia Konstantina; Savopoulos, Christos; Mastorakos, George; Hatzitolios, Apostolos I

    2016-01-01

    A 43-year-old woman, previously misdiagnosed as having primary hyperthyroidism and treated with antithyroid drugs, presented to us with overt hyperthyroidism, high levels of thyroid hormones and elevated thyroid-stimulating hormone (TSH). Μagnetic resonance imaging (MRI) revealed a pituitary microadenoma extending suprasellarly. The patient responded favorably to initial treatment with somatostatin analogs for 2 years but due to the escape phenomenon, TSH levels escalated and hyperthyroidism relapsed. Transsphenoidal adenomectomy was applied but recurrence was again observed due to incomplete tumor removal. Gamma knife radiosurgery was finally employed 5.5 years ago, resulting in complete disease remission without evidence of long-term complications to date. Thyrotropin-secreting adenomas (TSHomas) are rare with an estimated prevalence of about one case per million. We retrieved from the literature 14 cases of TSHomas treated by gamma knife radiosurgery and compared the outcomes. Our results demonstrate the efficacy and safety of gamma knife radiosurgery for achieving remission in most of the cases, suggesting validation of this technique as an effective treatment option for the management of recurrent TSHomas.

  15. Initial and postoperative hyponatremia associated with pituitary adenoma: a case report.

    PubMed

    Yamashiro, S; Fuwa, I; Seto, H; Ushio, Y

    1997-01-01

    This 67 year-old man experienced 3 episodes of symptomatic hyponatraemia. Radiological examination revealed a sellar lesion and the tumour was removed via the transsphenoidal route. Thereafter, he simultaneously developed intractable diabetes insipidus and serious hyponatraemia with persistent natriuresis. His level of atrial natriuretic peptide was not significantly elevated, however, his plasma aldosterone concentration was low. The oral administration of salt gradually improved his hyponatraemia as well as the coincident symptoms. By the administration of a mineralocorticoid, fludrocortisone acetate, we succeeded in maintaining his serum sodium level without salt replacement. We discuss the mechanism(s) and treatment of hyponatraemia associated with pituitary tumour.

  16. A critical reappraisal of MIB-1 labelling index significance in a large series of pituitary tumours: secreting versus non-secreting adenomas.

    PubMed

    Jaffrain-Rea, M L; Di Stefano, D; Minniti, G; Esposito, V; Bultrini, A; Ferretti, E; Santoro, A; Faticanti Scucchi, L; Gulino, A; Cantore, G

    2002-06-01

    Pituitary tumours are usually benign neoplasia, but may have a locally aggressive or malignant evolution. This study aimed to identify factors which mostly influence their proliferative activity, in order to clarify its value for clinical and research purposes. The proliferative index was determined in a prospective series of 132 pituitary tumours as the percentage of monoclonal antibody MIB-1-immunopositive cells and referred to as the MIB-1 labelling index (LI). Its distribution was analysed according to both univariate and multivariate models. A life-threatening pituitary tumour is presented separately. The mean LI was 1.24+/-1.59%, with significant differences between clinically secreting (CS) and clinically non-secreting (CNS) adenomas. In CS adenomas (n=65), LI was highly variable and markedly influenced by pre-operative pharmacological treatment (0.80+/-1.03 vs 2.06+/-2.39% in treated vs untreated cases, P=0.009); it decreased with patient's age (P=0.025, r=0.28) and increased with tumour volume and invasiveness. The influence of pre-operative treatment and macroscopic features on LI in this group was confirmed by multivariate analysis. In CNS adenomas (n=67), LI distribution was less variable than in CS adenomas (P<0.0001), it was age-independent and correlations with tumour volume, invasiveness or recurrence did not reach significance. In a rapidly growing parasellar tumour, the mean LI was 24% at first surgery and exceeded 50% at second surgery performed 4 months later. LI should be interpreted according to hormone secretion and pre-operative treatment. Unusually high LI values deserve particular attention.

  17. Prolactin-secreting pituitary adenoma in neuroleptic treated patients with psychotic disorder.

    PubMed

    Melkersson, K; Hulting, A L

    2000-01-01

    Three patients with psychoses and concomitant prolactin-secreting pituitary tumours are described. Patients A and B had bipolar and schizoaffective disorders, respectively. They had both been treated with neuroleptics for 20 years before the prolactinomas were revealed. Patient C developed a paranoid psychosis after two years of continuous bromocriptine treatment for a pituitary tumour. In patient A the prolactin level was successfully normalized and a good antipsychotic effect was maintained by combined therapy with haloperidol and quinagolide but not bromocriptine. In patient B the prolactinoma was removed by surgery, in view of the serious nature of the psychotic disorder, to avoid psychotic relapse by treatment with a dopamine agonist. In patient C a good result was obtained with the combination of clozapine and bromocriptine. These case reports support the view that neuroleptics being dopamine antagonists and dopamine agonistic agents which are the primary treatment of prolactinomas can cancel out each other's effects. The combination of clozapine and quinagolide is recommended as the treatment of choice for most patients.

  18. IgG4-related hypophysitis presenting as a pituitary adenoma with systemic disease.

    PubMed

    Hsing, Ming-Tai; Hsu, Hui-Ting; Cheng, Chun-Yuan; Chen, Chien-Min

    2013-04-01

    Hypophysitis is a rare inflammatory disorder that can mimic a pituitary tumor clinically or radiologically. Furthermore, immunoglobulin G4 (IgG4)-related systemic disease is only a just recently characterized disorder. It can manifest as a systemic disease involving multiple organs, including the pancreas, salivary glands, lungs, liver, bile duct, gallbladder, kidneys, and retroperitoneum. It is characterized by a high serum level of IgG4 clinically and dense lymphoplasmacytic infiltration with sclerosis and phlebitis histologically. Herein, we report the case of a man 66 years of age who presented with nausea, vomiting, and poor appetite with a body weight loss of 4 kg. Image study revealed a pituitary infundibulum mass, right-posterior mediastinal and paraspinal masses, as well as infiltrating masses in bilateral kidneys. Therefore, he received a thoracoscopic biopsy for the right-posterior mediastinal and paraspinal masses and a pathologic examination reported an IgG4-related inflammatory pseudotumor. Then, transsphenoidal removal of the infundibulum mass was performed. Histologically, the infundibulum mass represented a IgG4-related hypophysitis manifested as an infiltration of plasma cells, lymphocytes, histiocytes, and some eosinophils with a fair number of IgG4-immunoreactive plasma cells. After the operation was complete, the patient took 5 mg of prednisolone every 2 days for 3 months. A follow-up computed tomography scan revealed improvement of the infiltrating masses in the bilateral kidneys.

  19. Primary hypothyroidism-associated TSH-secreting pituitary adenoma/hyperplasia presenting as a bleeding nasal mass and extremely elevated TSH level.

    PubMed

    Ghannam, N N; Hammami, M M; Muttair, Z; Bakheet, S M

    1999-06-01

    A 41-year-old male with primary hypothyroidism and a huge TSH-secreting pituitary tumor presented with a bleeding nasal mass that was initially misdiagnosed as a paraganglioma. Other unique features of the case include lack of complaints related to hypothyroidism, an extremely elevated TSH level of 3474 mU/l, and a low prolactin level. The presence of primary hypothyroidism made differentiating TSH-secreting pituitary adenoma from secondary thyrotroph hyperplasia difficult. A low molar ratio of alpha-subunit to TSH on presentation, together with normalization of TSH level and a 50% reduction in the size of the tumor after 6 weeks of thyroxine replacement therapy, suggested the presence of thyrotroph hyperplasia. However, the lack of further decrease in the size of the tumor that was associated with increased metabolic activity on 18-FDG PET scan, intense uptake on octreotide scan, and an elevated alpha-subunit to TSH molar ratio despite the normalization of free T4 and TSH levels for 16 months suggested the coexistence of thyrotroph adenoma. Together, the findings support the view that thyrotroph adenoma/irreversible hyperplasia can result from long standing primary hypothyroidism.

  20. Pituitary Tumors

    MedlinePlus

    ... or milk production), sex hormones (control the menstrual cycle and other sexual functions), thyroid gland hormones (control the thyroid gland), adrenal gland hormones, and vasopressin (a hormone involved in water and electrolyte balance). Symptoms of pituitary adenoma and ...

  1. The Marine Metabolite SZ-685C Induces Apoptosis in Primary Human Nonfunctioning Pituitary Adenoma Cells by Inhibition of the Akt Pathway in Vitro

    PubMed Central

    Wang, Xin; Tan, Ting; Mao, Zhi-Gang; Lei, Ni; Wang, Zong-Ming; Hu, Bin; Chen, Zhi-Yong; She, Zhi-Gang; Zhu, Yong-Hong; Wang, Hai-Jun

    2015-01-01

    Nonfunctioning pituitary adenoma (NFPA) is one of the most common types of pituitary adenoma. The marine anthraquinone derivative SZ-685C has been isolated from the secondary metabolites of the mangrove endophytic fungus Halorosellinia sp. (No. 1403) which is found in the South China Sea. Recent research has shown that SZ-685C possesses anticancer and tumor suppressive effects. The tetrazolium-based colorimetric assay (MTT assay) to investigate the different effect of the marine compound SZ-685C on the proliferation of primary human NFPA cells, rat normal pituitary cells (RPCs) and rat prolactinoma MMQ cell lines. Hoechst 33342 dye/propidium iodide (PI) double staining and fluorescein isothiocyanate-conjugated Annexin V/PI (Annexin V-FITC/PI) apoptosis assays detected an enhanced rate of apoptosis in cells treated with SZ-685C. Enhanced expression levels of caspase 3 and phosphate and tensin homolog (PTEN) were determined by Western blotting. Notably, the protein expression levels of Akt were decreased when the primary human NFPA cells were treated with SZ-685C. Here, we show that SZ-685C induces apoptosis of human NFPA cells through inhibition of the Akt pathway in vitro. The understanding of apoptosis has provided the basis for novel targeted therapies that can induce death in cancer cells or sensitize them to established cytotoxic agents and radiation therapy. PMID:25806467

  2. Different Volumetric Measurement Methods for Pituitary Adenomas and Their Crucial Clinical Significance

    PubMed Central

    Chuang, Chi-Cheng; Lin, Shinn-Yn; Pai, Ping-Ching; Yan, Jiun-Lin; Toh, Cheng-Hong; Lee, Shih-Tseng; Wei, Kuo-Chen; Liu, Zhuo-Hao; Chen, Chung-Ming; Wang, Yu-Chi; Lee, Cheng-Chi

    2017-01-01

    Confirming the status of residual tumors is crucial. In stationary or spontaneous regression cases, early treatments are inappropriate. The long-used geometric calculation formula is 1/2 (length × width × height). However, it yields only rough estimates and is particularly unreliable for irregularly shaped masses. In our study, we attempted to propose a more accurate method. Between 2004 and 2014, 94 patients with pituitary tumors were enrolled in this retrospective study. All patients underwent transsphenoidal surgery and received magnetic resonance imaging (MRI). The pre- and postoperative volumes calculated using the traditional formula were termed A1 and A2, and those calculated using the proposed method were termed O1 and O2, respectively. Wilcoxon signed rank test revealed no significant difference between the A1 and O1 groups (P = 0.1810) but a significant difference between the A2 and O2 groups (P < 0.0001). Significant differences were present in the extent of resection (P < 0.0001), high-grade cavernous sinus invasion (P = 0.0312), and irregular shape (P = 0.0116). Volume is crucial in evaluating tumor status and determining treatment. Therefore, a more scientific method is especially useful when lesions are irregularly shaped or when treatment is determined exclusively based on the tumor volume. PMID:28098212

  3. Radiotherapy is Not Associated With Reduced Quality of Life and Cognitive Function in Patients Treated for Nonfunctioning Pituitary Adenoma

    SciTech Connect

    Beek, Andre P. van . E-mail: a.p.van.beek@int.umcg.nl; Bergh, Alphons C.M. van den; Berg, Linda M. van den; Berg, Gerrit van den; Keers, Joost C.; Langendijk, Johannes A.; Wolffenbuttel, Bruce H.R.

    2007-07-15

    Purpose: To assess the influence of different treatment modalities on long-term health-related quality of life (HR-QoL) and cognitive problems among patients who had been treated for nonfunctioning pituitary adenoma (NFA). Methods and Materials: Eighty-one patients (49 men and 32 women, aged 55 {+-} 10 years) with a minimal follow-up period of 1 year after treatment for NFA participated in this cross-sectional study. Sixty-two patients were initially treated by transsphenoidal surgery and 19 by craniotomy. Subsequently, 45 of these 81 subjects (56%) received additional radiotherapy (RT) after surgery because of a tumor remnant or regrowth. All subjects filled in standardized questionnaires measuring HR-QoL, depression, fatigue, and cognitive problems. Results: Patients who underwent additional RT more frequently underwent a craniotomy and were younger at surgery, but not at entering this study. They also used more hormonal substitution. Most HR-QoL domains showed a similar score in patients who underwent RT when compared with patients who did not receive RT. However, vitality and physical functioning proved to be better in RT subjects, and RT subjects also had better scores for depression and physical and mental fatigue (all p < 0.05). Some aspects of HR-QoL of patients who have been successfully treated for NFA are reduced compared with the normal population, but this was much more pronounced in the group that did not receive RT. In multivariate analysis, RT remained significantly associated with improved HR-QoL. No differences in cognitive function scores were observed. Conclusion: Postoperative RT in patients with NFA is not associated with reduced quality of life or cognition when compared with surgery alone.

  4. Hyperpolarization of the Membrane Potential Caused by Somatostatin in Dissociated Human Pituitary Adenoma Cells that Secrete Growth Hormone

    NASA Astrophysics Data System (ADS)

    Yamashita, Naohide; Shibuya, Naohiko; Ogata, Etsuro

    1986-08-01

    Membrane electrical properties and the response to somatostatin were examined in dissociated human pituitary adenoma cells that secrete growth hormone (GH). Under current clamp condition with a patch electrode, the resting potential was -52.4 ± 8.0 mV, and spontaneous action potentials were observed in 58% of the cells. Under voltage clamp condition an outward K+ current, a tetrodotoxin-sensitive Na+ current, and a Ca2+ current were observed. Cobalt ions suppressed the Ca2+ current. The threshold of Ca2+ current activation was about -60 mV. Somatostatin elicited a membrane hyperpolarization associated with increased membrane permeability in these cells. The reversal potential of somatostatin-induced hyperpolarization was -78.4 ± 4.3 mV in 6 mM K+ medium and -97.2 ± 6.4 mV in 3 mM K+ medium. These reversal potential values and a shift with the external K+ concentration indicated that membrane hyperpolarization was caused by increased permeability to K+. The hyperpolarized membrane potential induced by somatostatin was -63.6 ± 5.9 mV in the standard medium. This level was subthreshold for Ca2+ and Na+ currents and was sufficient to inhibit spontaneous action potentials. Hormone secretion was significantly suppressed by somatostatin and cobalt ions. Therefore, we suggest that Ca2+ entering the cell through voltage-dependent channels are playing an important role for GH secretion and that somatostatin suppresses GH secretion by blocking Ca2+ currents. Finally, we discuss other possibilities for the inhibitory effect of somatostatin on GH secretion.

  5. Radiosurgery of functioning pituitary adenomas: Comparison of different treatment techniques including dynamic and conformal arcs, shaped beams, and IMRT

    SciTech Connect

    Grabenbauer, Gerhard G. . E-mail: gg@strahlen.imed.uni-erlangen.de; Ernst-Stecken, Antje; Schneider, Florian; Lambrecht, Ulrike; Ganslandt, Oliver

    2006-11-15

    Purpose: Evaluation of different techniques including intensity-modulated radiotherapy (IMRT) for stereotactic radiosurgery (SRS) of pituitary adenoma (PA). Methods and Materials: Between January 2003 and February 2005, 152 SRS procedures were performed. Ten patients with PA were compared: conformal vs. dynamic arc treatment with micromultileaf collimator (mMLC) vs. circular collimators vs. 8-10 conformal static mMLC beams with and without IMRT. Prescribed total dose: 18 Gy (90%). Constraints: D{sub max} optic chiasm <8 Gy, Vol{sub 10Gy} temporal lobe <10 mL. End points: coverage, conformity index, homogeneity index (HI), Vol{sub 10Gy} temporal lobe. Results: For the end point 'improvement in coverage,' an advantage with IMRT was noted for 5 of 10 patients as compared with the dynamic arc approach. Volume treated >18 Gy outside the planning target volume was lowest in 9 of 10 patients after IMRT; 1 patient achieved better conformity with circular collimators. As for Vol{sub 10Gy} temporal lobe, an advantage was depicted for 1 of 10 patients with IMRT, the other techniques appearing equally effective in shielding the temporal lobe. With all techniques Vol{sub 10Gy} temporal lobe was <10 mL and D{sub max} optic chiasm <8 Gy. However, using circular collimators yielded the highest maximum dose with 39.8 Gy (HI, 2.2) as compared with 20.46-21.74 Gy (HI, 1.13-1.2) for other approaches. Conclusions: Novalis-based radiosurgery using dynamic arc treatment with mMLC is considered a safe and appropriate approach for SRS of PA.

  6. Transcranial approach to pituitary adenomas invading the cavernous sinus: A modification of the classical technique to be used in a low-technology environment

    PubMed Central

    Spallone, Aldo; Vidal, Roberto V.; Gonzales, Justo G.

    2010-01-01

    Objective: Pituitary adenomas invading the cavernous sinus represent a therapeutic challenge. Those tumors have been traditionally treated with incomplete surgical removal, observation and/ or adjunctive medical therapy, and radiotherapy. In relatively recent years, some authors have suggested a main direct surgical approach to cavernous sinus (CS) with the aim of complete removal of the adenoma, either by a modified trans-sphenoidal route, using or not an endoscopy-assisted approach, or by a transcranial direct approach. The latter has the advantage of allowing direct exposure of the lesion with a view of the surgical field unhindered by important neurovascular structures. Materials and Methods: We report a technical modification of the classical epidural approach for CS adenoma removal. This was used in 14 patients. Surgical technique included a fronto-orbito-zygomatic craniotomy with extradural anterior clinoidectomy, and intradural approach to the Hakuba’s triangle for intracavernous dissection. The tumors were removed under direct vision. Results: Total macroscopical removal was achieved in all but one case. This patient required postoperative radiation therapy as well as adjuvant dopaminergic regime for achieving control of preoperatively increased hormonal values. No other case required radiotherapy. Hormonal and/ or clinical control was also achieved in all the remaining cases. Out of the remaining 13 cases, all appeared to be tumor free at an average postoperative observation at 78 months (34 to 90 months). Significant surgical sequels were detected in only 1 case (persistent 3rd nerve palsy and moderate hemiparesis). Conclusions: This experience, though limited, would suggest that the transcranial limited CS exposure through the Hakuba’s triangle may allow adequate removal of intracavernous pituitary adenomas with very good long-term results and acceptable complication rate. PMID:20847907

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

    SciTech Connect

    Kopp, Christine; Theodorou, Marilena; Poullos, Nektarios; Jacob, Vesna; Astner, Sabrina T.; Molls, Michael; Grosu, Anca-Ligia

    2012-03-01

    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.

  8. TU-CD-304-02: Planning and Delivery of Fully Dynamic Trajectory Modulated Arc Therapy On Pituitary Adenoma: Dosimetric Advantages Over Conventional Volumetric Modulated Arc Therapy

    SciTech Connect

    Liang, J; Kim, S; Hristov, D; Otto, K

    2015-06-15

    Purpose: To assess the potential benefit of trajectory modulated arc therapy (TMAT) for treatments of small benign intracranial tumor, pituitary adenoma. Methods: A TMAT planning platform that incorporates complex source motion trajectory involving synchronized gantry rotation with translational and rotational couch movement was used for the study. The platform couples an interactive trajectory generation tool with a VMAT algorithm that performs multi-resolution, progressive sampling MLC optimization on a user-designed trajectory. A continuous couch rotation of 160° angular span with ±20° mini gantry arcs was used to emulate a non-coplanar horizontal arc-like trajectory. Compared to conventional non-coplanar gantry arcs (60°-100° gantry rotation with couch kicks), TMAT limited the unnecessary low to medium dose spread in the anterior and posterior directions, where primary OARs (e.g., brainstem, optic chiasm, optic nerves, and lens) are in close proximity to the targeted pituitary tumor volume. For 5 standard fractionation pituitary adenoma cases (50.4Gy/28fractions), TMAT and non-coplanar VMAT plans were generated and compared under equivalent objectives/constraints. TMAT delivery was implemented and demonstrated on Varian TrueBeam via XML scripts. Results: Both techniques showed good target coverage while OARs were able to meet the constraints on QUANTEC guidelines. Notably, TMAT decreased the dose deposition in the anterior-to-posterior direction surrounding PTV. TMAT significantly reduced the mean doses on brainstem, optic nerves, eyes and lens by 47.29%±13.17%, 28.51%±8.68%, 80.82%±8.71% and 65.38%±19.99% compared with VMAT, all p≤0.01. Percentage reductions of maximum point dose in eyes and lens were 75.68%±10.30% and 70.72%±18.62% respectively for TMAT versus VMAT, all p≤0.01. A representative isocentric TMAT pituitary plan was delivered via an XML script with 200 control points and 282 MUs. Conclusion: Deliverable TMAT plans were achieved in

  9. STA-MCA Bypass as a “Bridge” to Pituitary Surgery in a Patient with an Adenoma Occluding the Internal Carotid Artery: Case Report and Review of the Literature

    PubMed Central

    Lanterna, Luigi A.; Brembilla, Carlo; Signorelli, Antonio; Gritti, Paolo; Costi, Emanuele; Dorelli, Gianluigi; Bernucci, Claudio

    2015-01-01

    Occlusion of the intracranial internal carotid artery (ICA) by a pituitary adenoma with resulting cerebral ischemia is a very rare but devastating occurrence. The authors present a case in which a condition of symptomatic ICA occlusion due to a giant pituitary adenoma was successfully treated using a preliminary extraintracranial bypass as a “bridge” to the tumor removal. A 52-year-old patient presented with a minor stroke followed by pressure-dependent transient ischemic attacks consistent with a condition of hypoperfusion. MR imaging and a digital subtraction angiography revealed a pituitary adenoma occluding the ICA on the right side. He underwent a superficial temporal artery to middle cerebral artery (STA-MCA) bypass with the aim of revascularizing the ischemic hemisphere and reducing the risk of perioperative stroke or stroke evolution. The patient was subsequently operated on to remove the adenoma through a transsphenoidal approach. The postoperative course was uneventful and the patient has suffered no further ischemic events. When there are no emergency indications to decompress the optical pathways but the patient is at risk of impending stroke because of ICA occlusion, a two-step strategy consisting of a bypass and subsequent removal of the pituitary adenoma may be a valuable option. PMID:26425379

  10. Treatment protocols for growth hormone-secreting pituitary adenomas combined with craniofacial fibrous dysplasia: A case report of atypical McCune-Albright syndrome.

    PubMed

    Xu, Jia; Li, Xi; Lv, Chang-Sheng; Chen, Ying; Wang, Meng; Liu, Jian-Feng; Gui, Lai

    2014-09-01

    McCune-Albright syndrome (MAS) is a rare, post-zygotic (non-germline) disorder, characterized by hypersecretory endocrinopathies, fibrous dysplasia of the bone and café-au-lait macules. The most common endocrine dysfunction is gonadal hyperfunction; thus, hypersecretion of growth hormones (GHs) as a manifestation of endocrine hyperfunction in MAS is rarely reported. MAS affects both genders, although the majority of cases have been reported in young females. Atypical presentations of MAS, with only one or two of the classic symptoms, have been previously described, but remain particularly challenging due to the lack of a diagnostic phenotype. In patients with atypical MAS, analysis of mutations in the gene of the α-subunit of the stimulatory G-protein is limited; thus, diagnosis is based on clinical judgment. In the present study, a male with polyostotic fibrous dysplasia and GH-secreting pituitary adenomas, diagnosed with atypical MAS, was reported. The pituitary adenoma was effectively treated with radiotherapy and the patient underwent surgery for the polyostotic fibrous dysplasia, with marked improvements observed in appearance.

  11. Use of the metallothionein promoter-human growth hormone-releasing hormone (GHRH) mouse to identify regulatory pathways that suppress pituitary somatotrope hyperplasia and adenoma formation due to GHRH-receptor hyperactivation.

    PubMed

    Luque, Raul M; Soares, Beatriz S; Peng, Xiao-ding; Krishnan, Sonia; Cordoba-Chacon, Jose; Frohman, Lawrence A; Kineman, Rhonda D

    2009-07-01

    Hyperactivation of the GHRH receptor or downstream signaling components is associated with hyperplasia of the pituitary somatotrope population, in which adenomas form relatively late in life, with less than 100% penetrance. Hyperplastic and adenomatous pituitaries of metallothionein promoter-human GHRH transgenic (Tg) mice (4 and > 10 months, respectively) were used to identify mechanisms that may prevent or delay adenoma formation in the presence of excess GHRH. In hyperplastic pituitaries, expression of the late G(1)/G(2) marker Ki67 increased, whereas the proportion of 5-bromo-2'-deoxyuridine-labeled cells (S phase marker) did not differ from age-matched controls. These results indicate cell cycle progression is blocked, with further evidence suggesting that enhanced p27 activity may contribute to this process. For adenomas, formation was associated with loss of p27 activity (nuclear localization and mRNA). Increased endogenous somatostatin (SST) tone may also slow the conversion from hyperplastic to adenomatous state because mRNA levels for SST receptors, sst2 and sst5, were elevated in hyperplastic pituitaries, whereas adenomas were associated with a decline in sst1 and sst5 mRNA. Also, SST-knockout Tg pituitaries were larger and adenomas formed earlier compared with those of SST-intact Tg mice. Unexpectedly, these changes were independent of changes in proliferation rate within the hyperplastic tissue, suggesting that endogenous SST controls GHRH-induced adenoma formation primarily via modulation of apoptotic and/or cellular senescence pathways, consistent with the predicted function of some of the most differentially expressed genes (Casp1, MAP2K1, TNFR2) identified by membrane arrays and confirmed by quantitative real-time RT-PCR.

  12. Somatotropinomas, but not nonfunctioning pituitary adenomas, maintain a functional apoptotic RET/Pit1/ARF/p53 pathway that is blocked by excess GDNF.

    PubMed

    Diaz-Rodriguez, Esther; Garcia-Rendueles, Angela R; Ibáñez-Costa, Alejandro; Gutierrez-Pascual, Ester; Garcia-Lavandeira, Montserrat; Leal, Alfonso; Japon, Miguel A; Soto, Alfonso; Venegas, Eva; Tinahones, Francisco J; Garcia-Arnes, Juan A; Benito, Pedro; Angeles Galvez, Maria; Jimenez-Reina, Luis; Bernabeu, Ignacio; Dieguez, Carlos; Luque, Raul M; Castaño, Justo P; Alvarez, Clara V

    2014-11-01

    Acromegaly is caused by somatotroph cell adenomas (somatotropinomas [ACROs]), which secrete GH. Human and rodent somatotroph cells express the RET receptor. In rodents, when normal somatotrophs are deprived of the RET ligand, GDNF (Glial Cell Derived Neurotrophic Factor), RET is processed intracellularly to induce overexpression of Pit1 [Transcription factor (gene : POUF1) essential for transcription of Pituitary hormones GH, PRL and TSHb], which in turn leads to p19Arf/p53-dependent apoptosis. Our purpose was to ascertain whether human ACROs maintain the RET/Pit1/p14ARF/p53/apoptosis pathway, relative to nonfunctioning pituitary adenomas (NFPAs). Apoptosis in the absence and presence of GDNF was studied in primary cultures of 8 ACROs and 3 NFPAs. Parallel protein extracts were analyzed for expression of RET, Pit1, p19Arf, p53, and phospho-Akt. When GDNF deprived, ACRO cells, but not NFPAs, presented marked level of apoptosis that was prevented in the presence of GDNF. Apoptosis was accompanied by RET processing, Pit1 accumulation, and p14ARF and p53 induction. GDNF prevented all these effects via activation of phospho-AKT. Overexpression of human Pit1 (hPit1) directly induced p19Arf/p53 and apoptosis in a pituitary cell line. Using in silico studies, 2 CCAAT/enhancer binding protein alpha (cEBPα) consensus-binding sites were found to be 100% conserved in mouse, rat, and hPit1 promoters. Deletion of 1 cEBPα site prevented the RET-induced increase in hPit1 promoter expression. TaqMan qRT-PCR (real time RT-PCR) for RET, Pit1, Arf, TP53, GDNF, steroidogenic factor 1, and GH was performed in RNA from whole ACRO and NFPA tumors. ACRO but not NFPA adenomas express RET and Pit1. GDNF expression in the tumors was positively correlated with RET and negatively correlated with p53. In conclusion, ACROs maintain an active RET/Pit1/p14Arf/p53/apoptosis pathway that is inhibited by GDNF. Disruption of GDNF's survival function might constitute a new therapeutic route in

  13. Postoperative Low-Flow Cerebrospinal Fluid Leak of Endoscopic Endonasal Transsphenoidal Surgery for Pituitary Adenoma--Wait and See, or Lumbar Drain?

    PubMed

    Zhan, Rucai; Chen, Songyu; Xu, Shujun; Liu, James K; Li, Xingang

    2015-06-01

    To assess the effectiveness of continuous lumbar drainage (LD) for management of postoperative cerebrospinal fluid leaks after endoscopic endonasal transsphenoidal approach for resection of pituitary adenoma. Three hundred eighty-four medical records of patients who were admitted to our institute during a 2.5-year period were retrospectively reviewed, 33 of them experienced low-flow cerebrospinal fluid leak postoperatively. If LD was used, all patients with low-flow cerebrospinal fluid leak were classified into 2 groups, lumbar drained group and conservatively treated group. The age, sex, management of cerebrospinal fluid leaks, and related complications were reviewed. Statistical comparisons between the 2 groups were made using SPSS 19.0 (IBM Corp, Armonk, NY). The differences were considered statistically significant if the P value was less than 0.05.Thirty-three of 384 (8.6%) experienced low-flow postoperative cerebrospinal fluid leaks. Cured rate of cerebrospinal fluid leak was 94.4% (17/18) in continuous lumbar drained group, and 93.3% (14/15) in control group. There were 2 (11.2%) patients who developed meningitis in the LD group and 1 (5.6%) patient in the control group. One patient required endoscopic repair of skull base because of persistent cerebrospinal fluid leak in both groups, with the rates of 5.6% and 6.7%, respectively. There was no significant difference noted in each rate in both groups.Placement of LD may not be necessary for the management of low-flow postoperative cerebrospinal fluid leak after using endoscopic endonasal transsphenoidal approach to pituitary adenoma.

  14. Folate receptor-mediated boron-10 containing carbon nanoparticles as potential delivery vehicles for boron neutron capture therapy of nonfunctional pituitary adenomas.

    PubMed

    Dai, Congxin; Cai, Feng; Hwang, Kuo Chu; Zhou, Yongmao; Zhang, Zizhu; Liu, Xiaohai; Ma, Sihai; Yang, Yakun; Yao, Yong; Feng, Ming; Bao, Xinjie; Li, Guilin; Wei, Junji; Jiao, Yonghui; Wei, Zhenqing; Ma, Wenbin; Wang, Renzhi

    2013-02-01

    Invasive nonfunctional pituitary adenomas (NFPAs) are difficult to completely resect and often develop tumor recurrence after initial surgery. Currently, no medications are clinically effective in the control of NFPA. Although radiation therapy and radiosurgery are useful to prevent tumor regrowth, they are frequently withheld because of severe complications. Boron neutron capture therapy (BNCT) is a binary radiotherapy that selectively and maximally damages tumor cells without harming the surrounding normal tissue. Folate receptor (FR)-targeted boron-10 containing carbon nanoparticles is a novel boron delivery agent that can be selectively taken up by FR-expressing cells via FR-mediated endocytosis. In this study, FR-targeted boron-10 containing carbon nanoparticles were selectively taken up by NFPAs cells expressing FR but not other types of non-FR expressing pituitary adenomas. After incubation with boron-10 containing carbon nanoparticles and following irradiation with thermal neutrons, the cell viability of NFPAs was significantly decreased, while apoptotic cells were simultaneously increased. However, cells administered the same dose of FR-targeted boron-10 containing carbon nanoparticles without neutron irradiation or received the same neutron irradiation alone did not show significant decrease in cell viability or increase in apoptotic cells. The expression of Bcl-2 was down-regulated and the expression of Bax was up-regulated in NFPAs after treatment with FR-mediated BNCT. In conclusion, FR-targeted boron-10 containing carbon nanoparticles may be an ideal delivery system of boron to NFPAs cells for BNCT. Furthermore, our study also provides a novel insight into therapeutic strategies for invasive NFPA refractory to conventional therapy, while exploring these new applications of BNCT for tumors, especially benign tumors.

  15. A patient with Cushing disease lateralizing a pituitary adenoma by inferior petrosal sinus sampling using desmopressin: a case report

    PubMed Central

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

    2016-01-01

    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. PMID:27104179

  16. The diagnostic value of fused positron emission tomography/computed tomography in the localization of adrenocorticotropin-secreting pituitary adenoma in Cushing's disease.

    PubMed

    Alzahrani, Ali S; Farhat, Rafif; Al-Arifi, Abdullah; Al-Kahtani, Nora; Kanaan, Imad; Abouzied, Mohei

    2009-01-01

    Despite the high resolution of magnetic resonance imaging (MRI) of the pituitary gland, up to 40% of cases of Cushing's disease (CD) have normal MRI. Fused images of positron emission tomography and computed tomography (PET-CT) may have a potential diagnostic role in CD in general and in such cases in particular. Objective of this study is to explore the diagnostic potential of PET-CT for localization of adrenocorticotropin-secreting pituitary adenomas in CD. PET-CT was performed in 12 cases with de novo (7 cases) or persistent CD (5 cases) that were proven to have CD on biochemical, radiological and/or histopathological findings. These cases had a definite CD confirmed on histopathological and immunostaining examination of the subsequent transphenoidal surgical specimens (10 cases) and/or bilateral inferior petrosal sinus sampling (IPSS, 4 cases). PET-CT was positive in 7 of the 12 cases of CD (58%) showing a focal area of uptake in the pituitary gland. In these seven cases, MRI was positive in six (85.7%) but negative in one case (14.3%). In the other five cases with negative PET-CT, MRI was positive in two and negative in three cases. Of four cases with negative MRI, PET-CT was positive in one case (25%). We conclude that PET-CT is positive in around 60% of the cases of CD. Although the majority of cases with positive PET-CT had positive MRI, PET-CT may detect some cases with negative MRI and thus provides important diagnostic information. If these findings are confirmed in larger studies, PET-CT might become an important diagnostic technique, especially when the more invasive and technically demanding procedure of IPSS is not available or inconclusive.

  17. Coexistence of macroprolactinaemia and hyperprolactinaemia in women with oligo-/amenorrhoea is associated with high risk of pituitary adenomas.

    PubMed

    Lewandowski, Krzysztof C; Gasior-Perczak, Danuta; Kowalska, Aldona; Lewinski, Andrzej

    2014-05-01

    Macroprolactin may cause elevation of prolactin (PRL) concentrations measured by standard assays. In our study, we assessed the prevalence of pituitary lesions in women with macroprolactinaemia and either oligomenorrhoea or secondary amenorrhoea. Pituitary MRI scans were performed in 61 women aged 31.0  ±  6.7 years (mean  ±  SD), with raised PRL concentrations due to macroprolactinaemia, detected by 25% polyethylene glycol (PEG) precipitation method (PRL recovery <40%). After PEG precipitation of macroprolactin, free PRL concentrations were still raised in 36 (59%) women. Microadenomas were detected in 10 patients out of 61 (16.4%), with raised free PRL in 9 of these cases, while macroadenomas were detected in 4 out of 61 (6.6%) women, all of whom also had raised free PRL. In case of coexistence of macroprolactinaemia and raised free PRL after PEG precipitation of macroprolactin, the chance of finding of either a micro- or a macroadenoma was 36% (13 cases out of 36). We conclude that hyperprolactinaemia and macroprolactinaemia may coexist in the same patient. Furthermore, if free PRL is raised after PEG precipitation of macroprolactin, then the chance of finding either a pituitary micro- or macroadenoma in women with oligo-/amenorrhoea is over 30%. Therefore pituitary magnetic resonance imaging is mandatory in all such cases.

  18. Age-related Qualitative Histological and Quantitative Stereological Changes in the Equine Pituitary.

    PubMed

    Leitenbacher, J; Herbach, N

    2016-01-01

    The aim of this study was to characterize the age-related morphological changes in the equine pituitary and to identify features that allow distinction between pituitary pars intermedia dysfunction (PPID)-associated and non-functional/age-associated pars intermedia (PI) adenoma. Pituitary glands of all horses submitted for necropsy examination at the Institute of Veterinary Pathology, Ludwig Maximilians University Munich, between 2008 and 2012 were examined. The pituitary glands of 124 horses were weighed, cut into ∼2 mm slices and examined histologically. A slightly modified grading scheme (grades 1-5) was applied to evaluate histological alterations of the PI semiquantitatively. The volume fractions and total volumes of the three pituitary lobes, PI, pars distalis (PD) and pars nervosa (PN), as well as the total number and mean size of PI cells (PICs), were determined using state-of-the-art quantitative stereological methods. There were significant associations between histological grade, the appearance of PI adenomas, follicles and cysts in the PI, lipofuscin in the PN (P <0.001) and focal hyperplasia of chromophobes in the PD and age. In contrast, the appearance of follicles and cysts in the PD, invasion of basophil cells into the PN, haemorrhage and necrosis were not age dependent. PI adenomas were observed in 18% (22/124) of the animals, but only four horses were evidently suffering from PPID, therefore clinically overt/PPID-associated PI adenomas were found in 3% (4/124) of all horses. Most PI adenomas were incidental and considered non-functional. Pituitary weight, PI volume, total number and mean volume of PICs increased with age in all horses. The total PI volume and the number of PICs of horses exhibiting PPID-associated PI adenomas were significantly higher, while the mean size of PICs was smaller compared with that of horses showing non-PPID-associated adenoma, which suggests that different growth processes are responsible for adenoma formation

  19. Parathyroid adenoma

    MedlinePlus

    Hyperparathyroidism - parathryoid adenoma; Overactive parathyroid gland - parathyroid adenoma ... Parathyroid adenomas are the most common cause of hyperparathyroidism (overactive parathyroid glands), which leads to an increased ...

  20. Expression of type 5 somatostatin receptor in TSH-secreting pituitary adenomas: a possible marker for predicting long-term response to octreotide therapy.

    PubMed

    Yoshihara, Ai; Isozaki, Osamu; Hizuka, Naomi; Nozoe, Yasuko; Harada, Chie; Ono, Masami; Kawamata, Takakazu; Kubo, Osami; Hori, Tomokatsu; Takano, Kazue

    2007-02-01

    In TSH-secreting pituitary adenomas (TSHoma), octreotide (OCT) therapy reduces tumor size and TSH secretion in some cases but not in others. As OCT acts through various types of somatostatin receptors (SSTRs), the different responses of TSHoma to OCT might be explained by the differences of SSTR expression. We therefore studied the expression of subtype-specific SSTR mRNA transcripts in tumor tissues by RT-PCR. Type 2 (SSTR2) mRNA transcripts were detected in all 8 tumors but those of SSTR3 and SSTR5 were demonstrated only in 5 of them. Serum TSH levels were decreased by OCT administration test in all patients but OCT therapy was effective in two patients out of three. SSTR5 mRNA was detected in two tumors from the responder, but not in one tumor that was resistant to OCT. These observations suggest that the temporal decrease of TSH by OCT may be mediated by SSTR2, and that the long term response to OCT therapy may be related with the expression of SSTR5. Therefore, the expression of SSTR5 in TSHoma may be a useful marker for predicting the outcome of the therapy, but further studies with larger numbers of patients are necessary.

  1. Low expression of secreted frizzled-related protein 2 and nuclear accumulation of β-catenin in aggressive nonfunctioning pituitary adenoma

    PubMed Central

    WU, YOUTU; BAI, JIWEI; HONG, LINCHUAN; LIU, CHUNHUI; YU, SHENGYUAN; YU, GUOQIANG; ZHANG, YAZHUO

    2016-01-01

    The identification of a specific molecular marker for aggressiveness of nonfunctioning pituitary adenomas (NFPAs) is urgently required in order to guide the clinical diagnosis and treatment of NFPAs. In the present study, low expression of secreted frizzled-related protein 2 (sFRP2) in NFPAs was demonstrated by reverse transcription-quantitative polymerase chain reaction, western blot and immunohistochemical analyses. The results confirmed an abnormal accumulation of free β-catenin in the nuclei of NFPAs, which is the core step for the activation of the Wnt canonical signaling pathway. Furthermore, cyclin D1 and c-Myc, the downstream proteins of the Wnt canonical signaling pathway, were overexpressed in aggressive NFPAs. These findings demonstrated the activation of the Wnt canonical signaling pathway in aggressive NFPAs. In addition, sFRP2 expression was observed to be inversely correlated to the aggressiveness of NFPAs. Therefore, sFRP2 may act as a tumor suppressor through modulation of the cellular cytosolic pool of β-catenin in NFPAs. Furthermore, the expression of sFRP2 may serve as a biomarker for NFPAs aggressiveness and prognosis. PMID:27347125

  2. Gonadotropin-releasing hormone agonist-induced pituitary apoplexy

    PubMed Central

    Keane, Fergus; Navin, Patrick; Brett, Francesca; Dennedy, Michael C

    2016-01-01

    Summary Pituitary apoplexy represents an uncommon endocrine emergency with potentially life-threatening consequences. Drug-induced pituitary apoplexy is a rare but important consideration when evaluating patients with this presentation. We describe an unusual case of a patient with a known pituitary macroadenoma presenting with acute-onset third nerve palsy and headache secondary to tumour enlargement and apoplexy. This followed gonadotropin-releasing hormone (GNRH) agonist therapy used to treat metastatic prostate carcinoma. Following acute management, the patient underwent transphenoidal debulking of his pituitary gland with resolution of his third nerve palsy. Subsequent retrospective data interpretation revealed that this had been a secretory gonadotropinoma and GNRH agonist therapy resulted in raised gonadotropins and testosterone. Hence, further management of his prostate carcinoma required GNRH antagonist therapy and external beam radiotherapy. This case demonstrates an uncommon complication of GNRH agonist therapy in the setting of a pituitary macroadenoma. It also highlights the importance of careful, serial data interpretation in patients with pituitary adenomas. Finally, this case presents a unique insight into the challenges of managing a hormonal-dependent prostate cancer in a patient with a secretory pituitary tumour. Learning points While non-functioning gonadotropinomas represent the most common form of pituitary macroadenoma, functioning gonadotropinomas are exceedingly rare. Acute tumour enlargement, with potential pituitary apoplexy, is a rare but important adverse effect arising from GNRH agonist therapy in the presence of both functioning and non-functioning pituitary gonadotropinomas. GNRH antagonist therapy represents an alternative treatment option for patients with hormonal therapy-requiring prostate cancer, who also have diagnosed with a pituitary gonadotropinoma. PMID:27284452

  3. Clinical and Epidemiological Characteristics of Pituitary Tumours using a Web-based Pituitary Tumour Registry in Oman

    PubMed Central

    Al-Futaisi, Abdullah; Saif, Al-Yaarubi; Al-Zakwani, Ibrahim; Al-Qassabi, Salim; Al-Riyami, Shaden; Wali, Yasser

    2007-01-01

    Objective: From a recently instituted web-based pituitary tumour registry at Sultan Qaboos University Hospital, Oman, this study explores the results of comprehensive clinical evaluation, hormonal levels, radiological evidence of pituitary mass lesion using magnetic resonance (MRI) and the different treatment modalities. Methods: All patients who were diagnosed with pituitary mass tumours in our tertiary care endocrinology clinic between January 1998 and February 2006 were registered in the Oman pituitary tumour registry. Two physicians performed hospital chart review and data entry. Results: A total of 160 entries were made into the pituitary tumour registry. The overall mean age of the cohort was 32 ±12 years (age range 8–73 years). The majority of registrations were female (n=114; 71%). There were 81 patients with non-functioning adenomas (50.6%), 59 with prolactinoma (36.9%) eight with acromegaly (5%), seven with craniopharyngioma (4.4%), four with Cushing’s disease (2.5%) and one with sarcoidosis (0.6%). Sub-group analyses were done only for the subjects with the 3 most prevalent pituitary tumours (non-functioning adenomas, prolactinomas, and acromegaly). The most prevalent symptoms are amenorrhea-galactorrhea (n=55; 37%), headache (n=31; 21%) and fatigue (n=23; 16%). The most common treatment modality was medical (n=58; 39%), followed by observation (n=56; 38%), surgery (n=31; 21%) and surgery plus medical (n=3; 2%). None of the patients in this registry are recorded to have died. Conclusion: To our knowledge, this is the first pituitary tumour registry in the Arabian Gulf countries using a web-based programme. This tumour registry will enable us to characterize clinical and the epidemiological features of pituitary tumours in the Sultanate of Oman. PMID:21654941

  4. Aryl Hydrocarbon Receptor-Interacting Protein (AIP) N-Terminus Gene Mutations Identified in Pituitary Adenoma Patients Alter Protein Stability and Function.

    PubMed

    Formosa, Robert; Vassallo, Josanne

    2017-03-02

    Mutations spanning the entire aryl hydrocarbon receptor-interacting protein (AIP) gene have been found in isolated familial cases of pituitary adenomas (PA). Missense mutations located in the N-terminus of the gene have been identified in several patients. However, the functional significance of these mutations remains a matter of controversy. In most studies, the N-terminus of AIP has been shown to regulate protein stability and subcellular localization of the AIP-AHR-HSP90 complex but not to be involved in protein-protein interactions. Other studies found that the N-terminal domain interacts directly with other proteins. The aim of this study was to analyze whether specific N-terminus AIP mutations identified in PA patients would be functionally different from wild-type (WT) AIP. In vitro analyses were used to assess the role of known N-terminus variants, a locally identified mutant, R9Q, and three other commonly genotyped N-terminus mutations R16H, V49M and K103R are found in PA patients. Given the functional effect of WT AIP on cAMP signalling alterations caused by N-terminus mutants on this pathway were also analyzed in GH3 cells. Results indicate that N-terminus mutations lead to de-regulation of the effect of WT AIP on cAMP signalling and increased cAMP thresholds in GH3 cells resulting in increased growth hormone (GH) secretion. Cycloheximide chase analysis identified a variation in protein degradation patterns between WT and N-terminus variants. Therefore, both functional and structural studies reveal that N-terminus mutations in the AIP gene alter protein behaviour significantly and hence can truly be pathogenic in nature.

  5. Long-term results of hypofractionated stereotactic radiotherapy with CyberKnife for growth hormone-secreting pituitary adenoma: evaluation by the Cortina consensus.

    PubMed

    Iwata, Hiromitsu; Sato, Kengo; Nomura, Ryutaro; Tabei, Yusuke; Suzuki, Ichiro; Yokota, Naoki; Inoue, Mitsuhiro; Ohta, Seiji; Yamada, Shozo; Shibamoto, Yuta

    2016-06-01

    The aim of the present study was to evaluate the safety and feasibility of hypofractionated stereotactic radiotherapy (SRT) with CyberKnife for growth hormone-secreting pituitary adenoma (GH-PA). Fifty-two patients with GH-PA were treated with hypofractionated SRT between September 2001 and October 2012. Eight patients had clinically silent GH-PA and 44 were symptomatic. Only 1 patient was inoperable. The other patients had recurrent or postoperative residual tumors on MRI. All patients had received pharmacotherapy prior to SRT with a somatostatin analog, dopamine agonist, and/or GH receptor antagonist. The marginal doses were 17.4-26.8 Gy for the 3-fraction schedule and 20.0-32.0 Gy for the 5-fraction schedule. Endocrinological remission was assessed by the Cortina consensus criteria 2010 (random GH <1 ng/ml or nadir GH after an oral glucose tolerance test <0.4 ng/ml and normalization of age- and sex-adjusted insulin-like growth factor-1). The median follow-up period was 60 months (range 27-137). The 5-year overall survival, local control, and disease-free survival rates were 100, 100, and 96 %, respectively. Nine patients (5 clinically silent and 4 symptomatic patients) satisfied the Cortina criteria without receiving further pharmacotherapy, whereas the remaining 43 patients did not. No post-SRT grade 2 or higher visual disorder occurred. Symptomatic post-SRT hypopituitarism was observed in 1 patient. CyberKnife hypofractionated SRT is safe and effective when judged by imaging findings for GH-PA. However, it may be difficult to satisfy the Cortina consensus criteria in most symptomatic patients with SRT alone. Further investigations of optimal treatments are warranted.

  6. Dosimetric impact of multileaf collimator leaf width according to sophisticated grade of technique in the IMRT and VMAT planning for pituitary adenoma lesion

    PubMed Central

    Chae, Soo-Min; Lee, Ki Woong; Son, Seok Hyun

    2016-01-01

    We analyzed the difference in the dosimetric effect between 5-mm and 2.5-mm multileaf collimator (MLC) leaf width according to the sophisticated grades of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT). Nineteen patients with pituitary adenomas were selected for this study. The treatment plans were performed according to the size of the MLC (5-mm and 2.5-mm MLC), the type of technique (IMRT and VMAT), and the sophisticated grades of each technique (5-field, 9-field, 13-field, 17-field technique in IMRT and 1-arc and 2-arc techniques in VMAT). The downsizing effects of MLC leaf width were analyzed using target volume coverage (TVC), conformity index (CI), dose gradient index (GI), and normal tissue difference 70% isodose line and 50% isodose line. Upon replacing the 5-mm MLC with the 2.5-mm MLC, TVC and CI improved by 1.30% and 1.36%, respectively, in total plans. The TVC and CI improved by 1.68% and 1.67% in IMRT, respectively, and by 0.54% and 0.72% in VMAT, respectively. TVC improved by 2.53%, 1.82%, 1.34%, and 0.94%, and CI also improved by 2.70%, 1.81%, 1.24%, and 0.94%, in 5-field, 9-field, 13-field, and 17-field IMRT, respectively. TVC improved by 0.66% and 0.43%, and CI also improved by 0.93%, and 0.52% in 1-arc and 2-arc VMAT, respectively. Regarding the target coverage, there were dosimetric benefits of a smaller MLC leaf width. However, the downsizing effect of the MLC leaf width decreased with the use of a more precise RT technique and a more sophisticated grade of the same technique. PMID:27806336

  7. Radiation necrosis of the optic chiasm, optic tract, hypothalamus, and upper pons after radiotherapy for pituitary adenoma, detected by gadolinium-enhanced, T1-weighted magnetic resonance imaging: Case report

    SciTech Connect

    Tachibana, O.; Yamaguchi, N.; Yamashima, T.; Yamashita, J. )

    1990-10-01

    A 26-year-old woman was treated for a prolactin secreting pituitary adenoma by surgery and radiotherapy (5860 rads). Fourteen months later, she developed right hemiparesis and dysarthria. A T1-weighted magnetic resonance imaging scan using gadolinium contrast showed a small, enhanced lesion in the upper pons. Seven months later, she had a sudden onset of loss of vision, and radiation optic neuropathy was diagnosed. A T1-weighted magnetic resonance imaging scan showed widespread gadolinium-enhanced lesions in the optic chiasm, optic tract, and hypothalamus. Magnetic resonance imaging is indispensable for the early diagnosis of radiation necrosis, which is not visualized by radiography or computed tomography.

  8. Structure of the TPR domain of AIP: lack of client protein interaction with the C-terminal α-7 helix of the TPR domain of AIP is sufficient for pituitary adenoma predisposition.

    PubMed

    Morgan, Rhodri M L; Hernández-Ramírez, Laura C; Trivellin, Giampaolo; Zhou, Lihong; Roe, S Mark; Korbonits, Márta; Prodromou, Chrisostomos

    2012-01-01

    Mutations of the aryl hydrocarbon receptor interacting protein (AIP) have been associated with familial isolated pituitary adenomas predisposing to young-onset acromegaly and gigantism. The precise tumorigenic mechanism is not well understood as AIP interacts with a large number of independent proteins as well as three chaperone systems, HSP90, HSP70 and TOMM20. We have determined the structure of the TPR domain of AIP at high resolution, which has allowed a detailed analysis of how disease-associated mutations impact on the structural integrity of the TPR domain. A subset of C-terminal α-7 helix (Cα-7h) mutations, R304* (nonsense mutation), R304Q, Q307* and R325Q, a known site for AhR and PDE4A5 client-protein interaction, occur beyond those that interact with the conserved MEEVD and EDDVE sequences of HSP90 and TOMM20. These C-terminal AIP mutations appear to only disrupt client-protein binding to the Cα-7h, while chaperone binding remains unaffected, suggesting that failure of client-protein interaction with the Cα-7h is sufficient to predispose to pituitary adenoma. We have also identified a molecular switch in the AIP TPR-domain that allows recognition of both the conserved HSP90 motif, MEEVD, and the equivalent sequence (EDDVE) of TOMM20.

  9. Analysis of volumetric response of pituitary adenomas receiving adjuvant CyberKnife stereotactic radiosurgery with the application of an exponential fitting model

    PubMed Central

    Yu, Yi-Lin; Yang, Yun-Ju; Lin, Chin; Hsieh, Chih-Chuan; Li, Chiao-Zhu; Feng, Shao-Wei; Tang, Chi-Tun; Chung, Tzu-Tsao; Ma, Hsin-I; Chen, Yuan-Hao; Ju, Da-Tong; Hueng, Dueng-Yuan

    2017-01-01

    Abstract Tumor control rates of pituitary adenomas (PAs) receiving adjuvant CyberKnife stereotactic radiosurgery (CK SRS) are high. However, there is currently no uniform way to estimate the time course of the disease. The aim of this study was to analyze the volumetric responses of PAs after CK SRS and investigate the application of an exponential decay model in calculating an accurate time course and estimation of the eventual outcome. A retrospective review of 34 patients with PAs who received adjuvant CK SRS between 2006 and 2013 was performed. Tumor volume was calculated using the planimetric method. The percent change in tumor volume and tumor volume rate of change were compared at median 4-, 10-, 20-, and 36-month intervals. Tumor responses were classified as: progression for >15% volume increase, regression for ≤15% decrease, and stabilization for ±15% of the baseline volume at the time of last follow-up. For each patient, the volumetric change versus time was fitted with an exponential model. The overall tumor control rate was 94.1% in the 36-month (range 18–87 months) follow-up period (mean volume change of −43.3%). Volume regression (mean decrease of −50.5%) was demonstrated in 27 (79%) patients, tumor stabilization (mean change of −3.7%) in 5 (15%) patients, and tumor progression (mean increase of 28.1%) in 2 (6%) patients (P = 0.001). Tumors that eventually regressed or stabilized had a temporary volume increase of 1.07% and 41.5% at 4 months after CK SRS, respectively (P = 0.017). The tumor volume estimated using the exponential fitting equation demonstrated high positive correlation with the actual volume calculated by magnetic resonance imaging (MRI) as tested by Pearson correlation coefficient (0.9). Transient progression of PAs post-CK SRS was seen in 62.5% of the patients receiving CK SRS, and it was not predictive of eventual volume regression or progression. A three-point exponential model is of potential predictive value

  10. Endoscopic surgery of pituitary tumors.

    PubMed

    Dhepnorrarat, Rataphol Chris; Ang, Beng Ti; Sethi, Dharambir Singh

    2011-08-01

    Endoscopic pituitary surgery has been gaining wide acceptance as the first-line treatment of most functional pituitary adenomas. This technique has many advantages over traditional procedures, and growing evidence supports its use for endocrine control of functioning tumors. This article reviews data on the different modalities of treatment of functioning pituitary adenomas and compares the results. Endoscopic pituitary surgery controls tumor growth and endocrinopathy as well as or better than other treatment modalities. Complication rates are low and patient recovery is fast. Furthermore, surgery provides a means of achieving prompt decompression of neurologic structures and endocrine remission.

  11. Sellar gangliocytoma with adrenocorticotropic and prolactin adenoma.

    PubMed

    Kissiedu, Juliana O; Prayson, Richard A

    2016-02-01

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

  12. Local optometrists are a major source of referrals to a pituitary tumour clinic.

    PubMed

    Surchi, Haval; Jafar-Mohammadi, Bahram; Pal, Aparna; Cudlip, Simon; Grossman, Ashley B

    2017-03-01

    Pituitary adenomas can be identified pathologically in some 20-25% of autopsy specimens, but only around 1/1000 of the population have clinically significant tumours.Classic bitemporal hemianopia occurs as tumour expands. These visual symptoms are the most common objective manifestations of non-functioning pituitary adenomas, and demand urgent decompression to increase the probability of a complete normalisation of visual function. Delayed diagnosis may lead to irreversible visual loss.The onset of the visual deficit is usually gradual such that many patients might not seek medical consultation for months or even years. Thus, early diagnosis is critical but may be significantly delayed by a failure of concern by the patient or their clinicians.During our joint weekly Pituitary Clinic meeting of the Oxford University Hospitals Endocrinology and Neurosurgical teams, it became apparent that a large percentage of patients with pituitary gland lesions had their problem detected after a routine visit to a local optometrist. With this in mind, we conducted a retrospective study to investigate all referrals to our services over 2 years of patients with diagnosed non-functioning pituitary adenomas who required operative intervention. We found that the majority of patients presenting with visual loss has been initially seen and referred by an optometrist, while 12% had been referred by an optometrist when the patient was unaware that they had a significant visual problem. We conclude that optometrists in our region play a major role in diagnosing pituitary tumours at an early stage, almost certainly avoiding irreversible visual loss in some patients.

  13. Pituitary Apoplexy.

    PubMed

    Briet, Claire; Salenave, Sylvie; Bonneville, Jean-François; Laws, Edward R; Chanson, Philippe

    2015-12-01

    Pituitary apoplexy, a rare clinical syndrome secondary to abrupt hemorrhage or infarction, complicates 2%-12% of pituitary adenomas, especially nonfunctioning tumors. Headache of sudden and severe onset is the main symptom, sometimes associated with visual disturbances or ocular palsy. Signs of meningeal irritation or altered consciousness may complicate the diagnosis. Precipitating factors (increase in intracranial pressure, arterial hypertension, major surgery, anticoagulant therapy or dynamic testing, etc) may be identified. Corticotropic deficiency with adrenal insufficiency may be life threatening if left untreated. Computed tomography or magnetic resonance imaging confirms the diagnosis by revealing a pituitary tumor with hemorrhagic and/or necrotic components. Formerly considered a neurosurgical emergency, pituitary apoplexy always used to be treated surgically. Nowadays, conservative management is increasingly used in selected patients (those without important visual acuity or field defects and with normal consciousness), because successive publications give converging evidence that a wait-and-see approach may also provide excellent outcomes in terms of oculomotor palsy, pituitary function and subsequent tumor growth. However, it must be kept in mind that studies comparing surgical approach and conservative management were retrospective and not controlled.

  14. How effective is temozolomide for treating pituitary tumours and when should it be used?

    PubMed

    Halevy, Carmel; Whitelaw, Benjamin C

    2017-04-01

    Temozolomide (TMZ) has been shown as an effective treatment option in aggressive pituitary adenomas and carcinomas. This review analyses the published case series and demonstrates 42 % of patents show a radiological response and 27 % experience stable disease following TMZ. Prolactinomas and corticotroph tumours respond best to TMZ, showing approximately a 50 % response rate, with non-functioning tumours responding only half as frequently. Other factors that may predict the tumour's TMZ response include MGMT and MSH status, but neither is sufficiently robust to determine treatment decisions. TMZ has an accepted role in treating pituitary carcinoma and adenomas if radiation and surgery have failed to control tumour growth. To use TMZ on the basis of anticipated future aggression, as a primary therapy, or in preference to radiotherapy remains controversial.

  15. Octreotide and pasireotide (dis)similarly inhibit pituitary tumor cells in vitro.

    PubMed

    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

    2016-11-01

    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.

  16. Pituitary gigantism: Causes and clinical characteristics.

    PubMed

    Rostomyan, Liliya; Daly, Adrian F; Beckers, Albert

    2015-12-01

    Acromegaly and pituitary gigantism are very rare conditions resulting from excessive secretion of growth hormone (GH), usually by a pituitary adenoma. Pituitary gigantism occurs when GH excess overlaps with the period of rapid linear growth during childhood and adolescence. Until recently, its etiology and clinical characteristics have been poorly understood. Genetic and genomic causes have been identified in recent years that explain about half of cases of pituitary gigantism. We describe these recent discoveries and focus on some important settings in which gigantism can occur, including familial isolated pituitary adenomas (FIPA) and the newly described X-linked acrogigantism (X-LAG) syndrome.

  17. The role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C mutations in causing pituitary adenomas in a large cohort of children, adolescents, and patients with genetic syndromes.

    PubMed

    Stratakis, C A; Tichomirowa, M A; Boikos, S; Azevedo, M F; Lodish, M; Martari, M; Verma, S; Daly, A F; Raygada, M; Keil, M F; Papademetriou, J; Drori-Herishanu, L; Horvath, A; Tsang, K M; Nesterova, M; Franklin, S; Vanbellinghen, J-F; Bours, V; Salvatori, R; Beckers, A

    2010-11-01

    The prevalence of germline mutations in MEN1, AIP, PRKAR1A, CDKN1B and CDKN2CI is unknown among pediatric patients with pituitary adenomas (PA). In this study, we screened children with PA for mutations in these genes; somatic GNAS mutations were also studied in a limited number of growth hormone (GH) or prolactin (PRL)-secreting PA. We studied 74 and 6 patients with either isolated Cushing disease (CD) or GH- or PRL-secreting PA, respectively. We also screened four pediatric patients with CD, and four with GH/PRL-secreting tumors who had some syndromic features. There was one AIP mutation (p.Lys103Arg) among 74 CD patients. Two MEN1 mutations that occurred in patients with recurrent or difficult-to-treat disease were found among patients with CD. There was one MEN1 and three AIP mutations (p.Gln307ProfsX104, p.Pro114fsX, p.Lys241X) among pediatric patients with isolated GH- or PRL-secreting PA and one additional MEN1 mutation in a patient with positive family history. There were no mutations in the PRKAR1A, CDKN1B, CDKN2C or GNAS genes. Thus, germline AIP or MEN1 gene mutations are frequent among pediatric patients with GH- or PRL-secreting PA but are significantly rarer in pediatric CD; PRKAR1A mutations are not present in PA outside of Carney complex.

  18. TSH-secreting adenoma improved with cabergoline.

    PubMed

    Mouton, F; Faivre-Defrance, F; Cortet-Rudelli, C; Assaker, R; Soto-Ares, G; Defoort-Dhellemmes, S; Blond, S; Wemeau, J-L; Vantyghem, M-C

    2008-06-01

    TSH-secreting adenomas are rare tumors, representing only 0.5 to 2.5% of pituitary adenomas. Their main clinical characteristics include signs of thyrotoxicosis, diffuse goiter and a compressive syndrome. Biologically, free T4 and T3 serum levels are elevated, contrasting with inadequate serum TSH levels and increased alpha chains. Magnetic resonance (MR) imaging shows a pituitary tumor, the main differential diagnosis being resistance to thyroid hormones. Treatment is based on surgery, possibly associated with somatostatin analogs and radiotherapy. Though the long-term evolution of this rare pathology seems to have improved, some clinical situations are still a challenge to treat. We report one such case that was resistant to both stereotactic radiotherapy and somatostatin analogs, but surprisingly improved with cabergoline. We suggest that cabergoline should be considered as an alternative treatment in cases of pituitary adenomas that resist traditional treatments.

  19. Leptin and the pituitary.

    PubMed

    Sone, M; Osamura, R Y

    2001-01-01

    sufficient growth. (Localization and Functional Relevance of Leptin and Leptin Receptor in Rodents Pituitary) Aside from being the food intake inhibitor and the energy control factor, leptin takes part in controlling the pituitary hormones. Promoting the secretion of GH, PRL (prolactin), TSHbeta (thyroid stimulating hormone-beta, FSHbeta/LHbeta, and inhibiting the secretion of ACTH (adrenocorticotropic hormone) are the major changes of pituitary hormones which are brought on by leptin. The expressive localization is specific, and immunohistochemistry (IHC) method recognized leptin in granular state in FSHbeta, LHbeta and TSHbeta positive cells. In our biochemical examination, the bulk of the expression of leptin is recognized in fraction of the secretory granule. In particular, FSHbeta cells had the highest percentage rate of colocalized leptin in rat pituitary. On the other hand, leptin receptor has been reported to be found only in normal rat pituitary, human pituitary adenoma, and respective cell lines in pituitaries by the RT-PCR method until now, but we disclosed for the first time the localization of leptin receptor on the plasma membrane of GH-secreting cells with the IHC method that has not been cleared so far. These findings show that leptin and leptin receptor have been expressed in different cells, and that the rat pituitary glands entertain paracrine mechanism between leptin (FSHbeta/LHbeta cells) and leptin receptor (GH cells). The function of paracrine in this pituitary suggests a new point of view in hypothalamus-pituitary axis, and it shall be concerned with many aspects such as hormone secretions and proliferation/inhibition. (Human Pituitary Adenoma) Preliminary report of leptin and leptin-receptor relationship with pituitary adenoma that has secretion abnormality has been filed, and its manifestation is being observed by the RT-PCR. Leptin and leptin receptor are expressed in most adenoma, and it is thought to function by autocrine and paracrine pathway in

  20. Triple jeopardy in the pituitary.

    PubMed

    Goh, Kian-Peng; Lee, Hwei-Yee; Rajasoorya, Raja C

    2008-01-01

    Aggressive pituitary tumors are rare the pathogenesis is not well established. The development of pituitary tumor after apoplexy has also been rarely reported. We describe the sequential development of Cushing's disease, apoplexy and aggressive pituitary tumor in the same patient. A 31-year old male presented with eutopic ACTH dependent Cushing's syndrome which failed initial pituitary surgery. He underwent subsequent bilateral adrenalectomy for control of hypercortisolism. An episode of pituitary apoplexy then occurred which was followed by the development of a null-cell pituitary tumor. This second tumor exhibited an aggressive behavior with invasion into the surrounding structures and systemic spread clinically. This case provides important evidence for the hypotheses of the pathogenesis of aggressive pituitary tumors which could have arisen from surviving adenoma cells following apoplexy or as a de novo development of pituitary carcinoma from cells which were not part of the original adenoma. This is the first report of a transformation of Cushing's disease to an aggressive and invasive null cell tumor after pituitary irradiation, apoplexy and surgery.

  1. Cerebrospinal fluid rhinorrhoea in pituitary tumours1

    PubMed Central

    Cole, I E; Keene, Malcolm

    1980-01-01

    Three cases of CSF rhinorrhoea due to pituitary tumours are reported and the literature reviewed. The treatment of choice appears to be trans-sphenoidal exploration of the pituitary fossa with insertion of a free muscle graft followed by radiotherapy. The probability of the tumour being a prolactin-secreting adenoma is discussed. PMID:7017123

  2. Multidisciplinary Management of Pituitary Apoplexy

    PubMed Central

    Albani, Adriana; Angileri, Filippo Flavio; Esposito, Felice; Granata, Francesca; Ferreri, Felicia; Cannavò, Salvatore

    2016-01-01

    Pituitary apoplexy is a rare clinical syndrome due to ischemic or haemorrhagic necrosis of the pituitary gland which complicates 2–12% of pituitary tumours, especially nonfunctioning adenomas. In many cases, it results in severe neurological, ophthalmological, and endocrinological consequences and may require prompt surgical decompression. Pituitary apoplexy represents a rare medical emergency that necessitates a multidisciplinary approach. Modalities of treatment and times of intervention are still largely debated. Therefore, the management of patients with pituitary apoplexy is often empirically individualized and clinical outcome is inevitably related to the multidisciplinary team's skills and experience. This review aims to highlight the importance of a multidisciplinary approach in the management of pituitary apoplexy and to discuss modalities of presentation, treatment, and times of intervention. PMID:28074095

  3. Long-term (up to 18 years) effects on GH/IGF-1 hypersecretion and tumour size of primary somatostatin analogue (SSTa) therapy in patients with GH-secreting pituitary adenoma responsive to SSTa

    PubMed Central

    Maiza, Jean Christophe; Vezzosi, Delphine; Matta, Maria; Donadille, Florence; Loubes-Lacroix, Florence; Cournot, Maxime; Bennet, Antoine; Caron, Philippe

    2007-01-01

    Context The role of somatostatin analogues (SSTa) in the treatment of acromegaly. Objective To evaluate the antihormonal and antitumour efficacy of long-term (up to 18 years) primary treatment with SSTa in patients with GH-secreting pituitary adenoma responsive to SSTa. Design An open, prospective, single-centre, clinical study. Patients Thirty-six acromegalic patients, aged 17–75 years (postoral glucose tolerance test GH > 1 µg/l, increased IGF-1 for age and sex), were monitored in a single centre and treated with SSTa as first-line therapy. The mean pretreatment GH level was 13·5 ±3·1 µg/l, and IGF-1 (as a percentage of the value over the normal range) was 302 ± 26%. The patients had macroadenoma (n = 25), microadenoma (n = 8) or empty sella turcica (n = 3). The mean duration of treatment was 8 years (range 3–18 years). Hormonal and morphological monitoring was undertaken after 6 months, and then the patients were followed annually. Results After 1 year, the mean GH and IGF-1 levels had reduced considerably (GH: 2·4 ± 0·3 µg/l; IGF-1; 174 ± 14%, P < 0·01), and they continued to decrease over 10 years, with a mean GH level of 1·6 ± 0·1 µg/l and IGF-1 of 123 ± 18% (P = 0·02). GH < 2 µg/l, normal IGF-1, or both were observed in 25 (70%), 24 (67%) and 21 (58%) patients, respectively. The mean reduction in tumour volume was 43% (range 13–97%) and shrinkage > 20% was obtained in 21 patients (72%). SSTa treatment was well tolerated with few digestive or metabolic side-effects. Conclusion Long-term (up to 18 years) treatment with SSTa used as first-line therapy is effective from both an antihormonal and antitumour perspective, and is well tolerated in acromegalic patients. PMID:17524029

  4. Molecular Mechanisms Underlying Pituitary Pathogenesis.

    PubMed

    Sapochnik, Melanie; Nieto, Leandro Eduardo; Fuertes, Mariana; Arzt, Eduardo

    2016-04-01

    During the last years, progress has been made on the identification of mechanisms involved in anterior pituitary cell transformation and tumorigenesis. Oncogene activation, tumor suppressor gene inactivation, epigenetic changes, and microRNAs deregulation contribute to the initiation of pituitary tumors. Despite the high prevalence of pituitary adenomas, they are mostly benign, indicating that intrinsic mechanisms may regulate pituitary cell expansion. Senescence is characterized by an irreversible cell cycle arrest and represents an important protective mechanism against malignancy. Pituitary tumor transforming gene (PTTG) is an oncogene involved in early stages of pituitary tumor development, and also triggers a senescence response by activating DNA-damage signaling pathway. Cytokines, as well as many other factors, play an important role in pituitary physiology, affecting not only cell proliferation but also hormone secretion. Special interest is focused on interleukin-6 (IL-6) because its dual function of stimulating pituitary tumor cell growth but inhibiting normal pituitary cells proliferation. It has been demonstrated that IL-6 has a key role in promoting and maintenance of the senescence program in tumors. Senescence, triggered by PTTG activation and mediated by IL-6, may be a mechanism for explaining the benign nature of pituitary tumors.

  5. Seminoma and parathyroid adenoma in a snow leopard (Panthera unica).

    PubMed

    Doster, A R; Armstrong, D L; Bargar, T W

    1989-05-01

    A seminoma and parathyroid adenoma were diagnosed in an aged snow leopard. The ultrastructural appearance of the seminoma was similar to that described in the dog and in man. The lack of significant amounts of rough endoplasmic reticulum, Golgi complexes and free ribosomes in the parathyroid adenoma suggested that it was non-functional. Parathyroid adenoma has not been previously described in a large wild feline.

  6. Delayed sequelae of pituitary irradiation

    SciTech Connect

    Woodruff, K.H.; Lyman, J.T.; Lawrence, J.H.; Tobias, C.A.; Born, J.L.; Fabrikant, J.I.

    1984-01-01

    Since 1958, 781 patients at Lawrence Berkeley Laboratory have received helium-particle stereotactic radiosurgery to the adenohypophysis. Autopsy findings in 15 of these patients are reported. Ten patients received pituitary radiation (average dose, 116 Gy in six fractions) for progressive neovascularization retinopathy due to diabetes mellitus. Evidence of a time-dependent course of progressive fibrosis in their pituitary glands was found. Five patients were treated for eosinophilic adenomas. Although they had lower average doses of radiation (56 Gy in six fractions), their pituitary glands showed cystic cavitation of the adenomas. The adenomas thus appeared more radiosensitive than the normal pars anterior, which, in turn, was more radiosensitive than the adjacent neurohypophysis. No significant radiation changes were found in the surrounding brain or cranial nerves. The endocrine organs under pituitary control showed varying degrees of atrophy, and clinical tests revealed progressive hypofunction. It was concluded that charged-particle therapy produced a sharply delineated focal ral tests revealed progressive hypofunction. It was concluded that charged-particle therapy produced a sharply delineated focal radiation lesion confined to the pituitary gland but did not cause injury to the critical structures of the surrounding central nervous system.

  7. Three-dimensional reconstruction and morphological characterization of pituitary macroadenomas

    PubMed Central

    Wei, Lin; Jing, Jun-Jie; Zhang, Shang-Ming

    2016-01-01

    Introduction The aim was to investigate the relationship between the tumor (clinicopathologic and radiological) characteristics and the morphological parameters of pituitary macroadenoma or giant adenoma patients using a three-dimensional (3D) reconstructed model. Material and methods Magnetic resoanance imaging (MRI) was performed preoperatively; tumor grade was determined by the Knosp-Steiner classification and tumor morphology by the SIPAP classification. Pituitary adenomas and adjacent structures were reconstructed three-dimensionally by volume rendering. Results Fifty-two and 6 patients underwent surgery via the transnasal transsphenoidal or pterional approach, respectively. Knosp-Steiner grades I to IV adenomas were observed in 5.2%, 25.9%, 22.4% and 46.6% of the patients, respectively. The 3D model was reconstructed in all cases with superb delineation of tumor morphology and the spatial relationship between the tumor and adjacent tissues. Pituitary adenomas were categorized into intrasellar (13.8%), suprasellar (20.7%), infrasellar (17.2%), and lobulated adenomas (48.3%). Suprasellar adenomas had the smallest (2.27 ±3.22 cm3) and lobulated adenomas the largest volume (24.61 ±30.50 cm3). Intrasellar adenomas were all functioning, while 75%, 60% and 60.7%, respectively, of suprasellar, infrasellar and lobulated adenomas were nonfunctioning, with a significant association between tumor morphology and secretory function (p = 0.005). Conclusions Three-dimensional reconstruction of pituitary macroadenomas offers a simplified morphological classification of pituitary adenomas and may be helpful for neurosurgeons to categorize and characterize pituitary adenomas. PMID:27279851

  8. Colorectal cancer manifesting with metastasis to prolactinoma: report of a case involving symptoms mimicking pituitary apoplexy.

    PubMed

    Thewjitcharoen, Yotsapon; Shuangshoti, Shanop; Lerdlum, Sukalaya; Siwanuwatn, Rungsak; Sunthornyothin, Sarat

    2014-01-01

    Pituitary metastasis is an uncommon first presentation of systemic malignancy. The most common presenting symptom of pituitary metastasis is diabetes insipidus reflecting involvement of the stalk and/or posterior pituitary. We herein present a unique case of the coexistence of both a functioning pituitary adenoma (prolactinoma) and pituitary metastasis of advanced colorectal cancer with pituitary apoplexy as the first manifestation of underlying malignancy. The present case emphasizes the need to consider pituitary metastasis as a differential diagnosis in patients presenting with pituitary lesions and be aware that tumor-to-tumor metastasis can occur unexpectedly in those with pituitary metastases.

  9. MicroRNA-145 inhibits the activation of the mTOR signaling pathway to suppress the proliferation and invasion of invasive pituitary adenoma cells by targeting AKT3 in vivo and in vitro

    PubMed Central

    Zhou, Kai; Fan, Yan-Dong; Wu, Peng-Fei; Duysenbi, Serick; Feng, Zhao-Hai; Du, Guo-Jia; Zhang, Ting-Rong

    2017-01-01

    Purpose This study was designed to explore how miR-145 regulates the mTOR signaling pathway in invasive pituitary adenoma (IPA) by targeting AKT3. Methods A total of 71 cases of IPA tissues and 66 cases of non-IPA tissues were obtained in this study. In vitro, the IPA cells were assigned into blank control, empty plasmid, miR-145 mimic, miR-145 inhibitor, miR-145 mimic + rapamycin, miR-145 inhibitor + rapamycin and rapamycin groups. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were performed to detect the protein expressions of PI3K, AKT3, mTOR mRNA and the mRNA expression of miR-145 both in vivo and in vitro. Additionally, the S6K and RPS6 mRNA and protein expressions as well as the relative phosphorylation levels were determined in vitro. MTT assay, flow cytometry and transwell assay were used to testify the cell proliferation, apoptosis and invasion ability, respectively. Results The IPA tissues exhibited significantly lower expression of miR-145 but higher PI3K, AKT3 and mTOR mRNA and protein expressions when compared with the non-IPA tissues. Compared with the blank control and empty plasmid groups, the miR-145 mimic group showed significantly decreased PI3K, AKT3, mTOR, S6K and RPS6 mRNA and protein expressions as well as phosphorylation levels; besides, the IPA cell proliferation, migration and invasion ability were strongly inhibited, accompanied with the increased number of apoptotic cells. In the miR-145 inhibitor group, the PI3K, AKT3, mTOR, S6K and RPS6 mRNA and protein expressions as well as the phosphorylation levels were significantly increased; cell proliferation, migration and invasion ability were remarkably elevated, accompanied with reduced apoptotic cell number. Conclusion The study demonstrates that miR-145 inhibits the mTOR signaling pathway to suppress the IPA cell proliferation and invasion and promotes its apoptosis by targeting AKT3. PMID:28352194

  10. Clinicopathological correlation in pituitary gland metastasis presenting as anterior visual pathway compression.

    PubMed

    Luu, Susie T; Billing, Katie; Crompton, John L; Blumbergs, Peter; Lee, Andrew W; Chen, Celia S

    2010-06-01

    Pituitary gland metastases, albeit rare, remain an important differential in sellar and suprasellar tumours. Clinical and radiological features of pituitary metastases may be indistinguishable from benign suprasellar lesions such as a pituitary adenoma. Histopathology with immunohistochemical assay remains the key to the diagnosis of pituitary metastasis. We describe four patients with sellar lesions presenting with anterior visual pathway compression initially diagnosed as pituitary adenomas who on immunohistochemistry were found to have metastases to the pituitary. Classification of the cell histology determined the primary site of origin in some patients. This series demonstrates the importance of combining histopathology and immunohistochemistry in the diagnosis of suprasellar lesions.

  11. Gene Therapy for Pituitary Tumors

    PubMed Central

    Seilicovich, Adriana; Pisera, Daniel; Sciascia, Sandra A.; Candolfi, Marianela; Puntel, Mariana; Xiong, Weidong; Jaita, Gabriela; Castro, Maria G.

    2009-01-01

    Pituitary tumors are the most common primary intracranial neoplasms. Although most pituitary tumors are considered typically benign, others can cause severe and progressive disease. The principal aims of pituitary tumor treatment are the elimination or reduction of the tumor mass, normalization of hormone secretion and preservation of remaining pituitary function. In spite of major advances in the therapy of pituitary tumors, for some of the most difficult tumors, current therapies that include medical, surgical and radiotherapeutic methods are often unsatisfactory and there is a need to develop new treatment strategies. Gene therapy, which uses nucleic acids as drugs, has emerged as an attractive therapeutic option for the treatment of pituitary tumors that do not respond to classical treatment strategies if the patients become intolerant to the therapy. The development of animal models for pituitary tumors and hormone hypersecretion has proven to be critical for the implementation of novel treatment strategies and gene therapy approaches. Preclinical trials using several gene therapy approaches for the treatment of anterior pituitary diseases have been successfully implemented. Several issues need to be addressed before clinical implementation becomes a reality, including the development of more effective and safer viral vectors, uncovering novel therapeutic targets and development of targeted expression of therapeutic transgenes. With the development of efficient gene delivery vectors allowing long-term transgene expression with minimal toxicity, gene therapy will become one of the most promising approaches for treating pituitary adenomas. PMID:16457646

  12. A history of pituitary pathology.

    PubMed

    Asa, Sylvia L; Mete, Ozgur

    2014-03-01

    The history of pituitary pathology is a long one that dates back to biblical times, but the last 25 years have represented an era of "coming of age." The role of the pituitary in health and disease was the subject of many studies over the last century. With the development of electron microscopy, immunoassays, and immunohistochemistry, the functional alterations associated with pituitary disease have been clarified. The additional information provided by molecular genetic studies has allowed progress in understanding the pathogenesis of pituitary disorders. Nevertheless, many questions remain to be answered. For example, pathologists cannot morphologically distinguish locally aggressive adenomas from carcinomas when tumor is confined to the sella. Sadly, basal cell carcinoma, the most common carcinoma of skin, usually causes less morbidity than pituitary adenomas, which occur in almost 20 % of the general population, can cause significant illness and even death, and yet are still classified as benign. The opportunity to increase awareness of the impact of these common lesions on quality of life is the current challenge for physicians and patients. We anticipate that ongoing multidisciplinary approaches to pituitary disease research will offer new insights into diseases arising from this fascinating organ.

  13. Symptomatic Rathke's cleft cyst with a co-existing pituitary tumor; Brief review of the literature

    PubMed Central

    Babu, Ranjith; Back, Adam G.; Komisarow, Jordan M.; Owens, Timothy R.; Cummings, Thomas J.; Britz, Gavin W.

    2013-01-01

    Pituitary adenomas and Rathke's cleft cysts (RCCs) share a common embryological origin. Occasionally, these two lesions can present within the same patient. We present a case of a 39-year-old male who was found to have a large sellar lesion after complaints of persistent headaches and horizontal nystagmus. Surgical resection revealed components of a RCC co-existing with a pituitary adenoma. A brief review of the literature was performed revealing 38 cases of co-existing Rathke's cleft cysts and pituitary adenomas. Among the cases, the most common symptoms included headache and visual changes. Rathke's cleft cysts and pituitary adenomas are rarely found to co-exist, despite having common embryological origins. We review the existing literature, discuss the common embryology to these two lesions and describe a unique case from our institution of a co-existing Rathke's cleft cyst and pituitary adenoma. PMID:24551002

  14. Acromegaly with negative pituitary MRI and no evidence of ectopic source: the role of transphenoidal pituitary exploration?

    PubMed

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

    2011-12-01

    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.

  15. Animal models of pituitary neoplasia

    PubMed Central

    Lines, K.E.; Stevenson, M.; Thakker, R.V.

    2016-01-01

    Pituitary neoplasias can occur as part of a complex inherited disorder, or more commonly as sporadic (non-familial) disease. Studies of the molecular and genetic mechanisms causing such pituitary tumours have identified dysregulation of >35 genes, with many revealed by studies in mice, rats and zebrafish. Strategies used to generate these animal models have included gene knockout, gene knockin and transgenic over-expression, as well as chemical mutagenesis and drug induction. These animal models provide an important resource for investigation of tissue-specific tumourigenic mechanisms, and evaluations of novel therapies, illustrated by studies into multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome in which ∼30% of patients develop pituitary adenomas. This review describes animal models of pituitary neoplasia that have been generated, together with some recent advances in gene editing technologies, and an illustration of the use of the Men1 mouse as a pre clinical model for evaluating novel therapies. PMID:26320859

  16. [Cerebral infarction after pituitary apoplexy: Description of a case and review of the literature].

    PubMed

    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.

  17. Transforming growth factor-beta, transforming growth factor-beta receptor II, and p27Kip1 expression in nontumorous and neoplastic human pituitaries.

    PubMed Central

    Jin, L.; Qian, X.; Kulig, E.; Sanno, N.; Scheithauer, B. W.; Kovacs, K.; Young, W. F.; Lloyd, R. V.

    1997-01-01

    Transforming growth factor (TGF)-beta has been implicated in the regulation of normal and neoplastic anterior pituitary cell function. TGF-beta regulates the expression of various proteins, including p27Kip1 (p27), a cell cycle inhibitory protein. We examined TGF-beta, TGF-beta type II receptor (TGF-beta-RII), and p27 expression in normal pituitaries, pituitary adenomas, and carcinomas to analyze the possible roles of these proteins in pituitary tumorigenesis. Normal pituitary, pituitary adenomas, and pituitary carcinomas all expressed TGF-beta and TGF-beta-RII immunoreactivity. Reverse transcription polymerase chain reaction analysis showed TGF-beta 1, -beta 2, and -beta 3 isoforms and TGF-beta-RII in normal pituitaries and pituitary adenomas. Pituitary adenomas cells cultured for 7 days in defined media showed a biphasic response to TGF-beta with significant inhibition of follicle-stimulating hormone secretion at higher concentrations (10(-9) mol/L) and stimulation of follicle-stimulating hormone secretion at lower concentrations (10(-13) mol/L) of TGF-beta 1 in gonadotroph adenomas. Immunohistochemical analysis for p27 protein expression showed the highest levels in nontumorous pituitaries with decreased immunoreactivity in adenomas and carcinomas. When nontumorous pituitaries and various adenomas were analyzed for p27 and specific hormone production, growth hormone, luteinizing hormone, and thyroid-stimulating hormone cells and tumors had the highest percentages of cells expressing p27, whereas adrenocorticotrophic hormone cells and tumors had the lowest percentages. Immunoblotting analysis showed that adrenocorticotrophic hormone adenomas also had the lowest levels of p27 protein. Semiquantitative reverse transcription polymerase chain reaction and Northern hybridization analysis did not show significant differences in p27 mRNA expression in the various types of adenomas or in nontumorous pituitaries. In situ hybridization for p27 mRNA showed similar

  18. Pituitary magnetic resonance imaging in Cushing's disease.

    PubMed

    Vitale, Giovanni; Tortora, Fabio; Baldelli, Roberto; Cocchiara, Francesco; Paragliola, Rosa Maria; Sbardella, Emilia; Simeoli, Chiara; Caranci, Ferdinando; Pivonello, Rosario; Colao, Annamaria

    2017-03-01

    Adrenocorticotropin-secreting pituitary tumor represents about 10 % of pituitary adenomas and at the time of diagnosis most of them are microadenomas. Transsphenoidal surgery is the first-line treatment of Cushing's disease and accurate localization of the tumor within the gland is essential for selectively removing the lesion and preserving normal pituitary function. Magnetic resonance imaging is the best imaging modality for the detection of pituitary tumors, but adrenocorticotropin-secreting pituitary microadenomas are not correctly identified in 30-50 % of cases, because of their size, location, and enhancing characteristics. Several recent studies were performed with the purpose of better localizing the adrenocorticotropin-secreting microadenomas through the use in magnetic resonance imaging of specific sequences, reduced contrast medium dose and high-field technology. Therefore, an improved imaging technique for pituitary disease is mandatory in the suspect of Cushing's disease. The aims of this paper are to present an overview of pituitary magnetic resonance imaging in the diagnosis of Cushing's disease and to provide a magnetic resonance imaging protocol to be followed in case of suspicion adrenocorticotropin-secreting pituitary adenoma.

  19. A pediatric case of pituitary macroadenoma presenting with pituitary apoplexy and cranial nerve involvement: case report

    PubMed Central

    Özçetin, Mustafa; Karacı, Mehmet; Toroslu, Ertuğ; Edebali, Nurullah

    2016-01-01

    Pituitary adenomas usually arise from the anterior lobe of the pituitary gland and are manifested with hormonal disorders or mass effect. Mass effect usually occurs in nonfunctional tumors. Pituitary adenomas may be manifested with visual field defects or rarely in the form of total oculomotor palsy. Visual field defect is most frequently in the form of bitemporal hemianopsia and superior temporal defect. Sudden loss of vision, papilledema and ophthalmoplegia may be observed. Pituitary apoplexy is defined as an acute clinical syndrome characterized with headache, vomiting, loss of vision, ophthalmoplegia and clouding of consciousness. The problem leading to pituitary apoplexy may be decreased blood supply in the adenoma and hemorrhage following this decrease or hemorrhage alone. In this article, we present a patient who presented with fever, vomiting and sudden loss of vision and limited outward gaze in the left eye following trauma and who was found to have pituitary macroadenoma causing compression of the optic chiasma and optic nerve on the left side on cranial and pituitary magnetic resonance imaging. PMID:27738402

  20. Pituitary Medicine From Discovery to Patient-Focused Outcomes

    PubMed Central

    2016-01-01

    Context: This perspective traces a pipeline of discovery in pituitary medicine over the past 75 years. Objective: To place in context past advances and predict future changes in understanding pituitary pathophysiology and clinical care. Design: Author's perspective on reports of pituitary advances in the published literature. Setting: Clinical and translational Endocrinology. Outcomes: Discovery of the hypothalamic-pituitary axis and mechanisms for pituitary control, have culminated in exquisite understanding of anterior pituitary cell function and dysfunction. Challenges facing the discipline include fundamental understanding of pituitary adenoma pathogenesis leading to more effective treatments of inexorably growing and debilitating hormone secreting pituitary tumors as well as medical management of non-secreting pituitary adenomas. Newly emerging pituitary syndromes include those associated with immune-targeted cancer therapies and head trauma. Conclusions: Novel diagnostic techniques including imaging genomic, proteomic, and biochemical analyses will yield further knowledge to enable diagnosis of heretofore cryptic syndromes, as well as sub classifications of pituitary syndromes for personalized treatment approaches. Cost effective personalized approaches to precision therapy must demonstrate value, and will be empowered by multidisciplinary approaches to integrating complex subcellular information to identify therapeutic targets for enabling maximal outcomes. These goals will be challenging to attain given the rarity of pituitary disorders and the difficulty in conducting appropriately powered prospective trials. PMID:26908107

  1. [Broncho-pulmonary adenomas].

    PubMed

    Sousa, Vítor; Pinto, Eugénia; Franca, Teresa; Carvalho, Lina

    2004-01-01

    Adenomas of solitary gland type together with papillomas are the true benign tumours in or around the bronchial tree. Alveolar adenoma and papillary adenoma are more frequently observed in peripheral parenchime although this group of tumours is very rare and often incidentally diagnosed. Presenting usually as solitary nodules in adults after 45 years, are easily recognized because of distinct morphology but alveolar adenomas may be difficult to evaluate in frozen sections. Two cases of pleomorphic adenoma and alveolar adenoma are presented and a review of literature is made.

  2. Predictors of aggressive clinical phenotype among immunohistochemically confirmed atypical adenomas.

    PubMed

    Zaidi, Hasan A; Cote, David J; Dunn, Ian F; Laws, Edward R

    2016-12-01

    Despite formal pathological criteria, not all atypical pituitary adenomas display clinically aggressive behavior. We set out to determine which factors predict a clinically aggressive phenotype among a cohort of atypical pituitary adenomas. Medical records were retrospectively reviewed from April 2008 to July 2015. Of 569 pituitary adenomas, 47 (8.3%) patients were surgically treated for atypical adenomas as defined by the WHO criteria. Clinically aggressive adenomas were defined as occurring in those patients who necessitated additional therapeutic intervention after the index (first) surgery, including additional surgery, medical therapy, or radiosurgery. Forty-seven patients with histopathological and immunohistochemical confirmation of atypical adenomas were identified and of these, 23 were noted to have a clinically aggressive course. Among the remaining 24 patients, the disease remained quiescent after the index surgery. On univariate analysis, clinically aggressive lesions were more likely to have a larger axial diameter on MRI (2.9±1.9cm vs. 1.9±0.7cm, p=0.02), greater incidence of cavernous sinus invasion (65.2% vs. 20.8%, p<0.01), and greater incidence of clival extension (60.9% vs. 0, p<0.01) on preoperative imaging. The two groups were equivalent with regard to immunohistochemical staining for ACTH, HGH, LH, FSH, PRL, and TSH. Clinically aggressive lesions, however, trended towards a greater average MIB-1 proliferative index (7.5%±4.9 vs. 6.0%±3.6, p=0.03). On multivariate analysis, the MIB-1 proliferative index trended towards statistical significance (p=0.06) as an independent predictor of clinical aggressiveness. Atypical pituitary adenomas are defined by a rigid set of immunohistochemical markers, but not all necessarily demonstrate an aggressive clinical phenotype.

  3. Crooke's cell tumors of the pituitary.

    PubMed

    Di Ieva, Antonio; Davidson, Jennilee M; Syro, Luis V; Rotondo, Fabio; Montoya, Julian F; Horvath, Eva; Cusimano, Michael D; Kovacs, Kalman

    2015-05-01

    Crooke's cell adenomas are a rare type of pituitary neoplasm. They produce adrenocorticotropic hormone causing Cushing's disease or may be endocrinologically silent. These tumors are usually invasive, may exhibit aggressive clinical behavior, and often recur with a low success of cure after reoperation and/or radiotherapy. Due to their rarity, they present great difficulties in assessing prognosis, treatment, and clinical management. Neurosurgeons and physicians dealing with pituitary adenomas diagnosed as Crooke's cell adenomas have to be aware of their potential clinical aggressiveness to plan strict follow-up of patients and eventual multimodality treatment. We review here the published cases of Crooke's cell tumors, as well as the clinical and histopathological characteristics of these unusual neoplasms.

  4. Pituitary gene expression differs in D-galactose-induced cell senescence and steroid-induced prolactinomas.

    PubMed

    Zhang, Tiehui; Zhao, Binhai; Li, Jia; Zhang, Chunlei; Li, Hongzhi; Wu, Jiang; Zhang, Shiming; Hui, Guozhen

    2015-04-01

    In general, pituitary tumors are benign with low mitotic activity. Premature senescence has been considered to be a significant mechanism underlying this uniquely benign pituitary tumor. The present study aims to compare the expression of the associated proteins involved in premature senescence pathways among normal, aging and pituitary adenoma cells. We successfully induced the aging pituitary using continuous D‑galactose (D‑gal) injection as well as a prolactin‑secreting pituitary tumor via diethylstilbestrol implants. Compared with normal pituitary cells, the aging pituitary tissues revealed increased expression of IL‑6, C/EBPβ, p53, p21 and p16 and decreased expression of pituitary tumor transforming gene. In contrast, the expression of IL‑6, p21 and p16 was decreased in pituitary tumor cells compared with normal pituitary tissues. Taken together, multiple pathways including IL‑6/C/EBPβ, p53/p21 and p16 were activated in aging pituitary cells in response to D‑gal treatment. However, all these pathways were immune to pituitary tumors treated by chronic estrogen. The findings and the involvement of cytokines in a highly prevalent natural disease model (pituitary adenomas) indicate a potential use of this pathway as a target for effective therapy for tumor silencing and prevention of adenoma progression towards malignancy.

  5. Tumor suppression by MEG3 lncRNA in a human pituitary tumor derived cell line.

    PubMed

    Chunharojrith, Paweena; Nakayama, Yuki; Jiang, Xiaobing; Kery, Rachel E; Ma, Jun; De La Hoz Ulloa, Cristine S; Zhang, Xun; Zhou, Yunli; Klibanski, Anne

    2015-11-15

    Human clinically non-functioning pituitary adenomas (NFAs) account for approximately 40% of diagnosed pituitary tumors. Epigenetic mutations in tumor suppressive genes play an important role in NFA development. Maternally expressed gene 3 (MEG3) is a long non-coding RNA (lncRNA) and we hypothesized that it is a candidate tumor suppressor whose epigenetic silencing is specifically linked to NFA development. In this study, we introduced MEG3 expression into PDFS cells, derived from a human NFA, using both inducible and constitutively active expression systems. MEG3 expression significantly suppressed xenograft tumor growth in vivo in nude mice. When induced in culture, MEG3 caused cell cycle arrest at the G1 phase. In addition, inactivation of p53 completely abolished tumor suppression by MEG3, indicating that MEG3 tumor suppression is mediated by p53. In conclusion, our data support the hypothesis that MEG3 is a lncRNA tumor suppressor in the pituitary and its inactivation contributes to NFA development.

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

    PubMed

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

    2016-08-01

    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, indirectly, at the presence and position of the adenoma. The first aim of this retrospective study was to compare findings of a multiple slice dynamic scanning protocol with those of a single slice dynamic protocol using a single slice CT scanner. The second aim was to compare the CT findings with surgical findings, and surgical findings with histopathological findings. Computed tomography with single and multiple slice dynamic scanning protocols was performed in 86 dogs with pituitary-dependent hypercortisolism. Thirty dogs underwent transsphenoidal hypophysectomy and pituitary specimens were collected as tumor, normal, mixed and neurohypophyseal samples and processed for histology. The pituitary flush was not detected more frequent in multiple slice dynamic scanning series than in single slice dynamic scanning series. However, in non-enlarged pituitaries, the flush was seen significantly more frequently than in enlarged pituitaries. Prediction of the nature of the tissue during hypophysectomy by the surgeon was inconclusive. In conclusion, when using a single slice CT scanner, both single or multiple slice dynamic scanning protocols can be used for localization of the neurohypophyseal flush, and, indirectly, the adenoma. However, based on this study, the aim of surgery in dogs with pituitary-dependent hypercortisolism remains total adenohypophysectomy, and when the neurophypophysis is recognized, it may be left in situ.

  7. Posttransplantation lymphoproliferative disease involving the pituitary gland.

    PubMed

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

    2010-11-01

    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.

  8. Somatotroph pituitary tumors in budgerigars (Melopsittacus undulatus).

    PubMed

    Langohr, I M; Garner, M M; Kiupel, M

    2012-05-01

    A series of 11 pituitary tumors in budgerigars were classified on the basis of their clinical, gross, microscopic, and immunohistochemical characteristics. Affected birds were young to middle-aged. Clinically, neurologic signs--including difficulties flying, ataxia, and blindness--were most commonly reported. Additional clinical signs included weight loss, abnormal feathers or molting, increased respiratory efforts, and exophthalmos. Nine birds were diagnosed with chromophobic pituitary adenomas, and 2 birds had chromophobic pituitary carcinomas. Only 1 tumor was delimited to the pituitary gland; the other 10 variably invaded the brain, skull, and retrobulbar space. Distant metastases were identified in 2 birds. All tumors were immunohistochemically strongly positive for growth hormone, consistent with the diagnosis of somatotroph tumors. The common occurrence and early onset may suggest a genetic predisposition of budgerigars to develop somatotroph pituitary tumors with a high incidence of local invasion and with metastatic potential.

  9. Serum levels of beta-subunit of chorionic gonadotropin in patients with pituitary tumors.

    PubMed

    Gil-del-Alamo, P; Saccomanno, K; Lania, A; Pettersson, K S; Beck-Peccoz, P; Spada, A

    1995-07-01

    Many studies have shown that normal and tumoral pituitary is able to synthesize chorionic gonadotropin (CG). The aim of the present work was to investigate the circulating levels of free beta-subunit of CG (CG-beta) in a large number of patients with pituitary tumors in basal conditions and after thyrotropin-releasing hormone (TRH) injection. The study includes 27 healthy subjects, 23 patients with prolactinoma, 20 with growth hormone-secreting adenoma and 77 with non-functioning pituitary adenoma (NFPA). The CG-beta was evaluated using a new one-step immunometric assay employing two monoclonal antibodies directed against epitopes present only on the free CG-beta and showing a detection limit of 0.04 U/l and a cross-reactivity with complete CG < 0.01%. In basal conditions, serum CG-beta was undetectable in healthy subjects and in the majority of patients, while in seven patients with NFPA and four with prolactinoma the CG-beta values ranged between 0.05 and 0.72 U/l. In these 11 patients serum levels of intact CG were found within the normal range (normal range < 5 U/l), while two patients with NFPA and one with prolactinoma had levels of free alpha-subunit inappropriately high with respect to gonadotropins and thyrotropin. Injection of TRH caused CG-beta to increase in two out of 16 patients with NFPA, whereas it was ineffective in 12 healthy subjects and 10 patients with prolactinoma. The present data indicate that detectable level of CG-beta not associated with hypersecretion of the intact CG molecule may be observed in about 10% of patients with NFPA or prolactinoma, while abnormal CG-beta responses to TRH are observed infrequently in individual patients with NFPA.

  10. Identification of DLK1 variants in pituitary- and neuroendocrine tumors.

    PubMed

    Altenberger, T; Bilban, M; Auer, M; Knosp, E; Wolfsberger, S; Gartner, W; Mineva, I; Zielinski, C; Wagner, L; Luger, A

    2006-02-17

    In a gene chip analysis of common pituitary tumor types, one of the genes with the most impressive tissue-specific expression regulation was delta-like 1 (DLK1), which was strongly expressed in GH-secreting (GH-S) pituitary tumors. In addition to pituitary adenomas, various endocrine tumors were subjected to real-time-quantitative PCR revealing high expression of DLK1 in normal pituitary tissue, in GH-S-, in one prolactin-secreting pituitary adenoma and in pheochromocytomas. Additionally, three DLK1 gene-derived subvariants were identified. The first, lacking 204 bp--coding for epidermal growth factor-like domain 6 and parts of the juxtamembrane region--was named Secredeltin. In the other two splice variants (named Brevideltin and Brevideltinin), a stop codon is introduced due to a frame-shift, leading to truncated proteins of 204 and 213 aas, respectively.

  11. Pituitary tumors contain a side population with tumor stem cell-associated characteristics.

    PubMed

    Mertens, Freya; Gremeaux, Lies; Chen, Jianghai; Fu, Qiuli; Willems, Christophe; Roose, Heleen; Govaere, Olivier; Roskams, Tania; Cristina, Carolina; Becú-Villalobos, Damasia; Jorissen, Mark; Poorten, Vincent Vander; Bex, Marie; van Loon, Johannes; Vankelecom, Hugo

    2015-08-01

    Pituitary adenomas cause significant endocrine and mass-related morbidity. Little is known about the mechanisms that underlie pituitary tumor pathogenesis. In the present study, we searched for a side population (SP) in pituitary tumors representing cells with high efflux capacity and potentially enriched for tumor stem cells (TSCs). Human pituitary adenomas contain a SP irrespective of hormonal phenotype. This adenoma SP, as well as the purified SP (pSP) that is depleted from endothelial and immune cells, is enriched for cells that express 'tumor stemness' markers and signaling pathways, including epithelial-mesenchymal transition (EMT)-linked factors. Pituitary adenomas were found to contain self-renewing sphere-forming cells, considered to be a property of TSCs. These sphere-initiating cells were recovered in the pSP. Because benign pituitary adenomas do not grow in vitro and have failed to expand in immunodeficient mice, the pituitary tumor cell line AtT20 was further used. We identified a SP in this cell line and found it to be more tumorigenic than the non-SP 'main population'. Of the two EMT regulatory pathways tested, the inhibition of chemokine (C-X-C motif) receptor 4 (CXCR4) signaling reduced EMT-associated cell motility in vitro as well as xenograft tumor growth, whereas the activation of TGFβ had no effect. The human adenoma pSP also showed upregulated expression of the pituitary stem cell marker SOX2. Pituitaries from dopamine receptor D2 knockout (Drd2(-/-)) mice that bear prolactinomas contain more pSP, Sox2(+), and colony-forming cells than WT glands. In conclusion, we detected a SP in pituitary tumors and identified TSC-associated characteristics. The present study adds new elements to the unraveling of pituitary tumor pathogenesis and may lead to the identification of new therapeutic targets.

  12. Pituitary Tumors

    MedlinePlus

    ... pituitary is the "master control gland" - it makes hormones that affect growth and the functions of other glands in the body. Pituitary tumors are common, but often they don't cause health ... tumor produces hormones and disrupts the balance of hormones in your ...

  13. Pituitary Tumors

    MedlinePlus

    ... almost always benign (not cancerous), but can cause hormonal imbalances and interfere with the normal function of the pituitary gland. Because the pituitary affects so many functions of the body, ... the tumor mass or hormonal changes (either too much or too little hormone). ...

  14. Diagnosis and management of acromegaly: giant invasive adenoma.

    PubMed

    Cahyanur, Rahmat; Setyawan, Wawan; Sudrajat, Dedy G; Setyowati, Susie; Purnamasari, Dyah; Soewondo, Pradana

    2011-04-01

    Acromegaly is a rare disorder caused by excessive growth hormone. Majority of acromegaly are due to pituitary adenoma. It is estimated that 5% of pituitary adenoma become invasive and may grow to gigantic sizes (>4 cm in diameter). We would like to describe a man with giant invasive adenoma. We describe the case of 52-year-old man with acromegaly. The patient was presented to medical care because of hemichorea. He also had visual field defect, uncontrolled diabetes, and dyslipidemia. Hormonal profile showed increment of GH 2-hour after a standard 75-g oral glucose load and of high IGF-1 level with low level of FSH and LH. The next was performed by pituitary imaging. Magnetic resonance imaging showed a macroadenoma with diameter 2.3x3.5x6.6 cm3 that fills the sella tursica, and enlarges into suprasella, genu of corpus collosum, and invades third ventricle. This report describes a rare case of acromegalic patient with giant invasive adenoma. This could be a demonstrative case and lesson for diagnosis and manage acromegalic patient.

  15. PRKAR1A and the evolution of pituitary tumors.

    PubMed

    Kirschner, Lawrence S

    2010-09-15

    Carney complex (CNC) is an inherited tumor predisposition associated with pituitary tumors, including GH-producing pituitary adenomas and rare reports of prolactinomas. This disease is caused by mutations in PRKAR1A, which encodes the type 1A regulatory subunit of the cAMP-dependent protein kinase, PKA. Loss of PRKAR1A causes enhanced PKA signaling, which leads to pituitary tumorigenesis. Mutations in the gene have not been detected in sporadic pituitary tumors, but there is some data to suggest that non-genomic mechanisms may cause loss of protein expression. Unlike CNC patients, mice heterozygous for Prkar1a mutations do not develop pituitary tumors, although complete knockout of the gene in the Pit1 lineage of the pituitary produces GH-secreting pituitary adenomas. These data indicate that complete loss of Prkar1a/PRKAR1A is able to cause pituitary tumors in mice and men. The pattern of tumors is likely related to the signaling pathways employed in specific pituitary cell types.

  16. P27/CDKN1B Translational Regulators in Pituitary Tumorigenesis.

    PubMed

    Martins, C S; Camargo, R C; Saggioro, F P; Neder, L; Machado, H R; Moreira, A C; de Castro, M

    2016-12-01

    In pituitary tumors, P27(CDKN1B) is underexpressed. We aimed to clarify whether translational regulation underlies this phenomenon. This study evaluated the expression of P27/CDKN1B, its targets (CCNE1, CDK2) and translational regulators (DKC1, RPS13, miR221, miR222) and screened for DKC1 variants in sporadic pituitary adenomas. Samples were obtained during transsphenoidal surgery from 48 patients with pituitary adenomas: 10 ACTH-, 17 GH-secreting, and 21 nonfunctioning (NFPA). The control group comprised 7 normal pituitaries (NP) obtained during autopsies. Gene expression was assessed by RT-PCR and protein expression by immunohistochemistry. The 15 exons of DKC1 were sequenced. P27 protein underexpression was observed in all adenomas subtypes (p=0.001). CCNE1 mRNA (p=0.01) overexpression, but not protein, was observed in NFPA. No differential gene expression among groups was observed in CDKN1B regulators RPS13 (p=0.23) and DKC1 (p=0.34). The expression of miR221 and miR222 was similar among tumors and NP. Frequent DKC1 variants (SNPs) were found in exon 14 and in the 3'-UTR in similar frequency to NCBI-dsSNP databases. We also observed rare DKC1 variants in 11% of the studied tumor samples, indicating a high prevalence in pituitary adenomas, however, in silico studies failed to indicate deleterious effects. The high frequency of DKC1 variants may influence, in some extent, pituitary tumors development, without clear role in its tumorigenesis. Our data reinforce the P27 underexpression in pituitary adenomas and provide further evidence of the post-translational machinery involvement, although this phenomenon cannot be explained either by mis-expression of P27 translational regulators - DKC1, RPS13, miR221, miR222 - or directly by DKC1 mutations.

  17. Molecular genetics of the aip gene in familial pituitary tumorigenesis.

    PubMed

    Tahir, Asil; Chahal, Harvinder S; Korbonits, Márta

    2010-01-01

    Pituitary adenomas usually occur as sporadic tumors, but familial cases are now increasingly identified. As opposed to multiple endocrine neoplasia type 1 and Carney complex, in familial isolated pituitary adenoma (FIPA) syndrome no other disease is associated with the familial occurrence of pituitary adenomas. It is an autosomal dominant disease with incomplete variable penetrance. Approximately 20% of patients with FIPA harbour germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene located on 11q13. Patients with AIP mutations have an overwhelming predominance of somatotroph and lactotroph adenomas, which often present in childhood or young adulthood. AIP, originally identified as a molecular co-chaperone of several nuclear receptors, is thought to act as a tumor suppressor gene; overexpression of wild-type, but not mutant AIP, reduces cell proliferation while knockdown of AIP stimulates it. AIP is shown to bind various proteins, including the aryl hydrocarbon receptor, Hsp90, phosphodiesterases, survivin, RET and the glucocorticoid receptor, but currently it is not clear which interaction has the leading role in pituitary tumorigenesis. This chapter summarizes the available clinical and molecular data regarding the role of AIP in the pituitary gland.

  18. GENE THERAPY FOR THE TREATMENT OF PITUITARY TUMORS

    PubMed Central

    Rodriguez, Silvia S.; Castro, Maria G.; Brown, Oscar A.; Goya, Rodolfo G.; Console, Gloria M.

    2010-01-01

    Pituitary adenomas constitute the most frequent neuroendocrine pathology in humans. Current therapies include surgery, radiotherapy and pharmacological approaches. Although useful, none of them offers a permanent cure. Current research efforts to implement gene therapy in pituitary tumors include the treatment of experimental adenomas with adenoviral vector-mediated transfer of the suicide gene for thymidine kinase, which converts the prodrug ganciclovir into a toxic metabolite. In some cases, the suicide transgene has been placed under the control of pituitary cell-type specific promoters. Also, regulatable adenoviral vector systems are being assessed in gene therapy approaches for experimental pituitary tumors. Although the efficiency and safety of current viral vectors must be optimized before clinical use, they remain as highly promising therapeutic tools. PMID:20186255

  19. The retinoblastoma gene in human pituitary tumors

    SciTech Connect

    Cryns, V.L.; Arnold, A.; Alexander, J.M.; Klibanski, A. )

    1993-09-01

    Functional inactivation of the retinoblastoma (RB) tumor suppressor gene is important in the pathogenesis of many human tumors. Recently, the frequent occurrence of pituitary tumors was reported in mice genetically engineered to have one defective RB allele, a genetic background analogous to that of patients with familial retinoblastoma. The molecular pathogenesis of human pituitary tumors is largely unknown, and the potential role of RB gene inactivation in these neoplasms has not been examined. Consequently, the authors studied 20 human pituitary tumors (12 clinically nonfunctioning tumors, 4 somatotroph adenomas, 2 prolactinomas, and 2 corticotrophy adenomas) for tumor-specific allelic loss of the RB gene using a highly informative polymorphic locus within the gene. Control leukocyte DNA samples from 18 of these 20 patients were heterozygous at this locus, permitting genetic evaluation of their paired tumor specimens. In contrast to the pituitary tumors in the mouse model, none of these 18 human tumors exhibited RB allelic loss. These findings indicate that RB gene inactivation probably does not play an important role in the pathogenesis of common types of human pituitary tumors. 24 refs., 1 fig.

  20. Pituitary tumor

    MedlinePlus

    ... enough of its hormones. This condition is called hypopituitarism . The causes of pituitary tumors are unknown. Some ... Cyst Endocrine glands Gigantism Growth hormone test Hyperthyroidism Hypopituitarism Multiple endocrine neoplasia (MEN) I Prolactin blood test ...

  1. cAMP-specific PDE4 phosphodiesterases and AIP in the pathogenesis of pituitary tumors.

    PubMed

    Bolger, Graeme B; Bizzi, Mariana F; Pinheiro, Sergio V; Trivellin, Giampaolo; Smoot, Lisa; Accavitti, Mary-Ann; Korbonits, Márta; Ribeiro-Oliveira, Antonio

    2016-05-01

    PDE4 cyclic nucleotide phosphodiesterases regulate cAMP abundance in cells and therefore regulate numerous processes, including cell growth and differentiation. The rat PDE4A5 isoform (human homolog PDE4A4) interacts with the AIP protein (also called XAP2 or ARA-9). Germline mutations in AIP occur in approximately 20% of patients with Familial Isolated Pituitary Adenoma (FIPA) and 20% of childhood-onset simplex somatotroph adenomas. We therefore examined the protein expression of PDE4A4 and the closely related isoform PDE4A8 in normal human pituitary tissue and in pituitary adenomas. PDE4A4 had low expression in normal pituitary but was significantly overexpressed in somatotroph, lactotroph, corticotroph and clinically nonfunctioning gonadotroph adenomas (P<0.0001 for all subtypes). Likewise, PDE4A8 was expressed in normal pituitary and was also significantly overexpressed in the adenoma subtypes (P<0.0001 for all). Among the different adenoma subtypes, corticotroph and lactotroph adenomas were the highest and lowest expressed for PDE4A4, respectively, whereas the opposite was observed for PDE4A8. Naturally occurring oncogenic variants in AIP were shown by a two-hybrid assay to disrupt the ability of AIP to interact with PDE4A5. A reverse two-hybrid screen identified numerous additional variants in the tetratricopeptide repeat (TPR) region of AIP that also disrupted its ability to interact with PDE4A5. The expression of PDE4A4 and PDE4A8 in normal pituitary, their increased expression in adenomatous pituitary cells where AIP is meant to participate, and the disruption of the PDE4A4-AIP interaction by AIP mutants may play a role in pituitary tumorigenesis.

  2. Unusual Complication of Pituitary Macroadenoma: A Case Report and Review

    PubMed Central

    Abbas, Mohamed Said; AlBerawi, Mohamad Najm; Bozom, Issam Al; Shaikh, Nissar F.; Salem, Khalid Yacout

    2016-01-01

    Patient: Male, 48 Final Diagnosis: Pituitary apoplexy complicated by cerebral infarction Symptoms: Disturbed conscious level • loss of vision Medication: — Clinical Procedure: — Specialty: Radiology Objective: Unusual clinical course Background: Pituitary macroadenoma is a common benign tumor that usually presents with visual field defects or hormonal abnormalities. Cerebral infarction can be a complication of a large pituitary adenoma. We report a rare case of bilateral anterior cerebral arteries infarcts by a large pituitary macroadenoma with apoplexy. Case Report: A 48-year-old male patient presented with altered conscious level and sudden loss of vision for one-day duration. Magnetic resonance imaging of the brain showed a large seller and suprasellar hemorrhagic mass of pituitary origin, with associated bilateral areas of diffusion restriction in the frontal parasagittal regions, consistent with infarctions. Magnetic resonance angiography showed elevation and compression of A1 segment of both anterior cerebral arteries by the hemorrhagic pituitary macroadenoma. The patient underwent trans-sphenoidal resection of the pituitary adenoma, but unfortunately, ischemia was irreversible. Computed tomography (CT) done post-operatively showed hypodensity in the frontal and parietal parasagittal areas, which was also persistent in the follow up CT scans. The patient’s neurological function remained poor, with GCS of 8/15, in vegetative state. Conclusions: Vascular complications of the pituitary apoplexy, although uncommon, can be very severe and life threatening. Early detection of vascular compromise caused by hemorrhagic pituitary macroadenoma can prevent delay in intervention. Clinicians should also consider pituitary adenoma as a possible cause of stroke. PMID:27708253

  3. ACTH adenomas transforming their clinical expression: report of 5 cases.

    PubMed

    Zoli, Matteo; Faustini-Fustini, Marco; Mazzatenta, Diego; Marucci, Gianluca; De Carlo, Eugenio; Bacci, Antonella; Pasquini, Ernesto; Lanzino, Giuseppe; Frank, Giorgio

    2015-02-01

    OBJECT Adrenocorticotropic hormone (ACTH) adenomas have been recognized as a more aggressive and invasive subtype of pituitary adenomas. An additional and clinically relevant peculiarity of these tumors is their ability to modify their clinical expression from a silent form to Cushing disease or vice versa. The aim of this study was to review a series of patients with pituitary adenomas and analyze the clinical implications of the transformation of clinical expression in 5 cases that showed this phenomenon. METHODS The authors retrospectively reviewed a series of patients with pituitary adenoma and collected clinical, biohumoral, and neuroradiological data of those who presented with a transformation from silent ACTH adenomas to functioning tumors or vice versa. In all the cases, preoperative assessment consisted of brain MRI, ophthalmological examination, and complete baseline endocrinological investigation. In patients with clinical and/or biochemical findings suspicious for Cushing syndrome, a low-dose dexamethasone suppression test was performed to rule in or out this diagnosis. Endocrinological evaluations were repeated 1 month after surgery, 3 months after surgery, and every 6 months or annually thereafter. Ophthalmological evaluations and brain MRIs were repeated after 3 months and then every 6 or 12 months thereafter. RESULTS Five patients (2 men and 3 women) included in this series had corticotropic tumors that showed transformation from an endocrinologically silent form to manifest Cushing disease and vice versa. The mean age at presentation was 40 years (range 18-51 years). In 3 of these patients, a transformation from silent to functioning ACTH adenoma with manifest Cushing disease occurred. In 1 patient, the authors observed the transition from a functioning to a silent adenoma with spontaneous resolution of hypercortisolism. Another patient's silent adenoma "shifted" to a functioning adenoma and then regressed back to a silent form with spontaneous

  4. A case of pituitary apoplexy in pregnancy

    PubMed Central

    O'Sullivan, Anthony J; Davies, Mark A

    2014-01-01

    Summary Pituitary apoplexy is a rare event in pregnancy. A 41-year-old woman with a known pituitary microadenoma presented with visual disturbance and headache during the second trimester of pregnancy. Magnetic resonance imaging (MRI) demonstrated pituitary apoplexy with chiasmal compression. After treatment with corticosteroid therapy, she underwent transsphenoidal excision of the pituitary adenoma. Visual abnormalities were completely restored and pituitary function preserved. There was no evidence of impact on the foetus. The literature on the subject is reviewed with emphasis on the management of the apoplectic patient with mild and stable neuro-ophthalmological signs. Learning points There are no clear guidelines on the management of pituitary apoplexy in pregnancy. A multidisciplinary approach can minimise morbidity and mortality.Pituitary apoplexy has an unpredictable clinical course and determining which clinical situations warrant early surgery needs to take into consideration the presence and severity of neurological signs and their stability.The management of conscious apoplectic patients with absent or mild and stable neuro-ophthalmological signs is controversial. PMID:25031837

  5. Pituitary Gland Development and Disease: From Stem Cell to Hormone Production

    PubMed Central

    Davis, Shannon W.; Ellsworth, Buffy S.; Peréz Millan, María Inés; Gergics, Peter; Schade, Vanessa; Foyouzi, Nastaran; Brinkmeier, Michelle L.; Mortensen, Amanda H.

    2014-01-01

    Many aspects of pituitary development have become better understood in the last two decades. The signaling pathways regulating pituitary growth and shape have emerged, and the balancing interactions between the pathways are now appreciated. Markers for multi-potent progenitor cells are being identified, and signature transcription factors have been discovered for most hormone producing cell types. We now realize that pulsatile hormone secretion involves a 3-D integration of cellular networks. About a dozen genes are known to cause pituitary hypoplasia when mutated due to their essential roles in pituitary development. Similarly, a few genes are known that predispose to familial endocrine neoplasia, and several genes mutated in sporadic pituitary adenomas are documented. In the next decade we anticipate gleaning a deeper appreciation of these processes at the molecular level, insight into the development of the hypophyseal portal blood system, and evolution of better therapeutics for congenital and acquired hormone deficiencies and for common craniopharyngiomas and pituitary adenomas. PMID:24290346

  6. Pituitary gland development and disease: from stem cell to hormone production.

    PubMed

    Davis, Shannon W; Ellsworth, Buffy S; Peréz Millan, María Inés; Gergics, Peter; Schade, Vanessa; Foyouzi, Nastaran; Brinkmeier, Michelle L; Mortensen, Amanda H; Camper, Sally A

    2013-01-01

    Many aspects of pituitary development have become better understood in the past two decades. The signaling pathways regulating pituitary growth and shape have emerged, and the balancing interactions between the pathways are now appreciated. Markers for multipotent progenitor cells are being identified, and signature transcription factors have been discovered for most hormone-producing cell types. We now realize that pulsatile hormone secretion involves a 3D integration of cellular networks. About a dozen genes are known to cause pituitary hypoplasia when mutated due to their essential roles in pituitary development. Similarly, a few genes are known that predispose to familial endocrine neoplasia, and several genes mutated in sporadic pituitary adenomas are documented. In the next decade, we anticipate gleaning a deeper appreciation of these processes at the molecular level, insight into the development of the hypophyseal portal blood system, and evolution of better therapeutics for congenital and acquired hormone deficiencies and for common craniopharyngiomas and pituitary adenomas.

  7. [New aspects of tumor pathology of the pituitary].

    PubMed

    Saeger, W

    2015-05-01

    Pituitary adenomas have to be studied in detail for structural characteristics, especially regarding the degree of granulation and immunohistochemical hormone expression, such as growth hormone (GH), prolactin, adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), luteinizing hormone (LH) and proliferation markers (e.g. Ki-67 and p53) for correlation to clinical data and assessment of the prognosis. If histological and immunostaining data do not correlate to the patient data, explanations for the discrepancies must be found. All active adenoma types can also be present as inactive, so-called silent adenomas showing the same features. An increased Ki-67 index (> 3%), significant nuclear expression of protein p53 and mitoses are characteristic of atypical adenomas. Up to now the biological relevance of these atypical adenomas, especially their role as preneoplasms for pituitary carcinomas has not been fully elucidated. The only proof of a pituitary carcinoma is the existence of metastases. Extensive local invasion and a greatly increased Ki-67 index are not sufficient for this diagnosis. Craniopharyngiomas have to be classified into adamantinomatous types (intrasellar and suprasellar) and papillary types (only suprasellar). Regressive changes are found in adamantinomatous types only. Strong regression may lead to difficulties in the differential diagnosis of Rathke's cleft cysts with squamous metaplasia. Demonstration of nuclear expression of beta-catenin in these cases enables the diagnosis of craniopharyngioma. Papillary craniopharyngiomas are characterized by BRAF mutations that may be helpful in the differential diagnosis. All pituicytomas of the neurohypophysis, all spindle cell oncocytomas of the anterior pituitary and all granular cell tumors of the posterior pituitary express thyroid transcription factor 1 (TTF-1) and are thought to be variants of a common uniform spindle cell tumor of the pituitary.

  8. Glial-derived neurotropic factor and RET gene expression in normal human anterior pituitary cell types and in pituitary tumors.

    PubMed

    Japón, Miguel A; Urbano, Angel G; Sáez, Carmen; Segura, Dolores I; Cerro, Alfonso Leal; Diéguez, Carlos; Alvarez, Clara V

    2002-04-01

    Glial-derived neurotropic factor (GDNF) signaling is mediated through a 2-component system consisting of the so-called GDNF receptor-alpha (GFRalpha1), which binds to GDNF. This complex activates the tyrosine kinase receptor RET. In this paper we demonstrate GDNF, GFRalpha1, and RET mRNA and protein expression in the human anterior pituitary gland. Double immunohistochemistry of anterior pituitary sections showed GDNF immunoreactivity in more than 95% of somatotrophs and to a lesser extent in corticotrophs (20%); it was almost absent in the remaining cell types. Also, although more than 95% of somatotrophs were stained for RET, no positive immunostaining could be detected in other cell types. Furthermore, we have looked for GDNF and RET in human pituitary adenomas of various hormonal phenotypes. Strong positive immunostaining was found for c-RET in all of the GH-secreting adenomas screened as well as in 50% of ACTH-producing adenomas. Positive immunostaining for GDNF was found in all of the GH-secreting adenomas and in 10% of the corticotropinomas. Lastly, we found strong positive immunostaining for GFRalpha1 in 90% of the somatotropinomas and 50% of the corticotropinomas as well as in 1 of 8 prolactinomas and 1 of 13 nonfunctioning adenomas. All of the remaining pituitary tumors screened were negative for RET, GDNF, and GFRalpha1. This study indicates that GDNF may well be acting in the regulation of somatotroph cell growth and/or cell function in the normal human anterior pituitary gland. The expression of RET in all of the somatotropinomas and in 50% of the ACTH-producing tumors implies that GDNF and RET could be involved in the pathogenesis of pituitary tumors.

  9. Medullary thyroid carcinoma metastatic to the pituitary gland: an unusual site of metastasis.

    PubMed

    Williams, Michelle D; Asa, Sylvia L; Fuller, Gregory N

    2008-06-01

    We present a case of metastatic medullary thyroid carcinoma involving the pituitary gland of a 23-year-old woman with multiple endocrine neoplasia type 2b who presented with diabetes insipidus and visual loss. The diagnostic features, including cytomorphology and immunohistochemistry, used to differentiate pituitary adenoma from metastatic medullary carcinoma are discussed. Pituitary metastases and tumor-to-tumor metastases in this region are also highlighted.

  10. Optochiasmatic syndrome from adhesive arachnoiditis with coexisting hypophyseal adenoma: case report.

    PubMed

    Iraci, G; Carteri, A; Marin, G

    1977-03-01

    Adhesive arachnoiditis is an occasional finding during neurosurgical operations for pituitary adenoma, previously treated by radiation therapy. A case where an arachnoidal process was found in combination with an eosinophilic pituitary adenoma, which had never been treated by irradiation, is reported. A 44-year-old woman at the time of surgery with scarce endocrinologic symptoms had suffered visual loss from 2 episodes, 18 years apart. Analysis of her symptoms, neuro-ophthalmologic findings and neurodadiologic features suggest that her visual damage was due to an optochiasmatic arachnoiditis, rather than to the tumor itself.

  11. Contralateral adrenal suppression on adrenocortical scintigraphy provides good evidence showing subclinical cortisol overproduction from unilateral adenomas.

    PubMed

    Katabami, Takuyuki; Ishii, Satoshi; Obi, Ryusei; Asai, Shiko; Tanaka, Yasushi

    2016-12-30

    Unilateral and/or predominant uptake on adrenocortical scintigraphy (ACS) may be related to autonomous cortisol overproduction in patients with subclinical Cushing's syndrome (SCS). However, there is no information regarding whether increased tracer uptake on the tumor side or decreased uptake on the contralateral side on ACS is more greatly associated with inappropriate cortisol production. Therefore, we evaluated the relationship between quantitative (131)I-6β-iodomethyl-norcholesterol ((131)I-NP-59) uptake in both adrenal glands and parameters of autonomic cortisol secretion and attempted to set a cut off for SCS detection. The study included 90 patients with unilateral adrenal adenoma who fulfilled strict criteria. The diagnosis of SCS was based on serum cortisol ≥3.0 μg/dL after 1-mg dexamethasone suppression test (DST) with at least 1 other hypothalamus-pituitary-adrenal axis function abnormality. Twenty-two (27.7%) subjects were diagnosed with SCS. The uptake rate on the affected side in the SCS group was comparable to that in the non-functioning adenoma group. In contrast, the uptake rate on the contralateral side was lower and the laterality ratio significantly higher in the SCS group. The two ACS indices were correlated with serum cortisol levels after a 1-mg DST, but uptake on the tumor side was not. Tumor size was also important for the functional statuses of adrenal tumors and NP-59 imaging patterns. The best cut-off point for the laterality ratio to detect SCS was 3.07. These results clearly indicate that contralateral adrenal suppression in ACS is good evidence showing subclinical cortisol overproduction.

  12. Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland.

    PubMed

    Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

    2016-04-25

    Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2(+) and Sox9(+) adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors.

  13. Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland

    PubMed Central

    Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

    2016-01-01

    Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2+ and Sox9+ adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors. PMID:27109116

  14. [Thyrotropin--TSH secreting pituitary tumor].

    PubMed

    Zieliński, Grzegorz; Podgórski, Jan K; Warczyńska, Agnieszka; Koziarski, Andrzej; Zgliczyński, Wojciech

    2002-01-01

    Thyrotropin-releasing pituitary tumors represent 0.9 to 2.8% of all pituitary adenomas. They cause secondary or central hyperthyroidism. The diagnosis of these tumors has been increasing in the past 20 years. It was produced by introduction of the sensitive immunoradio-metric assay of TSH and better radiological imaging (magnetic resonance imaging). TSH--secreting pituitary adenomas are aggressive and invasive neoplasms. Most reports describe a poor outcome after pharmacological therapy, surgery and radiation therapy. Presently the diagnosis of thyrotropin-secreting pituitary tumor is based on the lack of: a. inhibition of TSH levels in the presence of increased free thyroid hormones; b. response of TSH to stimulation with TRH; c. and presence of a abnormal, neoplastic(adenomatous) intrasellar or parasellar mass. Surgical excision (selective adenomectomy) by the transsphenoidal route is the first treatment. Craniotomy should be reserved for parasellar tumors with significant lateral extension. Pharmacological pretreatment with long acting somatostatin analogues is recently a standard before surgery. This medical treatment of the TSH-omas is effective in reducing TSH and free thyroid hormone plasma levels. Administration of the somatostatin analogues causing tumor mass shrinkage and changes consistency. This pretreatment is effective therapy and improves surgical outcome especially in patients harbouring macroadenomas. Radiotherapy is noncurative and produces long term complications (hypopituitarism). Authors present and discuss current cure criteria of TSH-omas with reference to their clinical experience.

  15. Hereditary Pituitary Hyperplasia with Infantile Gigantism

    PubMed Central

    Gläsker, Sven; Vortmeyer, Alexander O.; Lafferty, Antony R. A.; Hofman, Paul L.; Li, Jie; Weil, Robert J.; Zhuang, Zhengping

    2011-01-01

    Context: We report hereditary pituitary hyperplasia. Objective: The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. Design: The study is a retrospective analysis of three cases from one family. Setting: The study was conducted at the National Institutes of Health, a tertiary referral center. Patients: A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. Interventions: The condition was treated by total hypophysectomy. Main Outcome Measure(s): We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. Results: All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. Conclusions: This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development. PMID:21976722

  16. Non-functional Avionics Requirements

    NASA Astrophysics Data System (ADS)

    Paulitsch, Michael; Ruess, Harald; Sorea, Maria

    Embedded systems in aerospace become more and more integrated in order to reduce weight, volume/size, and power of hardware for more fuel-effi ciency. Such integration tendencies change architectural approaches of system ar chi tec tures, which subsequently change non-functional requirements for plat forms. This paper provides some insight into state-of-the-practice of non-func tional requirements for developing ultra-critical embedded systems in the aero space industry, including recent changes and trends. In particular, formal requi re ment capture and formal analysis of non-functional requirements of avionic systems - including hard-real time, fault-tolerance, reliability, and per for mance - are exemplified by means of recent developments in SAL and HiLiTE.

  17. Heterozygous gsp mutation renders ion channels of human somatotroph adenoma cells unresponsive to growth hormone-releasing hormone.

    PubMed

    Yasufuku-Takano, J; Takano, K; Takei, T; Fukumoto, S; Teramoto, A; Takakura, K; Yamashita, N; Fujita, T

    1999-05-01

    Ionic mechanisms play an important role in the regulation of hormone secretion. The GHRH-induced GH release by human GH-secreting cells is transmitted through protein kinase A (PKA), which activates nonselective cation current (NSCC) and induces membrane depolarization, intracellular Ca2+ increase, and GH secretion. To evaluate whether ionic mechanisms have pathophysiological significance in GH oversecretion of GH-secreting pituitary adenomas, we examined four adenomas with constitutively active Gs alpha mutation (gsp mutation) and compared with three gsp-negative adenomas. In primary-cultured cells of gsp-positive adenomas, GHRH did not increase the NSCC under voltage-clamp experiments. Detailed examination showed that NSCC was maximally activated at the basal level and application of GHRH did not increase the current in these adenomas. Furthermore, by using single-cell RT-PCR method, we demonstrated for the first time at the single cell level that gsp mutation is heterozygous in GH-secreting pituitary adenomas. These indicate that heterozygous gsp mutation fully activates NSCC at the basal level, which may account for the GH oversecretion in gsp-positive GH-secreting pituitary adenomas.

  18. Pharmacoeconomic aspects of the treatment of pituitary gland tumours

    PubMed Central

    Sowiński, Jerzy; Piątek, Katarzyna; Zybek, Ariadna; Ruchała, Marek

    2013-01-01

    Nowadays physicians are under economic pressure; therefore therapeutic decisions based on safety, efficacy, and the effectiveness of the medication also require economic analysis. The aim of this review is to discuss data concerning the cost-effectiveness of drug therapy in patients with hormonally active pituitary adenomas, namely growth hormone, adrenocorticotropic hormone, thyroid-stimulating hormone-secreting pituitary adenomas, prolactinoma and pituitary incidentaloma. In acromegalic patients using lanreotide is cheaper for health care payers and more convenient for physicians and patients because of the opportunity for self/partner injections, lower clogging risk and possibility of longer intervals between injections, while the efficacy is comparable with octreotide. Patients with prolactinomas should be treated with novel dopamine agonists, such as cabergoline or quinagolide, however, bromocriptine still remains a cheaper and almost as effective alternative. There are no easy methods or algorithms, but in general, extracting the maximum value from the investment in treatment is essential. PMID:23788980

  19. Pharmacoeconomic aspects of the treatment of pituitary gland tumours.

    PubMed

    Sowiński, Jerzy; Sawicka, Nadia; Piątek, Katarzyna; Zybek, Ariadna; Ruchała, Marek

    2013-01-01

    Nowadays physicians are under economic pressure; therefore therapeutic decisions based on safety, efficacy, and the effectiveness of the medication also require economic analysis. The aim of this review is to discuss data concerning the cost-effectiveness of drug therapy in patients with hormonally active pituitary adenomas, namely growth hormone, adrenocorticotropic hormone, thyroid-stimulating hormone-secreting pituitary adenomas, prolactinoma and pituitary incidentaloma. In acromegalic patients using lanreotide is cheaper for health care payers and more convenient for physicians and patients because of the opportunity for self/partner injections, lower clogging risk and possibility of longer intervals between injections, while the efficacy is comparable with octreotide. Patients with prolactinomas should be treated with novel dopamine agonists, such as cabergoline or quinagolide, however, bromocriptine still remains a cheaper and almost as effective alternative. There are no easy methods or algorithms, but in general, extracting the maximum value from the investment in treatment is essential.

  20. Pituitary gland and beta-catenin signaling: from ontogeny to oncogenesis.

    PubMed

    Gueorguiev, Maria; Grossman, Ashley B

    2009-01-01

    Although pituitary tumors are mostly benign, they share certain molecular events with more malignant neoplasia, although their precise pathogenesis is far from established. The acquisition of new functional characteristics during their evolution suggests a multistep process that leads to tumor transformation. Mutations in classical tumor suppressor genes or oncogenes are infrequently associated with pituitary tumorigenesis. However, alterations in different signaling pathways, especially those involved in pituitary gland development, have emerged as significant features in pituitary adenomas. In particular, changes in inhibitory components of the beta-catenin pathway and its relationship to the cadherin family of peptides may well play an important role in tumorigenesis. We review and assess the role of the beta-catenin signaling pathway in the pathogenesis of pituitary adenomas.

  1. Thyrotropinoma with Graves’ disease detected by the fusion of indium-111 octreotide scintigraphy and pituitary magnetic resonance imaging

    PubMed Central

    Okuyucu, Kursat; Alagoz, Engin; Arslan, Nuri; Taslipinar, Abdullah; Deveci, Mehmet Salih; Bolu, Erol

    2016-01-01

    Thyroid-stimulating hormone-secreting pituitary adenoma (TSHoma) is a rare benign endocrinological tumor which produces TSH in the pituitary gland. Herein, we presented a female patient having TSHoma with Graves’ disease during and just after pregnancy that we found by indium-111 octreotide scintigraphy while investigating the patient for hyperthyroidism symptoms. PMID:27095865

  2. Vanishing Pituitary Macroadenoma: A Case Report

    PubMed Central

    Stepanyan, Hayk; Payne, Russell; Ouyang, Tao; Zacharia, Brad E

    2016-01-01

    Pituitary macroadenomas are the most common suprasellar lesions in adults and are typically managed surgically through transsphenoidal resection when symptomatic. Due to their close proximity to the optic chiasm, pituitary macroadenomas often present with signs of bitemporal hemianopsia. Alternatively, these tumors can cause mass effect, thus presenting with signs of elevated intracranial pressure or can present with signs and symptoms of endocrine dysfunction. Here, we discuss a 55-year-old male diagnosed with a non-functioning pituitary macroadenoma (NFPA) based on cranial imaging, ophthalmologic exam, and endocrine evaluation. Following diagnosis, the patient was scheduled for transsphenoidal hypophysectomy. On magnetic resonance imaging (MRI) done three and half months later for surgical planning, the tumor had almost completely regressed and only residual pituitary tissue was noted. We describe the presentation and clinical course of the patient, summarize chief differential diagnoses, and discuss potential managements of these conditions. PMID:27900232

  3. Endobronchial pleomorphic adenoma

    PubMed Central

    Ali, Syed Rizwan; Arrossi, Andrea Valeria; Mehta, Atul C.; Frye, Laura; Mazzone, Peter; Almeida, Francisco

    2016-01-01

    Pleomorphic adenomas are the most common tumors of the salivary glands. Rarely, they occur as benign lesions in the lungs in both the central airways and the lung parenchyma. Herein, we present a case of a 60-year-old smoker who was incidentally found to have an endobronchial mass while undergoing evaluation for a lung nodule. During bronchoscopy, a smooth globular nodule was identified at the main carina and removed using electrocautery snare. Histopathology examination revealed this to be a pleomorphic adenoma. PMID:28031854

  4. Silent Corticogonadotroph Adenomas: Clinical and Cellular Characteristics and Long-Term Outcomes

    PubMed Central

    Cooper, Odelia; Ben-Shlomo, Anat; Bonert, Vivien; Bannykh, Serguei; Mirocha, James

    2010-01-01

    Silent corticotrophins adenomas (SCAs) are clinically silent and non-secreting but immunostain positively for ACTH. We hypothesize that SCAs comprise both corticotroph and gonadotroph characteristics. Cohort analysis from 1994–2008 with follow-up time ranging from 1–15 years in a tertiary referral center. We compared preoperative and postoperative clinical results and tumor cytogenesis in 25 SCAs and 84 nonfunctioning adenomas in 109 consecutive patients diagnosed pre-operatively with nonfunctioning pituitary adenomas. Clinical outcomes were radiologic and hormonal measures. Pathologic outcomes were expression of relevant pituitary hormones, tissue-specific transcription factors, and electron microscopy features. Preoperative SCA presentation was similar to that observed for nonfunctioning adenomas. However, SCAs recurred postoperatively at a median of 3 years vs. 8 years for nonfunctioning adenomas (p<0.0001). Fifty-four percent of patients with SCAs had new onset postoperative hypopituitarism vs. 17% of nonfunctioning adenomas (p<0.025). SCAs (n=18) were immunopositive for ACTH, cytoplasmic and nuclear SF-1, NeuroD1, DAX-1, and alpha-gonadotropin subunit, but Tpit negative, and co-expression of tumor ACTH with either SF-1 or LH was detected. In contrast, functional corticotroph adenomas (n=11) were immunopositive for ACTH, nuclear SF-1, NeuroD1, and Tpit, but negative for DAX-1, a gonadotroph cell transcription factor. Gonadotroph adenomas (n=23) were immunonegative for ACTH and Tpit but positive for nuclear SF-1, NeuroD1, and DAX-1. SCA electron microscopy demonstrated ultrastructural features consistent with corticotroph and gonadotroph cells. As SCAs exhibit features consistent with both corticotroph and gonadotroph cytologic origin, we propose a pathologic and clinically distinct classification of SCAs as silent corticogonadotroph adenomas. PMID:20717480

  5. Stages of Pituitary Tumors

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  6. What Are Pituitary Tumors?

    MedlinePlus

    ... testicles. Prolactin causes milk production in the female breast. Its function in men is not known. Posterior pituitary The smaller, back part of the pituitary gland, known as the posterior pituitary, is really an ...

  7. Transsphenoidal surgery for pituitary tumours

    PubMed Central

    Massoud, A; Powell, M; Williams, R; Hindmarsh, P; Brook, C

    1997-01-01

    Accepted 29 January 1997
 OBJECTIVES—Transsphenoidal surgery (TSS) is the preferred method for the excision of pituitary microadenomas in adults. This study was carried out to establish the long term efficacy and safety of TSS in children.
STUDY DESIGN—A 14 year retrospective analysis was carried out on 23 children (16 boys and seven girls), all less than 18 years of age, who had undergone TSS at our centre.
RESULTS—Twenty nine transsphenoidal surgical procedures were carried out. The most common diagnosis was an adrenocorticotrophic hormone (ACTH) secreting adenoma (14 (61%) patients). The median length of follow up was 8.0 years (range 0.3-14.0 years). Eighteen (78%) patients were cured after the first procedure. No death was related to the operation. The most common postoperative complication was diabetes insipidus, which was transient in most patients. Other complications were headaches in two patients and cerebrospinal fluid leaks in two patients. De novo endocrine deficiencies after TSS in children were as follows: three (14%) patients developed panhypopituitarism, eight (73%) developed growth hormone insufficiency, three (14%) developed secondary hypothyroidism, and four (21%) developed gonadotrophin deficiency. Permanent ACTH deficiency occurred in five (24%) patients, though all patients received postoperative glucocorticoid treatment until dynamic pituitary tests were performed three months after TSS.
CONCLUSIONS—TSS in children is a safe and effective treatment for pituitary tumours, provided it is performed by surgeons with considerable experience and expertise. Surgical complications are minimal. Postoperative endocrine deficit is considerable, but is only permanent in a small proportion of patients.

 • Transsphenoidal surgery is a safe and effective treatment for pituitary tumours in children • Transsphenoidal surgery should be performed by surgeons with considerable experience and expertise • Surgical complications of

  8. [Hyperthyroidism due to a TSH-secreting pituitary tumor].

    PubMed

    Ban, Y; Kushima, K; Hara, H; Nagakura, H; Niitani, H; Azukizawa, M; Tsuboi, K; Ishikawa, N; Mimura, T; Ito, K

    1987-01-20

    A 28-year-old female with a 12-year history of goiter is presented. She had both clinical and laboratory evidence of hyperthyroidism, and her serum TSH was persistently and markedly elevated after treatment with antithyroid drugs. A TRH stimulation test resulted in no further rise in serum TSH after cessation of medication. Menses were regular and serum prolactin levels were normal. Serum LH and FSH responses to LHRH stimulation test were normal. No other evidence of pituitary or peripheral endocrine deficiencies existed. She underwent a subtotal thyroidectomy followed by 131I therapy three years later. A pituitary adenoma with sphenoidal and suprasellar extension was completely removed by transphenoidal approach. On light microscopy, it was mostly composed of chromophobic cells with occasional calcification showing sinusoidal pattern. On electron microscopy, most of the cells contained fine granules, which suggested thyrotroph. The immunoperoxidase technique revealed TSH beta in the cytoplasm of some adenoma cells. Three days postoperatively the patient's serum TSH levels returned to normal. TRH stimulation test produced a normal response in serum TSH. The patient was diagnosed hypothyroid by laboratory findings and is currently on thyroid replacement therapy. The patient became pregnant and delivered twice prior to the operation for pituitary adenoma. The previously reported TSH secreting adenomas associated with hyperthyroidism were reviewed.

  9. Genetics, gene expression and bioinformatics of the pituitary gland.

    PubMed

    Davis, Shannon W; Potok, Mary Anne; Brinkmeier, Michelle L; Carninci, Piero; Lyons, Robert H; MacDonald, James W; Fleming, Michelle T; Mortensen, Amanda H; Egashira, Noboru; Ghosh, Debashis; Steel, Karen P; Osamura, Robert Y; Hayashizaki, Yoshihide; Camper, Sally A

    2009-04-01

    Genetic cases of congenital pituitary hormone deficiency are common and many are caused by transcription factor defects. Mouse models with orthologous mutations are invaluable for uncovering the molecular mechanisms that lead to problems in organ development and typical patient characteristics. We are using mutant mice defective in the transcription factors PROP1 and POU1F1 for gene expression profiling to identify target genes for these critical transcription factors and candidates for cases of pituitary hormone deficiency of unknown aetiology. These studies reveal critical roles for Wnt signalling pathways, including the TCF/LEF transcription factors and interacting proteins of the groucho family, bone morphogenetic protein antagonists and targets of notch signalling. Current studies are investigating the roles of novel homeobox genes and pathways that regulate the transition from proliferation to differentiation, cell adhesion and cell migration. Pituitary adenomas are a common human health problem, yet most cases are sporadic, necessitating alternative approaches to traditional Mendelian genetic studies. Mouse models of adenoma formation offer the opportunity for gene expression profiling during progressive stages of hyperplasia, adenoma and tumorigenesis. This approach holds promise for the identification of relevant pathways and candidate genes as risk factors for adenoma formation, understanding mechanisms of progression, and identifying drug targets and clinically relevant biomarkers.

  10. NMR characterization of pituitary tumors

    SciTech Connect

    Osbakken, M.; Gonzales, J.; Page, R.

    1984-01-01

    Twelve patients (5 male, 7 female, mean age 37.9 +- 20) with pituitary tumors were extensively evaluated with NMR imaging using a 1.5K gauss resistive magnet. Saturation recovery (SR), inversion recovery (IR) and spin echo (SE) pulse sequences were used for qualitative characterization of the lesions. T/sub 1/ calculations were also performed for brain and pituitary. Tumor histology and endocrine status were correlated with NMR data. All tumors were large with suprasellar extension (6 with prolactin secretion, 6 without). Pituitary T/sub 1/'s ranged from .2 to .64, the mean T/sub 1/ being longer than that of brain (Brain = .4 +- .04; Pit = .48 +- .14). 3 patients with histological evidence of homogeneous adenomas had long T/sub 1/'s (0.58 +- .05). 3 patients with evidence of recent or old hemorhage into the pituitary had much shorter T/sub 1/'s (0.29 +- .12). There was no relationship between prolactin secretion and T/sub 1/. Qualitative T/sub 1/ and T/sub 2/ information can be obtained by using a combination of SR, IR, and SE images. Using this method in the patients, homogeneous adenomas had similar T/sub 1/'s and longer T/sub 2/'s compared to the brain, while patients with bleeds had shorter T/sub 1/'s and T/sub 2/'s. Image T/sub 1/ characteristics correlated well with the calculated T/sub 1/ values. The range of T/sub 1/ (and potentially T/sub 2/) values which occur in apparently similar lesions are most likely due to anatomical and pathophysiological variations in these lesions. It may be ultimately possible to separate different types of pathological processes based on NMR image T/sub 1/ and T/sub 2/ characteristics after careful comparative studies of NMR and histological data are completed. The combination of calculated T/sub 1/ and T/sub 2/ with image T/sub 1/ and T/sub 2/ information may also be useful in further characterization of lesions.

  11. Autocrine IL-6 mediates pituitary tumor senescence.

    PubMed

    Sapochnik, Melanie; Haedo, Mariana R; Fuertes, Mariana; Ajler, Pablo; Carrizo, Guillermo; Cervio, Andrés; Sevlever, Gustavo; Stalla, Günter K; Arzt, Eduardo

    2017-01-17

    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.

  12. V3 vasopressin receptor and corticotropic phenotype in pituitary and nonpituitary tumors.

    PubMed

    de Keyzer, Y; René, P; Lenne, F; Auzan, C; Clauser, E; Bertagna, X

    1997-01-01

    Pituitary corticotropic cells express a specific vasopressin receptor, called V1b or V3, through which vasopressin stimulates corticotropin secretion. We recently cloned a cDNA coding for this receptor and showed that it belongs to the G protein-coupled receptor family. V3 mRNA is readily detected by RT-PCR in normal human pituitaries and corticotropic pituitary adenomas but not in PRL or GH-secreting adenomas, thus demonstrating that, like POMC itself and the CRH receptor, V3 is a marker of the corticotropic phenotype. Nuclease protection experiments suggest that V3 is overexpressed in some corticotropic adenomas, and thus may play a role in tumor development by activating the phospholipase C-signalling pathway. In addition analysis of its expression in nonpituitary neuroendocrine tumors showed a striking association with carcinoids of the lung responsible for the ectopic ACTH syndrome.

  13. Expression of cyclooxygenase-2 (COX-2) in pituitary tumours

    PubMed Central

    Sokołowski, Grzegorz; Bałdys-Waligórska, Agata; Trofimiuk, Małgorzata; Adamek, Dariusz; Hubalewska-Dydejczyk, Alicja; Gołkowski, Filip

    2012-01-01

    Summary Background Microvessel density in angiogenesis is regarded as a prognostic factor of tumour invasiveness, independent of cell proliferation. In recent studies of pituitary tumours, correlation between the expression of cyclooxygenase-2 (COX-2) and micro-vascularization density and microvessel surface density has been established. We studied the expression of COX-2 in different types of pituitary adenomas to determine the usefulness of COX-2 expression as a prognostic factor of tumour progression or recurrence in patients with hypophyseal tumours. Material/Methods We retrospectively studied a group of 60 patients of mean age 46.7±17.6 (range, 18 to 85) years who underwent pituitary tumour surgery. Expression of COX-2, as determined by immunohistochemistry, was analyzed in relation to histopathology features of tumour, clinical symptoms, MR imaging and post-operative recurrence/progression of disease. Results COX-2 was expressed in adenomas of 87% of patients, with a median index value of 57.5% [IQR=60.5]. Highest COX-2 expression was observed in hormonally inactive adenomas and gonadotropinomas and lowest in prolactinomas. We found no differences in COX-2 expression with respect to patient age, gender, tumour size, degree of tumour invasiveness, or whether tumours were immunopositive or immunonegative for pituitary hormones, nor have we found any relation between COX-2 expression and recurrence or progression of tumour size. Conclusions COX-2 does not appear to be a predictive factor for recurrence or progression of tumour size. Nevertheless, due to the observed relatively high expression of COX-2 in pituitary adenomas, further studies with COX-2 inhibitors are justified in these tumours. PMID:22460097

  14. Metabolic Glucose Status and Pituitary Pathology Portend Therapeutic Outcomes in Acromegaly

    PubMed Central

    Cheng, Sonia; Serri, Omar; L. Asa, Sylvia; Ezzat, Shereen

    2013-01-01

    Introduction Acromegaly is frequently associated with impaired glucose tolerance and/or diabetes. To evaluate the relationship between glucose metabolism and acromegaly disease, we evaluated 269 consecutive patients from two referral centres. Methods Clinical presentation, pituitary tumor size and invasiveness, and pituitary pathology were captured in a dedicated database. Results 131 women and 138 men with a mean age of 53.8 years were included. Of these, 201 (74.7%) presented with a macroadenoma and 18 (6.7%) with a microadenoma. Radiographic invasion was present in 91 cases (33.8%). Mean tumor diameter was 1.86 cm (0.2–4.6). Pituitary histopathologic findings revealed pure GH-producing somatotroph adenomas (SA) in 147 patients, prolactin-production by mixed lactotroph (LA) and SA or mammosomatotroph adenoma (MSA) in 46 [22.4%], acidophil stem cell adenoma in 6 [2.9%], and other diagnoses in 6 [2.9%]. Medical treatment included octreotide in 96 [36.9%] and in combination with pegvisomant or dopamine agonists in 63 [24.2%]. Nearly 80% of patients achieved IGF-1 normalization. Importantly, patients with pure somatotroph adenomas were significantly more likely to present with abnormal glucose metabolism [48.7%] than those with mixed adenomas [9.7%] [p<0.001] independent of GH/IGF-1 levels or tumor invasiveness. Abnormal glucose metabolism and pituitary pathology also remained linked following IGF-1 normalization. Moreover patients with pure SA and abnormal glucose metabolism were significantly (p<0.001) less likely to achieve disease remission despite the same therapeutic strategies. Conversely, patients with mixed adenomas were more likely (OR: 2.766 (95% CI: 1.490–5.136) to achieve disease remission. Conclusions Patients with pure somatotroph adenomas are more likely than those with mixed adenomas to exhibit abnormal glucose metabolism. PMID:24039977

  15. Mild pituitary phenotype in 3- and 12-month-old Aip-deficient male mice.

    PubMed

    Lecoq, Anne-Lise; Zizzari, Philippe; Hage, Mirella; Decourtye, Lyvianne; Adam, Clovis; Viengchareun, Say; Veldhuis, Johannes D; Geoffroy, Valérie; Lombès, Marc; Tolle, Virginie; Guillou, Anne; Karhu, Auli; Kappeler, Laurent; Chanson, Philippe; Kamenický, Peter

    2016-10-01

    Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene predispose humans to pituitary adenomas, particularly of the somatotroph lineage. Mice with global heterozygous inactivation of Aip (Aip(+/-)) also develop pituitary adenomas but differ from AIP-mutated patients by the high penetrance of pituitary disease. The endocrine phenotype of these mice is unknown. The aim of this study was to determine the endocrine phenotype of Aip(+/-) mice by assessing the somatic growth, ultradian pattern of GH secretion and IGF1 concentrations of longitudinally followed male mice at 3 and 12 months of age. As the early stages of pituitary tumorigenesis are controversial, we also studied the pituitary histology and somatotroph cell proliferation in these mice. Aip(+/-) mice did not develop gigantism but exhibited a leaner phenotype than wild-type mice. Analysis of GH pulsatility by deconvolution in 12-month-old Aip(+/-) mice showed a mild increase in total GH secretion, a conserved GH pulsatility pattern, but a normal IGF1 concentration. No pituitary adenomas were detected up to 12 months of age. An increased ex vivo response to GHRH of pituitary explants from 3-month-old Aip(+/-) mice, together with areas of enlarged acini identified on reticulin staining in the pituitary of some Aip(+/-) mice, was suggestive of somatotroph hyperplasia. Global heterozygous Aip deficiency in mice is accompanied by subtle increase in GH secretion, which does not result in gigantism. The absence of pituitary adenomas in 12-month-old Aip(+/-) mice in our experimental conditions demonstrates the important phenotypic variability of this congenic mouse model.

  16. Cell cycle dysregulation in pituitary oncogenesis.

    PubMed

    Muşat, Madalina; Vax, Vladimir V; Borboli, Ninetta; Gueorguiev, Maria; Bonner, Sarah; Korbonits, Márta; Grossman, Ashley B

    2004-01-01

    in comparison with normal pituitaries, the load of p27 protein expression in corticotroph adenomas and pituitary carcinomas was shown to be much lower than those in normal pituitary tissue or other types of pituitary adenoma, suggesting that post-translational processing of p27 accelerates its removal from the nucleus. In respect to p27 degradation and its cellular compartmentalization, several pathways have been explored. Malignant tumours are associated with increased nuclear immunostaining for Jun-activation binding protein-1 (Jab1) which is responsible for phosphorylated p27 export from the nucleus. Corticotrophinomas are characterized by massively increased phosphorylation of p27 on Thr187, but are not associated with changes in Jab1. Macrophage inhibitory factor (MIF), which binds and inactivates Jab1, was noted to be over-expressed in tumours with abundant Jab1, suggesting that it may be part of a compensatory mechanism to moderate Jab1 activity. Proteasomal degradation of p27 requires its ubiquitylation by the SCF ubiquitin ligase, with specific addressing by the F-box protein Skp2 and its co-factor Cks1. Pituitary tumours with high p27 protein expression showed significantly less Skp2 expression than samples with low p27 immunostaining, suggesting that increased Skp2 could play at least a part in this process. No difference was observed in Cks1 mRNA levels between normal pituitaries and pituitary adenomas. The present data suggest that inhibition of growth and tumour development is sensitive not only to the absolute levels of p27 protein, but also to its cellular compartmentalization. Very recent findings from our group have established up-regulation of the serine-threonine kinase Akt in pituitary tumours compared to normal pituitary, which may cause phosphorylation of p27 on Thr157 and cytoplasmic retention of p27. PTTG protein is highly expressed in various human tumours, including pituitary tumours. While its mRNA levels are low in normal pituitary

  17. Pituitary apoplexy associated with cortisol-induced hyperglycemia and acute delirium.

    PubMed

    Weng, Yi-Ming; Chang, Meng-Wei; Weng, Chia-Sui

    2008-11-01

    Pituitary apoplexy indicates pituitary adenoma hemorrhage, which could result in acute pituitary insufficiency and mortality. The typical symptoms are headache, visual disturbance, nausea, vomiting, altered mental status, and panhypopituitarism. However, cortisol-induced hyperglycemia and acute delirium could be an initial presentation of a pituitary adenoma hemorrhage with stormy release of the adrenocorticotrophic hormone. A 28-year-old woman presented with severe vomiting, irritable state, and delusion. She had medical history of irregular menstrual cycles and marked body weight gain after her second childbirth 8 years ago. She was diagnosed of diabetic ketoacidosis 2 days before this visiting at local medical department. On physical examination, Cushing appearance without definite neurological deficit was disclosed. Further blood tests revealed high blood sugar, cortisol, and adrenocorticotrophic hormone levels without evidence of diabetic ketoacidosis. The brain computed tomography and magnetic resonance imaging showed pituitary macroadenoma and pituitary hemorrhage. Cushing disease with pituitary apoplexy was then diagnosed. Conservative management with delayed neurosurgery was applied. The patient became clear with normalized cortisol and blood sugar levels soon after. Follow-up computed tomography scan of the brain revealed no progression of tumor bleeding or mass effect. To our knowledge, pituitary apoplexy associated with cortisol-induced hyperglycemia and acute delirium has never been reported before. This case reminds us of pituitary apoplexy and its rare manifestations.

  18. Computed tomographic demonstration of the effects of bromocriptine on pituitary microadenoma size

    SciTech Connect

    Bonneville, J.F.; Poulignot, D.; Cattin, F.; Couturier, M.; Mollet, E.; Dietemann, J.L.

    1982-05-01

    A group of 17 strictly intrasellar prolactin-secreting pituitary adenomas between 2 and 9 mm in size was examined by computed tomography before and after bromocriptine therapy of 3 months to 1 year duration. These findings were compared with clinical and biological data. Bromocriptine therapy was effective clinically and biologically in 14 of the 17 cases. Of the 15 intrasellar adenomas in nonpregnant patients treated with bromocriptine, six disappeared completely with normalization of the pituitary appearance, five decreased approximately 50% in volume (three showed an increase in density, two a decrease), and four remained unchanged in size (two showed increased density, two showed very low densities).

  19. Akting and cycling: a tale of the pituitary.

    PubMed

    Grossman, Ashley B; Korbonits, Márta

    2004-01-01

    Pituitary tumours are characterized by a series of phenotypic abnormalities, but the molecular nature of the underlying defects has proved peculiarly intractable. Oncogenes and tumour suppressor genes involved in other tumours do not appear to play a major role in the pathogenesis of pituitary tumours. In addition, germline genetic disorders in which pituitary tumours are a common feature have not shed much light on the more common sporadic tumour. A number of defects in specific feedback regulation in the secretory tumours have been identified, but it is presently unclear as to what extent these are a consequence of the tumour, possibly enhancing its growth or survival, rather than the cause. However, recent studies on the cell cycle have demonstrated significant abnormalities that have been traced to a cytoplasmic kinase which appears to be abnormally expressed in the majority of pituitary adenomas, and we are beginning to see a possible unifying abnormality.

  20. Pituitary disease in MEN type 1 (MEN1): data from the France-Belgium MEN1 multicenter study.

    PubMed

    Vergès, Bruno; Boureille, Françoise; Goudet, Pierre; Murat, Arnaud; Beckers, Albert; Sassolas, Geneviève; Cougard, Patrick; Chambe, Béatrice; Montvernay, Corinne; Calender, Alain

    2002-02-01

    To date, data on pituitary adenomas in MEN type 1 (MEN1) still have to be evaluated. We analyzed the data of a large series of 324 MEN1 patients from a French and Belgian multicenter study. Data on pituitary disease were compared with those from 110 non-MEN1 patients with pituitary adenomas, matched for age, year of diagnosis, and follow-up period. Genetic analysis of the MEN1 gene was performed in 197 of the MEN1 patients. In our MEN1 series, pituitary disease occurred in 136 of 324 (42%), less frequently than hyperparathyroidism (95%, P < 0.001) and endocrine enteropancreatic tumors (54%, P < 0.01). Mean age of onset of pituitary tumors was 38.0+/-15.3 yr (range, 12-83 yr). Pituitary disease was associated with hyperparathyroidism in 90% of cases, with enteropancreatic tumors in 47%, with adrenal tumors in 16%, and with thoracic neuroendocrine tumors in 4%. Pituitary disease was the initial lesion of MEN1 in 17% of all MEN1 patients. MEN1 pituitary adenomas were significantly more frequent in women than in men (50% vs. 31%, P < 0.001). Among the 136 pituitary adenomas, there were 85 prolactinomas and 12 GH-secreting, 6 ACTH-secreting, 13 cosecreting, and 20 nonsecreting tumors. Eighty-five percent of MEN1-related pituitary lesions were macroadenomas (vs. 42% in non-MEN1 patients, P < 0.001), including 32% of invasive cases. Among secreting adenomas, hormonal hypersecretion was normalized, after treatment, in only 42% (vs. 90% in non-MEN1 patients, P < 0.001), with a median follow-up of 11.4 yr. No correlation was found between the type of MEN1 germ-line mutation and the presence or absence of pituitary adenoma. Our study, based on a large group of MEN1 patients, shows that pituitary adenomas occur in 42% of the cases and are characterized by a larger size and a more aggressive presentation than without MEN1.

  1. Undescended parathyroid adenoma

    PubMed Central

    Maawy, Ali A; Oh, Deborah K; Bouvet, Michael

    2015-01-01

    Undescended parathyroid adenomas are rare, representing 0.08% of all parathyroid adenomas; however, they make up 7% of the underlying cause of failed cervical exploration in patients with persistent primary hyperparathyroidism. A 43-year-old woman with no significant medical or family history presented with fatigue and was diagnosed with primary hyperparathyroidism; however, preoperative imaging including sestamibi scan and ultrasound was unable to identify the hyperfunctioning gland. She underwent a neck exploration and hemithyroidectomy and partial parathyroidectomy with failure of resolution of her disease. Subsequent work up including a CT of the neck demonstrated a 1.9 cm mass adjacent to the left submandibular gland. This was removed with postoperative normalisation of the patient's serum calcium and parathyroid hormone levels. PMID:25737222

  2. Is IGSF1 involved in human pituitary tumor formation?

    PubMed Central

    Faucz, Fabio R.; Horvath, Anelia D.; Azevedo, Monalisa F.; Levy, Isaac; Bak, Beata; Wang, Ying; Xekouki, Paraskevi; Szarek, Eva; Gourgari, Evgenia; Manning, Allison D.; de Alexandre, Rodrigo Bertollo; Saloustros, Emmanouil; Trivellin, Giampaolo; Lodish, Maya; Hofman, Paul; Anderson, Yvonne C; Holdaway, Ian; Oldfield, Edward; Chittiboina, Prashant; Nesterova, Maria; Biermasz, Nienke R.; Wit, Jan M.; Bernard, Daniel J.; Stratakis, Constantine A.

    2014-01-01

    IGSF1 is a membrane glycoprotein highly expressed in the anterior pituitary. Pathogenic mutations in the IGSF1 gene (on Xq26.2) are associated with X-linked central hypothyroidism and testicular enlargement in males. In this study we tested the hypothesis that IGSF1 is involved in the development of pituitary tumors, especially those that produce growth hormone (GH). IGSF1 was sequenced in 21 patients with gigantism or acromegaly and 92 healthy individuals. Expression studies with a candidate pathogenic IGSF1 variant were carried out in transfected cells and immunohistochemistry for IGSF1 was performed in sections from GH-producing adenomas, familial somatomammotroph hyperplasia and in normal pituitary. In two male patients, and in one female, with somatomammotroph hyperplasia from the same family, we identified the sequence variant p.N604T, which in silico analysis suggested could affect IGSF1 function. Of 60 female controls, two carried the same variant, and seven were heterozygous for other variants. Immunohistochemistry showed increase IGSF1 staining in the GH-producing tumor from the patient with the IGSF1 p.N604T variant compared to a GH-producing adenoma from a patient negative for any IGSF1 variants and to normal control pituitary tissue. The IGSF1 gene appears polymorphic in the general population. A potentially pathogenic variant identified in the germline of three patients with gigantism from the same family (segregating with the disease) was also detected in two healthy female controls. Variations in IGSF1 expression in pituitary tissue in patients with or without IGSF1 germline mutations point to the need for further studies of IGSF1 action in pituitary adenoma formation. PMID:25527509

  3. Thyrotrophin (TSH)-secreting pituitary macroadenoma with cavernous sinus invasion.

    PubMed

    Kon, Y C; Loh, K C; Tambyah, J A; Lim, L H; Marshall, J C

    2001-09-01

    Thyrotrophin (TSH)-secreting pituitary adenomas, although rare, should be recognised as a possible cause of normal or elevated serum TSH in the presence of elevated serum free thyroid hormone levels. Clinical hyperthyroidism may be mild or absent. Early recognition provides the best chance for surgical cure. We report a patient with a TSH-secreting pituitary tumour with cavernous sinus invasion. This case illustrates that multiple modalities of treatment are often necessary and complementary in achieving control of tumour growth and hormonal hypersecretion when these tumours are diagnosed late.

  4. Evidence of cellular senescence during the development of estrogen-induced pituitary tumors.

    PubMed

    Sabatino, Maria Eugenia; Petiti, Juan Pablo; Sosa, Liliana Del Valle; Pérez, Pablo Anibal; Gutiérrez, Silvina; Leimgruber, Carolina; Latini, Alexandra; Torres, Alicia Inés; De Paul, Ana Lucía

    2015-06-01

    Although pituitary adenomas represent 25% of intracranial tumors, they are usually benign, with the mechanisms by which these tumors usually avoid an invasive profile and metastatic growth development still remaining unclear. In this context, cellular senescence might constitute a plausible explanation for the benign nature of pituitary adenomas. In this study, we investigated the emergence of cellular senescence as a growth control mechanism during the progression of estrogen-induced pituitary tumors. The quantification of Ki67-immunopositive cells in the pituitaries of estrogenized male rats after 10, 20, 40, and 60 days revealed that the mitogenic potential rate was not sustained for the whole period analyzed and successively decreased after 10 days of estrogen exposure. In addition, the expression of cellular senescence features, such as the progressive rise in the enzymatic senescence-associated b-galactosidase (SA-b-gal) activity, IL6, IL1b, and TGFb expression, was observed throughout pituitary tumor development. Furthermore, tumoral pituitary cells also displayed nuclear pATM expression, indicating activated DNA damage signaling, with a significant increase in p21 expression also being detected. The associations among DNA damage signaling activation, SA-b-gal expression, and p21 may provide a reliable combination of senescence-associated markers for in vivo pituitary senescence detection. These results suggest a role for this cellular process in the regulation of pituitary cell growth. Thus, cellular senescence should be conceived as a contributing component to the benign nature of pituitary adenomas, thereby influencing the capability of the pituitary gland to avoid unregulated cell proliferation.

  5. Thyrotropin-secreting pituitary tumor and Hashimoto's disease: a novel association.

    PubMed

    Iskandar, Said B; Supit, Edwin; Jordan, Richard M; Peiris, Alan N

    2003-09-01

    A 69-year-old man was referred for elevated thyroid hormone levels. He had no symptoms apart from mild hyperhidrosis and heat intolerance with occasional headaches. Past medical history included a right hemithyroidectomy for a multinodular goiter and Hashimoto's disease. At presentation the patient had a firm, slightly enlarged left thyroid lobe. There were no visual abnormalities, and the rest of the physical findings were unremarkable. Laboratory findings included elevated values of free T4, free T3, total T3, thyrotropin-secreting hormone (TSH), antithyroglobulin, and antimicrosomal antibodies. Normal values were found for cortisol, prolactin, testosterone, follicle-stimulating hormone, luteinizing hormone, alpha-subunit, and thyroid-stimulating immunoglobulin. Thyroid 123I scan showed an increased 5-hour uptake of 23% and a 24-hour uptake of 53% with a diffuse uniform enlargement of the left side. TSH level did not increase after a thyrotropin-releasing hormone stimulation test. Serum sex hormone binding globulin was elevated. Magnetic resonance imaging of the pituitary revealed a pituitary macroadenoma with suprasellar extension to the optic chiasm. Histologic examination of the adenoma after transsphenoidal hypophysectomy showed cells that stained positive for TSH. TSH-secreting pituitary adenomas account for 1% of functioning pituitary tumors and are an exceedingly rare cause of hyperthyroidism. To our knowledge, this is the first report of pituitary tumor inducing hyperthyroidism in the setting of Hashimoto's disease. There is a possibility that TSH elevation related to Hashimoto's disease might have contributed to the development of a TSH-secreting pituitary adenoma.

  6. HMGA1-pseudogene expression is induced in human pituitary tumors

    PubMed Central

    Esposito, Francesco; De Martino, Marco; D'Angelo, Daniela; Mussnich, Paula; Raverot, Gerald; Jaffrain-Rea, Marie-Lise; Fraggetta, Filippo; Trouillas, Jacqueline; Fusco, Alfredo

    2015-01-01

    Numerous studies have established that High Mobility Group A (HMGA) proteins play a pivotal role on the onset of human pituitary tumors. They are overexpressed in pituitary tumors, and, consistently, transgenic mice overexpressing either the Hmga1 or the Hmga2 gene develop pituitary tumors. In contrast with HMGA2, HMGA1 overexpression is not related to any rearrangement or amplification of the HMGA1 locus in these tumors. We have recently identified 2 HMGA1 pseudogenes, HMGA1P6 and HMGA1P7, acting as competitive endogenous RNA decoys for HMGA1 and other cancer related genes. Here, we show that HMGA1 pseudogene expression significantly correlates with HMGA1 mRNA levels in growth hormone and nonfunctioning pituitary adenomas likely inhibiting the repression of HMGA1 through microRNAs action. According to our functional studies, these HMGA1 pseudogenes enhance the proliferation and migration of the mouse pituitary tumor cell line, at least in part, through their upregulation. Our results point out that the overexpression of HMGA1P6 and HMGA1P7 could contribute to increase HMGA1 levels in human pituitary tumors, and then to pituitary tumorigenesis. PMID:25894544

  7. Pleomorphic adenoma of the trachea.

    PubMed

    Sim, Da Woon; Oh, In Jae; Kim, Kyu Sik; Choi, Yoo Duk; Kwon, Yong Soo

    2014-07-01

    Endobronchial pleomorphic adenoma is an extremely rare condition. A 32-year-old woman with exertional dyspnea and cough presented with a carinal mass on chest CT scan. The tumor was successfully removed by rigid bronchoscopy using argon plasma coagulation. Biopsy confirmed the diagnosis of pleomorphic adenoma.

  8. Hepatocellular adenoma: An update.

    PubMed

    Vijay, Adarsh; Elaffandi, Ahmed; Khalaf, Hatem

    2015-11-08

    Hepatocellular adenomas (HCA) are rare benign liver tumors. Recent technological advancements have helped in the early identification of such lesions. However, precise diagnosis of hepatocellular incidentalomas remains challenging. Studies at the molecular level have provided new insights into the genetics and pathophysiology of these lesions. These in turn have raised questions over their existing management modalities. However, the rarity of the tumor still restricts the quality of evidence available for current recommendations and guidelines. This article provides a comprehensive review on the etiology, molecular biology, patho-physiology, clinical manifestations, and complications associated with HCA. It also elaborates on the genetic advancements, existing diagnostic tools and current guidelines for management for such lesions.

  9. Pituitary Somatostatin Receptor Signaling

    PubMed Central

    Ben-Shlomo, Anat; Melmed, Shlomo

    2010-01-01

    Somatostatin (SRIF) is a major regulator of pituitary function, mostly inhibiting hormone secretion and to a lesser extent pituitary cell growth. Five SRIF receptor subtypes (SSTR1–5) are ubiquitously expressed G-protein coupled receptors. In the pituitary, SSTR1, SSTR2, SSTR3 and SSTR5 are expressed, with SSTR2 and SSTR5 predominating. As new SRIF-analogs have recently been introduced for treatment of pituitary disease, we evaluate the current knowledge of cell-specific pituitary SRIF receptor signaling and highlight areas of future research for comprehensive understanding of these mechanisms. Elucidating pituitary SRIF receptor signaling enables understanding of pituitary hormone secretion and cell growth, and also points to future therapeutic development for pituitary disorders. PMID:20149677

  10. Growth hormone is a cellular senescence target in pituitary and nonpituitary cells.

    PubMed

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

    2013-08-27

    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.

  11. CT of pituitary abscess

    SciTech Connect

    Fong, T.C.; Johns, R.D.; Long, M.; Myles, S.T.

    1985-06-01

    Pituitary abscess is a rare condition, with only 50 cases reported in the literature. Of those, 29 cases were well documented for analysis. Preoperative diagnosis of pituitary abscess is difficult. The computed tomographic (CT) appearance of pituitary abscess was first described in 1983; the abscess was depicted by axial images with coronal reconstruction. The authors recently encountered a case of pituitary abscess documented by direct coronal CT of the sella turcica.

  12. Molecular genetic studies of sporadic pituitary tumors

    SciTech Connect

    Boggild, M.D.; Jenkinson, S.; McTernan, P.; Perrett, C.W.; Clayton, R.N.; Thakker, R.V.; Pistorello, M.; Boscaro, M.; Scanarini, M.

    1994-02-01

    Tumor formation may result from the activation of dominant oncogenes or by inactivation of recessive, tumor suppressor genes. The role of such mutations in the development of pituitary tumors has been studied. Tumors from 88 patients, representing the 4 major classes of adenoma, were investigated. In DNA extracted from matched leukocyte and tumor samples, allelic deletions were sought with 15 probes identifying restriction, fragment length polymorphisms on chromosomes 1, 5, 10, 11, 13, 17, 20, and 22. Evidence of amplification or rearrangement of 10 recognized cellular oncogenes (N-ras, mycL1, mycN, myc, H-ras, bcl1, H-stf1, sea, kraS2, and fos) was sought in tumor DNA. Activating dominant mutations of G{sub s{alpha}} were detected using the polymerase chain reaction to amplify exons 7-10 and hybridizing the product to normal and mutant allele-specific oligonucleotides. Allelic deletions on chromosome 11 were identified in 16 tumors (18%) representing all 4 major subtypes. Deletions on other autosomes were observed in less than 6% of tumors. Three adenomas had deletions on multiple autosomes, 2 of these were aggressive and recurrent. Mutations of G{sub s{alpha}} were confirmed to be specific to somatotrophinomas, being identified in 36% of such tumors in this series. No evidence of amplification or rearrangement of other recognized cellular oncogenes was found. Inactivation of a recessive oncogene on chromosome 11 is an important and possibly early event in the development of the four major types of pituitary adenoma, whereas activating mutations of G{sub s{alpha}} are confirmed to be specific to somatotropinomas. Two aggressive tumors were found to have multiple autosomal losses, suggesting a multistep progression in the development of tumors of this phenotype. 30 refs., 3 figs., 1 tab.

  13. Epidural Anesthesia for Caesarean Section in a Pregnant Patient with Pituitary Macroadenoma

    PubMed Central

    Babu, D. Dinesh; Sureshkumar, K; Patil, Shubhada A.

    2014-01-01

    Anaesthesia for patient with pituitary adenoma posted for non-neurosurgical surgeries is a challenge to the anaesthesiologist with the risk of sudden change in intracranial dynamics during administration of spinal anaesthesia or during stress response of general anaesthesia. There is a chance of increase in tumour size during antenatal period. A careful assessment of pituitary function and a screening of visual field and fundus examination are essential to rule out any mass effect. We are presenting the anaesthetic management of patient with pituitary macroadenoma posted for elective caesarean section done under epidural anaesthesia due to its rarity. PMID:25177577

  14. Evaluation of the retinal nerve fibre layer and ganglion cell complex thickness in pituitary macroadenomas without optic chiasmal compression

    PubMed Central

    Cennamo, G; Auriemma, R S; Cardone, D; Grasso, L F S; Velotti, N; Simeoli, C; Di Somma, C; Pivonello, R; Colao, A; de Crecchio, G

    2015-01-01

    Purpose The aim of this prospective study was to measure the thickness of the circumpapillary retinal nerve fibre layer (cpRNFL) and the ganglion cell complex (GCC) using spectral domain optical coherence tomography (SD-OCT) in a cohort of consecutive de novo patients with pituitary macroadenomas without chiasmal compression. Patients and methods Twenty-two consecutive patients with pituitary macroadenoma without chiasmal compression (16 men, 6 women, aged 45.2±14.6 years, 43 eyes) entered the study between September 2011 and June 2013. Among them, 31.8% harboured a growth hormone-secreting pituitary adenoma, 27.3% a prolactin-secreting pituitary adenoma, 27.3% a corticotrophin-secreting pituitary adenoma, and 13.6% a non-secreting pituitary tumour. Eighteen subjects (nine females, nine males, mean age 36.47±6.37 years; 33 eyes) without pituitary adenoma, with normal ophthalmic examination, served as controls. In both patients and controls, cpRNFL and GCC thicknesses were measured by SD-OCT. Results Patients were significantly older (P=0.02) than controls. Best corrected visual acuity, intraocular pressure, colour fundus photography, and automatic perimetry test were within the normal range in patients and controls. Conversely, cpRNFL (P=0.009) and GCC (P<0.0001) were significantly thinner in patients than in controls. The average GCC (r=0.306, P=0.046) significantly correlated with the presence of arterial hypertension. OCT parameters did not differ significantly between patients with a tumour volume above the median and those with a tumour volume below the median. Conclusion Pituitary macroadenomas, even in the absence of chiasmal compression, may induce GCC and retinal nerve fibre layer thinning. SD-OCT may have a role in the early diagnosis and management of patients with pituitary tumours. PMID:25853400

  15. Pituitary macroadenoma presenting with pituitary apoplexy, acromegaly and secondary diabetes mellitus - a case report

    PubMed Central

    Nganga, Hudson Kamau; Lubanga, Reuben Paul

    2013-01-01

    Pituitary adenomas are associated with significant morbidity. The usual symptoms on presentation are of endocrine dysfunction and mass effects. A 31-year-old African female presented with headache, irregular menses, blurring of vision in the right eye and complete loss of vision in the left eye for 1 year. She had coarse facial features, enlarged hands and feet. Her right eye had temporal hemianopia with decreased visual acuity and her left eye had no perception of light. Investigations revealed an elevated fasting blood sugar and an elevated prolactin and growth hormone level. A CT scan and MRI done showed a hemorrhagic pituitary macroadenoma. She was put on bromocriptine, ocreotide, analgesics and insulin. Thereafter, she underwent transphenoidal surgery, where near total resection of the tumor was achieved. Patient is doing well post-operatively. This case highlights the importance of the use of a high clinical index of suspicion and radiological findings in diagnosis. PMID:24062868

  16. A primer on pituitary injury for the obstetrician gynecologist: Simmond's disease, Sheehan's Syndrome, traumatic injury, Dahan's Syndrome, pituitary apoplexy and lymphocytic hypophysitis.

    PubMed

    Dahan, Michael H; Tan, Seang L

    2017-04-01

    The pituitary gland plays a critical role in reproduction. In response to the hypothalamus the anterior pituitary secretes prolactin, thyroid-stimulating hormone, adreno-corticotropic hormone, follicle-stimulating hormone, luteinizing hormone and growth hormone. Dysregulation in these hormones often lead to reproductive failure. Multiple mechanisms of pituitary injury exist. Simmond's disease is atrophy or destruction of the anterior lobe of the pituitary gland resulting in hypopituitarism. Sheehan's syndrome is post-partum pituitary injury due to massive hemorrhage. Traumatic injury resulting in hemorrhage in a non-pregnancy state can also cause partial or complete pituitary failure. Dahan's syndrome is pituitary injury due to severe vasospasm, without significant hemorrhage. Pituitary apoplexy is infarction of a pituitary adenoma and intra-mass hemorrhage with result injury to hormone production by the gland. Lymphocytic infiltration is the most common cause of hypophysitis and the mechanism is often unknown, although it may be autoimmune-related. The mechanism and treatments of each of these pathologies will be discussed in a context of reproduction.

  17. Mitotane reduces human and mouse ACTH-secreting pituitary cell viability and function.

    PubMed

    Gentilin, Erica; Tagliati, Federico; Terzolo, Massimo; Zoli, Matteo; Lapparelli, Marcello; Minoia, Mariella; Ambrosio, Maria Rosaria; Degli Uberti, Ettore C; Zatelli, Maria Chiara

    2013-09-01

    Medical therapy for Cushing's disease (CD) is currently based on agents mainly targeting adrenocortical function. Lately, pituitary-directed drugs have been developed, with limited efficacy. Mitotane, a potent adrenolytic drug, has been recently investigated for the treatment of CD, but the direct pituitary effects have not been clarified so far. The aim of our study was to investigate whether mitotane may affect corticotroph function and cell survival in the mouse pituitary cell line AtT20/D16v-F2 and in the primary cultures of human ACTH-secreting pituitary adenomas, as an in vitro model of pituitary corticotrophs. We found that in the AtT20/D16v-F2 cell line and in primary cultures, mitotane reduces cell viability by inducing caspase-mediated apoptosis and reduces ACTH secretion. In the AtT20/D16v-F2 cell line, mitotane reduces Pomc expression and blocks the stimulatory effects of corticotropin-releasing hormone on cell viability, ACTH secretion, and Pomc expression. These effects were apparent at mitotane doses greater than those usually necessary for reducing cortisol secretion in Cushing's syndrome, but still in the therapeutic window for adrenocortical carcinoma treatment. In conclusion, our results demonstrate that mitotane affects cell viability and function of human and mouse ACTH-secreting pituitary adenoma cells. These data indicate that mitotane could have direct pituitary effects on corticotroph cells.

  18. The pituitary stalk effect: is it a passing phenomenon?

    PubMed

    Bergsneider, Marvin; Mirsadraei, Leili; Yong, William H; Salamon, Noriko; Linetsky, Michael; Wang, Marilene B; McArthur, David L; Heaney, Anthony P

    2014-05-01

    Most patients with large pituitary tumors do not exhibit hyperprolactinemia as a result of pituitary lactotroph disinhibition (stalk effect). Studies have demonstrated that increased intrasellar pressure is associated with both "stalk effect" hyperprolactinemia and pituitary insufficiency. Our primary hypothesis was that, despite continued disinhibition, lactotroph failure is responsible for normoprolactinemia in patients with large macroadenomas. As a corollary, we proposed that the hyperprolactinemia phase, which presumably would precede the insufficiency/normoprolactinemic state, would more likely be discovered in premenopausal females and go unnoticed in males. Prospective, consecutive surgical series of 98 patients of clinically nonfunctional pituitary adenomas. Lactotroph insufficiency was inferred by the coexistence of insufficiency in another pituitary axis. The existence of pre-operative lactotroph disinhibition was inferred based on comparison of pre- versus post-operative prolactin levels. 87 % of patients with tumor size >20 mm and normoprolactinemia had pituitary insufficiency. Pre-operative prolactin in patients with pituitary insufficiency were lower than those with intact pituitary function. Prolactin levels dropped in nearly all patients, including patients with normoprolactinemia pre-operatively. Premenopausal women had smaller tumors and higher pre-operative prolactin levels compared to males. No premenopausal female exhibited evidence of pituitary insufficiency. Our study provides suggestive evidence that the "stalk effect" pathophysiology is the norm rather than the exception, and that the finding of normoprolactinemia in a patient with a large macroadenoma is likely a consequence of lactotroph insufficiency. In males, the hyperprolactinemia window is more likely to be missed clinically due to an absence of prolactin-related symptoms.

  19. [A case of GH and TSH secreting pituitary macroadenoma].

    PubMed

    Gołkowski, Filip; Buziak-Bereza, Monika; Stefańska, Agnieszka; Trofimiuk, Małgorzata; Pantofliński, Jacek; Huszno, Bohdan; Czepko, Ryszard; Adamek, Dariusz

    2006-01-01

    A case of GH and TSH secreting pituitary macroadenoma is reported. A 45-year-old female presented clinical features of acromegaly (the abnormal growth of the hands and feet, with lower jaw protrusion), diabetes mellitus, hypertension, nodular goiter and hyperthyroidism of unclear origin. NMR pituitary imaging revealed intra and extrasellar tumor. The laboratory examinations showed very high plasma levels of GH and IGF-1 and normal level of TSH coexisting with high plasma levels of free thyroid hormones. Pharmacological pretreatment with somatostatin analogues caused the substantial reduction of GH and TSH plasma levels. Histological and immunohistochemical examination of the tissue obtained at transsphenoidal surgery showed GH and TSH secreting adenoma. The laboratory examinations after surgery showed normal GH and IGF-1 plasma levels and reduced insulin requirement, what indicates radical operation. The very low plasma levels of TSH and free thyroid hormones after surgery and immunohistochemical examination suggest central hyperthyroidism due to TSH secreting pituitary tumor (thyrotropinoma).

  20. Hypertrichosis in a horse with alimentary T-cell lymphoma and pituitary involvement.

    PubMed

    Mitsui, Ikki; Jackson, L Paige; Couëtil, Laurent L; Lin, Tsang L; Ramos-Vara, José A

    2007-01-01

    A 13-year-old Quarterhorse mare had a 6-month history of diarrhea, progressive weight loss, and lethargy. At presentation the mare was hirsute, had hyperhidrosis, and abnormal fat distribution in addition to severe diarrhea. A presumptive clinical diagnosis of protein-losing enteropathy and pituitary pars intermedia dysfunction was made. T-cell lymphoma was diagnosed in a rectal biopsy specimen. The owner elected to euthanize the mare because of poor prognosis and the severity of the disease. At necropsy, the mare had hypertrichosis and the pituitary gland was diffusely enlarged. Histologically, neoplastic lymphocytes infiltrated the gastrointestinal mucosa, mesenteric lymph nodes, and the pituitary gland. In addition, there was hyperplasia of the pituitary gland pars intermedia. Pituitary adenoma was not present. Hypertrichosis in this case could have been triggered by a combination of adenomatous hyperplasia of pars intermedia and lymphoma resulting in disruption of the hypothalamic dopaminergic tone or disruption of the hypothalamic thermoregulatory center.

  1. Anterior pituitary cell antibodies detected in Hashimoto's thyroiditis and Graves' disease.

    PubMed

    Kobayashi, I; Inukai, T; Takahashi, M; Ishii, A; Ohshima, K; Mori, M; Shimomura, Y; Kobayashi, S; Hashimoto, A; Sugiura, M

    1988-10-01

    An immunofluorescence study using unfixed cryostat sections of rat pituitary glands was carried out on sera from 34 patients with Hashimoto's thyroiditis, 28 patients with Graves' disease, 10 patients with thyroid adenoma and 50 healthy subjects. After absorption of sera with rat liver tissues, 19 of 34 patients retained reactivity to anterior pituitary cell antibodies (PCA, 55.8%). On the other hand, immunofluorescence in anterior pituitary cells was faint and detected in only 2 of 28 patients with Graves' disease (7.1%) after absorption of their sera with rat liver aceton powder. A similar result was also obtained when PCA were compared in the sera of Hashimoto's thyroiditis and Graves' disease with high titers of thyroid microsomal autoantibodies. PCA were detected neither in the sera of patients with thyroid adenoma nor in the healthy subjects. The present study suggests that PCA were considerably more prevalent in Hashimoto's thyroiditis than in Graves' disease.

  2. Pertussis toxin inhibits somatostatin-induced K/sup +/ conductance in human pituitary tumor cells

    SciTech Connect

    Yamashita, N.; Kojima, I.; Shibuya, N.; Ogata, E.

    1987-07-01

    The effect of pertussis toxin on somatostatin-induced K/sup +/ current was examined in dissociated human pituitary tumor cells obtained from two acromegalic patients. Somatostatin-induced hyperpolarization or K/sup +/ current was observed in 20 of 23 cells in adenoma 1 and 10 of 11 cells in adenoma 2. After treatment with pertussis toxin for 24 h, these responses were completely suppressed (0/14 in adenoma, 1, 0/10 in adenoma 2). Spontaneous action potentials, K/sup +/, Na/sup +/, and Ca/sup 2 +/ currents were well preserved after pertussis toxin treatment. When crude membrane fraction was incubated with (/sup 32/P)NAD, a 41K protein was ADP-ribosylated by pertussis toxin. Hormone release was inhibited by somatostatin and this inhibition was blocked by pertussis toxin treatment.

  3. A case of coexistence of TSH/GH-secreting pituitary tumor and papillary thyroid carcinoma: Challenges in pathogenesis and management.

    PubMed

    Kiatpanabhikul, Phatharaporn; Shuangshoti, Shanop; Chantra, Kraisri; Navicharern, Patpong; Kingpetch, Kanaungnit; Houngngam, Natnicha; Snabboon, Thiti

    2017-03-06

    Co-existence of thyrotropin/growth hormone-secreting pituitary adenoma with differentiated thyroid carcinoma is exceedingly rare, with less than 15 cases having been reported. Its clinical presentation and treatment strategy are challenging. We report a case of pituitary macroadenoma, with clinical syndromes of acromegaly and hyperthyroidism, and a thyroid nodule, with cytologically confirmed to be a papillary thyroid carcinoma. Clinical implications, focusing on the strategy for proper management, and possible pathogenesis were discussed.

  4. Aryl hydrocarbon receptor activity modulates prolactin expression in the pituitary

    PubMed Central

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

    2012-01-01

    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 somatotroph and lactotroph 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 somato-lactotrope 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 pituitary hormones Lhb and Fshb in the absence of Ahr. Overall, these results demonstrate that AhR is important for pituitary hormone expression and suggests environmental dioxins can exert endocrine disrupting effects at the pituitary. PMID:22975028

  5. The dysfunction of inhibition control in pituitary patients: evidence from the Go/Nogo event-related potential study.

    PubMed

    Cao, Chenglong; Song, Jian; Yao, Shun; Yan, Yan; Li, Shun; Peng, Guibao; Ma, Pan; Du, Hao; Huang, Cheng; Ding, Huichao; He, Yuanzhi; Sun, Ronghui; Xu, Guozheng

    2017-03-22

    Pituitary tumor is an intracranial tumor; because of the development of neuroimaging technology in recent years, morbidity is likely to increase. Evidence showed impaired cognitive ability of patients with pituitary adenoma. There is evidence that neurobehavioral disorders are common in pituitary adenoma patients. This disorder is because of the cognitive and emotional function of the important functional areas of the brain oppressed and hormone imbalance. Individuals' mental activity is controlled by the brain and the abnormal mental activity is caused by both the structural abnormalities of the brain and neurochemical dysfunction. Event-related potentials have been used widely in the early assessment of cognitive functions associated with disease, taking advantage of the high temporal resolution, and then analyzing the characteristics of emotional competence from the perspective of cognitive processing. A visual Go/Nogo task was used. A larger Nogo-N2 and Nogo-P3 was found in the control group compared with the pituitary group. This reflects the nonphysiological process of conflict monitoring and inhibitory control in pituitary patients. The results also showed that the difference waves between Go and Nogo conditions (N2d and P3d) over the frontal electrode sites were more robust and earlier in the control group compared with the pituitary group, which reflects frontal dysfunction in the pituitary group. These data suggest reduced earlier and later stages of inhibitory processes in pituitary individuals, implicating the dysfunction of conflict detection and inhibitory control.

  6. General Information about Pituitary Tumors

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  7. Treatment Option Overview (Pituitary Tumors)

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  8. Treatment Options for Pituitary Tumors

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  9. Progress in transsphenoidal hypophysectomy for treatment of pituitary-dependent hyperadrenocorticism in dogs and cats.

    PubMed

    Meij, Björn; Voorhout, George; Rijnberk, Ad

    2002-11-29

    Cushing's disease or pituitary-dependent hyperadrenocorticism (PDH) is common in dogs and rare in cats. PDH is caused by a pituitary tumor producing adrenocorticotropin (ACTH). Pituitary imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is required to assess the size and location of the pituitary adenoma in relation to the surgical landmarks. In a specialized veterinary institution, microsurgical transsphenoidal hypophysectomy has proven to be a safe and effective treatment for dogs (n=84) and cats (n=7) with Cushing's disease. Pituitary surgery requires a team approach and the neurosurgeon performing hypophysectomies must master a learning curve. The surgical results compared favorably with those for dogs with PDH treated medically with mitotane at the same institution. The recurrence rate after initially successful surgery increases with longer follow up-times. Pituitary function testing in 39 dogs with PDH treated with hypophysectomy revealed that, much more so than the other adenohypophyseal cell types, residual corticotropes present in the sella turcica after surgery are functional. Such normal ACTH secreting cells may maintain normocorticism whereas residual adenoma cells may lead to mild recurrence after relatively long periods of remission. Microsurgical transsphenoidal hypophysectomy is an effective treatment for canine and feline Cushing's disease.

  10. Villous adenoma of the distal appendix.

    PubMed

    Taylor, J V; Thomas, M G; Kelly, S; Sutton, R

    1997-04-01

    Villous adenoma confined to the distal appendix has not been previously reported in conjunction with acute apendicitis. The presence of an adenoma indicates a need for further investigation due to an association with neoplasia elsewhere.

  11. Papillary tubular adenoma with marked tubular vacuolization.

    PubMed

    Hattori, N; Imakado, S; Kikuchi, K; Murakami, T; Furue, M

    1997-12-01

    We report a case of papillary tubular adenoma, arising on the knee joint. The overall histologic structure of the tumor is consistent with that of papillary tubular adenoma with slight interluminal papillary changes, but most of the tumor cells present vacuolization outlined by carcinoembryonic antigen staining, suggesting that this adenoma may have resulted from microlumen formation. This is, to our knowledge, the first reported case of a papillary tubular adenoma with marked tubular vacuolization.

  12. Clear cell myoepithelial carcinoma ex pleomorphic adenoma.

    PubMed

    Rabade, Nikhil R; Goel, Naina A

    2014-01-01

    Pleomorphic adenoma is the most common epithelial neoplasm of lacrimal gland. A clear cell myoepithelial carcinoma arising in the background of pleomorphic adenoma is common in the salivary glands but very rare in the lacrimal glands. We report the case of a 27 year old man whose lacrimal gland pleomorphic adenoma recurred several times over a period of four years and ultimately evolved into a clear cell myoepithelial carcinoma ex pleomorphic adenoma.

  13. Clinical and molecular features of a TSH-secreting pituitary microadenoma.

    PubMed

    Usui, Takeshi; Izawa, Shoichiro; Sano, Toshiaki; Tagami, Tetsuya; Nagata, Daisuke; Shimatsu, Akira; Takahashi, Jun A; Naruse, Mitsuhide

    2005-01-01

    We describe a case of a thyroid stimulating hormone (TSH)-secreting pituitary microadenoma, and report the systematic gene expression profile of the surgically- removed tumor. A 50-year-old woman was referred to our hospital because she had high TSH, free-T4, and free-T3 levels, and a pituitary tumor that was visualized with magnetic resonance imaging. Her basal TSH level was high even after a high T3 loading dose, and increased following administration of thyroid releasing hormone (TRH) even after administration of a high dose of exogenous T3. Her clinical symptoms and peripheral markers for T3 were responsive to exogenous T3. There was no thyroid hormone receptor (TR) beta gene mutation. The patient was diagnosed with a TSH-secreting pituitary adenoma, and trans-sphenoid surgery was performed. The histologic features and immunophenotype were consistent with a TSH-secreting pituitary adenoma. Reverse transcription-polymerase chain reaction analysis of pituitary hormones, pituitary-specific transcription factors, receptors, and transcriptional cofactors of clinical significance was performed on the removed tumor. The tumor expressed TSH, growth hormone, prolactin, alpha-subunit, pituitary transcription factor-1 (pit-1) but not proopiomelanocortin (POMC), prophet of pit-1 (prop-1) and pituitary cell-restricted T box factor (Tpit). TRbeta and TRH-receptor gene expression was normal. Three steroid receptor coactivators (SRC)-1, SRC-2, and SRC-3 were expressed. Nuclear receptor corepressor (N-CoR)2 was absent in the tumor, whereas nuclear receptor corepressor (N-CoR1) was expressed. Somatostatin receptor type 1 expression was significantly decreased, whereas type 4 receptor was expressed, which are unusual characteristics for pituitary tumors. The gene expression pattern in the tumor might have a role in the clinical features of this case.

  14. Pituitary apoplexy precipitating diabetes insipidus after living donor liver transplantation.

    PubMed

    Matsusaki, Takashi; Morimatsu, Hiroshi; Matsumi, Junya; Matsuda, Hiroaki; Sato, Tetsufumi; Sato, Kenji; Mizobuchi, Satoshi; Yagi, Takahito; Morita, Kiyoshi

    2011-02-01

    Pituitary apoplexy occurring after surgery is a rare but life-threatening acute clinical condition that follows extensive hemorrhagenous necrosis within a pituitary adenoma. Pituitary apoplexy has been reported to occur spontaneously in the majority of cases or in association with various inducing factors. Reported is a case of pituitary apoplexy complicated by diabetes insipidus following living donor liver transplantation (LDLT). To the best of our knowledge, this has not been previously reported. A 56-year-old woman with nonalcoholic steatohepatitis underwent LDLT from her daughter. The patient also required dopamine support and transfusions because of massive intraoperative bleeding. Postoperatively, her coagulopathy continued, and she underwent a second laparotomy because of unknown bleeding on postoperative day 7, when she needed transfusions and dopamine support to maintain her vital signs. She complained of severe headache, excessive thirst, frequent urination, and diplopia from postoperative day 10. She also had polyuria greater than 300 ml/h and was diagnosed with pituitary apoplexy precipitating diabetes insipidus on postoperative day 13. She was treated conservatively without surgery because of the hormonally inactive status and slight mass effect of her tumor. It is important for anesthesiologists and critical care personnel in LDLT settings to take into consideration this complication as a differential diagnosis.

  15. Screening for GPR101 defects in pediatric pituitary corticotropinomas.

    PubMed

    Trivellin, Giampaolo; Correa, Ricardo R; Batsis, Maria; Faucz, Fabio R; Chittiboina, Prashant; Bjelobaba, Ivana; Larco, Darwin O; Quezado, Martha; Daly, Adrian F; Stojilkovic, Stanko S; Wu, T John; Beckers, Albert; Lodish, Maya; Stratakis, Constantine A

    2016-03-09

    Cushing disease (CD) in children is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. Germline or somatic mutations in genes such as MEN1, CDKIs, AIP, and USP8 have been identified in pediatric CD, but the genetic defects in a significant percentage of cases are still unknown. We investigated the orphan G protein-coupled receptor GPR101, a gene known to be involved in somatotropinomas, for its possible involvement in corticotropinomas. We performed GPR101 sequencing, expression analyses by RT-qPCR and immunostaining, and functional studies (cell proliferation, pituitary hormones secretion, and cAMP measurement) in a series of patients with sporadic CD secondary to ACTH-secreting adenomas in whom we had peripheral and tumor DNA (N=36). No increased GPR101 expression was observed in tumors compared to normal pituitary (NP) tissues, nor did we find a correlation between GPR101 and ACTH expression levels. Sequence analysis revealed a very rare germline heterozygous GPR101 variant (p.G31S) in one patient with CD. Overexpression of the p.G31S variant did not lead to increased growth and proliferation, although modest effects on cAMP signaling were seen. GPR101 is not overexpressed in ACTH-secreting tumors compared to NPs. A rare germline GPR101 variant was found in one patient with CD but in vitro studies did not support a consistent pathogenic effect. GPR101 is unlikely to be involved in the pathogenesis of CD.

  16. Pituitary Gland Disorders Overview

    MedlinePlus

    ... in the anterior (front part) of the pituitary gl