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Sample records for acth-secreting pituitary adenomas

  1. 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

  2. Lycopene and Beta-Carotene Induce Growth Inhibition and Proapoptotic Effects on ACTH-Secreting Pituitary Adenoma Cells

    PubMed Central

    Leite de Oliveira, Felipe; Soares, Nathália; de Mattos, Rômulo Medina; Hecht, Fábio; Dezonne, Rômulo Sperduto; Vairo, Leandro; Goldenberg, Regina Coeli dos Santos; Gomes, Flávia Carvalho Alcântara; de Carvalho, Denise Pires; Gadelha, Mônica R.; Nasciutti, Luiz Eurico; Miranda-Alves, Leandro

    2013-01-01

    Pituitary adenomas comprise approximately 10–15% of intracranial tumors and result in morbidity associated with altered hormonal patterns, therapy and compression of adjacent sella turcica structures. The use of functional foods containing carotenoids contributes to reduce the risk of chronic diseases such as cancer and vascular disorders. In this study, we evaluated the influence of different concentrations of beta-carotene and lycopene on cell viability, colony formation, cell cycle, apoptosis, hormone secretion, intercellular communication and expression of connexin 43, Skp2 and p27kip1 in ACTH-secreting pituitary adenoma cells, the AtT20 cells, incubated for 48 and 96 h with these carotenoids. We observed a decrease in cell viability caused by the lycopene and beta-carotene treatments; in these conditions, the clonogenic ability of the cells was also significantly decreased. Cell cycle analysis revealed that beta-carotene induced an increase of the cells in S and G2/M phases; furthermore, lycopene increased the proportion of these cells in G0/G1 while decreasing the S and G2/M phases. Also, carotenoids induced apoptosis after 96 h. Lycopene and beta-carotene decreased the secretion of ACTH in AtT20 cells in a dose-dependent manner. Carotenoids blocked the gap junction intercellular communication. In addition, the treatments increased the expression of phosphorylated connexin43. Finally, we also demonstrate decreased expression of S-phase kinase-associated protein 2 (Skp2) and increased expression of p27kip1 in carotenoid-treated cells. These results show that lycopene and beta-carotene were able to negatively modulate events related to the malignant phenotype of AtT-20 cells, through a mechanism that could involve changes in the expression of connexin 43, Skp2 and p27kip1; and suggest that these compounds might provide a novel pharmacological approach to the treatment of Cushing’s disease. PMID:23667519

  3. Size reduction of an ACTH-secreting pituitary macroadenoma in Nelson's syndrome by sodium valproate: effect of withdrawal and re-institution of treatment.

    PubMed

    Loli, P; Berselli, M E; Vignati, F; De Grandi, C; Tagliaferri, M

    1988-11-01

    We describe herein the reduction in the size of an ACTH-secreting pituitary macroadenoma in a patient with Nelson's syndrome during chronic administration of sodium valproate, and the changes in tumour volume after withdrawal and re-institution of treatment. The patient had elevated plasma ACTH levels (1123-1255 pmol/l), which increased markedly after CRH stimulation. A first 4-month course of sodium valproate administration (600 mg/day, orally) was started. Plasma ACTH fell to 550-726 pmol/l with persistence of responsiveness to CRH; brain computed tomography showed a clearcut reduction of tumour size. One month after drug withdrawal, the tumour volume appeared unchanged and plasma ACTH values ranged between 374 and 440 pmol/l. One and a half year after drug withdrawal, a brain computed tomography showed re-expansion of the pituitary adenoma with evidence of suprasellar extension, which had never been seen previously. Plasma ACTH ranged between 113 and 199 pmol/l. A second course of sodium valproate was started; after three months, a brain computed tomography documented clearcut reduction of tumour volume from a suprasellar extension to a partially empty pituitary fossa. Plasma ACTH ranged from 396 to 542 pmol/l with persistence of responsiveness to CRH. The present report documents for the first time the reduction of tumour size in a patient with an ACTH-secreting macroadenoma by chronic administration of sodium valproate.

  4. Pituitary adenomas in childhood and adolescence.

    PubMed

    Jackman, Suzanne; Diamond, Frank

    2013-07-01

    Scientific advances are revealing the complexity of pituitary development, which is controlled by multiple transcription factors and signaling molecules. Unregulated pituitary cell growth, resulting in pituitary adenoma, is usually sporadic and results from monoclonal expansion of a single mutated cell. However, some adenomas develop as part of a genetic syndrome. Prolactinoma is the most common hormonally active pituitary adenoma in children. The non-functioning (non-secreting) pituitary adenoma is the second most common and often stains positive for GH, PRL, and/or TSH. While Cushing disease, resulting from an ACTH-secreting adenoma, commonly manifests as weight gain with growth deceleration in children, GH excess causes gigantism with rapid, accelerated growth inappropriate for the height of the family. TSH secreting pituitary adenomas are rare, and biochemical analysis will show an elevated thyroxine level with a non-suppressed or high TSH. Though the natural history of pituitary incidentalomas in children is unknown, adult practice guidelines are established. PMID:23957196

  5. 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

  6. Pregnancy and pituitary adenomas.

    PubMed

    Glezer, Andrea; Jallad, Raquel S; Machado, Marcio C; Fragoso, Maria C; Bronstein, Marcello D

    2016-09-01

    Infertility is frequent in patients harboring pituitary adenomas. The mechanisms involved include hypogonadism secondary to hormonal hypersecretion (prolactin, growth hormone and cortisol), stalk disconnection and pituitary damage. With the improvement of clinical and surgical treatment, pregnancy in women harboring pituitary adenomas turned into a reality. Pituitary hormonal hyper- and hyposecretion influences pregnancy outcomes, as well as pregnancy can interfere on pituitary tumors, especially in prolactinomas. We review literature about specific follow-up and management in pregnant women harboring prolactinomas, acromegaly, or Cushings disease and the impact of clinical and surgical treatment on each condition. PMID:26977888

  7. Clinical management of critically ill patients with Cushing's disease due to ACTH-secreting pituitary macroadenomas: effectiveness of presurgical treatment with pasireotide.

    PubMed

    Cannavo, S; Messina, E; Albani, A; Ferrau, F; Barresi, V; Priola, S; Esposito, F; Angileri, F

    2016-06-01

    The management of critically ill Cushing's disease (CD) patients is extremely challenging. Pasireotide is indicated for the treatment of CD patients when pituitary surgery is unfeasible or has not been curative, but no data are available about the use of this drug as pre-operative treatment in critically ill patients. We report the effects of presurgical pasireotide therapy in CD patients in whom hypercortisolism caused life-threatening hypokalemia, alkalosis, and cardio-respiratory complications precluding surgical approach. Clinical, biochemical, and radiological data of two critically ill patients with ACTH-secreting pituitary macroadenoma, before and during first-line presurgical pasireotide treatment (600 μg s.c. bid). During the first 21 days of treatment, pasireotide therapy induced a rapid, partial decrease of plasma ACTH, serum cortisol, and urinary free cortisol levels, with the consequent normalization of serum potassium concentration and arterial blood gases parameters, in both the patients. They did not experience unmanageable side effects and underwent endoscopic transsphenoidal surgery after 4 weeks of effective treatment. Pre-operative MRI evaluation did not show pituitary tumor shrinkage. Surgical cure of CD was obtained in the first patient, while debulking allowed the pharmacological control of hypercortisolism in the second case. We suggest that pasireotide can induce a rapid improvement of clinical and metabolic conditions in critically ill CD patients in whom surgical approach is considered hazardous and need to be delayed.

  8. Pituitary adenoma: a radiotherapeutic perspective.

    PubMed

    Platta, Christopher S; Mackay, Christopher; Welsh, James S

    2010-08-01

    Pituitary adenomas comprise approximately 10% to 20% of all central nervous system neoplasms whereas autopsy series have suggested that the incidence of pituitary adenoma in the general population may approach 25%. Several treatment modalities are used in the treatment of pituitary adenomas, including observation, surgery, medical intervention, and radiotherapy. The treatment modality employed depends greatly on the type of pituitary adenoma and presenting symptoms. This review will discuss the biology of pituitary adenomas and the current management principles for the treatment of prolactinomas, Cushing disease, acromegaly, and nonsecretory adenomas, with an emphasis on the published radiotherapeutic literature.

  9. Somatostatin receptor ligands and resistance to treatment in pituitary adenomas.

    PubMed

    Cuevas-Ramos, Daniel; Fleseriu, Maria

    2014-06-01

    Somatostatin (SST), an inhibitory polypeptide with two biologically active forms SST14 and SST28, inhibits GH, prolactin (PRL), TSH, and ACTH secretion in the anterior pituitary gland. SST also has an antiproliferative effect inducing cell cycle arrest and apoptosis. Such actions are mediated through five G-protein-coupled somatostatin receptors (SSTR): SSTR1-SSTR5. In GH-secreting adenomas, SSTR2 expression predominates, and somatostatin receptor ligands (SRLs; octreotide and lanreotide) directed to SSTR2 are presently the mainstays of medical therapy. However, about half of patients show incomplete biochemical remission, but the definition of resistance per se remains controversial. We summarize here the determinants of SRL resistance in acromegaly patients, including clinical, imaging features as well as molecular (mutations, SSTR variants, and polymorphisms), and histopathological (granulation pattern, and proteins and receptor expression) predictors. The role of SSTR5 may explain the partial responsiveness to SRLs in patients with adequate SSTR2 density in the cell membrane. In patients with ACTH-secreting pituitary adenomas, i.e. Cushing's disease (CD), SSTR5 is the most abundant receptor expressed and tumors show low SSTR2 density due to hypercortisolism-induced SSTR2 down-regulation. Clinical studies with pasireotide, a multireceptor-targeted SRL with increased SSTR5 activity, lead to approval of pasireotide for treatment of patients with CD. Other SRL delivery modes (oral octreotide), multireceptor-targeted SRL (somatoprim) or chimeric compounds targeting dopamine D2 receptors and SSTR2 (dopastatin), are briefly discussed. PMID:24647046

  10. Familial pituitary adenomas.

    PubMed

    Vandeva, S; Vasilev, V; Vroonen, L; Naves, L; Jaffrain-Rea, M-L; Daly, A F; Zacharieva, S; Beckers, A

    2010-12-01

    Pituitary adenomas are benign intracranial neoplasms that present a major clinical concern because of hormonal overproduction or compression symptoms of adjacent structures. Most arise in a sporadic setting with a small percentage developing as a part of familial syndromes such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), and the recently described familial isolated pituitary adenomas (FIPA) and MEN-4. While the genetic alterations responsible for the formation of sporadic adenomas remain largely unknown, considerable advances have been made in defining culprit genes in these familial syndromes. Mutations in MEN1 and PRKAR1A genes are found in the majority of MEN1 and CNC patients, respectively. About 15% of FIPA kindreds present with mutations of the aryl hydrocarbon receptor-interacting protein (AIP) gene. Mutations in the CDKN1B gene, encoding p27(Kip)¹ were identified in MEN4 cases. Familial tumours appear to differ from their sporadic counterparts not only in genetic basis but also in clinical characteristics. Evidence suggests that, especially in MEN1 and FIPA, they are more aggressive and affect patients at younger age, therefore justifying the importance of early diagnosis. In this review, we summarize the genetic and clinical characteristics of these familial pituitary adenomas. PMID:20961530

  11. 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. PMID:17561883

  12. 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.

  13. 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

  14. [Familial isolated pituitary adenoma syndrome].

    PubMed

    Dénes, Judit; Korbonits, Márta; Hubina, Erika; Kovács, Gábor László; Kovács, László; Görömbey, Zoltán; Czirják, Sándor; Góth, Miklós

    2011-05-01

    Familial pituitary adenomas occur in multiple endocrine neoplasia type 1, Carney complex, as well as in familial isolated pituitary adenoma syndrome. Familial isolated pituitary adenoma syndrome is an autosomal dominant disease with incomplete penetrance. Pituitary adenomas occur in familial setting but without any other specific tumors. In 20-40% of families with this syndrome, mutations have been identified in the aryl hydrocarbon receptor interacting protein gene while in the rest of the families the causative gene or genes have not been identified. Families carrying aryl hydrocarbon receptor interacting protein gene mutations have a distinct phenotype with younger age at diagnosis and a predominance of somatotroph and lactotroph adenomas. Germline mutations of the aryl hydrocarbon receptor interacting protein gene can be occasionally identified in usually young-onset seemingly sporadic cases. Genetic and clinical testing of relatives of patients with aryl hydrocarbon receptor interacting protein gene mutations can lead to earlier diagnosis and treatment at an earlier stage of the pituitary tumor. PMID:21498161

  15. Cushing's syndrome due to ectopic ACTH secretion.

    PubMed

    Cieszyński, Łukasz; Berendt-Obołończyk, Monika; Szulc, Michał; Sworczak, Krzysztof

    2016-01-01

    Cushing's syndrome (CS) is defined as a constellation of clinical signs and symptoms occurring due to hypercortisolism. Cortisol excess may be endogenous or exogenous. The most common cause of CS is glucocorticoid therapy with supraphysiological (higher than in the case of substitution) doses used in various diseases (e.g. autoimmune). One possible CS cause is ectopic (extra-pituitary) ACTH secretion (EAS) by benign or malignant tumours. Since its first description in 1963, EAS aetiology has changed, i.e. as well as small cell lung cancer (SCLC), higher incidence in other malignancies has been reported. Ectopic ACTH secretion symptoms are usually similar to hypercortisolism symptoms due to other causes. A clinical suspicion of CS requires laboratory investigations. There is no single and specific laboratory test for making a CS diagnosis, and therefore multiple dynamic tests should be ordered. A combination of multiple laboratory noninvasive and invasive tests gives 100% sensitivity and 98% specificity for EAS diagnosis. If the EAS is caused by localised malignancy, surgery is the optimal treatment choice. Radical tumour excision may be performed in 40% of patients, and 80% of them are cured of the disease. The authors present an interesting clinical case of EAS, which is always a huge diagnostic challenge for clinicians. (Endokrynol Pol 2016; 67 (4): 458-464). PMID:27387249

  16. The genetics of pituitary adenomas.

    PubMed

    Vandeva, Silvia; Jaffrain-Rea, Marie-Lise; Daly, Adrian F; Tichomirowa, Maria; Zacharieva, Sabina; Beckers, Albert

    2010-06-01

    Pituitary adenomas are one of the most frequent intracranial tumors with a prevalence of clinically-apparent tumors close to 1:1000 of the general population. They are clinically significant because of hormone overproduction and/or tumor mass effects in addition to the need for neurosurgery, medical therapies and radiotherapy. The majority of pituitary adenomas have a sporadic origin with recognized genetic mutations seldom being found; somatotropinomas are an exception, presenting frequent somatic GNAS mutations. In this and other phenotypes, tumorigenesis could possibly be explained by altered function of genes implicated in cell cycle regulation, growth factors or their receptors, cell-signaling pathways, specific hormonal factors or other molecules with still unclear mechanisms of action. Genetic changes, such as allelic loss or gene amplification, and epigenetic changes, usually by promoter methylation, have been implicated in abnormal gene expression, but alternative mechanisms may be present. Familial cases of pituitary adenomas represent 5% of all pituitary tumors. MEN1 mutations cause multiple endocrine neoplasia type 1 (MEN1), while the Carney complex (CNC) is characterized by mutations in the protein kinase A regulatory subunit-1alpha (PRKAR1A) gene or changes in a locus at 2p16. Recently, a MEN1-like condition, MEN4, was found to be related to mutations in the CDKN1B gene. The clinical entity of familial isolated pituitary adenomas (FIPA) is characterized by genetic defects in the aryl hydrocarbon receptor interacting protein (AIP) gene in about 15% of all kindreds and 50% of homogenous somatotropinoma families. Identification of familial cases of pituitary adenomas is important as these tumors may be more aggressive than their sporadic counterparts. PMID:20833337

  17. Multihormonal pituitary adenomas.

    PubMed

    Heitz, P U

    1979-01-01

    66 pituitary tumors detected at autopsy were investigated for the presence of corticotropin, beta-lipotrophin, growth hormone, prolactin, thyrotropin and gonadotropins by immunocytochemistry. 56 tumors contained hormone-producing cells; 45 were found to contain 2 or more hormones. This finding confirms and extends previous morphologic and clinical observations. The majority of pituitary tumors are mixed and they probably arise from impaired regulation at the hypothalamic and/or pituitary level.

  18. Pathophysiology and treatment of subclinical Cushing's disease and pituitary silent corticotroph adenomas [Review].

    PubMed

    Kageyama, Kazunori; Oki, Yutaka; Nigawara, Takeshi; Suda, Toshihiro; Daimon, Makoto

    2014-01-01

    Pituitary adrenocorticotropic hormone (ACTH)-secreting tumor presents with a variety of clinical features. We outlined the features of ACTH release and characteristics of corticotroph adenoma cells. We especially focused on the corticotroph adenomas in patients with no clinical features of Cushing's disease. Subclinical Cushing's disease is defined by ACTH-induced mild hypercortisolism without typical features of Cushing's disease. Silent corticotroph adenomas (SCAs) are defined by normal cortisol secretion and ACTH-immunopositive staining without autonomous ACTH secretion. Clinicians who are not well-informed about the disease may sometimes confuse SCAs (because of their clinically silent nature) with "subclinical Cushing's disease". The recent criteria for diagnosing subclinical Cushing's disease in Japan are presented. Cortisol measurement was recently standardized in Japan, so plasma cortisol cutoff level should be reconsidered for the diagnosis. In patients with uncontrolled diabetes and hypertension despite appropriate treatment, subclinical Cushing's disease may be efficiently detected. Subclinical Cushing's disease may be associated with metabolic change. In subclinical Cushing's disease, mild hypercortisolism due to autonomous secretion of ACTH contributes to metabolic change and treatment of subclinical hypercortisolism can reverse this change.

  19. Subclinical hyperfunctioning pituitary adenomas: The silent tumors

    PubMed Central

    Cooper, Odelia; Melmed, Shlomo

    2012-01-01

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

  20. 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.

  1. Double pituitary adenomas: six surgical cases.

    PubMed

    Sano, T; Horiguchi, H; Xu, B; Li, C; Hino, A; Sakaki, M; Kannuki, S; Yamada, S

    1999-05-01

    While double pituitary adenomas have been found in approximately 1% of autopsy pituitaries, those in surgically resected material have been only rarely reported. We report herein 6 cases of double pituitary adenomas, which consisted of two histologically and/or immunohistochemically different areas among approximately 450 surgical specimens. Five out of 6 patients were men and the age was ranged between 18 and 61 years old. All these 6 patients presented acromegaly or acrogigantism and hyperprolactinemia was noted in 3 patients. In 2 patients (cases 1 and 2) the two adenomas belonged to different adenoma groups (GH-PRL-TSH group and FSH/LH group), while in the remaining 4 patients (cases 3-6) the two adenomas belonged to the same group (GH-PRL-TSH group). Thus, in all patients at least one of the two adenomas was GH-producing adenoma. Reasons for a high incidence of GH-producing adenomas in surgically resected double pituitary adenomas may include the presence of a variety of histologic subtypes among GH-producing adenomas and the advantage of cytokeratin immunostaining to distinguish these subtypes. In regard to pathogenesis of double pituitary adenomas, adenomas in cases 1 and 2 may be of multicentric occurrence, while those in cases 3-6 may occur through different clonal proliferation within originally one adenoma, resulting in diverse phenotypic expressions. Since there were patients with familial MEN 1 (case 2) and familial pituitary adenoma unrelated MEN 1 (case 3), genetic background should be also considered. Double pituitary adenomas in surgically resected material may not be so infrequent. Further molecular analysis will provide new insights into understanding the pathogenesis of pituitary adenomas and their mechanisms of multidirectional phenotypic diffrentiation.

  2. Double pituitary adenomas: six surgical cases.

    PubMed

    Sano, T; Horiguchi, H; Xu, B; Li, C; Hino, A; Sakaki, M; Kannuki, S; Yamada, S

    1999-05-01

    While double pituitary adenomas have been found in approximately 1% of autopsy pituitaries, those in surgically resected material have been only rarely reported. We report herein 6 cases of double pituitary adenomas, which consisted of two histologically and/or immunohistochemically different areas among approximately 450 surgical specimens. Five out of 6 patients were men and the age was ranged between 18 and 61 years old. All these 6 patients presented acromegaly or acrogigantism and hyperprolactinemia was noted in 3 patients. In 2 patients (cases 1 and 2) the two adenomas belonged to different adenoma groups (GH-PRL-TSH group and FSH/LH group), while in the remaining 4 patients (cases 3-6) the two adenomas belonged to the same group (GH-PRL-TSH group). Thus, in all patients at least one of the two adenomas was GH-producing adenoma. Reasons for a high incidence of GH-producing adenomas in surgically resected double pituitary adenomas may include the presence of a variety of histologic subtypes among GH-producing adenomas and the advantage of cytokeratin immunostaining to distinguish these subtypes. In regard to pathogenesis of double pituitary adenomas, adenomas in cases 1 and 2 may be of multicentric occurrence, while those in cases 3-6 may occur through different clonal proliferation within originally one adenoma, resulting in diverse phenotypic expressions. Since there were patients with familial MEN 1 (case 2) and familial pituitary adenoma unrelated MEN 1 (case 3), genetic background should be also considered. Double pituitary adenomas in surgically resected material may not be so infrequent. Further molecular analysis will provide new insights into understanding the pathogenesis of pituitary adenomas and their mechanisms of multidirectional phenotypic diffrentiation. PMID:11081204

  3. [Old phenotype and new genotypes. Pituitary adenomas].

    PubMed

    Gérard, C; Jedidi, H; Petrossians, P; Krzesinski, F; Daly, A; Beckers, A

    2015-11-01

    Gigantism and acromegaly, usually caused by a pituitary adenoma linked inappropriate secretion of growth hormone (GH), are generally considered as very rare diseases, even if, according to some authors, their cumulative prevalence is about 1/5000. Starting from the historical case of a giant from Liège we shall describe the different types of GH pituitary adenomas and their pathophysiology. We shall particularly discuss rare forms of inherited GH secreting pituitary adenomas like the FIPA (familial inherited isolated pituitary adenomas) and the X-LAG (X linked acrogigantism), both described for the first time in Liège, in 2000 and 2014, respectively. PMID:26738269

  4. [Old phenotype and new genotypes. Pituitary adenomas].

    PubMed

    Gérard, C; Jedidi, H; Petrossians, P; Krzesinski, F; Daly, A; Beckers, A

    2015-11-01

    Gigantism and acromegaly, usually caused by a pituitary adenoma linked inappropriate secretion of growth hormone (GH), are generally considered as very rare diseases, even if, according to some authors, their cumulative prevalence is about 1/5000. Starting from the historical case of a giant from Liège we shall describe the different types of GH pituitary adenomas and their pathophysiology. We shall particularly discuss rare forms of inherited GH secreting pituitary adenomas like the FIPA (familial inherited isolated pituitary adenomas) and the X-LAG (X linked acrogigantism), both described for the first time in Liège, in 2000 and 2014, respectively.

  5. Medical Management of Functioning Pituitary Adenoma: An Update

    PubMed Central

    OKI, Yutaka

    2014-01-01

    The treatment of functioning pituitary adenoma (FPA) must achieve endocrinological remission as well as tumor size reduction. The first-line treatment of FPA except prolactinoma is transsphenoidal surgery (TSS). Medical treatments and/or radiation will be applied as adjuvant therapies succeeding to TSS. In patients with prolactinoma, dopamine agonists, especially cabergoline, are quite efficient. Dopamine agonists decrease plasma prolactin levels and induce shrinkage in most patients and can be ceased in some of them. In patients with acromegaly, dopamine agonists, somatostatin analogues, and growth hormone receptor antagonist have been used as a monotherapy or the combination, and the high remission rate can be achieved. Pasireotide having high affinity to type 5 somatostatin receptors will be available for the patients presenting resistance against type 2 receptor agonists, such as octreotide and lanreotide. The preceding treatment with somatostatin analogues is beneficial for improving the success rate of TSS. The chimera compounds of somatostatin analogues and dopamine agonists have been investigated. The medical treatments of Cushing's disease are challenging, if TSS is not successful. To suppress ACTH secretion, dopamine agonists and somatostatin analogues have been examined, but neither came to show a sufficient effect. Pasireotide reduces urinary cortisol excretion with a high remission rate. Adrenal enzyme inhibitors (AEIs), such as metyrapone, can inhibit cortisol synthesis form adrenal glands promptly and sufficiently in most of patients. LCI699, a newly developed AEI, is more potent than metyrapone and will be available. We should use available medical treatments for improving the prognosis and quality of life. PMID:25446388

  6. Prolactin-Secreting Pituitary Adenomas

    PubMed Central

    Martin, Mary C.; Schriock, Eldon D.; Jaffe, Robert B.

    1983-01-01

    Prolactin-secreting pituitary adenoma is a common cause of gynecologic problems that include oligomenorrhea, infertility, amenorrhea and galactorrhea. Diagnosis requires a combination of endocrine testing and radiologic evaluation. The diagnosis of macroadenomas is usually straightforward and these large tumors may be associated with mass effects such as severe headache, nerve palsies or visual changes. Microadenomas may be more subtle in presentation, and the diagnosis of hyperprolactinemia without radiologic evidence of a tumor frequently is problematic. The management of prolactin-secreting adenoma remains controversial, with no clear consensus or indication for surgical versus medical treatment. Surgical intervention is a realistic option for those patients who have access to an experienced neurosurgeon and who have tumor characteristics that offer a reasonable hope for cure. Many questions remain to be answered, including the cause, natural history of development and the optimum treatment for individual cases. Images PMID:6659490

  7. Non-functioning pituitary adenomas.

    PubMed

    Chanson, P; Brochier, S

    2005-01-01

    The vast majority (>80%) of clinically non-functioning pituitary adenomas (NFPAs) are gonadotroph-cell adenomas, as demonstrated by immunocytochemistry. However, they are rarely associated with increased levels of dimeric LH or FSH. Increased levels of uncombined subunits (free alpha-subunit mainly, LH-beta subunit more rarely) are more frequently encountered, but are generally modest. The main problems raised by NFPA are mass effects problems, responsible for optic chiasm compression or deficient hormone secretion resulting from compression of normal anterior pituitary cells. The therapeutic management of NFPA may require combination of different options. The strategy of observation only for patients with incidentally discovered pituitary adenomas may be appropriate, provided that the tumor is well-delimited, small, has no extension with risk of neurological or visual chiasm compression, and that a meticulous hormonal work-up has ruled out the possibility of a minimal hormonal hypersecretion. Transsphenoidal surgery allows improvement in visual disturbances due to chiasmal syndrome in most patients, and sometimes, in pituitary function. After surgery alone, nearly 30% (between 10 and 69%, according to the series) of patients relapse within 5 to 10 yr. Radiotherapy is proposed either as a systematic adjunct or only if a significant remnant persists. Systematic radiation therapy is supported by the low relapse rate (mean, 11%; range, 6-21%) observed when radiation therapy is systematically associated with surgery. However, irradiation is almost always followed by hypopituitarism which might be associated with a reduction in life expectancy, despite appropriate replacement therapy. Results of medical treatment are disappointing. Dopamine agonist bromocriptine decreases gonadotropin and alpha-subunit in vitro and in vivo, but, in clinical studies, was poorly effective in reducing supranormal gonadotropins and free subunits levels, and rarely produced a minimal tumoral

  8. Postoperative radiosurgery of pituitary adenomas.

    PubMed

    Valentino, V

    1991-01-01

    From 1984-1990, 52 patients with pituitary adenomas had postoperative radiosurgery for incomplete surgical removal or regrowth of the tumor. The atraumatic Greitz-Bergström fixation head device was adopted for the stereotactic procedure and irradiation was performed with a linear accelerator. Because of the variability of the tumor response, a 10-20 Gy single dose was directed at 1-2 targets and radiosurgery repeated if the result was unsatisfactory. The median radiation dose was 30 Gy. No adverse effects occurred. Regression of pretreatment symptoms caused by tumor mass was observed in 67% of patients. GH and PRL activity decreased in 20 patients, was stable in 11 and increased in 2 prolactinomas. CT studies showed disappearance of the tumor in 4 patients and shrinkage in 36. Postoperative radiosurgery is a valuable method of treatment whenever pituitary surgery has been incomplete.

  9. Pituitary adenoma-neuronal choristoma is a pituitary adenoma with ganglionic differentiation.

    PubMed

    Nguyen, Michaela T; Lavi, Ehud

    2015-12-01

    The presence of ganglion cells within an endocrine pituitary tumor has been named hamartoma, choristoma, gangliocytoma, or most recently pituitary adenoma-neuronal choristoma (PANCH). The presence of neuronal differentiation in regular pituitary adenomas has been previously suggested, however, its origin, the extent of its presence, and the relationship between the neuronal elements and the pituitary adenoma remain uncertain. Thus, to further explore the neuronal potential of pituitary tumors, we used immunohistochemistry on pituitary tumors of different grades, with a neuronal antigen protein (NeuN) antibody as a specific marker for mature neuronal differentiation. We found NeuN expression in 26.47% (9/34) cases of pituitary tumors without ganglionic differentiation (7 adenomas, 1 atypical adenoma and 1 pituitary carcinoma), in addition to NeuN expression in pituitary adenomas with ganglionic cells (2/2). Thus, neuronal expression is an innate property of pituitary adenomas. We propose that the rare presence of ganglionic cells in pituitary adenomas is not the result of a separate lesion or "collision sellar tumors", as previously suggested, but a ganglionic neuronal differentiation in an endocrine neoplasm. The ganglionic cells may be arising from uncommitted stem/progenitor cells that contain both neuronal and endocrine properties. A label of "pituitary adenoma with ganglionic differentiation" would better reflect the dual differentiation in a neuroendocrine tumor than the current label "PANCH".

  10. Nur77 gene expression levels were involved in different ACTH-secretion autonomy between Cushing's disease and subclinical Cushing's disease.

    PubMed

    Tabuchi, Yukiko; Kitamura, Tetsuhiro; Fukuhara, Atsunori; Mukai, Kosuke; Onodera, Toshiharu; Miyata, Yugo; Hamasaki, Toshimitsu; Oshino, Satoru; Saitoh, Youichi; Morii, Eiichi; Otsuki, Michio; Shimomura, Iichiro

    2016-06-30

    Cushing's disease (CD) and subclinical Cushing's disease (subCD) are both diseases caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. However, ACTH autonomy in subCD is weaker than in CD and there are no Cushingoid features in subCD. The differences of molecular mechanisms in ACTH autonomy between CD and subCD have not yet been reported. Therefore, we aimed to investigate the differences in molecular mechanisms of ACTH-secretion autonomy between CD and subCD. The study included 23 patients [7 CD, 6 subCD, and 10 non-functioning pituitary tumors (NFTs)] who underwent transsphenoidal surgery at the Osaka University Hospital between December 2009 and October 2013. Using quantitative real-time PCR, various ACTH-related gene expressions in tumor tissues from CD, subCD, and NFT were measured such as pro-opiomelanocortin (POMC), POMC transcription factor (Tpit, Pitx1, NeuroD1, and Nur77), POMC peptide processing enzymes (prohormone convertase: PC1/3 and PC2), and ACTH secretion-related factors (corticotropin-releasing hormone receptor 1: CRHR1 and glucocorticoid receptor α: GRα). Only Nur77 mRNA levels were significantly higher in CD than in subCD. Furthermore, we stained 6 CD and 6 subCD with anti-Nur77 antibody. All tumor samples from CD had Nur77 protein positive cells. On the other hand, Nur77 protein was expressed in only one tumor sample from subCD. This sample showed high expression of Nur77 mRNA. Nur77 is an important to regulate POMC transcription and negative-feedback by glucocorticoids. Nur77 gene expression levels might involve different autonomy of ACTH production between CD and subCD. PMID:27025408

  11. Nur77 gene expression levels were involved in different ACTH-secretion autonomy between Cushing's disease and subclinical Cushing's disease.

    PubMed

    Tabuchi, Yukiko; Kitamura, Tetsuhiro; Fukuhara, Atsunori; Mukai, Kosuke; Onodera, Toshiharu; Miyata, Yugo; Hamasaki, Toshimitsu; Oshino, Satoru; Saitoh, Youichi; Morii, Eiichi; Otsuki, Michio; Shimomura, Iichiro

    2016-06-30

    Cushing's disease (CD) and subclinical Cushing's disease (subCD) are both diseases caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. However, ACTH autonomy in subCD is weaker than in CD and there are no Cushingoid features in subCD. The differences of molecular mechanisms in ACTH autonomy between CD and subCD have not yet been reported. Therefore, we aimed to investigate the differences in molecular mechanisms of ACTH-secretion autonomy between CD and subCD. The study included 23 patients [7 CD, 6 subCD, and 10 non-functioning pituitary tumors (NFTs)] who underwent transsphenoidal surgery at the Osaka University Hospital between December 2009 and October 2013. Using quantitative real-time PCR, various ACTH-related gene expressions in tumor tissues from CD, subCD, and NFT were measured such as pro-opiomelanocortin (POMC), POMC transcription factor (Tpit, Pitx1, NeuroD1, and Nur77), POMC peptide processing enzymes (prohormone convertase: PC1/3 and PC2), and ACTH secretion-related factors (corticotropin-releasing hormone receptor 1: CRHR1 and glucocorticoid receptor α: GRα). Only Nur77 mRNA levels were significantly higher in CD than in subCD. Furthermore, we stained 6 CD and 6 subCD with anti-Nur77 antibody. All tumor samples from CD had Nur77 protein positive cells. On the other hand, Nur77 protein was expressed in only one tumor sample from subCD. This sample showed high expression of Nur77 mRNA. Nur77 is an important to regulate POMC transcription and negative-feedback by glucocorticoids. Nur77 gene expression levels might involve different autonomy of ACTH production between CD and subCD.

  12. MicroRNAs in Human Pituitary Adenomas

    PubMed Central

    Wang, Elaine Lu; Qian, Zhi Rong

    2014-01-01

    MicroRNAs (miRNAs) are a class of recently identified noncoding RNAs that regulate gene expression at posttranscriptional level. Due to the large number of genes regulated by miRNAs, miRNAs play important roles in many cellular processes. Emerging evidence indicates that miRNAs are dysregulated in pituitary adenomas, a class of intracranial neoplasms which account for 10–15% of diagnosed brain tumors. Deregulated miRNAs and their targets contribute to pituitary adenomas progression and are associated with cell cycle control, apoptosis, invasion, and pharmacological treatment of pituitary adenomas. To provide an overview of miRNAs dysregulation and functions of these miRNAs in pituitary adenoma progression, we summarize the deregulated miRNAs and their targets to shed more light on their potential as therapeutic targets and novel biomarkers. PMID:25548562

  13. Genetics Home Reference: familial isolated pituitary adenoma

    MedlinePlus

    ... 1,000 people. FIPA, though, is quite rare, accounting for approximately 2 percent of pituitary adenomas. More ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management These resources address the diagnosis or management of ...

  14. Cold inducible RNA binding protein upregulation in pituitary corticotroph adenoma induces corticotroph cell proliferation via Erk signaling pathway

    PubMed Central

    Fu, Wei; Tang, Hao; Chen, Xiao; Zhao, Yao; Zheng, Lili; Pan, Sijian; Wang, Weiqing; Bian, Liuguan; Sun, Qingfang

    2016-01-01

    Cushing's disease is caused by pituitary corticotroph adenoma, and the pathogenesis of it has remained obscure. Here, we showed that cold inducible RNA binding protein (CIRP) was markedly elevated in corticotroph tumors. Forced overexpression of CIRP in murine AtT20 pituitary corticotroph cell line increased corticotroph precursor hormone proopiomelanocortin (POMC) transcription, ACTH secretion and cellular proliferation. In vivo, CIRP overexpression promotes murine corticotroph tumor growth and enhances ACTH production. Mechanistically, we show that CIRP could promote AtT20 cells proliferation by inducing cyclinD1 and decreasing p27 expression via Erk1/2 signaling pathway. Clinically, CIRP overexpression is significantly correlated with Cushing's disease recurrence. CIRP appears to play a critical tumorigenesis function in Cushing's disease and its expression might be a useful biomarker for tumor recurrence. PMID:26824322

  15. Immunohistochemical detection of estrogen receptor alpha in pituitary adenomas and its correlation with cellular replication.

    PubMed

    Pereira-Lima, Julia F S; Marroni, Caroline P; Pizarro, Cristina B; Barbosa-Coutinho, Ligia M; Ferreira, Nelson P; Oliveira, Miriam C

    2004-03-01

    -positive adenomas and positive MIB-1 indexes were considered. It was concluded that, when present in pituitary tumors, ERalpha exhibits a high concentration, and is more common in nonfunctioning and invasive adenomas, but absent in ACTH-secreting ones.

  16. Mutation Analysis of Inhibitory Guanine Nucleotide Binding Protein Alpha (GNAI) Loci in Young and Familial Pituitary Adenomas

    PubMed Central

    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. PMID:25291362

  17. GIANT PITUITARY ADENOMA WITH NORMAL VISION AND MISLEADING RADIOLOGICAL FINDINGS.

    PubMed

    Khalid, Muhammad; Raina, Umer Farooq; uz Zaman, Khaleeq; Tahir, Muhammad

    2015-01-01

    Giant pituitary adenomas are rare and present with visual loss. Giant pituitary adenoma has rarely been reported presenting with normal vision. We report Giant pituitary adenoma with Normal vision in a 35 years old patient presenting with adult onset epilepsy and headache. PMID:26721053

  18. Paediatric pituitary adenomas: a decade of change.

    PubMed

    Guaraldi, Federica; Storr, Helen L; Ghizzoni, Lucia; Ghigo, Ezio; Savage, Martin O

    2014-01-01

    Pituitary adenomas, although rare in the paediatric age range and mostly benign, represent very challenging disorders for diagnosis and management. The recent identification of genetic alterations in young individuals with pituitary adenomas has broadened the scope of molecular investigations and contributed to the understanding of mechanisms of tumorigenesis. Recent identification of causative mutations of genes such as GNAS, PRKAR1A, MEN1 and AIP has introduced the concept of molecular screening of young apparently healthy family members. Population-based studies have reported a significantly higher number of affected subjects and genetic variations than expected. Radiological techniques have advanced, yet many microadenomas remain undetectable on scanning. However, experience with transsphenoidal and endoscopic pituitary surgery has led to higher rates of cure. Prolactinomas, corticotroph and somatotroph adenomas remain the most prevalent, with each diagnosis presenting its own challenges. As paediatric pituitary adenomas occur very infrequently within the paediatric age range, paediatric endocrine units cannot provide expert management in isolation. Consequently, close co-operation with adult endocrinology colleagues with experience of pituitary disease is strongly recommended. PMID:24525527

  19. [Clinical and genetic characterization of FIPA (familial isolated pituitary adenomas)].

    PubMed

    Beckers, A; Apetrii, P; Daly, A; Tichomirova, M; Vanbellingen, J F; Georges, M; Bours, V

    2009-01-01

    Pituitary adenomas are common brain tumours at autopsy and radiological series of unselected population. Historically, few epidemiologic data regarding the prevalence of clinically apparent pituitary adenomas have been available. Recently, a cross-sectional study conducted in Liège, Belgium, noted that clinically-apparent pituitary adenomas occurred with a prevalence of 1:1064 inhabitants, which is 3.5-5 times the previously reported prevalence. Pituitary adenomas occur predominantly as sporadic tumors, but also in a familial setting or associated to some familial/isolated tumoral syndromes. The recent characterization of the novel clinical entity FIPA (Familial Isolated Pituitary Adenomas) increased the prevalence of familial pituitary adenomas which account now for about 5% of pituitary tumors. Distinct genetic mechanisms are continuously identified and increase our understanding of the complex clinical presentation and sometimes unpredictable evolution of pituitary adenomas.

  20. 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.

  1. Incidental Superior Hypophygeal Artery Aneurysm Embedded within Pituitary Adenoma

    PubMed Central

    Choi, Hong-Seok; Kim, Min-Su; Jung, Young-Jin

    2013-01-01

    Intra-cranial aneurysm can be incidental findings in patients with pituitary adenomas, and are usually located outside the pituitary region. However, the coexistence of intrasellar (not intracranial) aneurysms with pituitary adenomas is extremely rare. We report a patient with an incidental superior hypophygeal aneurysm embedded within a non-functional pituitary adenoma which was treated by transsphenoidal surgery after endovascular coil embolization. PMID:24278658

  2. 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.

  3. 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

  4. The pituitary V3 vasopressin receptor and the corticotroph phenotype in ectopic ACTH syndrome.

    PubMed

    de Keyzer, Y; Lenne, F; Auzan, C; Jégou, S; René, P; Vaudry, H; Kuhn, J M; Luton, J P; Clauser, E; Bertagna, X

    1996-03-01

    Ectopic ACTH secretion occurs in highly differentiated and rather indolent tumors like bronchial carcinoids or, in contrast, in various types of aggressive and poorly differentiated neuroendocrine tumors. We explored this phenomenon using the recently cloned human pituitary V3 vasopressin receptor as an alternate molecular marker of the corticotroph phenotype. Expression of V3 receptor, corticotrophin releasing hormone (CRH) receptor, and proopiomelanocortin (POMC) genes was examined in tumors of pituitary and nonpituitary origin. A comparative RT-PCR approach revealed signals for both V3 receptor and CHR receptor mRNAs in 17 of 18 ACTH-secreting pituitary adenomas, and 6 of 6 normal pituitaries; in six growth hormone- or prolactin-secreting adenomas, a very faint V3 receptor signal was observed in three cases, and CRH receptor signal was undetected in all. Six of eight bronchial carcinoids responsible for the ectopic ACTH syndrome had both POMC and V3 receptor signals as high as those in ACTH-secreting pituitary adenomas; in contrast, no POMC signal and only a very faint V3 receptor signal were detected in six of eight nonsecreting bronchial carcinoids. Northern blot analysis showed V3 receptor mRNA of identical size in ACTH-secreting bronchial carcinoids and pituitary tumors. Other types of nonpituitary tumors responsible for ectopic ACTH syndrome presented much lower levels of both POMC and V3 receptor gene expression than those found in ACTH-secreting bronchial carcinoids. In contrast with the V3 receptor, CRH receptor mRNA was detected in the majority of neuroendocrine tumors irrespective of their POMC status. These results show that expression of the V3 receptor gene participates in the corticotroph phenotype. Its striking association with ACTH-secreting bronchial carcinoids defines a subset of nonpituitary tumors in which ectopic POMC gene expression is but one aspect of a wider process of corticotroph cell differentiation, and opens new possibilities of

  5. 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

  6. The Molecular Pathogenesis of Pituitary Adenomas: An Update

    PubMed Central

    Jiang, Xiaobing

    2013-01-01

    Pituitary tumors represent the most common intracranial neoplasms accompanying serious morbidity through mass effects and inappropriate secretion of pituitary hormones. Understanding the etiology of pituitary tumorigenesis will facilitate the development of satisfactory treatment for pituitary adenomas. Although the pathogenesis of pituitary adenomas is largely unknown, considerable evidence indicates that the pituitary tumorigenesis is a complex process involving multiple factors, including genetic and epigenetic changes. This review summarized the recent progress in the study of pituitary tumorigenesis, focusing on the role of tumor suppressor genes, oncogenes and microRNAs. PMID:24396688

  7. [Cushing syndrome due to ectopic ACTH secretion].

    PubMed

    Mendonça, B B; Madureira, G; Bloise, W; Albergaria, A; Halpern, A; Liberman, B; Villares, S M; Batista, M C; Avancini, V F; Nitterdorfi, C T

    1989-01-01

    The authors studied 8 patients (4 males and 4 females) with Cushing's syndrome due to ectopic ACTH secretion. Chronological age ranged from 15 to 45 years and duration of the disease ranged from 3 to 48 months. All patients presented typical signs of Cushing's syndrome, blood hypertension, and four of them had hyperpigmentation of the skin. Five patients had fasting hyperglycemia and all patients but one had serum hypokalemia (serum K = 2.2 to 3.9mEq/l). The circadian rhythm of cortisol was absent in all patients and basal cortisol levels were elevated in all patients but one. Basal ACTH levels evaluated in 7 patients were elevated in 6 (29 to 1050 pg/ml-MRC). One patient presented normal depression of urinary 17-OH after two days of dexamethasone and normal increase of urinary 17-OH and serum 11-dexycortisol after methyrapone. Four patients had carcinoid tumor (3 thymic and 1 bronchial), two had pancreatic islets cell tumors, one had bilateral pheochromocytoma and medular carcinoma of the thyroid, and one had oat cell carcinoma of the lung and medular carcinoma of the thyroid. Thoracic X-rays identified the ectopic ACTH secretion tumor in four cases, all confirmed by CT scan. Abdominal CT showed a difuse enlargement of the adrenals in seven cases and bilateral nodules in one case (pheochromocytomas). Six patients died within 3 years of the diagnosis. The authors concluded that clinical and hormonal findings could mislead the findings of ACTH ectopic secretion and Cushing's disease, and suggest that thoracic X-rays and CT scans of the skull, thorax, and abdome should be done in all cases of Cushing's syndrome. PMID:2559451

  8. Multiple Pituitary Adenomas: A Systematic Review

    PubMed Central

    Budan, Renata M.; Georgescu, Carmen E.

    2016-01-01

    PubMed, Scopus, and Web of Science Core Collection databases were systematically searched for studies reporting synchronous double or multiple pituitary adenomas (MPA), a rare clinical condition, with a vague pathogenesis. Multiple adenomas of the pituitary gland are referred to as morphologically and/or immunocytochemically distinct tumors that are frequently small-sized and hormonally non-functional, to account for the low detection rate. There is no general agreement on how to classify MPA, various criteria, such as tumor contiguity, immunoreactivity, and clonality analysis are being used. Among the component tumors, prolactin (PRL)-immunopositive adenomas are highly prevalent, albeit mute in the majority of cases. The most frequent clinical presentation of MPA is Cushing’s syndrome, given the fact that in more than 50% of reported cases at least one lesion stains for adrenocorticotrophic hormone (ACTH). Plurihormonal hyperactivity may be diagnosed in a patient with MPA when more than one tumor is clinically active (e.g., ACTH and PRL) or in cases with at least one composite tumor (e.g., GH and PRL), to complicate the clinical scenario. Specific challenges associated with MPA include high surgical failure rates, enforcing second-look surgery in certain cases, and difficult preoperative neuroradiological imaging evaluation, with an overall sensitivity of only 25% for magnetic resonance imaging to detect distinct multiple tumors. Alternatively, minor pituitary imaging abnormalities may raise suspicion, as these are not uncommon. Postoperative immunohistochemistry is mandatory and in conjunction to electron microscopy scanning and testing for transcription factors (i.e., Pit-1, T-pit, and SF-1) accurately define and classify the distinct cytodifferentiation of MPA. PMID:26869991

  9. Research Advances in Pituitary Adenoma and DNA Methylation.

    PubMed

    Wei, Zhen-Qing; Li, Yang; Li, Wei-Hua; Lou, Jia-Cheng; Zhang, Bo

    2016-08-01

    DNA methylation is closely related to the genesis and development of pituitary adenoma. Studies have shown that high methylation in the promoter region of potassium voltage-gated chanel,shaker related subfamily,beta member 2,O-6-methylguanine-DNA methyltransferase,echinoderm microtubule associated protein like 2 ,ras homolog family member D ,homeobox B1 ,NNAT, and P16 inhibits the expression of these genes and regulates of the proliferation of pituitary adenoma. DNA methylation is also closely related to invasive pituitary adenoma. Therefore,further study on molecular mechanism of DNA methylation of pituitary adenoma will offer a new strategy for the diagnosis and treatment of pituitary adenoma. PMID:27594164

  10. An Unusual Presentation of Pediatric Cushing Disease: Recurrent Corticotropinoma of the Posterior Pituitary Lobe

    PubMed Central

    Azevedo, Monalisa F.; Xekouki, Paraskevi; Keil, Meg F.; Lange, Eileen; Patronas, Nicholas; Stratakis, Constantine A

    2016-01-01

    Cushing’s syndrome (CS) is rare in childhood and adolescence and its diagnosis and work up are often challenging. We report the case of a 15-year-old girl with a recurrent corticotrophin (ACTH)-secreting adenoma, located in the posterior lobe of the pituitary gland. At the age of 11, she presented with classic CS symptoms; biochemical investigation was compatible with ACTH-dependent Cushing disease, although pituitary gland imaging did not show any tumor. Following transsphenoidal surgery (TSS), histopathological analysis identified an ACTH-secreting pituitary microadenoma arising from the posterior gland. The patient went into remission but 4 years later she presented with recurrent CS; this time, pituitary gland imaging showed a microadenoma located in the posterior lobe, which was resected after TSS. Posterior lobe pituitary adenomas are very rare and often hard to diagnose and treat; this is the first case of such a tumor causing recurrent Cushing’s disease in a child. PMID:20662335

  11. The history of pituitary surgery for Cushing disease.

    PubMed

    Mehta, Gautam U; Lonser, Russell R; Oldfield, Edward H

    2012-02-01

    Although he never performed a pituitary operation for the disease, Harvey Cushing was the first to describe and treat patients with Cushing disease (CD). Other surgeons at the time were reluctant to operate on the pituitary due to the normal sella on skull radiographs in CD and the unclear etiology of the disorder. To better define and understand factors influencing the history of pituitary surgery for CD, the authors analyzed historical texts related to CD biology, diagnosis, and treatment. Cushing's monograph on basophilic pituitary adenomas and cortisol excess appeared in 1932. One year later in 1933, Alfred Pattison performed the first successful pituitary operation for CD by implanting radon seeds in the sella. Resection of a pituitary adenoma for CD was attempted 1 month later in 1933 by Howard Naffziger, resulting in only transient improvement that corresponded to the lack of tumor in the resected tissue. Soon thereafter, Susman in 1935 and Costello in 1936 described pituitary basophilic adenomas at autopsy in patients without premorbid endocrinopathy. They concluded that the adrenal gland was the cause of CD, which resulted in a 3-decade abandonment of pituitary surgery for CD. Jules Hardy in 1963 used the operating microscope to perform the first selective removal of an adrenocorticotropic hormone (ACTH)-secreting microadenoma, which established a pituitary cause and defined the modern treatment of CD. Subsequent reports by Hardy, Laws, and Wilson resulted in widespread acceptance of pituitary surgery for CD. Initial reluctance to operate on the pituitary for CD was multifaceted and included general uncertainty surrounding the etiology of Cushing syndrome as well as a lack of early surgical success, both due to the small size of ACTH-secreting adenomas. Selective removal of ACTH-secreting adenomas identified the source of CD and ended the delay in acceptance of pituitary surgery for CD. PMID:21962161

  12. Coexisting rathke cleft cyst and pituitary adenoma presenting with pituitary apoplexy: report of two cases.

    PubMed

    Gessler, Florian; Coon, Valerie C; Chin, Steven S; Couldwell, William T

    2011-11-01

    The authors report two cases of coexisting Rathke cleft cyst (RCC) and pituitary macroadenoma. Both patients presented at the university hospital with pituitary apoplexy symptoms of sudden-onset headache while undergoing treatment with Coumadin (warfarin). Magnetic resonance imaging was consistent with a pituitary adenoma in one case and RCC in the other. Intraoperative findings and pathological work-up identified RCC along with adenomatous tissue displaying hemorrhagic pituitary adenoma in one and hemorrhagic RCC in the other. Clinical symptoms of pituitary apoplexy were present in both cases, making pituitary and RCC apoplexy clinically indistinguishable. RCC and concomitant pituitary adenoma are a rare intraoperative finding that must be considered as a differential diagnosis in patients with symptoms of pituitary adenoma apoplexy.

  13. VEGF and CD31 association in pituitary adenomas.

    PubMed

    Cristina, Carolina; Perez-Millan, María Inés; Luque, Guillermina; Dulce, Raúl Ariel; Sevlever, Gustavo; Berner, Silvia Inés; Becu-Villalobos, Damasia

    2010-09-01

    Pituitary tumors are usually less vascularized than the normal pituitary, and the role of angiogenesis in these adenomas is contentious. Appraisal of microvascular density and expression of the potent angiogenic vascular endothelial growth factor (VEGF) by immunohistochemistry has yielded controversial results, as a broad spectrum of immunostaining can be found. We determined the protein expression of VEGF and CD31, an endothelial marker, in a series of 56 surgically removed pituitary adenomas using Western blot assay. Prolactinomas had higher VEGF protein expression compared to nonfunctioning or ACTH- and GH-secreting adenomas, while CD31 was similar in the different adenoma histotypes. VEGF and CD31 were not affected by sex, age, years of adenoma evolution, or proliferation rate (Ki67 and PCNA) for all adenoma types. Only in nonfunctioning adenomas CD31 concentration increased significantly with age. There was a positive correlation between CD31 and VEGF expression when all adenoma histotypes were considered, or when prolactinomas and nonfunctioning adenomas were evaluated separately. The positive association of VEGF and CD31 expression suggests the participation of angiogenesis in adenoma development, while epithelial cell proliferation in pituitary tumors is not directly related to VEGF or CD31 expression, and other factors, such as primary genetic alterations may be involved. PMID:20473646

  14. A rare cause of Cushing's syndrome: an ACTH-secreting phaeochromocytoma

    PubMed Central

    Folkestad, Lars; Andersen, Marianne Skovsager; Nielsen, Anne Lerberg; Glintborg, Dorte

    2014-01-01

    Excess glucocorticoid levels cause Cushing's syndrome (CS) and may be due to pituitary, adrenal or ectopic tumours. Adrenocorticotropic hormone (ACTH) levels are useful in identifying adrenal tumours. In rare cases, ACTH-producing phaeochromocytomas are the cause of CS. We present two cases of ACTH-secreting phaeochromocytoma as the underlying cause of CS. In both cases, female patients presented with the classical clinical signs of CS and an adrenal mass. High ACTH levels raised the suspicion of an ACTH-secreting phaeochromocytoma. The diagnosis was confirmed by urinary catecholamine levels and positive fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET) CT (Case 1) and fluorodeoxyglucose PET-CT (Case 2). Both patients were treated with an α-blocker prior to surgical intervention. The two cases underline the importance of thorough diagnostic workup in patients with CS. An ACTH-secreting phaeochromocytoma should be checked for in patients with an adrenal mass and elevated ACTH levels. PMID:25297883

  15. 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

  16. Pathogenesis analysis of pituitary adenoma based on gene expression profiling

    PubMed Central

    WANG, WEIMIN; XU, ZHIMING; FU, LI; LIU, WEI; LI, XINGANG

    2014-01-01

    The aim of the current study was to investigate the pathogenesis of pituitary adenoma through screening of the differentially-expressed genes (DEGs) and proteins in normal pituitary and pituitary adenoma tissues, and analyzing the interactions among them. Following the acquisition of gene expression profiling data from a public functional genomics data repository, Gene Expression Omnibus, DEGs were screened in normal pituitary and pituitary adenoma tissues. Upregulated and downregulated DEGs were further identified through gene ontology functional enrichment analysis. Subsequently, the DEGs were mapped to the Search Tool for the Retrieval of Interacting Genes database, and the protein-protein interaction (PPI) networks of the upregulated and downregulated DEGs were constructed. Finally, the functional modules of the PPI network of the downregulated DEGs were analyzed. In total, 211 upregulated and 413 downregulated DEGs were screened between the normal pituitary and pituitary adenoma samples. Downregulated DEGs were associated with certain functions, including the immune response, hormone regulation and cell proliferation. Upregulated genes were associated with cation transport functions. Five modules were acquired from the PPI network of the downregulated DEGs. Transcription factors, including signal transducer and activator of transcription 3 (STAT3), interleukin 6 (IL-6), B-cell lymphoma 6 protein, early growth response 1, POU1F1, jun B proto-oncogene and FOS were the core nodes in the functional modules. In summary, the DEGs and proteins were identified through screening gene expression profiling and PPI networks. The results of the present study indicated that low expression levels of hormone- and immune-related genes facilitated the occurrence of pituitary adenoma. Low expression levels of IL-6 and STAT3 were significant in the dysimmunity of pituitary adenoma. Furthermore, the low expression level of POU1F1 contributed to the reduction in pituitary hormone

  17. Transnasal stereotactic surgery of pituitary adenomas concomitant with acromegaly.

    PubMed

    Metyolkina, L; Peresedov, V

    1995-01-01

    Since 1960 we have performed stereotactic transsphenoidal cryohypophysectomy in 70 patients with pituitary adenomas, 42 women and 28 men, aged 11-59 years. The dominant clinical syndrome was acromegaly in 50 patients, galactorrhea in 9, amenorrhea in 5, adiposogenital dystrophy in 4 and gigantism with mild endocrine symptomatology in 2 patients. In 67 patients the histological structure of the tumor was established by biopsy (50 patients with eosinophil adenoma, 10 with mixed-type adenoma, 4 with chromophobe adenoma and 3 with basophil adenoma). Somatotropic hormone, human growth hormone, prolactin, ACTH and 17-ketosteroid levels indicated active/inactive adenomas. In 42 cases the adenoma was only intrasellar, which was confirmed by contrast X-ray investigations, CT scanning, angiography and ophthalmological investigation. Transnasal stereotactic cryohypophysectomy was performed in all 70 cases using a stereotactic apparatus especially designed for operations on the pituitary. All patients (except 2) tolerated the operation well. No complications occurred. Vision deteriorated after operation in 1 patient. Thrombosis of the left middle cerebral artery developed in another patient. All the other patients noted improvement directly after operation - rapid diminution of signs of acromegaly and rapid restoration of normal values in hormonal tests. Six patients with continuing growth of the tumor underwent a second operation 1.5-6 years after the first operation. We conclude from our own clinical experience and information from the literature that transnasal stereotactic cryodestruction is highly effective and relatively safe in the management of pituitary adenoma. PMID:8916351

  18. Effects of RXR Agonists on Cell Proliferation/Apoptosis and ACTH Secretion/Pomc Expression

    PubMed Central

    Saito-Hakoda, Akiko; Uruno, Akira; Yokoyama, Atsushi; Shimizu, Kyoko; Parvin, Rehana; Kudo, Masataka; Saito-Ito, Takako; Sato, Ikuko; Kogure, Naotaka; Suzuki, Dai; Shimada, Hiroki; Yoshikawa, Takeo; Fujiwara, Ikuma; Kagechika, Hiroyuki; Iwasaki, Yasumasa; Kure, Shigeo; Ito, Sadayoshi; Sugawara, Akira

    2015-01-01

    Various retinoid X receptor (RXR) agonists have recently been developed, and some of them have shown anti-tumor effects both in vivo and in vitro. However, there has been no report showing the effects of RXR agonists on Cushing’s disease, which is caused by excessive ACTH secretion in a corticotroph tumor of the pituitary gland. Therefore, we examined the effects of synthetic RXR pan-agonists HX630 and PA024 on the proliferation, apoptosis, ACTH secretion, and pro-opiomelanocortin (Pomc) gene expression of murine pituitary corticotroph tumor AtT20 cells. We demonstrated that both RXR agonists induced apoptosis dose-dependently in AtT20 cells, and inhibited their proliferation at their higher doses. Microarray analysis identified a significant gene network associated with caspase 3 induced by high dose HX630. On the other hand, HX630, but not PA024, inhibited Pomc transcription, Pomc mRNA expression, and ACTH secretion dose-dependently. Furthermore, we provide new evidence that HX630 negatively regulates the Pomc promoter activity at the transcriptional level due to the suppression of the transcription factor Nur77 and Nurr1 mRNA expression and the reduction of Nur77/Nurr1 heterodimer recruiting to the Pomc promoter region. We also demonstrated that the HX630-mediated suppression of the Pomc gene expression was exerted via RXRα. Furthermore, HX630 inhibited tumor growth and decreased Pomc mRNA expression in corticotroph tumor cells in female nude mice in vivo. Thus, these results indicate that RXR agonists, especially HX630, could be a new therapeutic candidate for Cushing’s disease. PMID:26714014

  19. Signaling pathway networks mined from human pituitary adenoma proteomics data

    PubMed Central

    2010-01-01

    Background We obtained a series of pituitary adenoma proteomic expression data, including protein-mapping data (111 proteins), comparative proteomic data (56 differentially expressed proteins), and nitroproteomic data (17 nitroproteins). There is a pressing need to clarify the significant signaling pathway networks that derive from those proteins in order to clarify and to better understand the molecular basis of pituitary adenoma pathogenesis and to discover biomarkers. Here, we describe the significant signaling pathway networks that were mined from human pituitary adenoma proteomic data with the Ingenuity pathway analysis system. Methods The Ingenuity pathway analysis system was used to analyze signal pathway networks and canonical pathways from protein-mapping data, comparative proteomic data, adenoma nitroproteomic data, and control nitroproteomic data. A Fisher's exact test was used to test the statistical significance with a significance level of 0.05. Statistical significant results were rationalized within the pituitary adenoma biological system with literature-based bioinformatics analyses. Results For the protein-mapping data, the top pathway networks were related to cancer, cell death, and lipid metabolism; the top canonical toxicity pathways included acute-phase response, oxidative-stress response, oxidative stress, and cell-cycle G2/M transition regulation. For the comparative proteomic data, top pathway networks were related to cancer, endocrine system development and function, and lipid metabolism; the top canonical toxicity pathways included mitochondrial dysfunction, oxidative phosphorylation, oxidative-stress response, and ERK/MAPK signaling. The nitroproteomic data from a pituitary adenoma were related to cancer, cell death, lipid metabolism, and reproductive system disease, and the top canonical toxicity pathways mainly related to p38 MAPK signaling and cell-cycle G2/M transition regulation. Nitroproteins from a pituitary control related to

  20. Overview of genetic testing in patients with pituitary adenomas.

    PubMed

    Beckers, Albert; Rostomyan, Liliya; Daly, Adrian F

    2012-04-01

    Clinically-relevant pituitary adenomas occur with a prevalence of one case per 1000-1300 of the general population. Although most are sporadic, there are several inherited conditions that incur an increased risk of developing a pituitary adenoma. Multiple endocrine neoplasia type 1 and Carney complex (due to mutations in MEN1 and PRKAR1A, respectively) are established pituitary adenoma predisposition conditions, while multiple endocrine neoplasia type 4 (due to CDKN1B mutations) is an emerging rare condition. Familial isolated pituitary adenomas (FIPA) is a novel condition not associated with these multiple endocrine neoplasias. Mutations in the aryl hydrocarbon receptor interacting protein gene account for about 15% of FIPA kindreds and are associated with about 10-20% of macroadenomas that occur in children, adolescents and young adults. When treating a pituitary adenoma patient, relevant familial and clinical factors such as associated tumors or syndromic features should be assessed at the outset in order to guide the correct choice of genetic testing in appropriate individuals. PMID:22503805

  1. Brain sites mediating corticosteroid feedback inhibition of stimulated ACTH secretion

    SciTech Connect

    Jacobson, L.

    1989-01-01

    There is substantial evidence that the brain mediates stress-induced and circadian increases in ACTH secretion and that corticosteroid concentrations which normalize basal plasma ACTH are insufficient to normalize ACTH responses to circadian or stressful stimuli in adrenalectomized rats. To identify brain sites mediating corticosteroid inhibition of stimulated ACTH secretion, two approaches were used. The first compared brain ({sup 14}C)-2-deoxyglucose uptake in rats with differential ACTH responses to stress. Relative to sham-adrenalectomized (SHAM) rats, adrenalectomized rats replaced with low, constant corticosterone levels via a subcutaneous corticosterone pellet (B-PELLET) exhibited elevated and prolonged ACTH responses to a variety of stimuli. Adrenalectomized rate given a circadian corticosterone rhythm via corticosterone in their drinking water exhibited elevated ACTH levels immediately after stress, but unlike B-PELLET rats, terminated stress induced ACTH secretion normally relative to SHAMS. Therefore, the abnormal ACTH responses to stress in B-PELLET rats were due to the lack of both circadian variations and stress-induced increases in corticosterone. Hypoxia was selected as a standardized stimulus for correlating brain ({sup 14}C)-2-deoxyglucose uptake with ACTH secretion. In intact rats, increases in plasma ACTH and decreases in arterial PO{sub 2} correlated with the severity of hypoxia at arterial PCO{sub 2} below 60 mm Hg. Hypoxia PELLET vs. SHAM rats. However, in preliminary experiments, although hypoxia increased brain 2-deoxyglucose uptake in most brain regions, plasma ACTH correlated poorly with 2-deoxyglucose uptake at 12% and 10% O{sub 2}.

  2. Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary

    PubMed Central

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

    2014-01-01

    Purpose Recent studies suggest that adult pituitary stem cells may play a role in pituitary tumorigenesis. We sought to explore whether the Glial cell-line derived neurotrophic factor receptor alpha 2 (GFRα2), a recently described pituitary stem/progenitor marker, might be differentially expressed in pituitary adenomas versus normal pituitary. Methods The expression of GFRα2 and other members of the GFR receptor family (GFRα1, α3, α4) were analyzed using RT-PCR, western blot, and immunohistochemistry in 39 pituitary adenomas, 14 normal pituitary glands obtained at autopsy, and cDNA from 3 normal pituitaries obtained commercially. Results GFRα2 mRNA was ~2.6 fold under-expressed in functioning adenomas (P <0.01) and ~3.5 fold over-expressed in non-functioning adenomas (NFAs) (P <0.05) compared to normal pituitary. Among NFAs, GFRα2 was significantly over-expressed (~5-fold) in the gonadotropinoma subtype only (P<0.05). GFRα2 protein expression appeared to be higher in most NFAs, although there was heterogeneity in protein expression in this group. GFRα2 protein expression appeared consistently lower in functioning adenomas by IHC and western blot. In normal pituitary, GFRα2 was localized in Rathke’s remnant, the putative pituitary stem cell niche, and in corticotropes. Conclusion Our results suggest that the pituitary stem cell marker GFRα2 is under-expressed in functioning adenomas and over-expressed in NFAs, specifically gonadotropinomas. Further studies are required to elucidate whether over-expression of GFRα2 in gonadotropinomas might play a role in pituitary tumorigenesis. PMID:24402129

  3. 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

  4. 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

  5. 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. PMID:25077093

  6. Gigantism caused by growth hormone secreting pituitary adenoma

    PubMed Central

    Rhee, Noorisaem; Jeong, Kumi; Yang, Eun Mi

    2014-01-01

    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. PMID:25077093

  7. 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.

  8. Chondroid chordoma of the sella turcica mimicking a pituitary adenoma.

    PubMed

    Wu, Arthur W; Bhuta, Sunita; Salamon, Noriko; Martin, Neil; Wang, Marilene B

    2015-01-01

    We report an unusual case of a chondroid chordoma of the sella turcica that mimicked the clinical and radiologic presentation of the more common pituitary adenoma. A 50-year-old man presented with bitemporal visual field deficits. Magnetic resonance imaging (MRI) detected a sellar mass that was suggestive of a pituitary adenoma. However, the intraoperative appearance of the mass was not consistent with an adenoma, and frozen-section pathology was obtained. Pathology identified the mass as a malignant lesion. Based on this finding, the mass was treated more aggressively. Chondroid chordomas are rare and slowly growing but locally aggressive tumors. The prognosis depends on the ability to totally resect the mass, so differentiating this tumor from a benign lesion is critical. An intrasellar chordoma can be confused clinically and radiologically with a pituitary adenoma. These two lesions are nearly identical on MRI, although T2-weighted imaging sometimes demonstrates higher intensity with a chondroid chordoma. Computed tomography may be helpful in demonstrating bony destruction by these lesions, as can the presence of intralesional calcifications. Intraoperative findings of bony invasion or a purple-red color may also lead the surgeon to suspect a diagnosis other than pituitary adenoma.

  9. Familial acromegaly with pituitary adenoma. Report of three affected siblings.

    PubMed

    Abbassioun, K; Fatourehchi, V; Amirjamshidi, A; Meibodi, N A

    1986-03-01

    The authors report the cases of three brothers with pituitary adenomas who had classical findings of acromegaly and gigantism. Two had irreducibly elevated growth hormone (GH) values and underwent transsphenoidal microsurgical extirpation of their tumors. The third acromegalic brother had a normal GH value and evidence of panhypopituitarism; he had a small intrasellar tumor and a partially empty sella. The pattern of inheritance was probably autosomal recessive. A review of literature indicated that familial incidence of isolated acromegaly with pituitary adenomas is rare. PMID:3950729

  10. Expression pattern of the Hedgehog signaling pathway in pituitary adenomas.

    PubMed

    Yavropoulou, Maria P; Maladaki, Anna; Topouridou, Konstantina; Kotoula, Vasiliki; Poulios, Chris; Daskalaki, Emily; Foroglou, Nikolaos; Karkavelas, George; Yovos, John G

    2016-01-12

    Several studies have demonstrated the role of Wnt and Notch signaling in the pathogenesis of pituitary adenomas, but data are scarce regarding the role of Hedgehog signaling. In this study we investigated the differential expression of gene targets of the Hedgehog signaling pathway. Formalin-fixed, paraffin-embedded specimens from adult patients who underwent transphenoidal resection and normal human pituitary tissues that were obtained from autopsies were used. Clinical information and data from pre-operative MRI scan (extracellular tumor extension, tumor size, displacement of the optic chiasm) were retrieved from the Hospital's database. We used a customized RT(2) Profiler PCR Array, to investigate the expression of genes related to Notch and Hedgehog signaling pathways (PTCH1, PTCH2, GLI1, GLI3, NOTCH3, JAG1, HES1, and HIP). A total of 52 pituitary adenomas (32 non-functioning adenomas, 15 somatotropinomas and 5 prolactinomas) were used in the final analysis. In non-functioning pituitary adenomas there was a significant decrease (approximately 75%) in expression of all Hedgehog related genes that were tested, while Notch3 and Jagged-1 expression was found significantly increased, compared with normal pituitary tissue controls. In contrast, somatotropinomas demonstrated a significant increase in expression of all Hedgehog related genes and a decrease in the expression of Notch3 and Jagged-1. There was no significant difference in the expression of Hedgehog and Notch related genes between prolactinomas and healthy pituitary tissues. Hedgehog signalling appears to be activated in somatotropinomas but not in non-functioning pituitary adenomas in contrast to the expression pattern of Notch signalling pathway. PMID:26620835

  11. 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.

  12. Expression of growth hormone (GH)-releasing factor gene in GH-producing pituitary adenoma.

    PubMed

    Wakabayashi, I; Inokuchi, K; Hasegawa, O; Sugihara, H; Minami, S

    1992-02-01

    Pituitary cells synthesize various neuropeptides that influence pituitary hormone secretion. GH-releasing factor (GRF) may also be produced by normal or pituitary tumor cells. We examined GRF gene expression in pituitary tumors. Standard techniques for the analysis of GRF gene expression did not appear to be suitable. Highly sensitive reverse transcription coupled to polymerase chain reaction was used. Specimens of pituitary adenoma were obtained by transsphenoidal adenomectomy from six patients with acromegaly and three patients with no clinical evidence of pituitary hormone overproduction; non-functioning adenoma. Pituitary glands were collected at autopsy from three patients who died from nonendocrine disorders. A specific GRF gene transcript was detected in five out of six GH-producing pituitary adenomas, whereas this was not found in three separate specimens of nonfunctioning pituitary adenoma or anterior and posterior pituitary tissue. The data suggest that GRF is synthesized as an intrinsic product in human GH-producing pituitary adenoma.

  13. [The results of proton radiosurgery for pituitary endosellar adenomas].

    PubMed

    Granov, A M; Shalek, R A; Karlin, D L; Vinogradov, V M; Ialynych, N N; Pushkareva, T V; Zargarova, O P; Gerasimov, S V; Koshkin, Iu A

    2013-01-01

    465 patients with pituitary endosellar adenomas have passed irradiation on the synchrocyclotron PNPI (1000 MeV). Due to the high energy of the proton beam the rotating-convergent shoot-through technique was used. The single dose of 80-100 Gy was given. In patients with prolactin adenomas clinical remission was detected in 80%, and the stabilization of the disease was achieved in 15%. Pregnancies in 21 patients ended in the birth of healthy children, and 4 of them gave the birth twice. Complete clinical remission was observed in 92% of patients with Cushing's disease. Sustained recovery and full normalization of growth hormone level were observed during long-term follow-up in 86% of patients with acromegaly. There was significant reducing of the high hormone level on the fifth year of follow-up in any clinical form of pituitary adenomas while the development of the secondary hypopituitarism was not defected in the most of the patients. Clinical remission in patients with non-secreting adenomas was 95%. Irradiation by the proton beam was not accompanied by serious life-threatening complications. Thus this type of treatment for pituitary endosellar adenomas is highly effective and safe and, sometimes, the only method. PMID:24032220

  14. Functional Characteristics of Multipotent Mesenchymal Stromal Cells from Pituitary Adenomas.

    PubMed

    Megnis, Kaspars; Mandrika, Ilona; Petrovska, Ramona; Stukens, Janis; Rovite, Vita; Balcere, Inga; Jansone, Laima Sabine; Peculis, Raitis; Pirags, Valdis; Klovins, Janis

    2016-01-01

    Pituitary adenomas are one of the most common endocrine and intracranial neoplasms. Although they are theoretically monoclonal in origin, several studies have shown that they contain different multipotent cell types that are thought to play an important role in tumor initiation, maintenance, and recurrence after therapy. In the present study, we isolated and characterized cell populations from seven pituitary somatotroph, nonhormonal, and lactotroph adenomas. The obtained cells showed characteristics of multipotent mesenchymal stromal cells as observed by cell morphology, cell surface marker CD90, CD105, CD44, and vimentin expression, as well as differentiation to osteogenic and adipogenic lineages. They are capable of growth and passaging under standard laboratory cell culture conditions and do not manifest any hormonal cell characteristics. Multipotent mesenchymal stromal cells are present in pituitary adenomas regardless of their clinical manifestation and show no considerable expression of somatostatin 1-5 and dopamine 2 receptors. Most likely obtained cells are a part of tissue-supportive cells in pituitary adenoma microenvironment. PMID:27340409

  15. 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

  16. Functional Characteristics of Multipotent Mesenchymal Stromal Cells from Pituitary Adenomas

    PubMed Central

    Megnis, Kaspars; Mandrika, Ilona; Petrovska, Ramona; Stukens, Janis; Rovite, Vita; Balcere, Inga; Jansone, Laima Sabine; Peculis, Raitis; Pirags, Valdis

    2016-01-01

    Pituitary adenomas are one of the most common endocrine and intracranial neoplasms. Although they are theoretically monoclonal in origin, several studies have shown that they contain different multipotent cell types that are thought to play an important role in tumor initiation, maintenance, and recurrence after therapy. In the present study, we isolated and characterized cell populations from seven pituitary somatotroph, nonhormonal, and lactotroph adenomas. The obtained cells showed characteristics of multipotent mesenchymal stromal cells as observed by cell morphology, cell surface marker CD90, CD105, CD44, and vimentin expression, as well as differentiation to osteogenic and adipogenic lineages. They are capable of growth and passaging under standard laboratory cell culture conditions and do not manifest any hormonal cell characteristics. Multipotent mesenchymal stromal cells are present in pituitary adenomas regardless of their clinical manifestation and show no considerable expression of somatostatin 1–5 and dopamine 2 receptors. Most likely obtained cells are a part of tissue-supportive cells in pituitary adenoma microenvironment. PMID:27340409

  17. 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

  18. 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

  19. Transferrin and transferrin receptor in human hypophysis and pituitary adenomas.

    PubMed Central

    Tampanaru-Sarmesiu, A.; Stefaneanu, L.; Thapar, K.; Kontogeorgos, G.; Sumi, T.; Kovacs, K.

    1998-01-01

    Transferrin (Tf), a major transport protein for iron in the blood and an essential growth factor in some tissues, acts via specific transferrin receptor (TfR). We studied the cellular distribution of Tf and TfR gene expression in 50 human nontumorous autopsy pituitaries and 42 surgically removed pituitary adenomas. Tf and TfR mRNA accumulation was correlated with Ki-67 proliferation marker. In nontumorous pituitaries without iron deposits Tf immunoreactivity was localized in some growth hormone, prolactin, adrenocorticotropin, thyrotropin, and luteinizing hormone cells. Most adenohypophysial cells were immunopositive for TfR. In pituitaries with iron deposits, Tf and TfR were localized only in iron-free cells. Tf mRNA and protein were present in 27 and 32 adenomas, respectively; Ki-67 labeling index of tumors positive for Tf mRNA was significantly higher than in those without transcript (0.94% versus 0.51%; P < 0.025). A positive linear correlation between tumor growth fraction and Tf mRNA signal intensity was evident (r = 0.32; P = 0.04). TfR mRNA and encoded protein were demonstrated in 26 and 31 adenomas, respectively; Ki-67 immunoreactivities were not correlated with the presence of TfR transcripts and signal intensities. These data suggest that Tf may act as a growth-promoting factor for pituitary tumors. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:9466567

  20. 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.

  1. Mixed TSH- and HGH-secreting pituitary adenoma.

    PubMed

    Coculescu, M; Pop, A; Constantinovici, A; Oprescu, M; Temeli, E; Marinescu, I

    1982-01-01

    A man aged 36 was found to have an invasive pituitary adenoma with evolutive acromegaly and hyperthyroidism and a high serum level of HGH and TSH, suggesting a tumoral production of HGH and TSH. The serum concentration of HGH was above 180 ng/ml; there was also an inappropriately high serum level of TSH, which failed to decrease following the triiodothyronine suppression test and did not increase after TRH (0.4 mg i.v.). In the tumoral tissue removed during pituitary surgery, the concentration of TSH was 1,267.2 microU/g and that of HGH was 1,158.6 micrograms/g, showing that the pituitary adenoma secreted both TSH and HGH.

  2. Mammosomatotroph cell adenoma of the human pituitary: a morphologic entity.

    PubMed

    Horvath, E; Kovacs, K; Killinger, D W; Smyth, H S; Weiss, M H; Ezrin, C

    1983-01-01

    Nine cases of a hitherto undescribed morphologic entity, termed mammosomatotroph cell adenoma of the human pituitary, are reported. These tumors, occurring mostly in men, are invariably associated with acromegaly (or gigantism) and high-normal or slightly elevated blood prolactin levels, and it cannot be distinguished clinically from well-differentiated growth hormone cell or mixed growth hormone cell-prolactin cell adenomas. They show a slow growth rate and usually exhibit a diffuse pattern and intense cytoplasmic acidophilia by histology. The immunoperoxidase technique detects both growth hormone and prolactin within the same cells. Electron microscopy reveals monomorphous tumors with a fine structure markedly similar to that of well-differentiated, densely granulated growth hormone cell adenomas. An added feature and diagnostic marker of mammosomatotroph cell adenoma is the presence of extracellular deposits of secretory material. One tumor shows a marked abnormality of hormone packaging and storage, resulting in the cytoplasmic accumulation of pleomorphic bodies containing semicrystalline secretory material. PMID:6402839

  3. Metallothionein isoform 3 gene is differentially expressed in corticotropin-producing pituitary adenomas.

    PubMed

    Giorgi, R R; Correa-Giannella, M L C; Casarini, A P M; Machado, M C; Bronstein, M D; Cescato, V A; Giannella-Neto, D

    2005-01-01

    In order to search for candidate genes related to pituitary adenoma aggressiveness, the present investigation was intended to compare the mRNA expression profile from a pool of four nonfunctional pituitary adenomas (NFPA) with a spinal cord metastasis of a nonfunctional pituitary carcinoma (MNFPC). The metallothionein isoform 3 (MT3) gene was differentially expressed in nonfunctional adenomas in comparison to the metastasis of nonfunctional carcinoma. A microarray dataset comprising 19,881 probes was employed for comparing expression profiles of a spinal cord metastasis of a nonfunctional pituitary carcinoma with a pool of four nonfunctional pituitary adenomas. RT-qPCR confirmed the microarray findings and was used to investigate MT3 mRNA gene expression in tumor samples of a series of 52 different pituitary adenoma subtypes comprising 10 corticotropin (ACTH)-producing, 18 growth hormone (GH)-producing, 8 prolactin (PRL)-producing, and 16 nonfunctional adenomas. Microarray data analysis by GeneSifter program unveiled Gene Ontology terms related to zinc ion-binding activity closely related to MT3 function. MT3 mRNA expression was statistically significantly higher in ACTH-producing pituitary adenomas and in nonfunctional pituitary adenomas in comparison to the other pituitary adenoma subtypes. The more abundant expression of this gene in ACTH-producing pituitary adenomas suggests that MT3 could be related to distinct pituitary cell lineage regulating the activity of some transcription factor of importance in hormone production and/or secretion. PMID:16601360

  4. [Thyroid-stimulating hormone-secreting pituitary adenoma].

    PubMed

    Tóth, M; Rácz, K; Kiss, R; Fütö, L; Varga, I; Karlinger, K; Dékány, E; Czirják, S; Pásztor, E; Gláz, E

    1994-12-01

    A 40-year-old male patient with a 2 years history of recurring hyperthyroidism is presented with clinical hyperthyroidism and diffuse goiter. Despite thyreostatic treatment and surgical thyroid ablation the hyperthyroidism recurred. The patient had laboratory evidence of hyperthyroidism and his serum TSH was persistently and enormously elevated (T4:214 nmol/l, T3:6.9 nmol/l, TSH:218 mIU/l)> Computed tomography and magnetic resonance imaging confirmed a pituitary mass of 7 cm in a-p diameter, with supra-, parasellar and sphenoidal extension. The pituitary adenoma was partially resected by transsphenoidal surgery, which failed to result in a substantial decrease in the serum thyrotropin level. Pituitary irradiation and a long-term somatostatin analog octreotide treatment (300-600 micrograms/die) combined with bromocriptine therapy resulted in a significant, but still incomplete suppression of thyrotropin secretion (TSH level about 15 mIU/l) and persisting mild hyperthyroidism. The size of the adenoma was unchanged during the two years of highdose octreotide treatment period. According to our best knowledge this is the first reported case of a thyrotropin-secreting pituitary adenoma in Hungary. PMID:7991245

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

    PubMed Central

    Zhao, Peng; Hu, Wei; Wang, Hongyun; Yu, Shengyuan; Li, Chuzhong; Bai, Jiwei; Gui, Songbai; Zhang, Yazhuo

    2015-01-01

    Pituitary adenomas, monoclonal in origin, are the most common intracranial neoplasms. Altered gene expression as well as somatic mutations is detected frequently in pituitary adenomas. The purpose of this study was to detect differentially expressed genes (DEGs) and biological processes during tumor formation of pituitary adenomas. We performed an integrated analysis of publicly available GEO datasets of pituitary adenomas to identify DEGs between pituitary adenomas and normal control (NC) tissues. Gene function analysis including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) networks analysis was conducted to interpret the biological role of those DEGs. In this study we detected 3994 DEGs (2043 upregulated and 1951 downregulated) in pituitary adenoma through an integrated analysis of 5 different microarray datasets. Gene function analysis revealed that the functions of those DEGs were highly correlated with the development of pituitary adenoma. This integrated analysis of microarray data identified some genes and pathways associated with pituitary adenoma, which may help to understand the pathology underlying pituitary adenoma and contribute to the successful identification of therapeutic targets for pituitary adenoma. PMID:25642247

  6. 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. PMID:26683132

  7. 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.

  8. Abscess formation associated with pituitary adenoma: A case report: Changes in the MRI appearance of pituitary adenoma before and after abscess formation

    PubMed Central

    Kuge, Atsushi; Sato, Shinya; Takemura, Sunao; Sakurada, Kaori; Kondo, Rei; Kayama, Takamasa

    2011-01-01

    Background: Pituitary abscess is an extremely rare finding. The abscess may arise as a primary pituitary lesion or be associated with parasellar pathology. It is important for pituitary abscess treatments to perform early diagnosis. In this report, we describe a case of pituitary adenoma in which MRI findings changed during the follow-up period and strongly suggested progression to pituitary abscess arising from adenoma. Case Description: In a 73-year-old female, pituitary adenoma had been incidentally detected; MRI showed typical findings of pituitary adenoma, and we had followed up the pituitary lesion and clinical symptoms. Six months later, she had oculomotor nerve palsy and symptoms of hypopituitarism. Hematological examination revealed inflammation and hypopituitarism. MRI showed striking changes in the signal intensity of the pituitary lesion, and strongly suggested occurrence of sinusitis and pituitary abscess ascribed to pituitary adenoma. She was admitted and endoscopic transsphenoidal surgery was performed. The sellar floor was destroyed, and yellowish-white creamy pus was observed. A histopathological study using hematoxylin-eosin staining showed adenoma and inflammatory cells. Aerobic, anaerobic, and fungal cultures were negative. Antibiotics were administered and hormonal replacement was started. Neurological and general symptoms were improved, and postoperative MRI revealed complete evacuation of abscess and removal of tumor. Conclusions: Pituitary abscess within invasive pituitary adenoma is a rare entity, and shows high mortality. Early diagnosis of pituitary abscess is very important for the prompt surgery and initiation of treatment with antibiotics. In our case, changes in MRI findings were helpful to diagnose pituitary abscess, and endoscopic transsphenoidal surgery was an optimal surgical treatment. PMID:21297925

  9. 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

  10. 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.

  11. Genetic mutations in sporadic pituitary adenomas--what to screen for?

    PubMed

    Lecoq, Anne-Lise; Kamenický, Peter; Guiochon-Mantel, Anne; Chanson, Philippe

    2015-01-01

    Pituitary adenomas are benign intracranial neoplasms that can result in morbidity owing to local invasion and/or excessive or deficient hormone production. The prevalence of symptomatic pituitary adenomas is approximately 1:1,000 in the general population. The vast majority of these tumours occur sporadically and are not part of syndromic disorders. However, germline mutations in genes known to predispose individuals to familial pituitary adenomas are found in a few patients with sporadic pituitary adenomas. Mutations in AIP (encoding aryl-hydrocarbon receptor-interacting protein) are the most frequently observed germline mutations. The prevalence of these mutations in patients with sporadic pituitary adenomas is ∼4%, but can increase to 8-20% in young adults with macroadenomas or gigantism, and also in children. Germline mutations in MEN1 (encoding menin) result in multiple endocrine neoplasia type 1 and are found in very young patients with isolated sporadic pituitary adenomas, which highlights the importance of the chromosome 11q13 locus in pituitary tumorigenesis. In this Review, we describe the clinical features of patients with sporadic pituitary adenomas that are associated with AIP or MEN1 mutations, and discuss the molecular mechanisms that might be involved in pituitary adenoma tumorigenesis. We also discuss genetic screening of patients with sporadic pituitary adenomas and investigations of relatives of these patients who also have the same genetic mutations. PMID:25350067

  12. Paternal deprivation prior to adolescence and vulnerability to pituitary adenomas.

    PubMed

    Sobrinho, L G; Duarte, J S; Paiva, I; Gomes, L; Vicente, V; Aguiar, P

    2012-06-01

    It has been reported that women with prolactinoma were exposed, early in life, to an environment characterized by an absent or violent father. The present study was designed to evaluate whether paternal absence or violent paternal behavior were more prevalent in patients with pituitary adenomas (prolactinoma, acromegaly, non-secreting adenoma and Cushing's disease) compared to a control population. We conducted an observational case-control multicenter study. We interviewed 395 patients with prolactinoma (296 females and 99 males), 130 with acromegaly (87 females and 43 males), 237 with non-secreting adenoma (144 females and 93 males) and 68 with Cushing's disease (61 females and 7 males) and 365 patients from the same clinics with nodular thyroid disease or lymphocytic thyroiditis with euthyroidism as controls. Violent or absent fathers were significantly more prevalent in patients with prolactinoma or acromegaly than in controls (P = 0.001 and P = 0.002, respectively) but not in patients with non-secreting adenoma or corticotrophinoma. Absent fathers in prolactinoma and acromegaly versus controls: P = 0.001 and P = 0.119. Violent fathers in prolactinoma and acromegaly versus controls: P = 0.069 and P = 0.001. The prevalence of absent or violent fathers was also significantly higher in prolactinoma and acromegaly when compared to non-secreting adenoma (P = 0.039 and P = 0.033, respectively). Paternal deprivation before adolescence may be a risk factor for prolactinoma and acromegaly but not for non-secreting pituitary adenomas or Cushing's disease.

  13. 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. PMID

  14. Management of clinically non-functioning pituitary adenoma.

    PubMed

    Chanson, Philippe; Raverot, Gerald; Castinetti, Frédéric; Cortet-Rudelli, Christine; Galland, Françoise; Salenave, Sylvie

    2015-07-01

    Clinically NFPA is currently the preferred term for designing all the pituitary adenomas which are not hormonally active (in other words, not associated with clinical syndromes such as amenorrhea-galactorrhea in the context of prolactinomas, acromegaly, Cushing's disease or hyperthyroidism secondary to TSH-secreting adenomas). They account for 15-30% of pituitary adenomas. Diagnosis is usually made either in the context of mass effect due to a macroadenoma or, increasingly, fortuitously during imaging performed for some unrelated purpose; the latter case is known as pituitary incidentaloma. Surgery is indisputably indicated in case of tumoral syndrome, but other aspects of NFPA (hormonal work-up, follow-up, and especially postoperative follow-up, management of remnant or recurrence, the special case of incidentaloma, or apoplexy) remain controversial. The French Endocrinology Society (SFE) therefore set up an expert working group of endocrinologists, neurosurgeons, ophthalmologists, neuroradiologists, pathologists and biologists to draw up guidelines, at the 2012 SFE Congress in Toulouse, France. The present article presents the guidelines suggested by this group of French-speaking experts. PMID:26072284

  15. Cushing Disease After Treatment of Nonfunctional Pituitary Adenoma

    PubMed Central

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

    2015-01-01

    Abstract 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. PMID:26705201

  16. Recent clinical and pathophysiological advances in non-functioning pituitary adenomas.

    PubMed

    Korbonits, Márta; Carlsen, Eivind

    2009-04-01

    Pituitary adenomas are being recognized and diagnosed with increasing frequency. One of the most common forms of pituitary lesion is the clinically non-functioning pituitary adenoma (NFPA), which is often diagnosed incidentally. The vast majority of pituitary adenomas are sporadic, but familial adenomas can occur in the multiple pituitary adenoma type 1 syndrome, in Carney complex or in familial isolated pituitary adenoma. Distinguishing NFPA from prolactinomas can occasionally cause a differential diagnostic problem due to the 'stalk effect'. NFPA often show hormone synthesis on tissue immunostaining without causing clinical symptoms. Most often these are silent gonadotroph adenomas, with silent corticotroph or somatotroph adenomas occurring less frequently. It is unclear why these silent adenomas do not release hormones at a clinically recognizable level, although it is probable that there is a continuum between fully functional and completely silent adenomas. Another intriguing feature of NFPAs is the lack of clinical response to somatostatin analogues, despite the presence of somatostatin receptors and an often good response in the in vitro setting. Temozolomide has been successfully used for the treatment of a few aggressive pituitary adenomas, and the response to this drug could be influenced by the expression of the DNA repair enzyme O-6-methylguanine DNA methyltransferase. The early diagnosis, prediction of long-term outcome and treatment of NFPAs remain a challenge for endocrinologists. PMID:19407508

  17. Double, synchronous pituitary adenomas causing acromegaly and Cushing's disease. A case report and review of literature.

    PubMed

    Zieliński, Grzegorz; Maksymowicz, Maria; Podgórski, Jan; Olszewski, Włodzimierz T

    2013-06-01

    Double pituitary adenomas are very rare and present up to 1 % of pituitary adenomas in unselected autopsy series and up to 2 % in large surgical series. We report a case of a 47-year-old man presented slight clinical features of acromegaly with 2 years duration. Endocrine evaluation confirmed active acromegaly and revealed adrenocorticotropin hormone-dependent hypercortisolemia. Preoperative magnetic resonance imaging of the pituitary demonstrated clearly separated double microadenomas with different intensity. The patient underwent transsphenoidal surgery and both tumors were completely removed and were fixed separately. The histological and ultrastructural examination confirmed coincidence of the double, clearly separated pituitary adenomas in one gland. Postoperative function of the hypothalamo-hypophyseal axis was normalized. We conclude from this case and a literature review that double endocrinologically active pituitary adenomas leading to acromegaly and Cushing's disease may occur. Additionally, a review of the literature regarding multiple pituitary adenomas has also been performed.

  18. Ultrastructural study of mixed growth hormone & prolactin secreting pituitary adenomas.

    PubMed

    Sarkar, C; Dinda, A K; Roy, S; Kochupillai, N; Kharbanda, K; Tandon, P N

    1992-08-01

    An ultrastructural study was done on 15 mixed growth hormone (GH) and prolactin (PRL)-secreting pituitary adenomas surgically removed from acromegalic patients with hyper-prolactinaemia, in order to see whether the 2 hormones were present in the same cell or in different cells. Double labelling immunogold technique was used for simultaneous ultrastructural localization of GH and PRL. It was found that each neoplastic cell in these 15 tumours (30 to 50 cells were studied in each case) contained 4 populations of granules viz., (i) granules positive for only GH; (ii) granules positive for only PRL; (iii) granules positive for both GH and PRL; and (iv) granules negative for both GH and PRL (unlabelled). Though the relative percentage of these 4 types of granules varied from cell to cell even within the same tumour, the major population (49.9 to 96%) was constituted by the mixed granules showing labelling for both GH and PRL. Almost all the cells examined from each tumour appeared to be mammosomatotrophs. Thus, the study indicated that mammosomatotroph adenomas are perhaps more common among mixed GH and PRL--secreting pituitary adenomas than previously believed. It could be important to recognize these tumours from the therapeutic point of view.

  19. A silent follicle-stimulating hormone-producing pituitary adenoma in a teenage male.

    PubMed

    Tamiya, Hiroyuki; Fukuhara, Noriaki; Yoshida, Naohiro; Suzuki, Hisanori; Takeshita, Akira; Inoshita, Naoko; Nishioka, Hiroshi; Takeuchi, Yasuhiro; Sano, Toshiaki; Yamada, Shozo

    2011-12-01

    An 18-year-old male was referred to Toranomon Hospital seeking reoperation for recurrent clinically nonfunctioning pituitary adenoma. A pituitary macroadenoma was first suspected at age 15 due to intractable headaches. Endocrine data were unremarkable except slightly elevated serum follicle-stimulating hormone (FSH). Transsphenoidal surgery done at another hospital achieved partial tumor removal but the remaining tumor regrew 2 years after surgery. The recurrent tumor was completely and selectively removed on repeat surgery at Toranomon Hospital. Pathological examination confirmed a silent FSH-producing pituitary adenoma. Forty-five patients less than 20 years old underwent transsphenoidal surgery for pituitary adenoma at Toranomon Hospital between 1993 and 2010. Of the 45 patients, 36 (80.0%) had clinically functioning adenomas and the other 9 (20.0%) had clinically non-functioning adenomas. No patients, other than the present case, had a silent gonadotroph adenoma. In contrast, among 579 patients over 20 years old undergoing surgery for nonfunctioning pituitary adenomas between 2006 and 2010 at Toranomon Hospital, 304 (52.3%) had silent gonadotroph adenomas. Gonadotroph adenomas are more common with aging: for example, 37 (61.7%) of 60 patients more than 70 years old at the time of operation had gonadotroph adenomas. In conclusion, gonadotroph adenomas, especially silent gonadotroph adenomas, are extremely rare in childhood and adolescence.

  20. Human Pituitary Adenoma Proteomics: New Progresses and Perspectives.

    PubMed

    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

  1. 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. PMID:21450940

  2. Hypothalamic neuronal hamartoma associated with pituitary growth hormone cell adenoma and acromegaly.

    PubMed

    Asa, S L; Bilbao, J M; Kovacs, K; Linfoot, J A

    1980-01-01

    A hypothalamic neuronal hamartoma associated with a sparsely granulated growth hormone cell adenoma of the pituitary and acromegaly is reported. It is suggested that the patient had a primary neuronal tumor, whose neurosecretory activity promoted the development of the growth hormone secreting pituitary adenoma causing acromegaly.

  3. Analysis of regulatory networks constructed based on gene coexpression in pituitary adenoma.

    PubMed

    Gong, Jie; Diao, Bo; Yao, Guo Jie; Liu, Ying; Xu, Guo Zheng

    2013-12-01

    Gene coexpression patterns can reveal gene collections with functional consistency. This study systematically constructs regulatory networks for pituitary tumours by integrating gene coexpression, transcriptional and posttranscriptional regulation. Through network analysis, we elaborate the incidence mechanism of pituitary adenoma. The Pearson's correlation coefficient was utilized to calculate the level of gene coexpression. By comparing pituitary adenoma samples with normal samples, pituitary adenoma-specific gene coexpression patterns were identified. For pituitary adenoma-specific coexpressed genes, we integrated transcription factor (TF) and microRNA (miRNA) regulation to construct a complex regulatory network from the transcriptional and posttranscriptional perspectives. Network module analysis identified the synergistic regulation of genes by miRNAs and TFs in pituitary adenoma. We identified 142 pituitary adenoma-specific active genes, including 43 TFs and 99 target genes of TFs. Functional enrichment of these 142 genes revealed that the occurrence of pituitary adenoma induced abnormalities in intracellular metabolism and angiogenesis process. These 142 genes were also significantly enriched in adenoma pathway. Module analysis of the systematic regulatory network found that three modules contained elements that were closely related to pituitary adenoma, such as FGF2 and SP1, as well as transcription factors and miRNAs involved in the tumourigenesis. These results show that in the occurrence of pituitary adenoma, miRNA, TF and genes interact with each other. Based on gene expression, the proposed method integrates interaction information from different levels and systematically explains the occurrence of pituitary tumours. It facilitates the tracing of the origin of the disease and can provide basis for early diagnosis of complex diseases or cancer without obvious symptoms.

  4. Melanoma of the sellar region mimicking pituitary adenoma.

    PubMed

    Sidiropoulos, Michael; Syro, Luis V; Rotondo, Fabio; Scheithauer, Bernd W; Penagos, Luis Carlos; Uribe, Humberto; Ramirez, Maria Del Pilar; Horvath, Eva; Goth, Miklos; Kovacs, Kalman

    2013-04-01

    We report here the case of an 82-year-old woman who presented with visual disturbance. MRI demonstrated a sellar mass. The diagnosis of pituitary adenoma was made. She underwent transnasal surgery. Histologic, immunohistochemical and ultrastructural studies indicated that the tumor was a melanoma. Despite an exhaustive search for a primary lesion elsewhere, none was found. The sellar tumor was considered a primary lesion, although extrasellar primary tumor imaging cannot be excluded with 100% certainty. Reported examples of melanoma affecting the sellar region are few. They exhibit morphologic features identical to those of melanomas arising elsewhere. Although very rare, primary melanomas enter into the differential diagnosis of sellar lesions. PMID:22624497

  5. 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. PMID:26124750

  6. 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.

  7. 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

  8. Collision tumors of the sella: coexistence of pituitary adenoma and craniopharyngioma in the sellar region

    PubMed Central

    2013-01-01

    Collision tumors of the sellar region are relatively uncommon and consist mainly of more than one type of pituitary adenoma or a cyst or cystic tumor. The association of a pituitary adenoma and a craniopharyngioma is particularly rare. This study describes a rare occurrence in which a pituitary adenoma and a craniopharyngioma coexisted in the sellar region. The case involves a 47-year-old woman who underwent transsphenoidal surgery with subtotal tumor resection and reoperation using an interhemispheric transcallosal approach for total microsurgical resection of the tumor because the visual acuity in her left eye had re-deteriorated. Histopathological and immunohistochemical examinations of the excised tissue revealed a pituitary adenoma in the first operation and a craniopharyngioma in the second operation. Retrospective analysis found the coexistence of a pituitary adenoma and a craniopharyngioma, known as a collision tumor. Instead of the transsphenoidal approach, a craniotomy should be performed, to explore the suprasellar region. PMID:23919255

  9. 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

  10. 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

  11. [A case of pituitary adenoma progressing to pituitary apoplexy on the occasion of cerebral angiography].

    PubMed

    Suga, T; Kagawa, S; Goto, H; Yoshioka, K; Hosoya, T

    1996-05-01

    A case of pituitary adenoma which had progressed from subclinical pituitary apoplexy to subacute pituitary apoplexy on the occasion of cerebral angiography is reported. A 29-year-old man, complaining of bitemporal hemianopsia, was admitted to our department. Plain skull X-p revealed enlargement and double floor of the sella turcica. No abnormal calcification was revealed. CT demonstrated an isodensity mass with a diameter of 4 x 4 cm, and with ring enhancement in the suprasellar region. The mass extended from the intrasellar region to the suprasellar region and had a signal of high intensity on T1-weighted images. Endocrinological examination revealed hyperprolactinemia with a serum level of 422 ng/ml and normal reaction of anterior pituitary hormones. On 3rd March, digital subtraction angiography with 5F catheter was performed with the patient under sedation. The contrast medium was ioxaglic acid (Hexabrix 320). A volume of 6 ml with a speed of 4 ml per second was injected for the internal carotid angiogram. A total volume of 60 ml was used. Serum saline with 10 unit per ml of heparin sodium was also used for flushing. During angiography, the patient's blood pressure was 125/60-115/60mm Hg. DSA revealed upward displacement of the proximal portion of the anterior cerebral artery, pocket formation, and staining of the tumor capsule. Six hours later, he complained of retroorbital headache. Next morning, he noticed complete lack of left visual acuity. On 7th March, right visual acuity degenerated to blindness. CT revealed that the mass had increased its density. With bifrontal osteoplastic craniotomy, the tumor with marked intratumoral hemorrhage was resected. Its histology was chromophobe adenoma. The patient's right visual acuity improved rapidly. On the occasion of cerebral angiography, we could observe that subclinical pituitary apoplexy deteriorated to subacute pituitary apoplexy. Rosenbaum postulated that injection of contrast media increased intravascular

  12. 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

  13. CDK5 and its activator P35 in normal pituitary and in pituitary adenomas: relationship to VEGF expression.

    PubMed

    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

  14. 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

  15. Control of ACTH secretion by excitatory amino acids: functional significance and clinical implications.

    PubMed

    Jezova, Daniela

    2005-12-01

    The involvement of excitatory amino acids in the control of ACTH release is well established. Activation of ionotropic glutamate receptors has a stimulatory effect on ACTH release, while the role of metabotropic receptors is not yet understood in detail. Glutamatergic regulation of ACTH release has a clear significance for the stress response and neuroendocrine functions during development. A dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis has been reported in several psychiatric and neurological disorders. So far, only fractional indices on the clinical importance of the interaction between glutamate and ACTH secretion have been obtained in both preclinical and clinical studies. Some antidepressant drugs, such as tianeptine, which were found to modulate ACTH release, appear to interfere with brain glutamatergic system. Changes in ACTH and cortisol release may be of importance for mood stabilizing effects of antiepileptic drugs modulating glutamate release, such as lamotrigine. Brain glutamate and HPA axis interaction seems to be of importance in alcohol and drug abuse. Little information is available on ACTH release in response to glutamate-modulating drugs used in the treatment of schizophrenia and Alzheimer disease. Nevertheless, pharmacological interventions influencing interaction between glutamate and the HPA axis are promising treatment possibilities in psychiatry and neurology.

  16. 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.

  17. Optimal management of non-functioning pituitary adenomas.

    PubMed

    Greenman, Yona; Stern, Naftali

    2015-09-01

    Transsphenoidal surgery is the treatment of choice for large non-functioning pituitary adenomas (NFPA) and symptomatic patients. The therapeutic strategies for the management of NFPA after surgery, i.e., watchful waiting, irradiation, or medical therapy have not been compared by randomized controlled trials. Slow re-growth is common, but the natural history of untreated tumors is variable. Conservative follow-up is associated with progression rates of over 40 %. Radiation is highly effective in preventing residual tumor growth, but has serious long-term side effects. Finally, no medications are currently approved for the treatment of NFPA. In this review, we present our view of the optimal management of these tumors, which includes risk stratification for the identification of high-risk patients suitable for active intervention, leaving low-risk patients for careful monitoring. PMID:26179179

  18. Relationship between NF-κB, MMP-9, and MICA expression in pituitary adenomas reveals a new mechanism of pituitary adenomas immune escape.

    PubMed

    Chen, Zheng; Li, Zhenzhu; Chang, Yingwei; Ma, Lixin; Xu, Wenhu; Li, Meng; Li, Jianmin; Zhang, Wensheng; Sun, Qikai; An, Xiaojing; Li, Zefu

    2015-06-15

    The aim of this study was to examine the expression levels of NF-κB, MMP-9, and MICA and their relationship between each other in pituitary adenomas as a histological basis for the study of the expression and shedding mechanism of MICA and mechanism of immune escape of pituitary adenomas. Our study indicated that MICA, MMP-9 and NF-κB mRNA and protein levels were more highly expressed in pituitary adenomas than healthy tissues. The expression levels of NF-κB, MMP-9, and MICA were positively related in patients with pituitary adenomas. In conclusion, the activation of NF-κB can up-regulate the expression of MICA and induce the expression of MMP-9, which hydrolyzes MICA into sMICA to promote tumor immune escape. The interactions of NF-κB, MMP-9, and MICA play an important role in the development of pituitary adenomas, and MMP-9 could be used as a new target for inhibiting tumor cell immune escape.

  19. Incidence of Pituitary Apoplexy and Its Risk Factors in Chinese People: A Database Study of Patients with Pituitary Adenoma

    PubMed Central

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

    2015-01-01

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

  20. Pituitary adenoma in Carney complex: an immunohistochemical, ultrastructural, and immunoelectron microscopic study.

    PubMed

    Kurtkaya-Yapicier, O; Scheithauer, B W; Carney, J A; Kovacs, K; Horvath, E; Stratakis, C A; Vidal, S; Vella, A; Young, W F; Atkinson, J L D; Lloyd, R V; Kontogeorgos, G

    2002-01-01

    First described in 1985, Carney complex is a rare, heritable disorder featuring abnormal skin pigmentation, cardiac and cutaneous myxoma, melanotic schwannoma of psammomatous type, and endocrine abnormalities, including pituitary adenomas. Patients with the latter present with elevated growth hormone (GH) levels and acromegaly or gigantism. Prolactin (PRL) elevation may also be seen. The authors have investigated 2 resected pituitary adenomas from patients with Carney complex. One, a 19-year-old female acromegalic with elevated GH, IgF-1, and PRL levels, had a mammosomatotroph adenoma immunoreactive for GH and PRL. Ultrastructurally, GH and PRL were present in the same secretory granules. The second patient, a 27-year-old acromegalic, had a sparsely granulated GH cell adenoma that by immuno-electron microscopy revealed GH immunoreactivity only. The lack of morphologic similarity between the 2 adenomas indicatesthat pituitary tumors in patients with Carney complex may not exhibit the same phenotype. PMID:12537759

  1. TSH-secreting pituitary adenoma: benefits of pre-operative octreotide

    PubMed Central

    Healy, E; Cooke, R S; Ellis, P K; Harper, R; Hunter, S J

    2015-01-01

    Summary TSH-secreting pituitary adenomas are rare and the optimal investigation and management is uncertain. We describe a case of a 43 year-old woman with a TSH-secreting pituitary adenoma, highlighting diagnostic testing and our use, pre-operatively of somatostatin analogue therapy, which induced biochemical euthyroidism and a reduction in tumour size. Learning points The differential diagnosis of the syndrome of inappropriate TSH secretion is non-thyroidal illness, medications, assay interference due to heterophilic antibodies, thyroid hormone resistance and TSH-secreting pituitary adenoma.TRH stimulation test and triiodothyronine suppression test assist in differentiating thyroid hormone resistance and TSH-secreting pituitary adenoma.Somatostatin analogue therapy can induce biochemical euthyroidism and reduce tumour size. PMID:26113979

  2. 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

  3. 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. PMID:27517036

  4. 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

  5. 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

  6. Monomorphous Plurihormonal Pituitary Adenoma of Pit-1 Lineage in a Giant Adolescent with Central Hyperthyroidism.

    PubMed

    Pereira, Bernardo Dias; Raimundo, Luísa; Mete, Ozgur; Oliveira, Ana; Portugal, Jorge; Asa, Sylvia L

    2016-03-01

    Thyrotropin (TSH)-secreting pituitary adenomas are exceedingly rare at the pediatric age and no cases of co-secretion with other pituitary hormones in these tumors have been described in this age range. We present a case of a monomorphous plurihormonal pituitary adenoma that co-secreted TSH and GH in a pediatric patient. A 13-year-old male presented with increasing height velocity (17.75 cm/year, 9.55SD), weight loss, and visual impairment. Initial biochemical evaluations revealed secondary hyperthyroidism. A giant pituitary tumor compressing the surrounding structures was detected by magnetic resonance, and a transsphenoidal surgery was initially performed. Pathological examinations revealed an atypical, monomorphous plurihormonal Pit-1 lineage tumor with mixed features of silent subtype 3 adenoma and acidophil stem cell adenoma. In the postoperative period, secondary hyperthyroidism recurred with high levels of both GH and IGF1. In addition, due to tumor re-growth, a multimodality treatment plan was undertaken including surgery, somatostatin analogs, and radiotherapy. We report the first pediatric case of a plurihormonal TSH- and GH-secreting pituitary adenoma, further expanding the clinical manifestations of pediatric pituitary tumors. Comprehensive pathological evaluation and close follow-up surveillance are crucial to the prompt delivery of the best therapeutic options in the context of this particularly aggressive pituitary tumor. PMID:26330191

  7. Beta human chorionic gonadotropin (beta-hCG) expression in pituitary adenomas: relationship to endocrine function and tumour recurrence.

    PubMed

    Doyle, Paul M; Thiryayi, Waziq A; Joshi, Abhijit; du Plessis, Daniel; Kearney, Tara; Gnanalingham, Kanna K

    2009-01-01

    The beta subunit of human chorionic gonadotropin (beta-hCG) is a marker of malignancies. Recent studies have also reported its expression in pituitary adenomas, although its significance is unclear. In this retrospective study, the authors quantitatively investigated the immunohistochemical expression of beta-hCG in 123 patients undergoing surgery for pituitary adenomas and explored its relationship to the rest of the endocrine function, tumour recurrence and Ki-67 nuclear labelling. Based on the endocrine profile and immunohistochemistry, the pituitary adenomas were grouped into non-functioning (NFPA; N = 78) and functioning pituitary adenomas (N = 45). The latter included, 20 growth hormone (GH), 12 prolactin (PRL), 8 adreno-corticotrophin hormone (ACTH) and 5 mixed GH-PRL-producing adenomas. Ninety-three (76%) tumours were classified as primary and 30 (24%) tumours classified as recurrent adenomas. Immunohistochemically, 107 (87%) of pituitary adenomas expressed beta-hCG, which was more common in NFPA (91%) than functioning pituitary adenomas (80%). beta-hCG expression was not different between primary (86%) and recurrent pituitary adenomas (90%) and it was also not related to raised Ki-67 labelling. But, Ki-67 labelling was raised in recurrent pituitary adenomas (33%), compared to primary pituitary adenomas (11%). Although, beta-hCG is expressed in the majority of pituitary adenomas, more especially in NFPA, it is un-related to the risk of tumour recurrence or cellular proliferation as measured by Ki-67 nuclear labelling. The high incidence of beta-hCG expression in pituitary adenomas may provide a target for specific beta-hCG-directed tumour therapies in the future. PMID:19005764

  8. MR imaging analysis of posterior pituitary in patients with pituitary adenoma

    PubMed Central

    Wang, Shousen; Lin, Kunzhe; Xiao, Deyong; Zhao, Lin; Qin, Yong; Wei, Liangfeng

    2015-01-01

    Objective: This study is to investigate posterior pituitary bright spot (PPBS) occurrence, distribution and its influencing factors by analyzing MRI-T1WI images in patients with pituitary adenoma (PA). Methods: A total of 123 cases of PA patients were enrolled in this study. PPBS occurrence, distribution and MR signal characteristics were studied. The relationship of PPBS with PA morphology, tumor size, tumor height and immunohistochemical types were explored. Results: Among the 123 case of PA patients enrolled in the study, 98 cases were PPBS (+) and 25 cases were PPBS (-). According to tumor morphology, PA was divided into hourglass type (43 cases), barrel type (63 cases) and wedge type (17 cases). Occurrence rate of PPBS (+) in barrel type was less than those in hourglass and wedge types (P < 0.05). Tumor volume and height in PPBS (+) group were less than these in PPBS (-) group (P < 0.05). PPBS signal size in wedge and barrel types were larger than that of hourglass type (P < 0.05). Conclusions: Sagittal MRI-T1WI images could well show posterior pituitary and PPBS (+) was related to tumor morphology, volume and height but had nothing to do with immunohistochemical types. PMID:26221310

  9. Human growth hormone and prolactin secreting pituitary adenomas analyzed by in situ hybridization.

    PubMed

    Lloyd, R V; Cano, M; Chandler, W F; Barkan, A L; Horvath, E; Kovacs, K

    1989-03-01

    Acidophilic pituitary adenomas commonly produce growth hormone (GH) or prolactin (PRL), according to studies employing immunohistochemical and ultrastructural methods. To examine this question, in situ hybridization with oligonucleotide probes was done on routinely processed tissues received in the pathology laboratory to analyze for the presence of GH and PRL messenger RNA (mRNA) in 4 normal pituitaries, 10 prolactinomas, and 16 GH-secreting adenomas. Most acidophilic cells in normal pituitaries expressed either GH or PRL hormone and the respective mRNAs, but GH mRNA and PRL hormone were also detected in some of the same cells. Patients with a clinical diagnosis of prolactinoma had cells with only PRL mRNA in their tumors, while most (14 of 16) patients with a clinical diagnosis of acromegaly or gigantism had both GH and PRL mRNAs in their tumors. The GH adenomas varied in these studies. In situ hybridization was helpful in characterizing the adenoma from a patient with acromegaly who had immunoreactive PRL, but no immunoreactive GH in the resected tumor; in situ hybridization analysis revealed mRNAs for both GH and PRL in the same tumor cells. Our findings indicate that pituitary adenomas from patients with acromegaly commonly express PRL mRNA. It is concluded that in situ hybridization provides new information about the clinical biology and the histopathologic classification of pituitary adenomas. PMID:2466405

  10. Acromegaly due to a Macroinvasive Plurihormonal Pituitary Adenoma and a Rectal Carcinoid Tumor

    PubMed Central

    Chin, Sang Ouk; Hwang, Jin-Kyung; Rhee, Sang Youl; Chon, Suk; Oh, Seungjoon; Lee, Misu; Pellegata, Natalia S.

    2015-01-01

    A macroinvasive pituitary adenoma with plurihormonality usually causes acromegaly and hyperprolactinemia, and also accompanies with neurologic symptoms such as visual disturbances. However, its concurrent presentation with a rectal carcinoid tumor is rarely observed. This study reports the history, biochemical, colonoscopic and immunohistochemical results of a 48-year-old female with acromegaly and hyperprolactinemia. Despite the large size and invasive nature of the pituitary adenoma to adjacent anatomical structures, she did not complain of any neurologic symptoms such as visual disturbance or headache. Immunohistochemical staining of the surgical specimen from the pituitary adenoma revealed that the tumor cells were positive for growth hormone (GH), prolactin (PRL), and thyroid stimulating hormone (TSH). Staining for pituitary-specific transcription factor-1 (Pit-1) was shown to be strongly positive, which could have been possibly contributing to the plurihormonality of this adenoma. Colonoscopy found a rectal polyp that was identified to be a carcinoid tumor using immunohistochemical staining. A macroinvasive pituitary adenoma with concomitant rectal carcinoid tumor was secreting GH, PRL, and TSH, which were believed to be in association with over-expression of Pit-1. This is the first case report of double primary tumors comprising a plurihormonal pituitary macroadenoma and rectal carcinoid tumor. PMID:25559714

  11. 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

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

    PubMed

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

    2015-09-01

    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

  13. Post-surgical management of non-functioning pituitary adenoma.

    PubMed

    Cortet-Rudelli, Christine; Bonneville, Jean-François; Borson-Chazot, Françoise; Clavier, Lorraine; Coche Dequéant, Bernard; Desailloud, Rachel; Maiter, Dominique; Rohmer, Vincent; Sadoul, Jean Louis; Sonnet, Emmanuel; Toussaint, Patrick; Chanson, Philippe

    2015-07-01

    Post-surgical surveillance of non-functioning pituitary adenoma (NFPA) is based on magnetic resonance imaging (MRI) at 3 or 6 months then 1 year. When there is no adenomatous residue, annual surveillance is recommended for 5 years and then at 7, 10 and 15 years. In case of residue or doubtful MRI, prolonged annual surveillance monitors any progression. Reintervention is indicated if complete residue resection is feasible, or for symptomatic optic pathway compression, to create a safety margin between the tumor and the optic pathways ahead of complementary radiation therapy (RT), or in case of post-RT progression. In case of residue, unless the tumor displays elevated growth potential, it is usually recommended to postpone RT until progression is manifest, as efficacy is comparable whether treatment is immediate or postponed. The efficacy of the various RT techniques in terms of tumor volume control is likewise comparable. RT-induced hypopituitarism is frequent, whatever the technique. The choice thus depends basically on residue characteristics: size, delineation, and proximity to neighboring radiation-sensitive structures. Reduced rates of vascular complications and secondary brain tumor can be hoped for with one-dose or hypofractionated stereotactic RT, but there has been insufficient follow-up to provide evidence. Somatostatin analogs and dopaminergic agonists have yet to demonstrate sufficient efficacy. Temozolomide is an option in aggressive NFPA resistant to surgery and RT. PMID:26116412

  14. The role of proto-oncogene GLI1 in pituitary adenoma formation and cell survival regulation.

    PubMed

    Lampichler, Katharina; Ferrer, Patricio; Vila, Greisa; Lutz, Mirjam I; Wolf, Florian; Knosp, Engelbert; Wagner, Ludwig; Luger, Anton; Baumgartner-Parzer, Sabina

    2015-10-01

    The Hedgehog (Hh) pathway is an important regulator of early tissue patterning and stem cell propagation. It was found to be aberrantly activated in numerous types of human cancer and might be relevant in cancer stem cells. The identification of adult stem cells in the pituitary raised the question if tumor-initiating cells and Hh signaling are involved in pituitary adenoma formation. The present study aimed at the evaluation of Hh signaling in relation to stem cell and cell cycle markers in 30 human pituitary adenomas and in cultured murine adenoma cells. Therefore, expression levels of components of the Hh pathway, stem cell marker SOX2, cell cycle regulator tumor-protein 53 (TP53), proliferation marker Ki67 (MKI67) and superoxide dismutase 1 (SOD1) were evaluated in 30 human pituitary adenomas in comparison to control tissue. Modulation of cell function and target gene expression by the inhibition and activation of the Hh pathway were studied in murine adenoma cells. We show that transcription factor glioma-associated oncogene 1 (GLI1) is overexpressed in 87% of all pituitary adenomas. The expression of GLI1 significantly correlated with that of SOX2, TP53, MKI67 and SOD1. Inhibition of GLI1 resulted in the downregulation of the above genes and severe cell death in mouse adenoma cells. On the other hand, activation of the Hh pathway increased cell viability and target gene expression. In conclusion, our findings point toward an alternative, ligand-independent Hh pathway activation with GLI1 playing a major role in the cell survival of pituitary adenoma cells. PMID:26219678

  15. 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

  16. Neuroendocrine disorders: pituitary imaging.

    PubMed

    Faje, Alexander; Tritos, Nicholas A; Swearingen, Brooke; Klibanski, Anne

    2016-01-01

    Significant advances in pituitary imaging have taken place in the past several decades, including the introduction of magnetic resonance imaging (MRI). This imaging modality has vastly improved our ability to detect and characterize sellar masses and more accurately characterize the extent and spread of lesions in and around the sella. Intraoperative MRI may help improve the completeness of resection of sellar masses. Other imaging modalities, including magnetic resonance angiography, computed tomography (CT), and CT angiography, have an important role in specific cases. Interventional methods, including bilateral inferior petrosal sinus sampling, may establish the pituitary origin of corticotropin (ACTH) excess in patients with ACTH-dependent Cushing's syndrome. Pituitary imaging should be obtained in patients with pituitary hormone excess, hypopituitarism, or mass effect in the sella. Despite rapid advances in pituitary imaging, there are several diagnostic challenges remaining. Future research may help improve the radiographic detection of small sellar lesions, such as ACTH-secreting adenomas causing Cushing's disease, accurately characterize the type and extent of sellar pathologies, and provide prognostic information regarding their growth potential. PMID:27430447

  17. Gremlin, a Bone Morphogenetic Protein Antagonist, Is a Crucial Angiogenic Factor in Pituitary Adenoma

    PubMed Central

    Yoshida, Daizo; Kim, Kyongsong; Ishii, Yudo; Tahara, Shigeyuki; Teramoto, Akira; Morita, Akio

    2015-01-01

    Gremlin is an antagonist of bone morphogenetic protein (BMP) and a major driving force in skeletal modeling in the fetal stage. Several recent reports have shown that Gremlin is also involved in angiogenesis of lung cancer and diabetic retinopathy. The purpose of this study was to investigate the role of Gremlin in tumor angiogenesis in pituitary adenoma. Double fluorescence immunohistochemistry of Gremlin and CD34 was performed in pituitary adenoma tissues obtained during transsphenoidal surgery in 45 cases (7 PRLoma, 17 GHoma, 2 ACTHoma, and 2 TSHoma). Gremlin and microvascular density (MVD) were detected by double-immunofluorescence microscopy in CD34-positive vessels from tissue microarray analysis of 60 cases of pituitary adenomas (6 PRLoma, 23 GHoma, 22 NFoma, 5 ACTHoma, and 4 TSHoma). In tissue microarray analysis, MVD was significantly correlated with an increased Gremlin level (linear regression: P < 0.005,  r2 = 0.4958). In contrast, Gremlin expression showed no correlation with tumor subtype or Knosp score. The high level of expression of Gremlin in pituitary adenoma tissue with many CD34-positive vessels and the strong coherence of these regions indicate that Gremlin is associated with angiogenesis in pituitary adenoma cells. PMID:25834571

  18. 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.

  19. Double adenomas of the pituitary: a clinicopathological study of 11 tumors.

    PubMed

    Kontogeorgos, G; Scheithauer, B W; Horvath, E; Kovacs, K; Lloyd, R V; Smyth, H S; Rologis, D

    1992-11-01

    Of more than 3000 cases of surgically removed pituitary adenomas, 11 were defined as "double adenomas," i.e., 2 morphologically or immunocytologically distinct tumors. In 8 cases, the lesions exhibited differing histological features and immunophenotypes; in 2 specimens, distinct ultrastructural features were noted as well. In another instance, despite histological and immunocytological uniformity, the two neoplastic components demonstrated distinct ultrastructure. In yet another case, the two adenomas were consecutively removed; despite similar histological features, they differed in immunocytological and ultrastructural characteristics. Last, in one case, the adenoma was histologically uniform, but a portion of the mass exhibited immunoreactivity by ultrastructural features distinct from those of the remainder of the lesion. Hormonal excess attributed to both tumors could be correlated with endocrine manifestations in two cases. Double adenomas of the pituitary occur infrequently. In routine histological sections of surgical material, they are often difficult if not impossible to identify. Presented herein are clinical and endocrinological data on 10 cases of double pituitary adenomas correlated with morphological and immunocytochemical results. The literature regarding multiple adenomas is reviewed as are the diagnostic and therapeutic difficulties associated with these rare lesions. PMID:1331847

  20. [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. PMID:27605481

  1. 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.

  2. 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

  3. Pituitary adenomas: immunohistology and ultrastructural analysis of 118 tumors.

    PubMed

    Esiri, M M; Adams, C B; Burke, C; Underdown, R

    1983-01-01

    An analysis is presented of the immunohistological and ultrastructural features in a series of 118 surgically removed pituitary adenomas all of which were studied immunohistologically using antisera to growth hormone (GH), prolactin (PRL) ACTH, beta FSH, beta LH and beta TSH, and 75 of which were studied ultrastructurally. Results were analysed according to the mode of presentation of patients. Forty-one (35%) of the tumours were from patients with acromegaly or gigantism, ten (9%) from patients with Cushing's syndrome or Nelson's syndrome, 19 (16%) from patients with clinical features associated with hyperprolactinaemia and 48 (40%) from patients with space occupying lesions which appeared clinically to be overtly endocrinologically functionless. By light microscopy, using the immunoperoxidase (PAP) technique, immunoreactive GH was demonstrated in all the tumours from patients with acromegaly or gigantism, immunoreactive ACTH in all tumours from patients with Cushing's syndrome or Nelson's syndrome and immunoreactive PRL in 95% of tumours associated with effects of hyperprolactinaemia. Forty-five percent of the tumours from acromegalic patients contained some PRL-positive cells as well as GH-positive cells. Among the tumours which appeared clinically to be endocrinologically functionless were three tumours (from males) uniformly stained for immunoreactive PRL. Of the remainder, 60% were negative for immunoreactive hormones and 40% contained small numbers of cells which were positive for a variety of immunoreactive hormones. ACTH-cell and PRL-cell tumours had ultrastructural features as described in previous studies. Fifty percent of GH-cell tumours examined at the EM level contained fibrous bodies, while in the remainder these structures were not identified. Tumours with fibrous bodies were more likely to contain PRL as well as GH with immunoperoxidase. All tumours that were endocrinologically functionless and which were examined at the EM level contained

  4. Reduction in size of a thyrotropin-secreting pituitary adenoma treated with octreotide acetate (somatostatin analog).

    PubMed

    Lee, E J; Kim, K R; Lim, S K; Lee, H C; Kim, D I; Kim, S H; Huh, K B

    1994-07-01

    We present a 55-year-old female with a thyrotropin (TSH)-secreting pituitary adenoma who had been treated with somatostatin analog octreotide acetate (SMS 201-995) for 4 months. Subcutaneous injection of 100 micrograms octreotide acetate twice daily resulted in significant reduction of the TSH, thyroid hormone, and tumor size. During the treatment, there was no evidence of any side effects. We may conclude that octreotide acetate administration is an effective treatment in patients with TSH-secreting pituitary adenoma for suppressing TSH hypersecretion and reducing the size of the tumor.

  5. Invasive Growth Hormone Producing Pituitary Adenoma With Lymphocytic Infiltration: A Case Report and Literature Review

    PubMed Central

    Bidari-Zerehpoosh, Farahnaz; Sharifi, Gieve; Novin, Kambiz; Mortazavi, Nafiseh

    2015-01-01

    Introduction: We have presented a rare case of growth hormone (GH) producing pituitary adenoma with lymphocytic infiltration and brain parenchyma invasion. Case Presentation: A 37-year-old woman has presented with complaints of headache, amenorrhea and acromegalic features. Her laboratory studies showed markedly elevated levels of Insulin-like Growth Factor 1 (IGF-1), and low levels of follicle stimulating hormone and luteinizing hormone. Computerized tomography has revealed a pituitary mass without extra-sellar extension. The tumor has completely excised via trans-nasal endoscopic approach. Histologically, the tumor has diagnosed as a pituitary adenoma with GH positive cells. The serum IGF1 levels have gradually decreased to the normal range and the patient was symptom free for three and a half years when she has returned with complaint of visual impairment. The brain MRI that time has shown a supra-sellar mass growing independently into the remaining sellar part. Subsequently, surgical operation has performed via trans-nasal endoscopic approach. Histopathological and immunohistochemistry examination have revealed a rare case of growth hormone producing pituitary adenoma with brain invasion and lymphocytic infiltration. Conclusions: The aim of this publication was to present a rare case of growth hormone producing pituitary adenoma with brain invasion and lymphocytic infiltration. PMID:26855718

  6. 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

  7. B-RAF mutations are a rare event in pituitary adenomas.

    PubMed

    De Martino, I; Fedele, M; Palmieri, D; Visone, R; Cappabianca, P; Wierinckx, A; Trouillas, J; Fusco, A

    2007-01-01

    Pituitary tumors are a relatively common neoplasia whose pathogenesis is still largely unknown. Recent studies have revealed frequent activating mutations of the gene for B-RAF, an effector of Ras protein in the mitogen-activated protein kinase pathway, in several malignancies, including melanoma, thyroid, colorectal and ovarian cancer. However, analyses of B-RAF mutations in pituitary tumors have not been reported so far. Therefore, in the present study we have investigated the presence of the B-RAF mutations, by polymerase chain reaction (PCR) amplification of the hot spot exons 11 and 15, followed by direct sequencing, in 50 human pituitary adenomas, including 25 NFPA and 25 secreting adenomas (10 GH, 5 PRL, 6 LH and/or FSH, 4 GH/PRL). We found only one V600E mutation in a NFPA sample, suggesting that B-RAF mutations are a rare event in pituitary tumorigenesis. PMID:17318013

  8. Enhanced nestin expression and small blood vessels in human pituitary adenomas.

    PubMed

    Perez-Millan, María Inés; Berner, Silvia Inés; Luque, Guillermina María; De Bonis, Cristian; Sevlever, Gustavo; Becu-Villalobos, Damasia; Cristina, Carolina

    2013-09-01

    The role of angiogenesis in human pituitary tumor progression is questioned. Our aim was to characterize the morphologic changes that occur in the vasculature of pituitary adenomas, in correlation with the expression of nestin, a protein found in endothelial cells of newly formed vessels of developing organs. We also evaluated the relation of angiogenic markers and nestin with Ki-67 index. Immunohistochemical studies were performed on paraffin embedded samples of 47 pituitary adenomas and six normal pituitaries. We determined microvessel density (number of CD31+ or CD34+ vessels per square millimetre), vascular area (cumulative area occupied by vessels), average vessel size, and further classified vessels as small (< 100 μm2) or large (> 100 μm2). We correlated the above parameters with nestin expression and Ki-67 index. Lower vascular area compared to normal tissue was found in adenomas (p < 0.05). Interestingly, pituitary adenomas had significantly more small vessels than control pituitaries (p < 0.04 for CD31 and CD34). In tumors many capillaries were positive for nestin, while scarce staining was detected in controls, so that nestin positive area was significantly higher in tumors. Furthermore, nestin area correlated positively with the % of small vessels. Ki-67 correlated neither with vascular area nor with nestin expression. In human pituitary tumors there was a predominance of small capillaries in correlation with increased expression of the progenitor marker nestin. We suggest that angiogenesis is an active process in these tumors, in spite of their low total vascular area when compared to normal pituitaries.

  9. 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

  10. Transsphenoidal surgical treatment of pituitary adenomas in patients aged 80 years or older.

    PubMed

    Yunoue, Shunji; Tokimura, Hiroshi; Tominaga, Atsushi; Fujio, Shingo; Karki, Prasanna; Usui, Satoshi; Kinoshita, Yasuyuki; Habu, Mika; Moinuddin, F M; Hirano, Hirofumi; Arita, Kazunori

    2014-04-01

    To know the clinical characteristics of pituitary adenomas in the elderly patients aged 80 years or older who were surgically treated. From 1995 through 2012, 907 patients underwent surgery for the pituitary adenomas at Kagoshima- and Hiroshima University hospitals in Japan. Ten (1.1%) patients were aged 80 years or older. We retrospectively assessed the clinical characteristics including preoperative comorbidities, manifestations, neuroimaging findings, and endocrinologic features of these ten patients. The subjects included eight males and two females. Their ages ranged from 80 to 86 with mean of 83.1 years. Of these, besides one case of growth hormone-producing adenoma, others were clinically nonfunctioning adenoma. Six patients had modest comorbidities such as hypertension, cardiovascular diseases, diabetes mellitus, or chronic kidney dysfunction, and all patients were classified into grade 2-3 on American Society of Anesthesiologists' Physical Status grading. Transsphenoidal surgery was performed in all due to visual disturbance in eight, diabetes mellitus as an intercurrent illness of acromegaly in one, and for the purpose of preventing visual disturbance in one patient who had an adenoma impinging optic chiasm but still had normal visual field. The surgeries provided sufficient decompression of the optic pathways and improved visual disorder in all. In an acromegalic male, his comorbidities considerably improved. No permanent surgical morbidity ensued. More than three axes of anterior pituitary hormones were preoperatively impaired in all, which were rarely recovered. Transsphenoidal surgery is safe and efficient treatment way for patients aged 80 years or older with pituitary adenomas with chiasmatic symptoms when the patients' general condition is well preserved and pituitary hormonal deficiency is adequately replaced. PMID:24233259

  11. Quantitative evaluation of headache severity before and after endoscopic transsphenoidal surgery for pituitary adenoma.

    PubMed

    Wolf, Amparo; Goncalves, Sandy; Salehi, Fateme; Bird, Jeff; Cooper, Paul; Van Uum, Stan; Lee, Donald H; Rotenberg, Brian W; Duggal, Neil

    2016-06-01

    OBJECT The relationship between headaches, pituitary adenomas, and surgical treatment of pituitary adenomas remains unclear. The authors assessed the severity and predictors of self-reported headaches in patients referred for surgery of pituitary adenomas and evaluated the impact of endoscopic transsphenoidal surgery on headache severity and quality of life (QOL). METHODS In this prospective study, 79 patients with pituitary adenomas underwent endoscopic transsphenoidal resection and completed the Headache Impact Test (HIT-6) and the 36-Item Short Form Health Survey (SF-36) QOL questionnaire preoperatively and at 6 weeks and 6 months postoperatively. RESULTS Preoperatively, 49.4% of patients had mild headache severity, 13.9% had moderate severity, 13.9% had substantial severity, and 22.8% had intense severity. Younger age and hormone-producing tumors predisposed greater headache severity, while tumor volume, suprasellar extension, chiasmal compression, and cavernous sinus invasion of the pituitary tumors did not. Preoperative headache severity was found to be significantly associated with reduced scores across all SF-36 QOL dimensions and most significantly associated with mental health. By 6 months postoperatively, headache severity was reduced in a significant proportion of patients. Of the 40 patients with headaches causing an impact on daily living (moderate, substantial, or intense headache), 70% had improvement of at least 1 category on HIT-6 by 6 months postoperatively, while headache worsened in 7.6% of patients. The best predictors of headache response to surgery included younger age, poor preoperative SF-36 mental health score, and hormone-producing microadenoma. CONCLUSIONS The results of this study confirm that surgery can significantly improve headaches in patients with pituitary adenomas by 6 months postoperatively, particularly in younger patients whose preoperative QOL is impacted. A larger multicenter study is underway to evaluate the long

  12. 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

  13. Cerebral salt wasting syndrome in a patient with a pituitary adenoma.

    PubMed

    Singh, S K; Unnikrishnan, A G; Reddy, V S; Sahay, R K; Bhadada, S K; Agrawal, J K

    2003-03-01

    Cerebral salt wasting syndrome (CSWS) is often an unrecognized cause of hyponatremia that occurs in the setting of intracranial lesions. It is important to differentiate CSWS from the syndrome of inappropriate ADH secretion, as this would alter the management of hyponatremia. We describe a case of CSWS that occurred in association with a non-functioning pituitary adenoma.

  14. Endoscopic endonasal transsphenoidal surgery for treating pituitary adenoma via a sub-septum mucosa approach

    PubMed Central

    Nie, Sheng; Li, Keqin; Huang, Yi; Zhao, Jikuang; Gao, Xiang; Sun, Jie

    2015-01-01

    A novel sub-suptum mucusa approach was used to investigate the surgical method via an endonasal sub-septum-mucosa approach to pituitary adenoma under endoscopy. In this work, we aim to ensure the quality of operation and to reduce the operation trauma and complications. By endoscopy, the nasal mucosa was incised in the nasal septum, and all mucosal flaps were retained, a sub-septum-mucosa surgical corridor was made where the endoscope was used in the mucosa cavity for operation and to remove the pituitary adenoma. 52 patients (28 women, mean age 46.76 years) underwent endoscopic endonasal transsphenoidal sub-septum-mucosa approach for treating pituitary adenoma. 46 patients (88.5%) underwent gross total removal (GTR) for the tumor; 6 patients (11.5%) went through partial tumor removal (PTR). After operation, all nasal mucosa was retained, no complications such as nasal bleeding, loss of sense of smell or cerebrospinal fluid rhinorrhea. Our results showed that treating pituitary adenoma using endonasal transsphenoidal surgeries by keeping nasal mucosa under neuroendoscopy tend to have smaller trauma. This novel method more advanced since it provides a clear operation field, a flexible transformation of operation modes and leads to less postoperative complications. PMID:26131087

  15. Epigenetic Mechanisms Leading to Overexpression of HMGA Proteins in Human Pituitary Adenomas

    PubMed Central

    D’Angelo, Daniela; Esposito, Francesco; Fusco, Alfredo

    2015-01-01

    Overexpression of the high-mobility group A (HMGA)1 and HMGA2 proteins is a feature of all human pituitary adenoma (PAs) subtypes. However, amplification and/or rearrangement of the HMGA2 have been described in human prolactinomas, but rarely in other pituitary subtypes, and no genomic amplification of HMGA1 was detected in PAs. Here, we summarize the functional role of HMGA proteins in pituitary tumorigenesis and the epigenetic mechanisms contributing to HMGA overexpression in these tumors focusing on recent studies indicating a critical role of non-coding RNAs in modulating HMGA protein levels. PMID:26137461

  16. 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)

  17. 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

  18. Control of Stress-Induced ACTH Secretion by Vasopressin and CRH: Additional Evidence.

    PubMed

    Ramos, Adriana T; Tufik, Sergio; Troncone, Lanfranco R P

    2016-01-01

    Vasopressin and CRH have complementary roles in the secretion of ACTH following different stress modalities. The concomitant use of V1b and CRF1 receptor antagonists completely inhibits ACTH secretion in response to different stress modalities. The combination of the CRF1 antagonist SSR125543 with the V1b antagonist SSR149415 effectively suppressed plasma ACTH 1.30 h after injection in rats stressed by ether vapor inhalation for 1 min, restraint stress for 1 h or forced swimming for 5 min. The duration of the effect was also studied. The CRF1 antagonist effectively suppressed ACTH secretion in restraint stress, while the V1b antagonist was effective against ether inhalation. Both antagonists were necessary to block the forced swimming stress response. SSR125543 induced a prolonged effect and can be used in a model of prolonged HPA axis blockade. PMID:27221315

  19. 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

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

    PubMed

    Moisi, Marc; 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.

  1. Inhibitory effect of cyproheptadine on ACTH secretion in patients with Addison's disease.

    PubMed

    Loli, P; Frascatani, F; Gelli, D; Maggioni, M; Muratori, F; Ronzoni, M

    1983-01-01

    In 14 patients with Addison's disease plasma levels of ACTH were studied after administration of a single oral dose (16 mg) of cyproheptadine. The drug administration was followed by an inhibition of ACTH release. These results support the view that cyproheptadine may exert an inhibitory effect on ACTH secretion in subjects whose corticosteroid feedback mechanism is normal. We hypothesize that the effect of cyproheptadine might be related to its anti-serotonin or anti-histaminergic action.

  2. 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.

  3. 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. PMID:10366409

  4. 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

  5. Morphological effects of octreotide on growth hormone-producing pituitary adenomas.

    PubMed

    Ezzat, S; Horvath, E; Harris, A G; Kovacs, K

    1994-07-01

    The SRIH analog octreotide is a potent GH-inhibiting agent that has been used to effectively treat patients with acromegaly. To investigate the morphological changes induced by octreotide on GH-producing pituitary tumors, we examined 86 adenomas from acromegalic patients who participated in a multicenter study. GH- producing pituitary adenomas removed from 43 patients treated preoperatively with octreotide for 4 months were compared to those obtained from 43 untreated acromegalic patients. Tissue samples were studied by histology, immunohistochemistry, and transmission electron microscopy as well as light microscopic and ultrastructural morphometry. The morphological appearance of some tumors was unaltered by octreotide treatment. Necrotic changes were not apparent in any. Acidophilia and GH immunoreactivity were more pronounced in the octreotide-treated tumors. Perivascular and interstitial fibrosis was more prevalent in the octreotide group (72% vs. 42%). An increase in hormone granularity was obvious in 4 of 15 densely granulated and 2 of 9 sparsely granulated (SG) tumors from treated patients. A decrease in cell size was conspicuous in 4 of 15 densely granulated and 2 of 10 SG adenomas. There was a slight downward trend in the cell and cytoplasmic size in all treated tumors and a slight upward trend in secretory granule size in treated SG adenomas. Only 2 of 9 SG adenomas in the octreotide group, however, demonstrated a statistically significant reduction in cell and cytoplasmic size. There was no statistically significant change in the size of nuclei, secretory granules, or lysosomes between the 2 groups. Decreased cell size and increased granularity were not linked, however. We conclude that there are no striking morphological alterations in GH pituitary adenomas that can be consistently associated with octreotide treatment.

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

    PubMed Central

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

    2016-01-01

    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

  8. Mir-23b and miR-130b expression is downregulated in pituitary adenomas.

    PubMed

    Leone, Vincenza; Langella, Concetta; D'Angelo, Daniela; Mussnich, Paula; Wierinckx, Anne; Terracciano, Luigi; Raverot, Gerald; Lachuer, Joel; Rotondi, Sandra; Jaffrain-Rea, Marie-Lise; Trouillas, Jacqueline; Fusco, Alfredo

    2014-06-01

    MicroRNA (miRNA) deregulation plays a critical role in tumorigenesis. miR-23b and miR-130b are induced by thyrotropin in thyroid cells in a cAMP-dependent manner. The aim of our work has been to investigate the possible role of miR-23b and miR-130b in pituitary tumorigenesis. We have analyzed their expression in a panel of pituitary adenomas (PAs) including GH and NFPA adenomas. We report that miR-23b and miR-130b are drastically reduced in GH, gonadotroph and NFPA adenomas in comparison with normal pituitary gland. Interestingly, the overexpression of miR-23b and miR-130b inhibits cell proliferation arresting the cells in the G1 and G2 phase of the cell cycle, respectively. Moreover, we demonstrate that miR-23b and miR-130b target HMGA2 and cyclin A2 (CCNA2) genes, respectively. Finally, downregulation of miR-23b and miR-130b expression is associated with increased levels of their respective targets in human PAs. These findings suggest that miR-23b and miR-130b downregulation may contribute to pituitary tumorigenesis. PMID:24681352

  9. Facial Metrics in Children with Corticotrophin-Producing Pituitary Adenomas Suggest Abnormalities in Midface Development

    PubMed Central

    Keil, Margaret F.; Stratakis, Constantine A.

    2011-01-01

    Background Tumors of the hypothalamic-pituitary unit have been linked to genetic syndromes that are associated with midfacial abnormalities. Aim We hypothesized that mutations of genes that affect the development of the face (and consequently of the anterior pituitary) may be present in children with ACTH-producing pituitary adenomas, and if this is true then facial measurements would be different from those predicted by parental features. Methods We studied 20 children with cortico-tropinomas and a control group and their parents. All facial measurements were expressed according to standard deviation scores. Results Significant differences were seen between the children with pituitary adenomas and their parents for vertical facial height measures: nasal length (p <0.001), lower facial height (p <0.03) and overall facial height (p <0.01). Conclusion We conclude that some of the indices of midline craniofacial development, in particular those affecting the vertical axis, are different in children with corticotroph adenomas producing ACTH. PMID:19344074

  10. 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

  11. 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. PMID:17347873

  12. AIP mutation in pituitary adenomas in the 18th century and today.

    PubMed

    Chahal, Harvinder S; Stals, Karen; Unterländer, Martina; Balding, David J; Thomas, Mark G; Kumar, Ajith V; Besser, G Michael; Atkinson, A Brew; Morrison, Patrick J; Howlett, Trevor A; Levy, Miles J; Orme, Steve M; Akker, Scott A; Abel, Richard L; Grossman, Ashley B; Burger, Joachim; Ellard, Sian; Korbonits, Márta

    2011-01-01

    Gigantism results when a growth hormone-secreting pituitary adenoma is present before epiphyseal fusion. In 1909, when Harvey Cushing examined the skeleton of an Irish patient who lived from 1761 to 1783, he noted an enlarged pituitary fossa. We extracted DNA from the patient's teeth and identified a germline mutation in the aryl hydrocarbon-interacting protein gene (AIP). Four contemporary Northern Irish families who presented with gigantism, acromegaly, or prolactinoma have the same mutation and haplotype associated with the mutated gene. Using coalescent theory, we infer that these persons share a common ancestor who lived about 57 to 66 generations earlier. PMID:21208107

  13. 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

  14. Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC–ESI-MS–MS

    SciTech Connect

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

    2015-06-18

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

  15. Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC–ESI-MS–MS

    DOE PAGES

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

    2015-06-18

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

  16. Clival Ectopic Pituitary Adenoma Mimicking a Chordoma: Case Report and Review of the Literature.

    PubMed

    Karras, Constantine L; Abecassis, Isaac Josh; Abecassis, Zachary A; Adel, Joseph G; Bit-Ivan, Esther N; Chandra, Rakesh K; Bendok, Bernard R

    2016-01-01

    Background. Purely ectopic pituitary adenomas are exceedingly rare. Here we report on a patient that presented with an incidental clival mass thought to be a chordoma. Endonasal resection, tumor pathology, and endocrinology workup revealed a prolactinoma. Case Presentation. A 41-year-old male presented with an incidental clival lesion presumed to be a chordoma. On MRI it involved the entire clivus, extended laterally to the petroclival junction, and invaded the cavernous sinuses bilaterally, encasing both internal carotid arteries, without direct extension into the sella. Intraoperatively, it was clear that the tumor originated from the clivus and that the sellar dura was completely intact. Frozen-section pathology was consistent with a pituitary adenoma. Immunostaining was positive for synaptophysin and prolactin with a low Ki-67 index, suggestive of a prolactinoma. Additional immunohistochemical stains seen in chordomas (EMA, S100, and Brachyury) and other metastatic tumors were negative. A postoperative endocrine workup revealed an elevated serum prolactin of 881.3 ng/mL (normal < 20). Conclusions. In conclusion, it is crucial to maintain an extensive differential diagnosis when evaluating a patient with a clival lesion. Ectopic clival pituitary adenomas, although rare, may warrant an endocrinological workup preoperatively as the majority may respond to medical treatment.

  17. Stereotactic radiotherapy and radiosurgery for non-functioning and secreting pituitary adenomas.

    PubMed

    Minniti, Giuseppe; Clarke, Enrico; Scaringi, Claudia; Enrici, Riccardo Maurizi

    2016-01-01

    Radiotherapy (RT) is frequently employed in patients with residual or recurrent pituitary adenoma with excellent rates of tumor control and remission of hormonal hypersecretion. Advances in RT have improved with the use of stereotactic techniques either as fractionated stereotactic radiotherapy (FSRT) or stereotactic radiosurgery (SRS), all aiming to improve the dose distribution to the tumor while reducing the amount of normal brain receiving significant doses of radiation. We provide an overview of the recent published literature on the long-term efficacy and adverse effects of stereotactic irradiation in nonfunctioning and secreting pituitary adenomas. Both techniques are associated with excellent clinical outcomes; however, advantages and drawbacks of each of these techniques in terms of local control, hormonal excess normalization, and radiation-induced toxicity remain a matter of debate. In clinical practice, single-fraction SRS may represent a convenient approach to patients with small and medium-sized pituitary adenoma away at least 2 mm from the optic chiasm, whereas FSRT is preferred over SRS for lesions >2.5-3 cm in size and/or involving the anterior optic pathway. PMID:27330422

  18. Clival Ectopic Pituitary Adenoma Mimicking a Chordoma: Case Report and Review of the Literature

    PubMed Central

    Karras, Constantine L.; Abecassis, Isaac Josh; Abecassis, Zachary A.; Adel, Joseph G.; Bit-Ivan, Esther N.; Chandra, Rakesh K.; Bendok, Bernard R.

    2016-01-01

    Background. Purely ectopic pituitary adenomas are exceedingly rare. Here we report on a patient that presented with an incidental clival mass thought to be a chordoma. Endonasal resection, tumor pathology, and endocrinology workup revealed a prolactinoma. Case Presentation. A 41-year-old male presented with an incidental clival lesion presumed to be a chordoma. On MRI it involved the entire clivus, extended laterally to the petroclival junction, and invaded the cavernous sinuses bilaterally, encasing both internal carotid arteries, without direct extension into the sella. Intraoperatively, it was clear that the tumor originated from the clivus and that the sellar dura was completely intact. Frozen-section pathology was consistent with a pituitary adenoma. Immunostaining was positive for synaptophysin and prolactin with a low Ki-67 index, suggestive of a prolactinoma. Additional immunohistochemical stains seen in chordomas (EMA, S100, and Brachyury) and other metastatic tumors were negative. A postoperative endocrine workup revealed an elevated serum prolactin of 881.3 ng/mL (normal < 20). Conclusions. In conclusion, it is crucial to maintain an extensive differential diagnosis when evaluating a patient with a clival lesion. Ectopic clival pituitary adenomas, although rare, may warrant an endocrinological workup preoperatively as the majority may respond to medical treatment. PMID:26885420

  19. 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. PMID:26705201

  20. TFF3 knockout in human pituitary adenoma cell HP75 facilitates cell apoptosis via mitochondrial pathway

    PubMed Central

    Gao, Feng; Pan, Suxia; Liu, Bing; Zhang, Huanzhi

    2015-01-01

    Trefoil factor 3 (TFF3), a regulatory protein composed of 59 amino acids, has been suggested to be involved in pathogenesis, proliferation, differentiation, invasion, migration and apoptosis in multiple malignant tumors. This study thus investigated the effect of TFF3 knockout in human pituitary adenoma cell line HP75 on cell apoptosis and related pathways. RNA interference approach was used to knock down the expression of TFF3 protein. The gene silencing was validated by RNA denaturing gel electrophoresis and Western blotting. The effect of TFF3 knockout on cell apoptosis was analyzed by Western blotting and flow cytometry. TFF3 protein level in pituitary adenoma was about 3.61 ± 0.48 folds of that in normal tissues (P < 0.01). After transfecting with small interference RNA (siRNA) against TFF3, the apoptotic ration was significantly elevated (P < 0.01). Apoptosis related protein Bcl-2 and caspase-3 levels were remarkably depressed after siRNA transfection, while Bax and cleaved caspase-3 levels were elevated. TFF3 protein knockout can facilitate apoptosis of human pituitary adenoma HP75 cells via mitochondrial pathway. PMID:26823779

  1. TFF3 knockout in human pituitary adenoma cell HP75 facilitates cell apoptosis via mitochondrial pathway.

    PubMed

    Gao, Feng; Pan, Suxia; Liu, Bing; Zhang, Huanzhi

    2015-01-01

    Trefoil factor 3 (TFF3), a regulatory protein composed of 59 amino acids, has been suggested to be involved in pathogenesis, proliferation, differentiation, invasion, migration and apoptosis in multiple malignant tumors. This study thus investigated the effect of TFF3 knockout in human pituitary adenoma cell line HP75 on cell apoptosis and related pathways. RNA interference approach was used to knock down the expression of TFF3 protein. The gene silencing was validated by RNA denaturing gel electrophoresis and Western blotting. The effect of TFF3 knockout on cell apoptosis was analyzed by Western blotting and flow cytometry. TFF3 protein level in pituitary adenoma was about 3.61 ± 0.48 folds of that in normal tissues (P < 0.01). After transfecting with small interference RNA (siRNA) against TFF3, the apoptotic ration was significantly elevated (P < 0.01). Apoptosis related protein Bcl-2 and caspase-3 levels were remarkably depressed after siRNA transfection, while Bax and cleaved caspase-3 levels were elevated. TFF3 protein knockout can facilitate apoptosis of human pituitary adenoma HP75 cells via mitochondrial pathway.

  2. Drug-induced suppression of ACTH secretion does not promote anti-depressive or anxiolytic effects.

    PubMed

    Ramos, Adriana de Toledo; Homem, Karen Silvia de Carvalho; Suchecki, Deborah; Tufik, Sergio; Troncone, Lanfranco Ranieri Paolo

    2014-05-15

    Mammals respond to a real or perceived stress in an integrated physiological and psychological fashion. Psychiatric disorders like major depression and anxiety have been associated to stressful events. In a previous study we demonstrated that the stress-induced ACTH secretion can be robustly inhibited by the concurrent use of CRF1 (CP154,526 - Pfizer) and V1B (SSR149415 - Sanofi-Aventis) non-peptide antagonists. A proof of mechanism was offered by substituting CP154,526 by SSR125543 and obtaining the same results on three stress models: forced swimming, ether vapor inhalation and restraint. SSR125543 effectively blocked only restraint stress-induced ACTH secretion. We then challenged the hypothesis that the concurrent use of both antagonists would have a potent effect on behavioral models of anxiety and depression. Decreasing doses (30-0.1 mg/kg s.c.) of both drugs were tested in three behavioral models: Porsolt forced swimming test, elevated plus maze and social interaction. Results showed that these drugs had no effect on anxiety models (plus maze and social interaction) but significantly reduced immobility time in the forced swimming test, suggesting anti-depressive action in a dose-range from 1 to 30 mg/kg, not different from the reported in the literature referring to one drug or the other. This negates the proposed hypothesis of summation/potentiation of effects as observed in stress-induced ACTH secretion. These results point toward the involvement of extra-hypothalamic sites for the anti-depressive effects. Recent Phase II clinical research on anti-depressive effects of these drugs has failed rising strong criticisms against the predictive value of behavioral tests currently employed. PMID:24569014

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

    PubMed

    Barbieri, Federica; 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.

  4. 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

  5. Multicystic ovaries and pituitary pseudo-adenoma associated with primary hypothyroidism.

    PubMed

    Katulande, P; Kariyawasam, S S M; Senanayake, H M; Weerakkodi, M

    2013-01-01

    Ovarian hyperstimulation syndrome (OHSS) is a well known but poorly understood iatrogenic complication of superovulation. Spontaneous OHSS has been reported with pregnancy, polycystic ovary syndrome, primary hypothyroidism and pituitary adenoma. Only a few cases of massive ovarian enlargement in non-pregnant women with primary hypothyroidism have been reported in the English literature. A definitive pathophysiology remains uncertain, although several postulations were proposed. A 23-year-old nulliparous woman presented with transient bloating of her abdomen associated with menstruation for the last four cycles. She had nausea, headache, faintness, galactorrhoea and clinical signs and symptoms of hypothyroidism (swelling in the hands and feet, cold intolerance, decreased activity, excessive sleepiness, loss of hair and dry skin) for 6 months. Thyroid stimulating hormone and serum prolactin levels were highly elevated (> 100 μg/l and 4,095 μg/l, respectively) and free thyroxine level was low. Abdominal ultrasound showed bilateral multiple thin-walled ovarian cysts. Contrast enhanced CT of brain showed a pituitary macroadenoma. Treatment with levothyroxine was started and showed marked clinical improvement with return to normal menstruation within 4 months. Serial ultrasound showed gradual regression of the ovarian cysts within 6 months. Serum prolactin level was gradually diminished. Awareness that ovarian and pituitary enlargement may be associated with severe hypothyroidism which can be managed successfully, will spare patients dangerous and unnecessary operative intervention for ovarian cysts or pituitary adenoma.

  6. MJA Practice Essentials--Endocrinology. 9: Pituitary disease in adults.

    PubMed

    Hurley, David M; Ho, Ken K Y

    2004-04-19

    Pituitary adenomas are found in 10%-25% of unselected autopsy series and are evident in about 10% of asymptomatic individuals by magnetic resonance imaging. Diagnosis of pituitary disorders is often delayed by lack of awareness and the subtlety of symptoms and signs. Hypopituitarism is suspected when peripheral hormone concentrations are low without an elevation in the corresponding pituitary tropic hormone(s). Severe adult-onset growth-hormone deficiency results in reduced muscle mass, increased fat mass and diminished quality of life, which are reversed by growth hormone replacement therapy. While trans-sphenoidal surgery remains first-line treatment for acromegaly, drug treatment has an important role in controlling residual growth-hormone excess and, in some circumstances, as first-line treatment. Dopamine-agonist therapy (cabergoline or bromocriptine) is the treatment of choice for micro- and macroprolactinomas. In patients with suggestive clinical features, elevated 24-hour urine free cortisol level is usually sufficient to diagnose endogenous Cushing's syndrome; careful additional investigation is needed to determine whether the cause is Cushing's disease (pituitary adenoma secreting adrenocorticotropic hormone [ACTH]), ectopic ACTH secretion or adrenal disease. Heightened awareness is needed to detect the sometimes subtle symptoms and signs of pituitary disease

  7. Cushing's storm secondary to a rare case of ectopic ACTH secreting metastatic breast cancer

    PubMed Central

    Bucciarelli, Maura; Lee, Ya-Yu

    2015-01-01

    Summary Ectopic ACTH secretion from breast cancer is extremely rare. We report a case of a 30-year-old woman with a history of breast cancer, who presented with psychosis and paranoid behaviour. CT of the head showed white matter disease consistent with posterior reversible encephalopathy syndrome (PRES). Despite using mifepristone with multiple antihypertensives including lisinopril, spironolactone and metoprolol, she was hypertensive. Transaminitis did not allow mifepristone dose escalation and ketoconazole utilization. Etomidate infusion at a non-sedating dose in the intensive care unit controlled her hypertension and cortisol levels. She was transitioned to metyrapone and spironolactone. She was discharged from the hospital on metyrapone with spironolactone and underwent chemotherapy. She died 9 months later after she rapidly redeveloped Cushing's syndrome and had progressive metastatic breast cancer involving multiple bones, liver and lungs causing respiratory failure. Learning points Cushing's syndrome from ectopic ACTH secreting breast cancer is extremely rare.Cushing's syndrome causing psychosis could be multifactorial including hypercortisolism and PRES.Etomidate at non-sedating doses in intensive care setting can be effective to reduce cortisol production followed by transition to oral metyrapone. PMID:26525183

  8. Genetic and epigenetic mutations of tumor suppressive genes in sporadic pituitary adenoma.

    PubMed

    Zhou, Yunli; Zhang, Xun; Klibanski, Anne

    2014-04-01

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

  9. Genetic and epigenetic mutations of tumor suppressive genes in sporadic pituitary adenoma

    PubMed Central

    Zhou, Yunli; Zhang, Xun; Klibanski, Anne

    2013-01-01

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

  10. Assessment of clinicopathologic features in patients with pituitary adenomas in Northeast of Iran: A 13-year retrospective study

    PubMed Central

    Anvari, Kazem; Kalantari, Mahmoud Reza; Samini, Fariborz; Shahidsales, Soodabeh; Seilanian-Toussi, Mehdi; Ghorbanpour, Zakiyeh

    2015-01-01

    Background: Intracranial lesions of the pituitary gland are common pituitary adenomas, accounting for 6-10% of all symptomatic intracranial tumors. In this retrospective study, the clinicopathologic features and survival rate of pituitary adenomas were evaluated. Methods: The present retrospective study was conducted on 83 patients with pituitary adenomas, referring to radiation oncology departments of Ghaem and Omid Hospitals, Mashhad, Iran, over a period of 13 years (1999-2012). Data obtained from clinical records including clinical features, type of surgery (if performed), treatment modality, overall survival rate, and progression-free survival rate were analyzed. Results: Eighty-three patients including 44 males (53%) and 39 females (47%) participated in this study. The median age was 40 years (age range: 10-69 years). Chiasm compression was reported in 62 patients (74.4%), and 45.78% of the subjects suffered from headaches. Functional and non-functional adenomas were reported in 44 (53.01%) and 39 (46.99%) patients, respectively. In cases with functional and non-functional adenomas, the disease was controlled in 95 and 84.5% of the subjects for 3 years, respectively. Furthermore, 1- and 3-year survival rates for functional adenoma were 84.6 and 23%, respectively; the corresponding values were 90.9 and 22.7% in non-functional adenomas, respectively. Conclusion: In this study, a significant correlation between headache severity and type of adenoma was observed. So, application of surgery and radiotherapy together could be a highly effective approach for treating functional adenomas, although it is less efficient for the non-functional type. PMID:26885336

  11. 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

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

    PubMed

    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; Barlier, Anne

    2016-07-01

    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

  13. Peptide receptor radionuclide therapy in a patient with disabling non-functioning pituitary adenoma.

    PubMed

    Komor, Jan; Reubi, Jean Claude; Christ, Emanuel R

    2014-06-01

    Non-functioning pituitary adenoma (NFPA) with higher proliferation index (WHO II) are often a therapeutical challenge. Low somatostatin receptor expression in these tumors usually prevents a treatment with somatostatin analogs. In 1996, a 55-year-old patient was referred due to right-sided headache. A pituitary macroadenoma with infiltration into the right cavernous sinus was diagnosed. There was no visual field deficit and the clinical and biochemical work up was consistent with a NFPA. The patient underwent transsphenoidal surgery. Residual adenoma remained in the right cavernous sinus. Histologically, a null-cell adenoma with a high proliferation index was documented (MIB-1: 11.6%, WHO II). Somatostatin receptor autoradiography was performed in the surgical specimen showing a homogenous expression of sst2 receptors. Radiosurgery was completed with stable disease for 8 years. In 2004, the patient was diagnosed with an incomplete palsy of the right oculomotorius nerve and a significant increase in the volume of the adenoma in the right cavernous sinus. After a positive Octreoscan(®) the patient consented to an experimental therapy approach using Lutetium DOTATOC (3 × 200 mCi). The palsy of the oculomotorius nerve improved and remained stable until today (March 2013), the follow-up MRI scans demonstrated stable disease. This is the first case of a patient with a NFPA (WHO II) in whom PRRT successfully improved the local complications of the tumor for more than 8 years after ineffective surgery and gamma knife therapy. The determination of sst2 in vitro using autoradiography and in vivo by Octreoscan was instrumental to administer this therapy in a challenging situation. PMID:23740146

  14. Overexpression of EpCAM and Trop2 in pituitary adenomas

    PubMed Central

    Chen, Xin; Pang, Bo; Liang, Yu; Xu, Shang-Chen; Xin, Tao; Fan, Hai-Tao; Yu, Yan-Bing; Pang, Qi

    2014-01-01

    We sought to investigate the expression of EpCAM and Trop2 in Pituitary adenomas (PAs) and study the correlation of protein expression with invasiveness, proliferation, clinical functioning, recurrence/progression, and some other factors. We investigated the expression of EpCAM and Trop2 in 74 samples of PAs by immunohistochemistry and made correlative analysis of protein overexpression with clinicopathological parameters. Follow-up data was analyzed for recurrence/progression with Kaplan-Meier method and Multivariate Cox regression analysis. Immunohistochemistry results showed that overexpression rates of EpCAM and Trop2 were 51/74 (68.9%) and 43/74 (58.1%), respectively. For both EpCAM and Trop2, PAs with invasiveness showed a higher overexpression rate than PAs without invasiveness (PEpCAM = 0.001; PTrop2 = 0.006). Nonfunctional Pituitary adenomas (NFPAs) demonstrated a higher EpCAM overexpression than functional Pituitary adenomas (FPAs) (P = 0.026). Both EpCAM and Trop2 overexpression correlated significantly with expression of proliferation factor Ki-67 (PEpCAM = 0.011; PTrop2 = 0.000), but not with gender and age. Follow-up analysis revealed that Trop2 overexpression was a significantly predictive factor for recurrence/progression by means of Kaplan-Meier method d (P = 0.028) and Multivariate Cox regression analysis (P = 0.025). This study reveals that both EpCAM and Trop2 overexpression in PAs correlate significantly with invasiveness and proliferation. EpCAM presents a potential target for differential diagnosis and immunotherapy for NFPAs. Follow-up analysis shows that Trop2 is a predictive factor for recurrence/progression for PAs. PMID:25550831

  15. Effectiveness of computer-assisted perimetry in the diagnosis of pituitary adenomas.

    PubMed

    Cannavó, S; De Natale, R; Princi, P; Li Calzi, L; Aragona, A; Trimarchi, F

    1989-12-01

    Computer-assisted perimetry (CP) is a new method which quantifies the differential light sensitivity threshold and allows the statistical analysis of the data. It offers advantages as compared with manual methods. This study has been carried out in 27 patients with pituitary adenomas (four males and 23 females; 13 with prolactinomas; six with acromegaly, four with Cushing's disease and four with non-secreting adenomas). A skull X-ray and a computed tomodensitometry (CT), a manual Goldman perimeter and a computer assisted visual field examination were performed in all cases. The presence of a pituitary tumour was suggested by the X-ray and by the CT in 12 and 23 patients respectively out of the 27: the CT scan revealed a suprasellar extension in seven cases. Visual field defects were detected by means of the Goldman perimeter in six patients and by means of the computer-assisted technique in 25/27. The effectiveness of this new technique was proved by the concordance with the CT scan results in 21 cases and by the histological examination of the four adenomas which were not apparent at CT scan. A significant difference was found for both eyes (right eye, chi squared = 258, P less than 0.001; left eye, chi squared = 295.0, P less than 0.001) between patients and controls. No correlation existed between visual defects and the pituitary size apparent at CT scan. Six patients were evaluated with the CT and CP after 1 year of bromocriptine treatment; a slight reduction of size was documented with the CT in four cases, whereas a significant positive change in visual acuity was observed in five patients.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Cyproheptadine-mediated inhibition of growth hormone and prolactin release from pituitary adenoma cells of acromegaly and gigantism in culture.

    PubMed

    Ishibashi, M; Fukushima, T; Yamaji, T

    1985-08-01

    The effect of cyproheptadine on growth hormone (GH) and prolactin (Prl) secretion from cultured pituitary adenoma cells of acromegaly and pituitary gigantism was studied. When varying doses of cyproheptadine ranging from 0.01 to 1 microM were added to the incubation media, GH secretion was consistently inhibited and a dose-response relationship was observed between the cyproheptadine concentrations and the amounts of GH released into the media. In pituitary adenomas which concurrently produced and secreted Prl, cyproheptadine likewise suppressed Prl release in a dose-related manner. This effect of cyproheptadine was not blocked by coincubation with serotonin. Similarly, coincubation with a dopaminergic antagonist, haloperidol, failed to reverse the inhibitory action produced by cyproheptadine. When coincubated with dopamine, cyproheptadine further inhibited GH and Prl secretion. These results suggest that cyproheptadine possesses a direct action on human somatotroph adenoma cells to inhibit GH and Prl secretion by an unknown mechanism that is different from serotonergic and dopaminergic systems. PMID:2994332

  17. Innervated ectopic salivary gland associated with Rathke's cleft cyst clinically mimicking pituitary adenoma.

    PubMed

    Stefanits, Harald; Matula, Christian; Frischer, Josa M; Furtner, Julia; Hainfellner, Johannes A; Woehrer, Adelheid

    2013-01-01

    Herein, we report an exceptional case of a young female patient with progressive enlargement of a sellar mass, clinically suggestive of pituitary adenoma. Histopathology, however, demonstrated Rathke's cleft cyst associated with salivary gland remnants. In contrast to the majority of prior reports, the ectopic salivary glands were found in close proximity to the anterior pituitary lobe and showed active production of mucous secret, which caused progressive growth and symptoms in this patient. We further demonstrate nerve fibers surrounding the ectopic salivary glands, thereby suggesting parasympathetic innervation as a plausible mechanism triggering seromucous secretion. Neurosurgeons and neuropathologists need to be aware of this rare clinical condition expanding the spectrum of differential diagnoses of sellar masses. PMID:23254138

  18. Ectopic Acromegaly Arising from a Pituitary Adenoma within the Bony Intersphenoid Septum of a Patient with Empty Sella Syndrome

    PubMed Central

    Arzamendi, Audrey E.; Shahlaie, Kiarash; Latchaw, Richard E.; Lechpammer, Mirna; Arzumanyan, Hasmik

    2016-01-01

    Objective  To describe the work-up and treatment of rare ectopic acromegaly caused by a biopsy-proven somatotroph pituitary adenoma located within the bony intersphenoid septum of a patient with empty sella syndrome (ESS). Methods  We report the presentation, clinical course, diagnostic work-up, and lesion localization and treatment challenges encountered in a 55-year-old patient, with a brief review of relevant literature. Results  A 55-year-old African-American man presented with acromegaly and ESS. Attempts to definitively localize the causative tumor were unsuccessful, though petrosal sinus sampling supported central growth hormone production and imaging suggested bone-enclosed subsellar pituitary tissue. Endoscopic endonasal transphenoidal exploration was undertaken with resection of a somatotroph pituitary microadenoma, and subsequent clinical improvement and biochemical remission. Retrospective review revealed the patient's pituitary to have been located ectopically within a unique bony intersphenoid septum. Conclusion  This report describes the first known case of an ectopic pituitary adenoma located within the midline bony intersphenoid septum, which we postulate to have resulted from anomalous embryological pituitary migration. Intra-intersphenoid septal tumors should be considered in cases of apparent central acromegaly with ESS or absence of tumor tissue within the paranasal sinuses or other peripheral locations. Indexing  Acromegaly, ESS, pituitary adenoma, sphenoid sinus septum. PMID:27468406

  19. High prevalence of radiological vertebral fractures in women with prolactin-secreting pituitary adenomas.

    PubMed

    Mazziotti, Gherardo; Mancini, Tatiana; Mormando, Marilda; De Menis, Ernesto; Bianchi, Antonio; Doga, Mauro; Porcelli, Teresa; Vescovi, Pier Paolo; De Marinis, Laura; Giustina, Andrea

    2011-12-01

    Hyperprolactinemia may cause bone loss but data on fractures are scanty. The aim of this study was to evaluate the prevalence of vertebral fractures in women with prolactin (PRL)-secreting adenoma. In this cross-sectional study, 78 women (median age 45.5 years, range: 20-81) with PRL-secreting pituitary adenoma (66 with microadenoma and 12 with macroadenoma) and 156 control subjects, with normal PRL values and with comparable age to patients with hyperprolactinemia, were evaluated for vertebral fractures by a morphometric approach and for bone mineral density (BMD) by a dual-energy X-ray absorptiometry at lumbar spine. Vertebral fractures were shown in 25 patients with PRL-secreting adenoma (32.6%) and in 20 controls (12.8%, P < 0.001). Fractured patients were significantly older (P < 0.001) and had lower BMD T-score (P < 0.001), longer duration of disease (P < 0.001), higher serum PRL (P = 0.004) and lower serum IGF-I (P < 0.001) values as compared to patients who did not fracture. The prevalence of vertebral fractures was significantly (P < 0.001) higher in post-menopausal women with PRL-secreting adenoma as compared to pre-menopausal patients. Fractures occurred more frequently (P = 0.01) in patients with untreated hyperprolactinemia versus patients treated with cabergoline. Logistic regression analysis demonstrated that duration of disease maintained a significant correlation with vertebral fractures (odds ratio 1.16, C.I. 95% 1.02-1.33) even after correction for age, menopausal status, treatment with cabergoline, BMD, serum IGF-I and serum PRL values. Hyperprolactinemia is associated with high prevalence of radiological vertebral fractures in women with PRL-secreting adenoma.

  20. 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

    2015-01-01

    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. PMID:26593398

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

    PubMed Central

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

    2015-01-01

    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. PMID:26593398

  2. Acellular Dermal Allograft for Sellar Repair after Transsphenoidal Approach to Pituitary Adenomas

    PubMed Central

    Gaynor, Brandon G.; Benveniste, Ronald J.; Lieberman, Seth; Casiano, Roy; Morcos, Jacques J.

    2013-01-01

    Objectives Our practice has transitioned from using fat autograft to acellular dermal matrix (AlloDerm, LifeCell Corp, Woodlands, Texas, USA). We present the largest series to our knowledge of AlloDerm for sellar floor repair after transsphenoidal approach to pituitary adenoma and compare rates of postoperative cerebrospinal fluid (CSF) leak with an earlier cohort of patients whose CSF leaks were repaired with fat autograft. Design This is a retrospective cohort study comparing sellar repair with fat autograft versus inlay Alloderm between the years 2003 and 2012. The primary end point was postoperative CSF leak. Results A total of 429 patients (368 primary; 83 revision operations) without intraoperative lumbar drainage were included. A total of 18 postoperative CSF leaks were observed (3.9%). Intraoperative CSF leak occurred in 160 cases (35.5%). Among this subset of patients with intraoperative CSF leak, 95 underwent repair with AlloDerm and 46 underwent repair with fat autograft, with postoperative CSF leak rates of 8.4% and 15.2%, respectively (p = 0.34, chi-square test); 19 patients underwent repair with other techniques or no repair at all, with postoperative leak rate of 0%. Conclusions AlloDerm is an effective alternative to fat autograft in cases of low-flow CSF leak following transsphenoidal resection of pituitary adenoma. PMID:24436906

  3. Endoscopic endonasal cavernous sinus surgery, with special reference to pituitary adenomas.

    PubMed

    Frank, Giorgio; Pasquini, Ernesto

    2006-01-01

    Cavernous sinus surgery has always been a surgical challenge because of the high functional importance of this region and the associated high morbidity. The augmented peripheral vision of the endoscope has led to the development of surgical approaches that allow adequate exposure of the cavernous sinus, with a reduction in surgical morbidity. Since 1998, 65 patients with pituitary adenomas and intraoperative evidence of cavernous sinus invasion were treated with a purely endoscopic approach. Follow-up was of at least 6 (mean 51.2) months. There was no perioperative mortality and extremely low morbidity. Radical tumor removal was obtained in 21/35 cases with nonfunctioning adenomas. Hormonal remission was obtained in 13/30 functioning adenomas. One patient with partial hypopituitarism and 1 patient with persistent diabetes insipidus were seen. Three patients with delayed CSF leaks required endoscopic repair. In 1 patient with hemorrhagic infarction in a residual tumor, reintervention with craniotomy was necessary. We advocate the central role of surgery in the treatment of cavernous sinus tumors, since it allows definition of true cavernous sinus involvement, histopathological diagnosis and, when cure is not feasible, tumor volume reduction, which might be an important factor in the response to adjuvant therapy. PMID:16474216

  4. 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

  5. Nitroproteins from a human pituitary adenoma tissue discovered with a nitrotyrosine affinity column and tandem mass spectrometry.

    PubMed

    Zhan, Xianquan; Desiderio, Dominic M

    2006-07-15

    The aim of this study was to characterize endogenous nitroproteins, and those proteins that interact with nitroproteins, in a human pituitary nonfunctional adenoma so as to clarify the role of protein nitration in adenomas. A nitrotyrosine affinity column (NTAC) was used to preferentially enrich and isolate endogenous nitroproteins and nitroprotein-protein complexes from a tissue homogenate that was prepared from a human pituitary nonfunctional pituitary adenoma. The preferentially enriched endogenous nitroproteins and nitroprotein-protein complexes were subjected to trypsin digestion, desalination, and tandem mass spectrometry analysis. Nine nitroproteins (Rho-GTPase-activing protein 5, leukocyte immunoglobulin-like receptor subfamily A member 4 precursor, zinc finger protein 432, cAMP-dependent protein kinase type I-beta regulatory subunit, sphingosine-1-phosphate lyase 1, centaurin beta 1, proteasome subunit alpha type 2, interleukin 1 family member 6, and rhophilin 2) and three proteins (interleukin 1 receptor-associated kinase-like 2, glutamate receptor-interacting protein 2, and ubiquitin) that interacted with nitroproteins were discovered. The nitration site of each nitroprotein was located onto the functional domain where nitration occurred, and each nitroprotein was related to a corresponding functional system. Those data indicate that protein nitration might be an important molecular event in the formation of a human pituitary nonfunctional adenoma.

  6. Pituitary prolactinoma, pancreatic glucagonomas, and aldosterone-producing adrenal cortical adenoma: a suggested variant of multiple endocrine neoplasia type I.

    PubMed

    Gould, E; Albores-Saavedra, J; Shuman, J

    1987-12-01

    A case of a pituitary prolactinoma, pancreatic glucagonoma, and an aldosterone-producing adrenal cortical adenoma coexisting in a 65-year-old man is reported. This case may represent a sporadic variant of the multiple endocrine neoplasia syndrome type I first manifested by hyperaldosteronism.

  7. The role of radiation therapy in the management of non-functioning pituitary adenomas.

    PubMed

    Losa, M; Picozzi, P; Motta, M; Valle, M; Franzin, A; Mortini, P

    2011-09-01

    Surgical removal of non-functioning pituitary adenoma (NFPA) is the first-choice therapeutic option, but radical removal of the tumor cannot be accomplished in all patients. The best strategy to prevent regrowth of NFPA is still a matter of debate. Adjuvant radiotherapy is very effective in reducing recurrence rate after incomplete removal of NFPA, but concerns still exist about long-term toxicity of radiation. Different modalities have been developed to irradiate the pituitary region. One major distinction is between radiation techniques that deliver the total dose in multiple sessions using 3 fixed radiation beams and radiosurgical equipment that delivers the total dose to the target volume in a single treatment session. Progression-free survival of patients with NFPA treated by adjuvant radiotherapy is well above 90% at 5 yr in most studies and diminishes only slightly at 10 yr. Very few studies have a more prolonged follow-up. In comparison, the 5- and 10-yr estimated recurrence rate without adjuvant radiotherapy ranged from 15% to 51% and from 44% to 78%, respectively. Complications of radiation include rare but severe side-effects, such as secondary brain neoplasm, optic neuropathy, cerebrovascular accidents, and more frequent but less severe complications, such as pituitary deficiency. Optimal management of patients with residual or recurring NFPA after surgical debulking can be achieved through the judicious use of different treatment options, necessitating close cooperation between neurosurgeons, endocrinologists, and radiation oncologists. PMID:21427527

  8. Paradoxical migrating cyst: an unusual presentation of intraventricular neurocysticercosis with a coincidental pituitary adenoma.

    PubMed

    Ghosh, Shanchita; Al-Khalili, Rend; Liu, James K; Slasky, Shira E

    2014-06-01

    Intraventricular neurocysticercosis is an uncommon entity which may become symptomatic due to cerebrospinal fluid flow obstruction. Migration of intraventricular cysts through the ventricular spaces is a rare occurrence. This phenomenon is poorly understood but may be due to pressure changes within the ventricular cavities. We present a patient with intraventricular neurocysticercosis with paradoxical transaqueductal migration of the cyst from the cerebral aqueduct to the fourth ventricle shortly after ventricular drain placement for acute hydrocephalus. The patient also presented with a coincidental sellar and suprasellar mass, later pathologically proven to be a pituitary adenoma. The migration of this cyst resulted in spontaneous relief of obstruction at the cerebral aqueduct, thus restoring normal cerebrospinal fluid pathways and avoiding permanent shunting. We discuss the possible mechanisms and implications of cyst migration, and the diagnostic challenges of concomitant findings of a pituitary mass and neurocysticercosis. Although the presence of a sellar and suprasellar mass in a patient with known neurocysticercosis should raise clinical suspicion for the possibility of sellar neurocysticercosis, pituitary macroadenoma is a more common entity and a more likely etiology for a sellar lesion.

  9. 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

  10. 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.

  11. 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.

  12. 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. PMID:26262034

  13. The multimodal management of GH-secreting pituitary adenomas: predictive factors, strategies and outcomes

    PubMed Central

    Buliman, A; Tataranu, LG; Ciubotaru, V; Cazac, TL; Dumitrache, C

    2016-01-01

    Object. The aim of this study was to analyze a series of 28 patients with acromegaly who underwent a multimodal surgical, medical and radiosurgical therapy, with a special attention to the advantages, complications, and predictive factors of a successful outcome. Methods. 28 consecutive cases of GH-secreting pituitary adenomas, who underwent transsphenoidal endoscopic or microscopic surgery, between 1 January 2014 and 31 December 2014 were retrospectively reviewed. Tumors were classified according to the diameter, measured on MRI, as micro- or macroadenomas, and parasellar (cavernous sinus) tumor extension was analyzed based on the Knosp grading score. The mean follow-up period was of 18.4 months. Criteria justifying the complete hormonal remission were preoperative basal serum GH < 2.5 μg/ L, preoperative nadirGH < 1 ng/ L after OGTT and normal preoperative IGF–I levels age and sex-matched. Results. An overall complete hormonal remission rate was achieved in 64.3% of the patients. The remission rate was higher in patients with microadenomas (77.8%) than in those with macroadenomas (57.9%). A number of predictive factors, which might have interfered with the hormonal remission rate from a statistical, clinical and paraclinical point of view, were identified: tumor size (r = 0.625), preoperative GH serum levels (r = -0.517), cavernous sinus extension was quantified according to Knosp grading score (r = 0.469) and the degree of tumor subtotal resection (r = 0.598). Conclusions. Favorable hormonal and visual remission rates can be achieved after transsphenoidal resection of GH-secreting pituitary adenomas; however, the management remains challenging, the increased surgical experience being important for higher cure rates. If a biochemical hormonal cure is not achieved postoperatively, adjuvant medical or radio surgical therapy can be recommended. PMID:27453753

  14. The multimodal management of GH-secreting pituitary adenomas: predictive factors, strategies and outcomes.

    PubMed

    Buliman, A; Tataranu, L G; Ciubotaru, V; Cazac, T L; Dumitrache, C

    2016-01-01

    Object. The aim of this study was to analyze a series of 28 patients with acromegaly who underwent a multimodal surgical, medical and radiosurgical therapy, with a special attention to the advantages, complications, and predictive factors of a successful outcome. Methods. 28 consecutive cases of GH-secreting pituitary adenomas, who underwent transsphenoidal endoscopic or microscopic surgery, between 1 January 2014 and 31 December 2014 were retrospectively reviewed. Tumors were classified according to the diameter, measured on MRI, as micro- or macroadenomas, and parasellar (cavernous sinus) tumor extension was analyzed based on the Knosp grading score. The mean follow-up period was of 18.4 months. Criteria justifying the complete hormonal remission were preoperative basal serum GH < 2.5 μg/ L, preoperative nadirGH < 1 ng/ L after OGTT and normal preoperative IGF-I levels age and sex-matched. Results. An overall complete hormonal remission rate was achieved in 64.3% of the patients. The remission rate was higher in patients with microadenomas (77.8%) than in those with macroadenomas (57.9%). A number of predictive factors, which might have interfered with the hormonal remission rate from a statistical, clinical and paraclinical point of view, were identified: tumor size (r = 0.625), preoperative GH serum levels (r = -0.517), cavernous sinus extension was quantified according to Knosp grading score (r = 0.469) and the degree of tumor subtotal resection (r = 0.598). Conclusions. Favorable hormonal and visual remission rates can be achieved after transsphenoidal resection of GH-secreting pituitary adenomas; however, the management remains challenging, the increased surgical experience being important for higher cure rates. If a biochemical hormonal cure is not achieved postoperatively, adjuvant medical or radio surgical therapy can be recommended. PMID:27453753

  15. Clinical applications of somatostatin analogs for growth hormone-secreting pituitary adenomas.

    PubMed

    Wang, Ji-Wen; Li, Ying; Mao, Zhi-Gang; Hu, Bin; Jiang, Xiao-Bing; Song, Bing-Bing; Wang, Xin; Zhu, Yong-Hong; Wang, Hai-Jun

    2014-01-01

    Excessive growth hormone (GH) is usually secreted by GH-secreting pituitary adenomas and causes gigantism in juveniles or acromegaly in adults. The clinical complications involving cardiovascular, respiratory, and metabolic systems lead to elevated morbidity in acromegaly. Control of serum GH and insulin-like growth factor (IGF) 1 hypersecretion by surgery or pharmacotherapy can decrease morbidity. Current pharmacotherapy includes somatostatin analogs (SAs) and GH receptor antagonist; the former consists of lanreotide Autogel (ATG) and octreotide long-acting release (LAR), and the latter refers to pegvisomant. As primary medical therapy, lanreotide ATG and octreotide LAR can be supplied in a long-lasting formulation to achieve biochemical control of GH and IGF-1 by subcutaneous injection every 4-6 weeks. Lanreotide ATG and octreotide LAR provide an effective medical treatment, whether as a primary or secondary therapy, for the treatment of GH-secreting pituitary adenoma; however, to maximize benefits with the least cost, several points should be emphasized before the application of SAs. A comprehensive assessment, especially of the observation of clinical predictors and preselection of SA treatment, should be completed in advance. A treatment process lasting at least 3 months should be implemented to achieve a long-term stable blood concentration. More satisfactory surgical outcomes for noninvasive macroadenomas treated with presurgical SA may be achieved, although controversy of such adjuvant therapy exists. Combination of SA and pegvisomant or cabergoline shows advantages in some specific cases. Thus, an individual treatment program should be established for each patient under a full evaluation of the risks and benefits. PMID:24421637

  16. Clinical applications of somatostatin analogs for growth hormone-secreting pituitary adenomas

    PubMed Central

    Wang, Ji-wen; Li, Ying; Mao, Zhi-gang; Hu, Bin; Jiang, Xiao-bing; Song, Bing-bing; Wang, Xin; Zhu, Yong-hong; Wang, Hai-jun

    2014-01-01

    Excessive growth hormone (GH) is usually secreted by GH-secreting pituitary adenomas and causes gigantism in juveniles or acromegaly in adults. The clinical complications involving cardiovascular, respiratory, and metabolic systems lead to elevated morbidity in acromegaly. Control of serum GH and insulin-like growth factor (IGF) 1 hypersecretion by surgery or pharmacotherapy can decrease morbidity. Current pharmacotherapy includes somatostatin analogs (SAs) and GH receptor antagonist; the former consists of lanreotide Autogel (ATG) and octreotide long-acting release (LAR), and the latter refers to pegvisomant. As primary medical therapy, lanreotide ATG and octreotide LAR can be supplied in a long-lasting formulation to achieve biochemical control of GH and IGF-1 by subcutaneous injection every 4–6 weeks. Lanreotide ATG and octreotide LAR provide an effective medical treatment, whether as a primary or secondary therapy, for the treatment of GH-secreting pituitary adenoma; however, to maximize benefits with the least cost, several points should be emphasized before the application of SAs. A comprehensive assessment, especially of the observation of clinical predictors and preselection of SA treatment, should be completed in advance. A treatment process lasting at least 3 months should be implemented to achieve a long-term stable blood concentration. More satisfactory surgical outcomes for noninvasive macroadenomas treated with presurgical SA may be achieved, although controversy of such adjuvant therapy exists. Combination of SA and pegvisomant or cabergoline shows advantages in some specific cases. Thus, an individual treatment program should be established for each patient under a full evaluation of the risks and benefits. PMID:24421637

  17. 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.

  18. 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.

  19. 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.

  20. Effects of selective somatostatin analogs and cortistatin on cell viability in cultured human non-functioning pituitary adenomas.

    PubMed

    Padova, H; Rubinfeld, H; Hadani, M; Cohen, Z R; Nass, D; Taylor, J E; Culler, M D; Shimon, I

    2008-05-14

    Clinically "non-functioning" human pituitary adenomas (NFPA) constitute about 35% of pituitary adenomas. Somatostatin receptors (SSTR) expression in these adenomas has previously been described both in vitro and in vivo, without evidence for a correlation with tumor volume or the therapeutic efficacy of somatostatin analogs. This study was performed on 13 surgically removed pituitary macroadenomas, diagnosed before surgery as "non-functioning". In addition, 3 growth hormone (GH)-secreting adenomas served as controls. A specimen from each tumor was dispersed and digested to isolate and culture the tumor cells, and the in vitro effects of SSTR2 and SSTR5 selective analogs and Cortistatin (CST) (100nM) on cell viability were studied. The quantity of viable cells was estimated using the XTT method. RNA purification of tumor samples and subsequent RT-PCR studies for SSTR2 and SSTR5 expression were performed. Somatostatin analog with high affinity for SSTR2 reduced cell viability by 20-80% in 8 of 13 NFPAs studied, all expressing the SSTR2. The inhibitory effect on cell viability of SSTR5-selective analog was 15-80% in 10 of 13 NFPAs studied, all but three expressing the SSTR5. CST, however, effectively reduced cell viability in only 6 NFPAs. Cell viability was inhibited by all peptides studied in 2 out of 3 GH-secreting adenomas, expressing both receptors. The third adenoma responded to SSTR2 analog and expressed only SSTR2. These results suggest the involvement of SSTR2 and SSTR5 in the anti-proliferative effects of somatostatin; however, CST is less potent in reducing cell viability in these tumors. PMID:18276067

  1. [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.

  2. [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. PMID:27270145

  3. Cushing's Syndrome From Pituitary Microadenoma and Pulmonary Nodules.

    PubMed

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

    2016-03-01

    Cushing's syndrome is a state of cortisol excess, possibly from a tumor in the pituitary gland, the adrenal gland, or an ectopic nonpituitary ACTH-secreting source. The first form, pituitary in origin, was originally described by Harvey Cushing, MD, and was labeled as Cushing's disease. Long-term therapy with glucocorticoids also can lead to iatrogenic Cushing's syndrome. PMID:26906124

  4. Cushing's Syndrome From Pituitary Microadenoma and Pulmonary Nodules.

    PubMed

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

    2016-03-01

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

  5. 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

  6. Cushing's syndrome secondary to ectopic ACTH secretion: The University of Texas MD Anderson Cancer Center Experience

    PubMed Central

    Ejaz, Shamim; Vassilopoulou-Sellin, Rena; Busaidy, Naifa L.; Hu, Mimi I.; Waguespack, Steven G.; Jimenez, Camilo; Ying, Anita K.; Cabanillas, Maria; Abbara, Maher; Habra, Mouhammed Amir

    2011-01-01

    Background Cushing's syndrome (CS) secondary to ectopic ACTH secretion (EAS) has been described in association with a variety of tumors. The current experience with this syndrome is based on a few case series and individual case reports. Limited data are available about the tumors associated with CS-EAS in cancer center setting. This report describes CS-EAS at MD Anderson Cancer Center to further enhance our understanding and management of this syndrome. Methods This is a retrospective review for 43 patients with CS-EAS who were diagnosed between 1979 and 2009 at our institution. Results Different neuroendocrine tumors were associated with CS-EAS. Twenty one patients (48.9%) had tumors located in the chest cavity with bronchial carcinoid and small cell lung cancer representing the two most common causes. The ACTH source remained occult in 4 patients (9.3 %) despite extensive work-up. Clinical presentation was variable and the classical features of CS were not evident in some patients. Death occurred in 27 patients (62.8%) and the median overall survival was 32.2 months. Major morbidities included new onset or worsening hyperglycemia (77%), symptomatic venous thromboembolism (14%) and infections (23%). Conclusions In CS-EAS cases seen at a comprehensive cancer center, tumors originating in the chest cavity were the leading tumors associated with this syndrome. We suspect that CS-EAS is underreported because of the atypical presentation in some cases. Thus, we suggest careful evaluation of patients with neuroendocrine tumors to avoid missing co-existing CS-EAS. PMID:21412758

  7. Investigation of hypothalamic-pituitary disease.

    PubMed

    Lamberton, R P; Jackson, I M

    1983-11-01

    It can be readily appreciated from the preceding discussion that many endocrine and non-endocrine tests are available for the evaluation of patients with suspected hypothalamic-pituitary disease. The endocrine evaluation of these subjects should be tailored according to the type and extent of pathology suspected (see Tables 2 and 3). For patients with pituitary adenomas and clinical features of hyperpituitarism, such as hyperprolactinaemia, Cushing's disease or acromegaly, the initial tests should be directed at the hormone whose excess is suspected. For example, a glucose suppression test for acromegaly or dexamethasone suppression test for Cushing's disease should be performed early in the evaluation. The possibility of deficiencies of the other pituitary hormones should then be addressed in patients with secretory tumours, but initially in those with apparent non-functioning adenomas. In patients with large macroadenomas pituitary hormone deficiencies are almost invariable with GH and FSH/LH being the most commonly affected, followed by TSH and ACTH in that order (Snyder et al, 1979a; Valenta et al, 1982). Basal thyroid function tests, serum oestradiol or testosterone, and basal gonodotrophins should be routinely obtained in patients with macroadenomas. Additionally, the integrity of the pituitary-adrenal axis should be determined and an overnight water deprivation test for assessment of neurohypophyseal function is also recommended. GH stimulation testing is valuable as a test of pituitary function in patients with suspected pituitary tumours since GH reserve is lost very early in the development of hypopituitarism. Evaluation of the pituitary-thyroid axis with TRH or the pituitary gonadal axis with LHRH generally provides limited additional information of diagnostic value in individual patients with macroadenomas. However, the 'paradoxical' responses to TRH and LHRH may be useful as a biological marker following therapy in patients with GH- or ACTH-secreting

  8. 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

  9. 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

  10. Glucocorticoid Fast Feedback Inhibition of Stress-Induced ACTH Secretion in the Male Rat: Rate Independence and Stress-State Resistance.

    PubMed

    Osterlund, Chad D; Rodriguez-Santiago, Mariana; Woodruff, Elizabeth R; Newsom, Ryan J; Chadayammuri, Anjali P; Spencer, Robert L

    2016-07-01

    Normal glucocorticoid secretion is critical for physiological and mental health. Glucocorticoid secretion is dynamically regulated by glucocorticoid-negative feedback; however, the mechanisms of that feedback process are poorly understood. We assessed the temporal characteristics of glucocorticoid-negative feedback in vivo using a procedure for drug infusions and serial blood collection in unanesthetized rats that produced a minimal disruption of basal ACTH plasma levels. We compared the negative feedback effectiveness present when stress onset coincides with corticosterone's (CORT) rapidly rising phase (30 sec pretreatment), high plateau phase (15 min pretreatment), or restored basal phase (60 min pretreatment) as well as effectiveness when CORT infusion occurs after the onset of stress (5 min poststress onset). CORT treatment prior to stress onset acted remarkably fast (within 30 sec) to suppress stress-induced ACTH secretion. Furthermore, fast feedback induction did not require rapid increases in CORT at the time of stress onset (hormone rate independent), and those feedback actions were relatively long lasting (≥15 min). In contrast, CORT elevation after stress onset produced limited and delayed ACTH suppression (stress state resistance). There was a parallel stress-state resistance for CORT inhibition of stress-induced Crh heteronuclear RNA in the paraventricular nucleus but not Pomc heteronuclear RNA in the anterior pituitary. CORT treatment did not suppress stress-induced prolactin secretion, suggesting that CORT feedback is restricted to the control of hypothalamic-pituitary-adrenal axis elements of a stress response. These temporal, stress-state, and system-level features of in vivo CORT feedback provide an important physiological context for ex vivo studies of molecular and cellular mechanisms of CORT-negative feedback. PMID:27145013

  11. Glucocorticoid Fast Feedback Inhibition of Stress-Induced ACTH Secretion in the Male Rat: Rate Independence and Stress-State Resistance.

    PubMed

    Osterlund, Chad D; Rodriguez-Santiago, Mariana; Woodruff, Elizabeth R; Newsom, Ryan J; Chadayammuri, Anjali P; Spencer, Robert L

    2016-07-01

    Normal glucocorticoid secretion is critical for physiological and mental health. Glucocorticoid secretion is dynamically regulated by glucocorticoid-negative feedback; however, the mechanisms of that feedback process are poorly understood. We assessed the temporal characteristics of glucocorticoid-negative feedback in vivo using a procedure for drug infusions and serial blood collection in unanesthetized rats that produced a minimal disruption of basal ACTH plasma levels. We compared the negative feedback effectiveness present when stress onset coincides with corticosterone's (CORT) rapidly rising phase (30 sec pretreatment), high plateau phase (15 min pretreatment), or restored basal phase (60 min pretreatment) as well as effectiveness when CORT infusion occurs after the onset of stress (5 min poststress onset). CORT treatment prior to stress onset acted remarkably fast (within 30 sec) to suppress stress-induced ACTH secretion. Furthermore, fast feedback induction did not require rapid increases in CORT at the time of stress onset (hormone rate independent), and those feedback actions were relatively long lasting (≥15 min). In contrast, CORT elevation after stress onset produced limited and delayed ACTH suppression (stress state resistance). There was a parallel stress-state resistance for CORT inhibition of stress-induced Crh heteronuclear RNA in the paraventricular nucleus but not Pomc heteronuclear RNA in the anterior pituitary. CORT treatment did not suppress stress-induced prolactin secretion, suggesting that CORT feedback is restricted to the control of hypothalamic-pituitary-adrenal axis elements of a stress response. These temporal, stress-state, and system-level features of in vivo CORT feedback provide an important physiological context for ex vivo studies of molecular and cellular mechanisms of CORT-negative feedback.

  12. [Endoscopy versus microsurgery: results in a consecutive series of nonfunctioning pituitary adenomas].

    PubMed

    Kassis, S; De Battista, J C; Raverot, G; Jacob, M; Simon, E; Rabilloud, M; Froehlich, P; Trouillas, J; Borson-Chazot, F; Perrin, G; Jouanneau, E

    2009-12-01

    Microsurgical removal of nonfunctioning pituitary adenomas (NFPAs) is often subtotal. Removing the blind spots as viewed through the microscope, endoscopic surgery may improve the quality of removal. Our purpose was to compare the results of the two techniques in a series of NFPA patients operated on by a single surgeon. Thirty-six patients with newly diagnosed NFPAs were operated on using a purely endoscopic procedure and 29 with a microsurgical technique. All patients were explored pre- and postoperatively (at 3 and 6 months and then every 12 months) by endocrine assays, ophthalmologic exam, and 3D MRI. The endocrine and ophthalmologic results as well as the quality of resection and the complications from the two techniques were compared. The follow-up duration and the mean tumor volume (higher in the microsurgical group) were the only differences observed between the two groups. Tumor height and the invasion of the cavernous sinus were not different. All patients with preoperative visual impairment in the endoscopic group improved, whereas in the microsurgical group 90.9% improved, 4.5% were stabilized, and 4.5% worsened (p=ns). Regarding anterior pituitary functions, 42.8% of the patients improved in the endoscopic group, 45.7% remained stable, and 11.4% worsened compared to, respectively, 31, 44,8, and 24.1% in the microsurgical group (p=ns). Gross total removal was achieved in 86.1% for the endoscopic group and in only 65.5% for the microsurgical group (p=0.075). Morbidity was similar in the two groups. This retrospective series showed that endoscopic surgery compared to microsurgery increases the quality of NFPA removal with similar morbidity. PMID:19733369

  13. 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. PMID:25273395

  14. 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

  15. Metabolic abnormalities in pituitary adenoma patients: a novel therapeutic target and prognostic factor

    PubMed Central

    Zheng, Xin; Li, Song; Zhang, Wei-hua; Yang, Hui

    2015-01-01

    Metabolic abnormalities are common in cancers, and targeting metabolism is emerging as a novel therapeutic approach to cancer management. Pituitary adenoma (PA) is a type of benign tumor. Impairment of tumor cells’ metabolism in PA seems not to be as apparent as that of other malignant tumor cells; however, aberrant hormone secretion is conspicuous in most PAs. Hormones have direct impacts on systemic metabolism, which in turn, may affect the progression of PA. Nowadays, conventional therapeutic strategies for PA do not include modalities of adjusting whole-body metabolism, which is most likely due to the current consideration of the aberrant whole-body metabolism of PA patients as a passive associated symptom and not involved in PA progression. Because systemic metabolic abnormalities are presented by 22.3%–52.5% PA patients and are closely correlated with disease progression and prognosis, we propose that assessment of metabolic status should be emphasized during the treatment of PA and that control of metabolic abnormalities should be added into the current therapies for PA. PMID:26347444

  16. 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

  17. Smad3 and phospho-Smad3 are potential markers of invasive nonfunctioning pituitary adenomas

    PubMed Central

    Liu, Chunhui; Li, Zhenye; Wu, Dan; Li, Chuzhong; Zhang, Yazhuo

    2016-01-01

    Background Transforming growth factor-β (TGF-β) signaling plays important roles in tumor development. Nevertheless, the roles of TGF-β/Smad signaling in nonfunctioning pituitary adenomas (NFPAs) have not been fully studied. Methods Tumor samples were obtained from patients who had NFPAs and underwent endoscopic transsphenoidal surgery or craniotomy at Beijing Tiantan Hospital from March 2008 to December 2012. Immunohistochemistry was performed to determine the expression of Smad transducer proteins in NFPAs. Ki-67 was evaluated as an indicator of the proliferative activity of NFPAs. Results A total of 161 patients with NFPAs were identified; 59 (36.6%) had invasive NFPAs and 102 (63.4%) had noninvasive NFPAs. Protein levels of Smad3 and phospho-Smad3 (p-Smad3) were significantly lower in patients with invasive NFPAs than in patients with noninvasive NFPAs (P<0.05 and P<0.01, respectively). The Ki-67 index was markedly greater in invasive NFPAs than in noninvasive NFPAs (P<0.05) and was significant correlated with p-Smad3 levels (P<0.05, r=−0.702). Conclusion A low level of Smad3 and p-Smad3 proteins was associated with the invasion of NFPAs. PMID:27143922

  18. 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. PMID:18642089

  19. Investigation of Responsiveness to Thyrotropin-Releasing Hormone in Growth Hormone-Producing Pituitary Adenomas

    PubMed Central

    Chin, Sang Ouk; Hwang, You-Cheol; Jeong, In-Kyung; Oh, Seungjoon

    2013-01-01

    Objective. The aim of this study was to investigate how the paradoxical response of GH secretion to TRH changes according to tumor volumes. Methods. Patients with newly diagnosed acromegaly were classified as either TRH responders or nonresponders according to the results of a TRH stimulation test (TST), and their clinical characteristics were compared according to responsiveness to TRH and tumor volumes. Results. A total of 41 acromegalic patients who underwent the TST were included in this study. Between TRH responders and nonresponders, basal GH, IGF-I levels, peak GH levels, and tumor volume were not significantly different, but the between-group difference of GH levels remained near significant over the entire TST time. ΔGHmax-min during the TST were significantly different according to the responsiveness to TRH. Peak GH levels and ΔGHmax-min during the TST showed significantly positive correlations with tumor volume with higher levels in macroadenomas than in microadenomas. GH levels over the entire TST time also remained significantly higher in macroadenomas than in microadenomas. Conclusion. Our data demonstrated that the paradoxical response of GH secretion to TRH in GH-producing pituitary adenomas was not inversely correlated with tumor volumes. PMID:24348552

  20. Mononostril versus Binostril Endoscopic Transsphenoidal Approach for Pituitary Adenomas: A Systematic Review and Meta-Analysis

    PubMed Central

    Zhong, Chunyu; Li, Xiang; Li, Junyang; Li, Liwen; Yang, Youqing; Ma, Chiyuan

    2016-01-01

    Background Over the past several decades, the endoscopic endonasal transsphenoidal approach (EETA) has gradually become a preferred option of pituitary adenomas surgery because of its minimal invasiveness and high efficiency. However, some EETA operations were performed through one nostril (mononostril), while other EETA operations were performed through both nostrils (binostril). Therefore, we conducted this study to compare the pros and cons of these two methods in an attempted to confirm which method is more effective. Methods We executed a systematic literature search of PubMed, the Cochrane Library, and the Web of Science and Medline (1992–2015). The language is limited to English and all studies should meet the inclusion criteria. Comparisons were made for postoperative outcomes, complications, and other relevant parameters between the mononostril and the binostril group. Statistical analyses of categorical variables were undertaken by the use of Stata 12.0 and SPASS 19.0. Results Thirty studies, involving 4805 patients, were included. The two groups had similar results in GTR rate (included GTR rate of macroadenomas), hormonal remission rate, improvement in visual function, postoperative CSF leak, permanent diabetes insipidus, meningitis, and sinusitis. The binostril group had less temporary diabetes insipidus (2.9% vs. 5.3%, p = 0.022), less anterior pituitary insufficiency (2.3% vs. 6.4%, p = 0.000) and few hospitalization days (3.2 days vs. 4.4 days, p<0.05) than the mononostril group. However, the mononostril group had less rate of epistaxis (0.4% vs. 1.5%, p = 0.008) than the binostril group. For invasive macroadenomas, the binostril group seem to demonstrate a tendency towards better outcomes though there was no subgroup analysis between the two groups. Conclusion The binostril approach had less temporary diabetes insipidus, anterior pituitary insufficiency, and a shorter length of hospital stay, although they demonstrated a higher rate of epistaxis

  1. 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.

  2. 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

  3. 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.

  4. 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. PMID:27091627

  5. 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

  6. Outcome of Endoscopic Transsphenoidal Surgery in Combination with Somatostatin Analogues in Patients with Growth Hormone Producing Pituitary Adenoma

    PubMed Central

    Zhou, Tao; Wang, Fuyu; Meng, Xianghui; Ba, Jianmin; Wei, Shaobo

    2014-01-01

    Objective To determine the efficacy of endoscopic surgery in combination with long-acting somatostatin analogues (SSAs) in treating patients with growth hormone (GH)-secreting pituitary tumor. Methods We performed retrospective analysis of 133 patients with GH producing pituitary adenoma who underwent pure endoscopic transsphenoidal surgery in our center from January 2007 to July 2012. Patients were followed up for a range of 3-48 months. The radiological remission, biochemical remission and complication were evaluated. Results A total of 110 (82.7%) patients achieved radiological complete resection, 11 (8.2%) subtotal resection, and 12 (9.0%) partial resection. Eighty-eight (66.2%) patients showed nadir GH level less than 1 ng/mL after oral glucose administration. No mortality or severe disability was observed during follow up. Preoperative long-acting SSA successfully improved left ventricle ejection fraction (LVEF) and blood glucose in three patients who subsequently underwent success operation. Long-acting SSA (20 mg every 30 days) achieved biochemical remission in 19 out 23 (82.6%) patients who showed persistent high GH level after surgery. Conclusion Endoscopic transsphenoidal surgery can biochemically cure the majority of GH producing pituitary adenoma. Post-operative use of SSA can improve biochemical remission. PMID:25535518

  7. 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

  8. Proteomic and functional profiles of a follicle-stimulating hormone positive human nonfunctional pituitary adenoma.

    PubMed

    Wang, Xiaowei; Guo, Tianyao; Peng, Fang; Long, Ying; Mu, Yun; Yang, Haiyan; Ye, Ningrong; Li, Xuejun; Zhan, Xianquan

    2015-06-01

    Nonfunctional pituitary adenoma (NFPA) is highly heterogeneous with different hormone-expressed subtypes in NFPA tissues including follicle-stimulating hormone (FSH) positive, luteinizing hormone-positive, FSH/luteinizing hormone-positive, and negative types. To analyze in-depth the variations in the proteomes among different NFPA subtypes for our long-term goal to clarify molecular mechanisms of NFPA and to detect tumor biomarker for personalized medicine practice, a reference map of proteome of a human FSH-expressed NFPA tissue was described here. 2DE and PDQuest image analysis were used to array each protein. MALDI-TOF PMF and human Swiss-Prot databases with MASCOT search were used to identify each protein. A good 2DE pattern with high level of between-gel reproducibility was attained with an average positional deviation 1.98 ± 0.75 mm in the IEF direction and 1.62 ± 0.68 mm in the SDS-PAGE direction. Approximately 1200 protein spots were 2DE-detected and 192 redundant proteins that were contained in 141 protein spots were PMF-identified, representing 107 nonredundant proteins. Those proteins were located in cytoplasm, nucleus, plasma membrane, extracellular space, and so on, and those functioned in transmembrane receptor, ion channel, transcription/translation regulator, transporter, enzyme, phosphatase, kinase, and so on. Several important pathway networks were characterized from those identified proteins with DAVID and Ingenuity Pathway Analysis systems, including gluconeogenesis and glycolysis, mitochondrial dysfunction, oxidative stress, cell-cycle alteration, MAPKsignaling system, immune response, TP53-signaling, VEGF-signaling, and inflammation signaling pathways. Those resulting data contribute to a functional profile of the proteome of a human FSH-positive NFPA tissue, and will serve as a reference for the heterogeneity analysis of NFPA proteomes. PMID:25809007

  9. Fatal hemorrhage following trans--sphenoidal resection of a pituitary adenoma: a case report and review of the literature.

    PubMed

    Kepron, C; Cusimano, M; Pollanen, M S

    2010-12-01

    A 58-year-old woman with acromegaly developed massive epistaxis 7 days following trans-sphenoidal resection of a growth hormone-secreting pituitary adenoma. At autopsy, it was determined that the source of the hemorrhage was a rupture of the intracavernous segment of the internal carotid artery secondary to a bacterial arteritis. We describe the gross dissection and histologic examination undertaken in this unusual case, discuss the possible etiology of the infection and review the potential complications of this surgical approach with a view to improving forensic examination of these patients.

  10. Thyrotropin-secreting pituitary adenoma in an 11-year-old boy with type 1 autoimmune polyglandular syndrome.

    PubMed

    Mazerkina, Nadia; Trunin, Yuri; Gorelyshev, Sergey; Golanov, Andrey; Kadashev, Boris; Shishkina, Liudmila; Rotin, Daniil; Karmanov, Maxim; Orlova, Elizabet

    2016-02-01

    Thyrotropinomas (TSHomas) are rare pituitary adenomas, particularly in childhood. We present here the case of an 11-year-old boy with type 1 autoimmune polyglandular syndrome (APS1) and TSHoma which was diagnosed by elevated thyroid - stimulating hormone and thyroid hormones levels without evident clinical signs of hyperthyroidism. He was underwent partial resection of the tumor via transsphenoidal approach and subsequently radiation therapy. Consequently, 1 year after radiotherapy, the patient developed growth hormone deficiency, three and half years after radiation became euthyroid, and five and half years after treatment - hypothyroid. This is the first case of the coexistence of these two rare endocrine diseases in one patient. PMID:26244671

  11. 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

  12. Prevalence and incidence of pituitary adenomas: a population based study in Malta.

    PubMed

    Gruppetta, Mark; Mercieca, Cecilia; Vassallo, Josanne

    2013-12-01

    Epidemiological data is important to correctly quantify the extent of disease and needed health care resources. The aim of the study was to establish the prevalence and incidence of pituitary adenomas (PAs) in the same well defined population, with in-depth analysis of the various subtypes. The design involved a retrospective cross-sectional analysis of PA patients diagnosed prior to 31 July 2011 for prevalence estimates and those diagnosed between July 2000 and July 2011 for incidence estimation. A thorough search for patients with PAs was carried out in central hospital registries including outpatients departments, surgical registries, radiological department and specialty clinic databases. Prevalence rates/100,000 and Standardised incidence ratios (SIR)/100,000/year were worked out. The respective prevalence rates and SIR for PAs overall were 75.7/100,000, and 4.27/100,000/year, for Prolactinomas 35.0/100,000 and 2.05/100,000/year, for nonfunctioning PA 25.9/100,000 and 1.79/100,000/year and for GH-secreting PAs 12.5/100,000 and 0.31/100,000/year. The overall prevalence for macroadenomas was 32.8/100,000 and SIR was 1.49/100,000/year. The prevalence rate in males for PAs overall was 46.3/100,000 and SIR was 2.08/100,000/year and in females 104.8/100,000 and SIR was 6.58/100,000/year. Females had a lower proportion of macroadenomas than males (29.5 vs. 75.0%; P < 0.001) and macroadenomas tended to present at a later age compared to microadenomas (48 vs. 34.5; P < 0.001). The highest SIR was reached in the 30-39 age group at 7.42/100,000/year. Our data confirm the considerable disease burden that PAs bear on health care resources. Males and females have similar prevalence and SIR rates for macroadenomas but there is a significant increase in SIR in females of child bearing age compared to males. These observations may have important implications in terms of the economic burden and need for early intervention.

  13. 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

  14. High-mobility group A2 gene expression is frequently induced in non-functioning pituitary adenomas (NFPAs), even in the absence of chromosome 12 polysomy.

    PubMed

    Pierantoni, Giovanna Maria; Finelli, Palma; Valtorta, Emanuele; Giardino, Daniela; Rodeschini, Ornella; Esposito, Francesco; Losa, Marco; Fusco, Alfredo; Larizza, Lidia

    2005-12-01

    The high-mobility group A2 (HMGA2) gene has a critical role in benign tumors where it is frequently rearranged, and in malignant tumors, where it is overexpressed in the absence of structural modification of the HMGA2 locus. By previous fluorescence in situ hybridization (FISH) and reverse transcriptase PCR analyses on human prolactin-secreting pituitary adenomas we detected rearrangement of the HMGA2 gene and amplification of its native region associated with activated expression. These data indicated a role for the HMGA2 gene in the development of human pituitary prolactinomas, since they are consistent with the appearance of prolactin/growth hormone adenomas in transgenic mice overexpressing the HMGA2 gene. To assess a more general role for HMGA2 in pituitary oncogenesis, we investigated HMGA2 amplification and expression in a panel of non-functioning pituitary adenomas (NFPAs) which account for 25% of all pituitary adenomas. We provide evidence that out of 18 NFPA tumors tested, 12 expressed HMGA2, but, different from prolactinomas, only in two cases the upregulation of the gene could be associated with amplification and/or rearrangement of the HMGA2 locus. Increased dosage of chromosome 12 was found in the expressing and non-expressing NFPAs, confirming that this sole event is insufficient to drive up activation of the HMGA2 gene. A role for chromosome 12 polysomy to promote structural instability of HMGA2 is confirmed, but the mechanism via trisomy is less prevalent in the frequently diploid NFPAs than in the usually hyperdiploid prolactinomas. Micro-rearrangements of HMGA2 gene not detectable by FISH analysis and/or sequence alterations could contribute to upregulation of HMGA2 gene in pituitary adenomas of the NFPA subtype. However, it cannot be excluded that the HMGA2 overexpression may be due, in some NFPA patients, to the same, still mainly unknown, mechanisms responsible for HMGA2 overexpression in malignant neoplasias. PMID:16322327

  15. Systemic Sarcoidosis Unmasked by Cushing's Disease Surgical Treatment.

    PubMed

    Bongetta, Daniele; Zoia, Cesare; Lombardi, Francesco; Lovati, Elisabetta; Lucotti, Pietro; Gaetani, Paolo

    2016-01-01

    Diseases responsive to glucocorticoids, like sarcoidosis, are rarely masked by Cushing's syndrome. An ACTH secreting pituitary adenoma is a possible cause of Cushing's syndrome and its resection can make a subclinical sarcoidosis clear. Only few cases of sarcoidosis following the treatment of hypercortisolism are reported in literature. We report a case of sarcoidosis after the resection of an ACTH secreting pituitary adenoma. PMID:27525010

  16. Systemic Sarcoidosis Unmasked by Cushing's Disease Surgical Treatment

    PubMed Central

    Lombardi, Francesco; Lovati, Elisabetta; Gaetani, Paolo

    2016-01-01

    Diseases responsive to glucocorticoids, like sarcoidosis, are rarely masked by Cushing's syndrome. An ACTH secreting pituitary adenoma is a possible cause of Cushing's syndrome and its resection can make a subclinical sarcoidosis clear. Only few cases of sarcoidosis following the treatment of hypercortisolism are reported in literature. We report a case of sarcoidosis after the resection of an ACTH secreting pituitary adenoma. PMID:27525010

  17. Analysis of differential gene expression by bead-based fiber-optic array in growth-hormone-secreting pituitary adenomas.

    PubMed

    Jiang, Zhiquan; Gui, Songbo; Zhang, Yazhuo

    2010-09-01

    Growth-hormone-secreting pituitary adenomas (GHomas) account for approximately 20% of all pituitary neoplasms. However, the pathogenesis of GHomas remains to be elucidated. To explore the possible pathogenesis of GHomas, we used bead-based fiber-optic arrays to examine the gene expression in five GHomas and compared them to three healthy pituitaries. Four differentially expressed genes were chosen randomly for validation by quantitative real-time reverse transcription-polymerase chain reaction. We then performed pathway analysis on the identified differentially expressed genes using the Kyoto Encyclopedia of Genes and Genomes. Array analysis showed significant increases in the expression of 353 genes and 206 expressed sequence tags (ESTs) and decreases in 565 genes and 29 ESTs. Bioinformatic analysis showed that the genes HIGD1B, HOXB2, ANGPT2, HPGD and BTG2 may play an important role in the tumorigenesis and progression of GHomas. Pathway analysis showed that the wingless-type signaling pathway and extracellular-matrix receptor interactions may play a key role in the tumorigenesis and progression of GHomas. Our data suggested that there are numerous aberrantly expressed genes and pathways involved in the pathogenesis of GHomas. Bead-based fiber-optic arrays combined with pathway analysis of differentially expressed genes appear to be a valid method for investigating the pathogenesis of tumors. PMID:22993617

  18. MicroRNA profile indicates downregulation of the TGFβ pathway in sporadic non-functioning pituitary adenomas.

    PubMed

    Butz, Henriett; Likó, István; Czirják, Sándor; Igaz, Péter; Korbonits, Márta; Rácz, Károly; Patócs, Attila

    2011-06-01

    MicroRNAs (miRs) are small, 16-29 nucleotide long, non-coding RNA molecules which regulate the stability or translational efficiency of targeted mRNAs via RNA interference. MiRs participate in the control of cell proliferation, cell differentiation, signal transduction, cell death, and they play a role in carcinogenesis. The aims of our study were to analyse the expression profile of miRs in sporadic clinically non-functioning pituitary adenomas (NFPA) and in normal pituitary tissues, and to identify biological pathways altered in these pituitary tumors. MiR expression profiles of 12 pituitary tissue specimens (8 NFPA and 4 normal pituitary tissues) were determined using miR array based on quantitative real-time PCR with 678 different primers. Five overexpressed miRs and mRNA expression of Smads (Smad1-9), MEG and DLK1 genes were evaluated with individual Taqman assays in 10 NFPA and 10 normal pituitary tissues. Pathway analysis was performed by the DIANA-mirPath tool. Complex bioinformatical analysis by multiple algorithms and association studies between miRs, Smad3 and tumor size was performed. Of the 457 miRs expressed in both NFPA and normal tissues, 162 were significantly under- or overexpressed in NFPA compared to normal pituitary tissues Expression of Smad3, Smad6, Smad9, MEG and DLK1 was significantly lower in NFPA than in normal tissues. Pathway analysis together with in silico target prediction analysis indicated possible downregulation of the TGFβ signaling pathway in NFPA by a specific subset of miRs. Five miRs predicted to target Smad3 (miR-135a, miR-140-5p, miR-582-3p, miR-582-5p and miR-938) were overexpressed. Correlation was observed between the expression of seven overexpressed miRs and tumor size. Downregulation of the TGFβ signaling through Smad3 via miRs may have a possible role in the complex regulation of signaling pathways involved in the tumorigenesis process of NFPA. PMID:21063788

  19. A comparative study by age and gender of the pituitary adenoma and ACTH and alpha-MSH secretion in dogs with pituitary-dependent hyperadrenocorticism.

    PubMed

    Gallelli, M F; Cabrera Blatter, M F; Castillo, V

    2010-02-01

    Pituitary-dependent hyperadrenocorticism (PDH) is frequent in dogs. Little is known about its presentation in different age groups and its characteristics. Dividing the population under study (n=107) into three age groups we observed that 11.2% were young, 51.4% adults and 37.4% aged. Using magnetic resonance, pituitary tumours were intra-sellar (IS) in 30.8% and extra-sellar (ES) in 62.6% and the pars intermedia (PI) was affected in 6.5%. ES are predominant in females and IS in males (p<0.0001). In the adult-aged population, the ES and PI are predominant, while in the young, the IS predominate (p<0.0001). ACTH concentration was greater in the ES vs. IS (p<0.05). alpha-MSH did not present significant differences according to tumour size, showing a negative correlation (r=-0.47; p<0.01) vs. ACTH. Differences in adenoma size according to gender and their age-related frequency of apparition could be because of different origins of the corticotrophinoma.

  20. 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.

  1. 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.

  2. 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

  3. Effects of bromocriptine on CSF proteins and amines in patients with empty sella syndrome, acromegaly and prolactin producing pituitary adenomas.

    PubMed

    Brismar, K; Sidén, A; Werner, S

    1981-01-01

    The effect of the dopamine agonist bromocriptine (5-40 mg/day) on cerebrospinal fluid proteins and amines was studied in 7 hyperprolactinemic patients, 4 with empty sella syndrome and 3 patients with pituitary adenoma. Small as well as high doses of bromocriptine depressed the endogenously formed dopamine, noradrenalin and adrenalin. Five patients initially exhibited changes consistent with slight to marked blood-cerebrospinal-fluid (CSF) barrier disturbances and 5 abnormal CSF-protein fractions. One CSF-protein fraction (isolelectric points (pI) approximately 5.3 pH-units) became more prominent during bromocriptine treatment. Analyses of his fraction indicated that it represented a transferrin component. It is stated that bromocriptine treatment besides affecting amine and trace metal metabolism also affects protein metabolism.

  4. [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.

  5. Hyperprolactinemia in a patient with a pituitary adenoma receiving antipsychotic drug therapy.

    PubMed

    Carroll, Richard W; Christodoulou, Polyxeni; Baynes, Kevin C R; Kahn, David A

    2012-03-01

    Hyperprolactinemia is a common consequence of treatment with an antipsychotic medication. It can result in hypogonadism due to the inhibitory effect of elevated prolactin levels on the hypothalamic-pituitary-gonadal hormonal axis. We present a case of hypogonadism secondary to hyperprolactinemia in a patient taking antipsychotic medication, with radiological evidence of a pituitary microadenoma. The relevance and investigation of hyperprolactinemia in patients being treated with antipsychotic medications are discussed.

  6. [Familial pituitary tumors].

    PubMed

    Yoshimoto, K; Saito, S

    1995-11-01

    Familial pituitary tumors are relatively rare. Most commonly, they occur as a part of multiple endocrine neoplasia type 1 (MEN 1). However, familial pituitary adenomas unrelated MEN 1 (familial pituitary adenomas) are extremely rare. In review of MEN 1 in Japan, 60% of the patients with MEN 1 had pituitary tumors. Only 45 cases of familial pituitary adenomas have been reported from 20 families. In our review of familial pituitary adenomas, 30 (67%) of 45 reported cases are acromegaly or gigantism. This incidence is much higher than 28% in MEN 1 patients with pituitary tumors. Allelic deletions at 11q13 were identified in MEN 1 associated pituitary adenomas and familial pituitary adenomas in two gigantism brothers. PMID:8538028

  7. Short-term treatment with cabergoline can lead to tumor shrinkage in patients with nonfunctioning pituitary adenomas.

    PubMed

    Garcia, Erica C; Naves, Luciana A; Silva, Arthur O; de Castro, Lucas F; Casulari, Luiz A; Azevedo, Monalisa F

    2013-06-01

    This study was carried out to evaluate the effectiveness of cabergoline in the treatment of nonfunctioning pituitary adenomas (NFPA), in a short-term follow-up period. Nineteen patients (10 men and 9 women) followed at the University Hospital of Brasilia and harboring nonfunctioning pituitary macroadenomas were enrolled in the study. Eleven patients were previously submitted to transsphenoidal surgery, and in 8 patients no previous treatment had been instituted. Their response to the use of cabergoline (2 mg/week) by 6 months was evaluated. Significant tumor shrinkage (above 25 % from baseline tumor volume) was observed in 6 (31.6 %) of the 19 patients, and no adverse effects were observed during treatment. In 9 patients (47.4 %), a reduction in tumor volume of at least 10 % was noted, whereas tumor growth was observed in four patients (increase above 25 % was only observed in one patient). Cabergoline (2 mg/week) can lead to significant tumor shrinkage in NFPA in a considerable number of patients, and this effect can be observed early (6 months after starting medication). Thus, this therapeutic strategy may be a low cost and safe alternative for treatment of NFPA in patients with remnant or recurrent tumor after transsphenoidal surgery or in those not operated by contraindications or refusal to surgical procedure. PMID:22740242

  8. Matrix metalloproteinase-9 and -2 and tissue inhibitor of matrix metalloproteinase-2 in invasive pituitary adenomas: A systematic review and meta-analysis of case-control trials.

    PubMed

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

    2016-06-01

    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

  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. 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.

  12. High-resolution 18F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging for pituitary adenoma detection in Cushing disease

    PubMed Central

    Chittiboina, Prashant; Montgomery, Blake K.; Millo, Corina; Herscovitch, Peter; Lonser, Russell R.

    2016-01-01

    OBJECT High-resolution PET (hrPET) performed using a high-resolution research tomograph is reported as having a resolution of 2 mm and could be used to detect corticotroph adenomas through uptake of 18F-fluorodeoxyglucose (18F-FDG). To determine the sensitivity of this imaging modality, the authors compared 18F-FDG hrPET and MRI detection of pituitary adenomas in Cushing disease (CD). METHODS Consecutive patients with CD who underwent preoperative 18F-FDG hrPET and MRI (spin echo [SE] and spoiled gradient recalled [SPGR] sequences) were prospectively analyzed. Standardized uptake values (SUVs) were calculated from hrPET and were compared with MRI findings. Imaging findings were correlated to operative and histological findings. RESULTS Ten patients (7 females and 3 males) were included (mean age 30.8 ± 19.3 years; range 11–59 years). MRI revealed a pituitary adenoma in 4 patients (40% of patients) on SE and 7 patients (70%) on SPGR sequences. 18F-FDG hrPET demonstrated increased 18F-FDG uptake consistent with an adenoma in 4 patients (40%; adenoma size range 3–14 mm). Maximum SUV was significantly higher for 18F-FDG hrPET–positive tumors (difference = 5.1, 95% CI 2.1–8.1; p = 0.004) than for 18F-FDG hrPET–negative tumors. 18F-FDG hrPET positivity was not associated with tumor volume (p = 0.2) or dural invasion (p = 0.5). Midnight and morning ACTH levels were associated with 18F-FDG hrPET positivity (p = 0.01 and 0.04, respectively) and correlated with the maximum SUV (R = 0.9; p = 0.001) and average SUV (R = 0.8; p = 0.01). All 18F-FDG hrPET–positive adenomas had a less than a 180% ACTH increase and 18F-FDG hrPET–negative adenomas had a greater than 180% ACTH increase after CRH stimulation (p = 0.03). Three adenomas were detected on SPGR MRI sequences that were not detected by 18F-FDG hrPET imaging. Two adenomas not detected on SE (but no adenomas not detected on SPGR) were detected on 18F-FDG hrPET. CONCLUSIONS While 18F-FDG hrPET imaging can detect

  13. Intracranial hemorrhage from undetected aneurysmal rupture complicating transphenoidal pituitary adenoma resection.

    PubMed

    Rustagi, Tarun; Uy, Edilfavia Mae; Rai, Mridula; Kannan, Subramanian; Senatus, Patrick

    2011-08-01

    We report a case of a 39-year-old man who presented with a nonfunctioning pituitary macroadenoma which extended into the suprasellar region. He underwent a transcranial resection of the tumor followed eight months later by transsphenoidal surgery for the residual tumor. Postoperatively he developed massive subarachnoid and intraventricular hemorrhage. A cerebral angiogram revealed a leaking anterior communicating artery aneurysm which was not seen on the computed tomography angiography and magnetic resonance angiography before the surgery. Complications of transsphenoidal surgery, particularly vascular hemorrhagic complications, and risk of rupture of undetected aneurysms are discussed.

  14. A review on the diagnosis and treatment of patients with clinically nonfunctioning pituitary adenoma by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism.

    PubMed

    Vieira, Leonardo; Boguszewski, Cesar L; Araújo, Luiz Antônio de; Bronstein, Marcello D; Miranda, Paulo Augusto C; Musolino, Nina R de C; Naves, Luciana A; Vilar, Lucio; Ribeiro-Oliveira, Antônio; Gadelha, Mônica R

    2016-08-01

    Clinically nonfunctioning pituitary adenomas (NFPA) are the most common pituitary tumors after prolactinomas. The absence of clinical symptoms of hormonal hypersecretion can contribute to the late diagnosis of the disease. Thus, the majority of patients seek medical attention for signs and symptoms resulting from mass effect, such as neuro-ophthalmologic symptoms and hypopituitarism. Other presentations include pituitary apoplexy or an incidental finding on imaging studies. Mass effect and hypopituitarism impose high morbidity and mortality. However, early diagnosis and effective treatment minimizes morbidity and mortality. In this publication, the goal of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism is to provide a review of the diagnosis and treatment of patients with NFPA, emphasizing that the treatment should be performed in reference centers. This review is based on data published in the literature and the authors' experience. Arch Endocrinol Metab. 2016;60(4):374-90. PMID:27533614

  15. Antiproliferative, antiinvasive, and proapoptotic activity of folate receptor α-targeted liposomal doxorubicin in nonfunctional pituitary adenoma cells.

    PubMed

    Liu, Xiaohai; Ma, Sihai; Dai, Congxin; Cai, Feng; Yao, Yong; Yang, Yakun; Feng, Ming; Deng, Kan; Li, Guiling; Ma, Wenbing; Xin, Bing; Lian, Wei; Xiang, Guangya; Zhang, Bo; Wang, Renzhi

    2013-04-01

    There is an urgent need for novel therapeutic strategies for the treatment of nonfunctional pituitary adenomas (NFPAs), especially those that are invasive. The folate receptor (FR)α is overexpressed in several cancers, including NFPA. The aim of this study was to determine the efficacy of FRα-targeted liposomes loaded with doxorubicin (F-L-DOX) in the treatment of NFPA. We evaluated targeting, cytotoxicity, antiinvasive, and proapoptotic activity of F-L-DOX in 25 primary cell lines derived from patients with NFPAs. We found that these liposomes effectively targeted NFPA cells through FRα and that endocytosis of the liposomes was blocked by 1mM free folic acid. F-L-DOX inhibited proliferation of NFPA cells and promoted apoptosis through activation of caspase-8, caspase-9, and caspase-3/7 more effectively than L-DOX. Furthermore, F-L-DOX also exerted greater antiinvasive ability in NFPA cells than L-DOX through suppression of the secretion of matrix metalloproteinase-2 and matrix metalloproteinase-9. Addition of 1mM free folic acid significantly reduced the pleotropic effects of F-L-DOX in NFPA cells, suggesting that FRα plays a critical role in mediating the antitumor effect of F-L-DOX. Our findings warrant further investigation of F-L-DOX as an alternative therapeutic strategy for the treatment of NFPAs that express FRα. PMID:23462961

  16. Activation of RAF/MEK/ERK and PI3K/AKT/mTOR pathways in pituitary adenomas and their effects on downstream effectors.

    PubMed

    Dworakowska, D; Wlodek, E; Leontiou, C A; Igreja, S; Cakir, M; Teng, M; Prodromou, N; Góth, M I; Grozinsky-Glasberg, S; Gueorguiev, M; Kola, B; Korbonits, M; Grossman, A B

    2009-12-01

    Raf/MEK/ERK and phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) cascades are key signalling pathways interacting with each other to regulate cell growth and tumourigenesis. We have previously shown B-Raf and Akt overexpression and/or overactivation in pituitary adenomas. The aim of this study is to assess the expression of their downstream components (MEK1/2, ERK1/2, mTOR, TSC2, p70S6K) and effectors (c-MYC and CYCLIN D1). We studied tissue from 16 non-functioning pituitary adenomas (NFPAs), six GH-omas, six prolactinomas and six ACTH-omas, all collected at transsphenoidal surgery; 16 normal autopsy pituitaries were used as controls. The expression of phospho and total protein was assessed with western immunoblotting, and the mRNA expression with quantitative RT-PCR. The expression of pSer217/221 MEK1/2 and pThr183 ERK1/2 (but not total MEK1/2 or ERK1/2) was significantly higher in all tumour subtypes in comparison to normal pituitaries. There was no difference in the expression of phosphorylated/total mTOR, TSC2 or p70S6K between pituitary adenomas and controls. Neither c-MYC phosphorylation at Ser 62 nor total c-MYC was changed in the tumours. However, c-MYC phosphorylation at Thr58/Ser62 (a response target for Akt) was decreased in all tumour types. CYCLIN D1 expression was higher only in NFPAs. The mRNA expression of MEK1, MEK2, ERK1, ERK2, c-MYC and CCND1 was similar in all groups. Our data indicate that in pituitary adenomas both the Raf/MEK/ERK and PI3K/Akt/mTOR pathways are upregulated in their initial cascade, implicating a pro-proliferative signal derangement upstream to their point of convergence. However, we speculate that other processes, such as senescence, attenuate the changes downstream in these benign tumours. PMID:19620247

  17. 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. PMID:23522762

  18. Impulse control disorders in patients with dopamine agonist-treated prolactinomas and non-functioning pituitary adenomas: a case-control study

    PubMed Central

    Bancos, Irina; Nannenga, Michael R.; Bostwick, J. Michael; Silber, Michael H.; Erickson, Dana; Nippoldt, Todd B.

    2014-01-01

    Objective We aimed to assess the prevalence of impulse control disorders (ICDs) in patients with prolactin-secreting adenomas treated with dopamine agonists (DAs), to identify associated factors, and compare it with a group of patients with non-functioning pituitary adenoma. Subjects, Design and Measurement In a postal survey, 77 patients from Group A (patients with prolactinomas and present or past use of DAs) and 70 patients from Group B (patients with non-functioning pituitary adenoma and no history of DA therapy) responded to a questionnaire on compulsive shopping, pathologic gambling, hypersexuality and punding. Associated clinical information was obtained through the survey and review of medical electronic records. Results The total ICD prevalence was 24.68% in Group A and 17.1% in Group B (p=0.31). Group A had an increased rate of hypersexuality (p=0.03). Subgroup analysis revealed that men in Group A had a significantly increased frequency of total ICDs when compared to men in Group B (27.7% versus 3.7%, p=0.01). No differences in rates of total ICDs were found between women of Groups A and B (20% versus 25.6%, p=0.78). No association with type, dose, or duration of treatment with DA was noted. Conclusions Males with prolactinomas treated with DAs were 9.9 times more likely to develop an ICD than their counterparts with non-functioning pituitary adenomas. Until prospective studies on the relationship of DA use in prolactinoma patients and ICDs are available, the authors propose that prolactinoma patients be forewarned of possible ICD development with DA therapy. PMID:24274365

  19. 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 ...

  20. [Anterior pituitary hypersecretion syndromes].

    PubMed

    Gómez, F; Steinhäuslin, F; Crottaz, B; Temler, E

    1987-01-17

    Anterior pituitary hypersecretion can be due to abnormal hypothalamic regulation, decreased peripheral hormone feedback or pituitary tumor. In some cases hypersecretion gives rise to a typical clinical syndrome involving acromegaly, hyperprolactinemia, and excess corticotropin (ACTH). The etiology of acromegaly is a growth hormone (GH)-secreting pituitary tumor in the vast majority of cases. Hyperprolactinemia and excess cortisol, however, may be due to many causes among which prolactin (PRL)- and ACTH-secreting pituitary tumors are not frequent. Glycoprotein-secreting pituitary tumors, especially gonadotropin (LH and FSH) and free subunits usually do not cause a typical excess hormone syndrome. Perhaps for this reason they are seldom recognized clinically, although histopathological studies are increasingly disclosing the gonadotrope nature of many pituitary tumors. Mixed hormonal secretions are common. When pituitary hormone secretion can be selectively suppressed by medical therapy, a significant reduction of tumor size is by no means rare. In other cases, pituitary irradiation or surgery, or even treatment aimed at a peripheral target gland, may be necessary. PMID:3029861

  1. Hypothalamic-pituitary function in myotonic dystrophy.

    PubMed

    Mahler, C; Parizel, G

    1982-01-01

    Function of the hypothalamic-pituitary axis was investigated in seven patients with myotonic dystrophy (MD). HGH and ACTH secretion were normal. TSH response to TRH was impaired in about half the cases, without concomitant thyroid dysfunction. LH and FSH levels were often elevated, with inconsistent response to LH-RH stimulation, Gonadotrophin disturbances in MD have previously been attributed to a primary gonadal lesion, characteristically seen in this disease. High prolactin levels in six of our seven patients however suggest that gonadal failure may be also be due to hyperprolactinemia through the direct anti-gonadal effect of prolactin and its interference with hypothalamic-pituitary regulation of gonadotrophin secretion.

  2. The role of FSCN1 in migration and invasion of pituitary adenomas.

    PubMed

    Liu, Chunhui; Gao, Hua; Cao, Lei; Gui, Songbai; Liu, Qian; Li, Chuzhong; Li, Dan; Gong, Lei; Zhang, Yazhuo

    2016-01-01

    The prediction of invasion or malignant behavior in PAs remains challenging. FSCN1, an actin-bundling protein, is associated with increased risk of mortality and metastasis in various cancer types. The objective of the study was to evaluate the expression of FSCN1 in 312 PAs cases, and to analyze its association with clinicopathologic features and invasion of PAs, thus serving as a promoter of cancer invasion. In non-function PAs (NFPA), FSCN1 nuclear-positive cases were 53/97 in the invasive group (IPA), and 21/115 in the noninvasive group (nIPA) (ⅹ(2) = 30.65, p = 0.004). FSCN1 cytoplasm-positive cases were 36/97 in IPA, and 8/107 in nIPA (ⅹ(2) = 29.09, p = 0.000). In growth hormone adenomas (GHomas), FSCN1 nuclear-positive were 10/13 in IPA, and 3/37 in nIPA (ⅹ(2) = 23.67, p = 0.000). FSCN1 cytoplasm-positive were 8/13 in IPA, and 2/37 in nIPA (Table 3 ⅹ(2) = 18.94, p = 0.000). Overall, a significant difference was found between FSCN1 expression and tumor size (ⅹ(2) = 46.21, p = 0.000), not age (ⅹ(2) = 2.09, p = 0.148). In the high FSCN1 expression group, 27/137 cases (19.7%) had tumor recurrence, and 10/175 cases (5.7%) in low FSCN1 level (ⅹ(2) = 14.40 p = 0.000). Reduction of FSCN1 suppressed the invasion level of GH3 cells through transwells test. In addition, reduction of FSCN1 can obviously down-regulate the level of Notch1 and DLL3. Our data may help in deciding whether FSCN1 can be a predictor for invasion and recurrence of PAs. PMID:26522130

  3. 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

  4. The marine metabolite SZ-685C induces apoptosis in primary human nonfunctioning pituitary adenoma cells by inhibition of the Akt pathway in vitro.

    PubMed

    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

    2015-03-01

    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

  5. 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

  6. The marine metabolite SZ-685C induces apoptosis in primary human nonfunctioning pituitary adenoma cells by inhibition of the Akt pathway in vitro.

    PubMed

    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

    2015-03-01

    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.

  7. Feline pituitary-dependent hyperadrenocorticism and insulin resistance due to a plurihormonal adenoma.

    PubMed

    Cross, Emily; Moreland, Richard; Wallack, Seth

    2012-02-01

    A 12-year-old female spayed domestic short-haired cat presented for lethargy, poor hair coat, alopecia, difficulty walking, and mild polyuria/polydipsia. The cat's skin tore easily in the neck area during routine restraint for blood draw. Physical examination, blood analysis, and ultrasound imaging were all consistent with pituitary-dependent hyperadrenocorticism (PDH) with secondary insulin-resistant diabetes mellitus, which was nonketotic. Insulin therapy, fluids, and diet change were initiated for the diabetes mellitus and the owner reported improvement in clinical signs although the blood glucose measurements remained elevated. Surgical repair of the torn skin was successful. Although a guarded prognosis was given to the owner because of an advanced stage of hyperadrenocorticism, and the limited treatment options currently available for feline PDH, trilostane was agreed on as an initial therapeutic option. The day trilostane was to be initiated, the cat presented with dyspnea and the owner chose to euthanize. Because of the rarity of hyperadrenocorticism disease in the cat, permission was obtained by the owner for a necropsy to confirm suspected PDH as the underlying cause for insulin resistance and skin fragility syndrome.

  8. 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.

  9. 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.

  10. Identification of the proteomic variations of invasive relative to non-invasive non-functional pituitary adenomas.

    PubMed

    Zhan, Xianquan; Desiderio, Dominic M; Wang, Xiaowei; Zhan, Xiaohan; Guo, Tianyao; Li, Maoyu; Peng, Fang; Chen, Xiaoyu; Yang, Haiyan; Zhang, Pengfei; Li, Xuejun; Chen, Zhuchu

    2014-08-01

    The incomplete surgery section of invasive non-functional pituitary adenomas (NFPAs) carries the increased risks of complications and requires adjuvant radiotherapy and medications. It is necessary to clarify the molecular mechanisms and markers of invasiveness to guide the management of NFPA patients. The study aimed to proteomic variations of invasive and non-invasive NFPAs and sought the protein markers for invasive NFPAs. Invasive (n = 4) and non-invasive (n = 4) NFPA tissues were analyzed (n = 3-5/each tissue) with 2DE and PDQuest software. Twenty-four high-resolution 2DE gels were quantitatively compared to determine differentially expressed proteins (DEPs) between invasive and non-invasive NFPAs. Approximately 1200 protein spots were detected in each 2DE map, and 103 differential spots (64 upregulated and 39 downregulated) were identified. Among those 103 differential spots, 57 DEPs (30 upregulated and 27 downregulated) were characterized with peptide mass fingerprint and MS/MS. Gene-ontology (GO) and ingenuity pathway analyses of those DEPs revealed pathway networks including mitochondrial dysfunction, oxidative stress, mitogen-activated protein kinase signaling abnormality, TR/RXR activation, proteolysis abnormality, ketogenesis and ketolysis, cyclin-dependent kinase C signaling abnormality, and amyloid processing that were significantly associated with invasive characteristics of invasive NFPA. Those data demonstrate that proteomic variations exist between invasive and non-invasive NFPAs. 2DE-based comparative proteomics is an effective approach to identify proteomic variations and pathway network variations. Those findings will serve as a basis to understand the molecular mechanisms of invasive NFPAs and to discover protein markers to effectively manage patients with invasive NFPAs. PMID:24729304

  11. Over-expression of vascular endothelial growth factor in pituitary adenomas is associated with extrasellar growth and recurrence.

    PubMed

    Sánchez-Ortiga, Ruth; Sánchez-Tejada, Laura; Moreno-Perez, Oscar; Riesgo, Pedro; Niveiro, Maria; Picó Alfonso, Antonio M

    2013-09-01

    Some pituitary adenomas (PA) demonstrate aggressive behavior with local invasion and recurrences. Angiogenesis is regarded as an essential step in the formation of solid tumors. The aim of this study is to find out whether angiogenic factors may have information about the aggressiveness of PA that could be useful in determining the frequency of follow-up and whether adjuvant therapy is necessary. In this retrospective descriptive study, we evaluated vascular endothelial growth factors (VEGF) and VEGF receptor (KDR) mRNA expression by RT-PCR analysis on 46 human PA samples. Clinical data, histological subtype and radiologic characteristics were studied to determine the associations between the variables and the pre-operative behavior of the tumor. In addition, we monitored 12 patients without adjuvant post-operative therapies over 46 months after surgery, determining progression of tumor remnants and its association with these markers. VEGF expression correlates with KDR expression (r = 0.40, p = 0.006). VEGF demonstrates different expression between histological subtypes (p = 0.036). The extension at magnetic resonance imaging showed that VEGF expression was related to suprasellar extension (p = 0.007), being expressed more on tumors with extrasellar growth than intrasellar ones (p = 0.008). Our results demonstrate a 27.5 times increased risk of extrasellar growth when VEGF expression exceeds 0.222 normalized copy number (NCN) (p = 0.002). Likewise, tumors with KDR greater than 0.750 NCN had less recurrence-free survival time (p = 0.032). Our results suggest that the expression of VEGF and its receptor could be a marker for poor outcome after partial tumor resection. These data should be considered in future studies evaluating angiogenic factors as therapeutic targets in patients with PA.

  12. 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.

  13. Use of radioguided surgery with [111In]-pentetreotide in the management of an ACTH-secreting bronchial carcinoid causing ectopic Cushing's syndrome.

    PubMed

    Grossrubatscher, E; Vignati, F; Dalino, P; Possa, M; Belloni, P A; Vanzulli, A; Bramerio, M; Marocchi, A; Rossetti, O; Zurleni, F; Loli, P

    2005-01-01

    Intraoperative [111In]-pentetreotide scintigraphy with a hand-held gamma detector probe has recently been proposed to increase the intraoperative detection rate of small neuroendocrine tumors and their metastases. We report a case of a 28-yr-old woman with ectopic Cushing's syndrome due to an ACTH-secreting bronchial carcinoid, in whom the use of radioguided surgery improved disease management. At presentation, radiolabeled pentetreotide scintigraphy was the only procedure able to detect the ectopic source of ACTH. After radiologic confirmation, the patient underwent removal of a bronchial carcinoid, with disease persistence. After surgery, pentetreotide scintigraphy showed pathologic uptake in the mediastinum not previously detected at surgery and only subsequently confirmed by radiologic studies. Despite a second thoracic exploration, hormonal, scintigraphic, and radiological evidence of residual disease persisted. Radioguided surgery was then performed using a hand-held gamma probe 48 h after iv administration of a tracer dose of radiolabeled [111In-DTPA-D-Phe1]-pentetreotide, which permitted detection and removal of multiple residual mediastinal lymph node metastases. Clinical and radiologic cure, with no evidence of tracer uptake at pentetreotide scintigraphy, was subsequently observed. The use of an intraoperative gamma counter appears a promising procedure in the management of metastatic ACTH-secreting bronchial carcinoids. PMID:15816375

  14. Use of radioguided surgery with [111In]-pentetreotide in the management of an ACTH-secreting bronchial carcinoid causing ectopic Cushing's syndrome.

    PubMed

    Grossrubatscher, E; Vignati, F; Dalino, P; Possa, M; Belloni, P A; Vanzulli, A; Bramerio, M; Marocchi, A; Rossetti, O; Zurleni, F; Loli, P

    2005-01-01

    Intraoperative [111In]-pentetreotide scintigraphy with a hand-held gamma detector probe has recently been proposed to increase the intraoperative detection rate of small neuroendocrine tumors and their metastases. We report a case of a 28-yr-old woman with ectopic Cushing's syndrome due to an ACTH-secreting bronchial carcinoid, in whom the use of radioguided surgery improved disease management. At presentation, radiolabeled pentetreotide scintigraphy was the only procedure able to detect the ectopic source of ACTH. After radiologic confirmation, the patient underwent removal of a bronchial carcinoid, with disease persistence. After surgery, pentetreotide scintigraphy showed pathologic uptake in the mediastinum not previously detected at surgery and only subsequently confirmed by radiologic studies. Despite a second thoracic exploration, hormonal, scintigraphic, and radiological evidence of residual disease persisted. Radioguided surgery was then performed using a hand-held gamma probe 48 h after iv administration of a tracer dose of radiolabeled [111In-DTPA-D-Phe1]-pentetreotide, which permitted detection and removal of multiple residual mediastinal lymph node metastases. Clinical and radiologic cure, with no evidence of tracer uptake at pentetreotide scintigraphy, was subsequently observed. The use of an intraoperative gamma counter appears a promising procedure in the management of metastatic ACTH-secreting bronchial carcinoids.

  15. 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.

  16. Combined high-field intraoperative magnetic resonance imaging and endoscopy increase extent of resection and progression-free survival for pituitary adenomas

    PubMed Central

    Sylvester, Peter T.; Evans, John A.; Zipfel, Gregory J.; Chole, Richard A.; Uppaluri, Ravindra; Haughey, Bruce H.; Getz, Anne E.; Silverstein, Julie; Rich, Keith M.; Kim, Albert H.; Dacey, Ralph G.

    2014-01-01

    Purpose The clinical benefit of combined intraoperative magnetic resonance imaging (iMRI) and endoscopy for transsphenoidal pituitary adenoma resection has not been completely characterized. This study assessed the impact of microscopy, endoscopy, and/or iMRI on progression-free survival, extent of resection status (gross-, near-, and subtotal resection), and operative complications. Methods Retrospective analyses were performed on 446 transsphenoidal pituitary adenoma surgeries at a single institution between 1998 and 2012. Multivariate analyses were used to control for baseline characteristics, differences during extent of resection status, and progression-free survival analysis. Results Additional surgery was performed after iMRI in 56/156 cases (35.9 %), which led to increased extent of resection status in 15/156 cases (9.6 %). Multivariate ordinal logistic regression revealed no increase in extent of resection status following iMRI or endoscopy alone; however, combining these modalities increased extent of resection status (odds ratio 2.05, 95 % CI 1.21–3.46) compared to conventional transsphenoidal microsurgery. Multivariate Cox regression revealed that reduced extent of resection status shortened progression-free survival for near- versus gross-total resection [hazard ratio (HR) 2.87, 95 % CI 1.24–6.65] and sub- versus near-total resection (HR 2.10; 95 % CI 1.00–4.40). Complication comparisons between microscopy, endoscopy, and iMRI revealed increased perioperative deaths for endoscopy versus microscopy (4/209 and 0/237, respectively), but this difference was non-significant considering multiple post hoc comparisons (Fisher exact, p = 0.24). Conclusions Combined use of endoscopy and iMRI increased pituitary adenoma extent of resection status compared to conventional transsphenoidal microsurgery, and increased extent of resection status was associated with longer progression-free survival. Treatment modality combination did not significantly impact

  17. Candida albicans endophthalmitis in a patient with a non-functioning pituitary adenoma evolving into Cushing׳s disease: A case report.

    PubMed

    Lee, Eun Kyoung; Kim, Jung Hee; Yu, Hyeong Gon

    2014-10-01

    A 53-year-old woman presented with complaints of blurred vision in the left eye. She had been treated for recurrent non-functioning pituitary adenoma (NFPA). A vitreous biopsy followed by histopathologic examination showed the presence of Candida albicans. Meanwhile, Cushing׳s disease was diagnosed and gamma knife surgery was performed. Vitrectomy and antifungal treatment improved ocular infection and inflammation. Herein, we describe the first case of C. albicans endophthalmitis in a patient with NFPA evolving into Cushing׳s disease. PMID:25379398

  18. Candida albicans endophthalmitis in a patient with a non-functioning pituitary adenoma evolving into Cushing׳s disease: A case report

    PubMed Central

    Lee, Eun Kyoung; Kim, Jung Hee; Yu, Hyeong Gon

    2014-01-01

    A 53-year-old woman presented with complaints of blurred vision in the left eye. She had been treated for recurrent non-functioning pituitary adenoma (NFPA). A vitreous biopsy followed by histopathologic examination showed the presence of Candida albicans. Meanwhile, Cushing׳s disease was diagnosed and gamma knife surgery was performed. Vitrectomy and antifungal treatment improved ocular infection and inflammation. Herein, we describe the first case of C. albicans endophthalmitis in a patient with NFPA evolving into Cushing׳s disease. PMID:25379398

  19. Bilateral and simultaneous venous sampling of inferior petrosal sinuses for ACTH and PRL determination: preoperative localization of ACTH-secreting microadenomas.

    PubMed

    Vignati, F; Berselli, M E; Scialfa, G; Boccardi, E; Loli, P

    1989-04-01

    We report our experience on venous sampling of the inferior petrosal sinuses for basal and CRH-stimulated ACTH and PRL gradients in 8 patients with surgically proven Cushing's disease who had normal preoperative neuroradiological studies. In 7 patients basal plasma ACTH concentrations in the inferior petrosal sinus ipsilateral to the tumor were higher than in the contralateral sinus; the gradients were enhanced by oCRH administration. In one out of two patients who had previously undergone unsuccessful pituitary microsurgery, neither basal nor oCRH-induced ACTH increases led to correct localization of the microadenoma within the pituitary. In 4 out of 7 patients basal serum PRL concentrations in the inferior petrosal sinus ipsilateral to the tumor were higher than in the contralateral; only two out of 4 showed an increase in PRL levels after oCRH injection. Our study confirms that simultaneous and bilateral venous sampling of inferior petrosal sinuses is a valuable means to identify the site of microadenomas in patients with Cushing's disease without neuroradiological evidence of the tumor. This procedure may give misleading results in patients previously operated on. Unilateral or predominant increases of PRL concentration during catheterization of the inferior petrosal sinuses, when present, always lateralize to the side of the corticotroph adenoma, providing a possible additional signal of the presence of the tumor.

  20. NC-16PREDICTORS OF POST-SURGICAL QUALITY OF LIFE IN PATIENTS WITH NON-FUNCTIONAL PITUITARY ADENOMA: THE INFLUENCE OF NEUROBEHAVIORAL FUNCTIONS

    PubMed Central

    Yang, Chih-Yu; Yang, Shih-Hung; Yang, Chi-Cheng

    2014-01-01

    INTRODUCTION: Non-functional pituitary adenoma (NFPA) is one of the commonest subtypes of the pituitary adenomas. Although NFPA was benign, the mass effect of the adenoma would cause hypopituitarism or other complications which may affect the cognitive functions, emotional status or quality of life (QoL). Unfortunately, most of the previous studies were cross-sectional and could not reveal the changes of cognitive functions after surgery. This study thus aims to prospectively evaluate the neurobehavioral functions and related factors in patients with NFPA. METHOD: In this prospective study, 36 subjects with NFPA were recruited. Neurobehavioral functions, which included memory, executive function and speed of information processing, were evaluated. Depression, anxiety and QoL, were also examined by self-reported questionnaires. All participants were evaluated at the time of pre-operation, three and six months after surgery. RESULT: The substantial improvements in the memory, executive function and information processing were found. In respect to the emotional status and the QoL, depression and anxiety decreased significantly, while the physical QoL has a significant improvement. Importantly, the results showed that the pre-surgical psychological QoL was significantly associated with the post-surgical physical and global QoLs. In addition, the post-surgical social QoL was significantly negatively associated with the post-surgical disinhibited symptoms. CONCLUSION: This study not only revealed the post-surgical progression of neurobehavioral functions in patients with NFPA, but showed the principal predictors of post-surgical outcomes in those patients. It thus merits a comprehensive evaluation of neurobehavioral functions when patients with NFPA ready for the surgical treatments.

  1. 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

  2. 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

  3. Do the Aryl Hydrocarbon Receptor Interacting Protein Variants (Q228K and Q307R) Play a Role in Patients with Familial and Sporadic Hormone-Secreting Pituitary Adenomas?

    PubMed Central

    Ogret, Yeliz Duvarci; Oguz, Fatma Savran

    2015-01-01

    Aim: The aim of this study was to examine mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene by sequence analysis of exons 1–6 using leukocyte genomic DNA obtained from a cohort of familial isolated pituitary adenoma (FIPA) and apparent sporadic functional pituitary adenoma Turkish patients. Methods: Fourteen FIPA and 90 sporadic pituitary adenoma (somatotrophinoma, prolactinoma, and corticotrophinoma) patients, 1 sporadic gigantism case, and 70 healthy controls were included in the study. Results: We did not detect AIP mutations in patients with FIPAs or sporadic pituitary adenomas, including the gigantism case. Only two exonic homozygous missense single-nucleotide polymorphisms (rs641081 [Q228K] and rs4930195 [Q307R]) were identified in the AIP locus. Minor allele frequencies of the Q307R and Q228K variants were significantly higher in FIPA patients compared to controls. In addition, the minor allele frequency of the Q228K variant was significantly increased in patients with sporadic somatotrophinomas compared to controls, whereas the minor allele frequency of the Q307R variant was significantly increased in corticotrophinoma patients compared to controls. Conversely, the minor allele frequencies of Q228R and Q307R variants were similar between patients with prolactinomas and controls. No AIP gene mutation or variant was observed in the sporadic gigantism patient. These results suggest that Q228K and Q307R variants in the AIP gene might be involved in the genetic susceptibility to familial and sporadic pituitary adenomas (somatotrophinoma and corticotrophinoma) in the Turkish population. PMID:25938168

  4. The expression of TGF-β1, Smad3, phospho-Smad3 and Smad7 is correlated with the development and invasion of nonfunctioning pituitary adenomas

    PubMed Central

    2014-01-01

    Background Transforming growth factor β (TGF-β) signaling functions as a suppressor or a promoter in tumor development, depending on the tumor stage and type. However, the role of TGF-β signaling in nonfunctioning pituitary adenomas (NFPAs) has not been explored. Methods TGF-β1, Smad2, phospho-Smad2 (p-Smad2), Smad3, phospho-Smad3 (p-Smad3), Smad4, and Smad7 were detected in 5 cases of normal anterior pituitaries, 29 cases of invasive NFPAs, and 21 cases of noninvasive NFPAs by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemical analysis. Results The Smad3 and p-Smad3 protein levels gradually decreased from normal anterior pituitaries, noninvasive NFPAs, to invasive NFPAs. However, there were no significant differences in Smad2 (P = 0.122) and p-Smad2 protein levels (P = 0.101) or Smad2 mRNA level (P = 0.409). In addition, the TGF-β1 mRNA level gradually decreased while the Smad7 mRNA level gradually increased from normal anterior pituitaries, noninvasive NFPAs, to invasive NFPAs. Furthermore, proliferating cell nuclear antigen (PCNA) mRNA level was markedly increased in invasive NFPAs compared to noninvasive ones (P < 0.01), and its level was negatively correlated with Smad3 mRNA level (P < 0.01). Conclusion The activity of TGF-β signaling may be restrained in NFPAs and is correlated with the development and invasion of NFPAs. PMID:24636138

  5. ACTH producing pulmonary carcinoid and pituitary macroadenoma: a fortuitous association?

    PubMed

    Wong, M; Isa, S H Md; Kamaruddin, N A; Khalid, B A K

    2007-06-01

    We report a case of a 45 year-old man who presented initially with a non-functioning pituitary macroadenoma. A routine chest radiography done preoperatively revealed a right lung nodule which was confirmed by computed tomography (CT) of the thorax. Transfrontal hypophysectomy was performed while a conservative approach was taken for the lung nodule. Four years later, he presented acutely with adrenocorticotrophic hormone (ACTH) dependent Cushing's syndrome which resolved following a right lobectomy. Histological examination revealed an atypical carcinoid. To our knowledge, this is the first reported case of an ectopic ACTH secreting pulmonary carcinoid found in association with a non-functioning pituitary macroadenoma.

  6. Pituitary Non-Functioning Adenoma Disclosed at 18F-Choline PET/CT to Investigate a Prostate Cancer Relapse.

    PubMed

    Maffione, Anna Margherita; Mandoliti, Giovanni; Pasini, Felice; Colletti, Patrick M; Rubello, Domenico

    2016-10-01

    We report the incidental finding of a pituitary macroadenoma on an F-choline PET/CT in a patient with recurrent prostate cancer. The pituitary gland was clearly enlarged and intensely FDG avid (SUVmax, 6.6). The diagnosis was confirmed by a subsequent contrast-enhanced MR evaluation, and the macroadenoma was classified as nonfunctioning on the basis of normality of the specific serum hormonal profile. A follow-up F-choline PET/CT scan performed after 6 months revealed stable dimension, and uptake of the pituitary macroadenoma patient deceased 1 month later. At autopsy, intracytoplasmic vesicles containing growth and prolactin hormones were observed at immunohistochemistry. PMID:27500509

  7. [Successful treatment using detachable coils for traumatic carotid cavernous fistula as a complication of transsphenoidal surgery for a pituitary adenoma: a case report].

    PubMed

    Kobayashi, N; Abe, T; Furuya, H; Dohi, K; Shimazu, M; Sasaki, K; Izumiyama, H; Matsumoto, K; Ohki, S; Nemoto, S

    2000-02-01

    We report a case of a patient with traumatic carotid cavernous fistula (CCF) caused by transnasal-transsphenoidal surgery, who was successfully treated using detachable coils. A 47-year-old man was admitted to our hospital because of severe headache. He was confirmed to have a nonfunctioning pituitary adenoma with presellar-type sphenoid sinus. Cerebral angiography initially disclosed no vascular lesions. A transnasal-transsphenoidal adenomectomy was performed. When the anterior wall of the sphenoid sinus was dissected with a chisel, the chisel deeply stuck into the posterolateral part of the sinus. Profuse arterial bleeding was observed through the sphenoid sinus. The bleeding was stopped easily by compression and packing with bone wax. The operation was continued, the sellar floor was opened widely and the tumor was removed subtotally. The medial wall of the cavernous sinus was intact. Histological examination revealed a pituitary adenoma. Immediately after surgery, the patient noticed a bruit. He developed chemosis and abducent palsy on the right side. Cerebral angiography displayed a high-flow CCF, which was attributed to the carotid artery injury caused by the transnasal-transsphenoidal surgery. The CCF disappeared after two-staged embolization using detachable coils, 1st transvenous and 2nd transarterial. Ten months later, cerebral angiography showed persistent occlusion of the fistula, and the patient experienced no tumor recurrence. It is suggested that drilling is a safer procedure than using a chisel for dissection of a sphenoid sinus with incomplete pneumatization. Endovascular treatment using detachable coils proved useful to manage the CCF, an unusual complication of transsphenoidal surgery.

  8. 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.

  9. 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. PMID:23334699

  10. β-Arrestin 1 and 2 and G protein-coupled receptor kinase 2 expression in pituitary adenomas: role in the regulation of response to somatostatin analogue treatment in patients with acromegaly.

    PubMed

    Gatto, Federico; Feelders, Richard; van der Pas, Rob; Kros, Johan M; Dogan, Fadime; van Koetsveld, Peter M; van der Lelij, Aart-Jan; Neggers, Sebastian J C M M; Minuto, Francesco; de Herder, Wouter; Lamberts, Steven W J; Ferone, Diego; Hofland, Leo J

    2013-12-01

    Recent in vitro studies highlighted G protein-coupled receptor kinase (GRK)2 and β-arrestins as important players in driving somatostatin receptor (SSTR) desensitization and trafficking. Our aim was to characterize GRK2 and β-arrestins expression in different pituitary adenomas and to investigate their potential role in the response to somatostatin analog (SSA) treatment in GH-secreting adenomas (GHomas). We evaluated mRNA expression of multiple SSTRs, GRK2, β-arrestin 1, and β-arrestin 2 in 41 pituitary adenomas (31 GHomas, 6 nonfunctioning [NFPAs], and 4 prolactinomas [PRLomas]). Within the GHomas group, mRNA data were correlated with the in vivo response to an acute octreotide test and with the GH-lowering effect of SSA in cultured primary cells. β-Arrestin 1 expression was low in all 3 adenoma histotypes. However, its expression was significantly lower in GHomas and PRLomas, compared with NFPAs (P < .01). GRK2 expression was higher in PRLomas and NFPAs compared with GHomas (P < .05). In the GHoma group, GRK2 expression was inversely correlated to β-arrestin 1 (P < .05) and positively correlated to β-arrestin 2 (P < .0001). SSA treatment did not affect GRK2 and β-arrestin expression in GHomas or in cultured rat pituitary tumor GH3 cells. Noteworthy, β-arrestin 1 was significantly lower (P < .05) in tumors responsive to octreotide treatment in vitro, whereas GRK2 and SSTR subtype 2 were significantly higher (P < .05). Likewise, β-arrestin 1 levels were inversely correlated with the in vivo response to acute octreotide test (P = .001), whereas GRK2 and SSTR subtype 2 expression were positively correlated (P < .05). In conclusion, for the first time, we characterized GRK2, β-arrestin 1, and β-arrestin 2 expression in a representative number of pituitary adenomas. β-Arrestin 1 and GRK2 seem to have a role in modulating GH secretion during SSA treatment.

  11. Neurology of the pituitary.

    PubMed

    Samarasinghe, Shanika; Emanuele, Mary Ann; Mazhari, Alaleh

    2014-01-01

    The anterior pituitary hormones are essential for reproduction, growth, metabolic homeostasis, stress response, and adaptation to changes in the external environment. Each pituitary hormone is secreted in a distinctive pulsatile manner reflecting its regulation by the central nervous system through a complex interaction between hypothalamic neuroendocrine pathways, feedback effects from peripheral target gland hormones, and intrapituitary mechanisms. While the most common cause of a pituitary mass is an adenoma, the differential diagnosis is broad and includes pituitary hyperplasia, lymphocytic hypophysitis, craniopharyngioma among others. Patients with pituitary adenomas can be asymptomatic or present with symptoms due to mass effect, pituitary hormone dysfunction, or both. Prolactinomas represent 40% of pituitary adenomas, the majority of which are microadenomas. Hyperfunction of growth hormone and ACTH are far less common, while TSH-producing tumors are exceedingly rare. Hypopituitarism in patients with pituitary adenomas can be partial or complete. The clinical picture will depend on the type, degree, and rapidity of onset of pituitary hormone deficiency. An MRI specifically focused on the sellar region is the imaging modality of choice to detect pituitary pathology. Management of pituitary tumors ranges from observation of nonfunctioning microadenomas through medical, surgical, and radiotherapeutic approaches dependent on tumor type, function, size, and invasiveness.

  12. Treatment with octreotide LAR in clinically non-functioning pituitary adenoma: results from a case-control study.

    PubMed

    Fusco, Alessandra; Giampietro, Antonella; Bianchi, Antonio; Cimino, Vincenzo; Lugli, Francesca; Piacentini, Serena; Lorusso, Margherita; Tofani, Anna; Perotti, Germano; Lauriola, Libero; Anile, Carmelo; Maira, Giulio; Pontecorvi, Alfredo; De Marinis, Laura

    2012-12-01

    Surgical cure cannot be achieved in most patients with invasive non-functioning pituitary macroadenoma (NFPA). Short-term residual tumor treatment with somatostatin analogs has produced disappointing results. This prospective case-control study assessed the efficacy of chronic treatment with long acting octreotide (octreotide LAR) on tumor volume in patients harboring post-surgical NFPA residue. The study population comprised 39 patients with NFPAs not cured by surgery. All patients underwent somatostatin receptor scintigraphy at least 6 months after the last surgery. Patients with a positive pituitary level octreoscan at (n = 26) received octreotide LAR (20 mg every 28 days) for ≥ 12 months (mean follow-up 37 ± 18 months) (Treated group). Moreover, a fragment of tumor tissue from patients in the treated group was retrospectively collected to assess the immunohistochemical expression of somatostatin receptor subtypes (SSTRs). The patients with a negative octreoscan (n = 13) formed the control group (mean follow-up 37 ± 16 months). Hormonal, radiological and visual field parameters were periodically assessed. In the treated group, all tumors expressed at least one SSTR subtype. The SSTR5 subtype was the most abundant, followed by SSTR3. The tumor residue increased in five of 26 patients (19%) in the treated group and in seven of 13 controls (53%). Visual field and pituitary function did not change in any patient. This study indicates that SSTR5 and SSTR3 are the most frequently expressed SSTR subtypes in NFPAs and supports a potential role of SSTR subtypes in stabilization of tumor remnant from NFPAs. PMID:22207350

  13. 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.

  14. 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

  15. 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. PMID:24282035

  16. Management of pituitary tumors.

    PubMed

    Post, K D; Muraszko, K

    1986-11-01

    Pituitary adenomas represent the only true adenomas of the cranial cavity. In 1000 asymptomatic pituitary glands examined at autopsy, there was a 22.4 per cent incidence of undetected microadenomas. Advances in diagnostic endocrinology, in radiologic imaging, and in surgical and medical treatments have brought many more patients to the attention of the authors. Over the last 10 years, their treatment approaches have evolved to those presented in this article.

  17. Solitary fibrous tumor of the sella mimicking pituitary adenoma: an uncommon tumor in a rare location-a case report.

    PubMed

    Furlanetto, Tania Weber; Pinheiro, Cláudio Faria Pitta; Oppitz, Paulo Petry; de Alencastro, Luiz Carlos; Asa, Sylvia L

    2009-01-01

    Solitary fibrous tumor (SFT) is rarely located in the central nervous system, and sella turcica involvement was reported in only two patients. We report the case of a 28-year-old man with a SFT of the sella turcica mimicking a pituitary nonfunctioning macroadenoma. He presented with optic nerve compression caused by a heterogeneous tumor located in the sellar and suprasellar area. At surgery, the tumor was hard and infiltrated the sellar diaphragm, so that resection resulted in a cerebrospinal fluid fistula. His postoperative course was also complicated by complete central diabetes insipidus, hypopituitarism, and two episodes of meningitis. After surgical resection, the diagnosis of SFT was reached on the basis of histological and immunohistochemical studies. He was discharged after 49 days. Ten months after surgery, he was clinically well, and magnetic resonance images showed no evidence of residual or recurrent tumor. SFT should be considered in the differential diagnosis of sellar and parasellar tumors.

  18. Reduction in size of a thyrotropin- and gonadotropin-secreting pituitary adenoma treated with octreotide acetate (somatostatin analog).

    PubMed

    Sy, R A; Bernstein, R; Chynn, K Y; Kourides, I A

    1992-03-01

    TSH as well as alpha-subunit, secretion has been shown to decrease after the administration of the somatostatin analog octreotide acetate (SMS 201-995). We have studied a 59-yr-old, male patient with a TSH- and gonadotropin-secreting tumor who, because of severe cardiomyopathy, was treated with long-term somatostatin analog rather than surgical resection of the pituitary tumor. Thirteen weeks of treatment with thrice daily sc injection of 100 micrograms octreotide acetate resulted in decreased TSH and alpha-subunit secretion, normal serum thyroid hormone levels, reduction in LH and testosterone level, and significant tumor size reduction. Long-term treatment for 51 weeks has not been associated with any significant side effects. We have shown that octreotide acetate may be a therapeutically valuable modality for certain patients with neoplastic inappropriate secretion of TSH (NIST). A probable effect of octreotide acetate on neoplastic gonadotropes, as evidenced by the reduction of the LH level with a concomitant decrease in testosterone level, is, likewise, suggested.

  19. Familial pituitary tumors.

    PubMed

    Alband, Neda; Korbonits, Márta

    2014-01-01

    Pituitary adenomas are benign intracranial neoplasms that present a major clinical concern due to hormone overproduction and/or tumor mass effects. The majority of pituitary adenomas occur sporadically; however, familial cases are increasingly being recognized, such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), and familial isolated pituitary adenoma (FIPA). Familial pituitary tumors appear to differ from their sporadic counterparts both in their genetic basis and in clinical characteristics. Evidence suggests that, especially in MEN1 and FIPA, tumors are more aggressive and affect patients at a younger age, therefore justifying the importance of early diagnosis, while in Carney complex pituitary hyperplasia is common. The genetic alterations responsible for the formation of familial pituitary syndromes include the MEN1 gene, responsible for about 80% of MEN1 cases, the regulatory subunit of the protein kinase A, PRKAR1A, responsible for about 70% of Carney complex cases, and AIP, the gene coding the aryl hydrocarbon receptor interacting protein, responsible for about 20% of FIPA cases. Rarely other genes have also been found responsible for familial pituitary adenoma cases. McCune-Albright syndrome (MAS) also has a genetic origin due to mosaic mutations in the G protein-coupled α subunit coded by the GNAS1 gene. In this chapter, we summarize the genetic and clinical characteristics of these familial pituitary syndromes and MAS. PMID:25248598

  20. Pituitary gigantism.

    PubMed

    Daughaday, W H

    1992-09-01

    Pituitary gigantism is a rare condition whose association with McCune-Albright syndrome suggests that mutations in alpha-subunit of a Gs protein are an important cause of this condition. In addition to somatotroph adenoma, it is now recognized that somatotroph hyperplasia can also result from increased levels of growth hormone-releasing hormone. Transgenic rats with hypersomatotrophism are prone to renal and hepatic pathology. PMID:1521516

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

    PubMed

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

    2012-12-01

    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 immunocytochemistry 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 neurosurgeon 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

  2. 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. PMID:26961771

  3. 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

  4. 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.

  5. 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.

  6. Integrative proteomics and transcriptomics revealed that activation of the IL-6R/JAK2/STAT3/MMP9 signaling pathway is correlated with invasion of pituitary null cell adenomas.

    PubMed

    Feng, Jie; Yu, Sheng-Yuan; Li, Chu-Zhong; Li, Zhen-Ye; Zhang, Ya-Zhuo

    2016-11-15

    Non-functioning pituitary adenomas (NFPAs) are a highly heterogeneous group, but few studies have explored the invasion mechanism of specific subtypes of NFPAs. The objective of this study was to investigate the differential molecular expression patterns and the critical biological signaling pathways involved in the invasion of pituitary null cell adenomas (PNCAs) through integrative proteomics and transcriptomics. A total of 1160 genes and 283 proteins were found to be differentially expressed in invasive and non-invasive PNCAs. The differentially expressed molecules related to invasion were enriched in 15 canonical signaling pathways, 15 clusters of diseases or biological functions and 5 upstream molecules. Among them, the majority of the differentially expressed molecules were found to be involved in transport of molecule, migration of cells and cell movement. Notably, IL-6 was a significantly activated upstream regulator, and the IL6R/JAK2/STAT3 cascade was found to play a critical role in acute phase response signaling, which was the most significant canonical signaling pathway. Furthermore, we validated the overexpression of IL-6R, JAK2, STAT3, p-STAT3 and MMP9 in invasive PNCAs. Our data suggest that overactivation of the IL-6R/JAK2/STAT3/MMP9 pathway is critical for the invasion of PNCAs. PMID:27465831

  7. 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. PMID:23300914

  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 Central

    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. PMID:23300914

  9. 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. PMID:26414232

  10. Advances in understanding pituitary tumors

    PubMed Central

    Renner, Ulrich; Karl Stalla, Günter

    2014-01-01

    Pituitary tumors are common in the general population. Since neuroimaging techniques have improved, pituitary tumors are more often diagnosed incidentally. About 16.7% of the general population show changes in the pituitary gland. Predominantly, pituitary tumors are benign pituitary adenomas. Pituitary carcinomas or aggressive pituitary tumors are extremely rare. They might develop from benign adenomas. New genetic and epigenetic abnormalities help us to understand pituitary tumorigenesis and might lead to therapeutical targeting drugs in the future. Macroadenomas (>1 cm) can lead to visual field disturbances, compression of cranial nerves, hypopituitarism, and infiltration of the cavernous sinuses. The functional status of the pituitary tumor is important. About half to one third of all pituitary tumors are non-functioning pituitary adenomas. The other pituitary tumors show a specific pattern of hormone secretion. About 25% to 41% of all pituitary tumors are prolactinomas, acromegaly with production of growth hormone represents 10% to 15% of adenomas, Cushing's disease with production of adrenocorticotropic hormone accounts for 10%, and other hormonal characteristics are less common. Transsphenoidal resection and total adenomectomy are desirable. Radiosurgery has enriched the surgical treatment options. Surgical treatment is the intervention of choice except for prolactinomas, where pharmaceutical treatment is recommended. Pharmaceutical treatment consists of dopamine agonists such as cabergoline and somatostatin analogues that include octreotide and pasireotide; retinoic acid is of theoretical interest while peroxisome proliferator-activated receptor-gamma-ligands are not clinically useful. In acromegaly, pegvisomant is a further treatment option. Temozolomide should be considered in aggressive pituitary tumors. In general, pharmaceutical options developed recently have extended the repertoire of treatment possibilities of pituitary tumors. PMID:24592317

  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. 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. PMID:26314658

  13. Clinically silent somatotroph adenomas are common

    PubMed Central

    Wade, Alisha N; Baccon, Jennifer; Grady, M Sean; Judy, Kevin D; O’Rourke, Donald M; Snyder, Peter J

    2011-01-01

    Objective Somatotroph adenomas are typically recognized when they secrete GH excessively and cause acromegaly. Both ‘silent’ somatotroph adenomas (immunohistochemical evidence of GH excess without biochemical or clinical evidence) and ‘clinically silent’ somatotroph adenomas (immunohistochemical and biochemical evidence but no clinical evidence) have occasionally been reported. The relative frequency of each presentation is unknown. The goal of this study was, therefore, to determine the frequency of clinically silent somatotroph adenomas, a group that is potentially recognizable in vivo. Design We retrospectively identified 100 consecutive patients who had surgically excised and histologically confirmed pituitary adenomas. Methods Each pituitary adenoma was classified immunohistochemically by pituitary cell type. Somatotroph adenomas were further classified as ‘classic’ (obvious clinical features of acromegaly and elevated serum IGF1), ‘subtle’ (subtle clinical features of acromegaly and elevated IGF1), ‘clinically silent’ (no clinical features of acromegaly but elevated IGF1), and ‘silent’ (no clinical features of acromegaly and normal IGF1). Results Of the 100 consecutive pituitary adenomas, 29% were gonadotroph/glycoprotein, 24% somatotroph, 18% null cell, 15% corticotroph, 6% lactotroph, 2% thyrotroph, and 6% not classifiable. Of the 24 patients with somatotroph adenomas, classic accounted for 45.8%, subtle 16.7%, clinically silent 33.3%, and silent 4.2%. Conclusions Clinically silent somatotroph adenomas are more common than previously appreciated, representing one-third of all somatotroph adenomas. IGF1 should be measured in all patients with a sellar mass, because identification of a mass as a somatotroph adenoma expands the therapeutic options and provides a tumor marker to monitor treatment. PMID:21493729

  14. Dynamics of the regulation of the hypothalamo-pituitary-adrenal (HPA) axis determined using a nonsurgical method for collecting pituitary venous blood from horses.

    PubMed

    Alexander, S L; Irvine, C H; Donald, R A

    1996-01-01

    Since 1985, we have applied our nonsurgical technique for collecting pituitary venous (PitVen) blood from ambulatory horses to investigate the regulation of adrenocorticotropic hormone (ACTH) secretion. This method offers particular advantages for studying the hypothalamo-pituitary-adrenal axis since its benign nature enables hypothalamic and pituitary interactions to be monitored without disturbing the animal, and the horse's large blood volume allows 3- to 4-ml samples to be collected as frequently as every 20s for prolonged periods so that the secretion patterns of ACTH and its secretagogues can be precisely defined. When PitVen blood was sampled every 20 or 30s during the circadian maximum, arginine vasopressin (AVP) and ACTH secretion patterns were complex and irregular, with mean interpeak intervals of approximately 5 min. Despite their erratic patterns, AVP and ACTH secretions were closely coupled on cross-correlation analysis. By contrast, PitVen corticotropin-releasing hormone (CRH) concentrations were low, relatively stable, and not consistently related to ACTH secretion. However, when cortisol negative feedback was reduced acutely by metyrapone infusion, CRH and AVP secretion were stimulated. Mathematical modeling suggested that CRH had become the more effective secretagogue and that much of the ACTH response was mediated by increased pituitary responsiveness to CRH. Elevated blood osmolality triggered synchronous AVP and ACTH secretion, without altering PitVen CRH. In this case, the source of PitVen AVP was presumably the magnocellular/neurohypophysial pathway, which is thought to respond primarily to changes in blood osmolality and pressure. Our results suggest that this pathway also participates in ACTH regulation. We have studied the effect of several perturbations and found, as have others, that the secretagogues released vary with the stimulus given. For example, vigorous exercise promptly raised PitVen AVP and ACTH, but not PitVen CRH

  15. 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. PMID:26585365

  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. Temozolomide-Induced Shrinkage of Invasive Pituitary Adenoma in Patient with Nelson's Syndrome: A Case Report and Review of the Literature

    PubMed Central

    Kurowska, Maria; Nowakowski, Andrzej; Zieliński, Grzegorz; Malicka, Joanna; Tarach, Jerzy S.; Maksymowicz, Maria; Denew, Piotr

    2015-01-01

    Introduction. Invasive tumours in Nelson's syndrome need aggressive therapy. Recent reports have documented the efficacy of temozolomide (TMZ) in the treatment of adenomas resistant to conventional management. Objective. The review of the literature concerning TMZ treatment of atypical corticotroph adenomas and a case study of 56-year-old woman who developed Nelson's syndrome. Treatment Proceeding. The patient with Cushing's disease underwent transsphenoidal adenomectomy followed by a 27-month-long period of remission. Due to a regrowth of the tumor, she underwent two reoperations followed by stereotactic radiotherapy. Because of treatment failures, bilateral adrenalectomy was performed. Then she developed Nelson's syndrome. A fourth transsphenoidal adenomectomy was performed, but there was a rapid recurrence. Five months later, she underwent a right frontotemporal craniotomy. Due to a rapid regrowth of the tumour, the patient did not receive gamma-knife therapy and was treated with cabergoline and somatostatin analogue for some time. Only TMZ therapy resulted in marked clinical, biochemical, and radiological improvement. To date, this is the first case of invasive corticotroph adenoma in Nelson's syndrome treated with temozolomide in Poland. Conclusion. In our opinion, temozolomide can be an effective treatment option of invasive adenomas in Nelson's syndrome. PMID:26221547

  18. Parathyroid adenoma

    MedlinePlus

    Hyperparathyroidism - parathryoid adenoma; Overactive parathyroid gland - parathyroid adenoma ... The parathyroid glands in the neck help control calcium use and removal by the body. They do this by producing parathyroid ...

  19. Pituitary incidentaloma.

    PubMed

    Orija, Israel B; Weil, Robert J; Hamrahian, Amir H

    2012-02-01

    Pituitary incidentalomas (PIs) are commonly encountered in clinical practice. While most are microincidentalomas (<1 cm) and not functional, in some cases their identification may lead to discovery of unrecognized abnormalities such as pituitary hormonal deficiencies, excess hormone secretion or visual field defects. Although the majority are pituitary adenomas, the potential list of differential diagnosis is extensive. A limited biochemical work up for asymptomatic patients with microincidentalomas, to include measurement of prolactin and IGF-1, is reasonable, with further studies to be tailored based on the clinical picture. All patients with macroincidentalomas (≥1 cm) should be evaluated for hypopituitarism and undergo visual field testing if the sellar mass abuts or compresses the optic chiasm. Most PIs can be followed, closely without surgery over time, but some may require surgical removal, especially if they are found to be macroincidentalomas at presentation, encroaching on or abutting the optic chiasm, or are found to be functional, excluding prolactinomas. Recovery of pituitary function may be seen in some patients with mass effect following resection of a sellar mass. The association of headache and pituitary incidentalomas remains a diagnostic challenge. There are no randomized controlled studies to guide the follow up approach when surgery is not indicated; most of the follow up algorithms in the literature are based on personal experience. Most retrospective series on natural history indicate that microincidentalomas tend not to grow; without a need for long-term follow up unless the patient becomes symptomatic. Macroincidentalomas, on the other hand, have a propensity to grow and need a more aggressive follow up approach to minimize morbidity. PMID:22305452

  20. [Two autopsy cases of primary pituitary carcinoma].

    PubMed

    Negishi, K; Suzuki, T; Masuda, Y; Masugi, Y; Teramoto, A; Ohama, E

    1988-05-01

    We studied two autopsy cases of primary pituitary carcinoma. Case-1. A 45 year old female was admitted on Oct. 4 1978, with a complaint of right homonymous hemianopsia. And diagnosis was pituitary adenoma. Partial removal of pituitary tumor was performed on Oct. 23 1978. She died on Dec. 5 1978 due to bleeding of gastrointestinal tract. Autopsy disclosed a pituitary carcinoma invading the left hypothalamus, mamillary body, optic and V cranial nerves, and mid brain as well as sphenoid bone. No extracranial metastasis was noted. Case-2. A 44 year old female with a history of acromegaly for 6 years was admitted with a complaint of headache on May 8 1976. She was diagnosed as having pituitary adenoma. The subtotal removal of pituitary tumor was performed on May 21 1976 and followed by 4500 rad irradiation. At this time, pathological diagnosis was eosinophilic adenoma. Seven years later, she complained of progressive right hearing disturbance, dysarthria and ataxic gait 1983. The second subtotal removal of pituitary tumor was performed with a diagnosis of recurrence of pituitary adenoma on Oct. 7 1983. After the operation, she complicated sepsis and died on Jan. 14 1984. An autopsy disclosed a pituitary carcinoma from residual pituitary gland, continuously extending to the subarachnoid space of the pons, and invading right cerebello-pontine angle and cerebellum. The histological examination revealed pituitary carcinoma with high pleomorphism and glioblastoma multiform-like feature were within the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Presentation of a functional pituitary adenoma as a significant decrease in prostate-specific antigen level in a patient followed for prostate cancer.

    PubMed

    Grotas, Aaron B; Nagler, Harris M

    2006-12-01

    The stimulatory role of testosterone in the production and release of prostate-specific antigen (PSA) has been well characterized. Testosterone production by the testes is dependent on a functional hypothalamic-pituitary-gonadal axis. High prolactin levels have been shown to disrupt this axis, resulting in decreases in gonadotropins and testosterone levels. We report a patient with prostate cancer and elevated PSA levels followed with "watchful waiting" for several years who experienced a precipitous decrease in PSA level over a 3 month period. The patient was found to have an asymptomatic prolactin-secreting pituitary macroadenoma.

  2. 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. PMID:20507346

  3. Efficacy of a dopamine-somatostatin chimeric molecule, BIM-23A760, in the control of cell growth from primary cultures of human non-functioning pituitary adenomas: a multi-center study.

    PubMed

    Florio, Tullio; Barbieri, Federica; Spaziante, Renato; Zona, Gianluigi; Hofland, Leo J; van Koetsveld, Peter M; Feelders, Richard A; Stalla, Günter K; Theodoropoulou, Marily; Culler, Michael D; Dong, Jesse; Taylor, John E; Moreau, Jacques-Pierre; Saveanu, Alexandru; Gunz, Ginette; Dufour, Henry; Jaquet, Philippe

    2008-06-01

    Dopamine D2 and somatostatin receptors (sstrs) were reported to affect non-functioning pituitary adenoma (NFPA) proliferation in vitro. However, the reported results differ according to the experimental conditions used. We established an experimental protocol allowing reproducible evaluation of NFPA cell proliferation in vitro, to test and compare the antiproliferative effects of dopamine and somatostatin analogs (alone or in combination) with the activity of the dopamine-somatostatin chimeric molecule BIM-23A760. The protocol was utilized by four independent laboratories, studying 38 fibroblast-deprived NFPA cell cultures. Cells were characterized for GH, POMC, sstr1-sstr5, total dopamine D2 receptor (D2R) (in all cases), and D2 receptor long and short isoforms (in 15 out of 38 cases) mRNA expression and for alpha-subunit, LH, and FSH release. D2R, sstr3, and sstr2 mRNAs were consistently observed, with the dominant expression of D2R (2.9+/-2.6 copy/copy beta-glucuronidase; mean+/-s.e.m.), when compared with sstr3 and sstr2 (0.6+/-1.0 and 0.3+/-0.6 respectively). BIM-23A760, a molecule with high affinity for D2R and sstr2, significantly inhibited [3H]thymidine incorporation in 23 out of 38 (60%) NFPA cultures (EC50=1.2 pM and Emax=-33.6+/-3.7%). BIM-23A760 effects were similar to those induced by the selective D2R agonist cabergoline that showed a statistically significant inhibition in 18 out of 27 tumors (compared with a significant inhibition obtained in 17 out of 27 tumors using BIM-23A760, in the same subgroup of adenomas analyzed), while octreotide was effective in 13 out of 27 cases. In conclusion, superimposable data generated in four independent laboratories using a standardized protocol demonstrate that, in vitro, chimeric dopamine/sstr agonists are effective in inhibiting cell proliferation in two-thirds of NFPAs. PMID:18509006

  4. Health-related quality of life in pituitary diseases.

    PubMed

    Crespo, Iris; Valassi, Elena; Santos, Alicia; Webb, Susan M

    2015-03-01

    In the last 15 years, worse health-related quality of life (QoL) has been reported in patients with pituitary diseases compared with healthy individuals. Different QoL questionnaires have shown incomplete physical and psychological recovery after therapy. Residual impairments often affect QoL even long-term after successful treatment of pituitary adenomas. In this article, knowledge of factors that affect QoL in pituitary diseases is reviewed. The focus is on 5 pituitary diseases: Cushing syndrome, acromegaly, prolactinomas, nonfunctioning pituitary adenomas, and hypopituitarism.

  5. Genetically Engineered Mouse Models of Pituitary Tumors

    PubMed Central

    Cano, David A.; Soto-Moreno, Alfonso; Leal-Cerro, Alfonso

    2014-01-01

    Animal models constitute valuable tools for investigating the pathogenesis of cancer as well as for preclinical testing of novel therapeutics approaches. However, the pathogenic mechanisms of pituitary-tumor formation remain poorly understood, particularly in sporadic adenomas, thus, making it a challenge to model pituitary tumors in mice. Nevertheless, genetically engineered mouse models (GEMMs) of pituitary tumors have provided important insight into pituitary tumor biology. In this paper, we review various GEMMs of pituitary tumors, highlighting their contributions and limitations, and discuss opportunities for research in the field. PMID:25136513

  6. 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.

  7. Blood, pituitary, and brain renin-angiotensin systems and regulation of secretion of anterior pituitary gland.

    PubMed

    Ganong, W F

    1993-07-01

    In addition to increasing blood pressure, stimulating aldosterone and vasopressin secretion, and increasing water intake, angiotensin II affects the secretion of anterior pituitary hormones. Some of these effects are direct. There are angiotensin II receptors on lactotropes and corticotropes in rats, and there may be receptors on thyrotropes and other secretory cells. Circulating angiotensin II reaches these receptors, but angiotensin II is almost certainly generated locally by the pituitary renin-angiotensin system as well. There are also indirect effects produced by the effects of brain angiotensin II on the secretion of hypophyseotropic hormones. In the anterior pituitary of the rat, the gonadotropes contain renin, angiotensin II, and some angiotensin-converting enzyme. There is debate about whether these cells also contain small amounts of angiotensinogen, but most of the angiotensinogen is produced by a separate population of cells and appears to pass in a paracrine fashion to the gonadotropes. An analogous situation exists in the brain. Neurons contain angiotensin II and probably renin, but most angiotensin-converting enzyme is located elsewhere and angiotensinogen is primarily if not solely produced by astrocytes. Angiotensin II causes secretion of prolactin and adrenocorticotropic hormone (ACTH) when added to pituitary cells in vitro. Paracrine regulation of prolactin secretion by angiotensin II from the gonadotropes may occur in vitro under certain circumstances, but the effects of peripheral angiotensin II on ACTH secretion appear to be mediated via the brain and corticotropin-releasing hormone (CRH). In the brain, there is good evidence that locally generated angiotensin II causes release of norepinephrine that in turn stimulates gonadotropin-releasing hormone-secreting neurons, increasing circulating luteinizing hormone. In addition, there is evidence that angiotensin II acts in the arcuate nuclei to increase the secretion of dopamine into the portal

  8. Delayed sequelae of pituitary irradiation.

    PubMed

    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 radiation lesion confined to the pituitary gland but did not cause injury to the critical structures of the surrounding central nervous system.

  9. 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.

  10. Pituitary autoimmunity: 30 years later

    PubMed Central

    Caturegli, Patrizio; Lupi, Isabella; Landek-Salgado, Melissa; Kimura, Hiroaki; Rose, Noel R.

    2012-01-01

    Pituitary autoimmunity encompasses a spectrum of conditions ranging from histologically proven forms of lymphocytic hypophysitis to the presence of pituitary antibodies in apparently healthy subjects. Hypophysitis is a rare but increasingly recognized disorder that typically presents as a mass in the sella turcica. It mimics clinically and radiologically other non-secreting sellar masses, such as the more common pituitary adenoma. Hypophysitis shows a striking temporal association with pregnancy, and it has been recently described during immunotherapies that block CTLA-4. Several candidate pituitary autoantigens have been described in the last decade, although none has proven useful as a diagnostic tool. This review summarizes the advances made in the field since the publication of the first review on pituitary autoimmunity, and the challenges that await clarification. PMID:18774118

  11. 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

  12. 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.

  13. Pituitary gland

    MedlinePlus

    ... glands. Located above the pituitary gland is the hypothalamus. The hypothalamus decides which hormones the pituitary should release by ... messages. In response to hormonal messages from the hypothalamus, the pituitary gland releases the following hormones: GH ( ...

  14. 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

  15. 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.

  16. The Pituitary in Gigantism.

    PubMed

    Scheithauer, Bernd W.; Kovacs, Kalman T.; Stefaneanu, Lucia; Horvath, Eva; Kane, Laurie A.; Young, William F.; Lloyd, Ricardo V.; Randall, Raymond V.; Davis, Dudley H.

    1995-01-01

    To compare the pituitary pathology of gigantism to that of acromegaly, 19 surgically resected lesions were studied from 10 males and 9 females, ages 13-49 (mean, 19 yr) with excessive height (>/=95th percentile), onset of disease prior to puberty, elevated growth hormone (GH) levels despite glucose suppression, and a pathologically confirmed GH-producing pituitary mass. One patient had MEN-I. The lesions included 18 adenomas and 1 case of pure hyperplasia. The median, mean, and range of serum GH and prolactin (PRL) levels were 64, 235, 5-1000 ng/mL and 47, 146, 29-770 ng/mL, respectively. Of the 8 adenoma specimens accompanied by nontumoral pituitary (i.e., tissue wherein the presence of hyperplasia was assessable), 3 (37%) demonstrated both. Of the 18 tumors, 78% were macroadenomas and 22% were grossly invasive; their immunophenotypes included GH (5%), GH and PRL (19%), and GHPRL and a glycoprotein hormone, usually TSH and/or a-subunit (76%). Of the 10 adenoma-containing lesions subject to electron microscopy (EM), 2 consisted of GH cells alone; 2 of mammosomatotroph (MS) cells alone; 1 of GH and MS cells; 1 of GH and PRL cells; 2 of GH, PRL, and MS cells; 1 of GH, PRL, and glycoprotein cells; and 1 was a subtype 3 adenoma. Ultrastructurally, GH cells and/or MS cells predominated in these lesions. Immuno-EM of one CH and PRL cell and of one GH-PR-MS tumor showed GH and PRL to be present not only in single cells but within the same granules. Nine of 12 adenoma-associated lesions subject to combined in situ hybridization (ISH) and immunostaining showed double labeling for PRL (or GH) mRNA and for GH (or PRL), respectively, features indicating MS differentiation. In the 4 lesions exhibiting hyperplasia, either alone (1) or in association with adenoma (3), EM showed MS cells in 3, and immuno-EM as well as combined immunohistochemistry and ISH showed double labeling for GH and PRL in both of the 2 cases studied. In summary, although in terms of their tinctorial

  17. 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

  18. Dural invasion by pituitary tumours.

    PubMed

    Shaffi, O M; Wrightson, P

    1975-04-23

    In 12 cases of pituitary tumour the dura mater of the sella turcica or diaphragma sellae in contact with the tumour was examined histologically. In nine cases tumour cells were found lying deep in the substance of the dura. Dura from the sella of seven subjects without pituitary disease, obtianed at autopsy, showed no inclusions of pituitary tissue. Four of the cases studied were known before death to suffer from an invasive pituitary adenoma. Of eight surviving cases operated upon in the last two years, five showed dural invasion by tumour. The present report suggests that the condition may be more frequent than expected and that with more study it may provide an index of prognosis. It also defines a requirement for the surgeon aiming to prevent recurrence of tumour after operation or to achieve a complete endocrine ablation.

  19. Pathology of growth hormone-producing tumors of the human pituitary.

    PubMed

    Kovacs, K; Horvath, E

    1986-02-01

    This paper reviews the morphologic features of growth hormone-producing tumors of the human pituitary. These tumors are associated with elevated blood growth hormone levels and acromegaly or gigantism and can be classified into the following morphologically distinct entities by the combined application of histology, immunocytology, and electron microscopy: densely granulated growth hormone cell adenoma; sparsely granulated growth hormone cell adenoma; mixed growth hormone cell- prolactin cell-adenoma; acidophil stem cell adenoma; mammosomatotroph cell adenoma; growth hormone cell carcinoma; plurihormonal adenoma with growth hormone production. PMID:3303228

  20. Relationship between receptor binding and biopotency of somatostatin-14 and somatostatin-28 in mouse pituitary tumor cells.

    PubMed

    Srikant, C B; Heisler, S

    1985-07-01

    Somatostatin-14 (S-14) acts via specific receptors to inhibit basal as well as hormone- and forskolin-stimulated ACTH secretion in tumor cells (AtT-20/D16-16) of mouse anterior pituitary. In addition S-14 inhibits the stimulated but not basal cAMP accumulation. The potency of somatostatin-28 (S-28) for regulating these processes in these tumor cells has not been reported. In this study we have investigated the relationship between receptor-binding affinities of S-14 and S-28 and their biopotency in these cells. Membrane receptors for S-14 characterized using [125I-Tyr11]S-14 as the radioligand [maximum binding capacity (Bmax) = 1.28 +/- 0.1 pmol/mg; dissociation constant (Kd) = 1.1 +/- 0.04 nM] bound S-28 with 3-fold greater affinity than S-14. Binding sites quantitated using an S-28 analog [Leu8, D-Trp22, 125I-Tyr25]S-28 as radioligand (Bmax = 1.18 +/- 0.15 pmol/mg; Kd = 0.08 +/- 0.06 nM) also exhibited greater affinity for S-28 than S-14. Forskolin-stimulated cAMP accumulation and ACTH secretion in these cells were inhibited to a greater extent (4- and 9-fold, respectively) by S-28 than S-14. Preincubation of the cells with S-14 and S-28 (10(-7) M) resulted in a marked decrease (36% and 71%, respectively) of S-14 receptor concentration. Coincubation of the cells with both S-14 and S-28 led to 56% decrease in S-14 receptor binding. The responsiveness of the cells to forskolin stimulation of ACTH secretion and cAMP accumulation was significantly enhanced by preincubation with S-14 (10(-7) M) whereas the responsiveness to forskolin was completely abolished by preincubation with S-28. Simultaneous exposure of the cells to both S-14 and S-28 resulted in a partial reversal of the inhibiting effect of S-28 on forskolin-stimulated cAMP accumulation in these cells but did not result in a partial reversal of the inhibitory effect of S-28 on forskolin-stimulated ACTH secretion in these cells. These results demonstrate that S-28 is more potent than S-14 in AtT-20/D16

  1. 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

  2. Pituitary Disorders

    MedlinePlus

    ... the "master control gland" - it makes hormones that affect growth and the functions of other glands in the body. With pituitary disorders, you often have too much or too little of one of your hormones. Injuries can cause pituitary disorders, but the most common cause is a pituitary tumor.

  3. Analysis of IMP3 expression in normal and neoplastic human pituitary tissues.

    PubMed

    Righi, Alberto; Zhang, Shuya; Jin, Long; Scheithauer, Bernd W; Kovacs, Kalman; Kovacs, Gabor; Goth, Miklos I; Korbonits, Marta; Lloyd, Ricardo V

    2010-03-01

    Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal protein highly expressed in fetal tissue and malignant tumors but rarely found in adult benign tissues. In various tumors, IMP3 expression is correlated with increased tumor aggressiveness and reduced overall survival. To our knowledge, IMP3 expression has not been investigated in pituitary tumors. We analyzed the immunohistochemical expression of IMP3 in five normal pituitary tissues and 75 pituitary tumors (64 adenomas and 11 carcinomas) to determine if specific tumor types expressed IMP3 and if there were differences in IMP3 expression between adenomas and carcinomas. Immunohistochemical analysis showed that IMP3 was positive in four (80%) normal pituitaries with focal stain in a subset of normal anterior pituitary cells. IMP3 was expressed in 31% (20/64) of adenomas and in 36% (4/11) of carcinomas. A slightly higher level of IMP3 expression was observed in PRL-GH-TSH adenomas compared to the other types of pituitary adenomas. Expression of IMP3 was not significantly higher in carcinomas than in adenomas (p = 0.737). RT-PCR and Western Blotting supported the heterogeneous expression of IMP3. These results indicate that IMP3 is expressed both in normal and in neoplastic pituitary gland tissues without significant differences in expression levels in pituitary carcinomas. PMID:19898970

  4. [The oncocytic adenoma of the larynx (author's transl)].

    PubMed

    Lindenberger, J

    1982-04-01

    We report about a case of an oncocytic adenoma of the larynx and review briefly the few cases mentioned in literature. Oncocytic adenomas are benign and very rare tumors of the salivary glands, characterized by the proliferation of oncocytes from epithelial duct cells and lymphoid tissue. The exact role of the peculiar oncocytic cells in the pathogenesis of the tumor is still unknown; the transformation of normal epithelial duct cells to oncocytes can occur in the tongue, pharynx, larynx, trachea, bronchi, oesophagus, salivary glands, pituitary gland, liver, uterine tubes and nasal mucosa, mostly in adults. The oncocytic adenomas which occur in elderly patients only may be treated by surgery.

  5. [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.

  6. 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. PMID:21900544

  7. 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. PMID:27473973

  8. Management of large aggressive nonfunctional pituitary tumors: experimental medical options when surgery and radiation fail.

    PubMed

    Miller, Brandon A; Rutledge, W Caleb; Ioachimescu, Adriana G; Oyesiku, Nelson M

    2012-10-01

    Pituitary adenomas are generally considered benign tumors; however, a subset of these tumors displays aggressive behavior and are not easily cured. The protocol for nonsurgical treatment of aggressive pituitary lesions is less standardized than that of other central nervous system tumors. Aggressive surgical treatment, radiation, dopamine agonists, antiangiogenic drugs, and other chemotherapeutics all have roles in the treatment of aggressive pituitary tumors. More studies are needed to improve outcomes for patients with aggressive pituitary tumors.

  9. Metastatic salivary pleomorphic adenoma.

    PubMed

    Sim, D W; Maran, A G; Harris, D

    1990-01-01

    Pleomorphic adenomas of the salivary gland are usually regarded as benign tumours. We report a case in which a solitary pulmonary metastasis arose from a pleomorphic adenoma of the right parotid gland. The mechanism of metastasis is discussed.

  10. Imaging of pituitary pathology.

    PubMed

    Buchfelder, Michael; Schlaffer, Sven

    2014-01-01

    Modern imaging techniques play a vital role in the diagnosis, surveillance, and treatment monitoring of patients with pituitary disease. For its high soft tissue contrast, magnetic resonance (MR) imaging provides detailed information about the localization and extent of a lesion. It is thus, to date, the most important imaging technique for documenting or ruling out structural lesions. It is usually the first and only imaging procedure to be employed in pituitary pathology. While large pituitary adenomas are reliably depicted in standard T1-weighted sequences, small microadenomas, such as in Cushing's disease, may only become visible if repeat studies, sophisticated techniques and high-field scanners are employed. For monitoring treatment effects after surgical procedures, drug applications, or irradiation, follow-up studies with identical parameters should be employed, preferably at the same investigation site. Some space is devoted to intraoperative imaging, which not only allows assessment of how radical tumor resection needs to be during pituitary tumor surgery, but also provides extremely accurate structural data for neuronavigation. Less frequent lesions, such as craniopharyngiomas, meningiomas, germ cell tumors, gliomas, skull base tumors, hypothalamic hamartomas, vascular malformations, inflammatory and developmental lesions and other, even less frequent pathologies should be considered in the differential diagnosis. The particular strength of computed tomography (CT) is the direct depiction of calcification, a weakness of MRI, and the high resolution of bone structures at the skull base. This chapter presents the characteristics of both frequent and less commonly encountered tumoral lesions, with an emphasis on computed tomography and magnetic resonance imaging. PMID:25248586

  11. 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 ...

  12. A clinically novel AIP mutation in a patient with a very large, apparently sporadic somatotrope adenoma

    PubMed Central

    Daly, Adrian F; Quinones-Hinojosa, Alfredo; Thiry, Albert; Beckers, Albert

    2014-01-01

    Summary Heterozygous germline inactivating mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene lead to pituitary adenomas that most frequently present in the setting of familial isolated pituitary adenoma syndrome, usually as somatotropinomas and prolactinomas. More recently, they have been found in a significant percentage of young patients presenting with pituitary macroadenoma without any apparent family history. We describe the case of a 19-year-old man who presented with a gigantic somatotropinoma. His family history was negative. His peripheral DNA showed a heterozygous AIP mutation (p.I13N), while tumor tissue only had the mutated allele, showing loss of heterozygosity (LOH) and suggesting that the mutation caused the disease. Learning points AIP mutations may be observed in sporadic somatotrope adenomas occurring in young patients.LOH is a strong indicator that an AIP variant is disease causing.Somatotrope adenomas in carriers of AIP mutations are generally larger and more difficult to cure. PMID:25136448

  13. Management of nonfunctioning pituitary incidentaloma.

    PubMed

    Galland, Françoise; Vantyghem, Marie-Christine; Cazabat, Laure; Boulin, Anne; Cotton, François; Bonneville, Jean-François; Jouanneau, Emmanuel; Vidal-Trécan, Gwénaelle; Chanson, Philippe

    2015-07-01

    Prevalence of pituitary incidentaloma is variable: between 1.4% and 27% at autopsy, and between 3.7% and 37% on imaging. Pituitary microincidentalomas (serendipitously discovered adenoma <1cm in diameter) may increase in size, but only 5% exceed 10mm. Pituitary macroincidentalomas (serendipitously discovered adenoma>1cm in diameter) show increased size in 20-24% and 34-40% of cases at respectively 4 and 8years' follow-up. Radiologic differential diagnosis requires MRI centered on the pituitary gland. Initial assessment of nonfunctioning (NF) microincidentaloma is firstly clinical, the endocrinologist looking for signs of hypersecretion (signs of hyperprolactinemia, acromegaly or Cushing's syndrome), followed up by systematic prolactin and IGF-1 assay. Initial assessment of NF macroincidentaloma is clinical, the endocrinologist looking for signs of hormonal hypersecretion or hypopituitarism, followed up by hormonal assay to screen for hypersecretion or hormonal deficiency and by ophthalmologic assessment (visual acuity and visual field) if and only if the lesion is near the optic chiasm (OC). NF microincidentaloma of less than 5mm requires no surveillance; those of≥5mm are not operated on but rather monitored on MRI at 6months and then 2years. Macroincidentaloma remote from the OC is monitored on MRI at 1year, with hormonal exploration (for anterior pituitary deficiency), then every 2years. When macroincidentaloma located near the OC is managed by surveillance rather than surgery, MRI is recommended at 6months, with hormonal and visual exploration, then annual MRI and hormonal and visual assessment every 6months. Surgery is indicated in the following cases: evolutive NF microincidentaloma, NF macroincidentaloma associated with hypopituitarism or showing progression, incidentaloma compressing the OC, possible malignancy, non-compliant patient, pregnancy desired in the short-term, or context at risk of apoplexy.

  14. Gene mutations in Cushing's disease

    PubMed Central

    Xiong, Qi; Ge, Wei

    2016-01-01

    Cushing's disease (CD) is a severe (and potentially fatal) disease caused by adrenocorticotropic hormone (ACTH)-secreting adenomas of the pituitary gland (often termed pituitary adenomas). The majority of ACTH-secreting corticotroph tumors are sporadic and CD rarely appears as a familial disorder, thus, the genetic mechanisms underlying CD are poorly understood. Studies have reported that various mutated genes are associated with CD, such as those in menin 1, aryl hydrocarbon receptor-interacting protein and the nuclear receptor subfamily 3 group C member 1. Recently it was identified that ubiquitin-specific protease 8 mutations contribute to CD, which was significant towards elucidating the genetic mechanisms of CD. The present study reviews the associated gene mutations in CD patients. PMID:27588171

  15. Pituitary carcinoma with intraspinal metastasis: report of two cases and review of the literature

    PubMed Central

    Wang, Yin Qian; Fan, Tao; Zhao, Xin Gang; Liang, Cong; Qi, Xue Ling; Li, Jian Yi

    2015-01-01

    Pituitary carcinomas are rare malignant neoplasms with diagnostic and management challenges. Patients with pituitary carcinomas have extremely poor outcomes. In this report, the authors describe two cases of pituitary carcinomas with intraspinal metastasis (Case 1: 42-year-old man with a history of pituitary adenoma 16 years ago developed an intraspinal lesion at C4-C5; Case 2: 26-year-old women with a history of growth hormone-producing pituitary adenoma 9 years ago developed intraspinal lesion in the sacral canal). Both patients underwent spine surgery. The intraspinal lesions were confirmed as metastatic pituitary carcinomas based on the histomorphology and immunohistochemical stains. The authors reviewed the literature for the diagnosis, treatment, and prognosis of intraspinal metastasis from pituitary carcinomas. PMID:26464743

  16. 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. PMID:20451576

  17. Primary immune thrombocytopenia accompanied by pituitary apoplexy.

    PubMed

    Tsuji, Takahiro; Mochinaga, Hiromi; Yamasaki, Hiroshi; Tsuda, Hiroyuki

    2016-07-01

    An 83-year-old woman was admitted to our hospital with a severe headache and purpura. She had previously been diagnosed with idiopathic thrombocytopenia purpura (ITP) and achieved complete remission with steroid therapy. Steroid therapy had been completed one week prior to the current admission. The recurrence of severe thrombocytopenia (<1.0×10(4) platelets/μl) was detected and a CT scan revealed pituitary hemorrhage without pituitary adenoma. She received steroid therapy combined with intravenous immunoglobulin, which resulted in the amelioration of ITP and improvements in the pituitary hemorrhage. Intracranial hemorrhage, which is the most serious bleeding manifestation in ITP, is relatively uncommon. Pituitary apoplexy in ITP is extremely rare. PMID:27498733

  18. Pituitary gigantism causing diabetic ketoacidosis.

    PubMed

    Alvi, N S; Kirk, J M

    1999-01-01

    Although growth hormone excess (acromegaly) in association with glucose intolerance and diabetes mellitus is well documented in adult medicine, it is much less common in the paediatric age group. We report the case of a 13 year-old boy who presented with tall stature secondary to a large growth hormone secreting adenoma of the pituitary gland. Random growth hormone was 630 mIU/l and did not suppress during an oral glucose tolerance test. Following debulking of the tumour, he developed diabetic ketoacidosis requiring insulin treatment, but after further surgery glucose handling returned to normal. He has been started on testosterone to arrest further increase in height. PMID:10614552

  19. 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

  20. [Multihormonal and multifunctional hypophyseal adenoma and the acromegaly syndrome].

    PubMed

    Dusková, J; Marek, J; Povýsil, C

    2000-07-19

    Woman 75-year-old treated 30 years for syndrome of acromegaly refused pituitary surgery and irradiation. Five years and nine months before death she had a colon carcinoma successfully removed. Multinodular hyperfunctional goitre was treated with carbimazole. For six last years of life corticosteroids were given as a replacement therapy. Her cause of death was the heart failure due to acromegalic heart disease. In autopsy a large intrasellar and extrasellar pituitary adenoma without rests of nonneoplastic tissue was found. Nevertheless the target peripheral endocrine glands except ovaries, were not atrophic. A multinodular goitre and diffuse adrenocortical hyperplasia were revealed. Histology, and immunohistochemistry demonstrated that mot neoplastic cells were producing GH and ACTH, dispersly Prl, scattered cells were positive for beta-subunit of FSH, LH, TSH. Electron microscopy proved most of the cells to be densely granulated. We classify the adenoma according to the newly proposed WHO pituitary tumours classification (1) as plurihormonal, hyperfunctional, extrasellar, typical adenoma from densely granulated cells. We conclude that in plurihormonal adenomas with dominant (in the case referred acromegalic) symptomatology the additional hormonal production should be monitored as a possible source of important complications.

  1. Cushing's disease: management by transsphenoidal pituitary microsurgery.

    PubMed

    Bigos, S T; Somma, M; Rasio, E; Eastman, R C; Lanthier, A; Johnston, H H; Hardy, J

    1980-02-01

    Over 15 yr, 24 patients underwent transsphenoidal pituitary surgery for Cushing's disease with a median follow-up of 12 months. Cures included 7 patients with normal sella turcicas (6 microadenomas), 6 patients with focal depressions (6 microadenomas) of the sella (grade I), and 3 patients (3 adenomas) with enlarged sellas (grade II). Three patients with sella destruction (grades III and IV), 2 with normal sellas, and 1 with focal sella depression (grade I) were not cured. Two apparent cures (microadenomas) recurred. Tumor histology revealed 19 basophilic adenomas; electron microscopy (14 tumors) and immunochemical studies (10 tumors) revealed only ACTH cells. Circadian rhythm returned in 6 cured patients. Impotence (in 2), amenorrhea (in 7), and galactorrhea (in 3) resolved in affected cured patients. The major surgical complication was hemorrhage at the operative site (3 patients). Transsphenoidal pituitary surgery is a valuable method for managing Cushing's disease in many patients.

  2. Large Intracranial Aneurysm after Transsphenoidal Surgery for Pituitary Macroadenoma

    PubMed Central

    Yoon, Kyeong-Wook; Cho, Chun-Sung

    2014-01-01

    Uncontrolled cerebrospinal fluid (CSF) leakage after transsphenoidal surgery (TSS) for pituitary adenoma can lead to meningitis. Intracranial mycotic pseudoaneurysm is a rare complication in central nervous system infection. Large single pseudoaneurysm is more uncommon. Most mycotic aneurysms occur due to endocarditis. The present patient had no heart problem and was infected by CSF leakage after transsphenoidal surgery. We present a case of large ruptured mycotic pseudoaneurysm as a complication of cerebral infection after TSS for pituitary macroadenoma. PMID:24851153

  3. Pituitary tumors in childhood: update of diagnosis, treatment and molecular genetics.

    PubMed

    Keil, Margaret F; Stratakis, Constantine A

    2008-04-01

    Pituitary tumors are rare in childhood and adolescence, with a reported prevalence of up to one per 1 million children. Only 2-6% of surgically treated pituitary tumors occur in children. Although pituitary tumors in children are almost never malignant and hormonal secretion is rare, these tumors may result in significant morbidity. Tumors within the pituitary fossa are mainly of two types: craniopharyngiomas and adenomas. Craniopharyngiomas cause symptoms by compressing normal pituitary, causing hormonal deficiencies and producing mass effects on surrounding tissues and the brain; adenomas produce a variety of hormonal conditions such as hyperprolactinemia, Cushing disease and acromegaly or gigantism. Little is known about the genetic causes of sporadic lesions, which comprise the majority of pituitary tumors, but in children, more frequently than in adults, pituitary tumors may be a manifestation of genetic conditions such as multiple endocrine neoplasia type 1, Carney complex, familial isolated pituitary adenoma and McCune-Albright syndrome. The study of pituitary tumorigenesis in the context of these genetic syndromes has advanced our knowledge of the molecular basis of pituitary tumors and may lead to new therapeutic developments. PMID:18416659

  4. Pituitary Tumors in Childhood: an update in their diagnosis, treatment and molecular genetics

    PubMed Central

    Keil, Margaret F.; Stratakis, Constantine A.

    2009-01-01

    Pituitary tumors are rare in childhood and adolescence, with a reported prevalence of up to 1 per million children. Only 2 - 6% of surgically treated pituitary tumors occur in children. Although pituitary tumors in children are almost never malignant and hormonal secretion is rare, these tumors may result in significant morbidity. Tumors within the pituitary fossa are of two types mainly, craniopharyngiomas and adenomas; craniopharyngiomas cause symptoms by compressing normal pituitary, causing hormonal deficiencies and producing mass effects on surrounding tissues and the brain; adenomas produce a variety of hormonal conditions such as hyperprolactinemia, Cushing disease and acromegaly or gigantism. Little is known about the genetic causes of sporadic lesions, which comprise the majority of pituitary tumors, but in children, more frequently than in adults, pituitary tumors may be a manifestation of genetic conditions such as multiple endocrine neoplasia type 1 (MEN 1), Carney complex, familial isolated pituitary adenoma (FIPA), and McCune-Albright syndrome. The study of pituitary tumorigenesis in the context of these genetic syndromes has advanced our knowledge of the molecular basis of pituitary tumors and may lead to new therapeutic developments. PMID:18416659

  5. Clinical features and differential diagnosis of pituitary tumours with emphasis on acromegaly.

    PubMed

    Hennessey, J V; Jackson, I M

    1995-04-01

    Pituitary adenomas are frequently encountered, benign intracranial tumours. Clinically classified according to their capacity to produce and secrete hormones, pituitary tumours are diagnosed from the clinical manifestations and biochemical findings of specific pituitary hormone overproduction or of impaired pituitary function due to pressure on normal pituitary cells, the pituitary stalk or the hypothalamus. Additionally, the tumour may result in neurological manifestations due to its effect as an intracranial space-occupying lesion. Pituitary adenomas may present acutely with pituitary apoplexy after intrapituitary haemorrhage or infarction. The subsequent hypofunction of the pituitary with concomitant neurological sequelae of an expanding intracranial mass are often associated with excruciating headache, diplopia and visual field defects. Gradually developing neurological deficits or secondary endocrine failure over several years may precede the recognition of non-secretory tumours (30-40% of pituitary adenomas) as well as some of the hormone-producing adenomas, especially when they expand beyond the confines of the sella turcica. Asymptomatic masses occur in the pituitary in 5-27% of unselected autopsy series. About 10-20% of pituitaries imaged as part of a brain study contain lesions 'consistent with a pituitary adenoma', with about half being pituitary adenomas ('incidentalomas'). Many advocate screening such cases for a wide spectrum of pituitary function abnormalities. Clinical judgement should be utilized to determine the extent of the work-up and the frequency of follow-up. Acromegaly, a clinical syndrome caused by excess growth hormone secretion, accounts for one-sixth of resected pituitary tumours. This disorder leads to chronic progressive disability and a shortened life span, with approximately 50% of untreated acromegalic patients experiencing premature death. The prevalence of acromegaly has been estimated to range from 50 to 70 per million, with the

  6. Clinical features and differential diagnosis of pituitary tumours with emphasis on acromegaly.

    PubMed

    Hennessey, J V; Jackson, I M

    1995-04-01

    Pituitary adenomas are frequently encountered, benign intracranial tumours. Clinically classified according to their capacity to produce and secrete hormones, pituitary tumours are diagnosed from the clinical manifestations and biochemical findings of specific pituitary hormone overproduction or of impaired pituitary function due to pressure on normal pituitary cells, the pituitary stalk or the hypothalamus. Additionally, the tumour may result in neurological manifestations due to its effect as an intracranial space-occupying lesion. Pituitary adenomas may present acutely with pituitary apoplexy after intrapituitary haemorrhage or infarction. The subsequent hypofunction of the pituitary with concomitant neurological sequelae of an expanding intracranial mass are often associated with excruciating headache, diplopia and visual field defects. Gradually developing neurological deficits or secondary endocrine failure over several years may precede the recognition of non-secretory tumours (30-40% of pituitary adenomas) as well as some of the hormone-producing adenomas, especially when they expand beyond the confines of the sella turcica. Asymptomatic masses occur in the pituitary in 5-27% of unselected autopsy series. About 10-20% of pituitaries imaged as part of a brain study contain lesions 'consistent with a pituitary adenoma', with about half being pituitary adenomas ('incidentalomas'). Many advocate screening such cases for a wide spectrum of pituitary function abnormalities. Clinical judgement should be utilized to determine the extent of the work-up and the frequency of follow-up. Acromegaly, a clinical syndrome caused by excess growth hormone secretion, accounts for one-sixth of resected pituitary tumours. This disorder leads to chronic progressive disability and a shortened life span, with approximately 50% of untreated acromegalic patients experiencing premature death. The prevalence of acromegaly has been estimated to range from 50 to 70 per million, with the

  7. 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

  8. 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

  9. Protein western array analysis in human pituitary tumours: insights and limitations.

    PubMed

    Ribeiro-Oliveira, Antônio; Franchi, Giulia; Kola, Blerina; Dalino, Paolo; Pinheiro, Sérgio Veloso Brant; Salahuddin, Nabila; Musat, Madalina; Góth, Miklós I; Czirják, Sándor; Hanzély, Zoltán; da Silva, Deivid Augusto; Paulino, Eduardo; Grossman, Ashley B; Korbonits, Márta

    2008-12-01

    The molecular analysis of pituitary tumours has received a great deal of attention, although the majority of studies have concentrated on the genome and the transcriptome. We aimed to study the proteome of human pituitary adenomas. A protein array using 1005 monoclonal antibodies was used to study GH-, corticotrophin- and prolactin-secreting as well as non-functioning pituitary adenomas (NFPAs). Individual protein expression levels in the tumours were compared with the expression profile of normal pituitary tissue. Out of 316 proteins that were detected in the pituitary tissue samples, 116 proteins had not previously been described in human pituitary tissue. Four prominent differentially expressed proteins with potential importance to tumorigenesis were chosen for validation by immunohistochemistry and western blotting. In the protein array analysis heat shock protein 110 (HSP110), a chaperone associated with protein folding, and B2 bradykinin receptor, a potential regulator of prolactin secretion, were significantly overexpressed in all adenoma subtypes, while C-terminal Src kinase (CSK), an inhibitor of proto-oncogenic enzymes, and annexin II, a calcium-dependent binding protein, were significantly underexpressed in all adenoma subtypes. The immunohistochemical analysis confirmed the overexpression of HSP110 and B2 bradykinin receptor and underexpression of CSK and annexin II in pituitary adenoma cells when compared with their corresponding normal pituitary cells. Western blotting only partially confirmed the proteomics data: HSP110 was significantly overexpressed in prolactinomas and NFPAs, the B2 bradykinin receptor was significantly overexpressed in prolactinomas, annexin II was significantly underexpressed in somatotrophinomas, while CSK did not show significant underexpression in any tumour. Protein expression analysis of pituitary samples disclosed both novel proteins and putative protein candidates for pituitary tumorigenesis, though validation using

  10. Pituitary tumor

    MedlinePlus

    ... visual field loss, drooping eyelids or changes in color vision Headache Lack of energy Nasal drainage of clear fluid Nausea and vomiting Problems with the sense of smell In rare cases, these symptoms occur suddenly and can be severe ( pituitary apoplexy ).

  11. A decade of pituitary microsurgery. The Herbert Olivecrona lecture.

    PubMed

    Wilson, C B

    1984-11-01

    The author reviews his experience with surgical treatment of 1000 pituitary tumors, the majority of which were endocrine-active. The criteria of grading, the microsurgical technique used, and the postoperative results are presented. The mortality rate was 0.2% overall, with no deaths in the group of 774 patients with endocrine-active adenomas. PMID:6092567

  12. 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

  13. Magnetic Resonance Imaging of Pituitary Tumors.

    PubMed

    Bonneville, Jean-François

    2016-01-01

    Magnetic Resonance Imaging (MRI) is currently considered a major keystone of the diagnosis of diseases of the hypothalamic-hypophyseal region. However, the relatively small size of the pituitary gland, its location deep at the skull base and the numerous physiological variants present in this area impede the precise assessment of the anatomical structures and, particularly, of the pituitary gland itself. The diagnosis of the often tiny lesions of this region--such as pituitary microadenomas--is then difficult if the MRI technology is not optimized and if potential artifacts and traps are not recognized. Advanced MRI technology can not only depict small lesions with greater reliability, but also help in the differential diagnosis of large tumors. In these, defining the presence or absence of invasion is a particularly important task. This review describes and illustrates the radiological diagnosis of the different tumors of the sellar region, from the common prolactinomas, nonfunctioning adenomas and Rathke's cleft cysts, to the less frequent and more difficult to detect corticotroph pituitary adenomas in Cushing's disease, and other neoplastic and nonneoplastic entities. Finally, some hints are given to facilitate the differential diagnosis of sellar lesions. PMID:27003878

  14. 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

  15. Silencing of RASSF3 by DNA Hypermethylation Is Associated with Tumorigenesis in Somatotroph Adenomas

    PubMed Central

    Zhao, Shuwei; Wu, Jian; Fan, Jingping; Liao, Jianchun

    2013-01-01

    The pathogenic mechanisms underlying pituitary somatotroph adenoma formation, progression are poorly understood. To identify candidate tumor suppressor genes involved in pituitary somatotroph adenoma tumorigenesis, we used HG18 CpG plus Promoter Microarray in 27 human somatotroph adenomas and 4 normal human adenohypophyses. RASSF3 was found with frequent methylation of CpG island in its promoter region in somatotroph adenomas but rarely in adenohypophyses. This result was confirmed by pyrosequencing analysis. We also found that RASSF3 mRNA level correlated negatively to its gene promoter methylation level. RASSF3 hypermethylation and downregulation was also observed in rat GH3 and mouse GT1.1 somatotroph adenoma cell lines. 5-Aza-2′ deoxycytidine and trichostatin-A treatment induced RASSF3 promoter demethylation, and restored its expression in GH3 and GT1.1 cell lines. RASSF3 overexpression in GH3 and GT1.1 cells inhibited proliferation, induced apoptosis accompanied by increased Bax, p53, and caspase-3 protein and decreased Bcl-2 protein expression. We also found that the antitumor effect of RASSF3 was p53 dependent, and p53 knockdown blocked RASSF3-induced apoptosis and growth inhibition. Taken together, our results suggest that hypermethylation-induced RASSF3 silencing plays an important role in the tumorigenesis of pituitary somatotroph adenomas. PMID:23555615

  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. Interferon-alpha stimulates the hypothalamic-pituitary-adrenal axis in vivo and in vitro.

    PubMed

    Gisslinger, H; Svoboda, T; Clodi, M; Gilly, B; Ludwig, H; Havelec, L; Luger, A

    1993-03-01

    The successful therapeutic use of interferon-alpha (IFN-alpha) in myeloproliferative disorders offered the possibility to test its acute and long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis in humans. ACTH and cortisol plasma concentrations were measured in 8 patients hourly starting from 4 p.m. through 12 p.m. on three occasions. The first time all patients were studied before initiation of therapy, when the vehicle was injected alone. The patients were studied again on day 1 of IFN-alpha therapy (5 million units) and once more after 3 weeks of therapy. On the control day, plasma concentrations of ACTH and cortisol were in the range expected for this time of day. In contrast, after the first administration of IFN-alpha a significant stimulation of the HPA axis was observed. After 3 weeks of IFN-alpha therapy, no significant stimulation of the HPA axis occurred after administration of IFN-alpha. IFN-alpha-induced adaptive changes in the HPA axis were also indicated by a significantly enhanced ACTH and cortisol response to exogenously administered supramaximal doses of corticotropin-releasing hormone (CRH) when the patients had been on IFN-alpha treatment for 3 weeks. To determine the exact locus of the IFN-alpha action, in vitro experiments were performed using rat hypothalamic organ and primary pituitary and adrenal cell culture systems. Thereby a significant stimulation of hypothalamic CRH secretion and rat adrenal corticosterone production was observed after INF-alpha at concentrations of 5 x 10(-8) M or 10(-7) M respectively. In contrast, no direct IFN-alpha effect on pituitary ACTH secretion could be observed in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Effects of beacon on the rat pituitary-adrenocortical axis response to stress.

    PubMed

    Rucinski, Marcin; Spinazzi, Raffaella; Ziolkowska, Agnieszka; Nussdorfer, Gastone G; Malendowicz, Ludwik K

    2005-08-01

    Beacon is a peptide expressed in the rat hypothalamus and adrenal cortex, which is involved in the central regulation of feeding and inhibits basal and agonist-stimulated glucocorticoid secretion from adrenocortical cells. In vivo studies on beacon have not yet been carried out, and therefore we investigated the effects of a subcutaneous (sc) injection of beacon on the response of rat hypothalamo-pituitary-adrenal axis to stress. Handling and sc injection per se elicited a moderate increase in the plasma concentrations of ACTH and corticosterone, which was counteracted by beacon. Similarly, beacon dampened ACTH and corticosterone responses to ether stress. In contrast, beacon did not affect ACTH response to cold stress, although it was able to induce a moderate lowering in the corticosterone response. Taken together, these findings allow us to draw the following conclusions: i) beacon inhibits handling/injection- and ether stress-activated, but not cold stress-activated, neural mechanism(s) responsible for stimulation of ACTH secretion and the ensuing increase in corticosterone production; and ii) the beacon-induced dampening in corticosterone response to stress also involves a direct inhibitory effect on the adrenal-cortex secretory activity. The physiological relevance of beacon as endogenous anti-stress agent remains to be evaluated.

  19. Silent corticotroph adenoma with adrenal cortical choristoma: a rare but distinct morphological entity.

    PubMed

    Mete, Ozgur; Ng, Thomas; Christie-David, Darshika; McMaster, Jacqueline; Asa, Sylvia L

    2013-09-01

    This report describes a case of pituitary adenoma with interspersed adrenal cortical cells. The pituitary cells were confirmed to be corticotrophs with Tpit and adrenocorticotropic hormone immunohistochemistry, whereas the adrenal cortical cells were verified to be such with steroidogenic factor-1 (SF-1), inhibin, calretinin, and Melan A staining. The presence of normal adrenal cortical cells in the heterotopic location of the sella fulfills the definition of choristoma. The origin of adrenal cortical cells within a pituitary adenoma remains unexplained. The important role of SF-1 in both pituitary and adrenal cortex may explain a relationship that supports the possibility of an abnormal proliferation and differentiation of uncommitted mesenchymal stem cells within the sella. However, it remains possible that misplaced adrenal cortical cells derived during embryogenesis give rise to this rare but distinct morphological entity that can pose a difficult diagnostic dilemma. The approach to differential diagnosis is discussed.

  20. 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

  1. Pituitary tumours: acromegaly.

    PubMed

    Chanson, Philippe; Salenave, Sylvie; Kamenicky, Peter; Cazabat, Laure; Young, Jacques

    2009-10-01

    Excessive production of the growth hormone (GH) is responsible for acromegaly. It is related to a pituitary GH-secreting adenoma in most cases. Prevalence is estimated 40-130 per million inhabitants. It is characterised by slowly progressive acquired somatic disfigurement (mainly involving the face and extremities) and systemic manifestations. The rheumatologic, cardiovascular, respiratory and metabolic consequences determine its prognosis. The diagnosis is confirmed by an increased serum GH concentration, unsuppressible by an oral glucose load and by detection of increased levels of insulin-like growth factor-I (IGF-I). Treatment is aimed at correcting (or preventing) tumour compression by excising the disease-causing lesion, and at reducing GH and IGF-I levels to normal values. When surgery, the usual first-line treatment, fails to correct GH/IGF-I hypersecretion, medical treatment with somatostatin analogues and/or radiotherapy can be used. The GH-receptor antagonist (pegvisomant) is helpful in patients who are resistant to somatostatin analogues. Thanks to this multistep therapeutic strategy, adequate hormonal disease control is achieved in most cases, allowing a normal life expectancy. PMID:19945023

  2. Somatostatin-14 and somatostatin-28 pretreatment down-regulate somatostatin-14 receptors and have biphasic effects on forskolin-stimulated cyclic adenosine, 3',5'-monophosphate synthesis and adrenocorticotropin secretion in mouse anterior pituitary tumor cells.

    PubMed

    Heisler, S; Srikant, C B

    1985-07-01

    Activation of somatostatin-14 (S-14) receptors on mouse AtT-20 pituitary tumor cells by S-14 or somatostatin-28 (S-28) inhibits forskolin-stimulated cAMP synthesis and ACTH secretion. In this study, the effects of prolonged exposure of cells to S-14 or S-28 was found to reduce, in a time- and concentration-dependent fashion, the density of S-14 receptors without affecting the affinity of these sites for [125I]Tyr11-S-14. This response was rapidly reversible after removal of peptide from incubation media. Additionally, S-14 and S-28 pretreatment also resulted in a time-dependent sensitizing effect on forskolin-stimulated cAMP formation and ACTH secretion which preceded S-14 receptor down-regulation. Enhancement of the forskolin response was concentration dependent, with maximal effects observed at 10(-8) M with either peptide. Higher pretreatment concentrations of S-14 resulted in an abolition of the enhanced biological response to forskolin; pretreatment with S-28 (10(-6) M) depressed forskolin- and (-)isoproterenol-induced cAMP formation below levels observed in nonpretreated cells. The enhancing effect of S-14 and S-28 required new protein synthesis, since it was partially blocked by cycloheximide; the depressor effect was independent of new protein synthesis. Both the enhanced and depressed forskolin responses after peptide pretreatment were reversible after withdrawal of S-14 or S-28; normalization of the forskolin response (cAMP formation and ACTH secretion) followed the return to control levels of S-14 receptor density. Pretreatment of cells with 10(-8) M or 10(-6) M S-28 increased and decreased, respectively, the ACTH secretory response to agonists which act in the absence of prior cAMP synthesis such as 8-bromo-cAMP, A-23187, and phorbol ester. The data suggest that S-14 receptor down-regulation is not causally associated with the sensitizing effects of S-14 and S-28 on adenylate cyclase and that the S-14 receptor may be also coupled to other effector

  3. Recurrent gain-of-function USP8 mutations in Cushing's disease.

    PubMed

    Ma, Zeng-Yi; Song, Zhi-Jian; Chen, Jian-Hua; Wang, Yong-Fei; Li, Shi-Qi; Zhou, Liang-Fu; Mao, Ying; Li, Yi-Ming; Hu, Rong-Gui; Zhang, Zhao-Yun; Ye, Hong-Ying; Shen, Ming; Shou, Xue-Fei; Li, Zhi-Qiang; Peng, Hong; Wang, Qing-Zhong; Zhou, Dai-Zhan; Qin, Xiao-Lan; Ji, Jue; Zheng, Jie; Chen, Hong; Wang, Yin; Geng, Dao-Ying; Tang, Wei-Jun; Fu, Chao-Wei; Shi, Zhi-Feng; Zhang, Yi-Chao; Ye, Zhao; He, Wen-Qiang; Zhang, Qi-Lin; Tang, Qi-Sheng; Xie, Rong; Shen, Jia-Wei; Wen, Zu-Jia; Zhou, Juan; Wang, Tao; Huang, Shan; Qiu, Hui-Jia; Qiao, Ni-Dan; Zhang, Yi; Pan, Li; Bao, Wei-Min; Liu, Ying-Chao; Huang, Chuan-Xin; Shi, Yong-Yong; Zhao, Yao

    2015-03-01

    Cushing's disease, also known as adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (PAs) that cause excess cortisol production, accounts for up to 85% of corticotrophin-dependent Cushing's syndrome cases. However, the genetic alterations in this disease are unclear. Here, we performed whole-exome sequencing of DNA derived from 12 ACTH-secreting PAs and matched blood samples, which revealed three types of somatic mutations in a candidate gene, USP8 (encoding ubiquitin-specific protease 8), exclusively in exon 14 in 8 of 12 ACTH-secreting PAs. We further evaluated somatic USP8 mutations in additional 258 PAs by Sanger sequencing. Targeted sequencing further identified a total of 17 types of USP8 variants in 67 of 108 ACTH-secreting PAs (62.04%). However, none of these mutations was detected in other types of PAs (n = 150). These mutations aggregate within the 14-3-3 binding motif of USP8 and disrupt the interaction between USP8 and 14-3-3 protein, resulting in an elevated capacity to protect EGFR from lysosomal degradation. Accordingly, PAs with mutated USP8 display a higher incidence of EGFR expression, elevated EGFR protein abundance and mRNA expression levels of POMC, which encodes the precursor of ACTH. PAs with mutated USP8 are significantly smaller in size and have higher ACTH production than wild-type PAs. In surgically resected primary USP8-mutated tumor cells, USP8 knockdown or blocking EGFR effectively attenuates ACTH secretion. Taken together, somatic gain-of-function USP8 mutations are common and contribute to ACTH overproduction in Cushing's disease. Inhibition of USP8 or EGFR is promising for treating USP8-mutated corticotrophin adenoma. Our study highlights the potentially functional mutated gene in Cushing's disease and provides insights into the therapeutics of this disease.

  4. 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 ...

  5. Idiopathic Granulomatous Hypophysitis Mimicking Pituitary Abscess

    PubMed Central

    Kong, Xiangyi; Wang, Renzhi; Yang, Yi; Wu, Huanwen; Su, Changbao; Ma, Wenbin; Li, Yongning; Xing, Bing; Lian, Wei; Xu, Zhiqin; Yao, Yong; Ren, Zuyuan

    2015-01-01

    Abstract Idiopathic granulomatous hypophysitis (IGH) is a rare inflammatory disease of the pituitary that commonly presents with enlargement of the pituitary gland. Clinically and radiologically, IGH is a rare sellar entity easily to be misdiagnosed as a pituitary adenoma. Through such a case, we aim to present this rarity and emphasize the importance to correctly diagnose confusing pituitary lesions comprehensively by clinical presentations, radiological signs, and biopsy. We present an uncommon case of IGH in a 19-year-old man. The patient was admitted to the hospital with severe headache, vomiting, and vision's sharp decline. Magnetic resonance imaging showed a sellar lesion with obvious cystic change and ring enhancement. The disease course including diagnosis and treatment was presented and analyzed in detail. The pertinent literature is reviewed regarding this uncommon entity. The patient underwent surgical exploration and partial resection via the transsphenoidal approach. The pathologic findings suggested IGH giving no significant evidences of systemic granulomatous disease and venereal disease. Large dose methylprednisolone was then used. The pituitary function recovered, but there was no apparent improvement of his vision. IGH is a rarely occurred inflammatory disease of unknown etiology. It is difficult to diagnose preoperatively and is often misdiagnosed. Although rare, IGH should be kept in mind in terms of differential diagnosis of sellar region lesions. PMID:26181544

  6. Pituitary tumors: pathophysiology, clinical manifestations and management.

    PubMed

    Arafah, B M; Nasrallah, M P

    2001-12-01

    Pituitary tumors are frequently encountered intracranial neoplasms. They present with a variety of clinical manifestations that include symptoms and signs of excessive hormone secretion by the tumor, signs of hormone deficits by the normal pituitary gland and others related to expansion of the tumor mass and the resulting compression of surrounding structures such as the optic chiasm and cranial nerves. Advances in molecular biology, immunocytochemical staining and imaging, and the introduction of new treatment options have improved our understanding of the natural history of these adenomas and their management. Available treatments include surgical, medical and radiation therapy. Although the primary treatment for each tumor type may vary, it is important to consider all available options and select the most applicable for that patient. The interaction of all members of management team, including the primary care provider, the endocrinologist and the neurosurgeon in selecting the treatment course can only improve therapeutic outcome. Regardless of the initial choice of treatment,follow-up of all patients should be maintained indefinitely. The managing physician should be familiar with the natural history and long-term complications of pituitary adenomas, and with the side effects of treatments given over the years. PMID:11733226

  7. Pituitary Stone or Calcified Pituitary Tumor? Three Cases and Literature Review

    PubMed Central

    Chentli, Farida; Safer-Tabi, Amel

    2015-01-01

    Introduction: Pituitary stone or pituitary calculus is a scientific enigma characterized by a large calcification in the pituitary sella. It can be discovered incidentally or in a patient with endocrine and/or neurological problems. Its mechanism is not understood. In this article, we described three patients harboring a large pituitary calcification. Case Presentation: The first case was observed in a 27-year-old woman who consulted for secondary amenorrhea. The second case concerned a woman who consulted for infertility, and the third one was observed in an 11-year and nine-month-old girl who was sent to our department for short stature. Clinical examination was normal in both adults. The pediatric case had dwarfism with lack of pubertal development. Hormonal assessment showed hyperprolactinemia in both women and thyrotroph and somatotroph deficits in the child. Radiologic exploration discovered pituitary calcifications measuring 10, 11, and 45 mm without any cystic or solid mass. Conclusions: Radiological findings pleaded for a pituitary stone, but calcified adenomas in women, and calcified craniopharyngioma in the pediatric case could not be excluded, as our three patients were not operated on. PMID:26401144

  8. Study to Allow Access to Pasireotide for Patients Benefiting From Pasireotide Treatment in a Novartis-sponsored Study.

    ClinicalTrials.gov

    2016-10-10

    Cushing's Disease,; Acromegaly,; Neuroendocrine Tumors,; Pituitary Tumors; Ectopic ACTH Secreting (EAS) Tumors,; Dumping Syndrome,; Prostate Cancer,; Melanoma Negative for bRAF,; Melanoma Negative for nRAS

  9. 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.

  10. Identification of aromatase activity in rodent pituitary cell strains.

    PubMed

    Callard, G V; Petro, Z; Tashjian, A H

    1983-07-01

    To date, biochemical evidence has been presented for hypophysial aromatization in only one species, a teleost fish, although the pituitary glands of several mammals have been reported to be aromatase negative. To reinvestigate this problem, established clonal strains of rodent pituitary cells (GH3, GH4C1, and AtT20/D16) were incubated at 37 C for 6-48 h in serum-less medium containing [7-3H]androstenedione. Radiolabeled metabolites were isolated by solvent extraction, thin layer chromatography, and phenolic partition. The authenticity of the estrogenic products in both cells and incubation medium was verified by methylation and recrystallization to constant specific activity. Measurement of androgen metabolites was also validated by recrystallization of selected samples. Authentic estrone and 17 beta-estradiol were identified in cultures of the two PRL- and GH-secreting clones, and there were strain differences in the quantity of estrogen produced (GH3 greater than GH4C1). Under the same conditions, aromatization was not detectable in the ACTH-secreting line (AtT20/D16). A time-yield analysis of androgen metabolism in GH4C1 cells showed that aromatization was linear for 12 h after labeling, but that substrate was diverted mainly to 5 alpha-reducing pathways. Large amounts of highly polar metabolites accumulated 24 and 48 h after the addition of [3H]androgen, and subsequent hydrolysis revealed that these were sulfo- and glucuronoconjugates. The metabolic fate of estrogen in GH4C1 cultures was investigated indirectly by adding a radioinert estrone trap together with the radiolabeled androgen substrate and was also tested in separate cultures by adding [3H]estrone and [3H]estradiol directly. Although the two estrogens were interconverted, there was no evidence that formed or added estrogen was extensively metabolized or conjugated. We conclude that the expression of aromatase activity in hypophysial cells is not a property of all transformed lines but may be dictated

  11. Identification of aromatase activity in rodent pituitary cell strains.

    PubMed

    Callard, G V; Petro, Z; Tashjian, A H

    1983-07-01

    To date, biochemical evidence has been presented for hypophysial aromatization in only one species, a teleost fish, although the pituitary glands of several mammals have been reported to be aromatase negative. To reinvestigate this problem, established clonal strains of rodent pituitary cells (GH3, GH4C1, and AtT20/D16) were incubated at 37 C for 6-48 h in serum-less medium containing [7-3H]androstenedione. Radiolabeled metabolites were isolated by solvent extraction, thin layer chromatography, and phenolic partition. The authenticity of the estrogenic products in both cells and incubation medium was verified by methylation and recrystallization to constant specific activity. Measurement of androgen metabolites was also validated by recrystallization of selected samples. Authentic estrone and 17 beta-estradiol were identified in cultures of the two PRL- and GH-secreting clones, and there were strain differences in the quantity of estrogen produced (GH3 greater than GH4C1). Under the same conditions, aromatization was not detectable in the ACTH-secreting line (AtT20/D16). A time-yield analysis of androgen metabolism in GH4C1 cells showed that aromatization was linear for 12 h after labeling, but that substrate was diverted mainly to 5 alpha-reducing pathways. Large amounts of highly polar metabolites accumulated 24 and 48 h after the addition of [3H]androgen, and subsequent hydrolysis revealed that these were sulfo- and glucuronoconjugates. The metabolic fate of estrogen in GH4C1 cultures was investigated indirectly by adding a radioinert estrone trap together with the radiolabeled androgen substrate and was also tested in separate cultures by adding [3H]estrone and [3H]estradiol directly. Although the two estrogens were interconverted, there was no evidence that formed or added estrogen was extensively metabolized or conjugated. We conclude that the expression of aromatase activity in hypophysial cells is not a property of all transformed lines but may be dictated

  12. 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.

  13. 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. PMID:27621108

  14. Pituitary granulomatosis with polyangiitis

    PubMed Central

    Slabu, Hannah; Arnason, Terra

    2013-01-01

    Granulomatosis with polyangiitis (GPA) is a small vessel vasculitis that can affect several organs, most commonly the respiratory tract and kidneys. Pituitary involvement is exceptionally rare. Most case reports of GPA of the pituitary gland have been described in middle-aged women who have concomitant ears, nose and throat involvement. The most frequent manifestation is diabetes insipidus due to a preponderance of posterior pituitary infiltration. The majority of cases sustain permanent damage to the pituitary gland even with remission of the underlying granulomatous disease. Here, the authors describe a case of pituitary GPA involving both the anterior and posterior pituitary glands with permanent residual pituitary insufficiency. PMID:23645699

  15. Pathogenesis of pituitary tumors.

    PubMed

    Yu, Run; Melmed, Shlomo

    2010-01-01

    Pituitary tumors are common and mostly benign neoplasia which cause excess or deficiency of pituitary hormones and compressive damage to adjacent organs. Oncogene activation [e.g. PTTG (pituitary tumor-transforming gene) and HMGA2], tumor suppressor gene inactivation (e.g. MEN1 and PRKAR1A), epigenetic changes (e.g. methylation) and humoral factors (e.g. ectopic production of stimulating hormones) are all possible pituitary tumor initiators; the micro-environment of pituitary tumors including steroid milieu, angiogenesis and abnormal cell adhesion further promote tumor growth. Senescence, a cellular defence mechanism against malignant transformation, may explain the benign nature of at least some pituitary tumors. We suggest that future research on pituitary tumor pathogenesis should incorporate systems approaches, and address regulatory mechanisms for pituitary cell proliferation, development of new animal models of pituitary tumor and isolation of functional human pituitary tumor cell lines. PMID:20541667

  16. Identification of stimulatory and inhibitory inputs to the hypothalamic-pituitary-adrenal axis during hypoglycaemia or transport in ewes.

    PubMed

    Smith, R F; French, N P; Saphier, P W; Lowry, P J; Veldhuis, J D; Dobson, H

    2003-06-01

    This study used the novel approach of statistical modelling to investigate the control of hypothalamic-pituitary-adrenal (HPA) axis and quantify temporal relationships between hormones. Two experimental paradigms were chosen, insulin-induced hypoglycaemia and 2 h transport, to assess differences in control between noncognitive and cognitive stimuli. Vasopressin and corticotropin-releasing hormone (CRH) were measured in hypophysial portal plasma, and adrenocorticotropin hormone (ACTH) and cortisol in jugular plasma of conscious sheep, and deconvolution analysis was used to calculate secretory rates, before modelling. During hypoglycaemia, the relationship between plasma glucose and vasopressin or CRH was best described by log10 transforming variables (i.e. a positive power-curve relationship). A negative-feedback relationship with log10 cortisol concentration 2 h previously was detected. Analysis of the "transport" stimulus suggested that the strength of the perceived stimulus decreased over time after accounting for cortisol facilitation and negative-feedback. The time course of vasopressin and CRH responses to each stimulus were different However, at the pituitary level, the data suggested that log10 ACTH secretion rate was related to log10 vasopressin and CRH concentrations with very similar regression coefficients and an identical ratio of actions (2.3 : 1) for both stimuli. Similar magnitude negative-feedback effects of log10 cortisol at -110 min (hypoglycaemia) or -40 min (transport) were detected, and both models contained a stimulatory relationship with cortisol at 0 min (facilitation). At adrenal gland level, cortisol secretory rates were related to simultaneously measured untransformed ACTH concentration but the regression coefficient for the hypoglycaemia model was 2.5-fold greater than for transport. No individual sustained maximum cortisol secretion for longer than 20 min during hypoglycaemia and 40 min during transport. These unique models demonstrate

  17. The role of oestradiol in sexually dimorphic hypothalamic-pituitary-adrena axis responses to intracerebroventricular ethanol administration in the rat.

    PubMed

    Larkin, J W; Binks, S L; Li, Y; Selvage, D

    2010-01-01

    Systemic ethanol (EtOH) administration activates the hypothalamic-pituitary-adrenal (HPA) axis of rats in a sexually dimorphic manner. The present studies tested the role played by the central nervous system (CNS) in this phenomenon. To localise the effects of the drug to the brain, we utilised an experimental paradigm whereby a small, nontoxic amount of the drug was delivered via intracerebroventricular (i.c.v.) injection. EtoH administered i.c.v. rapidly diffuses throughout the cerebrospinal fluid and brain, and does not cause neuronal damage or have any long-term physiological or behavioural effects. Experimental groups included intact males, intact cycling females, and ovariectomised (OVX) animals with or without replacement oestradiol (E(2)). Intracerebroventricular EtOH-induced HPA hormonal activation was determined by measuring plasma adrenocorticotrophin (ACTH) levels. Activation of brain areas that both regulate HPA function and are responsive to gonadal hormones was determined using expression of the transcription factor c-fos (Fos) as a marker of neuronal activity. We observed sex- and oestrous cycle- dependent differences in HPA activation by EtOH as measured by both these parameters. ACTH secretion was highest in females in pro-oestrus or oestrus, just prior to or after the endogenous peak of E(2), as was Fos expression in the paraventricular nucleus of the hypothalamus (PVN) and the locus coreuleus (LC) of the brainstem. In OVX animals, E(2) replacement caused an increase in PVN and LC Fos expression in response to i.c.v. EtOH compared to OVX controls, but a decrease in ACTH secretion. Taken together, these results indicate that at the level of the CNS, EtOH stimulates HPA activity more robustly at times when the effects of E(2) are high, but that E(2) alone is not responsible for this effect. The data further suggest that the LC plays an important role in the circuitry, which appears to be different from that activated following the systemic

  18. Is IGSF1 involved in human pituitary tumor formation?

    PubMed

    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

    2015-02-01

    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 the sections of GH-producing adenomas, familial somatomammotroph hyperplasia, and in normal pituitary. We identified the sequence variant p.N604T, which in silico analysis suggested could affect IGSF1 function, in two male patients and one female with somatomammotroph hyperplasia from the same family. Of 60 female controls, two carried the same variant and seven were heterozygous for other variants. Immunohistochemistry showed increased IGSF1 staining in the GH-producing tumor from the patient with the IGSF1 p.N604T variant compared with a GH-producing adenoma from a patient negative for any IGSF1 variants and with 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.

  19. 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

  20. Dissociated hypopituitarism after spontaneous pituitary apoplexy in acromegaly

    PubMed Central

    Mir, Shahnaz Ahmad; Masoodi, Shariq Rashid; Bashir, Mir Iftikhar; Wani, Arshad Iqbal; Farooqui, Khalid Jamal; Kanth, Basharat; Bhat, Abdul Rashid

    2013-01-01

    Introduction: Pituitary apoplexy is an uncommon event and usually occurs in non-functioning pituitary tumors. Among the functioning tumors, prolactinomas are the ones most likely to apoplexy. Apoplexy in growth hormone (GH) producing adenomas is a very rare event with less than thirty cases reported worldwide. Objective: To describe a case of spontaneous pituitary apoplexy in acromegaly. Case Report: A 55 year old smoker male presented to the our outpatient clinic in 2004 with complaints of gradual onset increase in the size of hands and feet, bilateral knee pain, increased sweating and blurring of vision. Investigations uncovered diabetes mellitus by a casual blood glucose of 243 mg/dl and HbA1c of 8.5%. Growth hormone suppression test using 75 gram oral glucose showed a 60 minute growth hormone of 105 ng/ml. Magnetic resonance imaging of the sellar region showed a 12.0 mm × 10.0 mm pituitary adenoma. The patient was planned for transsphenoidal tumor decompression. However, the patient was lost to follow up. Eight-years later, he presented in the emergency department of our institute with sudden onset headache, vomiting and decreased level of consciousness of one day duration. CT scan of the head with focus on the sella was suggestive of apoplexy which was later confirmed by the MRI of the sellar region. Conclusion: Although acromegaly can remit following apoplexy of the responsible pituitary adenoma, long term follow up is needed for early detection of the development of deficiency of pituitary hormones which may occur over years following the event as well as to detect tumor regrowth which again may occur several years later. PMID:24251123

  1. Is IGSF1 involved in human pituitary tumor formation?

    PubMed

    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

    2015-02-01

    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 the sections of GH-producing adenomas, familial somatomammotroph hyperplasia, and in normal pituitary. We identified the sequence variant p.N604T, which in silico analysis suggested could affect IGSF1 function, in two male patients and one female with somatomammotroph hyperplasia from the same family. Of 60 female controls, two carried the same variant and seven were heterozygous for other variants. Immunohistochemistry showed increased IGSF1 staining in the GH-producing tumor from the patient with the IGSF1 p.N604T variant compared with a GH-producing adenoma from a patient negative for any IGSF1 variants and with 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

  2. Cyclic Cushing's disease with misleading inferior petrosal sinus sampling results during a trough phase.

    PubMed

    Bonert, Vivien; Bose, Namrata; Carmichael, John D

    2015-02-01

    Diagnosing Cushing's syndrome is challenging and is further hampered when investigations are performed in a patient with cyclic Cushing's syndrome. A subset of patients with Cushing's syndrome exhibit periods of abnormal cortisol secretion with interspersed normal secretion. Patients can have periods of clinical improvement during these quiescent phases or remain symptomatic. Initial diagnostic testing can be challenging because of the unpredictable durations of the peak and trough phases, and it is especially challenging when the diagnosis of cyclic Cushing's syndrome has not yet been determined. Here, the authors present the case of a patient with Cushing's disease with a pathology-proven adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma and whose initial inferior petrosal sinus sampling (IPSS) results were deemed indeterminate; further studies elucidated the diagnosis of cyclic Cushing's syndrome. Repeat IPSS was diagnostic of a central source for ACTH secretion, and the patient was treated successfully with transsphenoidal resection. Literature concerning the diagnosis and management of cyclic Cushing's syndrome is also reviewed.

  3. 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

  4. Pituitary tumors. Current concepts in diagnosis and management.

    PubMed Central

    Aron, D C; Tyrrell, J B; Wilson, C B

    1995-01-01

    Diagnostic advances have resulted in earlier and more frequent recognition of pituitary tumors. Pituitary tumors cause problems owing to the hormones they secrete or the effects of an expanding sellar mass--hypopituitarism, visual field abnormalities, and neurologic deficits. Prolactin-secreting tumors (prolactinomas), which cause amenorrhea, galactorrhea, and hypogonadism, constitute the most common type of primary pituitary tumors, followed by growth hormone-secreting tumors, which cause acromegaly, and corticotropin-secreting tumors, which cause Cushing's syndrome. Hypersecretion of thyroid-stimulating hormone, the gonadotrophins, or alpha-subunits is unusual. Nonfunctional tumors currently represent only 10% of all clinically diagnosed pituitary adenomas, and some of these are alpha-subunit-secreting adenomas. Insights into the pathogenesis and biologic behavior of these usually benign tumors have been gained from genetic studies. We review some of the recent advances and salient features of the diagnosis and management of pituitary tumors, including biochemical and radiologic diagnosis, transsphenoidal surgery, radiation therapy, and medical therapy. Each type of lesion requires a comprehensive but individualized treatment approach, and regardless of the mode of therapy, careful follow-up is essential. Images PMID:7747500

  5. Pituitary apoplexy syndrome as the manifestation of intracranial tuberculoma

    PubMed Central

    Verma, Rajesh; Patil, Tushar B; Lalla, Rakesh

    2014-01-01

    Pituitary apoplexy syndrome is characterised by acute neuro-ophthalmological features and usually occurs due to bleeding in a pituitary adenoma. It is an unusual presentation of tuberculoma, as only few similar cases have been reported previously. A 17-year-old girl presented with headache, vomiting, altered sensorium and vision loss. MRI of the brain revealed ring enhancing sellar lesions with other enhancing lesions and leptomeningeal enhancement. Cerebrospinal fluid microscopy, biochemistry and PCR for tuberculosis confirmed tubercular meningitis. The patient was treated with antituberculous therapy and was asymptomatic at the end of treatment. PMID:24675800

  6. 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. PMID:25792544

  7. [Endoscopic transsphenoidal resection of pituitary adenomas invading the cavernous sinus].

    PubMed

    Kalinin, P L; Sharipov, O I; Pronin, I N; Kutin, M A; Fomichev, D V; Kadashev, B A; Shkarubo, A N; Alekseev, S N; Astaf'eva, L I; Tropinskaya, O F; Dobrovol'sky, G F; Shul'ts, E I; Andreev, D N; Voronina, I A; Kurnosov, A B

    2016-01-01

    Аденомы гипофиза — доброкачественные новообразования, которые в 10—15% случаев врастают в кавернозный синус (КС). Существуют различные виды микрохирургических и эндоскопических доступов, с помощью которых возможно проводить удаление опухолей из полости КС — сравнительно небольшого и труднодоступного анатомического образования, включающего важные нейроваскулярные структуры. Материал и методы. Исследуемая группа — 97 пациентов с аденомами гипофиза (АГ), которые врастали в КС и были удалены с использованием эндоскопической техники (в 62 случаях АГ из полости КС резецировались из стандартного эндоскопического эндоназального транссфеноидального доступа, в 35 наблюдениях применялся латеральный расширенный транссфеноидальный эндоскопический доступ). Группа сравнения — больные с АГ с латероселлярным распространением, которые оперировались с помощью микрохирургических экстраинтрадурального (n=14) и транссфеноидального (n=149) доступов. Степень инвазии АГ в полость КС в исследуемой группе определялась согласно Knosp Scale. Результаты. В исследуемой группе тотального удаления опухоли удалось достичь в 49 (50,5%) случаях, субтотального в 39 (40,2%), частичного — в 9 (9,3%) наблюдениях. При наличии зрительных расстройств (n=70) улучшение зрения было достигнуто в 41,4% наблюдений. Ухудшение зрения выявлено в 11,4% случаев, не отмечено какой-либо динамики в 47,1% наблюдений. Среди пациентов, которые не имели зрительных нарушений до операции (27,8%), отрицательной динамики в послеоперационном периоде выявлено не было. Появление/нарастание глазодвигательных нарушений в исследуемой группе выявлено в 14 (14,4%) случаях. Гормональная ремиссия заболевания среди пациентов с гормонально-активными АГ в исследуемой группе произошла у 12 (26,7%) пациентов. В исследуемой группе не было случаев назальной ликвореи и менингитов, а также летальных исходов. Заключение. Эндоскопическое эндоназальное транссфеноидальное удаление АГ с распространением в КС является более эффективным и более безопасным способом хирургического лечения в сравнении с микрохирургическими методиками (транссфеноидальный и интра-экстрадуральный доступ). Применение латерального расширенного транссфеноидального эндоскопического доступа позволяет резецировать АГ с массивной инвазией в КС (Grade III и Grade IV по Knosp Scale) с меньшим количеством послеоперационных осложнений по сравнению с экстраинтрадуральным доступом (p<0,05).

  8. Oligodendroglioma occurring after radiation therapy for pituitary adenoma.

    PubMed Central

    Huang, C I; Chiou, W H; Ho, D M

    1987-01-01

    A 38 year old male dentist developed an oligodendroglioma of the left medial temporal lobe and parasellar region 12 years after radiotherapy with 6600 rads of acromegaly. The 30 cases of radiation-induced gliomas reported in the English literature are reviewed and analysed. The criteria for defining radiation-induced tumours of the central nervous system are proposed as follows: the tumour has a long quiescent "latency period", a location in the previously irradiated field, a verified histological difference from a primary condition, and does not arise from a primary condition associated with a genetic syndrome such as neurofibromatosis or tuberous sclerosis. The reported case fulfilled these criteria but appears to be the only reported radiation-induced oligodendroglioma. Images PMID:3325615

  9. 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

  10. Giant intrathyroidal parathyroid adenoma

    PubMed Central

    Vilallonga, Ramon; Zafón, Carlos; Migone, Raul; Baena, Juan Antonio

    2012-01-01

    Primary hyperparathyroidism (PHPT) is not an uncommon endocrine disorder. However, acute primary hyperparathyroidism, or parathyroid crisis (PC), is a rare clinical entity characterized by life-threatening hypercalcemia of a sudden onset in patients with PHPT. We describe a patient with PC who presented with acute worsening of depressive symptoms, nausea and vomiting, and required emergency surgery. Serum calcium, alkaline phosphatase, and parathyroid hormone were elevated and serum phosphorus was low. An emergency hemithyroidectomy was performed because of none medical control of hypercalcemia. A giant intrathyroidal parathyroid adenoma was diagnosed. PHTP can be a life-threatening situation for patients, requiring immediate surgical treatment. A giant intrathyroidal parathyroid adenoma is an uncommon cause of PC. PMID:22787355

  11. Tubuloalveolar adenoma of salivary gland.

    PubMed

    Pulitzer, D R; Reed, R J; Megehee, J A

    1985-06-01

    An unusual monomorphic salivary gland adenoma, occurring in a 57-year-old woman, is described. The lesion was histologically similar to the so-called tubular adenoma; however, occasional microscopic foci of serous (acinar cell) differentiation were present. The term tubuloalveolar adenoma is proposed to describe salivary gland tumors that are histologically benign and composed of cells resembling those of normal intercalated ducts and secretory units (acini).

  12. Pleomorphic adenoma of the palate.

    PubMed

    Erdem, Mehmet Ali; Cankaya, Abdulkadir Burak; Güven, Gülşah; Olgaç, Vakur; Kasapoğlu, Cetin

    2011-05-01

    Pleomorphic adenoma is the most common mixed benign tumor of major salivary glands. Approximately 80% of these tumors arise in the parotid gland, whereas 7% arise in the minor salivary glands. The most common sites for minor salivary gland where pleomorphic adenoma arises are the palates followed by lips and cheek. We report a palate mass in a 46-year-old male patient. The initial cytologic diagnosis by fine-needle aspiration biopsy was pleomorphic adenoma. This report describes a case of pleomorphic adenoma regarding all distinctive diagnoses with the review of the literature.

  13. Canalicular adenoma of the palate.

    PubMed

    Yüce, Salim; Uysal, Ismail Önder; Doğan, Mansur; Ersin, Tuncer; Müderris, Suphi

    2012-09-01

    Canalicular adenomas are uncommon, benign epithelial neoplasm of the salivary glands that usually involve the upper lip and the buccal mucosa of elderly people. Differential diagnosis of the canalicular adenoma versus adenocarcinoma is important because it may result in unjustified radiotherapy or extensive and aggressive surgery. Despite the benign nature of canalicular adenomas, complete surgical removal and a regular clinical follow-up are recommended. The current study describes the diagnostic procedures, surgical management, and follow-up of a canalicular adenoma involving the palate of a 79-year-old man.

  14. 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

  15. Pleomorphic adenoma of the epiglottis.

    PubMed

    Baptista, P M; Garcia-Tapia, R; Vazquez, J J

    1992-10-01

    Pleomorphic adenoma is the most common benign tumor of the major salivary glands. A pleomorphic adenoma in the larynx constitutes a rarity. A small number of cases have been reported in the literature. We report on a case seen in our hospital, and have reviewed those cases published in the medical literature during the last 25 years.

  16. Prostatic adenoma of ductal origin.

    PubMed

    Min, K W; Gyorkey, F

    1980-07-01

    A case of prostatic adenoma believed to originate from the prostatic duct is described. There were morphologic similarities to basal cell adenomas of salivary glands, and it was concluded that the tumor is a benign counterpart of "salivary gland" carcinomas, rarely observed in the prostate.

  17. Characterization of the Hypothalamic-Pituitary-Adrenal-Axis in Familial Longevity under Resting Conditions

    PubMed Central

    Jansen, Steffy W.; Roelfsema, Ferdinand; Akintola, Abimbola A.; Oei, Nicole Y.; Cobbaert, Christa M.; Ballieux, Bart E.; van der Grond, Jeroen; Westendorp, Rudi G.; Pijl, Hanno; van Heemst, Diana

    2015-01-01

    Objective The hypothalamic-pituitary-adrenal (HPA)-axis is the most important neuro-endocrine stress response system of our body which is of critical importance for survival. Disturbances in HPA-axis activity have been associated with adverse metabolic and cognitive changes. Humans enriched for longevity have less metabolic and cognitive disturbances and therefore diminished activity of the HPA axis may be a potential candidate mechanism underlying healthy familial longevity. Here, we compared 24-h plasma ACTH and serum cortisol concentration profiles and different aspects of the regulation of the HPA-axis in offspring from long-lived siblings, who are enriched for familial longevity and age-matched controls. Design Case-control study within the Leiden Longevity study cohort consisting of 20 middle-aged offspring of nonagenarian siblings (offspring) together with 18 partners (controls). Methods During 24 h, venous blood was sampled every 10 minutes for determination of circulatory ACTH and cortisol concentrations. Deconvolution analysis, cross approximate entropy analysis and ACTH-cortisol-dose response modeling were used to assess, respectively, ACTH and cortisol secretion parameters, feedforward and feedback synchrony and adrenal gland ACTH responsivity. Results Mean (95% Confidence Interval) basal ACTH secretion was higher in male offspring compared to male controls (645 (324-1286) ngl/L/24 h versus 240 (120-477) ng/L/24 h, P = 0.05). Other ACTH and cortisol secretion parameters did not differ between offspring and controls. In addition, no significant differences in feedforward and feedback synchrony and adrenal gland ACTH responsivity were observed between groups. Conclusions These results suggest that familial longevity is not associated with major differences in HPA-axis activity under resting conditions, although modest, sex-specific differences may exist between groups that might be clinically relevant. PMID:26193655

  18. 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

  19. Pleomorphic adenoma of the palate.

    PubMed

    Clauser, Luigi; Mandrioli, Stefano; Dallera, Vittorio; Sarti, Elisabetta; Galiè, Manilio; Cavazzini, Luigi

    2004-11-01

    Pleomorphic adenoma, is the most common tumor (50%) of the major and minor salivary glands. Seventy percent of the tumors of the minor salivary glands are pleomorphic adenomas, and the most common intraoral site is the palate, followed by the upper lip and buccal mucosa. Pleomorphic adenoma appears as a painless firm mass and, in most cases, does not cause ulceration of the overlying mucosa. Generally it is mobile, except when it occurs in the hard palate. Intraoral mixed tumors, especially those noted within the palate, lack a well-defined capsule. Lesions of the palate frequently involve periosteum or bone. Approximately 25% of benign mixed tumors undergo malignant transformation. Treatment for the pleomorphic adenoma is radical surgery. Inadequate resection leads to local recurrence. The authors report a palate pleomorphic adenoma in a 67-year-old female patient.

  20. Hepatocellular adenoma: An update.

    PubMed

    Vijay, Adarsh; Elaffandi, Ahmed; Khalaf, Hatem

    2015-11-01

    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.

  1. Human pituitary tissue secretes a potent growth factor for chondrocyte proliferation.

    PubMed

    Kasper, S; Friesen, H G

    1986-01-01

    We report the secretion from human pituitary tumor fragments in organ culture of a potent mitogen for chondrocyte proliferation. Primary human pituitary cell and organ cultures were established from pituitary fragments obtained from patients with acromegaly, prolactinomas, and nonfunctional adenomas. The conditioned culture medium contained a mitogenic factor(s) that stimulated rabbit fetal chondrocyte proliferation, causing up to an 8-fold increase in cell number when added to Ham's F-10 medium in the presence of 10% fetal bovine serum. Blood leaking into the surgical field after the adenomectomy is known to contain very high concentrations of pituitary hormones. Serum samples, obtained from this venous "ooze" collected at the site of pituitary surgery, also were found to contain chondrocyte growth-promoting activity. Some venous serum samples stimulated chondrocyte proliferation in a dose-dependent manner down to a 1:10 dilution of 1 microliter serum, indicating that the material being secreted was very potent indeed. Gel filtration on Sephadex G-100 and analytical gel isoelectric focusing of culture media or serum samples from the pituitary fossa demonstrated that the growth factor secreted from the pituitary tumor fragments as well as from the venous serum is similar, if not identical, to chondrocyte growth factor (mol wt, 43,000; pI 7.6-7.9) purified from human pituitaries collected at autopsy. These results suggest that the chondrocyte growth-promoting factor(s) may not only be secreted by pituitary tumor fragments but by normal human pituitary tissue as well.

  2. Reevaluation of conventional pituitary irradiation in the therapy of acromegaly.

    PubMed

    Jaffe, C A

    1999-06-01

    External beam pituitary irradiation has been frequently used in the treatment of growth hormone (GH) secreting pituitary adenomas. Many studies have demonstrated that serum GH declines rapidly and reliably following treatment and early "cure" rates, based on a basal serum GH below 10 micrograms/L were as high as 80%. The definition of "cure" has become more stringent over time and retrospective studies have indicated that GH must be below 2.5 micrograms/L for acromegalics to achieve mortality rates comparable to a normal population. Only 20% of irradiated patients will achieve this goal by 10 yr. Even fewer will achieve a normal serum insulin-like growth factor I (IGF-I) levels. Although pituitary irradiation still has a role in the control of tumor size, its importance as a treatment for normalizing serum GH is being reevaluated. PMID:11081173

  3. Parallel stimulation of ACTH, beta-LPH + beta-endorphin and alpha-MSH release by alpha-adrenergic agents in rat anterior pituitary cells in culture.

    PubMed

    Raymond, V; Lépine, J; Giguère, V; Lissitzky, J C; Côté, J; Labrie, F

    1981-06-01

    Characteristics of the alpha-adrenergic stimulation of ACTH, beta-endorphin + beta-LPH and alpha-MSH release were studied in rat anterior pituitary cells in primary culture. Parallel changes of ACTH, beta-endorphin + beta-LPH and alpha-MSh release were found under all stimulatory and inhibitory conditions by natural and synthetic catecholamine agonists and antagonists. (-)Epinephrine and (-)norepinephrine lead to a 8--10-fold stimulation of peptide release at ED50 values of 20 and 90 nM, respectively. The stereoselectivity of the alpha-adrenergic stimulatory action on peptide release is indicated by a 100-fold higher activity of (-)- than (+)norepinephrine while (-)epinephrine is 10 times more potent than the corresponding (+) stereoisomer. The involvement of a typical alpha-adrenergic mechanism in the control of release of ACTH, beta-endorphin and related peptides in rat anterior pituitary gland is indicated by the following order of potency of a series of catecholaminergic agents (ED50 values): (-)epinephrine (20 nM) greater than (-)norepinephrine (90 nm) greater than phenylephrine (400 nM) greater than isoproterenol (6000 nM). The stimulatory effect of (-)epinephrine or phenylephrine is completely reversed by low concentrations of the alpha-adrenergic antagonist phentolamine while the beta-adrenergic antagonist propranolol has no effect up to 10 muM. Beside providing an easily accessible pure population of post-synaptic alpha-adrenergic receptors having potential applications as a model for other less accessible alpha-adrenergic brain systems, the present data suggest the possibility of the direct involvement of a catecholamine in the physiological control of ACTH secretion in the rat anterior pituitary gland.

  4. The use of the terms monomorphic adenoma, basal cell adenoma, and canalicular adenoma as applied to salivary gland tumors.

    PubMed

    Gardner, D G; Daley, T D

    1983-12-01

    There is considerable confusion in the literature concerning the terms monomorphic adenoma, basal cell adenoma, and canalicular adenoma. This article traces the history of these terms as applied to the pathology of salivary gland tumors and attempts to clarify their usage. It is recommended (1) that monomorphic adenoma be used, as it was originally intended, as a nosologic grouping for all benign epithelial salivary gland tumors that are not pleomorphic adenomas, (2) that basal cell adenoma be used to identify a specific entity that is one component of the monomorphic adenoma group and exhibits a number of histologic subtypes, and (3) that canalicular adenoma be used to describe another entity, distinct from basal cell adenomas but also belonging to the monomorphic adenoma group.

  5. Clinical significance of screening for subclinical Cushing's disease in patients with pituitary tumors.

    PubMed

    Tamada, Daisuke; Kitamura, Tetsuhiro; Otsuki, Michio; Oshino, Satoru; Saitoh, Youichi; Shimomura, Iichiro

    2016-01-01

    Cushing's syndrome (CS) is a clinical state caused by chronic excess of glucocorticoid, and results in hypertension, impaired glucose tolerance, and dyslipidemia. Recently, a mild state of pituitary CS without typical Cushingoid appearance (subclinical Cushing's disease; SCD) has been identified. However, the true prevalence of SCD and its effect on metabolic disorders remain obscure. The aim of this prospective study was to determine the prevalence of SCD according to the guideline proposed by the working group of the Japanese Ministry of Health, Welfare and Labor, and to assess the outcome of surgery on metabolic disorders. The prevalence of SCD was investigated in 105 consecutive patients diagnosed with pituitary adenomas by MRI. ACTH-dependent hypercortisolism was diagnosed based on the results of the 0.5 mg dexamethasone suppression test (serum cortisol >3.0 μg/dL) plus one positive finding of the following two tests: midnight serum cortisol level >5.0 μg/dL or ACTH increase >50% after 1-deamino-5-D-arginine vasopressin (DDAVP) challenge. The final diagnosis of SCD was established by positive staining for ACTH in surgically-excised pituitary adenoma. Three patients (4.8%) were diagnosed with SCD among 62 patients with pituitary adenoma. Transsphenoidal adenomectomy partially resulted in improvement of blood pressure and glucose metabolism in SCD patients. Our results emphasize the importance of SCD screening in patients with pituitary tumors, especially in those patients with metabolic disorders.

  6. Adrenocorticotropin (ACTH) and corticosterone secretion by perifused pituitary and adrenal glands from rodents exposed to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD).

    PubMed

    Pitt, J A; Buckalew, A R; House, D E; Abbott, B D

    2000-10-26

    Although in utero maternal stress has been shown to have lasting effects on rodent offspring, fetal effects of chemically-induced alterations of the maternal hypothalamic-pituitary-adrenal axis (HPA) have not been well studied. This study examined the effects of in vivo 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on pituitary-adrenal function in the male rat, pregnant female rat and pregnant female mouse. The secretion of adrenocorticotropin (ACTH) and corticosterone (CORT) in pituitary and adrenal glands, respectively, was assessed in ex vivo perifusion cultures. Male and pregnant female (gestation day 8) Sprague-Dawley rats were gavaged once with 10 microgram/kg TCDD, pregnant female mice once with 24 microgram/kg TCDD, and euthanized 10 days later. Hemi-pituitary (rat) or whole anterior pituitaries (mice) and right adrenal glands from the same animal were quartered, perifused under baseline and stimulated conditions. In both males and pregnant females, TCDD did not affect corticotropin releasing hormone (CRH)-stimulated ACTH secretion. Neither total pituitary ACTH nor plasma ACTH was altered in either sex or species by TCDD treatment. ACTH-stimulated CORT secretion was not affected by TCDD in either sex or species, and adrenal tissue and plasma CORT levels were unchanged in males and pregnant females by TCDD. However, the plasma ACTH:CORT ratio was decreased about 46% in male rats treated with TCDD. Plasma CORT levels were 23-fold higher and plasma ACTH levels were 1.5-fold higher in pregnant females than in male rats. In male versus female rats, adrenal CORT and anterior pituitary ACTH tissue levels were about 7.5- and 1.75-fold higher and ACTH, respectively. Female mouse adrenal tissue CORT was about 4-fold greater than female rat. The reduced plasma ACTH:CORT ratio in the male rat suggests that TCDD disturbs HPA function. Exposure of male rat to a 5-fold higher dose in earlier studies clearly demonstrated effects of TCDD on male rat HPA. The present

  7. High prevalence rate of pituitary incidentaloma: is it associated with the age-related decline of the sex hormones levels?

    PubMed

    Kastelan, Darko; Korsic, Mirko

    2007-01-01

    Incidental pituitary adenoma is the common finding during brain imaging. According to multistep model of pituitary tumourigenesis genetic alterations provide the initiating event that transforms cells while hormones play a role in promoting cell proliferation. Development of pituitary adenoma in a case of excessive hypophysiotrophic hormones production or reduced feedback suppression by target gland hormones emphasizes the importance of hormonal stimulation in pituitary tumourigenesis. Pituitary hyperplasia has been reported in pregnancy, hypothyroidism and conditions such as CRH or GHRH hypersecretion. Moreover, recent study reported one case of gonadotroph macroadenoma and two cases of gonadotroph cells hyperplasia in patients with Klinefelter syndrome probably due to protracted stimulation of gonadotroph cells because of lack of androgen feedback. Significant changes of the hypothalamic-pituitary-gonadal axis occurred with aging. In females, after menopause, estradiol level decreases by 35-fold and estrone level by 20-fold that results in increased gonadotropins levels. Similarly, FSH, but not LH, level is increased with advancing age in men, too, although the age-related difference in the level is less in comparison with women. Regarding these data, we hypothesised that high prevalence rate of pituitary incidentaloma in the elderly is associated with age-related decline in sex hormones levels and subsequent lack of feedback suppression leading to permanent gonadotrophs stimulation which is the crucial step in the pituitary tumour development. According to previously mentioned multistep model of pituitary tumourigenesis, incidentaloma will develop only in persons with already present intrinsic pituitary cell defects. However, further studies have to answer the questions of whether the incidence of pituitary tumours is more frequent in elderly, whether women with late onset menopause or those taking long-term hormone replacement therapy have lower rate of

  8. Rapid Pituitary Apoplexy Regression: What Is the Time Course of Clot Resolution?

    PubMed Central

    Jackson, Devon L.; Van Gompel, Jamie J.

    2015-01-01

    A 29-year-old male patient with a functioning pituitary macroadenoma is discussed. The pituitary mass was detected by MRI after the patient presented with sudden onset of headache, suggestive of an apoplectic event. The headache resolved with analgesic medications. Within a follow-up period of one week, the pituitary mass had spontaneously regressed to nearly half its original size without any therapy. The patient never reported any visual complaints and displayed no signs of hypopituitarism. Elevated prolactin levels were present. Seven weeks after the initial event, the pituitary mass showed continued regression on MRI. Prolactin levels remained elevated. This case provides a unique look at the rapid spontaneous regression of mass effect that may occur following apoplexy of a pituitary adenoma. PMID:25861507

  9. 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. PMID:17459849

  10. Developed diplopia and ptosis due to a nonfunctioning pituitary macroadenoma during pregnancy

    PubMed Central

    Lee, Hye-Ran; Lee, Keun-Young

    2014-01-01

    Physiologic pituitary enlargement is common during normal pregnancy. However, symptoms such as diplopia, blurred vision and headache resulting from physiologic pituitary enlargement are very rare during pregnancy. A 39-year-old woman complained of sudden diplopia and left eye ptosis at 33th weeks of gestation. An magnetic resonance imaging (MRI) demonstrated the pituitary enlargement compressing the optic chiasm. Notwithstanding the medication of bromocriptine, her symptoms did not regress during pregnancy. At 5 months after delivery, her symptoms dramatically resolved without any surgery, and her visual acuity was normalized. Her MRI scan also revealed more decreased size of pituitary gland compared to antenatal MRI. We report a case of visual loss due to the physiologic pituitary enlargement of nonfunctioning adenoma during pregnancy, which regressed spontaneously after delivery without any surgery. PMID:24596820

  11. Craniopharyngioma in a patient with acromegaly due to a pituitary macroadenoma.

    PubMed

    El-Bilbeisi, Hazem; Ghannam, Mohammad; Nimri, Caramella F; Ahmad, Azmi T

    2010-01-01

    We present the first reported case of a craniopharyngioma as a second primary tumor in a patient with acromegaly due to a growth hormone (GH)-secreting pituitary adenoma. The patient was lost for follow-up for 18 years after trans-sphenoidal pituitary surgery for a GH-secreting pituitary adenoma. She presented with headaches and decreased visual acuity, and showed unsuppressed GH in an oral glucose load test with high IGF-1 levels. Brain MRI showed a suprasellar cystic mass and the patient underwent surgery for cyst drainage resulting in postoperative improvement in her vision. Biopsy of the mass confirmed the diagnosis of a craniopharyngioma. We stress the need for close follow-up of patients with acromegaly with adequate control of GH and IGF-1 levels.

  12. Pediatric Cushing's disease: Management Issues.

    PubMed

    Savage, Martin O; Storr, Helen L

    2012-12-01

    Cushing's disease (CD), caused by an ACTH-secreting pituitary corticotroph adenoma, is the commonest cause of Cushing syndrome in children over 5 years of age. It is rare in the pediatric age range and presents difficult diagnostic and therapeutic challenges. Key presenting features include weight gain, growth failure and change in facial appearance. Most pediatric endocrinologists have limited experience managing children or adolescents with CD and thus benefit from close consultation with adult colleagues. We describe a diagnostic protocol which broadly follows the model for adult patients. Treatment strategies are examined and appraised. The management of pediatric CD patients after cure is also discussed. PMID:23565371

  13. Canalicular adenoma of buccal mucosa.

    PubMed

    Maamouri, F; Bellil, K; Bellil, S; Chelly, I; Mekni, A; Kchir, N; Haouet, S; Zitouna, M

    2007-06-01

    Canalicular adenoma is a benign tumor which comprises 1% of salivary gland neoplasms and 4% of minor salivary gland tumors. It occurs in the upper lip mucosa in about 90% of cases. The next most common location is the buccal mucosa (9.5% of tumors). We present herein a new case of canalicular adenoma of buccal mucosa involving a 74-year-old man. He was suffering of a slowly growing and painless nodule of the right buccal mucosa. The treatment was surgery and histological findings were consistent with the diagnosis of canalicular adenoma. No recurrence was noted one year later.

  14. Pituitary diseases and bone.

    PubMed

    Mazziotti, Gherardo; Chiavistelli, Silvia; Giustina, Andrea

    2015-03-01

    Pituitary hormones have direct and indirect effects on bone remodeling, and skeletal fragility is a frequent complication of pituitary diseases. Fragility fractures may occur in many patients with prolactinomas, acromegaly, Cushing disease, and hypopituitarism. As in other forms of secondary osteoporosis, pituitary diseases generally affect bone quality more than bone quantity, and fractures may occur even in the presence of normal or low-normal bone mineral density, making difficult the prediction of fractures in these settings. Treatment of excess and defective pituitary hormone generally improves skeletal health, although some patients remain at high risk for fractures, necessitating treatment with bone-active drugs.

  15. 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 ...

  16. 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 ...

  17. Competing interests in a lung cancer with metastasis to the pituitary gland: syndrome of inappropriate ADH secretion versus diabetes insipidus.

    PubMed

    Gulsin, Gaurav Singh; Jacobs, Madeleine Louisa Bryson; Gohil, Shailesh; Thomas, Adam; Levy, Miles

    2016-01-01

    Metastases to the pituitary gland are rare; cancers that most commonly metastasize to the pituitary are breast and lung cancers. No specific computed tomography or magnetic resonance imaging features reliably distinguish primary pituitary masses from metastases. A combination of a detailed clinical assessment together with specialist endocrine and neuroradiology support is essential to make the rare diagnosis of a pituitary metastasis. We present the case of a man with metastatic lung cancer, initially presenting as hypopituitarism. Subtle features in the history, together with neuroimaging findings atypical for pituitary adenomas, provided clues that the diagnosis was one of the pituitary metastases. Treatment of diabetes insipidus (DI) with replacement antidiuretic hormone (ADH) was complicated by extreme difficulties in achieving a satisfactory sodium and water balance. This was the result of coexistent DI and syndrome of inappropriate ADH secretion perpetuated by the patient's primary lung cancer, a phenomenon not previously described in the literature. PMID:27274855

  18. Competing interests in a lung cancer with metastasis to the pituitary gland: syndrome of inappropriate ADH secretion versus diabetes insipidus.

    PubMed

    Gulsin, Gaurav Singh; Jacobs, Madeleine Louisa Bryson; Gohil, Shailesh; Thomas, Adam; Levy, Miles

    2016-01-01

    Metastases to the pituitary gland are rare; cancers that most commonly metastasize to the pituitary are breast and lung cancers. No specific computed tomography or magnetic resonance imaging features reliably distinguish primary pituitary masses from metastases. A combination of a detailed clinical assessment together with specialist endocrine and neuroradiology support is essential to make the rare diagnosis of a pituitary metastasis. We present the case of a man with metastatic lung cancer, initially presenting as hypopituitarism. Subtle features in the history, together with neuroimaging findings atypical for pituitary adenomas, provided clues that the diagnosis was one of the pituitary metastases. Treatment of diabetes insipidus (DI) with replacement antidiuretic hormone (ADH) was complicated by extreme difficulties in achieving a satisfactory sodium and water balance. This was the result of coexistent DI and syndrome of inappropriate ADH secretion perpetuated by the patient's primary lung cancer, a phenomenon not previously described in the literature.

  19. Competing interests in a lung cancer with metastasis to the pituitary gland: syndrome of inappropriate ADH secretion versus diabetes insipidus

    PubMed Central

    Gulsin, Gaurav Singh; Jacobs, Madeleine Louisa Bryson; Gohil, Shailesh; Thomas, Adam; Levy, Miles

    2016-01-01

    Metastases to the pituitary gland are rare; cancers that most commonly metastasize to the pituitary are breast and lung cancers. No specific computed tomography or magnetic resonance imaging features reliably distinguish primary pituitary masses from metastases. A combination of a detailed clinical assessment together with specialist endocrine and neuroradiology support is essential to make the rare diagnosis of a pituitary metastasis. We present the case of a man with metastatic lung cancer, initially presenting as hypopituitarism. Subtle features in the history, together with neuroimaging findings atypical for pituitary adenomas, provided clues that the diagnosis was one of the pituitary metastases. Treatment of diabetes insipidus (DI) with replacement antidiuretic hormone (ADH) was complicated by extreme difficulties in achieving a satisfactory sodium and water balance. This was the result of coexistent DI and syndrome of inappropriate ADH secretion perpetuated by the patient's primary lung cancer, a phenomenon not previously described in the literature. PMID:27274855

  20. Hepatocellular adenoma: An update

    PubMed Central

    Vijay, Adarsh; Elaffandi, Ahmed; Khalaf, Hatem

    2015-01-01

    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. PMID:26557953