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Sample records for non-functioning pituitary adenomas

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

    PubMed Central

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

    2016-01-01

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

  2. Non-functioning pituitary adenomas: growth and aggressiveness.

    PubMed

    Øystese, Kristin Astrid; Evang, Johan Arild; Bollerslev, Jens

    2016-07-01

    Pituitary adenomas (PAs) are common, comprising approximately one third of all intracranial tumors. Non-functioning pituitary adenomas (NFPAs) are the most common PAs. Although usually benign, the NFPAs represent therapeutic challenges because of their location close to the optic chiasm and nerves, and the proximity to the pituitary gland. The therapeutic alternatives are surgery and radiation. To date there is no effective medical treatment. NFPAs are classified according to different modalities, but there are no reliable marker of aggressiveness to guide the clinician in monitoring the patient. More information on growth patterns with constituent biological markers are needed to tailor the care of this patient group. Studies characterizing the membrane receptors of NFPAs have shown promising results, which may give rise to the development of medical treatment. PMID:27066792

  3. 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

  4. 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

  5. Biological and radiological exploration and management of non-functioning pituitary adenoma.

    PubMed

    Raverot, Gérald; Assié, Guillaume; Cotton, François; Cogne, Muriel; Boulin, Anne; Dherbomez, Michèle; Bonneville, Jean François; Massart, Catherine

    2015-07-01

    Non-functioning pituitary adenoma may be totally asymptomatic and discovered "incidentally" during radiological examination for some other indication, or else induce tumoral signs with compression of the optic chiasm and pituitary dysfunction. Non-functioning adenomas are mainly gonadotroph, but may also be "silent". Treatment strategy depends on initial clinical, biological, ophthalmological and radiological findings. The present French Society of Endocrinology Consensus work-group sought to update the pitfalls associated with hormone assay and outline a hormonal exploration strategy for diagnosis and follow-up, without overlooking the particularities of silent adenoma. We also drew up basic rules for initial exploration and radiological follow-up of both operated and non-operated pituitary adenomas. PMID:26122495

  6. 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

  7. 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

  8. 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

  9. Double pituitary adenomas.

    PubMed

    Iacovazzo, D; Bianchi, A; Lugli, F; Milardi, D; Giampietro, A; Lucci-Cordisco, E; Doglietto, F; Lauriola, L; De Marinis, L

    2013-04-01

    Double pituitary adenomas represent up to 2.6 % of pituitary adenomas in large surgical series and up to 3.3 % of patients with Cushing's disease have been found to have double or multiple pituitary adenomas. We report the case of a 60-year-old male patient whose medical history began in 2002 with erectile dysfunction; hyperprolactinemia was found and MRI showed a 6-mm area of delayed enhancement in the lateral portion of the right pituitary lobe. Treatment with cabergoline was started with normalization of prolactin levels; the following MRI, performed in 2005 and 2008, showed shrinkage of the pituitary lesion. In 2005, the patient began to manifest weight gain, hypertension, and facial plethora, but no further evaluations were done. In January 2010, the patient came to our attention and underwent multiple tests that suggested Cushing's disease. A new MRI was negative. Bilateral inferior petrosal sinus sampling showed significant pituitary-to-peripheral ratio and, in May 2010, the patient underwent exploratory pituitary surgery with evidence of a 1-2-mm white-coloured midline area compatible with pituitary adenoma that was surgically removed. Post-operatively, the patient's clinical conditions improved with onset of secondary hypoadrenalism. The histologic examination confirmed a pituitary adenoma (immunostaining was found to be positive for ACTH and negative for prolactin). We report the case of an ACTH-producing microadenoma metachronous to a prolactin secreting microadenoma although not confirmed histologically, shrunk by medical treatment. A review of data in the literature regarding double or multiple pituitary adenomas has also been done. PMID:23325364

  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. [Treatment of pituitary adenomas].

    PubMed

    Mezosi, Emese; Nemes, Orsolya

    2009-09-27

    According to epidemiological studies, the prevalence of pituitary adenomas is 16.5% and the majority of them are "incidentalomas". The symptoms of pituitary disorders are often non-specific; disturbances of pituitary function, compression symptoms, hypophysis apoplexy or accidental findings may help the diagnosis. The hormonal evaluation of pituitary adenomas is different from the algorithm used in the disorders of peripheral endocrine organs. The first-line therapy of prolactinomas are the dopamine agonists, and the aims of the treatment are to normalize the prolactin level, restore fertility in child-bearing age, decrease tumor mass, save or improve the residual pituitary function and inhibit the relapse of the disease. The available dopamine agonists in Hungary are bromocriptine and quinagolide. In case of tumors with good therapeutic response, medical therapy can be withdrawn after 3-5 years; hyperprolactinemia will not recur in 2/3 of these patients. Neurosurgery is the primary therapy of GH-, ACTH-, TSH-producing and inactive adenomas. In the last decades, significant improvement has been reached in surgical procedures, resulting in low mortality rates. Acromegalic patients with unresectable tumors have a great benefit from somatostatin analog treatment. The growth hormone receptor antagonist pegvisomant is the newest modality for the treatment of acromegaly. The medical therapy of Cushing's disease is still based on the inhibition of steroid production. A new, promising somatostatin analog, pasireotide is evaluated in clinical trials. The rare TSH-producing tumor can respond to both dopamine agonist and somatostatin analog therapy. The application of conventional radiotherapy has decreased; radiotherapy is mainly used in the treatment of invasive, incurable or malignant tumors. Further studies are needed to elucidate the exact role of radiosurgery and fractionated stereotaxic irradiation in the treatment of pituitary tumors. PMID:19758960

  12. 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

  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. PMID:24282035

  14. Synchronous pituitary adenoma and pituicytoma.

    PubMed

    Neidert, Marian C; Leske, Henning; Burkhardt, Jan-Karl; Kollias, Spyros S; Capper, David; Schrimpf, Daniel; Regli, Luca; Rushing, Elisabeth J

    2016-01-01

    Pituicytoma is a rare benign neoplasm arising in the sellar region, usually found in the posterior lobe and/or pituitary stalk. Here, we report the case of a 67-year-old woman who presented with bitemporal hemianopsia and visual impairment accompanied by mildly elevated prolactin. Pathologic and molecular examination of the tissue removed transsphenoidally revealed 2 distinct tumors: pituitary adenoma and pituicytoma. To the best of our knowledge, histologically proven pituicytoma and pituitary adenoma have never been reported together. PMID:26476569

  15. 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

  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. Growth hormone secreting pituitary adenoma with admixed gangliocytoma and ganglioglioma.

    PubMed

    Jukes, Alistair; Allan, Rodney; Rawson, Robert; Buckland, Michael E

    2016-09-01

    Pituitary adenomas are the most common tumours found in the sellar region and, when both functioning and non-functioning adenomas are combined, account for 7-15% of primary brain tumours in adults. Rarely, admixed or discrete groups of cells comprising two or more tumour subtypes are seen; the so-called 'collision tumour'. We present a case of a 54-year-old-woman with a growth hormone-secreting pituitary adenoma admixed with both ganglioglioma and gangliocytoma. The possible mechanisms by which this may occur include a pre-existing gangliocytoma promoting the development of pituitary adenoma by hypersecretion of releasing hormones or aberrant migration of hypothalamic neurons in early embryogenesis. PMID:27068013

  18. Gamma knife radiosurgery for pituitary adenomas.

    PubMed

    Ježková, Jana; Marek, Josef

    2016-09-01

    Pituitary adenomas are frequently occurring intracranial neoplasms. The aim of the treatment of pituitary adenomas is to normalize hormonal hypersecretion, to preserve the normal pituitary function, to reserve or treat impaired pituitary function and to control tumor growth and its mechanical effects on the surrounding structures. Treatment modalities include surgical, medical and radiation therapy. Radiosurgery is mainly used as a secondary line treatment after surgery for residual or recurrent tumors. The antiproliferative effect is achieved by LKG irradiation in more than 90% of patients. Regarding the functioning pituitary adenomas, the manifestation of the treatment effect is slow and depends mainly on the type of adenoma. Gamma knife irradiation is safe when the maximal doses to pituitary and infundibulum are respected. PMID:26899535

  19. 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

  20. 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

  1. Ectopic suprasellar pituitary adenoma. A case report.

    PubMed

    Caranci, F; Cirillo, L; Bartiromo, F; Ferraioli, M; Del Basso De Caro, M L; Esposito, F; Cappabianca, P; Brunetti, A; Elefante, R

    2007-01-31

    The occurrence of a pituitary adenoma located entirely outside the sella turcica, so-called ectopic adenoma, is extremely rare. We report a case of a non secreting-pituitary adenoma located above the diaphragma sellae, with no invasion into the sella turcica, confirmed at surgery. The tumor was initially treated unsuccessfully by operations via the transphenoidal route. After initial negative exploration by the transphenoidal route, the patient was successfully treated by an endoscopic endonasal transphenoidal approach extended to the tuberculum sellae and the posterior planum sphenoidale to access the suprasellar supraglandular region. A brief review of ectopic adenomas and a discussion of the preoperative diagnosis are presented. PMID:24351300

  2. 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 ...

  3. Diagnostic imaging of dopamine receptors in pituitary adenomas.

    PubMed

    de Herder, Wouter W; Reijs, Ambroos E M; Feelders, Richard A; van Aken, Maarten O; Krenning, Eric P; van der Lely, Aart-Jan; Kwekkeboom, Dik J

    2007-04-01

    Dopamine D2 receptor scintigraphy of pituitary adenomas is feasible by single-photon emission computed tomography using (123)I-S-(-)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-hydroxy-3-iodo-6-methoxybenzamide ((123)I-IBZM) and (123)I-epidepride. (123)I-epidepride is generally superior to (123)I-IBZM for the visualization of D2 receptors on pituitary macroadenomas. However, (123)I-IBZM and (123)I-epidepride scintigraphy are generally not useful to predict the response to dopaminergic treatment in pituitary tumour patients. These techniques might allow discrimination of non-functioning pituitary macroadenomas from other non-tumour pathologies in the sellar region. Dopamine D2 receptors on pituitary tumours can also be studied using positron emission tomography with (11)C-N-raclopride and (11)C-N-methylspiperone. PMID:17413189

  4. 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

  5. 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

  6. 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.

  7. Clinicopathological correlates of extrasellar growth patterns in pituitary adenomas.

    PubMed

    Sarkar, Sauradeep; Chacko, Ari G; Chacko, Geeta

    2015-07-01

    We reviewed clinical, imaging and histopathology details of 297 patients who underwent surgery for pituitary adenomas, with an equal distribution of functional and non-functioning tumors, to examine clinicopathological correlates of extrasellar growth. Knosp grades of 3 and 4 on MRI defined cavernous sinus invasion, Hardy grades of C and D defined significant suprasellar/subfrontal extension, and intraoperative evidence of tumor eroding through the clivus or sellar floor defined infrasellar invasion. Disease status at follow-up was known in 246 patients overall, including 35 patients who were evaluated for progression of residual disease on serial imaging. On univariate analysis, we found several statistically significant associations (p < 0.05) including adenoma size with age, sex and tumor protein p53 reactivity; cavernous sinus invasion with size, non-functional status, increased mitotic activity, an elevated MIB-1 proliferation index and p53 reactivity; suprasellar/subfrontal extension with p53 reactivity; and infrasellar invasion with age and tumor size. When adjusting for confounders with logistic regression, several significant associations were evident including adenoma size with male sex and p53 reactivity; cavernous sinus invasion with size and elevated MIB-1 proliferation index; suprasellar/subfrontal extension with p53 reactivity; and infrasellar invasion with adenoma size alone. Patients with early progression of postoperative residual tumor were younger with a non-significant trend towards higher MIB-1 proliferation indices. Individual patterns of extrasellar growth in pituitary adenomas are associated with unique clinical and immunohistochemical profiles. Younger patients with elevated MIB-1 values are probably at high risk for early recurrence of non-functioning tumors. Definitions of atypia must be standardized before more robust assumptions about tumor biology can be established. PMID:25979255

  8. 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

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

    PubMed

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

    2015-05-01

    We report a patient with Cushing's disease (CD) and two pituitary adenomas that demonstrated different imaging characteristics and therefore suggest an alternative imaging strategy for these patients. A 42-year-old woman presented with signs and symptoms of CD. Biochemical evaluation confirmed hypercortisolemia and suggested CD. On pituitary MRI with spoiled gradient recalled acquisition in the steady-state and T1-weighted spin echo protocols, a 5mm hypoenhancing region typical for a pituitary adenoma was identified on the left. However, after surgical resection the patient remained hypercortisolemic and pathology revealed a non-functional adenoma. At early repeat surgical exploration a 10mm adenoma was found in the right side of the gland. Postoperatively the patient became hypocortisolemic and pathology demonstrated an adrenocorticotropic hormone (ACTH)-staining adenoma. On review of the initial MRI this tumor corresponded to a region of contrast retention best visualized on delayed fluid attenuated inversion recovery (FLAIR) imaging. While the incidentaloma in this case demonstrated classical imaging characteristics of a pituitary adenoma the larger ACTH-secreting tumor was best appreciated by contrast retention. This suggests a role for delayed postcontrast FLAIR imaging in the preoperative evaluation of CD. ACTH-secreting tumors causing CD cause significant morbidity. Due to their small size, a pituitary adenoma is frequently not identified on imaging despite endocrinologic testing suggesting CD. Regardless of improvements in MRI, many tumors are only identified at surgical exploration. PMID:25827866

  10. 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

  11. 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

  12. 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. PMID:16391867

  13. 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

  14. Effect of Hypoxia on DDR1 Expression in Pituitary Adenomas

    PubMed Central

    Li, Shouchun; Zhang, Zhiwen; Xue, Jinghui; Guo, Xiaoming; Liang, Shuli; Liu, Aijun

    2015-01-01

    Background Pituitary adenoma is a common intracranial tumor in neurosurgery. Some pituitary adenomas have the characteristics of invasive growth make them unable to be removed completely by surgery leading to easy relapse. Discoidin domain receptor l (DDR1) is a new kind of tyrosine kinase receptor on the cell surface. DDR1 can be activated by tumor microenvironment signal in tumorigenesis, increasing MMP-2/9 expression and promoting the invasive ability of tumor cells. Anoxia can promote tumor growth and metastasis. This study investigated the impact of anoxic environment DDR1 expression in pituitary adenoma. Material/Methods A primary hypoxia pituitary adenoma cell model was established and treated with DDR1 inhibitor nilotinib. Real-time PCR and Western blot were used to detect DDR1 mRNA and protein expression. ELISA was used to detect MMP-2/9 changes. MTT method was used to detect pituitary adenoma cell proliferation. We used a transwell chamber to determine pituitary adenoma cell invasion ability. Results DDR1 mRNA and protein were significantly overexpressed under hypoxia (P<0.05). MMP-2 and MMP-9 expression was obviously increased in supernatant (P<0.05). Pituitary adenoma cell proliferation and invasive ability improved markedly under hypoxia (P<0.05). Nilotinib could reduce DDR1 expression, decrease MMP-2 and MMP-9 expression, and inhibit pituitary adenoma cells proliferation and invasion. Conclusions Hypoxia can increase DDR1 expression in pituitary adenoma cells, leading to improved MMP-2 and MMP-9 secretion, and promoting pituitary adenoma cell proliferation and invasion. PMID:26286316

  15. 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

  16. Challenging neck mass: non-functional giant parathyroid adenoma.

    PubMed

    Mossinelli, Chiara; Saibene, Alberto Maria; De Pasquale, Loredana; Maccari, Alberto

    2016-01-01

    A 46-year-old man was referred to our ear, nose and throat department after the accidental discovery of a large retrotracheal mass. In order to obtain the diagnosis and to plan treatment he underwent a full battery of tests (CT, MRI, blood tests, hormonal assays, ultrasounds, thyroid scintigraphy, urine tests and fine-needle aspiration of the mass), but none of these was able to define the true nature of such cervical mass. Only after surgical excision and histological evaluation, it was diagnosed as an exceptional case of giant non-functional parathyroid adenoma. PMID:27535730

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

    SciTech Connect

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

    1983-08-01

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

  18. 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

  19. 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

  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. Clinical Impact of the Current WHO Classification of Pituitary Adenomas.

    PubMed

    Saeger, W; Honegger, J; Theodoropoulou, M; Knappe, U J; Schöfl, C; Petersenn, S; Buslei, R

    2016-06-01

    WHO classifications should be used for comparing the results from different groups of pathologist and clinicians by standardized histopathological methods. Our present report describes the important parameters of pituitary adenoma pathology as demand of the WHO classification for correlation to endocrine data and prognosis. The combination of HE stain based structures with immunostainings for pituitary hormones allows subclassification of adenomas as the best method not only for correlations to clinical hyperfunctions but also for statements to the sensitivity of drug therapies (somatostatin analogs, dopamine agonists). GH-, PRL- and ACTH-secreting pituitary adenomas are further classified based on the size and number of their secretory granules by electron microscopy, or as is mostly the case nowadays by cytokeratin staining pattern, into densely and sparsely granulated. Granulation pattern may be considered for the prediction of treatment response in patients with GH-secreting adenomas, since the sparsely granulated subtype was shown to be less responsive to somatostatin analog treatment. For prognosis, it is important to identify aggressive adenomas by measurements of the Ki-67 index, of the number of mitoses, and of nuclear expression of p53. Among the criteria for atypical adenomas, high Ki-67 labeling index and invasive character are the most important adverse prognostic factors. Promising molecular markers have been identified that might supplement the currently used proliferation parameters. For defining atypical adenomas in a future histopathological classification system, we propose to provide the proliferative potential and the invasive character separately. PMID:26860936

  2. 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

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

    PubMed

    Ogawa, Yoshikazu; Tominaga, Teiji; Ikeda, Hidetoshi

    2007-07-01

    Thyroid-stimulating hormone (TSH)-secreting pituitary adenoma accounts for 1% of pituitary adenoma and often manifests as invasive macroadenoma. If the TSH value is not high enough to cause clinical symptoms presenting as inappropriate secretion of TSH, the tumor may be missed or misdiagnosed as Graves disease. Some of these patients receive inadequate treatment with the antithyroid agent, radioiodine treatment, and thyroidectomy. This tumor is also known as a tough and firm tumor because of the significant interstitial fibrosis. We report two cases of TSH-secreting pituitary adenomas which were comparatively small. Although a tough and difficult operation was expected, actual tumor dissection was easy and gross total removal was achieved within less than 3 hours. We discuss the relationship between the intraoperative findings and histopathology, as well as the ultrastructure and endocrinology. PMID:17633511

  4. Intrasellar schwannoma mimicking pituitary adenoma: a case report.

    PubMed

    Whee, Sung Mock; Lee, Jung Il; Kim, Jong Hyun

    2002-02-01

    Intrasellar location of schwannoma is extremely rare, although intracranial schwannomas account for up to 8% of all primary brain tumors. An unusual case of an intrasellar schwannoma radiographically and clinically simulating a pituitary adenoma is reported. A 39-yr-old man presented a 10-month history of visual disturbance and decreased libido. Neurological examination showed poor visual acuity of both eyes with bitemporal hemianopsia. Computed tomography and magnetic resonance imaging showed a sellar tumor with suprasellar extension. Pituitary adenoma was considered as a preoperative diagnosis. The tumor was removed through a trans-sphenoidal approach. Microscopic examination of the tumor revealed schwannoma. PMID:11850608

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

    PubMed Central

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

    2016-01-01

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

  6. 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

  7. 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

  8. Ovarian Hyperstimulation Caused by Gonadotroph Pituitary Adenoma--Review.

    PubMed

    Halupczok, Jowita; Kluba-Szyszka, Anna; Bidzińska-Speichert, Bożena; Knychalski, Bartłomiej

    2015-01-01

    Ovarian hyperstimulation syndrome (OHSS) occurs mostly as an iatrogenic complication of assisted reproductive technology. Gonadotroph pituitary adenomas are rarely associated with OHSS. To the authors' knowledge, to date only 30 cases of spontaneous ovarian stimulation associated with gonadotroph adenomas have been reported in women and only 2 in children. The most common symptoms in such cases included menstrual disturbances, abdominal or pelvic pain, abdominal distension and increased girth. Galactorrhea, nausea and vomiting were also reported. Neurological symptoms occurred when the size of the pituitary tumor reached at least 20 mm. Transvaginal ultrasound examination usually demonstrated enlarged multicystic ovaries. MRIs of the pituitary revealed macroadenomas up to 61 mm in maximum diameter. The hormonal profiles of the reported cases showed normal or elevated FSH levels, suppressed LH levels, elevated estradiol levels and supranormal concentrations of prolactin. Transsphenoidal surgery is the therapy of choice, however other treatment modalities can be utilized in selected cases. PMID:26469116

  9. 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.

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

    PubMed

    Sharman, Mellora; FitzGerald, Louise; Kiupel, Matti

    2013-10-01

    An 8-year-old, male neutered, domestic longhair cat was referred for investigation of insulin-resistant diabetes mellitus. Routine haematology, serum biochemistry, urinalysis (including culture), total T4 and urine creatinine:cortisol ratio were unremarkable, but markedly increased insulin-like growth factor-1 concentration was identified and a pituitary mass was subsequently documented. The cat was treated conservatively with the dopamine agonist L-deprenyl and was re-presented 16 months later for worsening polyuria, polydipsia, polyphagia, marked lumbar muscle atrophy, development of a pendulous abdomen and marked thinning of the abdominal skin. Hyperadrenocorticism was diagnosed based on abdominal ultrasonography, dexamethasone suppression testing and endogenous adrenocorticotropic hormone (ACTH). The cat was treated with trilostane (30 mg q24h PO) and showed some clinical improvement, but developed an opportunistic fungal infection and skin fragility syndrome 4.5 months after commencing treatment, and was euthanased. A double-pituitary adenoma comprising a discrete somatotroph adenoma and a separate plurihormonal adenoma (positive immunoreactivity for ACTH, melanocyte-stimulating hormone and follicle-stimulating hormone) was identified on post-mortem examination. These two pituitary adenomas were suspected to have arisen as independent neoplastic entities with the plurihormonal tumour either being clinically silent at the initial presentation or having developed over the subsequent 16 months. PMID:23553410

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

    PubMed

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

    2015-10-01

    We report a 27-year-old woman with amenorrhea and galactorrhea with mildly elevated serum prolactin levels. Her MRI demonstrated a cystic macroadenoma in the left aspect of the sella and a small microadenoma in the right aspect of the sella. Endoscopic transsphenoidal resection of the tumors revealed two histologically distinct tumors. The left tumor was consistent with a silent corticotroph macroadenoma and the right tumor was a prolactin producing microadenoma. Isolated double pituitary adenomas that are clearly separated by normal pituitary gland tissue are extremely rare. The incidence is approximately 0.37-2.6%. The coexistence of double adenomas can pose diagnostic and management challenges for the pituitary neuroendocrine team. PMID:26067545

  12. 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

  13. 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.

  14. 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

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

    PubMed

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

    2014-03-01

    Pituitary adenoma (PA) is a common benign neuroendocrine tumor; however, the incidence and proportion of hormone-producing PAs in Korean patients remain unknown. Authors analyzed 506 surgically resected and pathologically proven pituitary lesions of the Seoul National University Hospital from 2006 to 2011. The lesions were categorized as: PAs (n = 422, 83.4%), Rathke's cleft cysts (RCCs) (n = 54, 10.6%), inflammatory lesions (n = 8, 1.6%), meningiomas (n = 4), craniopharyngiomas (n = 4), granular cell tumors (n = 1), metastatic renal cell carcinomas (n = 2), germinomas (n = 1), ependymomas (n = 1), and unsatisfactory specimens (n = 9, 1.8%). PAs were slightly more prevalent in women (M: F = 1:1.17) with a mean age of 48.8 yr (9-80 yr). Immunohistochemical analysis revealed that prolactin-producing PAs (16.6%) and growth hormone-producing adenomas (9.2%) were the most common functional PAs. Plurihormonal PAs and nonfunctioning (null cell) adenomas were found in 14.9% and 42.4% of patients with PAs, respectively. The recurrence rate of PAs was 11.1%, but nearly 0% for the remaining benign lesions such as RCCs. 25.4% of patients with PAs were treated by gamma-knife after surgery due to residual tumors or regrowth of residual tumor. In conclusion, the pituitary lesions and the proportions of hormone-producing PAs in Korean patients are similar to those of previous reports except nonfunctioning (null cell) PAs, which are unusually frequent. PMID:24616591

  17. 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

  18. [Hyperthyroidism caused by a TSH producing pituitary adenoma].

    PubMed

    Prasch, F; Knosp, S E; Steinbach, R; Wogritsch, S; Hurtl, I; Greifeneder, M; Holm, C; Najemnik, C; Dudczak, R

    1999-01-01

    Elevated levels of free triiodothyronine (fT3) of 8.8 ng/dl (normal range 2.0 to 4.2) and free thyroxin (fT4) of 3.5 pg/ml (0.8 to 1.7) were found in the course of an examination of a 53-year old patient due to a planned hysterectomy. As thyrotropin (TSH) also was elevated with 5.8 mU/l (0.4 to 4.5), these findings corresponded to an inappropriate secretion of TSH (IST). Additional examinations revealed a blunted rise of TSH secretion after i.v. injection of 200 micrograms thyrotropin releasing hormone (TRH) as well as lacking suppression of TSH secretion after oral doses of 75 micrograms T3 during one week. alpha-TSH levels with 3.7 micrograms/l were elevated in comparison to a matched normal sample just as the molar ratio alpha-TSH/TSH with 6.95 and sex hormone-binding globulin (SHBG) with 175 nmol/l and showed an absence of inhibition in the T3 suppression test. These results were suggestive of neoplastic inappropriate secretion of TSH (nIST) due to a TSH-secreting pituitary adenoma. In concordance, the magnetic resonance imaging (MRI) showed a 1 cm tumor in the sella. The adenoma could also be visualized by 111In-octreotide and 123I-epidepride scintigraphies of the pituitary gland. After transsphenoidal resection, histological examination of the tumor resulted in the finding of a TSH-secreting adenoma. Postoperative TSH levels were not detectable, indicating the complete removal of the adenoma. Levels of fT3 and fT4 were slightly below normal with 1.9 pg/ml and 0.7 ng/dl, respectively. A control scintigraphy with 111In-octreotide following an equivocal MRI showed no uptake in the pituitary. PMID:10230475

  19. A thyrotropin-secreting pituitary adenoma as a cause of thyrotoxic periodic paralysis.

    PubMed

    Alings, A M; Fliers, E; de Herder, W W; Hofland, L J; Sluiter, H E; Links, T P; van der Hoeven, J H; Wiersinga, W M

    1998-11-01

    We describe a patient with thyrotoxic periodic paralysis (TPP) caused by a thyrotropin-secreting pituitary adenoma. The diagnosis TPP was based on the combination of episodes of reversible hypokalaemic paralysis, hyperthyroidism and electrophysiological findings. A thyrotropin-secreting pituitary adenoma was diagnosed on the basis of endocrinological function tests and MRI of the pituitary gland. Before transsphenoidal resection of the adenoma, treatment with octreotide restored euthyroidism both clinically and biochemically. Immunocytochemistry of the pituitary adenoma was positive for TSH exclusively. Incubation with octreotide or quinagolide induced decreased TSH and alpha-subunit production by the cultured adenoma cells, in agreement with the pre-operative in vivo data. This paper is the first to describe in vivo and in vitro characteristics of a thyrotropin-secreting pituitary adenoma in a patient presenting with periodic paralysis. PMID:9854688

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

    PubMed

    Amlashi, Fatemeh G; Tritos, Nicholas A

    2016-06-01

    Inappropriate secretion of TSH was first described in 1960 in a patient with evidence of hyperthyroidism and expanded sella on imaging. It was later found that a type of pituitary adenoma that secretes TSH (thyrotropinoma) was the underlying cause. The objective of the present review article is to summarize data on the epidemiology, pathogenesis, diagnosis, and management of thyrotropinomas. The prevalence of thyrotropinomas is lower than that of other pituitary adenomas. Early diagnosis is now possible thanks to the availability of magnetic resonance imaging and sensitive laboratory assays. As a corollary, many patients now present earlier in the course of their disease and have smaller tumors at the time of diagnosis. Treatment also has evolved over time. Transsphenoidal surgery is still considered definitive therapy. Meanwhile, radiation therapy, including radiosurgery, is effective in achieving tumor control in the majority of patients. In the past, radiation therapy was used as second line treatment in patients with residual or recurrent tumor after surgery. However, the availability of somatostatin analogs, which can lead to normalization of thyroid function as well as shrink these tumors, has led to an increase in the role of medical therapy in patients who are not in remission after pituitary surgery. In addition, dopamine agonists have shown some efficacy in the management of these tumors. Better understanding of the molecular pathogenesis of thyrotropinomas may lead to rationally designed therapies for patients with thyrotropinomas. PMID:26792794

  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. Disulfiram sensitizes pituitary adenoma cells to temozolomide by regulating O6-methylguanine-DNA methyltransferase expression.

    PubMed

    Zhao, Yachao; Xiao, Zheng; Chen, Wenna; Yang, Jinsheng; Li, Tao; Fan, Bo

    2015-08-01

    O6-methylguanine-DNA methyltransferase (MGMT) activity is responsible for temozolomide (TMZ) resistance in patients harboring aggressive pituitary adenomas. Recently, disulfiram (DSF) has been shown to induce the loss of MGMT protein and increase TMZ efficacy in glioblastoma cells, while CD133+ nestin+ cells isolated from the cell population have been implicated as pituitary adenoma stem-like cells. However, whether DSF is able to potentiate the cytotoxic effects of TMZ on human pituitary adenoma cells has not been investigated to date. In the present study, CD133+ nestin+ phenotype cells were isolated from primary cultured human pituitary adenoma cells using microbeads. It was found that DSF reduced MGMT protein expression and sensitized human pituitary adenoma cells and stem-like cells to TMZ in vitro, while the proteasome inhibitor PS-341 abrogated the inhibitory effect of DSF on MGMT in vitro. The sensitizing effect of DSF was also verified in primary cultured human pituitary adenoma cells in vivo. The results of the present study suggested that DSF can increase the efficacy of the anti-tumor effect of TMZ on human pituitary adenoma cells and CD133+ nestin+ stem like cells via the ubiquitin-proteasomal MGMT protein elimination route. DSF combined with TMZ may be an effective therapeutic strategy against aggressive pituitary adenomas. PMID:25937029

  3. Emerging Histopathological and Genetic Parameters of Pituitary Adenomas: Clinical Impact and Recommendation for Future WHO Classification.

    PubMed

    Saeger, W; Petersenn, S; Schöfl, C; Knappe, U J; Theodoropoulou, M; Buslei, R; Honegger, J

    2016-06-01

    The review assesses immunohistochemical findings of somatostatin receptors and of metalloproteinases in different pituitary adenoma types and the significance of molecular genetic data. Current evidence does not support routine immunohistochemical assessment of somatostatin or dopamine receptor subtype expression on hormone-secreting or nonfunctioning pituitary adenomas. Further prospective studies are needed to define its role for clinical decision making. Until then we suggest to restrict membrane receptor profiling to individual cases or for study purposes. The problems of adenoma expansion and invasion are discussed. Despite partially contradictory publications, proteases clearly play a major role in permission of infiltrative growth of pituitary adenomas. Therefore, detection of at least MMP-2, MMP-9, TIMP-2, and uPA seems to be justified. Molecular characterization is important for familial adenomas, adenomas in MEN, Carney complex, and McCune-Albright syndrome and can gain insight into pathogenesis of sporadic adenomas. PMID:26874696

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

    PubMed Central

    Rim, Chai Hong; Yang, Dae Sik; Park, Young Je; Yoon, Won Sup; Lee, Jung Ae

    2011-01-01

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

  5. 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

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

    PubMed

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

    2014-08-01

    Persistent trigeminal artery (PTA) is the most frequent embryonic communication between the carotid and vertebrobasilar systems. However, hormonal changes or the association of PTA with other sellar lesions, such as pituitary adenomas, are extremely rare. The aim of the present study was to report two patients with intrasellar PTA and simultaneous pituitary adenoma in order to emphasize the importance of differential diagnoses for sellar lesions. Case 1. A female patient, 41 years old, was admitted with a history of chronic headache (> 20 years). Pituitary magnetic resonance imaging (MRI) showed a rounded lesion in the left portion of the pituitary gland suggestive of adenoma (most likely clinically non-functioning adenoma). In addition to this lesion, the MRI demonstrated ecstasy of the right internal carotid artery and imaging suggestive of an intrasellar artery that was subsequently confirmed by an angio-MRI of the cerebral vessels as PTA. Case 2. A female patient, 42 years old, was admitted with a history of amenorrhea and galactorrhea in 1994. Laboratorial investigation revealed hyperprolactinemia. Pituitary MRI showed a small hyposignal area in the anterior portion of pituitary gland suggestive of a microadenoma initiated by a dopaminergic agonist. Upon follow-up, aside from the first lesion, the MRI showed a well delineated rounded lesion inside the pituitary gland, similar to a vessel. Angio-MRI confirmed a left primitive PTA. Failure to recognize these anomalous vessels within the sella might lead to serious complications during transsphenoidal surgery. Therefore, although their occurrence is uncommon, a working knowledge of vascular lesions in the sella turcica or pituitary gland is important for the differential diagnosis of pituitary lesions, especially pituitary adenomas. PMID:25211451

  7. 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. PMID:26845092

  8. 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

  9. Factors Influencing Disconnection Hyperprolactinemia and Reversal of Serum Prolactin after Pituitary Surgery in a Non-Functioning Pituitary Macroadenoma

    PubMed Central

    Kumran, Thinesh; Haspani, Saffari; Malin Abdullah, Jafri; Alias, Azmi; Ven, Fan Rui

    2016-01-01

    Background To investigate factors influencing disconnection hyperprolactinemia, including tumour volume, degree of pituitary stalk displacement and extent of tumour growth based on a modified Wilson-Hardy classification in a non-functioning pituitary macroadenoma and to confirm reductions in serum prolactin levels after endoscopic transphenoidal surgery. Methods This prospective, descriptive study was conducted in the Department of Neurosurgery, General Hospital Kuala Lumpur from Jan 1, 2011 to Jan 1, 2013. Forty patients fulfilling the inclusion criteria were enrolled. All patients underwent endoscopic transphenoidal resection of non-functioning pituitary macroadenoma. Pituitary stalk angle, tumour volume and extent of tumour growth were measured from Magnetic Resonance Imaging (MRI) pre- and post-operatively. These variables were compared to serum prolactin levels measured pre and post operatively. SPSS 21 was used to perform statistical analyses. Results In 40 patients, the mean tumour volumes were 10.58 cm3 (SD 7.81) pre-operatively and 3.1 cm3 (SD 3.45) post-operatively. There was a 70% reduction in tumour volume post-operatively (P < 0.01). The mean serum prolactin was 457 mIU/L (SD 66.93) pre-operatively and 297 mIU/L (SD 6.73) post-operatively. There was a 65% reduction in prolactin serum levels after surgery (P < 0.01). The mean pituitary stalk angles were 93.45 ± 3.89 degrees pre-operatively and 51.45 ± 1.46 degrees post-operatively (P = 0.01). The mean pituitary stalk angle in the control group was 50.4 ± 8.80 degrees. Hence, there was a 98% reduction in pituitary stalk angle after surgery (P < 0.01). This study showed a linear correlation between the pre-operative and post-operative tumour volumes and serum prolactin levels (P = 0.01 pre-and post-operative) and between serum prolactin levels and pituitary stalk angle (P = 0.20 pre-operative; P = 0.01 post-operative). Conclusion Tumour volume and pituitary stalk angle displacement have positive

  10. 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

  11. 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

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

    PubMed

    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

    2015-08-11

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

  13. Protein kinase C (PKC) activity and PKC messenger RNAs in human pituitary adenomas.

    PubMed

    Jin, L; Maeda, T; Chandler, W F; Lloyd, R V

    1993-02-01

    Protein kinase C (PKC) is involved in the differentiation and growth regulation of a variety of tissues including anterior pituitary gland cells. To determine the distribution of PKC in different types of adenomas, PKC activity was analyzed in human pituitary tumors and the effects of hypothalamic hormone stimulation on PKC activity were examined in cultured adenoma cells. Gonadotroph (LH/FSH) and null cell adenomas had significantly higher levels of particulate, soluble, and total PKC activity compared with growth hormone (GH) adenomas (P < 0.05). Chronic stimulation of null cell adenomas with gonadotropin hormone-releasing hormone or of one GH adenoma with GH-releasing hormone for 7 days did not significantly alter total PKC activity in pituitary cells cultured in serum-free medium. Localization of the calcium-dependent PKC isozymes (alpha, beta and gamma) by immunohistochemistry and in situ hybridization revealed predominantly PKC alpha in all adenomas and variable expression of PKC beta and gamma in some tumors. When the calcium-independent PKC isozymes (delta, epsilon, and zeta) were localized by in situ hybridization, normal and neoplastic pituitaries expressed abundant mRNA for PKC epsilon, whereas some tumors and one normal pituitary had a few cells positive for PKC zeta mRNA as evaluated by grain density and the number of cells labeled. These results indicate that there is a variable distribution of PKC mRNA isozymes in human pituitary adenomas and that normal pituitaries and pituitary adenoma cells express the mRNA for both the calcium-dependent and some of the calcium-independent PKC isozymes. Chronic treatment with the hypothalamic gonadotropin hormone-releasing hormone and GH-releasing hormone, which increased LH/FSH and GH secretion, respectively, did not increase PKC activity in cultured adenoma cells. The presence of calcium-dependent and calcium-independent PKC isozymes in normal and neoplastic pituitary cells indicates that PKC probably plays a

  14. 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

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

    PubMed

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

    2015-01-01

    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 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. PMID:25737012

  16. Medical therapies in pituitary adenomas: Current rationale for the use and future perspectives.

    PubMed

    Cuny, Thomas; Barlier, Anne; Feelders, Richard; Weryha, Georges; Hofland, Leo J; Ferone, Diego; Gatto, Federico

    2015-02-01

    Pituitary adenomas (PA) represent in the majority of cases, benign tumors whose treatment currently associate surgery, medical therapies and radiotherapy in a multidisciplinary approach. While trans-sphenoidal surgery remains, except for prolactin-secreting adenomas, the first-line treatment of PA, it can considerably be hampered by the existence of an invasive and/or aggressive tumor for which medical therapies are often requested. In this review, we extensively discuss, both at molecular and clinical levels, the medical therapies currently used and in development in the different phenotypes of pituitary adenomas. PMID:25556152

  17. 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

  18. 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

  19. 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

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

    PubMed

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

    2016-09-15

    Invasion of tumor cells critically depends on cell-cell or cell-extracellular matrix interactions. Enzymes capable of modulating these interactions belong to the proteinase families of ADAM (a disintegrin and metalloprotease) and MMP (matrix metalloprotease) proteins. Our objective is to examine their expression levels and evaluate the relationship between expression levels and cavernous sinus invasion in pituitary adenomas. Tissue samples from 35 patients with pituitary adenomas were analyzed. Quantitative real-time polymerase chain reaction (qPCR) was employed to assess mRNA expression levels for ADAM and MMP genes. Protein levels were examined using immunohistochemistry and Western Blot. Correlation analyses between expression levels and clinical parameters were performed. By silencing ADAM12 and MMP-14 with siRNA in a mouse pituitary adenoma cell line (TtT/GF), their cellular effects were investigated. In our study, nine women and 26 men were included, with a mean age of 53.1 years (range 15-84 years) at the time of surgery. There were 19 cases with cavernous sinus invasion. The proteins ADAM12 and MMP-14 were significantly up-regulated in invasive adenomas compared to noninvasive adenomas. Both human isoforms of ADAM12 (ADAM12L and ADAM12s) were involved in tumor invasion; moreover, ADAM12L was found to correlate positively with Ki-67 proliferation index in pituitary adenomas. In TtT/GF pituitary adenoma cells, silencing of ADAM12 and MMP-14 significantly inhibited cell invasion and migration, respectively, whereas only silencing of ADAM12 suppressed cell proliferation. We conclude that ADAM12 and MMP-14 are associated with cavernous sinus invasion in pituitary adenomas, which qualifies these proteins in diagnosis and therapy. PMID:27144841

  1. 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

  2. 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

  3. [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

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

    PubMed

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

    2016-07-01

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

  5. What's New in Pituitary Tumor Research and Treatment?

    MedlinePlus

    ... Next Topic Additional resources for pituitary tumors What’s new in pituitary tumor research and treatment? Research into ... of non-functioning adenomas, which may lead to new medical therapies for these tumors. Imaging tests such ...

  6. A double pituitary adenoma presenting as a prolactin-secreting tumor with partial response to medical therapy. Case report.

    PubMed

    Coiré, Claire I; Smyth, Harley S; Rosso, Dominic; Horvath, Eva; Kovacs, Kalman

    2010-06-01

    Double pituitary adenomas are difficult to recognize pre-operatively as only a single mass may be appreciated on imaging. We present herein a giant prolactin-secreting pituitary adenoma in a middle-aged man that had responded partially to dopamine agonist therapy. The excised specimen demonstrated a double adenoma. The prolactin-producing one displayed the expected morphological changes resulting from medical therapy, while the other, a gonadotroph adenoma, did not. The failure of tumor shrinkage can be attributed to the presence of a double adenoma, a previously unreported cause of failure of medical therapy in prolactinoma. PMID:20058099

  7. 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

  8. 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

  9. Neurotrophins, their receptors and KI-67 in human GH-secreting pituitary adenomas: an immunohistochemical analysis.

    PubMed

    Artico, M; Bianchi, E; Magliulo, G; De Vincentiis, M; De Santis, E; Orlandi, A; Santoro, A; Pastore, F S; Giangaspero, F; Caruso, R; Re, M; Fumagalli, L

    2012-01-01

    Pituitary adenomas are a diverse group of tumors arising from the pituitary gland. Typically, they are small, slow-growing, hormonally inactive lesions that come to light as incidental findings on radiologic or postmortem examinations, although some small, slow-growing lesions with excessive hormonal activity may manifest with a clinical syndrome. The family of neurotrophins plays a key role in the development and maintenance of the pituitary endocrine cell function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity. The objective of our experimental study is to investigate the localization of the neurotrophins, their relative receptors and to detect the expression level of Ki-67 to determine whether all these factors participate in the transformation and development of human pituitary adenomas. A very strong expression of Neurotrophin-3 (NT-3) and its receptor TrKC was observed in the extracellular matrix (ECM) and vessel endothelium, together with a clear/marked presence of Brain-derived neurotrophic factor (BDNF), and its receptor TrKB, thus confirming their direct involvement in the progression of pituitary adenomas. On the contrary, NGF (Nerve growth factor) and its receptor TrKA and p75NTR were weakly expressed in the epithelial gland cells and the ECM. PMID:22507324

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

    SciTech Connect

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

    1990-02-01

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

  14. Prolactin-producing pituitary adenoma with atypical spindle cell morphology: a case report.

    PubMed

    Inoue, Ritsurou; Aoki, Mikiko; Matsumoto, Yoshihisa; Haraoka, Seiji; Kazekawa, Kiyoshi; Nabeshima, Kazuki

    2015-01-01

    Reported herein is a 25-year-old woman who was treated for a large and highly atypical prolactin-producing pituitary adenoma. On presentation, she exhibited right hemiparesis and left-sided visual loss, associated with amenorrhea. A massive (>5 cm) intra- and suprasellar lesion was seen on imaging, and her serum prolactin level was 4408 ng/ml. The patient received dopamine agonist treatment preoperatively for 4 weeks. To resect the tumor, a two-stage excision was required. Histologically, the specimen was composed of polygonal or spindle cells showing marked nuclear pleomorphism and/or multinucleation. Fibrosis was also focally conspicuous. Differential diagnoses included pituitary adenoma, pituitary carcinoma, pituicytoma, paraganglioma, spindle cell oncocytoma, and meningioma. Immunohistochemically, the tumor cells were positive for prolactin, chromogranin-A, and synaptophysin, but were negative for glial fibrillary acidic protein, S-100 protein, epithelial membrane antigen, and vimentin. No apparent cerebrospinal or systemic metastases are found. Ultimately, prolactin-producing pituitary adenoma was diagnosed. Our case highlights the difficulty in definitively diagnosing an unusual prolactin-producing adenoma based on histopathology alone and the importance of referring to clinical information and immunohistochemical findings when deriving the diagnosis. PMID:26228535

  15. Interleukin-2 and interleukin-2 receptor expression in human corticotrophic adenoma and murine pituitary cell cultures.

    PubMed Central

    Arzt, E; Stelzer, G; Renner, U; Lange, M; Müller, O A; Stalla, G K

    1992-01-01

    The production of IL-1 and IL-6 by pituitary cells has recently been demonstrated. In this study we investigated the expression of IL-2 and its receptor (IL-2R) by pituitary cells of different species. In Northern blots, a single hybridizing band of 1 kb, identical to that in normal stimulated lymphocytes, was obtained with specific IL-2 probes. In the mouse AT-20 pituitary tumor cell line, IL-2 mRNA expression was detected after stimulation with corticotropin-releasing hormone or phorbol myristate acetate. In human corticotrophic adenoma cells, basal IL-2 mRNA expression as well as IL-2 secretion were further stimulated by phorbol myristate acetate. Both adenoma and AtT-20 cells showed detectable amounts of IL-2R mRNA and by immunofluorescence, IL-2R membrane expression. In addition, dual immunofluorescence studies in rat anterior pituitary cells demonstrated colocalization of IL-2R with ACTH-positive cells and other cell types expressing the receptor. In addition to the action of lymphocyte-produced IL-2, this cytokine may have a paracrine or autocrine regulatory role within the pituitary. It remains to be established whether IL-2 production occurs in the normal pituitary or is intrinsic to the process of tumor development of these cells. IL-2 may be involved in the growth control of pituitary cells. Images PMID:1331177

  16. 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. PMID:27489751

  17. 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

  18. Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas.

    PubMed

    Mete, Ozgur; Gomez-Hernandez, Karen; Kucharczyk, Walter; Ridout, Rowena; Zadeh, Gelareh; Gentili, Fred; Ezzat, Shereen; Asa, Sylvia L

    2016-02-01

    Originally classified as a variant of silent corticotroph adenoma, silent subtype 3 adenomas are a distinct histologic variant of pituitary adenoma of unknown cytogenesis. We reviewed the clinical, biochemical, radiological, immunohistochemical and ultrastructural features of 31 silent subtype 3 adenomas to clarify their cellular origin. Among 25 with clinical and/or radiological data, all were macroadenomas; there was cavernous sinus invasion in 30% of cases and involvement of the clivus in 17% of cases. Almost 90% of patients were symptomatic; 67% had mass effect symptoms, 37% were hypogonadal and 8% had secondary adrenal insufficiency. Significant hormonal excess in 29% of cases included hyperthyroidism in 17%, acromegaly in 8% and hyperprolactinemia above 150 μg/l in 4%. Two individuals with hyperprolactinemia who were younger than 30 years had multiple endocrine neoplasia type 1. Immunohistochemically, all 31 tumors were diffusely positive for the pituitary lineage-specific transcription factor Pit-1. Although three only expressed Pit-1, others revealed variable positivity for one or more hormones of Pit-1 cell lineage (growth hormone, prolactin, thyroid-stimulating hormone), as well as alpha-subunit and estrogen receptor. Most tumors exhibited perinuclear reactivity for keratins with the CAM5.2 antibody; scattered fibrous bodies were noted in five (16%) tumors. The mean MIB-1 labeling index was 4% (range, 1-9%). Fourteen cases examined by electron microscopy were composed of a monomorphous population of large polygonal or elongated cells with nuclear spheridia. Sixty-five percent of patients had residual disease after surgery; after a mean follow-up of 48.4 months (median 41.5; range=2-171) disease progression was documented in 53% of those cases. These data identify silent subtype 3 adenomas as aggressive monomorphous plurihormonal adenomas of Pit-1 lineage that may be associated with hyperthyroidism, acromegaly or galactorrhea and amenorrhea. Our

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

    PubMed Central

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

    2015-01-01

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

  20. Somatic IDH1 mutation in a pituitary adenoma of a patient with Maffucci syndrome.

    PubMed

    Hao, Shuyu; Hong, Christopher S; Feng, Jie; Yang, Chunzhang; Chittiboina, Prashant; Zhang, Junting; Zhuang, Zhengping

    2016-06-01

    Maffucci syndrome is a rare disease characterized by multiple enchondromas and soft-tissue hemangiomas. Additionally, neuroendocrine tumors including pituitary adenomas have been described in these patients. The underlying genetic etiology lies in somatic mosaicism of mutations in isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2). This report describes a patient with Maffucci syndrome who presented with intracranial tumors of the skull base and suprasellar region. The patient underwent resection of both intracranial tumors, revealing histopathological diagnoses of chondrosarcoma and pituitary adenoma. DNA sequencing of the tumors was performed to identify common IDH1/2 mutations. Clinical, radiological, and biochemical assessments were performed. Genotypic studies used standard Sanger sequencing in conjunction with a target-specific peptide nucleic acid to detect IDH1 mutations in tumor tissues. DNA sequencing demonstrated identical IDH1 mutations (c.394C > T) in both tumors. To the authors' knowledge, this report provides the first genetic evidence for the inclusion of pituitary adenomas among tumors characterizing Maffucci syndrome. In patients who are newly diagnosed with Maffucci syndrome, it is appropriate to monitor for development of pituitary pathology and neuroendocrine dysfunction. PMID:26473790

  1. 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

  2. Simultaneous occurrence of cerebellar medulloblastoma and pituitary adenoma: A case report

    PubMed Central

    Samaras, Vassilis; Samaras, Efstathios; Stergiou, Ioanna; Konstantopoulou, Paraskevi; Arnaoutoglou, Christos; Arnaoutoglou, Marianthi; Varsos, Vassilis; Barbatis, Calypso

    2008-01-01

    Purpose We present the unusual occurrence of two distinct neoplasms in a 42-year-old woman with an operated pituitary adenoma 18 years ago. Methods Clinical history, magnetic resonance imaging studies and histopathological findings were utilized for our diagnostic considerations. Results Concomitant presence of a cerebellar medulloblastoma secondary disseminated within the spinal canal and a pituitary macroadenoma, was identified. Conclusion To the best of our knowledge, this is the first reported case in which these two neoplasms are simultaneously occurred in the same individual. A short review of the literature is performed. PMID:18811959

  3. Emotional disorders in patients with different types of pituitary adenomas and factors affecting the diagnostic process.

    PubMed

    Flitsch, J; Spitzner, S; Lüdecke, D K

    2000-01-01

    A prospective study of 48 patients with pituitary adenomas, 19 adenomas causing Cushing's disease, 18 adenomas causing acromegaly, and 11 clinically hormone-inactive adenomas (inactive adenomas), was performed to study emotional disorders occurring before and after transsphenoidal microsurgery. Factors which led to an obvious delay in the diagnostic process were identified. - The tools utilised were an interview and repeated personality assessments. The personality assessments were begun preoperatively and continued for about half a year postoperatively. The interview data, including retrospective statements regarding somatic difficulties, was analysed. - The thesis of a uniform psychopathology due to the influence of elevated hormone levels, and a lack in patients' sensitivity towards their changed appearance in acromegaly could not be confirmed. A high variability of reported emotional problems was found. The most common psychopathological signs for Cushing's disease were excitability and depression, for acromegaly fatigue/loss of energy was the most frequent complaint. Six to eight months postoperatively, a majority of patients noticed an increase of physical well-being. In acromegaly, the time span between first consultation and diagnosis averaged 6.2 years, in Cushing's disease it was 4.3 years, and in inactive adenomas it was 3.9 years. Only a small part of the delay in diagnosis, less than two years, could be attributed to the patients' hesitation to consult a physician. PMID:11083069

  4. Epithelial and organ-related marker expression in pituitary adenomas.

    PubMed

    Cykowski, Matthew D; Takei, Hidehiro; Baskin, David S; Rivera, Andreana L; Powell, Suzanne Z

    2016-08-01

    The histologic expression of epithelial and organ-related immunohistochemical markers in primary sellar region tumors has received little attention to date. This lack of empirical data may lead to mistaken assumptions in the evaluation of sellar region neoplasms. To address this issue, the frequency and specificity of epithelial (cytokeratin 7(CK7), CK20) and organ-related differentiation markers (gross cystic disease fluid protein-15 (GCDFP-15), thyroid transcription factor-1 (TTF-1), Napsin A, paired box 8 (PAX-8), hepatocyte paraffin 1 (HepPar1) and estrogen receptor (ER)) were studied in 40 patients with adenomas comprising five hormonal sub-types. Non-parametric statistical procedures were used to examine associations between marker expression and tumor sub-type. CK7 and CK20 immunoreactivity were seen in 48% and 8% of tumors, respectively, although never in a diffuse pattern. CK20 expression was nearly exclusive to corticotrophs, whereas CK7 frequently highlighted cells with dendritic-type morphology. The specificity of organ-related differentiation markers was 100% (monoclonal Napsin A, GCDFP-15 and TTF-1), 97% (HepPar1 and PAX-8), 90% (polyclonal Napsin A) and 72% (ER); no tumors demonstrated significant co-expression of these organ-related markers with either CK7 or CK20. The first major conclusion of this study is that CK7 staining in adenoma is more frequent than has been previously than has been previously described. CK7 immunoreactive cells often displayed a dendritic-type morphology, including within large macroadenomas, which raises the question as to whether these represent tumor cells with folliculo-stellate cell-type differentiation, as these also have dendritic cell-type morphology and express CK7 in non-neoplastic glands. The second major conclusion, which confirms earlier findings, is that CK20 staining is a very infrequent immunohistochemical finding in adenomas that is virtually limited to corticotrophs and thus is helpful in diagnostic

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

    SciTech Connect

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

    1989-06-15

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

  6. 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

  7. 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

  8. 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

  9. 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. PMID:26885420

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

    SciTech Connect

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

    2007-01-01

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

  11. Hormone Secretion by Pituitary Adenomas Is Characterized by Increased Disorderliness and Spikiness but More Regular Pulsing

    PubMed Central

    Pereira, Alberto M.; Biermasz, Nienke R.; Veldhuis, Johannes D.

    2014-01-01

    Context: Hormone secretion by functioning pituitary tumors is characterized by increased basal (nonpulsatile) secretion, enhanced pulse frequency, amplified pulse mass, and increased disorderliness. Objective: The objective of the study was to quantify (subtle) abnormalities of hormone secretion by pituitary adenomas and the influence of selective pituitary surgery and suppressive medications on these parameters. Methods: Approximate entropy (ApEn) was quantified with a refined algorithm, spikiness by a new method to evaluate sudden short-lived increases in hormone levels, and pulsing regularity, determined with a fully automated deconvolution program. These 3 distinct measures of secretory disruption were compared in untreated and treated patients with acromegaly, prolactinoma, and Cushing's disease together with matching profiles in healthy controls. Results: ApEn and spikiness were markedly increased in all untreated patient groups and normalized after pituitary surgery in acromegaly and hypercortisolism. In contrast, hormone-suppressive medical treatment in acromegaly and prolactinoma did not normalize ApEn. Spikiness normalized in acromegalic patients but not in prolactinoma. GH and cortisol pulsing regularity was elevated in acromegaly and Cushing's disease, respectively, and normalized after surgery. Medical treatment caused normalization of pulsing regularity in acromegaly but not in prolactinoma patients. Conclusion: This study extends the understanding of disorganized hormone secretion by hyperfunctioning pituitary adenomas. The new findings are increased spikiness in all 3 tumor groups and increased pulsing regularity in GH- and ACTH-secreting adenomas. The mechanisms behind the marked pattern irregularity and the selective normalization by surgical and medical therapies are not established yet but may include diminished feedback signaling in addition to the anatomical and functional disorganization of intrapituitary cell networks. PMID:25014002

  12. Expression of Eag1 K+ channel and ErbBs in human pituitary adenomas: cytoskeleton arrangement patterns in cultured cells.

    PubMed

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

    2013-01-01

    Pituitary adenomas can invade surrounded tissue, but the mechanism remains elusive. Ether à go-go-1 (Eag1) potassium channel and epidermal growth factor receptors (ErbB1 and ErbB2) have been associated to invasive phenotypes or poor prognosis in cancer patients. However, cells arrange their cytoskeleton in order to acquire a successful migration pattern. We have studied ErbBs and Eag1 expression, and cytoskeleton arrangements in 11 human pituitary adenomas. Eag1, ErbB1 and ErbB2 expression were studied by immunochemistry in tissue and cultured cells. The cytoskeleton arrangement was analyzed in cultured cells by immunofluorescence. Normal pituitary tissue showed ErbB2 expression and Eag1 only in few cells. However, Eag1 and ErbB2 were expressed in all the tumors analyzed. ErbB1 expression was observed variable and did not show specificity for a tumor characteristic. Cultured cells from micro- and macro-adenomas clinically functional organize their cytoskeleton suggesting a mesenchymal pattern, and a round leucocyte/amoeboid pattern from invasive clinically silent adenoma. Pituitary tumors over-express EGF receptors and the ErbB2 repeated expression suggests is a characteristic of adenomas. Eag 1 was express, in different extent, and could be a therapeutic target. The cytoskeleton arrangements observed suggest that pituitary tumor cells acquire different patterns: mesenchymal, and leucocyte/amoeboid, the last observed in the invasive adenomas. Amoeboid migration pattern has been associated with high invasion capacity. PMID:23413122

  13. 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

  14. Trigeminal Neuralgia as an Unusual Isolated Symptom of Pituitary Adenoma: Case Report and Review of the Literature.

    PubMed

    Gurcan, Oktay; Gurcay, Ahmet Gurhan; Kazanci, Atilla; Yildirim, Ali Erdem; Turkoglu, Omer Faruk; Komurcu, Hatice Ferhan; Beskonakli, Ethem

    2016-01-01

    Pituitary adenomas account for approximately 10% of intracranial tumors and 5% are locally invasive. Cavernous sinus invasion by pituitary tumors presents mostly with cranial nerve palsies, especially involving the third, fourth and sixth cranial nerves, which is well documented in the literature. However, an isolated complaint of trigeminal neuralgia due to pituitary adenoma is an extremely rare entity with a limited number of reported cases. A 51-year-old female patient presented to our clinic with complaints of pain and numbness on the left side of face for six months, with each event lasting 5-10 seconds. No improvement was obtained with administration of carbamazepine therapy. Magnetic resonance imaging of the sellar region revealed a mass with the left cavernous sinus invasion. The patient underwent surgery via endoscopic transsphenoidal approach and after than radiosurgery with gamma-knife. The patient's complaints resolved totally after gamma-knife radiosurgery. We report herein a case of pituitary adenoma with an isolated complaint of trigeminal neuralgia. Pituitary adenomas may be presented with cavernous sinus invasion and multiple cranial nerve palsies but isolated trigeminal neuralgia due to pituitary adenoma is an extremely rare entity. PMID:26768887

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

    PubMed

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

    2014-12-01

    Dopamine agonists are considered as the first line therapy in prolactin (PRL) secreting pituitary adenomas inducing a normalization of serum PRL and reduction of tumor size. It is known that serum PRL levels, obtained during treatment, are a predictor of tumor shrinkage. Whether PRL suppression below the lower limit of the normal range is related to a greater chance of tumor shrinkage than just its normalization has not been established. This retrospective cohort study was carried out in a tertiary center. Clinical records of 151 patients with PRL-secreting pituitary adenomas (73 micro-, 78 macroadenomas) treated with cabergoline for at least 24 months were analyzed. The adenoma size was analyzed by MRI before and after 24 months of treatment. PRL levels were evaluated every 6 months, assigning a score at each time point (PRL 0 = suppressed; 1 = normal; 2 = above normal). The total score, after 24 months of treatment, was expressed as the sum of the score at each time point and ranged between 0 and 8. A tumor shrinkage was observed in 102/151 patients (67.5%) and it was significantly associated to a lower PRL total score (p = 0.021, OR = 0.85, CI = 0.73-0.97), being significantly more frequent in patients with suppressed PRL than in those with normal PRL (p = 0.045, OR = 0.42, CI = 0.18-0.98) at 24 months. Cabergoline therapy with the goal of achieving PRL levels below the lower limit of normal range can increase the chance to obtain tumor shrinkage of PRL-secreting pituitary adenomas. PMID:25230324

  16. 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

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

    PubMed

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

    2015-05-01

    In rare cases, pancytopenia results from hormonal deficiencies that arise in the setting of panhypopituitarism. Here we describe the unusual case of a 60-year-old man who presented with progressive fatigue and polyuria, and whose laboratory workup revealed a deficiency of the five hormones associated with the action of the anterior pituitary (thyroid hormone, testosterone, cortisol, prolactin, and insulin-like growth factor-1). Imaging of the pituitary demonstrated a cystic mass consistent with a pituitary adenoma replacing much of the normal pituitary tissue. His symptoms and hematologic abnormalities rapidly resolved with prednisone and levothyroxine supplementation. While the majority of reported cases of panhypopituitarism with bone marrow suppression are the result of peripartum sepsis or hemorrhage leading to pituitary gland necrosis (Sheehan's syndrome), it is also important to consider the diagnosis of hypopituitarism in patients with hypothyroidism, low cortisol levels, and pancytopenia. The causal relationship between pancytopenia and panhypopituitarism is not well understood, though it does reinforce the important influence of these endocrine hormones on the health of the bone marrow. PMID:25583570

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

    PubMed

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

    2014-01-01

    Thyroid stimulating hormone-secreting pituitary adenomas (TSHomas) are uncommon tumors of the anterior pituitary gland. Patients with TSHomas may present with hyperthyroidism, but the incidence of thyroid storm due to TSHomas has yet to be determined. We report a rare case of thyroid storm caused by TSHoma in a 54-year-old woman. Preoperatively she had symptoms of excessive sweating and palpitation. Blood tests showed inappropriate secretion of TSH with blood TSH 6.86 μ U/mL, fT3 19.8 pg/mL, and fT4 5.95 ng/dL. Magnetic resonance imaging (MRI) revealed a pituitary tumor with maximum diameter of 13 mm that was extirpated through transsphenoidal route. After operation the patient was stuporous and thyroid storm occurred presenting with hyperthermia, hypertension, and tachycardia. It was well managed with nicardipine, midazolam, steroids, and potassium iodide. Immunohistochemical staining of tumor specimen was positive for TSH and growth hormone (GH). One year after operation, fT3 and fT4 levels were still high. As her tumor was diagnosed to be GH- and TSH-producing adenoma, octreotide injection therapy was started, which normalized thyroid hormone levels. This is the second reported case with thyroid storm due to TSHoma and emphasizes the importance of strategies with interdisciplinary cooperation for prevention of such emergency conditions. PMID:25132171

  19. Differential DNA methylome profiling of nonfunctioning pituitary adenomas suggesting tumour invasion is correlated with cell adhesion.

    PubMed

    Gu, Ye; Zhou, Xinyao; Hu, Fan; Yu, Yong; Xie, Tao; Huang, Yuying; Zhao, Xinzhi; Zhang, Xiaobiao

    2016-08-01

    Global and gene-specific changes to the epigenome are hallmarks of most tumours including those of pituitary origin, and this fact might offer important clues about diagnostic and therapeutic applications. We performed global DNA methylation screening with 6 invasive and 6 noninvasive nonfunctioning pituitary adenomas (PA) to investigate whether DNA methylation was associated with the invasion of nonfunctioning pituitary adenomas. An additional seven PAs were included as an independent cohort to validate the initial results. Five thousand nine hundred thirty-one CpGs were selected (△β ≥0.15 and p value ≤0.01) as differentially methylated sites (DMSs). The hypomethylated DMSs in the invasive PAs were significantly more than the hypermethylated sites. Cluster analysis of 339 CpGs (△β ≥0.25 and p value ≤0.001) demonstrated a complete distinction between the invasive and noninvasive nonfunctioning groups. GO analysis of the three hundred seven corresponding genes shown they were involved in homophilic cell adhesion, cell-cell adhesion, cell adhesion and biological adhesion. The mRNA expression of GALNT9 which contain a validated DMS was significantly downregulated in invasive group. Our findings indicate that the differential DNA methylome profiling of invasive and noninvasive nonfunctioning PAs suggesting tumour invasion is correlated with cell adhesion. PMID:27168190

  20. 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

  1. Treatment Complexities of a Young Woman Suffering Psychosis and Pituitary Adenoma

    PubMed Central

    Sigman, Maxine; Drury, Kate

    2011-01-01

    This paper is a clinical description of the presentation, therapy, and pharmacological management of a 28-year-old woman who had nine admissions to a psychiatry ward, the last four within one year. It became clear that the treatments, which the patient had received concurrently for ten years for a pituitary adenoma and for psychotic symptoms, were counteractive. The case highlights the importance of the role of prolactin in psychosis and of an interdisciplinary team approach when patients present with complex symptoms. PMID:22937400

  2. 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

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

    PubMed Central

    Zhou, Ying; Zhu, Yicheng; Wang, Wenze

    2016-01-01

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

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

    PubMed

    Zhou, Ying; Zhu, Yicheng; Wang, Wenze; Xing, Bing

    2016-03-01

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

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

    PubMed Central

    2010-01-01

    Pituitary adenomas are associated with a variety of clinical manifestations resulting from excessive hormone secretion and tumor mass effects, and require a multidisciplinary management approach. This article discusses the treatment modalities for the management of patients with a prolactinoma, Cushing's disease and acromegaly, and summarizes the options for medical therapy in these patients. First-line treatment of prolactinomas is pharmacotherapy with dopamine agonists; recent reports of cardiac valve abnormalities associated with this class of medication in Parkinson's disease has prompted study in hyperprolactinemic populations. Patients with resistance to dopamine agonists may require other treatment. First-line treatment of Cushing's disease is pituitary surgery by a surgeon with experience in this condition. Current medical options for Cushing's disease block adrenal cortisol production, but do not treat the underlying disease. Pituitary-directed medical therapies are now being explored. In several small studies, the dopamine agonist cabergoline normalized urinary free cortisol in some patients. The multi-receptor targeted somatostatin analogue pasireotide (SOM230) shows promise as a pituitary-directed medical therapy in Cushing's disease; further studies will determine its efficacy and safety. Radiation therapy, with medical adrenal blockade while awaiting the effects of radiation, and bilateral adrenalectomy remain standard treatment options for patients not cured with pituitary surgery. In patients with acromegaly, surgery remains the first-line treatment option when the tumor is likely to be completely resected, or for debulking, especially when the tumor is compressing neurovisual structures. Primary therapy with somatostatin analogues has been used in some patients with large extrasellar tumors not amenable to surgical cure, patients at high surgical risk and patients who decline surgery. Pegvisomant is indicated in patients who have not responded to

  6. 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

  7. 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. PMID:21301967

  8. Role of MMP-2 (-1306 C/T) Polymorphism in Pituitary Adenoma

    PubMed Central

    Liutkeviciene, Rasa; Vilkeviciute, Alvita; Kriauciuniene, Loresa; Bernotas, Giedrimantas; Tamasauskas, Arimantas; Zaliuniene, Dalia

    2016-01-01

    Purpose. To determine if the frequency of the genotype of MMP-2 (-1306 C/T) Rs243865 has an influence on the development of pituitary adenoma (PA). Methods. The study enrolled n = 84 patients with PA and a random sample of the population n = 318 (reference group). The genotyping test of MMP-2 (-1306 C/T) was carried out using the real-time polymerase chain reaction method. Results. Analysis of MMP-2 (-1306 C/T) gene polymorphism has not revealed any differences in the genotype (C/C, C/T, and T/T) distribution between the PA patients and the reference group (as follows: 50%, 44%, and 6% versus 59.75%, 33.96%, and 6.29%). MMP-2 (-1306) C/C genotype was rarely observed in noninvasive PA compared to healthy controls: 35.1% versus 59.75%; p = 0.0049, as well C/C genotype being more frequently detected in nonrecurrence PA compared to healthy controls: 46.5% versus 59.75%; p = 0.0468. MMP-2 (-1306) C/T genotype was more frequently present in PA females compared to healthy controls females: 49.1% versus 33.66%; p = 0.041. Conclusion. Patients with noninvasive and nonrecurrence pituitary adenoma were the carriers of the C/C genotype significantly more frequently than their control counterparts and the C/T genotype in females was more frequent. PMID:27051552

  9. Outcomes and Complications of Endoscopic Versus Microscopic Transsphenoidal Surgery in Pituitary Adenoma.

    PubMed

    Guvenc, Gonul; Kizmazoglu, Ceren; Pinar, Ercan; Imre, Abdülkadir; Kaya, Ismail; Bezircioglu, Hamdi; Yuceer, Nurullah

    2016-06-01

    This retrospective study aimed to define outcomes and complications of endoscopic versus microscopic transsphenoidal surgery in pituitary adenoma. Data of 94 patients who underwent transsphenoidal endoscopic (n = 45) or microscopic surgery (n = 49) between June 2000 and June 2014 for pituitary adenoma, performed at Katip Çelebi University Hospital, were retrospectively analyzed. The patients' symptomatology, type of adenoma, radiologic findings, surgical outcomes, and preoperative and postoperative complications were investigated. The total subtotal resection rate was 73.4% (69 patients) and partial resection rate was 26.6% (25 patients). Total subtotal resection rate was 77.6% (38 patients) in the microscopic group and 68.9% (31 patients) in the endoscopic group. Total resection was seen more often in the endoscopic group than in the microscopic group, with no significant difference between the groups. Four patients (8.2%) in the microscopic group had postoperative cerebrospinal fluid leak compared with 3 patients (6.7%) in the endoscopic group. Two patients (2.1%) had hematoma, with 1 patient each in the endoscopic and microscopic group. Panhypopituitarism development rate was higher in the endoscopic group (no significant difference between the 2 groups). One patient (2%) developed blindness in the microscopic group and 1 (2.2%) had meningitis in the endoscopic group. Based on this study, the total resection rate was higher in the microscopic group than in the endoscopic group. However, outcomes and complication rate did not differ significantly between the 2 surgical techniques. Both techniques have advantages and disadvantages. Prospective randomized controlled trials should be conducted to compare the 2 surgical methods. PMID:27213744

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

    SciTech Connect

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

    2008-04-01

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

  11. 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

  12. Relationship between pituitary adenoma texture and collagen content revealed by comparative study of MRI and pathology analysis

    PubMed Central

    Wei, Liangfeng; Lin, Shun-an; Fan, Kaichun; Xiao, Deyong; Hong, Jingfang; Wang, Shousen

    2015-01-01

    This study is to reveal the relationship between pituitary adenomas and tumor texture by comparing MRI and pathologic results. Preoperative imaging data of 38 cases of pituitary adenoma patients and collagen content of tumor specimens measured by histopathological were analyzed and compared. T2WI and diffusion coefficient assessment were used to reveal the relationship between tumor texture and collagen content. There were 13 cases of soft texture, 17 cases of medium texture and 8 cases of tough texture tumors. Signal intensity of different texture Pituitary adenomas had significant difference on T2WI and ADC map (P < 0.05). The signal intensity ratio of tumor and pons on T2WI had high consistency with tumor texture. Mean collagen contents of soft, medium and tough texture group were 1.51% ± 0.91%, 7.35% ± 2.99% and 18.10% ± 8.24%, respectively. There were significant differences in collagen content of different texture tumors (P < 0.01). The signal intensity of T2WI and ADC images have prediction value for pituitary adenomas texture and T2WI is more reliable. PMID:26550206

  13. 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. PMID:24291479

  14. Pathology, Pathogenesis and Therapy of Growth Hormone (GH)-producing Pituitary Adenomas: Technical Advances in Histochemistry and Their Contribution

    PubMed Central

    Osamura, Robert Y.; Egashira, Noboru; Kajiya, Hanako; Takei, Mao; Tobita, Maya; Miyakoshi, Takashi; Inomoto, Chie; Takekoshi, Susumu; Teramoto, Akira

    2009-01-01

    Growth hormone (GH)-producing adenomas (GHomas) are one of the most frequently-occurring pituitary adenomas. Differentiation of hormone-producing cells in the pituitary gland is regulated by transcription factors and co-factors. The transcription factors include Pit-1, Prop-1, NeuroD1, Tpit, GATA-2, SF-1. Aberrant expression of transcription factors such as Pit-1 results in translineage expression of GH in adrenocorticotropic hormone-producing adenomas (ACTHomas). This situation has been substantiated by GFP-Pit-1 transfection expression in the AtT20 cell line. Experimentally, GHomas have been induced in GH-releasing hormone (GHRH) or Prop-1 transgenic animals. Immunohistochemical detection of somatostatin receptor (SSTR2a) has recently emphasized their role in the response of GHomas to somatostatin analogue therapy. In this review, the advances in technology and their contribution to cell biology and medical practice are discussed. PMID:19759870

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

    PubMed Central

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

    2002-01-01

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

  16. 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

  17. 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

  18. 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.

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

    PubMed Central

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

    2012-01-01

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

  20. Postoperative Low-Flow Cerebrospinal Fluid Leak of Endoscopic Endonasal Transsphenoidal Surgery for Pituitary Adenoma

    PubMed Central

    Zhan, Rucai; Chen, Songyu; Xu, Shujun; Liu, James K.; Li, Xingang

    2015-01-01

    Abstract To assess the effectiveness of continuous lumbar drainage (LD) for management of postoperative cerebrospinal fluid leaks after endoscopic endonasal transsphenoidal approach for resection of pituitary adenoma. Three hundred eighty-four medical records of patients who were admitted to our institute during a 2.5-year period were retrospectively reviewed, 33 of them experienced low-flow cerebrospinal fluid leak postoperatively. If LD was used, all patients with low-flow cerebrospinal fluid leak were classified into 2 groups, lumbar drained group and conservatively treated group. The age, sex, management of cerebrospinal fluid leaks, and related complications were reviewed. Statistical comparisons between the 2 groups were made using SPSS 19.0 (IBM Corp, Armonk, NY). The differences were considered statistically significant if the P value was less than 0.05. Thirty-three of 384 (8.6%) experienced low-flow postoperative cerebrospinal fluid leaks. Cured rate of cerebrospinal fluid leak was 94.4% (17/18) in continuous lumbar drained group, and 93.3% (14/15) in control group. There were 2 (11.2%) patients who developed meningitis in the LD group and 1 (5.6%) patient in the control group. One patient required endoscopic repair of skull base because of persistent cerebrospinal fluid leak in both groups, with the rates of 5.6% and 6.7%, respectively. There was no significant difference noted in each rate in both groups. Placement of LD may not be necessary for the management of low-flow postoperative cerebrospinal fluid leak after using endoscopic endonasal transsphenoidal approach to pituitary adenoma. PMID:26080170

  1. 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

  2. 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.

  3. GH-Producing Pituitary Adenoma and Concomitant Rathke's Cleft Cyst: A Case Report and Short Review.

    PubMed

    Tamura, Ryota; Takahashi, Satoshi; Emoto, Katsura; Nagashima, Hideaki; Toda, Masahiro; Yoshida, Kazunari

    2015-01-01

    Concomitant pituitary adenoma (PA) and Rathke's cleft cyst (RCC) are rare. In some cases, such PA is known to produce pituitary hormones. A 53-year-old man was admitted to our hospital with a diagnosis of lacunar infarction in the left basal ganglia. Magnetic resonance imaging (MRI) incidentally showed a suprasellar mass with radiographic features of RCC. When he consulted with a neurosurgical outpatient clinic, acromegaly was suspected based on his appearance. A diagnosis of growth hormone- (GH-) producing PA was confirmed from hormonal examinations and additional MRI. Retrospectively, initial MR images also showed intrasellar mass that is compatible with the diagnosis of PA other than suprasellar RCC. The patient underwent endonasal-endoscopic removal of the PA. Since we judged that the RCC of the patient was asymptomatic, only the PA was completely removed. The postoperative course of the patient was uneventful and GH levels gradually normalized. Only 40 cases of PA with concomitant RCC have been reported to date, including 13 cases of GH-producing PA. In those 13 cases, RCC tended to be located in the sella turcica, and suprasellar RCC like this case appears rare. In a few cases, concomitant RCCs were fenestrated, but GH levels normalized postoperatively as in the cases without RCC fenestration. If radiographic imaging shows typical RCC, and PA is not obvious at first glance, the possibility of concomitant PA still needs to be considered. In terms of treatment, removal of the RCC is not needed to achieve hormone normalization. PMID:25883817

  4. Risk of thromboembolic events in patients with prolactinomas compared with patients with nonfunctional pituitary adenomas.

    PubMed

    Mon, Sann Yu; Alkabbani, Abdulrahman; Hamrahian, Amir; Thorton, Julie N; Kennedy, Lawrence; Weil, Robert; Olansky, Leann; Doshi, Krupa; Makin, Vinne; Hatipoglu, Betul

    2013-12-01

    Prolactin has been proposed as a potent coactivator of platelet aggregation, possibly contributing to thromboembolic events. The objective of the study was to evaluate the relationship between prolactinoma and deep vein thrombosis (DVT), pulmonary embolism (PE), and cerebrovascular accident (CVA). Subjects were identified from a prospectively maintained pituitary database at the Cleveland Clinic. We retrospectively reviewed the charts of 544 subjects: 347 patients with prolactinomas (prolactinoma group) and 197 patients with nonfunctional pituitary adenomas (control group). Main outcome measures were DVT, PE and CVA. We found that 19 (5.5%) patients in the prolactinoma group and five (2.5%) patients in the control group had documented DVT, PE, or CVA, but this difference was not significant (p = 0.109). However, the mean initial prolactin level was higher at the time of diagnosis among prolactinoma patients than among controls (815.23 ng/ml vs. 15.90 ng/ml; p < 0.001). Among prolactinoma patients, 15 (5.5%) of 275 patients who underwent medical treatment (with cabergoline, bromocriptine, pergolide and/or other drug) and 4 (5.6%) of 72 patients who underwent transsphenoidal surgery had documented DVT, PE, or CVA, which suggests that dopaminergic therapy did not influence the risk of thromboembolic events. Hyperprolactinemia per se does not appear to predispose to a hypercoagulable state. PMID:23203499

  5. [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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed

    Ahmed, Asma; Furqan, Saira; Islam, Najmul

    2012-01-01

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

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

    PubMed

    Ma, Jun; Liu, Pinan

    2014-01-01

    Growth-hormone staining pituitary adenoma is a popular disease of the central nervous system. We noticed some patients have accompanying cystic disorders. Several cases of concomitant growth-hormone (GH)-staining pituitary adenoma and other cystic changes have been reported but with no further investigation. We report a case of adult growth-hormone staining pituitary adenoma with accompanying polycystic changes of multiple systems, as well as hypertension and nephrolithiasis. Preoperative clinical assessment revealed intrasellar tumor, multinodular thyroid disorder, renal cysts, and hepatic cysts, with increased serum growth-hormone level and normal thyroid hormone level. The total tumor resection was performed via endoscopic transsphenoidal approach. The pathologic analysis reported growth-hormone staining pituitary adenoma. The postoperative course was uneventful. The endocrine testing was normal soon after the operation and the patient remained well for a follow-up period of eight months. This is the fifth report about simultaneous growth-hormone staining pituitary adenoma and polycystic changes of the kidneys and the liver. With review of the literature we speculate that the abnormal growth hormone secretion of the pituitary adenoma may arouse sequential cystic changes of multiple systems through some IGF-I involved pathways. PMID:25038593

  10. 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

  11. 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

  12. 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

  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. 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

  15. 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

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

    PubMed

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

    2012-09-01

    A 39-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) presented with acromegaly and a pituitary macroadenoma. There was a family history of this renal disorder. She had undergone surgery for pituitary adenoma 6 years prior. Physical examination disclosed bitemporal hemianopsia and elevation of both basal growth hormone (GH) 106 ng/mL (normal 0-5) and insulin-like growth factor (IGF-1) 811 ng/mL (normal 48-255) blood levels. A magnetic resonance imaging scan disclosed a 3.0 cm sellar and suprasellar mass with both optic chiasm compression and left cavernous sinus invasion. Pathologic, cytogenetic, molecular and in silico analysis was undertaken. Histologic, immunohistochemical and ultrastructural studies of the lesion disclosed a sparsely granulated somatotroph adenoma. Standard chromosome analysis on the blood sample showed no abnormality. Sequence analysis of the coding regions of PKD1 and PKD2 employing DNA from both peripheral leukocytes and the tumor revealed the most common PKD1 mutation, 5014_5015delAG. Analysis of the entire SSTR5 gene disclosed the variant c.142C>A (p.L48M, rs4988483) in the heterozygous state in both blood and tumor, while no pathogenic mutations were noted in the MEN1, AIP, p27Kip1 and SSTR2 genes. To our knowledge, this is the fourth reported case of a GH-producing pituitary adenoma associated with ADPKD, but the first subjected to extensive morphological, ultrastructural, cytogenetic and molecular studies. The physical proximity of the PKD1 and SSTR5 genes on chromosome 16 suggests a causal relationship between ADPKD and somatotroph adenoma. PMID:21744088

  17. 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

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

    PubMed Central

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

    2015-01-01

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

  19. 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

  20. Vestibular schwannoma and pituitary adenoma in the same patient: coincidence or novel clinical association?

    PubMed

    Carlson, Matthew L; Patel, Neil S; Glasgow, Amy E; Habermann, Elizabeth B; Grossardt, Brandon R; Link, Michael J

    2016-05-01

    Over the years the authors have evaluated a number of patients with vestibular schwannomas (VS) who have also been diagnosed with a pituitary adenoma (PA). No associations between these tumors have been established to date. The objective of the current study is to investigate the epidemiological association between VS and PA via a population-based study and to supplement these data with a retrospective case series of 12 patients who were evaluated at the authors' center over the past 15 years. An analysis of the Surveillance, Epidemiology, and End Results database including all patients identified with a diagnosis of VS and/or PA was performed. A comparison between the observed and expected annual incidence was calculated and population differences between those with VS + PA were compared with single tumor populations. 9888 patients with VS and 26,577 patients with PA were identified among 822.9 million person-years. Within these populations, 31 patients were diagnosed with both tumor types. Overall, 1 in every 319 patients with VS was also diagnosed with a PA. The average annual incidence for VS was 1.2 per 100,000 persons per year while the average PA rate was 3.2 per 100,000 persons per year. The observed rate of co-incident VS and PA was greater than what is expected by chance alone assuming independence. The cohort of patients with coexisting VS and PA were older and more commonly male compared to VS-only or PA-only groups. These data strongly suggest that a common environmental or genetic predisposition exists for VS and PA development. Further study of this population may help elucidate the cause of tumorigenesis in a subset of patients with seemingly sporadic tumors. PMID:26903014

  1. Identification of candidate target genes of pituitary adenomas based on the DNA microarray.

    PubMed

    Zhou, Wei; Ma, Chun-Xiao; Xing, Ya-Zhou; Yan, Zhao-Yue

    2016-03-01

    The present study aimed to explore molecular mechanisms involved in pituitary adenomas (PAs) and to discover target genes for their treatment. The gene expression profile GSE4488 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using the Limma package and analyzed by two‑dimensional hierarchical clustering. Gene ontology (GO) and pathway enrichment analyses were performed in order to investigate the functions of DEGs. Subsequently, the protein‑protein interaction (PPI) network was constructed using Cytoscape software. DEGs were then mapped to the connectivity map database to identify molecular agents associated with the underlying mechanisms of PAs. A total of 340 upregulated and 49 downregulated DEGs in PA samples compared with those in normal controls were identified. Hierarchical clustering analysis showed that DEGs were highly differentially expressed, indicating their aptness for distinguishing PA samples from normal controls. Significant gene ontology terms were positive regulation of immune system-associated processes for downregulated DEGs and skeletal system development for upregulated DEGs. Pathways significantly enriched by DEGs included extracellular matrix (ECM)‑receptor interaction, the Hedgehog (Hh) signaling pathway and neuroactive ligand‑receptor interaction. The PPI network was constructed with 117 nodes, 123 edges and CD44 and Gli2 as hub nodes. Furthermore, depudecin, a small molecule drug, was identified to be mechanistically associated with PA. The genes CD44 and Gli2 have important roles in the progression of PAs via ECM‑receptor interaction and the Hh signaling pathway and are therefore potential target genes of PA. In addition, depudecin may be a candidate drug for the treatment of PAs. PMID:26782791

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

    PubMed Central

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

    2015-01-01

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

  3. 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

  4. 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

  5. Effect of repeated transsphenoidal surgery in recurrent or residual pituitary adenomas: A systematic review and meta-analysis

    PubMed Central

    Heringer, Lindolfo Carlos; de Oliveira, Matheus Fernandes; Rotta, José Marcus; Botelho, Ricardo Vieira

    2016-01-01

    Background: Recurrent or residual pituitary adenomas previously treated by transsphenoidal surgery are not uncommon. There are no strongly established guidelines to perform treatment of such cases. The objective of this study is to elucidate the effect of transsphenoidal reoperation in residual or recurrent pituitary adenomas. Methods: We made a systematic review of the literature to elucidate this effect through electronic search in MEDLINE/PubMed and Cochrane Central database. PRISMA statement was used as a basis for this systematic review and analysis of the risk of bias was made according to the Grading of Recommendations, Assessment, Development and Evaluation recommendations. Results: In this review, fifteen studies were finally pooled analyzed. Although remission rates (RRs) and follow-up periods varied widely, from 149 patients with growth hormone-secreting tumors the mean RR was 44.5%, from 273 patients with adrenocorticotropic hormone-secreting tumors the mean RR was 55.5% and among 173 patients with nonsecreting tumors, RR was 76.1%. There was significant higher RR in nonsecreting tumors. Mean follow-up was 32.1 months. No difference was found between microscopic and endoscopic techniques. Conclusions: A second transsphenoidal surgery is accompanied by a chance of remission in approximately half of cases with secreting tumors. In nonsecreting ones, success is higher. PMID:26958420

  6. Case report of sarcoma of the sella caused by postoperative radiotherapy for a prolactin-producing pituitary adenoma.

    PubMed

    Kurosaki, Masamichi; Kambe, Atsushi; Ishibashi, Minako; Watanabe, Takashi; Horie, Yasushi

    2014-07-01

    We report a case of sarcomatous transformation of a prolactin (PRL)-producing pituitary adenoma in a 27-year-old man. He originally presented with bitemporal visual disturbance, headache, and hyperprolactinemia 8 years earlier. Tumor shrinkage was confirmed by magnetic resonance imaging (MRI) during treatment with dopamine-receptor agonist. However, 3 years later transsphenoidal surgery had to be performed because of tumor re-growth. Histopathological examination revealed a PRL-producing adenoma with fibrotic changes. One year later, he presented with right-sided visual disturbance, and tumor re-growth was confirmed using MRI. He underwent transcranial surgery, followed by radiation therapy (50 Gy in 25 fractions). The histological and immunostaining features were similar in both specimens obtained from the two operations. Four years later, he presented with left-sided visual disturbance, and tumor re-growth was confirmed using MRI. The mass lesion dramatically increased in size within 2 months, and partial removal of the tumor by craniotomy was performed. The specimen was histologically diagnosed as malignant fibrous histiocytoma (MFH). Regardless of aggressive chemotherapy, his clinical symptoms and imaging findings worsened rapidly. He died 7 months after the diagnosis of MFH. Because patients with pituitary tumor undergoing radiotherapy face the possibility of developing such neoplasm, long-term follow-up is required. PMID:24446079

  7. 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

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

    PubMed Central

    2014-01-01

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

  9. 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. PMID:26720589

  10. Surgical outcomes of the endoscopic endonasal transsphenoidal approach for large and giant pituitary adenomas: institutional experience with special attention to approach-related complications.

    PubMed

    Constantino, Edson Rocha; Leal, Rafael; Ferreira, Christian Cândido; Acioly, Marcus André; Landeiro, José Alberto

    2016-05-01

    Objective In this study, we investigate our institutional experience of patients who underwent endoscopic endonasal transsphenoidal approach for treatment of large and giant pituitary adenomas emphasizing the surgical results and approach-related complications. Method The authors reviewed 28 consecutive patients who underwent surgery between March, 2010 and March, 2014. Results The mean preoperative tumor diameter was 4.6 cm. Gross-total resection was achieved in 14.3%, near-total in 10.7%, subtotal in 39.3%, and partial in 35.7%. Nine patients experienced improvement in visual acuity, while one patient worsened. The most common complications were transient diabetes insipidus (53%), new pituitary deficit (35.7%), endonasal adhesions (21.4%), and cerebrospinal fluid leak (17.8%). Surgical mortality was 7.1%. Conclusions Endoscopic endonasal transsphenoidal surgery is a valuable treatment option for large or giant pituitary adenomas, which results in high rates of surgical decompression of cerebrovascular structures. PMID:27191235

  11. Impact of nasoseptal flap elevation on sinonasal quality of life in endoscopic endonasal approach to pituitary adenomas.

    PubMed

    Jalessi, Maryam; Jahanbakhshi, Amin; Amini, Elahe; Kamrava, Seyyed Kamran; Farhadi, Mohammad

    2016-05-01

    To evaluate the impact of nasoseptal flap (NSF) elevation on sinonasal quality of life (QOL) in patients with pituitary adenomas who underwent endoscopic endonasal trans-sphenoidal approach (EETSA), the data of 106 eligible patients were included from February 2011 to December 2014. The scores of Sinonasal Outcome Test (SNOT-22) Questionnaire were assessed in case (that received reconstruction with NSF) and control groups preoperatively as well as 1, 3, 6, and more than 12 months postoperatively. Nine most related sinonasal questions were evaluated separately (9Q). There were no significant inter-group differences in the mean SNOT-22, 9Q, and sense of taste/smell scores in preoperative and all postoperative assessments. Within each group, a significant improvement of SNOT-22 and 9Q scores were noted after 12 months of surgery compared to preoperative data. In the NSF group, comparison of the pre- and first postoperative evaluation revealed a significant deterioration in 9Q score (p = 0.007) and "sense of taste/smell" (p < 0.001) which both returned to baseline in the 3rd month. Patients who used nasal paper mask for more than 100 "hour-days" showed a better SNOT-22 scores at 1st (p = 0.04) and 3rd (p < 0.001) months after surgery. Patients with adrenocorticotropic hormone (ACTH) secretory adenomas showed significantly higher scores of SNOT-22 in all postoperative assessments compared to the others. Although nasal symptoms deteriorated at first postoperative month (compare to preoperative data) in the NSF group, no negative impacts on the sinonasal QOL was showed comparing to the control group. ACTH-secreting adenomas could be assumed as a risk factor for poorer sinonasal QOL in EETSA. PMID:26220192

  12. 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

  13. Surgical Outcomes Using a Medial-to-Lateral Endonasal Endoscopic Approach to Pituitary Adenomas Invading the Cavernous Sinus

    PubMed Central

    Woodworth, Graeme F.; Patel, Kunal S.; Shin, Benjamin; Burkhardt, Jan-Karl; Tsouris, A. John; McCoul, Edward D.; Anand, Vijay K.; Schwartz, Theodore H.

    2014-01-01

    OBJECT To detail the extent of resection and complications with endonasal endoscopic surgery for pituitary tumors invading the cavernous sinus (CS) using a moderately aggressive approach to maximize extent of resection through the medial cavernous sinus wall while minimizing the risk of cranial neuropathy and blood loss. Tumor in the medical cavernous sinus was aggressively pursued while tumor in the lateral cavernous sinus was debulked in preparation for radiosurgery. METHODS A prospective surgical database of consecutive endonasal pituitary surgeries with verified CS invasion on intraoperative visual inspection was reviewed. The extent of resection as a whole and within the CS was assessed by an independent neuroradiologist using pre- and post-operative Knosp-Steiner (KS) categorization and volumetrics of the respective magnetic resonance images. The extent of resection and clinical outcomes were compared for medial (KS1-2) and lateral (KS3-4) lesions. RESULTS Thirty-six consecutive patients with pituitary adenomas involving the CS who had surgery via an endonasal endoscopic approach were identified. The extent of resection was 84.6% for KS 1–2 and 66.6% for KS 3–4 (p=.04). Gross-total resection was 53.8% for KS 1–2 and 8.7% for KS 3–4 (p=.0006). Of six patients (16.8%) with pre-operative cranial neuropathies, all showed subjective improvement after surgery. Surgical complications included 2 transient post-operative cranial neuropathies (5.6%), 1 postoperative CSF leak (2.8%), 1 reoperation for mucocele (2.8%) and 1 infection (2.8%). CONCLUSIONS The endoscopic endonasal “medial-to-lateral” approach permits safe debulking of tumors in the medial and lateral CS. Although GTR rates are moderate, particularly in the lateral CS, the risk of permanent cranial neuropathy is extremely low with a high chance of improvement of pre-existing deficits. This approach can also facilitate targeting for post-operative radiosurgery. PMID:24527820

  14. 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.

  15. 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

  16. 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...

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

    PubMed

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

    2015-03-01

    The aim of the study was to establish if the null cell adenoma (NCA) forms a distinct subgroup with unique clinicopathological characteristics within the nonfunctioning pituitary adenoma group particularly in relation to the silent gonadotroph adenomas (SGAs). We identified 31 patients with the pathological diagnosis of NCA verified by routine histology and immunohistochemistry with distinct differentiation from SGAs by an established negative testing for SF-1 at the Toronto Western Hospital between December 2004 and August 2010. We reviewed their demographic data, clinical features, magnetic resonance imaging, and the histologic variables: MIB-1, FGFR4, and P27. We compared these to 63 SGAs identified within the same period. All the NCAs were macroadenomas with diameter ranging from 15-57 mm and tumor volumes between 1.95-53.5 mm(3). Preoperative cavernous sinus tumor growth was able to predict the presence of a residual after surgery (p = 0.023). Furthermore, preoperative cavernous sinus extension (p = 0.002) and negative P27 expression (p = 0.035) were able to independently predict the subsequent growth of the postoperative tumor residual. Comparing the NCA to SGA, we found that MIB-1 was higher in NCA (mean ± SD = 3.43 ± 2.76 %) compared to SGAs (mean ± SD = 2.49 ± 1.41 %) (p = 0.044). The preoperative and postoperative tumor volume doubling times (TVDTs) displayed a negative correlation in the SGA (r = -0.855, p = 0.002) while in the NCA, a positive correlation was evident (r = 0.718, p = 0.029). Our study suggests that the NCAs are a distinct group with differing behavioral characteristics from the SGAs. It also appears that the finding of cavernous sinus extension on preoperative imaging and a negative P27 expression on immunohistochemistry in NCAs may be valuable tools in predicting residual tumor growth which may impact on postoperative care. PMID:25403448

  18. 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 ...

  19. Evidence for possible role of toll-like receptor 3 mediating virus-induced progression of pituitary adenomas.

    PubMed

    Zheng, Xin; Li, Song; Zang, Zhenle; Hu, Jintao; An, Jiayin; Pei, Xiangdong; Zhu, Feng; Zhang, Weihua; Yang, Hui

    2016-05-01

    Tumor-related viruses are known to be involved in initiation and progression of certain tumors. However, the relationship between virus and pituitary adenomas (PAs) remains unknown. Here, we investigated infection status of three types of viruses (HPV16, HHV6B and HSV1) and expression level of toll-like receptor 3 (TLR3) in 60 human PA samples. We also determined the role of TLR3 signaling pathway on a PA cell line (GH3). We firstly found that positive rates of HPV16 and HHV6B infection were significantly higher in invasive PA samples than in noninvasive samples (P < 0.01). Similarly, TLR3 mRNA and protein expression also increased in invasive PA samples (P < 0.01). In vitro analysis indicated that GH3 cell proliferation and survival were enhanced by TLR3 activation, which was accompanied by NF-κB activation. Our data indicate that HPV16 and HHV6B viruses may be involved in promoting the progression of PA by activating the TLR3 signaling pathway. PMID:26891958

  20. 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

  1. 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.

  2. 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.

  3. Effects of somatostatin-14 and the receptor-specific somatostatin analogs on chromogranin A and alpha-subunit (alpha-SU) release from "clinically nonfunctioning" pituitary adenoma cells incubated in vitro.

    PubMed

    Pawlikowski, M; Lawnicka, H; Pisarek, H; Kunert-Radek, J; Radek, M; Culler, M D

    2007-03-01

    The aim of the study was to examine the effect of somatostatin (SST) and its analogs on the release of chromogranin A (CgA) and alpha-subunit (alpha-SU) from clinically non-functioning pituitary adenomas incubated in vitro. Seven pituitary macroadenomas surgically removed were investigated. All of the tumors were diagnosed before surgery as non-functioning, but they expressed either gonadotropins or their subunits as detected by immunohistochemistry. Two tumors additionally expressed prolactin and growth hormone. All adenomas also expressed chromogranin A (CgA) and at least 3 of 5 subtypes of somatostatin receptors. The cells isolated from the examined tumors were exposed in vitro to either native SST-14 or the following receptor-specific SST analogs: BIM-23926 (agonist of sst1 receptor), BIM-23120 (agonist of sst2 receptor), BIM-23206 (agonist of sst5 receptor) and BIM23A387 (somatostatin/dopamine chimera). The concentration of CgA was measured by means of ELISA method and of alpha-SU was measured by an immunoradiometric method. It was found that the exposure on SST-14 resulted in the decrease of CgA and alpha-SU release from tumor cells in majority of samples, and the effect on CgA was positively correlated with the expression of sst3 and also with the sst2A/sst2B expressions ratio. The inhibitory effect of SST-14 on CgA and alpha-SU seems also to correlate negatively with the expression of sst2B. CgA inhibition also correlates positively with sst5 expression. Among the other compounds studied, only the sst2 agonist decreased the release in all the investigated samples. The remaining substances (agonists of sst1 and sst5 and SST/DA chimera) produced the divergent changes (increased or decreased release, depending on the sample). The data suggest that the inhibition of CgA (and possibly of alpha-SU) release by SST is mediated via subtypes sst2A, sst3 and sst5, whereas sst2B subtype may induce the opposite effect. PMID:17440235

  4. 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.

  5. Locally produced estrogen through aromatization might enhance tissue expression of pituitary tumor transforming gene and fibroblast growth factor 2 in growth hormone-secreting adenomas.

    PubMed

    Ozkaya, Hande Mefkure; Comunoglu, Nil; Keskin, Fatma Ela; Oz, Buge; Haliloglu, Ozlem Asmaz; Tanriover, Necmettin; Gazioglu, Nurperi; Kadioglu, Pinar

    2016-06-01

    Aromatase, a key enzyme in local estrogen synthesis, is expressed in different pituitary tumors including growth hormone (GH)-secreting adenomas. We aimed to evaluate aromatase, estrogen receptor α (ERα), estrogen receptor β (ERβ), pituitary tumor transforming gene (PTTG), and fibroblast growth factor 2 (FGF2) expressions in GH-secreting adenomas, and investigate their correlation with clinical, pathologic, and radiologic parameters. This cross-sectional study was conducted in a tertiary center in Turkey. Protein expressions were determined via immunohistochemical staining in ex vivo tumor samples of 62 patients with acromegaly and ten normal pituitary tissues. Concordantly increased aromatase, PTTG, and FGF2 expressions were detected in the tumor samples as compared with controls (p < 0.001 for all). None of the tumors expressed ERα while ERβ was detected only in mixed somatotroph adenomas. Aromatase, ERβ, PTTG expressions were not significantly different between patients with and without remission (p > 0.05 for all). FGF2 expression was significantly higher in patients without postoperative and late remission (p = 0.002 and p = 0.012, respectively), with sphenoid bone invasion, optic chiasm compression, and somatostatin analog resistance (p = 0.005, p = 0.033, and p = 0.013, respectively). Aromatase, PTTG and FGF2 expressions were positively correlated with each other (r = 0,311, p = 0.008 for aromatase, FGF2; r = 0.380, p = 0.001 for aromatase, PTTG; r = 0.400, p = 0.001 for FGF2, PTTG). PTTG-mediated FGF2 upregulation is associated with more aggressive tumor features in patients with acromegaly. Also, locally produced estrogen through aromatization might have a role in this phenomenon. PMID:26578364

  6. 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

  7. STA-MCA Bypass as a “Bridge” to Pituitary Surgery in a Patient with an Adenoma Occluding the Internal Carotid Artery: Case Report and Review of the Literature

    PubMed Central

    Lanterna, Luigi A.; Brembilla, Carlo; Signorelli, Antonio; Gritti, Paolo; Costi, Emanuele; Dorelli, Gianluigi; Bernucci, Claudio

    2015-01-01

    Occlusion of the intracranial internal carotid artery (ICA) by a pituitary adenoma with resulting cerebral ischemia is a very rare but devastating occurrence. The authors present a case in which a condition of symptomatic ICA occlusion due to a giant pituitary adenoma was successfully treated using a preliminary extraintracranial bypass as a “bridge” to the tumor removal. A 52-year-old patient presented with a minor stroke followed by pressure-dependent transient ischemic attacks consistent with a condition of hypoperfusion. MR imaging and a digital subtraction angiography revealed a pituitary adenoma occluding the ICA on the right side. He underwent a superficial temporal artery to middle cerebral artery (STA-MCA) bypass with the aim of revascularizing the ischemic hemisphere and reducing the risk of perioperative stroke or stroke evolution. The patient was subsequently operated on to remove the adenoma through a transsphenoidal approach. The postoperative course was uneventful and the patient has suffered no further ischemic events. When there are no emergency indications to decompress the optical pathways but the patient is at risk of impending stroke because of ICA occlusion, a two-step strategy consisting of a bypass and subsequent removal of the pituitary adenoma may be a valuable option. PMID:26425379

  8. Prospective comparison of sinonasal outcomes after microscopic sublabial or endoscopic endonasal transsphenoidal surgery for nonfunctioning pituitary adenomas.

    PubMed

    Pledger, Carrie L; Elzoghby, Mohamed A; Oldfield, Edward H; Payne, Spencer C; Jane, John A

    2016-08-01

    OBJECT Both endoscopic and microscopic transsphenoidal approaches are accepted techniques for the resection of pituitary adenomas. Although studies have explored patient outcomes for each technique individually, none have prospectively compared sinonasal and quality of life outcomes in a concurrent series of patients at the same institution, as has been done in the present study. METHODS Patients with nonfunctioning adenomas undergoing transsphenoidal surgery were assessed for sinonasal function, quality of life, and pain using the Sino-Nasal Outcome Test-20 (SNOT-20), the short form of the Nasal Obstruction Symptom Evaluation (NOSE) instrument, the SF-36, and a headache scale. Eighty-two patients undergoing either endoscopic (47 patients) or microscopic (35 patients) surgery were surveyed preoperatively and at 24-48 hours, 2 weeks, 4 weeks, 8 weeks, and 1 year after surgery. RESULTS Patients who underwent endoscopic and microscopic transsphenoidal surgery experienced a similar recovery pattern, showing an initial increase in symptoms during the first 2 weeks, followed by a return to baseline by 4 weeks and improvement beyond baseline functioning by 8 weeks. Patients who underwent endoscopic surgery experienced better sinonasal outcomes at 24-48 hours (SNOT total p = 0.015, SNOT rhinologic subscale [ssRhino] p < 0.001), 2 weeks (NOSE p = 0.013), and 8 weeks (SNOT total p = 0.032 and SNOT ssRhino p = 0.035). By 1 year after surgery, no significant differences in sinonasal outcomes were observed between the 2 groups. Headache scales at 1 year improved in all dimensions except duration for both groups (total result 73%, p = 0.004; severity 46%, p < 0.001; frequency 53%, p < 0.001), with 80% of either microscopic or endoscopic patients experiencing improvement or resolution of headache symptoms. Endoscopic and microscopic patients experienced reduced vitality preoperatively compared with US population norms and remained low postoperatively. By 8 weeks after surgery

  9. Determination of cell proliferation using Mcm2 antigen and evaluation of apoptosis and TGF-beta1 expression in GH-secreting or clinically nonfunctioning pituitary adenomas.

    PubMed

    Dallago, Cristina Micheletto; Barbosa-Coutinho, Ligia Maria; Ferreira, Nelson Pires; Meurer, Rosalva; Pereira-Lima, Julia Fernanda Semmelmann; Oliveira, Miriam da Costa

    2010-03-01

    Pituitary adenomas (PA) occasionally show aggressive behavior, with invasion of the surrounding tissues. The identification of markers able to recognize aggressive PA in early stages remains a challenge. We aimed to determine the expression of a new cell proliferation marker, Mcm2, and the presence of apoptosis in PA, and to evaluate the association of clinicopathological features with the apoptotic and proliferative indices. Additionally, the TGF-beta1 expression, an inducer of apoptosis, was determined. The proliferative index was determined in GH-secreting or clinically nonfunctioning PA using immunohistochemical (IH) methods for Mcm2 and Ki-67 antigens. The apoptosis was assessed by the TUNEL method and the TGF-beta1 expression by IH. A significant positive correlation was found between log Mcm2 index and log Ki-67 index (p < 0.001). Mcm2 and Ki-67 detected a similar number of proliferating cells. Mcm2 index showed a significant association with tumor extension (p = 0.02), but not with tumor invasion. Apoptosis was detected in 17% of the adenomas, with a maximum apoptotic index of 0.77%. Immunoreactivity to TGF-beta1 was observed in 77% of the adenomas, showing an association with tumor extension. We concluded that, in this sample, Mcm2 was similar to Ki-67 in the identification of the proliferating cells and that apoptosis was rare. PMID:20174894

  10. A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up.

    PubMed

    Trouillas, Jacqueline; Roy, Pascal; Sturm, Nathalie; Dantony, Emmanuelle; Cortet-Rudelli, Christine; Viennet, Gabriel; Bonneville, Jean-François; Assaker, Richard; Auger, Carole; Brue, Thierry; Cornelius, Aurélie; Dufour, Henry; Jouanneau, Emmanuel; François, Patrick; Galland, Françoise; Mougel, François; Chapuis, François; Villeneuve, Laurent; Maurage, Claude-Alain; Figarella-Branger, Dominique; Raverot, Gérald; Barlier, A; Bernier, M; Bonnet, F; Borson-Chazot, F; Brassier, G; Caulet-Maugendre, S; Chabre, O; Chanson, P; Cottier, J F; Delemer, B; Delgrange, E; Di Tommaso, L; Eimer, S; Gaillard, S; Jan, M; Girard, J J; Lapras, V; Loiseau, H; Passagia, J G; Patey, M; Penfornis, A; Poirier, J Y; Perrin, G; Tabarin, A

    2013-07-01

    Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy. PMID:23400299

  11. A patient with Cushing disease lateralizing a pituitary adenoma by inferior petrosal sinus sampling using desmopressin: a case report.

    PubMed

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

    2016-03-01

    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

  12. 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

  13. Postoperative Low-Flow Cerebrospinal Fluid Leak of Endoscopic Endonasal Transsphenoidal Surgery for Pituitary Adenoma--Wait and See, or Lumbar Drain?

    PubMed

    Zhan, Rucai; Chen, Songyu; Xu, Shujun; Liu, James K; Li, Xingang

    2015-06-01

    To assess the effectiveness of continuous lumbar drainage (LD) for management of postoperative cerebrospinal fluid leaks after endoscopic endonasal transsphenoidal approach for resection of pituitary adenoma. Three hundred eighty-four medical records of patients who were admitted to our institute during a 2.5-year period were retrospectively reviewed, 33 of them experienced low-flow cerebrospinal fluid leak postoperatively. If LD was used, all patients with low-flow cerebrospinal fluid leak were classified into 2 groups, lumbar drained group and conservatively treated group. The age, sex, management of cerebrospinal fluid leaks, and related complications were reviewed. Statistical comparisons between the 2 groups were made using SPSS 19.0 (IBM Corp, Armonk, NY). The differences were considered statistically significant if the P value was less than 0.05.Thirty-three of 384 (8.6%) experienced low-flow postoperative cerebrospinal fluid leaks. Cured rate of cerebrospinal fluid leak was 94.4% (17/18) in continuous lumbar drained group, and 93.3% (14/15) in control group. There were 2 (11.2%) patients who developed meningitis in the LD group and 1 (5.6%) patient in the control group. One patient required endoscopic repair of skull base because of persistent cerebrospinal fluid leak in both groups, with the rates of 5.6% and 6.7%, respectively. There was no significant difference noted in each rate in both groups.Placement of LD may not be necessary for the management of low-flow postoperative cerebrospinal fluid leak after using endoscopic endonasal transsphenoidal approach to pituitary adenoma. PMID:26080170

  14. Direct effects of vitamin D3 analogues on G-protein mediated signalling systems in rat osteosarcoma cells and rat pituitary adenoma cells.

    PubMed

    Mortensen, B M; Lund, H W; Jablonski, G; Paulssen, R H; Gordeladze, J O

    1995-06-01

    In normal rats treated with 1,25(OH)2D3 or 24,25(OH)2D3, serum Ca2+, ALP, PRL and GH are significantly altered. In order to study the primary effect of vitamin D3 analogues on target organ function, rat UMR 106 osteosarcoma and GH3 pituitary adenoma cells in monolayer culture were exposed accordingly. Surprisingly, prolonged exposure of these cell lines to physiological levels of either 1,25(OH)2D3 or 24,25(OH)2D3 did not significantly affect the secretory parameters (ALP, PRL or GH) tested. However, 1,25(OH)2D3 exposure significantly reduced PTH- and Gpp(NH)p-elicited AC as well as Gpp(NH)p-stimulated PLC activities in the UMR 106 cells. These changes were accompanied by an increase and decrease in the membrane contents of the G-protein subunits G36 beta and Gq/11 alpha, respectively. In contrast, 24,25(OH)2D3 remained without significant biological effect on these signalling systems despite concomitantly augmented levels of G36 beta. TRH- and Gpp(NH)p-elicited PLC activities in the GH3 cells were significantly reduced by 1,25(OH)2D3 with a concurrent reduction in cellular amounts of Gq/11 alpha, however, 24,25(OH)2D3 did not significantly alter any signalling systems nor G-proteins analyzed. It is concluded that the osteoblastic and pituitary cell secretion of ALP, PRL and GH remain unaffected by the presence of 1,25(OH)2D3 and 24,25(OH)2D3, despite distinct alterations in components of G-protein mediated signalling pathways. Hence, other factors like ambient Ca2+ may be responsible for the perturbed secretory patterns of ALP and PRL seen in vitamin D3 treated rats. PMID:7579039

  15. 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

  16. 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

  17. 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

  18. Assessing the presence of abnormal regulation of cortisol secretion by membrane hormone receptors: in vivo and in vitro studies in patients with functioning and non-functioning adrenal adenoma.

    PubMed

    Dall'Asta, C; Ballarè, E; Mantovani, G; Ambrosi, B; Spada, A; Barbetta, L; Colombo, P; Travaglini, P; Loli, P; Beck-Peccoz, P

    2004-08-01

    Regulation of cortisol secretion by aberrant hormone receptors may play a role in the pathogenesis of ACTH-independent Cushing's syndrome. In this study, the topic was evaluated by combining in vivo and in vitro approaches. Cortisol responses to various stimuli (standard meal, GnRH + TRH, cisapride, vasopressin, glucagon) were assessed in 6 patients with clinical or subclinical adrenal Cushing's syndrome, and non-functioning adrenal adenoma in two cases. Abnormal responses were observed in three patients with Cushing's syndrome; one patient showed a gastric inhibitory polypeptide (GIP)-dependent cortisol rise after meal, together with responses after GnRH and cisapride; the second patient showed an LH-dependent cortisol response to GnRH, and in the third cortisol rose after cisapride. The pattern of receptor expression performed by RT-PCR showed that while GIP-R was only expressed in tumor from the responsive patient, 5-hydroxytryptamine type 4 receptor and LH-R were also present in normal adrenal tissues and tissues from non-responsive patients. Interestingly, an activating mutation of Gsalpha gene was identified in one of these tumors. Therefore, cortisol responses to agents operating via Gs protein coupled receptors (in one case associated with Gsalpha mutation) were found in Cushing's patients, while these responses were absent in the others. The finding of receptor expression in normal and non-responsive tumors suggests that different mechanisms are probably involved in inducing in vivo cortisol responses. PMID:15326569

  19. 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

  20. 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.

  1. 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

  2. [Intrapituitary adenoma metastasis from lung cancer with progressive cranial nerve palsies: a case report and literature review].

    PubMed

    Fujimori, Takeshi; Okauchi, Masanobu; Shindo, Atsushi; Kawanishi, Masahiko; Miyake, Keisuke; Kawai, Nobuyuki; Tamiya, Takashi

    2014-10-01

    We report a rare case of metastasis to a preexisting pituitary adenoma. An 80-year-old man with a history of pituitary adenoma and lung cancer presented with recent onset of bilateral visual impairment, oculomotor nerve palsies, and severe headache. A CT scan revealed a pituitary tumor expanding into the suprasellar region and infiltrating the bilateral cavernous sinuses. We performed transsphenoidal surgery and diagnosed the tumor as lung cancer metastasis to the pituitary adenoma. After the surgery, visual impairment and severe headache were resolved, and the patient underwent radiation therapy for the residual tumor. To the best of our knowledge, 20 cases of metastases to pituitary adenomas have been reported in the literature. Clinical features of metastasis to a pituitary adenoma are different from those of metastasis to normal pituitary gland. In the case of a pituitary lesion with acute aggravation, one should be aware of the possibility of metastasis to preexisting pituitary adenomas. PMID:25266586

  3. 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

  4. Molecular Imaging of Pituitary Pathology.

    PubMed

    de Herder, Wouter W

    2016-01-01

    The presence of large numbers and/or the high affinity of dopamine D2 and/or somatostatin receptors on pituitary adenomas may enable their visualization with radionuclide-coupled receptor agonists or antagonists. However, the role of these imaging modalities in the differential diagnosis of or therapeutic purposes for pituitary lesions is very limited. Only in very specific cases might these molecular imaging techniques become helpful. These include the differential diagnosis of pituitary lesions, ectopic production of pituitary hormones, such as adrenocorticotrophic hormone, growth hormone (GH) or their releasing hormones (corticotropin-releasing hormone and GH-releasing hormone), and the localization of metastases from pituitary carcinomas. PMID:27002335

  5. 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

  6. Pituitary metastases from the oncocytic variant of follicular thyroid carcinoma: a case report and diagnostic dilemmas.

    PubMed

    Matyja, Ewa; Zieliński, Grzegorz; Witek, Przemysław; Kamiński, Grzegorz; Grajkowska, Wiesława; Maksymowicz, Maria

    2013-01-01

    Metastases to the pituitary gland and sella turcica are uncommon. The distinction between primary and secondary metastatic pituitary tumours is challenging as carcinomas from distant sites might closely resemble, both clinically and histopathologically, non-functional adenomas or primary pituitary carcinomas. Among metastases to pituitary gland ones from thyroid carcinoma are extremely rare. We present a unique case of a 53-year-old male patient with a past history of thyroid carcinoma who underwent repeated surgeries over a period of 7 years for a sellar-parasellar mass with paranasal sinus involvement. Morphologically, the tumour was composed of solid sheaths of monomorphic cells exhibiting oncocytic features. In electron microscope images, the cytoplasm of tumour cells was filled with numerous mitochondria. The tumour was negative for pituitary hormones but exhibited immunoreactivity for cytokeratin AE1/AE3, thyroglobulin and thyroid transcription factor 1 (TTF-1). Based on the clinical data and immunophenotypic profile, the tumour was finally diagnosed as an oncocytic variant of follicular thyroid carcinoma. To our knowledge, this is probably the first report of such peculiar histopathological variant of follicular thyroid carcinoma metastasizing to the pituitary gland. The diagnostic dilemmas considering oncocytic features of the presented case are discussed. PMID:24114644

  7. 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

  8. Cerebrospinal fluid rhinorrhoea in pituitary tumours1

    PubMed Central

    Cole, I E; Keene, Malcolm

    1980-01-01

    Three cases of CSF rhinorrhoea due to pituitary tumours are reported and the literature reviewed. The treatment of choice appears to be trans-sphenoidal exploration of the pituitary fossa with insertion of a free muscle graft followed by radiotherapy. The probability of the tumour being a prolactin-secreting adenoma is discussed. PMID:7017123

  9. [Pituitary apoplexy in a young woman.

    PubMed

    Lewis, Anna; Jarløv, Anne Elisabeth; Holm, Kirsten; Cleemann, Line

    2014-04-22

    Pituitary apoplexy occurs when a preexisting pituitary adenoma undergoes acute haemorrhage, infarct or both. The patho-genesis is not fully understood but macroadenomas and prolactinomas have been reported as being predisposed to apoplexy. Only a few cases are described in the paediatric population. We present a 17-year-old woman with secondary amenorrhoea, headache and blurred vision. An MRI showed a pituitary apoplexy in a preexisting macroadenoma. The majority of milder cases resolve spontaneously. Close monitoring of the pituitary function is important to detect pituitary insufficiency witch may need long-term hormone replacement therapy. PMID:25351468

  10. 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. PMID:26718581

  11. 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.

  12. 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

  13. Radiosurgery for infundibulum adenoma: stalk dose implications.

    PubMed

    Sokolowski, Jennifer D; Cohen-Inbar, Or; Sheehan, Jason P

    2016-09-01

    Treating pituitary adenomas in the infundibulum with stereotactic radiosurgery (SRS), achieving tumor volume control while preserving pituitary endocrine function and visual function, is challenging. We present a case of a recurrent remnant infundibular lesion treated with Gamma Knife surgery (GKS). The mass was treated with microsurgical resection twice, and the residual stalk lesion was treated with single-session SRS employing a margin dose of 15 Gy to the infundibulum. Five years after GKS, tumor regression persists without visual dysfunction or hypopituitarism. Radiosurgical doses of 30 Gy to the pituitary stalk may be tolerated by patients while maintaining endocrine function. PMID:27435739

  14. Adenoma

    Cancer.gov

    Well circumscribed areas consisting of cuboidal to columnar cells lining alveoli. The size is usually less than 5 mm in diameter. These lesions retain preexisting alveolar structure and tend to be multiple in existing mouse models. Absence of pronounced fibrovascular stroma, as well as more "plump" shape of epithelial cells, may be the reason for different appearance of mouse adenomas, as compared to their human counterparts. Differentiation between a small adenoma and focal hyperplasia can be very difficult. At the same time, no absolute criteria exist for distinguishing a large adenoma from a well-differentiated adenocarcinoma. Among features indicating benign character are a small size, and absence of vascular invasion. Well delineated demarcation and absence of lepidic growth are considered by some as indicators of a benign character. Bland character of nuclei is a main feature of human adenomas. By this criterion many mouse adenomas could be assigned to adenocarcinomas. However, unlike in humans, mouse tumors rarely metastasize during the time of their observation.

  15. Animal models of pituitary neoplasia

    PubMed Central

    Lines, K.E.; Stevenson, M.; Thakker, R.V.

    2016-01-01

    Pituitary neoplasias can occur as part of a complex inherited disorder, or more commonly as sporadic (non-familial) disease. Studies of the molecular and genetic mechanisms causing such pituitary tumours have identified dysregulation of >35 genes, with many revealed by studies in mice, rats and zebrafish. Strategies used to generate these animal models have included gene knockout, gene knockin and transgenic over-expression, as well as chemical mutagenesis and drug induction. These animal models provide an important resource for investigation of tissue-specific tumourigenic mechanisms, and evaluations of novel therapies, illustrated by studies into multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome in which ∼30% of patients develop pituitary adenomas. This review describes animal models of pituitary neoplasia that have been generated, together with some recent advances in gene editing technologies, and an illustration of the use of the Men1 mouse as a pre clinical model for evaluating novel therapies. PMID:26320859

  16. Outcomes of endoscopic transsphenoidal pituitary surgery.

    PubMed

    Dallapiazza, Robert F; Jane, John A

    2015-03-01

    Since the 1990s, endoscopic transsphenoidal surgery for pituitary adenomas has increased in popularity. Outcomes of endoscopic surgery for clinically secretory adenomas are favorable, and results for nonfunctional tumors reveal high rates of complete resection, improvements in vision, and low rates of complications. This article discusses some of the recent studies reporting outcomes from endoscopic series for Cushing disease, acromegaly, prolactin-secreting tumors, and nonfunctioning macroadenomas. PMID:25732647

  17. Pituitary abscess.

    PubMed

    Rudwan, M A

    1977-05-28

    Three cases of pituitary abscess are presented. The history of recurrent attacks of aseptic meningitis, together with radiological and clinical features suggestive of pituitary tumor, appear to form a fairly typical picture of the condition. Long follow-up was possible in two of the cases. There are no radiological features which distinguish the lesion from pituitary tumor, hence the importance of recognizing the significance of such a clinical presentation with radiological evidence of sellar enlargement. Pituitary abscesses seem to occur in preexisting pituitary tumors. The possible relationship with pituitary infarction is discussed. PMID:865667

  18. Pituitary gland

    MedlinePlus Videos and Cool Tools

    ... gland is the hypothalamus. The hypothalamus decides which hormones the pituitary should release by sending it either ... the hypothalamus, the pituitary gland releases the following hormones: GH (growth hormone) – increases size of muscle and ...

  19. 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

  20. 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

  1. Malignant intrasellar meningioma presenting as an invasive pituitary macroadenoma: A rare case report and literature review

    PubMed Central

    ZHOU, PEIZHI; YIN, SENLIN; JIANG, SHU; CAI, BOWEN

    2016-01-01

    Intrasellar meningiomas are rare tumors that have the ability to mimic non-functioning pituitary adenomas. The majority of meningiomas are slow-growing and benign, therefore an intrasellar meningioma with malignant histological features is extremely rare. The present study describes the case of a malignant diaphragm meningioma that was controlled through combined chemotherapy, following subtotal surgical resection. The patient's symptoms ceased and no tumor recurrence was detected at the 3-year follow-up. Hormone levels were also observed as normal. Further investigation of similar cases may aid in achieving an accurate pre-operative diagnosis. This would prove particularly beneficial in regards to intrasellar meningiomas due to their specific location and surgical treatment. The present study analyzes the requirement of chemotherapy for the treatment of these unique tumors. PMID:26893694

  2. Pituitary tumor

    MedlinePlus

    ... The pituitary is a small gland at the base of the brain. It regulates the body's balance of many hormones. ... cause symptoms and are never diagnosed during the person's lifetime. ... at the base of the brain. The pituitary helps control the ...

  3. 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. PMID:26054868

  4. 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

  5. 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

  6. 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

  7. Histopathological and immunohistochemical characterization of spontaneous pituitary tumors in dwarfs derived from Wistar Hannover GALAS rats.

    PubMed

    Kokoshima, Hiroko; Yamada, Naoaki; Doi, Takuya; Tsuchitani, Minoru; Yamate, Jyoji

    2016-01-01

    Histopathological and immunohistochemical characteristics of spontaneous pituitary adenomas found in dwarfs derived from Wistar Hanover GALAS are being described for the first time. The adenomas were seen in 5 males aged 48 weeks or older and in 11 females aged 34 weeks or older. Immunohistochemically, 13 cases without post-mortem changes could be evaluated; 4 Thyroid stimulating hormone (TSH)-containing adenomas, 2 TSH- and prolactin (PRL)-containing adenomas, 1 PRL-containing adenoma and 6 all-negative adenomas that did not react to any of the examined anti-hormone antibodies. The most common type were TSH-containing pituitary adenomas (a total of 6 cases; 46%) which occurred exclusively in females; the tumors consisted mainly of basophilic or amphophilic cells with bizarre nuclei and neoplastic cells and were positive for TSH in varying degrees. The TSH-containing pituitary adenomas, a characteristic of this mutant rat, could be induced by genetically-controlled hypothyroidism in dwarf rats, with higher sensitivity to possible disturbance of the pituitary-thyroid axis in females. PMID:26597119

  8. Pituitary Changes in Prop1 Transgenic Mice: Hormone Producing Tumors and Signet-ring Type Gonadotropes

    PubMed Central

    Egashira, Noboru; Minematsu, Takeo; Miyai, Syunsuke; Takekoshi, Susumu; Camper, Sally A.; Osamura, Robert Y.

    2008-01-01

    Prophet of Pit-1 (Prop1) is an early transcription factor that delays the appearance of gonadotropin in the developing pituitaries. Prop1 transgenic (Tg) mice have been shown to generate pituitary tumors that either produce TSH or are non-hormone producing. In our series of Prop1 Tg mice, only 5 out of 9 female mice produced pituitary adenomas, and the adenomas were only GH, PRL, GH and PRL, PRL and gonadotropin or TSH producing. The pituitary cells that surrounded these adenomas showed hyperplasia of the corresponding hormone producing cells; i.e. the GH cells were increased in the pituitary that contained GH producing adenoma. In addition, although the adenomas lacked the expression of Prop1, the non-neoplastic pituitary cells showed expression of Prop1. The Prop1 Tg mice also showed vacuolated cells with eccentric nuclei, which are characteristic of “signet-ring hypertrophic cells”. Using immunohistochemistry, these signet ring hypertrophic cells were found to be positive for gonadotropin. Taken together, our results suggest a (1) tumorigenic effect of Prop1 in the pituitaries, and (2) causative effects of signet ring-type gonadotropes. PMID:18636109

  9. The retinoblastoma gene in human pituitary tumors

    SciTech Connect

    Cryns, V.L.; Arnold, A.; Alexander, J.M.; Klibanski, A. )

    1993-09-01

    Functional inactivation of the retinoblastoma (RB) tumor suppressor gene is important in the pathogenesis of many human tumors. Recently, the frequent occurrence of pituitary tumors was reported in mice genetically engineered to have one defective RB allele, a genetic background analogous to that of patients with familial retinoblastoma. The molecular pathogenesis of human pituitary tumors is largely unknown, and the potential role of RB gene inactivation in these neoplasms has not been examined. Consequently, the authors studied 20 human pituitary tumors (12 clinically nonfunctioning tumors, 4 somatotroph adenomas, 2 prolactinomas, and 2 corticotrophy adenomas) for tumor-specific allelic loss of the RB gene using a highly informative polymorphic locus within the gene. Control leukocyte DNA samples from 18 of these 20 patients were heterozygous at this locus, permitting genetic evaluation of their paired tumor specimens. In contrast to the pituitary tumors in the mouse model, none of these 18 human tumors exhibited RB allelic loss. These findings indicate that RB gene inactivation probably does not play an important role in the pathogenesis of common types of human pituitary tumors. 24 refs., 1 fig.

  10. 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

  11. Xanthogranulomatous hypophysitis: a rare and often mistaken pituitary lesion

    PubMed Central

    Gopal-Kothandapani, Jaya Sujatha; Bagga, Veejay; Wharton, Stephen B; Connolly, Daniel J; Sinha, Saurabh

    2015-01-01

    Summary Xanthogranulomatous hypophysitis (XGH) is a very rare form of pituitary hypophysitis that may present both clinically and radiologically as a neoplastic lesion. It may either be primary with an autoimmune aetiology and can occur in isolation or as a part of autoimmune systemic disease or secondary as a reactive degenerative response to an epithelial lesion (e.g. craniopharyngioma (CP), Rathke's cleft cyst, germinoma and pituitary adenomas) or as a part of a multiorgan systemic involvement such as tuberculosis, sarcoidosis or granulomatosis. It may also present with a variation of symptoms in children and adults. Our case series compares the paediatric and adult presentations of XGH and the differential diagnoses considered in one child and two adult patients, highlighting the wide spectrum of this condition. Endocrine investigations suggested panhypopituitarism in all three patients and imaging revealed a suprasellar mass compressing the optic chiasm suggestive of CP or Rathke's cleft cyst in one patient and non-functioning pituitary macroadenoma in two patients. Magnetic resonance imaging (MRI) demonstrated mixed signal intensities on T1- and T2-weighted sequences. Following endoscopic transsphenoidal surgery, histological analysis revealed necrotic material with a xanthogranulomatous reaction confirming XGH in two patients and a necrobiotic granulomatous chronic inflammatory infiltrate with neutrophils in one patient, which is not typical of current descriptions of this disorder. This case series describes the wide spectrum of XGH disease that is yet to be defined. Mixed signal intensities on T1- and T2-weighted MRI sequences may indicate XGH and diagnosis is confirmed by histology. Histological variation may indicate an underlying systemic process. Learning points XGH is a rare form of pituitary hypophysitis with a wide clinical and histological spectrum and can mimic a neoplastic lesion.XGH primarily presents with growth arrest in children and pubertal

  12. Nipple adenoma in infancy.

    PubMed

    Clune, James E; Kozakewich, Harry P; VanBeek, Christine A; Labow, Brian I; Greene, Arin K

    2009-11-01

    We report the first patient with a nipple adenoma presenting in infancy. Nipple adenoma is a benign lesion typically affecting women between 45 and 55 years of age. This lesion can occur in the pediatric population and should be included in the differential diagnosis of an infantile breast lesion. Management of children with nipple adenoma requires consideration for breast development; excision before maturity may cause nipple-areola deformity or injury to the breast bud. PMID:19944237

  13. Pituitary Tumors

    MedlinePlus

    ... org Tel: 773-577-8750; 800-886-2282 Fax: 847-827-9918 National Brain Tumor Society 55Chapel ... http://www.braintumor.org Tel: 866-455-3214 Fax: 617-924-9998 Pituitary Network Association P.O. ...

  14. Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland.

    PubMed

    Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

    2016-01-01

    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

  15. 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

  16. 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

  17. 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 ...

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

    PubMed

    Wang, Xiong; Ge, Li; Cui, Yuanqing; Lang, Cuihong; Hao, Cuifang

    2014-04-01

    FSH-secreting pituitary adenomas can affect sexual and reproductive function. In this article, we have reported the case of a 32-year-old male with secondary infertility. The patient had sexual and reproductive disturbances. The test results of the blood samples indicated obviously decreased testosterone (T) and estradiol (E2) levels. Based on previous hormonal results, the patient received pituitary stimulation and human chorionic gonadotropin (hCG) tests. Both follicle stimulating hormone (FSH) and luteinizing hormone (LH) showed low response during the pituitary stimulation test. The results of the hCG test indicated that T/E2 could recover to a normal level. In addition, this patient was diagnosed with pituitary macroadenoma, which was supported by the pituitary MRI. The man's sexual and reproductive functions recovered following surgery. The pathological results confirmed that the tumor tissue was an FSH-secreting pituitary adenoma by immunohistochemical staining. The purpose of this report was to review the relative literature and discuss the influence of FSH-secreting pituitary adenomas on hormones through the hypothalamus-pituitary-testis axis. PMID:24696774

  19. Thyrotropinoma with Graves’ disease detected by the fusion of indium-111 octreotide scintigraphy and pituitary magnetic resonance imaging

    PubMed Central

    Okuyucu, Kursat; Alagoz, Engin; Arslan, Nuri; Taslipinar, Abdullah; Deveci, Mehmet Salih; Bolu, Erol

    2016-01-01

    Thyroid-stimulating hormone-secreting pituitary adenoma (TSHoma) is a rare benign endocrinological tumor which produces TSH in the pituitary gland. Herein, we presented a female patient having TSHoma with Graves’ disease during and just after pregnancy that we found by indium-111 octreotide scintigraphy while investigating the patient for hyperthyroidism symptoms. PMID:27095865

  20. Thyrotropinoma with Graves' disease detected by the fusion of indium-111 octreotide scintigraphy and pituitary magnetic resonance imaging.

    PubMed

    Okuyucu, Kursat; Alagoz, Engin; Arslan, Nuri; Taslipinar, Abdullah; Deveci, Mehmet Salih; Bolu, Erol

    2016-01-01

    Thyroid-stimulating hormone-secreting pituitary adenoma (TSHoma) is a rare benign endocrinological tumor which produces TSH in the pituitary gland. Herein, we presented a female patient having TSHoma with Graves' disease during and just after pregnancy that we found by indium-111 octreotide scintigraphy while investigating the patient for hyperthyroidism symptoms. PMID:27095865

  1. 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

  2. Occurrence of extensive spherical amyloid deposits in a prolactin-secreting pituitary macroadenoma: a radiologic-pathologic correlation.

    PubMed

    Levine, Steven N; Ishaq, Shmaila; Nanda, Anil; Wilson, Jon D; Gonzalez-Toledo, Eduardo

    2013-08-01

    Pituitary adenomas are the most common tumors of the sellar region, but the occurrence of spherical amyloid deposits in a pituitary adenoma is rare. We describe the clinical features, radiologic characteristics, and pathologic findings of 45-year-old man who presented with galactorrhea, hypogonadism, and hyperprolactinemia who had a pituitary adenoma with extensive spherical amyloid deposits. Approximately 30 cases have been reported, almost exclusively in patients with prolactinomas. Treatment with dopaminergic agonists will result in the expected reduction in prolactin levels; however, in most cases, macroadenomas with spherical amyloid deposits fail to decrease in size. The source of the amyloid deposits in prolactinomas is not clearly defined but may be due to abnormal processing of prolactin or its prohormone. These adenomas with spherical amyloid have a characteristic appearance on magnetic resonance imaging with low or heterogeneous intensity on T1 and low intensity on T2-weighted images. Following infusion of gadolinium, there is enhancement of the periphery but not most of the tumor mass. These magnetic resonance imaging characteristics are different than those of typical pituitary adenomas. These differences should alert clinicians to the possibility of extensive spherical amyloid deposits in a prolactin-secreting pituitary adenoma, which may have important clinical implications. In this report, we correlate the radiologic finds with the pathology and compared them with other sellar and parasellar lesions. PMID:23602507

  3. [Thyroid Adenomas in Children].

    PubMed

    Morozov, D A; Pimenova, E S; Mirokova, E D

    2015-01-01

    According to the papers thyroid nodules are quite rare in the first two decades of life. However, there are some exceptions, relating to areas with an iodine deficiency or affected by radioactive fallout, where the risk of nodules and carcinomas is increased. Therefore, it is a great challenge for the physician to distinguish between benign and malignant lesions preoperatively, and not only in these areas of greater risk. The authors analyzed current works, which are devoted to diagnostics and treatment of adenomas of thyroid gland in children. This literature review is based on works dedicated to epidemiology, histotypes study, and methods of diagnostics, surgical treatment, prognosis and complications of this pathology. The current tendencies in surgical approaches, intraoperative monitoring of recurrent laryngeal nerve are also discussed. The actuality of this problem is connected with last decade increase of adenomas in structure of thyroid gland nodules, increase of number of patients with multiple adenomas and with polypathias: adenomas with nodular goiter, autoimmune thyroiditis and cancer in children. The difficulties of diagnostic of adenomas are related to the similar clinical symptoms, cytogenetic characteristics of growth of benign and malignant lesions of thyroid gland. Additionally there is no systematic review about thyroid adenomas in children recent years. PMID:26846075

  4. 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

  5. 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

  6. Effects of Carbenoxolone on the Canine Pituitary-Adrenal Axis

    PubMed Central

    Teshima, Takahiro; Matsumoto, Hirotaka; Okusa, Tomoko; Nakamura, Yumi; Koyama, Hidekazu

    2015-01-01

    Cushing’s disease caused by pituitary corticotroph adenoma is a common endocrine disease in dogs. A characteristic biochemical feature of corticotroph adenomas is their relative resistance to suppressive negative feedback by glucocorticoids. The abnormal expression of 11beta-hydroxysteroid dehydrogenase (11HSD), which is a cortisol metabolic enzyme, is found in human and murine corticotroph adenomas. Our recent studies demonstrated that canine corticotroph adenomas also have abnormal expression of 11HSD. 11HSD has two isoforms in dogs, 11HSD type1 (HSD11B1), which converts cortisone into active cortisol, and 11HSD type2 (HSD11B2), which converts cortisol into inactive cortisone. It has been suggested that glucocorticoid resistance in corticotroph tumors is related to the overexpression of HSD11B2. Therefore it was our aim to investigate the effects of carbenoxolone (CBX), an 11HSD inhibitor, on the healthy dog’s pituitary-adrenal axis. Dogs were administered 50 mg/kg of CBX twice each day for 15 days. During CBX administration, no adverse effects were observed in any dogs. The plasma adrenocorticotropic hormone (ACTH), and serum cortisol and cortisone concentrations were significantly lower at day 7 and 15 following corticotropin releasing hormone stimulation. After completion of CBX administration, the HSD11B1 mRNA expression was higher, and HSD11B2 mRNA expression was significantly lower in the pituitaries. Moreover, proopiomelanocortin mRNA expression was lower, and the ratio of ACTH-positive cells in the anterior pituitary was also significantly lower after CBX treatment. In adrenal glands treated with CBX, HSD11B1 and HSD11B2 mRNA expression were both lower compared to normal canine adrenal glands. The results of this study suggested that CBX inhibits ACTH secretion from pituitary due to altered 11HSD expressions, and is potentially useful for the treatment of canine Cushing’s disease. PMID:26262685

  7. 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

  8. Response of silent corticotroph pituitary carcinoma to chemotherapy: case report.

    PubMed

    He, Lucy; Forbes, Jonathan A; Carr, Kevin; Highfield Nickols, Hilary; Utz, Andrea; Moots, Paul; Weaver, Kyle

    2016-06-01

    Silent pituitary corticotroph carcinomas are rare, with only six previously described cases in the literature. We report a patient with a silent pituitary corticotroph adenoma treated with multiple trans-sphenoidal resections. Twelve years after her initial presentation, she returned with leptomeningeal metastases to the posterior fossa, foramen magnum, and numerous other subarachnoid locations involving the spine. Histopathology obtained from the metastatic foci was identical to previous trans-sphenoidal specimens - consistent with the diagnosis of corticotroph pituitary carcinoma. A carboplatin and etoposide chemotherapy regimen successfully arrested disease progression and produced regression of multiple radiographically documented leptomeningeal deposits. To the authors' knowledge, this is the first report of a patient with silent pituitary carcinoma treated successfully with chemotherapy. PMID:27150544

  9. Adenoma-Like Adenocarcinoma

    PubMed Central

    Gonzalez, Raul S.; Cates, Justin M.M.; Washington, M. Kay; Beauchamp, R. Daniel; Coffey, Robert J.; Shi, Chanjuan

    2015-01-01

    Aims A subset of colorectal carcinomas (CRCs) architecturally and cytologically resembles adenomatous change, making them difficult to diagnose on biopsy. This subset has not been well-characterized to date. Methods and results For 35 carcinomas with adenomatous-like areas (cytologic and surface architectural appearance that would be insufficient to warrant a diagnosis of adenocarcinoma if evaluated on biopsy), we recorded staging information, molecular data, clinical outcome, whether precursor adenoma was present, and whether prior biopsy had been diagnosed as malignant. Despite advanced T-category in 23 (66%) tumors, only 7 (20%) had nodal metastases, and only 5 patients (15%) developed distant metastases. Fifteen cases (43%) had been diagnosed as adenoma on biopsy. Twenty-one resections (60%) showed no residual associated adenoma, including 9 called adenoma on biopsy. Median follow-up was 44 months. Four patients (12%) died of disease; 22 were alive at last follow-up. KRAS mutation was seen in 14/24 (58%), and 4/17 (24%) were microsatellite-unstable. Patients had significantly improved survival compared to a cohort of patients with conventional well-differentiated CRC after controlling for age and stage (p=0.011). Conclusions Adenoma-like adenocarcinoma is an uncommon variant of CRC with a low rate of metastasis and good prognosis. Biopsy diagnosis of this lesion may be challenging. PMID:25913616

  10. 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