Giant pituitary adenoma: histological types, clinical features and therapeutic approaches.

PubMed

Iglesias, Pedro; Rodríguez Berrocal, Víctor; Díez, Juan José

2018-06-16

Giant pituitary adenomas comprise about 6-10% of all pituitary tumors. They are mostly clinically non-functioning adenomas and occur predominantly in males. The presenting symptoms are usually secondary to compression of neighboring structures, but also due to partial or total hypopituitarism. Functioning adenomas give rise to specific symptoms of hormonal hypersecretion. The use of dopamine agonists is considered a first-line treatment in patients with giant macroprolactinomas. Somatostatin analogs can also be used as primary treatment in cases of growth hormone and thyrotropin producing giant adenomas, although remission of the disease is not achieved in the vast majority of these patients. Neurosurgical treatment, either through transsphenoidal or transcranial surgery, continues to be the treatment of choice in the majority of patients with giant pituitary adenomas. The intrinsic complexity of these tumors requires the use of different therapies in a combined or sequential way. A multimodal approach and a therapeutic strategy involving a multidisciplinary team of expert professionals form the basis of the therapeutic success in these patients.

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. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Peroxisome proliferator-activated receptor (PPAR)gamma is highly expressed in normal human pituitary gland.

PubMed

Bogazzi, F; Russo, D; Locci, M T; Chifenti, B; Ultimieri, F; Raggi, F; Viacava, P; Cecchetti, D; Cosci, C; Sardella, C; Acerbi, G; Gasperi, M; Martino, E

2005-11-01

Expression of peroxisome proliferator-activated receptor (PPAR)gamma in normal pituitary seems to be restricted to ACTH-secreting cells. The aim of the study was to evaluate the expression of PPARgamma in normal human pituitary tissue and to study its localization in the pituitary secreting cells. Normal pituitary tissue samples were obtained form 11 patients with non-secreting adenoma who underwent surgical excision of the tumor. Expression of PPARgamma was evaluated by immunostaining and western blotting; localization of PPARgamma in each pituitary secreting cell lineage was evaluated by double immunofluorescence using confocal microscopy. Pituitary non-functioning adenomas served as Controls. PPARgamma was highly expressed in all pituitary samples with a (mean +/- SD) 81 +/- 6.5% of stained cells; expression of PPARgamma was confirmed by western blotting. Non-functioning pituitary adenomas had 74 +/- 11% PPARgamma positive cells. Expression of PPARy was either in cytoplasm or nuclei. In addition, treatment of GH3 cells, with a PPARgamma ligand was associated with traslocation of the receptor from cytoplasm into the nucleus. Double immunostaining revealed that every pituitary secreting cell (GH, TSH, LH, FSH, PRL and ACTH) had PPARgamma expressed. The present study demonstrated that PPARgamma is highly expressed in every normal pituitary secreting cell lineage. It can translocate into the nucleus by ligand binding; however, its role in pituitary hormone regulation remains to be elucidated.

Non-functioning pituitary adenoma database: a useful resource to improve the clinical management of pituitary tumors.

PubMed

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

2006-12-01

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

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

PubMed

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

2007-01-01

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

Lack of normal MR enhancement of the pituitary gland: findings in three siblings with combined pituitary hormone deficiency.

PubMed

Falcone, S; Sanchez, J; Quencer, R M

1998-02-01

We present the MR appearance of the sella turcica in three sibling dwarfs with combined pituitary hormone deficiency in which MR images revealed a peripheral curvilinear band of enhancement about the pituitary gland in all three patients, a normal-size pituitary gland in two siblings, a mildly enlarged pituitary gland in one sibling, and a thin infundibulum and a normal posterior pituitary bright spot in all three siblings. Possible antecedents include an abnormal vascular supply, pituitary gland replacement by a nonfunctioning adenoma, a proteinaceous cyst, or a hamartoma.

Lineage-Specific Restraint of Pituitary Gonadotroph Cell Adenoma Growth

PubMed Central

Chesnokova, Vera; Zonis, Svetlana; Zhou, Cuiqi; Ben-Shlomo, Anat; Wawrowsky, Kolja; Toledano, Yoel; Tong, Yunguang; Kovacs, Kalman; Scheithauer, Bernd; Melmed, Shlomo

2011-01-01

Although pituitary adenomas are usually benign, unique trophic mechanisms restraining cell proliferation are unclear. As GH-secreting adenomas are associated with p53/p21-dependent senescence, we tested mechanisms constraining non-functioning pituitary adenoma growth. Thirty six gonadotroph-derived non-functioning pituitary adenomas all exhibited DNA damage, but undetectable p21 expression. However, these adenomas all expressed p16, and >90% abundantly expressed cytoplasmic clusterin associated with induction of the Cdk inhibitor p15 in 70% of gonadotroph and in 26% of somatotroph lineage adenomas (p = 0.006). Murine LβT2 and αT3 gonadotroph pituitary cells, and αGSU.PTTG transgenic mice with targeted gonadotroph cell adenomas also abundantly expressed clusterin and exhibited features of oncogene-induced senescence as evidenced by C/EBPβ and C/EBPδ induction. In turn, C/EBPs activated the clusterin promoter ∼5 fold, and elevated clusterin subsequently elicited p15 and p16 expression, acting to arrest murine gonadotroph cell proliferation. In contrast, specific clusterin suppression by RNAis enhanced gonadotroph proliferation. FOXL2, a tissue-specific gonadotroph lineage factor, also induced the clusterin promoter ∼3 fold in αT3 pituitary cells. As nine of 12 pituitary carcinomas were devoid of clusterin expression, this protein may limit proliferation of benign adenomatous pituitary cells. These results point to lineage-specific pathways restricting uncontrolled murine and human pituitary gonadotroph adenoma cell growth. PMID:21464964

Endoscopic endonasal transsphenoidal surgery: surgical results of 228 pituitary adenomas treated in a pituitary center.

PubMed

Gondim, Jackson A; Schops, Michele; de Almeida, João Paulo C; de Albuquerque, Lucas Alverne F; Gomes, Erika; Ferraz, Tânia; Barroso, Francisca Andréa C

2010-01-01

Pituitary tumors are challenging tumors in the sellar region. Surgical approaches to the pituitary have undergone numerous refinements over the last 100 years. The introduction of the endoscope have revolutionized pituitary surgery. The aim of this study is to report the results of a consecutive series of patients undergoing pituitary surgery using a pure endoscopic endonasal approach and to evaluate the efficacy and safety of this procedure. We reviewed the data of 228 consecutive patients who underwent endonasal transsphenoidal adenoma removal over an 10-year period. Pre- and post-operative hormonal status (at least 3 months after surgery) were analyzed and compared with clinical parameters presented by the patients. Tumor removal rate, endocrinological outcomes, and complications were retrospectively assessed in 228 patients with pituitary adenomas who underwent 251 procedures between December 1998 and December 2007. There were 93 nonfunctioning adenomas, 58 growth hormone-secreting, 41 prolactin-secreting, 28 adrenocorticotropin hormone secreting, 7 FSH-LH secreting and 1 thyroid-stimulating hormone-secreting adenomas. Gross total removal was achieved in 79.3% of the cases after a median follow-up of 61.5 months. The remission results for patients with nonfunctioning adenomas was 83% and for functioning adenomas were 76.3% (70.6% for GH hormone-secreting, 85.3% for prolactin hormone-secreting, 71.4% for ACTH hormone-secreting, 85.7% for FSH-LH hormone-secreting and 100% for TSH hormone-secreting), with no recurrence at the time of the last follow-up. Post-operative complications were present in 35 (13.9%) cases. The most frequent complications were temporary and permanent diabetes insipidus (six and two cases, respectively), syndrome of inappropriate antidiuretic hormone secretion (two cases) and CSF leaks (eight cases). There was no death related to the procedure in this series. The endoscopic endonasal approach for resection of pituitary adenomas, provides acceptable results representing a safe alternative procedure to the microscopic approach. This less invasive method, associated with a small number of complications, provides excellent tumor removal rates and represents an important tool for the achievement of good results in the pituitary surgery, mainly for the complete removal of large adenomas.

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

IGF-I levels reflect hypopituitarism severity in adults with pituitary dysfunction.

PubMed

Tirosh, Amit; Toledano, Yoel; Masri-Iraqi, Hiba; Eizenberg, Yoav; Tzvetov, Gloria; Hirsch, Dania; Benbassat, Carlos; Robenshtok, Eyal; Shimon, Ilan

2016-08-01

To evaluate the utility of Insulin-like growth factor I (IGF-I) standard deviation score (SDS) as a surrogate marker of severity of hypopituitarism in adults with pituitary pathology. We performed a retrospective data analysis, including 269 consecutive patients with pituitary disease attending a tertiary endocrine clinic in 1990-2015. The medical files were reviewed for the complete pituitary hormone profile, including IGF-I, and clinical data. Age-adjusted assay reference ranges of IGF-I were used to calculate IGF-I SDS for each patient. The main outcome measures were positive and negative predictive values of low and high IGF-I SDS, respectively, for the various pituitary hormone deficiencies. IGF-I SDS correlated negatively with the number of altered pituitary axes (p < 0.001). Gonadotropin was affected in 76.6 % of cases, followed by thyrotropin (58.4 %), corticotropin (49.1 %), and prolactin (22.7 %). Positive and negative predictive values yielded a clear trend for the probability of low/high IGF-I SDS for all affected pituitary axes. Rates of diabetes insipidus correlated with IGF-I SDS values both for the full study population, and specifically for patients with non-functioning pituitary adenomas. IGF-I SDS can be used to evaluate the somatotroph function, as a valid substitute to absolute IGF-I levels. Moreover, IGF-I SDS predicted the extent of hypopituitarism in adults with pituitary disease, and thus can serve as a marker of hypopituitarism severity.

Comparison of endoscopic and microscopic trans-sphenoidal pituitary surgery: early results in a single centre.

PubMed

Razak, Adam A; Horridge, Michelle; Connolly, Daniel J; Warren, Daniel J; Mirza, Showkat; Muraleedharan, Vakkat; Sinha, Saurabh

2013-02-01

Pituitary surgery has seen a recent shift from a microscopic to an endoscopic trans-sphenoidal approach. We present our early experience with endoscopic surgery and compare the outcome with our recent microscopic experience. From January 2008 until present time, 80 consecutive patients underwent trans-sphenoidal pituitary surgery in our institution. Until September 2009, all patients had a microscopic trans-septal approach. After this time, the patients underwent endoscopic trans-sphenoidal surgery. All patients underwent pre- and post-operative MRI and full endocrinological evaluation. Data was collected prospectively including tumour volume, endocrine function, visual function, length of stay and complications. There were 40 patients in each group. In the microscopic group, there were 26 non-functioning tumours and 14 functioning tumours. In the endoscopic group, there were 24 non-functioning and 16 functioning tumours. There were significantly better results in terms of tumour resection (p = 0.002) and remission (p = 0.018) in the endoscopic group. In this group there was also a lower incidence of CSF leaks and a shorter length of stay for secreting tumours (p = 0.005). 1 patient in the endoscopic group died at day 43 post-operatively, having initially presented in a poor clinical state with pituitary apoplexy. Microscopic trans-sphenoidal surgery remains the benchmark for future surgical techniques. Our early results suggest that endoscopic trans-sphenoidal surgery provides favourable results in both tumour resection and control of secreting tumours in comparison with microscopic surgery. Further longer-term evaluation is required to ensure the outcome of endoscopic surgery.

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

PubMed

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

2017-01-01

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

Analysis of differential gene expression by bead-based fiber-optic array in nonfunctioning pituitary adenomas.

PubMed

Jiang, Z; Gui, S; Zhang, Y

2011-05-01

Nonfunctioning pituitary adenomas (NFPAs) are relatively common, accounting for 30% of all pituitary adenomas; however, their pathogenesis remains enigmatic. To explore the possible pathogenesis of NFPAs, we used fiber-optic BeadArray to examine gene expression in 5 NFPAs compared with 3 normal pituitaries. 4 differentially expressed genes were chosen randomly for validation by reverse transcriptase-real time quantitative polymerase chain reaction (RT-qPCR). We then analyzed the differentially expressed gene profile with Kyoto Encyclopedia of Genes and Genomes (KEGG). The array analysis indentified significant increases in the expression of 1,402 genes and 383 expressed sequence tags (ESTs), and decreases in 1,697 genes and 113 ESTs in the NFPAs. Bioinformatic and pathway analysis showed that the genes HIGD1B, FAM5C, PMAIP1 and the pathway cell-cycle regulation may play an important role in tumorigenesis and progression of NFPAs. Our data suggest fiber-optic BeadArray combined with pathway analysis of differential gene expression profile appears to be a valid approach for investigating the pathogenesis of tumors. © Georg Thieme Verlag KG Stuttgart · New York.

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

PubMed Central

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

2015-01-01

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

Clinical characteristics of pain in patients with pituitary adenomas.

PubMed

Dimopoulou, C; Athanasoulia, A P; Hanisch, E; Held, S; Sprenger, T; Toelle, T R; Roemmler-Zehrer, J; Schopohl, J; Stalla, G K; Sievers, C

2014-11-01

Clinical presentation of pituitary adenomas frequently involves pain, particularly headache, due to structural and functional properties of the tumour. Our aim was to investigate the clinical characteristics of pain in a large cohort of patients with pituitary disease. In a cross-sectional study, we assessed 278 patients with pituitary disease (n=81 acromegaly; n=45 Cushing's disease; n=92 prolactinoma; n=60 non-functioning pituitary adenoma). Pain was studied using validated questionnaires to screen for nociceptive vs neuropathic pain components (painDETECT), determine pain severity, quality, duration and location (German pain questionnaire) and to assess the impact of pain on disability (migraine disability assessment, MIDAS) and quality of life (QoL). We recorded a high prevalence of bodily pain (n=180, 65%) and headache (n=178, 64%); adrenocorticotropic adenomas were most frequently associated with pain (n=34, 76%). Headache was equally frequent in patients with macro- and microadenomas (68 vs 60%; P=0.266). According to painDETECT, the majority of the patients had a nociceptive pain component (n=193, 80%). Despite high prevalence of headache, 72% reported little or no headache-related disability (MIDAS). Modifiable factors including tumour size, genetic predisposition, previous surgery, irradiation or medical therapy did not have significant impact neither on neuropathic pain components (painDETECT) nor on headache-related disability (MIDAS). Neuropathic pain and pain-related disability correlated significantly with depression and impaired QoL. Pain appears to be a frequent problem in pituitary disease. The data suggest that pain should be integrated in the diagnostic and therapeutic work-up of patients with pituitary disease in order to treat them appropriately and improve their QoL. © 2014 European Society of Endocrinology.

Pituitary Adenoma Apoplexy in an Adolescent: A Case Report and Review of the Literature

PubMed Central

Zijlker, Hero; Schagen, Sebastian; Wit, Jan Maarten; Biermasz, Nienke; van Furth, Wouter; Oostdijk, Wilma

2017-01-01

We present a 13-year-old boy who was admitted with complaints of a state of progressive sleepiness and a sudden headache with vomiting and fever. Laboratory testing showed hypoglycemia, multiple pituitary hormonal deficiencies, and an elevated C-reactive protein level. A cranial magnetic resonance imaging (MRI) showed an opaque sphenoid sinus and an intrasellar mass suggesting hemorrhage, so that we suspected pituitary apoplexy (PA) originating from a non-functioning adenoma, although a pituitary abscess could not completely be excluded. The boy was treated with antibiotics, hydrocortisone, and levothyroxine. Due to his rapid clinical improvement, no surgery was performed and we considered the diagnosis of PA as confirmed. At follow-up, the MRI scan showed a small residual lesion. Pituitary deficiencies of growth hormone, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone, and vasopressin persisted. A literature search of all well-documented cases of PA in children or adolescents (n=30, 13 boys and 17 girls) indicated that this condition is rare below 20 years of age but must be considered when a patient experiences headache with or without visual disturbances, even in the presence of clinical and laboratory signals suggestive of pituitary abscess. MRI neuroimaging is helpful in the differential diagnosis. In both conditions, the possibility of ACTH deficiency should always be considered, investigated, and treated. In cases without severe neuro-ophthalmological deficits and/or with a rapid and positive response to acute medical management, one can abstain from surgical treatment. PMID:28588003

Assessment of Environmental and Hereditary Influence on Development of Pituitary Tumors Using Dermatoglyphic Traits and Their Potential as Screening Markers.

PubMed

Gradiser, Marina; Matovinovic Osvatic, Martina; Dilber, Dario; Bilic-Curcic, Ines

2016-03-17

The aim of this study was to assess environmental and hereditary influence on development of pituitary tumors using dermatoglyphic traits. The study was performed on 126 patients of both genders with pituitary tumors (60 non-functional and 66 functional pituitary tumor patients) in comparison to the control group of 400 phenotypically healthy individuals. Statistical analysis of quantitative and qualitative traits of digito-palmar dermatoglyphics was performed, and hormonal status was determined according to the standard protocols. Although we did not find markers that could specifically distinguish functional from non-functional tumors, we have found markers predisposing to the development of tumors in general (a small number of ridges between triradius of both hands, a smaller number of ridges between the triradius of c-d rc R), those for endocrine dysfunction (increased number of arches and reduced number of whorls, difference of pattern distribution in the I3 and I4 interdigital space), and some that could potentially be attributed to patients suffering from pituitary tumors (small number of ridges for variables FRR 5, smaller number of ridges in the FRL 4 of both hands and difference of pattern distribution at thenar of I1 and I2 interdigital space). The usage of dermatoglyphic traits as markers of predisposition of pituitary tumor development could facilitate the earlier detection of patients in addition to standard methods, and possibly earlier treatment and higher survival rate. Finally, our results are consistent with the hypothesis about multifactorial nature of pituitary tumor etiology comprised of both gene instability and environmental factors.

Assessment of Environmental and Hereditary Influence on Development of Pituitary Tumors Using Dermatoglyphic Traits and Their Potential as Screening Markers

PubMed Central

Gradiser, Marina; Matovinovic Osvatic, Martina; Dilber, Dario; Bilic-Curcic, Ines

2016-01-01

The aim of this study was to assess environmental and hereditary influence on development of pituitary tumors using dermatoglyphic traits. The study was performed on 126 patients of both genders with pituitary tumors (60 non-functional and 66 functional pituitary tumor patients) in comparison to the control group of 400 phenotypically healthy individuals. Statistical analysis of quantitative and qualitative traits of digito-palmar dermatoglyphics was performed, and hormonal status was determined according to the standard protocols. Although we did not find markers that could specifically distinguish functional from non-functional tumors, we have found markers predisposing to the development of tumors in general (a small number of ridges between triradius of both hands, a smaller number of ridges between the triradius of c–d rc R), those for endocrine dysfunction (increased number of arches and reduced number of whorls, difference of pattern distribution in the I3 and I4 interdigital space), and some that could potentially be attributed to patients suffering from pituitary tumors (small number of ridges for variables FRR 5, smaller number of ridges in the FRL 4 of both hands and difference of pattern distribution at thenar of I1 and I2 interdigital space). The usage of dermatoglyphic traits as markers of predisposition of pituitary tumor development could facilitate the earlier detection of patients in addition to standard methods, and possibly earlier treatment and higher survival rate. Finally, our results are consistent with the hypothesis about multifactorial nature of pituitary tumor etiology comprised of both gene instability and environmental factors. PMID:26999178

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

PubMed

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

2017-09-01

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

Pituitary Apoplexy due to the Diagnostic Test in a Cushing"s Disease Patient.

PubMed

Kuzu, Fatih; Unal, Mustafa; Gul, Sanser; Bayraktaroglu, Taner

2018-01-01

Pituitary apoplexy is a medical condition that needs urgent diagnosis and treatment. It may occur spontaneously or may be precipitated by a variety of reasons including dynamic endocrine tests. Although pituitary apoplexy is usually seen in nonfunctional pituitary adenoma, it can also be seen in ACTH secreting macroadenomas. ACTH secreting adenomas present usually as microadenomas and in these patients apoplexy is rarely seen. In this paper we present a 30-year-old male patient with a history of Cushing"s disease who suffered from pituitary apoplexy after the 1 mg dexamethasone suppression test. He underwent endoscopic endonasal transsphenoidal surgery and his symptoms and signs were significantly improved.

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

Endoscopic endonasal transsphenoidal surgery in elderly patients with pituitary adenomas.

PubMed

Gondim, Jackson A; Almeida, João Paulo; de Albuquerque, Lucas Alverne F; Gomes, Erika; Schops, Michele; Mota, Jose Italo

2015-07-01

With the increase in the average life expectancy, medical care of elderly patients with symptomatic pituitary adenoma (PA) will continue to grow. Little information exists in the literature about the surgical treatment of these patients. The aim of this study was to present the results of a single pituitary center in the surgical treatment of PAs in patients > 70 years of age. In this retrospective study, 55 consecutive elderly patients (age ≥ 70 years) with nonfunctioning PAs underwent endoscopic transsphenoidal surgery at the General Hospital of Fortaleza, Brazil, between May 2000 and December 2012. The clinical and radiological results in this group were compared with 2 groups of younger patients: < 60 years (n = 289) and 60-69 years old (n = 30). Fifty-five patients ≥ 70 years of age (average age 72.5 years, range 70-84 years) underwent endoscopic surgery for treatment of PAs. The mean follow-up period was 50 months (range 12-144 months). The most common symptoms were visual impairment in 38 (69%) patients, headache in 16 (29%) patients, and complete ophthalmoplegia in 6 (10.9%). Elderly patients presented a higher incidence of ophthalmoplegia (p = 0.032) and a lower frequency of pituitary apoplexy before surgery (p < 0.05). Tumors with cavernous sinus invasion were treated surgically less frequently than in younger patients. Although patients with an American Society of Anesthesiologists score of 3 were more common in the elderly group (p < 0.05), no significant difference regarding surgical time, extent of resection, and hospitalization were observed. Elderly patients presented with more complications than patients < 60 years (32.7% vs 10%, p < 0.05). Complications observed in the elderly group included 5 CSF leaks (9%), 2 permanent diabetes insipidus cases (3.6%), 4 postoperative refractory hypertension cases (7.2%), 1 myocardial ischemia (1.8%), and 1 death (1.8%). Postoperative new anterior pituitary deficit was more common in the younger group (< 60 years old: 17.7%) than in the elderly (≥ 70 years old: 12.7%); however, there was no statistical difference. Endoscopic transsphenoidal surgery for elderly patients with PAs may be associated with higher complication rates, especially secondary to early transitory complications, when compared with surgery performed in younger patients. Although the worst preoperative clinical status might be observed in this group, age alone is not associated with a worst final prognosis after endoscopic removal of nonfunctioning PAs.

Endocrinology Update: Hypopituitarism.

PubMed

Heidelbaugh, Joel J

2016-12-01

Hypopituitarism is defined as a deficiency of one or more pituitary hormones due to a decline in function of the pituitary gland and/or hypothalamus, which can result in higher risks of morbidity and mortality and decreased quality of life. Although hypopituitarism is a rare condition, it commonly develops after traumatic brain injury and in the setting of functioning and nonfunctioning pituitary adenomas. The diagnosis is based on detailed investigation of symptoms of target endocrine gland function relative to the corresponding pituitary hormone deficiency. The clinical manifestations of hypopituitarism result from the degree of the specific hormone deficiency. A thorough and longitudinal history and physical examination, including visual field testing, are paramount. Management consists of prompt pharmacotherapy, surgery, and/or radiotherapy to restore normal endocrine function and quality of life. In most patients with anterior and posterior pituitary hormone deficiency, corresponding hormone replacement is the mainstay of therapy. The prognosis for patients with hypopituitarism depends on the manner of and age at presentation, degree and severity of hormonal impairment, and response to medical and surgical therapies. Patients with hypopituitarism require lifelong monitoring of serum hormone levels and symptoms of hormone deficiency or excess. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

A cross-sectional study to investigate long-term cognitive function in people with treated pituitary Cushing's disease.

PubMed

Heald, A; Parr, C; Gibson, C; O'driscoll, K; Fowler, H

2006-10-01

It has been proposed that exposure to high levels of endogenous steroids in untreated pituitary Cushing's disease damages hippocampal structures leading to impairment in learning and memory processes. We hypothesised that patients with treated pituitary Cushing's disease would perform significantly worse on tests of cognitive ability than those with nonfunctioning pituitary adenomas. Sixteen adults with pituitary Cushing's disease (PCD) and 16 adults with non-functioning pituitary adenomas (NFA) undertook the following comprehensive neuropsychological assessments: National Adult Reading Test (NART: premorbid abilities), California Verbal Learning Test (CVLT 2 UK: learning and recall), Stroop (executive functioning), Trail-Making Test (TMT: executive functioning and attention), Adult Memory and Information Processing Battery (AMIPB: Information Processing Speed and Story Recall subtests). There was no significant difference in premorbid IQ scores (NFA mean=101 SD=13; PCD mean=102, SD=13), in verbal learning nor any significant difference in the percentage of verbal material retained in story recall (AMIPB). Performance on higher executive tasks Stroop and TMT and on measures of information processing was similar. However, there were significant decrements between some mean scores for both groups and published normative data with a clear association between higher HADS depression scores and impaired objective memory and attention which was not specific to PCD. We found no difference in cognitive function between patients with PCD and NFA. The results suggest a discrepancy between patients' subjective perception of functional cognitive impairments and objective findings on psychometric testing and point to the influence of affective symptoms on cognitive performance, particularly in Cushing's disease.

Circular RNA In Invasive and Recurrent Clinical Nonfunctioning Pituitary Adenomas: Expression Profiles and Bioinformatic Analysis.

PubMed

Wang, Jianpeng; Wang, Dong; Wan, Dehong; Ma, Qingxia; Liu, Qian; Li, Jiye; Li, Zhaojian; Gao, Yang; Jiang, Guohui; Ma, Leina; Liu, Jia; Li, Chuzhong

2018-06-14

The invasion and recurrence of clinical nonfunctioning pituitary adenomas (NFA) often lead to surgical treatment failure. Circular RNAs (circRNAs) are a novel class of RNAs whose 3' and 5' ends are joined together and have been shown to play important roles in cancer development. Up to now, the roles of circRNAs remain unclear in invasive and recurrent NFA. We detected and summarized the circRNA expression pattern in 75 NFA tissues from 10 non-invasive cases and 65 invasive cases and 9 pairs NFA tumor tissues from 9 recurrent cases by circRNA microarrays. Accordingly, functional enrichment analysis and pathway analysis were performed and circRNA-microRNA(miRNA) network were generated by bioinformatic analysis tools. 5 new invasive NFA samples and 5 non-invasive NFA samples were collected to measure the microarray results. 570 dysregulated circRNAs (Invasive Tumor vs. Non-invasive Tumor) and 10 up-regulated circRNAs (Recurrent tumor Tissue vs. First surgery tumor Tissue) were identified based on the situation (FC>2, P<0.05). The parental genes of the dysregulated circRNAs in the comparison between invasion tumor and non-invasion tumor were found to be enriched in some cell adhesion signaling pathways such as Focal adhesion, Hippo signaling pathway, PI3K-Akt signaling pathway, and Adherens junction. The circRNA-miRNA network showed that the dysregulated circRNA may function as miRNA sponges. This is the first study to conduct and comprehensively analyze the circRNA expression profile in invasive and recurrent NFA. Our finding will provide evidence for the significance of circRNAs in NFA diagnosis, prognosis and clinical treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Expression Analysis of Dopamine Receptor Subtypes in Normal Human Pituitaries, Nonfunctioning Pituitary Adenomas and Somatotropinomas, and the Association between Dopamine and Somatostatin Receptors with Clinical Response to Octreotide-LAR in Acromegaly

PubMed Central

Neto, Leonardo Vieira; Machado, Evelyn de O.; Luque, Raul M.; Taboada, Giselle F.; Marcondes, Jorge B.; Chimelli, Leila M. C.; Quintella, Leonardo Pereira; Niemeyer, Paulo; de Carvalho, Denise P.; Kineman, Rhonda D.; Gadelha, Mônica R.

2009-01-01

Context: Dopamine receptor (DR) and somatostatin receptor subtype expression in pituitary adenomas may predict the response to postsurgical therapies. Objectives: Our objectives were to assess and compare the mRNA levels of DR1-5 and somatostatin receptors 1–5 in normal pituitaries (NPs), nonfunctioning pituitary adenomas (NFPAs), and somatotropinomas. In addition, we determined whether the level of DR expression correlates with the in vivo response to octreotide-LAR in acromegalic patients. Design and Patients: Eight NPs, 30 NFPAs, and 39 somatotropinomas were analyzed for receptor mRNA levels by real-time RT-PCR. The DR2 short variant was estimated as the DR2 long/DR2 total (DR2T). The relationship between DR expression and the postsurgical response to octreotide-LAR was assessed in 19 of the acromegalic patients. Results: DR3 was not detected. The relationship between expression levels of DR subtypes in NPs and somatotropinomas was DR2T⋙DR4≫DR5>DR1, whereas in NFPAs, DR2T⋙DR4≫DR1>DR5. The DR2 short variant was the predominant DR2 variant in the majority of samples. In acromegalics treated with octreotide-LAR, DR1 was negatively correlated with percent GH reduction (3 months: r = −0.67, P = 0.002; and 6 months: r = −0.58, P = 0.009), and DR5 was positively correlated with percent IGF-I reduction (3 months: r = 0.55, P = 0.01; and 6 months: r = 0.47, P = 0.04). Conclusions: DR2 is the predominant DR subtype in NPs, NFPAs, and somatotropinomas. The fact that DR1, DR4, and DR5 are also expressed in many adenomas tested suggests that these receptors might also play a role in the therapeutic impact of postsurgical medical therapies in patients with NFPA and acromegaly. This was supported by the finding that the in vivo response to octreotide-LAR was negatively associated with DR1 and positively associated with DR5. PMID:19293270

Folate receptor-mediated boron-10 containing carbon nanoparticles as potential delivery vehicles for boron neutron capture therapy of nonfunctional pituitary adenomas.

PubMed

Dai, Congxin; Cai, Feng; Hwang, Kuo Chu; Zhou, Yongmao; Zhang, Zizhu; Liu, Xiaohai; Ma, Sihai; Yang, Yakun; Yao, Yong; Feng, Ming; Bao, Xinjie; Li, Guilin; Wei, Junji; Jiao, Yonghui; Wei, Zhenqing; Ma, Wenbin; Wang, Renzhi

2013-02-01

Invasive nonfunctional pituitary adenomas (NFPAs) are difficult to completely resect and often develop tumor recurrence after initial surgery. Currently, no medications are clinically effective in the control of NFPA. Although radiation therapy and radiosurgery are useful to prevent tumor regrowth, they are frequently withheld because of severe complications. Boron neutron capture therapy (BNCT) is a binary radiotherapy that selectively and maximally damages tumor cells without harming the surrounding normal tissue. Folate receptor (FR)-targeted boron-10 containing carbon nanoparticles is a novel boron delivery agent that can be selectively taken up by FR-expressing cells via FR-mediated endocytosis. In this study, FR-targeted boron-10 containing carbon nanoparticles were selectively taken up by NFPAs cells expressing FR but not other types of non-FR expressing pituitary adenomas. After incubation with boron-10 containing carbon nanoparticles and following irradiation with thermal neutrons, the cell viability of NFPAs was significantly decreased, while apoptotic cells were simultaneously increased. However, cells administered the same dose of FR-targeted boron-10 containing carbon nanoparticles without neutron irradiation or received the same neutron irradiation alone did not show significant decrease in cell viability or increase in apoptotic cells. The expression of Bcl-2 was down-regulated and the expression of Bax was up-regulated in NFPAs after treatment with FR-mediated BNCT. In conclusion, FR-targeted boron-10 containing carbon nanoparticles may be an ideal delivery system of boron to NFPAs cells for BNCT. Furthermore, our study also provides a novel insight into therapeutic strategies for invasive NFPA refractory to conventional therapy, while exploring these new applications of BNCT for tumors, especially benign tumors.

Perioperative management of the hypothalamic-pituitary-adrenal axis in patients with pituitary adenomas: an Australasian survey.

PubMed

Joseph, S P; Ho, J T; Doogue, M P; Burt, M G

2012-10-01

There is limited consensus regarding optimal glucocorticoid administration for pituitary surgery to prevent a potential adrenal crisis. To assess the investigation and management of the hypothalamic-pituitary-adrenal (HPA) axis in patients undergoing trans-sphenoidal hypophysectomy in Australasia. A questionnaire was sent to one endocrinologist at each of 18 centres performing pituitary surgery in Australasia. Using hypothetical case vignettes, respondents were asked to describe their investigation and management of the HPA axis for a patient with a: non-functioning macroadenoma and intact HPA axis, non-functioning macroadenoma and HPA deficiency and growth hormone secreting microadenoma undergoing trans-sphenoidal hypophysectomy. Responses were received from all 18 centres. Seventeen centres assess the HPA axis preoperatively by measuring early morning cortisol or a short synacthen test. Preoperative evaluation of the HPA status influenced glucocorticoid prescription by 10 centres, including 2/18 who would not prescribe perioperative glucocorticoids for a patient with a macroadenoma and an intact HPA axis. Tumour size influenced glucocorticoid prescribing patterns at 7/18 centres who prescribe a lower dose or no glucocorticoids for a patient with a microadenoma. Choice of investigations for definitive postoperative assessment of the HPA axis varied with eight centres requesting an insulin tolerance test, four centres a 250 µg short synacthen test and six centres requesting other tests. There is wide variability in the investigation and management of perioperative glucocorticoid requirements for patients undergoing pituitary surgery in Australasia. This may reflect limited evidence to define optimal management and that further well-designed studies are needed. © 2011 The Authors; Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

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.

Spindle cell oncocytoma of the adenohypophysis in a woman: a case report and review of the literature.

PubMed

Mlika, M; Azouz, H; Chelly, I; Saïd, I Ben; Jemel, H; Haouet, S; Zitouna, M; Kchir, N

2011-02-14

Spindle cell oncocytoma of the adenohypophysis is a rare tumour recently reported by Roncaroli et al. in 2002. This tumour is considered a grade I tumour by the World Health Organization. We describe what is, to the best of our knowledge, the 14th case of its kind in the literature. A 45-year-old African woman presented clinical and radiological findings related to a nonfunctioning pituitary adenoma. The diagnosis was made on the basis of histological and immunohistochemical findings. The purpose of this work is to report a rare pituitary tumour and to describe its histological and immunohistochemical features, which were characterized by the expression of thyroid transcription factor 1 antigen by tumour cells. This fact could support the theory of a possible common origin of these tumours in pituicytomas. In fact, thyroid transcription factor 1 is considered to be a specific marker of pituicytes.

Clinical problem solving: monster on the hook--case problems in neurosurgery.

PubMed

Muh, Carrie R; Boulis, Nicholas M; Chandler, William F; Barkan, Ariel L; Mosunjac, Marina B; Oyesiku, Nelson M

2011-03-01

Nonfunctioning and functioning pituitary tumors can present in numerous ways. They may be difficult to diagnose correctly and, even with proper treatment, may lead to complications. We present the case of a patient who presented with a large, invasive sellar mass and underwent both medical and surgical treatment for this lesion. The patient's course did not progress as was expected from his initial workup. The patient's history, physical examination, laboratory values, pathologic specimens, and radiologic findings are discussed. His management before, during, and after medical therapy and surgery is reviewed by pituitary experts from 2 different institutions. Aspects of diagnosis and management of sellar lesions are presented and reviewed in the literature. Neurosurgeons frequently treat patients with sellar lesions and should remember that despite modern laboratory, pathologic, and radiologic techniques, the diagnosis and treatment of these lesions is not always clear.

cAMP-specific PDE4 Phosphodiesterases and AIP in the Pathogenesis of Pituitary Tumors

PubMed Central

Bolger, Graeme B.; Bizzi, Mariana Ferreira; Brant Pinheiro, Sergio Veloso; Trivellin, Giampaolo; Smoot, Lisa; Accavitti, Mary-Ann; Korbonits, Márta; Ribeiro-Oliveira, Antonio

2016-01-01

PDE4 cyclic nucleotide phosphodiesterases regulate cAMP abundance in cells and thereby regulate numerous processes, including cell growth and differentiation. The rat PDE4A5 isoform (human homologue PDE4A4) interacts with the AIP protein (also called XAP2 or ARA-9). Germline mutations in AIP occur in approximately 20% of patients with Familial Isolated Pituitary Adenoma (FIPA) and 20% of childhood-onset simplex somatotroph adenomas. We therefore examined the protein expression of PDE4A4 and the closely-related isoform PDE4A8 in normal human pituitary tissue and in pituitary adenomas. PDE4A4 had low expression in normal pituitary, but was significantly over-expressed in somatotroph, lactotroph, corticotroph and clinically non-functioning gonadotroph adenomas (P<0.0001 for all subtypes). Likewise, PDE4A8 was expressed in normal pituitary and was also significantly over-expressed in the adenoma subtypes (P<0.0001 for all). Among the different adenoma subtypes, corticotroph and lactotroph adenomas were the highest and lowest expressed for PDE4A4, respectively, whereas the opposite was observed for PDE4A8. Naturally occurring oncogenic variants in AIP were shown by a two-hybrid assay to disrupt the ability of AIP to interact with PDE4A5. A reverse-two-hybrid screen identified numerous additional variants in the TPR region of AIP that also disrupted its ability to interact with PDE4A5. The expression of PDE4A4 and PDE4A8 in normal pituitary, their increased expression in adenomatous pituitary cells where AIP is meant to participate, and the disruption of the PDE4A4-AIP interaction by AIP mutants may play a role in pituitary tumorigenesis. PMID:27267386

Multihormonal pituitary adenoma concomitant with Pit-1 and Tpit lineage cells causing acromegaly associated with subclinical Cushing's disease: a case report.

PubMed

Takiguchi, Tomoko; Koide, Hisashi; Nagano, Hidekazu; Nakayama, Akitoshi; Fujimoto, Masanori; Tamura, Ai; Komai, Eri; Shiga, Akina; Kono, Takashi; Higuchi, Seiichiro; Sakuma, Ikki; Hashimoto, Naoko; Suzuki, Sawako; Miyabayashi, Yui; Ishiwatari, Norio; Horiguchi, Kentaro; Nakatani, Yukio; Yokote, Koutaro; Tanaka, Tomoaki

2017-09-02

A functional pituitary adenoma can produce multiple anterior-pituitary hormones, such as growth hormone (GH) -producing adenomas (GHoma) with prolactin or thyrotropin stimulating hormone production in the same lineage. However, it is very rare that acromegaly shows subclinical Cushing's disease (SCD) beyond the lineage. Here we describe the involvement of intratumoral coexistence with 2 types of hormone-producing cells associated with different lineage in acromegaly concomitant with SCD. In our study, we performed clinical evaluation of the patient showing acromegaly with SCD. To elucidate the mechanisms of this pathology, we analyzed immunohistochemistry and gene expression of anterior-pituitary hormones and transcriptional factors in the resected pituitary tumor. On immunohistochemical staining, most of the tumor cells were strongly stained for GH antibody, while some cells were strongly positive for adrenocorticotropic hormone (ACTH). Gene expression analysis of a transsphenoidal surgery sample of the pituitary gland revealed that ACTH-related genes, such as POMC, Tpit, and NeuroD1 mRNA, had higher expression in the tumor tissue than the nonfunctional adenoma but lower expression compared to an adenoma of typical Cushing's disease. Further, double-labeling detection methods with a fluorescent stain for ACTH and GH demonstrated the coexistence of ACTH-positive cells (GH-negative) among the GH-positive cells in the tumor. Additionally, Pit-1 expression was reduced in the ACTH-positive cells from tumor tissue primary culture. Here we described a case of a pituitary tumor diagnosed with acromegaly associated with SCD. We performed quantitative-expression analyses of transcriptional factors of the tumor tissue and immunohistochemistry analysis of tumor-derived primary culture cells, which suggested that the multihormonal pituitary adenoma concomitant with Pit-1 and Tpit lineage cells caused acromegaly associated with SCD.

The dopamine-somatostatin chimeric compound BIM-23A760 exerts antiproliferative and cytotoxic effects in human non-functioning pituitary tumors by activating ERK1/2 and p38 pathways.

PubMed

Peverelli, Erika; Olgiati, Luca; Locatelli, Marco; Magni, Paolo; Fustini, Marco Faustini; Frank, Giorgio; Mantovani, Giovanna; Beck-Peccoz, Paolo; Spada, Anna; Lania, Andrea

2010-02-28

The study investigated the effects of the dopamine-somatostatin chimeric compound BIM-23A760 on cell proliferation and apoptosis in cultured cells from human non-functioning pituitary tumors (NFPTs). Both BIM-23A760 and the dopaminergic agonist BIM-53097 induced a significant inhibition of cell proliferation associated with increased p27 expression, together with a significant increase in caspase-3 activity. Conversely, null or marginal effects were elicited by somatostatin analogs. Moreover, BIM-23A760 and BIM-53097 induced ERK1/2 and p38 phosphorylation and the blockade of these pathways prevented both the antiproliferative and the pro-apoptotic effects of these drugs. In conclusions the chimeric compound BIM-23A760 is able to exert cytostatic and cytotoxic effects in NFPTs, these phenomena being mainly mediated by DR2D and involving ERK1/2 and p38 pathways activation. 2009 Elsevier Ireland Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Julian O.; Ma, Roy; Division of Radiation Oncology and Developmental Radiotherapeutics, University of British Columbia, Vancouver

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,more » 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.« less

Functional Gonadotroph Adenomas: Case Series and Report of Literature

PubMed Central

Cote, David J.; Smith, Timothy R.; Sandler, Courtney N.; Gupta, Tina; Bale, Tejus A.; Bi, Wenya Linda; Dunn, Ian F.; De Girolami, Umberto; Woodmansee, Whitney W.; Kaiser, Ursula B.; Laws, Edward R.

2016-01-01

Background Functional gonadotroph adenomas (FGA) are rare tumors of the pituitary gland that secrete biologically active gonadotropins. Objective To advance clinical understanding of FGA. Methods We performed a retrospective review of adult patients who underwent resection of a pituitary lesion between August 1997 and October 2014 and remain under care at our center. We identified patients who had pathologic and biochemical confirmation of FGA, as defined by lack of serum LH/FSH suppression in the setting of elevated gonadal steroids, associated clinical symptoms, or both. Results FGA was documented in seven patients (five men, two women) over a 17-year period. Clinical findings at presentation included visual field deficits in five patients, headache in three, sexual dysfunction in three, and ovarian cysts in both women. Each patient underwent lesional resection (six by the endonasal transsphenoidal approach, one by craniotomy with transsphenoidal reoperation). Analysis of tumor samples revealed immunopositivity for FSH/LH in five patients and FSH only in two patients. Post-operative follow-up (median 10 mo, range 4-213 mo) indicated remission in six of seven patients. Conclusion FGA can pose both a diagnostic and therapeutic challenge. The tumor is often diagnosed as a nonfunctioning macroadenoma after presenting with non-specific symptoms, and is the cause of significant morbidity. FGA should be considered in the differential diagnosis of patients harboring pituitary adenomas with reproductive dysfunction. Transsphenoidal resection is the initial treatment of choice, and can reduce endocrine dysfunction, resolve headaches, improve visual impairment, and provide tissue for detailed analysis. PMID:26692108

A cellular and molecular basis for the selective desmopressin-induced ACTH release in Cushing disease patients: key role of AVPR1b receptor and potential therapeutic implications.

PubMed

Luque, R M; Ibáñez-Costa, A; López-Sánchez, L M; Jiménez-Reina, L; Venegas-Moreno, E; Gálvez, M A; Villa-Osaba, A; Madrazo-Atutxa, A M; Japón, M A; de la Riva, A; Cano, D A; Benito-López, P; Soto-Moreno, A; Gahete, M D; Leal-Cerro, A; Castaño, J P

2013-10-01

Desmopressin is a synthetic agonist of vasopressin receptors (AVPRs). The desmopressin stimulation test is used in the diagnosis and postsurgery prognosis of Cushing disease (CD). However, the cellular and molecular mechanisms underlying the desmopressin-induced ACTH increase in patients with CD are poorly understood. The objectives of this study were to determine, for the first time, whether desmopressin acts directly and exclusively on pituitary corticotropinoma cells to stimulate ACTH expression/release and to elucidate the cellular and molecular mechanisms involved in desmopressin-induced ACTH increase in CD. A total of 8 normal pituitaries (NPs), 23 corticotropinomas, 14 nonfunctioning pituitary adenomas, 17 somatotropinomas, and 3 prolactinomas were analyzed for AVPR expression by quantitative real-time RT-PCR. Primary cultures derived from corticotropinomas, nonfunctioning pituitary adenomas, somatotropinomas, prolactinomas, and NPs were treated with desmopressin, and ACTH secretion/expression, [Ca(2+)]i kinetics, and AVPR expression and/or proliferative response were evaluated. The relationship between AVPR expression and plasma adrenocorticotropin/cortisol levels obtained from desmopressin tests was assessed. Desmopressin affects all functional parameters evaluated in corticotropinoma cells but not in NPs or other pituitary adenomas cells. These effects might be due to the dramatic elevation of AVPR1b expression levels found in corticotropinomas. In line with this notion, the use of an AVPR1b antagonist completely blocked desmopressin stimulatory effects. Remarkably, only AVPR1b expression was positively correlated with elevated plasma adrenocorticotropin levels in corticotropinomas. The present results provide a cellular and molecular basis to support the desmopressin stimulation test as a reliable, specific test for the diagnosis and postsurgery prognosis of CD. Furthermore, our data indicate that AVPR1b is responsible for the direct/exclusive desmopressin stimulatory pituitary effects observed in CD, thus opening the possibility of exploring AVPR1b antagonists as potential therapeutic tools for CD treatment.

Trophic and neurotrophic factors in human pituitary adenomas (Review).

PubMed

Spoletini, Marialuisa; Taurone, Samanta; Tombolini, Mario; Minni, Antonio; Altissimi, Giancarlo; Wierzbicki, Venceslao; Giangaspero, Felice; Parnigotto, Pier Paolo; Artico, Marco; Bardella, Lia; Agostinelli, Enzo; Pastore, Francesco Saverio

2017-10-01

The pituitary gland is an organ that functionally connects the hypothalamus with the peripheral organs. The pituitary gland is an important regulator of body homeostasis during development, stress, and other processes. Pituitary adenomas are a group of tumors arising from the pituitary gland: they may be subdivided in functional or non-functional, depending on their hormonal activity. Some trophic and neurotrophic factors seem to play a key role in the development and maintenance of the pituitary function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity. Several lines of evidence suggest that trophic and neurotrophic factors may be involved in pituitary function, thus suggesting a possible role of the trophic and neurotrophic factors in the normal development of pituitary gland and in the progression of pituitary adenomas. Additional studies might be necessary to better explain the biological role of these molecules in the development and progression of this type of tumor. In this review, in light of the available literature, data on the following neurotrophic factors are discussed: ciliary neurotrophic factor (CNTF), transforming growth factors β (TGF‑β), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), vascular endothelial growth inhibitor (VEGI), fibroblast growth factors (FGFs) and epidermal growth factor (EGF) which influence the proliferation and growth of pituitary adenomas.

Spindle cell oncocytoma of the adenohypophysis in a woman: a case report and review of the literature

PubMed Central

2011-01-01

Introduction Spindle cell oncocytoma of the adenohypophysis is a rare tumour recently reported by Roncaroli et al. in 2002. This tumour is considered a grade I tumour by the World Health Organization. Case presentation We describe what is, to the best of our knowledge, the 14th case of its kind in the literature. A 45-year-old African woman presented clinical and radiological findings related to a nonfunctioning pituitary adenoma. The diagnosis was made on the basis of histological and immunohistochemical findings. Conclusion The purpose of this work is to report a rare pituitary tumour and to describe its histological and immunohistochemical features, which were characterized by the expression of thyroid transcription factor 1 antigen by tumour cells. This fact could support the theory of a possible common origin of these tumours in pituicytomas. In fact, thyroid transcription factor 1 is considered to be a specific marker of pituicytes. PMID:21320334

Folate receptor {alpha} regulates cell proliferation in mouse gonadotroph {alpha}T3-1 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yao, Congjun; Evans, Chheng-Orn; Stevens, Victoria L.

We have previously found that the mRNA and protein levels of the folate receptor alpha (FR{alpha}) are uniquely over-expressed in clinically human nonfunctional (NF) pituitary adenomas, but the mechanistic role of FR{alpha} has not fully been determined. We investigated the effect of FR{alpha} over-expression in the mouse gonadotroph {alpha}T3-1 cell line as a model for NF pituitary adenomas. We found that the expression and function of FR{alpha} were strongly up-regulated, by Western blotting and folic acid binding assay. Furthermore, we found a higher cell growth rate, an enhanced percentage of cells in S-phase by BrdU assay, and a higher PCNAmore » staining. These observations indicate that over-expression of FR{alpha} promotes cell proliferation. These effects were abrogated in the same {alpha}T3-1 cells when transfected with a mutant FR{alpha} cDNA that confers a dominant-negative phenotype by inhibiting folic acid binding. Finally, by real-time quantitative PCR, we found that mRNA expression of NOTCH3 was up-regulated in FR{alpha} over-expressing cells. In summary, our data suggests that FR{alpha} regulates pituitary tumor cell proliferation and mechanistically may involve the NOTCH pathway. Potentially, this finding could be exploited to develop new, innovative molecular targeted treatment for human NF pituitary adenomas.« less

How to deal with giant pituitary adenomas: transsphenoidal or transcranial, simultaneous or two-staged?

PubMed

Han, Sheng; Gao, Wei; Jing, Zhitao; Wang, Yunjie; Wu, Anhua

2017-04-01

Giant pituitary adenomas (diameter >4 cm) are a challenge to treat, and there is no consensus on the optimal surgical strategy. We report here our experience in surgical management of these lesions. Adult patients with giant pituitary adenomas (n = 62; 54 non-functioning and eight hormone-secreting adenomas) who underwent surgical resection at our hospital from 2009 to 2015 were retrospectively reviewed. Surgical and clinical outcomes were analyzed. Single transsphenoidal and transcranial approaches were used in 43 (69.4%) and four (6.5%) patients, respectively. A combined transsphenoidal and transcranial approach was used in 13 patients (20.9%) and in two patients (3.2%), a transcranial procedure was followed 3 months later by a transsphenoidal approach. Greater than 90% resection was achieved in 47 cases (75.8%). During a mean follow-up period of 46.9 months, 49 patients (79%) showed improved visual impairment scores, while none experienced visual deterioration. There was no post-operative hemorrhage or mortality. A total of 27 patients (43.5%) received adjuvant medical and/or radiation therapy. At last follow-up, eight patients (12.9%) had recurrence. For giant pituitary adenoma, the transsphenoidal and transcranial approaches should be combined flexibly based on the characteristics of the tumor. In certain cases, a simultaneous combined approach can maximize tumor extirpation and lower the risk of swelling and bleeding of the residual tumor.

Endonasal endoscopic surgery in pituitary adenomas: Surgical results in a series of 86 consecutive patients.

PubMed

López-García, R; Abarca-Olivas, J; Monjas-Cánovas, I; Picó Alfonso, A M; Moreno-López, P; Gras-Albert, J R

2018-03-23

The endoscopic endonasal approach has become the gold standard for the surgical treatment of pituitary adenomas. The aim of this study is to present the results obtained in our hospital in purely endoscopic surgery of pituitary adenomas. From February 2011 to August 2016, we conducted a prospective study on a series of 86 patients with pituitary adenoma, all of whom underwent surgery with a purely endoscopic endonasal approach. The 'four hands-two nostrils' technique was performed in all cases by a surgical team composed of an ENT surgeon and a neurosurgeon. Mean follow-up was 32 months. All patients were evaluated according to clinical, radiological and endocrinological criteria. In our series, 53% were women and 47% men. The age ranged from 14 to 84 years of age, with a mean of 54 years of age. The most common initial symptom was visual deficit (42%), followed by hormonal hyperfunction (21%), with acromegaly being the most common clinical syndrome. The most common tumours were non-functioning tumours (73%), while GH-secreting tumours (65%) were the most common functioning adenoma. Regarding tumour size, 76% were macroadenomas, 11% microadenomas and 13% giant adenomas. Approximately 63% of the adenomas exhibited suprasellar extension and 37% involved invasion of the cavernous sinus (Knosp grade ≥3). Total excision was achieved in 77% of the cases. After the intervention, visual improvement was achieved in 91% and remission of endocrine hyperfunction in up to a 73% of cases. The most common complication was anterior pituitary insufficiency of at least one axis (9%). There were no cases of postoperative cerebrospinal fluid fistula. In terms of surgical quality, our results are similar to those of published series, and demonstrate the efficacy and safety of the endoscopic endonasal approach as the surgical treatment of choice for pituitary adenomas. However, further studies with a higher sample size are necessary to obtain clinically significant results. Copyright © 2018 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

Endoscopic Transsphenoidal Surgery Outcomes in 331 Nonfunctioning Pituitary Adenoma Cases After a Single Surgeon Learning Curve.

PubMed

Kim, Jung Hee; Lee, Jung Hyun; Lee, Ji Hyun; Hong, A Ram; Kim, Yoon Ji; Kim, Yong Hwy

2018-01-01

The outcomes of recent endoscopic surgery of nonfunctioning pituitary adenomas (NFPAs) are controversial when compared with traditional microscopic surgery. We aimed to assess the outcomes of endoscopic transsphenoidal surgeries performed by 1 surgeon with 7 years of experience and elucidate the predictive factors for surgical outcomes for NFPAs. We included 331 patients (155 men and 176 women) with clinical NFPAs who underwent transsphenoidal surgery because of visual symptoms by a single surgeon in Seoul National University Hospital from March 2010 to May 2016. We assessed the tumor removal rate, hormonal outcomes, visual outcomes, and complications. The gross total resection rate of endoscopic transsphenoidal surgery for NFPAs by a single surgeon was 74.9%. Cavernous sinus invasion, a high Knosp grade, large tumor size, previous surgery, and lack of surgical experience in the neurosurgeon elevated the risk for residual tumors. Visual deficits were improved in 73.4% of the patients, which was associated with tumor size, preoperative visual impairment score, previous radiation, and surgical experience. Hormonal status was improved in 15.4% and aggravated in 32.9% after surgery. There were no predictors for hormonal recovery. Transient diabetes insipidus (DI) was the most common complication (9.1%), and among these patients, 3.0% had persistent DI. Endoscopic transsphenoidal surgery by a well-experienced surgeon was an effective and safe treatment for NFPAs, but the hormonal outcomes were not changed compared with previous reports of microscopic surgery. Large tumor size and cavernous sinus invasion were still the barriers for achieving total resection. Copyright © 2017 Elsevier Inc. All rights reserved.

Acromegaly diagnosed in a young woman presenting with headache and arthritis.

PubMed

Nachtigall, Lisa B

2006-10-01

A 38-year-old woman presented with severe headaches to her primary-care physician. The patient had been diagnosed with rheumatoid arthritis and had begun having headache 4 years previously. An MRI scan revealed an 11-12 mm pituitary tumor. Her physical examination was unremarkable for the classic acral or facial changes characteristic of acromegaly, and she was referred for neuroendocrine consultation for a presumed nonfunctioning adenoma. MRI of the pituitary, and laboratory investigations that included measurement of serum insulin-like growth factor 1 (IGF1) and prolactin levels. In view of the elevated level of IGF1 and presence of a pituitary adenoma, the patient was diagnosed with acromegaly caused by a pituitary adenoma that secretes growth hormone. The patient underwent trans-sphenoidal surgery, which resulted in resolution of joint pain and headache, eradication of the tumor mass, normal IGF1 levels, and appropriate suppression of growth hormone (confirmed by oral glucose tolerance test postoperatively).

Does Low-Field Intraoperative Magnetic Resonance Improve the Results of Endoscopic Pituitary Surgery? Experience of the Implementation of a New Device in a Referral Center.

PubMed

García, Sergio; Reyes, Luis; Roldán, Pedro; Torales, Jorge; Halperin, Irene; Hanzu, Felicia; Langdon, Cristobal; Alobid, Isam; Enseñat, Joaquim

2017-06-01

To assess the contribution of low-field intraoperative magnetic resonance (iMRI) to endoscopic pituitary surgery. We analyzed a prospective series of patients undergoing endoscopic endonasal surgery for pituitary macroadenomas assisted with a low-field iMRI (PoleStarN30, 0.15 T [Medtronic]). Clinical, radiologic, and surgical variables were analyzed and compared with our fully endoscopic historic cohort operated on without iMRI assistance. A bibliographic review of pituitary surgery assisted with iMRI was conducted. Thirty patients (57% female; mean age, 55 years) were prospectively analyzed. The most frequent tumor subtype was nonfunctioning macroadenoma (50%). The average Knosp grade was 2.3 and mean tumor size was 18 mm. Surgical and positioning time were 102 and 47 minutes, respectively. Hospital stay and complication rates were similar to our historical cohort for pituitary surgery. Mean follow-up was 10 months. Complete resection (CR) was achieved in 83% of patients. Seven patients (23%) benefited from iMRI assistance and achieved a CR in their surgeries. All patients except 1 experienced hormonal activity remission. iMRI sensitivity and specificity was 0.8 and 1, respectively. Although not statistically significant, CR rates were globally 11.5% superior in iMRI series compared with our historical cohort. This difference was independent of cavernous sinus invasiveness grade (CR rate increased 12.5% for Knosp grade 0-2 and 8.1% for Knosp grade 3-4). Low-field iMRI is a useful and safe assistance even in advanced surgical techniques such as endoscopy. Its contribution is limited by the intrinsic features of the tumor. Further randomized studies are required to confirm the cost-effectiveness of iMRI in pituitary surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

A high-throughput analysis of the IDH1(R132H) protein expression in pituitary adenomas.

PubMed

Casar-Borota, Olivera; Øystese, Kristin Astrid Berland; Sundström, Magnus; Melchior, Linea; Popovic, Vera

2016-08-01

Inactivating mutations of isocitrate dehydrogenase (IDH) 1 and 2, mitochondrial enzymes participating in the Krebs tricarboxylic acid cycle play a role in the tumorigenesis of gliomas and also less frequently in acute myeloid leukemia and other malignancies. Inhibitors of mutant IDH1 and IDH2 may potentially be effective in the treatment of the IDH mutation driven tumors. Mutations in the succinate dehydrogenase, the other enzyme complex participating in the Krebs cycle and electron transfer of oxidative phosphorylation occur in the paragangliomas, gastrointestinal stromal tumors, and occasionally in the pituitary adenomas. We aimed to determine whether the IDH1(R132H) mutation, the most frequent IDH mutation in human malignancies, occurs in pituitary adenomas. We performed immunohistochemical analysis by using a monoclonal anti-IDH1(R132H) antibody on the tissue microarrays containing specimens from the pituitary adenomas of different hormonal types from 246 patients. In positive samples, the status of the IDH1 gene was further examined by molecular genetic analyses. In all but one patient, there was no expression of mutated IDH1(R132H) protein in the tumor cells by immunohistochemistry. Only one patient with a recurring clinically non-functioning gonadotroph adenoma demonstrated IDH1(R132H)-immunostaining in both the primary tumor and the recurrence. However, no mutation in the IDH1 gene was detected using different molecular genetic analyses. IDH1(R132H) mutation occurs only exceptionally in pituitary adenomas and does not play a role in their pathogenesis. Patients with pituitary adenomas do not seem to be candidates for treatment with the inhibitors of mutant IDH1.

G protein abnormalities in pituitary adenomas.

PubMed

Spada, A; Lania, A; Ballarè, E

1998-07-25

It has been demonstrated that the majority of secreting and nonsecreting adenomas is monoclonal in origin suggesting that these neoplasia arise from the replication of a single mutated cell, in which growth advantage results from either activation of protooncogenes or inactivation of antioncogenes. Although a large number of genes has been screened for mutations, only few genetic abnormalities have been found in pituitary tumors such as allelic deletion of chromosome 11q13 where the MEN-1 gene has been localised, and mutations in the gene encoding the alpha subunit of the stimulatory Gs and Gi2 protein. These mutations constitutively activate the alpha subunit of the Gs and Gi2 protein by inhibiting their intrinsic GTPase activity. Both Gs alpha and Gi2alpha can be considered products of protooncogenes (gsp and gip2, respectively) since gain of function mutations that activate mitogenic signals have been recognized in human tumors. Gsp oncogene is found in 30-40% of GH-secreting adenomas, in a low percentage of nonfunctioning and ACTH-secreting pituitary adenomas, in toxic thyroid adenomas and differentiated thyroid carcinomas. The same mutations, occurred early in embriogenesis, have been also identified in tissues from patients affected with the McCune Albright syndrome. These mutations result in an increased cAMP production and in the subsequent overactivation of specific pathways involved in both cell growth and specific programmes of cell differentiation. By consequence, the endocrine tumors expressing gsp oncogene retain differentiated functions. The gip2 oncogene has been identified in about 10% of nonfunctioning pituitary adenomas, in tumors of the ovary and the adrenal cortex. However, it remains to be established whether Gi proteins activate mitogenic signals in pituitary cells. Since Gi proteins are involved in mediating the effect of inhibitory neurohormones on intracellular effectors, it has been proposed that in pituitary tumors the low expression of these proteins, particularly Gi1-3alpha, may contribute to uncontrolled pituitary cells growth by preventing the transduction of inhibitory signals. While by in vitro mutagenesis it has been demonstrated that activated mutant of Gq alpha, G12alpha, G13alpha and Gz alpha are fully oncogenic, it remains to be proved whether or not these abnormalities might naturally occur in human tumors and, in particular, in pituitary adenomas.

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

PubMed Central

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

2014-01-01

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kopp, Christine, E-mail: Christine.Kopp@lrz.tu-muenchen.de; Theodorou, Marilena; Poullos, Nektarios

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 wasmore » 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.« less

Hypogonadotropic Hypogonadism in Non-Functioning Pituitary Adenomas: Impact of Intervention.

PubMed

Monteiro, Diana Margarida; Freitas, Paula; Vieira, Romana; Carvalho, Davide

2017-06-01

To determine the prevalence of hypogonadotropic hypogonadism (HH) among patients with non-functioning pituitary adenomas (NFPA) and the post-surgery outcome on pituitary gonadotropins secretion (PGS); to determine the prevalence of erectile dysfunction (ED) on male patients with NFPA, to evaluate the impact of testosterone replacement therapy (TRT) in those with HH. Retrospective evaluation of gonadal function in 109 NFPA patients (45 males), with a mean age of 51.8 years, diagnosed on the last 10 years. ED questionnaire applied to 34 male patients. Male patients with NFPA were significantly older (males 58.1±15.8 vs. females 47.4±16.94; p=0.001). Most patients had macroadenomas (67%; p=0.001) and only a minority were incidentalomas (19%; p<0.001). Prevalence of HH was 40% (60% on males, 25% on females; p<0.001). Surgery was performed in 54% of all patients (71% of males, 42% of females; p<0.003). After intervention, 14% became HH, 69% maintained previous function and 17% improved. On the questionnaire, 76% reported having ED, 54% of which had HH and 21% were under TRT. Of the patients under TRT, 79% still had ED. Median age of patients with ED was significantly higher [with ED 65 vs. without 49 years; p=0.012). There was no BMI difference between patients with or without TRT (28.0 vs. 27.4 Kg/m 2 ). NFPA was more frequent in older rather than younger patients. Males were older, had more HH and surgery. There was no significant improvement of pituitary function with surgery (17%) and 13% became iatrogenic HH. TRT had a low efficacy to improve ED in these patients. © Georg Thieme Verlag KG Stuttgart · New York.

Transsphenoidal surgery assisted by a new guidance device: results of a series of 747 cases.

PubMed

Tao, Yang; Jian-wen, Gu; Yong-qin, Kuang; Li-bin, Yang; Hai-dong, Huang; Wen-tao, Yang; Xue-min, Xing

2011-10-01

The objective of this study is to report the efficacy and safety of microsurgical transsphenoidal surgery using a frame for sella guidance in a series of patients with untreated pituitary adenoma. In this study, seven hundred and forty-seven patients undergoing transsphenoidal resection of a pituitary adenoma involving use of the frame were included. Follow-up of twelve to one hundred months was performed in all patients. During the procedures using the frame, pituitary adenomas were fully exposed, and no cavernous sinus haemorrhage due to anteroposterior displacement or internal carotid artery lesion due to right-and-left deviation occurred. The duration of the surgical procedure ranged from 28 min to 87 min with a mean of 44 min. The most frequent tumour type was prolactin-secreting adenoma (32.4%), followed by clinically non-functioning adenoma (NFPA) (28.5%), growth hormone-secreting adenoma (25.0%), and adrenocorticotropin-secreting adenoma (13.7%). Normalisation of visual defects occurred in 226 (42.2%) of the 535 patients with visual disturbances. Normalisation of hormone occurred in 458 of 551 patients with endocrine-active tumour in the follow-up period. Two patients died as a consequence of surgery. The endonasal transsphenoidal technique is a safe, quick, and effective approach to pituitary adenomas. Our guidance frame allows the surgeon to open and close the wound rapidly, which avoids trajectory deviation and shortens the duration of the surgical procedure. Copyright © 2011 Elsevier B.V. All rights reserved.

Overexpression of stromal cell-derived factor 1 and its receptor CXCR4 induces autocrine/paracrine cell proliferation in human pituitary adenomas.

PubMed

Barbieri, Federica; Bajetto, Adriana; Stumm, Ralf; Pattarozzi, Alessandra; Porcile, Carola; Zona, Gianluigi; Dorcaratto, Alessandra; Ravetti, Jean-Louis; Minuto, Francesco; Spaziante, Renato; Schettini, Gennaro; Ferone, Diego; Florio, Tullio

2008-08-15

Hypothalamic or locally produced growth factors and cytokines control pituitary development, functioning, and cell division. We evaluated the expression of the chemokine stromal cell-derived factor 1 (SDF1) and its receptor CXCR4 in human pituitary adenomas and normal pituitary tissues and their role in cell proliferation. The expression of SDF1 and CXCR4 in 65 human pituitary adenomas and 4 human normal pituitaries was determined by reverse transcription-PCR, immunohistochemistry, and confocal immunofluorescence. The proliferative effect of SDF1 was evaluated in eight fibroblast-free human pituitary adenoma cell cultures. CXCR4 mRNA was expressed in 92% of growth hormone (GH)-secreting pituitary adenomas (GHoma) and 81% of nonfunctioning pituitary adenomas (NFPA), whereas SDF1 was identified in 63% and 78% of GHomas and NFPAs, respectively. Immunostaining for CXCR4 and SDF1 showed a strong homogenous labeling in all tumoral cells in both GHomas and NFPAs. In normal tissues, CXCR4 and SDF1 were expressed only in a subset of anterior pituitary cells, with a lower expression of SDF1 compared with its cognate receptor. CXCR4 and SDF1 were not confined to a specific cell population in the anterior pituitary but colocalized with discrete subpopulations of GH-, prolactin-, and adrenocorticorticotropic hormone-secreting cells. Conversely, most of the SDF1-containing cells expressed CXCR4. In six of eight pituitary adenoma primary cultures, SDF1 induced a statistically significant increase in DNA synthesis that was prevented by the treatment with the CXCR4 antagonist AMD3100 or somatostatin. CXCR4 and SDF1 are overexpressed in human pituitary adenomas and CXCR4 activation may contribute to pituitary cell proliferation and, possibly, to adenoma development in humans.

Analysis of short- and long-term metabolic effects of growth hormone replacement therapy in adult patients with craniopharyngioma and non-functioning pituitary adenoma.

PubMed

Profka, E; Giavoli, C; Bergamaschi, S; Ferrante, E; Malchiodi, E; Sala, E; Verrua, E; Rodari, G; Filopanti, M; Beck-Peccoz, P; Spada, A

2015-04-01

Adult patients operated for craniopharyngioma develop more frequently GH deficiency (GHD) than patients operated for non-functioning pituitary adenoma (NFPA). The aim of the study was to compare both short- (1 year) and long-term (5 years) effects of rhGH in 38 GHD adult patients (19 operated for Craniopharyngioma (CP) and 19 for NFPA). IGF-I levels, body composition (BF%), BMI, lipid profile and glucose homeostasis were evaluated in all patients. Pituitary MRI was performed at baseline and during follow-up, as needed. At baseline no difference between the two groups was observed, apart from a higher prevalence of diabetes insipidus in CP patients (79 vs 21%). After 12 months, IGF-I SDS normalized and BF% significantly decreased only in the NFPA group. During long-term treatment, decrease in BF% and improvement in lipid profile shown by reduction in total- and LDL-cholesterol were present in NFPA group only, while increase in insulin levels and HbA1c and decrease of QUICKI were observed in CP patients only. Accordingly, after long-term therapy, the prevalence of metabolic syndrome (MS) was significantly higher in CP than in NFPA group (37% in CP and in 5% in NFPA group; p < 0.05). The present data suggest that CP patients are less sensitive to the positive rhGH effects on lipid profile and BF% and more prone to insulin sensitivity worsening than NFPA patients, resulting in increased prevalence of MS in CP only.

Increased prevalence of psychopathology and maladaptive personality traits after long-term cure of Cushing's disease.

PubMed

Tiemensma, Jitske; Biermasz, Nienke R; Middelkoop, Huub A M; van der Mast, Roos C; Romijn, Johannes A; Pereira, Alberto M

2010-10-01

Psychopathology and maladaptive personality traits are often observed during the active phase of Cushing's disease (CD). We hypothesized that patients with long-term cure of CD show persistent psychopathology and maladaptive personality traits. Four questionnaires on frequently occurring psychopathology in somatic illnesses were used, including the Apathy Scale, Irritability Scale, Hospital Anxiety and Depression Scale, and Mood and Anxiety Symptoms Questionnaire short-form. Personality was assessed using the Dimensional Assessment of Personality Pathology short-form (DAPPs). We included 51 patients cured of CD (16% men, 53 ± 13 yr) and 51 matched controls. In addition, we included 55 patients treated for nonfunctioning pituitary macroadenomas (55% men, 62 ± 10 yr), and 55 matched controls. Mean duration of remission was 11 yr (range 1-32 yr). Compared with matched controls, patients cured from CD scored significantly worse on virtually all questionnaires. Compared with nonfunctioning pituitary macroadenoma patients, patients treated for CD scored worse on apathy (P < 0.001), irritability (P < 0.001), anxiety (P < 0.001), negative affect and lack of positive affect (P < 0.001 on both scales), somatic arousal (P < 0.001), and 11 of 18 subscales of the Dimensional Assessment of Personality Pathology short-form (P < 0.05). Patients with long-term cured CD show an increased prevalence of psychopathology and maladaptive personality traits. These observations suggest irreversible effects of previous glucocorticoid excess on the central nervous system rather than an effect of pituitary tumors and/or their treatment in general. This may also be of relevance for patients treated with high doses of exogenous glucocorticoids.

Systematic Investigation of Expression of G2/M Transition Genes Reveals CDC25 Alteration in Nonfunctioning Pituitary Adenomas.

PubMed

Butz, Henriett; Németh, Kinga; Czenke, Dóra; Likó, István; Czirják, Sándor; Zivkovic, Vladimir; Baghy, Kornélia; Korbonits, Márta; Kovalszky, Ilona; Igaz, Péter; Rácz, Károly; Patócs, Attila

2017-07-01

Dysregulation of G1/S checkpoint of cell cycle has been reported in pituitary adenomas. In addition, our previous finding showing that deregulation of Wee1 kinase by microRNAs together with other studies demonstrating alteration of G2/M transition in nonfunctioning pituitary adenomas (NFPAs) suggest that G2/M transition may also be important in pituitary tumorigenesis. To systematically study the expression of members of the G2/M transition in NFPAs and to investigate potential microRNA (miRNA) involvement. Totally, 80 NFPA and 14 normal pituitary (NP) tissues were examined. Expression of 46 genes encoding members of the G2/M transition was profiled on 34 NFPA and 10 NP samples on TaqMan Low Density Array. Expression of CDC25A and two miRNAs targeting CDC25A were validated by individual quantitative real time PCR using TaqMan assays. Protein expression of CDC25A, CDC25C, CDK1 and phospho-CDK1 (Tyr-15) was investigated on tissue microarray and immunohistochemistry. Several genes' expression alteration were observed in NFPA compared to normal tissues by transcription profiling. On protein level CDC25A and both the total and the phospho-CDK1 were overexpressed in adenoma tissues. CDC25A correlated with nuclear localized CDK1 (nCDK1) and with tumor size and nCDK1 with Ki-67 index. Comparing primary vs. recurrent adenomas we found that Ki-67 proliferation index was higher and phospho-CDK1 (inactive form) was downregulated in recurrent tumors compared to primary adenomas. Investigating the potential causes behind CDC25A overexpression we could not find copy number variation at the coding region nor expression alteration of CDC25A regulating transcription factors however CDC25A targeting miRNAs were downregulated in NFPA and negatively correlated with CDC25A expression. Our results suggest that among alterations of G2/M transition of the cell cycle, overexpression of the CDK1 and CDC25A may have a role in the pathogenesis of the NFPA and that CDC25A is potentially regulated by miRNAs.

Intraoperative magnetic resonance imaging assessment of non-functioning pituitary adenomas during transsphenoidal surgery.

PubMed

Patel, Kunal S; Yao, Yong; Wang, Renzhi; Carter, Bob S; Chen, Clark C

2016-04-01

To review the utility of intraoperative imaging in facilitating maximal resection of non-functioning pituitary adenomas (NFAs). We performed an exhaustive MEDLINE search, which yielded 5598 articles. Upon careful review of these studies, 31 were pertinent to the issue of interest. Nine studies examined whether intraoperative MRI (iMRI) findings correlated with the presence of residual tumor on MRI taken 3 months after surgical resection. All studies using iMRI of >0.15T showed a ≥90% concordance between iMRI and 3-month post-operative MRI findings. 24 studies (22 iMRI and 2 intraoperative CT) examined whether intraoperative imaging improved the surgeon's ability to achieve a more complete resection. The resections were carried out under microscopic magnification in 17 studies and under endoscopic visualization in 7 studies. All studies support the value of intraoperative imaging in this regard, with improved resection in 15-83% of patients. Two studies examined whether iMRI (≥0.3T) improved visualization of residual NFA when compared to endoscopic visualization. Both studies demonstrated the value of iMRI in this regard, particularly when the tumor is located lateral of the sella, in the cavernous sinus, and in the suprasellar space. The currently available literature supports the utility of intraoperative imaging in facilitating increased NFA resection, without compromising safety.

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 arrest in adolescents. In adults, the presentation may vary.A combination of hypopituitarism and mixed signal intensity lesion on MRI is suggestive of XGH and should be considered in the differential diagnosis of sellar lesions.Radical surgery is the treatment of choice and carries an excellent prognosis with no recurrence. PMID:25759759

Congenital combined pituitary hormone deficiency attributable to a novel PROP1 mutation (467insT).

PubMed

Nose, Osamu; Tatsumi, Keita; Nakano, Yukiko; Amino, Nobuyuki

2006-04-01

Combined pituitary hormone deficiency (CPHD) is an anterior pituitary disorder, commonly resulting in growth retardation. PROP1 gene mutations appear to be frequently responsible for CPHD, particularly in Middle and Eastern Europe and the Americas, but few cases have been reported in Japan. Two sisters (aged 8.4 and 4.3 years at presentation) exhibited proportional short stature from about 2 years of age. Genetic analysis determined the nature and location of mutations. Pituitary size by magnetic resonance imaging (MRI) indicated only slight hypoplasia, while hormone analysis revealed deficiencies in secretion of growth hormone (GH), thyroid stimulating hormone, prolactin and gonadotropins; adrenocortinotropin secretion appeared adequate. Genetic analysis revealed a novel familial inherited PROP1 mutation. A unique insertion mutation was found in codon 156 (467insT) located in the transcription-activating region of the PROP1 gene. The resulting PROP1 protein (191 amino acids) would lack the transcription activation domain and consequently be non-functional. Gene analysis suggested that the siblings had inherited a unique autosomal recessive PROP1 gene mutation resulting in severe GH deficiency and subsequent growth retardation.

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

PubMed

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

2014-01-01

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

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

The somatostatin analogue octreotide confers sensitivity to rapamycin treatment on pituitary tumor cells.

PubMed

Cerovac, Vesna; Monteserin-Garcia, Jose; Rubinfeld, Hadara; Buchfelder, Michael; Losa, Marco; Florio, Tullio; Paez-Pereda, Marcelo; Stalla, Günter K; Theodoropoulou, Marily

2010-01-15

Rapamycin and its analogues have significant antiproliferative action against a variety of tumors. However, sensitivity to rapamycin is reduced by Akt activation that results from the ablative effects of rapamycin on a p70 S6K-induced negative feedback loop that blunts phosphoinositide 3-kinase (PI3K)-mediated support for Akt activity. Thus, sensitivity to rapamycin might be increased by imposing an upstream blockade to the PI3K/Akt pathway. Here, we investigated this model using the somatostatin analogue octreotide as a tool to decrease levels of activated Ser(473)-phosphorylated Akt (pAkt-Ser(473)) in pituitary tumor cells that express somatostatin receptors. Octreotide increased levels of phosphorylated insulin receptor substrate-1 that were suppressed by rapamycin, subsequently decreasing levels of pAkt-Ser(473) through effects on phosphotyrosine phosphatase SHP-1. Octreotide potentiated the antiproliferative effects of rapamycin in immortalized pituitary tumor cells or human nonfunctioning pituitary adenoma cells in primary cell culture, sensitizing tumor cells even to low rapamycin concentrations. Combined treatment of octreotide and rapamycin triggered G(1) cell cycle arrest, decreasing E2F transcriptional activity and cyclin E levels by increasing levels of p27/Kip1. These findings show that adjuvant treatment with a somatostatin analogue can sensitize pituitary tumor cells to the antiproliferative effects of rapamycin.

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. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Intraoperative Identification of a Normal Pituitary Gland and an Adenoma Using Near-Infrared Fluorescence Imaging and Low-Dose Indocyanine Green.

PubMed

Verstegen, Marco J T; Tummers, Quirijn R J G; Schutte, Pieter J; Pereira, Alberto M; van Furth, Wouter R; van de Velde, Cornelis J H; Malessy, Martijn J A; Vahrmeijer, Alexander L

2016-09-01

The intraoperative distinction between normal and abnormal pituitary tissue is crucial during pituitary adenoma surgery to obtain a complete tumor resection while preserving endocrine function. Near-infrared (NIR) fluorescence imaging is a technique to intraoperatively visualize tumors by using indocyanine green (ICG), a contrast agent allowing visualization of differences in tissue vascularization. Although NIR fluorescence imaging has been described in pituitary surgery, it has, in contrast to other surgical areas, never become widely used. To evaluate NIR fluorescence imaging in pituitary surgery, both qualitatively and quantitatively, and to assess the additional value of resecting adenoma tissue under NIR fluorescence guidance. We included 10 patients planned to undergo transnasal transsphenoidal selective adenomectomy. Patients received multiple intravenous administrations of 5 mg ICG, up to a maximum of 15 mg per patient. Endoscopic NIR fluorescence imaging was performed at multiple points in time. The NIR fluorescent signal in both the adenoma and pituitary gland was obtained, and the fluorescence contrast ratio was assessed. Four patients had Cushing disease, 1 had acromegaly, and 1 had a prolactinoma. Four patients had a nonfunctioning macroadenoma. In 9 of 10 patients with a histologically proven pituitary adenoma, the normal pituitary gland showed a stronger fluorescent signal than the adenoma. A fluorescence contrast ratio of normal pituitary gland to adenoma of 1.5 ± 0.2 was obtained. In 2 patients; adenoma resection was actually performed under NIR fluorescence guidance instead of under white light. NIR fluorescence imaging can easily and safely be implemented in pituitary surgery. The timing of ICG administration is important for optimal results and warrants further study. It appears that injection of ICG can best be postponed until some part of the normal pituitary gland is identified. Subsequent repeated low-dose ICG administrations improved the distinction between adenoma and gland.

Somatotropinomas, but not nonfunctioning pituitary adenomas, maintain a functional apoptotic RET/Pit1/ARF/p53 pathway that is blocked by excess GDNF.

PubMed

Diaz-Rodriguez, Esther; Garcia-Rendueles, Angela R; Ibáñez-Costa, Alejandro; Gutierrez-Pascual, Ester; Garcia-Lavandeira, Montserrat; Leal, Alfonso; Japon, Miguel A; Soto, Alfonso; Venegas, Eva; Tinahones, Francisco J; Garcia-Arnes, Juan A; Benito, Pedro; Angeles Galvez, Maria; Jimenez-Reina, Luis; Bernabeu, Ignacio; Dieguez, Carlos; Luque, Raul M; Castaño, Justo P; Alvarez, Clara V

2014-11-01

Acromegaly is caused by somatotroph cell adenomas (somatotropinomas [ACROs]), which secrete GH. Human and rodent somatotroph cells express the RET receptor. In rodents, when normal somatotrophs are deprived of the RET ligand, GDNF (Glial Cell Derived Neurotrophic Factor), RET is processed intracellularly to induce overexpression of Pit1 [Transcription factor (gene : POUF1) essential for transcription of Pituitary hormones GH, PRL and TSHb], which in turn leads to p19Arf/p53-dependent apoptosis. Our purpose was to ascertain whether human ACROs maintain the RET/Pit1/p14ARF/p53/apoptosis pathway, relative to nonfunctioning pituitary adenomas (NFPAs). Apoptosis in the absence and presence of GDNF was studied in primary cultures of 8 ACROs and 3 NFPAs. Parallel protein extracts were analyzed for expression of RET, Pit1, p19Arf, p53, and phospho-Akt. When GDNF deprived, ACRO cells, but not NFPAs, presented marked level of apoptosis that was prevented in the presence of GDNF. Apoptosis was accompanied by RET processing, Pit1 accumulation, and p14ARF and p53 induction. GDNF prevented all these effects via activation of phospho-AKT. Overexpression of human Pit1 (hPit1) directly induced p19Arf/p53 and apoptosis in a pituitary cell line. Using in silico studies, 2 CCAAT/enhancer binding protein alpha (cEBPα) consensus-binding sites were found to be 100% conserved in mouse, rat, and hPit1 promoters. Deletion of 1 cEBPα site prevented the RET-induced increase in hPit1 promoter expression. TaqMan qRT-PCR (real time RT-PCR) for RET, Pit1, Arf, TP53, GDNF, steroidogenic factor 1, and GH was performed in RNA from whole ACRO and NFPA tumors. ACRO but not NFPA adenomas express RET and Pit1. GDNF expression in the tumors was positively correlated with RET and negatively correlated with p53. In conclusion, ACROs maintain an active RET/Pit1/p14Arf/p53/apoptosis pathway that is inhibited by GDNF. Disruption of GDNF's survival function might constitute a new therapeutic route in acromegaly.

MEN4 and CDKN1B mutations: the latest of the MEN syndromes.

PubMed

Alrezk, Rami; Hannah-Shmouni, Fady; Stratakis, Constantine A

2017-10-01

Multiple endocrine neoplasia (MEN) refers to a group of autosomal dominant disorders with generally high penetrance that lead to the development of a wide spectrum of endocrine and non-endocrine manifestations. The most frequent among these conditions is MEN type 1 (MEN1), which is caused by germline heterozygous loss-of-function mutations in the tumor suppressor gene MEN1 MEN1 is characterized by primary hyperparathyroidism (PHPT) and functional or nonfunctional pancreatic neuroendocrine tumors and pituitary adenomas. Approximately 10% of patients with familial or sporadic MEN1-like phenotype do not have MEN1 mutations or deletions. A novel MEN syndrome was discovered, initially in rats (MENX), and later in humans (MEN4), which is caused by germline mutations in the putative tumor suppressor CDKN1B The most common phenotype of the 19 established cases of MEN4 that have been described to date is PHPT followed by pituitary adenomas. Recently, somatic or germline mutations in CDKN1B were also identified in patients with sporadic PHPT, small intestinal neuroendocrine tumors, lymphoma and breast cancer, demonstrating a novel role for CDKN1B as a tumor susceptibility gene for other neoplasms. In this review, we report on the genetic characterization and clinical features of MEN4. © 2017 Society for Endocrinology.

Glial-derived neurotropic factor and RET gene expression in normal human anterior pituitary cell types and in pituitary tumors.

PubMed

Japón, Miguel A; Urbano, Angel G; Sáez, Carmen; Segura, Dolores I; Cerro, Alfonso Leal; Diéguez, Carlos; Alvarez, Clara V

2002-04-01

Glial-derived neurotropic factor (GDNF) signaling is mediated through a 2-component system consisting of the so-called GDNF receptor-alpha (GFRalpha1), which binds to GDNF. This complex activates the tyrosine kinase receptor RET. In this paper we demonstrate GDNF, GFRalpha1, and RET mRNA and protein expression in the human anterior pituitary gland. Double immunohistochemistry of anterior pituitary sections showed GDNF immunoreactivity in more than 95% of somatotrophs and to a lesser extent in corticotrophs (20%); it was almost absent in the remaining cell types. Also, although more than 95% of somatotrophs were stained for RET, no positive immunostaining could be detected in other cell types. Furthermore, we have looked for GDNF and RET in human pituitary adenomas of various hormonal phenotypes. Strong positive immunostaining was found for c-RET in all of the GH-secreting adenomas screened as well as in 50% of ACTH-producing adenomas. Positive immunostaining for GDNF was found in all of the GH-secreting adenomas and in 10% of the corticotropinomas. Lastly, we found strong positive immunostaining for GFRalpha1 in 90% of the somatotropinomas and 50% of the corticotropinomas as well as in 1 of 8 prolactinomas and 1 of 13 nonfunctioning adenomas. All of the remaining pituitary tumors screened were negative for RET, GDNF, and GFRalpha1. This study indicates that GDNF may well be acting in the regulation of somatotroph cell growth and/or cell function in the normal human anterior pituitary gland. The expression of RET in all of the somatotropinomas and in 50% of the ACTH-producing tumors implies that GDNF and RET could be involved in the pathogenesis of pituitary tumors.

Pit-1/growth hormone factor 1 splice variant expression in the rhesus monkey pituitary gland and the rhesus and human placenta.

PubMed

Schanke, J T; Conwell, C M; Durning, M; Fisher, J M; Golos, T G

1997-03-01

We have examined the expression of Pit-1 messenger RNA (mRNA) splice variants in the nonhuman primate pituitary and in rhesus and human placenta. Full-length complementary DNAs (cDNAs) representing Pit-1 and the Pit-1 beta splice variants were cloned from a rhesus monkey pituitary cDNA library and were readily detectable by RT-PCR with rhesus pituitary gland RNA. The Pit-1T variant previously reported in mouse pituitary tumor cell lines was not detectable in normal rhesus pituitary tissue, although two novel splice variants were detected. A cDNA approximating the rat Pit-1 delta 4 variant was cloned but coded for a truncated and presumably nonfunctional protein. Only by using a nested RT-PCR approach were Pit-1 and Pit-1 beta variants consistently detectable in both human and rhesus placental tissue. The Pit-1 beta variant mRNA was not detectable in JEG-3 choriocarcinoma cells unless the cells were stimulated with 8-Br-cAMP. Immunoblot studies with nuclear extracts from primary rhesus syncytiotrophoblast cultures or JEG-3 choriocarcinoma cells indicated that although mRNA levels were very low, Pit-1 protein was detectable in differentiated cytotrophoblasts, and levels increased after treatment with 8-Br-cAMP. Two major species of Pit-1 protein were detected that corresponded to the two major bands in rat pituitary GH3 cell nuclear extracts. Low levels of slightly larger bands also were seen, which may represent Pit-1 beta protein or phosphorylated species. We conclude that Pit-1 splice variants expressed in the primate pituitary gland differ from those in the rodent gland and that the Pit-1 and Pit-1 beta mRNAs expressed in the placenta give rise to a pattern of protein expression similar to that seen in pituitary cells, which is inducible by treatment with 8-Br-cAMP.

Recent Evolution of Endoscopic Endonasal Surgery for Treatment of Pituitary Adenomas

PubMed Central

NISHIOKA, Hiroshi

2017-01-01

For the treatment of pituitary tumors, microscopic transsphenoidal surgery has been considered the “gold standard” since the late 1960s. Over the last two decades, however, a worldwide shift towards endoscopic endonasal surgery is in progress for many reasons. These include a wide panoramic view, improved illumination, an ability to look around anatomical corners using angled tip and, in addition, application to the extended approaches for parasellar tumors. Both endoscopic and microscopic approaches appear equally effective for nonfunctioning adenomas without significant suprasellar or lateral extensions, whereas the endoscopic approach may improve outcomes associated with the extent of resection and postoperative complications for larger tumors. Despite many theoretical benefits in the endoscopic surgery, remission rates of functioning adenomas do not substantially differ between the approaches in experienced hands. The endoscopic approach is a valid alternative to the microscopic approach for adenomas. The benefits will be more appreciated in the extended surgery for parasellar tumors. PMID:28239067

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

PubMed

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

2016-11-01

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

Transient Exacerbation of Nasal Symptoms following Endoscopic Transsphenoidal Surgery for Pituitary Tumors: A Prospective Study.

PubMed

Davies, Benjamin M; Tirr, Erica; Wang, Yi Yuen; Gnanalingham, Kanna K

2017-06-01

Object  Endoscopic transsphenoidal surgery is the commonest approach to pituitary tumors. One disadvantage of this approach is the development of early postoperative nasal symptoms. Our aim was to clarify the peak onset of these symptoms and their temporal evolution. Methods  The General Nasal Patient Inventory (GNPI) was administered to 56 patients undergoing endoscopic transsphenoidal surgery for pituitary tumors preoperatively and at 1 day, 3 days, 2 weeks, 3 months, and 6 to 12 months postoperatively. Most patients underwent surgery for pituitary adenomas ( N  = 49; 88%) and through a uninostril approach ( N  = 55; 98%). Total GNPI (0-135) and scores for the 45 individual components were compared. Results  GNPI scores peaked at 1 to 3 days postoperatively, with rapid reduction to baseline by 2 weeks and below baseline by 6 to 12 months postsurgery ( p  < 0.01). Of the 45 individual symptoms on the GNPI scale, 19 (42%) worsened transiently after surgery ( p  < 0.05). Functioning tumors had a higher GNPI scores at postoperative day 1 and 3 than nonfunctioning tumors, although their temporal evolution was the same ( p  < 0.05). Conclusions  Nasal morbidity following endoscopic transsphenoidal pituitary surgery is common, but transient, more so in the functioning subgroup. Nasal symptoms improve below baseline by 6 to 12 months, without the need for specific long-term postoperative interventions in the vast majority of patients.

Change in the immunophenotype of a somatotroph adenoma resulting in gigantism.

PubMed

Thawani, Jayesh P; Bailey, Robert L; Burns, Carrie M; Lee, John Y K

2014-01-01

Examining the pathologic progression of a pituitary adenoma from the point of a prepubescent child to an adult with gigantism affords us an opportunity to consider why patients may develop secretory or functioning tumors and raises questions about whether therapeutic interventions and surveillance strategies could be made to avoid irreversible phenotypic changes. A patient underwent a sublabial transsphenoidal resection for a clinically non-functioning macroadenoma in 1999. He underwent radiation treatment and was transiently given growth hormone (GH) supplementation as an adolescent. His growth rapidly traversed several percentiles and he was found to have elevated GH levels. The patient became symptomatic and was taken for a second neurosurgical procedure. Pathology and immunohistochemical staining demonstrated a significantly higher proportion of somatotroph cells and dense granularity; he was diagnosed with a functional somatotroph adenoma. While it is likely that the described observations reflect the manifestations of a functional somatotroph adenoma in development, it is possible that pubertal growth, GH supplementation, its removal, or radiation therapy contributed to the described endocrine and pathologic changes.

Clinical efficacy and safety of surface imaging guided radiosurgery (SIG-RS) in the treatment of benign skull base tumors.

PubMed

Lau, Steven K M; Patel, Kunal; Kim, Teddy; Knipprath, Erik; Kim, Gwe-Ya; Cerviño, Laura I; Lawson, Joshua D; Murphy, Kevin T; Sanghvi, Parag; Carter, Bob S; Chen, Clark C

2017-04-01

Frameless, surface imaging guided radiosurgery (SIG-RS) is a novel platform for stereotactic radiosurgery (SRS) wherein patient positioning is monitored in real-time through infra-red camera tracking of facial topography. Here we describe our initial clinical experience with SIG-RS for the treatment of benign neoplasms of the skull base. We identified 48 patients with benign skull base tumors consecutively treated with SIG-RS at a single institution between 2009 and 2011. Patients were diagnosed with meningioma (n = 22), vestibular schwannoma (n = 20), or nonfunctional pituitary adenoma (n = 6). Local control and treatment-related toxicity were retrospectively assessed. Median follow-up was 65 months (range 61-72 months). Prescription doses were 12-13 Gy in a single fraction (n = 18), 8 Gy × 3 fractions (n = 6), and 5 Gy × 5 fractions (n = 24). Actuarial tumor control rate at 5 years was 98%. No grade ≥3 treatment-related toxicity was observed. Grade ≤2 toxicity was associated with symptomatic lesions (p = 0.049) and single fraction treatment (p = 0.005). SIG-RS for benign skull base tumors produces clinical outcomes comparable to conventional frame-based SRS techniques while enhancing patient comfort.

Significant improvement of intractable headache after transsphenoidal surgery in patients with pituitary adenomas; preoperative neuroradiological evaluation and intraoperative intrasellar pressure measurement.

PubMed

Hayashi, Yasuhiko; Kita, Daisuke; Iwato, Masayuki; Fukui, Issei; Oishi, Masahiro; Tsutsui, Taishi; Tachibana, Osamu; Nakada, Mitsutoshi

2016-04-01

Headache is the most common symptom of both primary and metastatic brain tumor, and is generally considered the primary symptom in patients with large pituitary adenomas. However, patients with small pituitary adenomas rarely complain of intractable headache, and neurosurgeons are unsure whether such small adenomas actually contribute to headache. If conventional medical treatments for headache prove ineffective, surgical removal of the adenoma can be considered as an alternative management strategy. We conducted a retrospective review of 180 patients who underwent transsphenoidal surgery (TSS) for pituitary adenomas at Kanazawa University Hospital between 2006 and 2014. Patients with acute phase intratumoral hemorrhage were excluded. We identified nine patients with intractable headache as the chief complaint associated with small pituitary adenoma (diameters 15.8 ± 2.6 mm, 11-20 mm), non-functioning in eight, and prolactin-secreting in one. The preoperative neuroradiological studies and headache characteristics were assessed retrospectively, and the intrasellar pressure evaluation was performed during TSS in the last seven patients. All nine patients had complete or substantial resolution of their formerly intractable headache after TSS. Headaches consisted of ocular pain ipsilateral to the adenoma localization within the sella in four cases and bifrontal headache in five. Magnetic resonance imaging of these patients revealed small diaphragmatic foramen, which were so narrow that only the pituitary stalk could pass. Computed tomography scans showed ossification beneath the sellar floor in the sphenoid sinus, presellar type in six cases, and choncal type in three. The adenomas included cysts in seven cases. There was no cavernous sinus invasion. Intrasellar pressure measurements averaged 41.5 ± 8.5 mmHg, range 34-59, significantly higher than in control patients without headache (n = 12), namely 22.2 ± 10.6 mmHg (16-30). In this study, the authors demonstrated the validity of TSS in the treatment of intractable headache associated with pituitary adenoma. The presence of ocular pain, especially ipsilateral to the adenoma, integrity of the diaphragm sella, and ossification in the sphenoid sinus, cyst or hemorrhage and the absence of cavernous sinus invasion were the indications for TSS for patients complaining of intractable headache and having pituitary adenomas.

Primary Hypothyroidism with Exceptionally High Prolactin-A Really Big Deal.

PubMed

Khorassanizadeh, Rahim; Sundaresh, Vishnu; Levine, Steven N

2016-07-01

Primary hypothyroidism can cause both hyperprolactinemia and pituitary hyperplasia. The degree of hyperprolactinemia is generally modest, and rarely do prolactin concentrations exceed 100 ng/mL (4.34 nmol/L). This combination of hyperprolactinemia and pituitary gland enlargement might raise suspicion for a prolactinoma or a nonfunctioning adenoma limiting the ability of hypothalamic dopamine to inhibit prolactin production, the so-called "stalk effect." We describe a 30-year-old female with headaches, galactorrhea, and hyperprolactinemia with a presumptive diagnosis of a prolactinoma. She had hypothyroidism after treatment of Graves disease at age 17 years but was noncompliant with levothyroxine replacement. Thyroid-stimulating hormone (TSH) was 263 mIU/L, FT4 was 3.01 pmol/L, and prolactin was 323 ng/mL (14.06 nmol/L). Magnetic resonance imaging (MRI) demonstrated increased volume of the pituitary gland with homogeneous enhancement with gadolinium. Levothyroxine treatment for 2 weeks decreased her TSH to130 mIU/L, but her total prolactin remained elevated at 386 ng/mL (16.78 nmol/L). Further testing identified that 76% of the total prolactin was macroprolactin. Primary hypothyroidism can cause hyperprolactinemia, and prolonged disease may lead to pituitary hyperplasia. However, a marked elevation of prolactin should raise suspicion to investigate additional etiologies for hyperprolactinemia. Our case exemplifies a dual etiology for hyperprolactinemia and pituitary hyperplasia caused by both hypothyroidism and macroprolactin. This knowledge is invaluable for clinicians to avoid unnecessary management with dopamine agonists and/or surgery. This patient's prolactin was 323 ng/mL (14.06 nmol/L). Before our case, the highest prolactin in a hypothyroid patient reported in the literature was 253 ng/mL (11.0 nmol/L). Copyright © 2016 Elsevier Inc. All rights reserved.

Recovery of HPA Axis Function After Successful Gonadotropin-Induced Pregnancy and Delivery in a Woman With Panhypopituitarism: Case Report and Review.

PubMed

Wang, Yi; Zhang, Qiongyue; Yang, Jianzhi; Zhao, Xiaolong; He, Min; Shou, Xuefei; Li, Shiqi; Li, Yiming; Wang, Yongfei; Ye, Hongying

2015-09-01

Hypopituitarism is defined as the partial or complete defect of anterior pituitary hormone secretion. Patients with hypopituitarism usually need life-long hormone replacement therapy. However, in this case, we report a patient with panhypopituitarism whose hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered after pregnancy and delivery. In this case study, we reported the case management and conducted a review of literature to identify the possible mechanism of pituitary function recovery. The patient who suffered from secondary amenorrhea was found a nonfunctioning pituitary macroadenoma, and the hormone test showed serum cortisol, FT3, FT4, thyrotropic hormone, and prolactin were at normal range. After surgical removal of the tumor which invasion in the sellar region, the patient had panhypopituitarism confirmed by the routine hormone test. Though spontaneous pregnancy is impossible in female patients with panhypopituitarism, the patient was restored fertility by the help of artificial reproductive techniques. After the confirmation of the pregnancy, levothyroixine was increased to 75 μg daily and readjusted to 150 μg daily before delivery according to the monthly measurement thyroid function. Hydrocortisone 10 mg daily replaced cortisone acetate; the dose was increased according to the symptoms of morning sickness. A single stress dose of hydrocortisone (200 mg) was used before elective cesarean delivery and was tapered to the dose of 10 mg per day in 1 week. Levothyroixine was reduced to 75 μg daily after delivery. During follow-up, her hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered. The peak serum cortisol level could increase to 19.08 μg/dL by insulin-induced hypoglycemia. However, growth hormone remained unresponsive to the insulin-tolerance test, and thyroid hormone still needed exogenous supplementation. Hormone replacement therapy needed closely followed by endocrinologist and multidisciplinary cooperation during the pregnancy of patients with hypopituitarism. This case indicates that the pituitary function may partially recover after pregnancy in panhypopituitarism patients.

Psychometrics of Multiple Choice Questions with Non-Functioning Distracters: Implications to Medical Education.

PubMed

Deepak, Kishore K; Al-Umran, Khalid Umran; AI-Sheikh, Mona H; Dkoli, B V; Al-Rubaish, Abdullah

2015-01-01

The functionality of distracters in a multiple choice question plays a very important role. We examined the frequency and impact of functioning and non-functioning distracters on psychometric properties of 5-option items in clinical disciplines. We analyzed item statistics of 1115 multiple choice questions from 15 summative assessments of undergraduate medical students and classified the items into five groups by their number of non-functioning distracters. We analyzed the effect of varying degree of non-functionality ranging from 0 to 4, on test reliability, difficulty index, discrimination index and point biserial correlation. The non-functionality of distracters inversely affected the test reliability and quality of items in a predictable manner. The non-functioning distracters made the items easier and lowered the discrimination index significantly. Three non-functional distracters in a 5-option MCQ significantly affected all psychometric properties (p < 0.5). The corrected point biserial correlation revealed that the items with 3 functional options were psychometrically as effective as 5-option items. Our study reveals that a multiple choice question with 3 functional options provides lower most limit of item format that has adequate psychometric property. The test containing items with less number of functioning options have significantly lower reliability. The distracter function analysis and revision of nonfunctioning distracters can serve as important methods to improve the psychometrics and reliability of assessment.

Change in the immunophenotype of a somatotroph adenoma resulting in gigantism

PubMed Central

Thawani, Jayesh P.; Bailey, Robert L.; Burns, Carrie M.; Lee, John Y. K.

2014-01-01

Background: Examining the pathologic progression of a pituitary adenoma from the point of a prepubescent child to an adult with gigantism affords us an opportunity to consider why patients may develop secretory or functioning tumors and raises questions about whether therapeutic interventions and surveillance strategies could be made to avoid irreversible phenotypic changes. Case Description: A patient underwent a sublabial transsphenoidal resection for a clinically non-functioning macroadenoma in 1999. He underwent radiation treatment and was transiently given growth hormone (GH) supplementation as an adolescent. His growth rapidly traversed several percentiles and he was found to have elevated GH levels. The patient became symptomatic and was taken for a second neurosurgical procedure. Pathology and immunohistochemical staining demonstrated a significantly higher proportion of somatotroph cells and dense granularity; he was diagnosed with a functional somatotroph adenoma. Conclusions: While it is likely that the described observations reflect the manifestations of a functional somatotroph adenoma in development, it is possible that pubertal growth, GH supplementation, its removal, or radiation therapy contributed to the described endocrine and pathologic changes. PMID:25396071

Monitoring performance, pituitary-adrenal hormones and mood profiles: how to diagnose non-functional over-reaching in male elite junior soccer players.

PubMed

Schmikli, Sándor L; de Vries, Wouter R; Brink, Michel S; Backx, Frank Jg

2012-11-01

To verify if in male elite junior soccer players a minimum 1-month performance decrease is accompanied by a mood profile and hormone levels typical of non-functional over-reaching (NFOR). A prospective case-control study using a monthly performance monitor with a standardised field test to detect the performance changes. Players with a performance decrease lasting at least 1 month were compared with control players without a performance decrease on mood scores and pre-exercise and postexercise levels of stress hormones. Sporting field and sports medical laboratory. Ninety-four young elite soccer players were monitored during the 2006-2008 seasons. Twenty-one players were invited to the laboratory, seven of whom showed a significant performance decrease. Performance change over time, scores on the profile of mood states and premaximal and postmaximal exercise serum levels of adrenocorticotropic hormone (ACTH), growth hormone (GH) and cortisol. Players with a performance decrease showed psychological and hormonal changes typical of the non-functional state of over-reaching. Scores were higher on depression and anger, whereas the resting GH levels and ACTH levels after maximal exercise were reduced. ACTH and GH were capable of classifying all but one player correctly as either NFOR or control. Performance-related criteria in field tests are capable of identifying players with worsened mood and adaptations of the endocrine system that fit the definition of NFOR. Performance, mood and hormone levels may therefore be considered as valid instruments to diagnose NFOR in young elite soccer players.

Incidence of Diabetes Insipidus in Postoperative Period among the Patients Undergoing Pituitary Tumour Surgery.

PubMed

Kadir, M L; Islam, M T; Hossain, M M; Sultana, S; Nasrin, R; Hossain, M M

2017-07-01

Post operative complications after pituitary tumour surgery vary according to procedure. There are several surgical procedures being done such as transcranial, transsphenoidal microsurgical and transsphenoidal endoscopic approaches. One of the commonest complications is diabetes insipidus (DI). Our main objective was to find out the incidence of diabetes insipidus in post operative period among patients undergoing surgical intervention for pituitary tumour in our institute. The presence of diabetes insipidus in the postoperative period was established by measuring serum Na+ concentration, hourly urine output and urinary specific gravity to find out the incidence of diabetes insipidus in postoperative period in relation to age, gender, tumour diameter, function of tumour (i.e., either hormone secreting or not) and operative procedure used for surgical resection of pituitary tumor. As it is the most common postoperative complication so, in this study we tried to find out how many of the patients develop diabetes insipidus in postoperative period following surgical resection of pituitary tumour. This cross sectional type of observational study was carried out in the department of Neurosurgery, BSMMU from May 2014 to October 2015 on 33 consecutive patients who underwent surgical intervention for pituitary tumour for the first time. Data was collected by using a data collection sheet. The incidence of diabetes insipidus was found 23.1% of patients in <30 year age group, 38.5% of patients in 31-40 year age group and 38.5% of patients in ≥40 year age group (p=0.764). In case of distribution of patients according to gender 38.5% of male and 61.5% of female developed diabetes insipidus (p=0.073). Regarding tumour size 30.8% and 69.2% of patients developed diabetes insipidus having tumour diameter <30mm and ≥30mm respectively (p=0.590). In case of operative procedure 69.2% of patients developed diabetes insipidus who was operated by transsphenoidal endoscopic approach, 23.1% and 7.7% of patients developed diabetes insipidus who underwent pituitary tumour resection through transsphenoidal microscopic approach and transcranial microscopic approach respectively (p=0.432). 17.6% of patients develop DI having functioning pituitary macroadenoma and 62.5% of patients develop DI having nonfunctioning pituitary macroadenoma. This observational study has been performed to find out the incidence of diabetes insipidus. Incidence of postoperative DI is more at or around the age of 40 years. It is slightly predominant in female. Most of the patients manifest DI in the first 24 hours of surgical intervention. Incidence of DI is low among patients having functioning pituitary macroadenoma.

Etiology of Hypopituitarism in Adult Patients: The Experience of a Single Center Database in the Serbian Population

PubMed Central

Pekić, S.; Miljić, D.; Popović, V.; Stojanović, M.; Petakov, M.

2017-01-01

There are only a few published studies related to the population-based etiology of hypopituitarism. New risks for developing hypopituitarism have been recognized in the last 10 years. Aim. To present data regarding the etiology of hypopituitarism collected in a tertiary center over the last decade. This is a cross-sectional database study. Patients and Methods. We included 512 patients (pts) with hypopituitarism, with a mean age of 45.9 ± 1.7 yrs (range: 18–82; male: 57.9%). Results. Nonfunctional pituitary adenomas were presented in 205 pts (40.5%), congenital causes in 74 pts (14.6%), while acromegaly and prolactinomas were presented in 37 (7.2%) and 36 (7.0%) patients, respectively. Craniopharyngiomas were detected in 30 pts (5.9%), and head trauma due to trauma brain injury-TBI and subarachnoid hemorrhage-SAH in 27 pts (5.4%). Survivors of hemorrhagic fever with renal syndrome (HFRS) and those with previous cranial irradiation were presented in the same frequency (18 pts, 3.5% each). Conclusion. The most common causes of hypopituitarism in our database are pituitary adenomas. Increased awareness of the other causes of pituitary dysfunction, such as congenital, head trauma, extrapituitary cranial irradiation, and infections, is the reason for a higher frequency of these etiologies of hypopituitarism in the presented database. PMID:28702053

Secondary Intracranial Tumors Following Radiotherapy for Pituitary Adenomas: A Systematic Review

PubMed Central

Yamanaka, Ryuya; Sato, Toshiteru; Hayano, Azusa; Takashima, Yasuo

2017-01-01

Pituitary adenomas are often treated with radiotherapy for the management of tumor progression or recurrence. Despite the improvement in cure rates, patients treated by radiotherapy are at risk of development of secondary malignancies. We conducted a comprehensive literature review of the secondary intracranial tumors that occurred following radiotherapy to pituitary adenomas to obtain clinicopathological characteristics. The analysis included 48 neuroepithelial tumors, 37 meningiomas, and 52 sarcomas which were published between 1959–2017, although data is missing regarding overall survival and type of irradiation in a significant proportion of the reports. The average onset age for the pituitary adenoma was 37.2 ± 14.4 years and the average latency period before the diagnosis of the secondary tumor was 15.2 ± 8.7 years. Radiotherapy was administered in pituitary adenomas at an average dose of 52.0 ± 19.5 Gy. The distribution of pituitary adenomas according to their function was prolactinoma in 10 (7.2%) cases, acromegaly in 37 (27.0%) cases, Cushing disease in 4 (2.9%) cases, PRL+GH in 1 (0.7%) case, non-functioning adenoma in 57 (41.6%) cases. Irradiation technique delivered was lateral opposing field in 23 (16.7%) cases, 3 or 4 field technique in 27 (19.6%) cases, rotation technique in 10 (7.2%) cases, radio surgery in 6 (4.3%) cases. Most of the glioma or sarcoma had been generated after lateral opposing field or 3/4 field technique. Fibrosarcomas were predominant before 1979 (p < 0.0001). The median overall survival time for all neuroepithelial tumors was 11 months (95% confidence intervals (CI), 3–14). Patients with gliomas treated with radiotherapy exhibited a non-significant positive trend with longer overall survival. The median overall survival time for sarcoma cases was 6 months (95% CI, 1.5–9). The median survival time in patients with radiation and/or chemotherapy for sarcomas exhibited a non-significant positive trend with longer overall survival. In patients treated with radiotherapy for pituitary adenomas, the risk of secondary tumor incidence warrants a longer follow up period. Moreover, radiation and/or chemotherapy should be considered in cases of secondary glioma or sarcoma following radiotherapy to the pituitary adenomas. PMID:28786923

Alterations in diurnal rhythmicity in patients treated for nonfunctioning pituitary macroadenoma: a controlled study and literature review.

PubMed

Joustra, S D; Thijs, R D; van den Berg, R; van Dijk, M; Pereira, A M; Lammers, G J; van Someren, E J W; Romijn, J A; Biermasz, N R

2014-08-01

Patients treated for nonfunctioning pituitary macroadenomas (NFMAs) have fatigue and alterations in sleep characteristics and sleep-wake rhythmicity frequently. As NFMAs often compress the optic chiasm, these complaints might be related to dysfunction of the adjacent suprachiasmatic nucleus (SCN). We aimed to explore whether indirect indices of SCN functioning are altered in the long term after surgery for NFMAs. We studied 17 NFMA patients in long-term remission after transsphenoidal surgery, receiving adequate and stable hormone replacement for hypopituitarism, and 17 control subjects matched for age, gender, and BMI. Indirect indices of SCN function were assessed from 24-h ambulatory recordings of skin and core body temperatures, blood pressure, and salivary melatonin levels. Altered melatonin secretion was defined as an absence of evening rise, considerable irregularity, or daytime values >3 pg/ml. We additionally studied eight patients treated for craniopharyngioma. Distal-proximal skin temperature gradient did not differ between NFMAs and control subjects, but proximal skin temperature was decreased during daytime (P=0.006). Core body temperature and non-dipping of blood pressure did not differ, whereas melatonin secretion was often altered in NFMAs (OR 5.3, 95% CI 0.9-30.6). One or more abnormal parameters (≥2.0 SDS of control subjects) were observed during nighttime in 12 NFMA patients and during daytime in seven NFMA patients. Similar patterns were observed in craniopharyngioma patients. Heterogeneous patterns of altered diurnal rhythmicity in skin temperature and melatonin secretion parameters were observed in the majority of patients treated for NFMAs. On a group level, both NFMA and craniopharyngioma patients showed a lower daytime proximal skin temperature than control subjects, but other group averages were not significantly different. The observations suggest altered function of central (or peripheral) clock machinery, possibly by disturbed entrainment or damage of the hypothalamic SCN by the suprasellar macroadenoma or its treatment. © 2014 European Society of Endocrinology.

Fractures in pituitary adenoma patients from the Dutch National Registry of Growth Hormone Treatment in Adults.

PubMed

van Varsseveld, N C; van Bunderen, C C; Franken, A A M; Koppeschaar, H P F; van der Lely, A J; Drent, M L

2016-08-01

The effects of growth hormone (GH) replacement therapy on fracture risk in adult GH deficient (GHD) patients with different etiologies of pituitary GHD are not well known, due to limited data. The aim of this study was to investigate characteristics and fracture occurrence at start of (baseline) and during long-term GH replacement therapy in GHD adults previously treated for Cushing's disease (CD) or acromegaly, compared to patients with previous nonfunctioning pituitary adenoma (NFPA). From the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide surveillance study in severe GHD adults, all patients using ≥30 days of GH replacement therapy with previous NFPA (n = 783), CD (n = 180) and acromegaly (n = 65) were selected. Patient characteristics, fractures and potential influencing factors were investigated. At baseline, patients with previous CD were younger, more often female and had more often a history of osteopenia or osteoporosis, whereas patients with previous acromegaly had more often received cranial radiotherapy and a longer duration between treatment of their pituitary tumor and start of adult GH replacement therapy. During follow-up, a fracture occurred in 3.8 % (n = 39) of all patients. Compared to patients with previous NFPA, only patients with previous acromegaly had an increased fracture risk after 6 years of GH replacement therapy. During GH replacement therapy, an increased fracture risk was observed in severe GHD adult patients previously treated for acromegaly, but not in those previously treated for CD, compared to severe GHD adult patients using GH replacement therapy because of previous NFPA. Further studies are needed to confirm these findings and to elucidate potential underlying mechanisms.

Endoscopic Endonasal Versus Microscopic Transsphenoidal Surgery for Recurrent and/or Residual Pituitary Adenomas.

PubMed

Esquenazi, Yoshua; Essayed, Walid I; Singh, Harminder; Mauer, Elizabeth; Ahmed, Mudassir; Christos, Paul J; Schwartz, Theodore H

2017-05-01

Surgery for recurrent/residual pituitary adenomas is increasingly being performed through endoscopic surgery. Whether this new technology has altered the indications and outcomes of surgery is unknown. We conducted a systematic review and meta-analysis of published studies to compare the indications and outcomes between microscopic and endoscopic approaches. A PubMed search was conducted (1985-2015) to identify surgical series of endoscopic endonasal and microscopic transsphenoidal resection of residual or recurrent pituitary adenomas. Data were extracted regarding tumor characteristics, surgical treatment, extent of resection, endocrine remission, visual outcome, and complications. Twenty-one studies met inclusion criteria. A total of 292 patients were in the endoscopic group, and 648 patients were in the microscopic group. Endoscopic cases were more likely nonfunctional (P < 0.001) macroadenomas (P < 0.001) with higher rates of cavernous sinus invasion (P = 0.012). The pooled rate of gross total tumor resection was 53.5% for the endoscopic group and 46.6% for the microscopic group. Endocrine remission was achieved in 53.0% and 46.7% of patients, and visual improvement occurred in 73.2% and 49.6% for the endoscopic and microscopic groups. Cerebrospinal fluid leak and pituitary insufficiency were higher in the endoscopic group. This meta-analysis indicates that the use of the endoscope to reoperate on residual or recurrent adenomas has only led to modest increases in resection rates. However, larger more complex cases are being tackled, so direct comparisons are misleading. The most dramatic change has been in visual improvement along with modest increases in risk. Reoperation for recurrent or residual adenomas is a safe and effective treatment option. Copyright © 2017 Elsevier Inc. All rights reserved.

Nasal symptoms following endoscopic transsphenoidal pituitary surgery: assessment using the General Nasal Patient Inventory.

PubMed

Wang, Yi Yuen; Srirathan, Vinothan; Tirr, Erica; Kearney, Tara; Gnanalingham, Kanna K

2011-04-01

The endoscopic approach for pituitary tumors is a recent innovation and is said to reduce the nasal trauma associated with transnasal transsphenoidal surgery. The authors assessed the temporal changes in the rhinological symptoms following endoscopic transsphenoidal surgery for pituitary lesions, using the General Nasal Patient Inventory (GNPI). The GNPI was administered to 88 consecutive patients undergoing endoscopic transsphenoidal surgery at 3 time points (presurgery, 3-6 months postsurgery, and at final follow-up). The total GNPI score and the scores for the individual GNPI questions were calculated and differences between groups were assessed once before surgery, several months after surgery, and at final follow-up. Of a maximum possible score of 135, the mean GNPI score at 3-6 months postsurgery was only 12.9 ± 12 and was not significantly different from the preoperative score (10.4 ± 13) or final follow-up score (10.3 ± 10). Patients with functioning tumors had higher GNPI scores than those with nonfunctioning tumors for each of these time points (p < 0.05). Individually, a mild increase in symptom severity was seen for symptoms attributable to the nasal trauma of surgery, with partial recovery (nasal sores and bleeding) or complete recovery (nasal blockage, painful sinuses, and unpleasant nasal smell) by final follow-up (p < 0.05). Progressive improvements in symptom severity were seen for symptoms more attributable to tumor mass preoperatively (for example, headaches and painkiller use [p < 0.05]). In total, by final follow-up 8 patients (9%) required further treatment or advice for ongoing nasal symptoms. Endoscopic transsphenoidal surgery is a well-tolerated minimally invasive procedure for pituitary fossa lesions. Overall patient-assessed nasal symptoms do not change, but some individual symptoms may show a mild worsening or overall improvement.

Gross total resection of pituitary adenomas after endoscopic vs. microscopic transsphenoidal surgery: a meta-analysis.

PubMed

Almutairi, Reem D; Muskens, Ivo S; Cote, David J; Dijkman, Mark D; Kavouridis, Vasileios K; Crocker, Erin; Ghazawi, Kholoud; Broekman, Marike L D; Smith, Timothy R; Mekary, Rania A; Zaidi, Hasan A

2018-05-01

Microscopic transsphenoidal surgery (mTSS) is a well-established method to address adenomas of the pituitary gland. Endoscopic transsphenoidal surgery (eTSS) has become a viable alternative, however. Advocates suggest that the greater illumination, panoramic visualization, and angled endoscopic views afforded by eTSS may allow for higher rates of gross total tumor resection (GTR). The aim of this meta-analysis was to determine the rate of GTR using mTSS and eTSS. A meta-analysis of the literature was conducted using PubMed, EMBASE, and Cochrane databases through July 2017 in accordance with PRISMA guidelines. Seventy case series that reported GTR rate in 8257 pituitary adenoma patients were identified. For all pituitary adenomas, eTSS (GTR=74.0%; I 2  = 92.1%) was associated with higher GTR as compared to mTSS (GTR=66.4%; I 2  = 84.0%) in a fixed-effect model (P-interaction < 0.01). For functioning pituitary adenomas (FPAs) (n = 1170 patients), there was no significant difference in GTR rate between eTSS (GTR=75.8%; I 2  = 63.9%) and mTSS (GTR=75.5%; I 2  = 79.0%); (P-interaction = 0.92). For nonfunctioning pituitary adenomas (NFPAs) (n = 2655 patients), eTSS (GTR=71.0%; I 2  = 86.4%) was associated with higher GTR as compared to mTSS (GTR=60.7%; I 2  = 87.5%) in a fixed-effect model (P-interaction < 0.01). None of the associations were significant in a random-effect model (all P-interaction > 0.05). No significant publication bias was identified for any of the outcomes. Among patients who were not randomly allocated to either approach, eTSS resulted in a higher rate of GTR as compared to mTSS for all patients and for NFPA patients alone, but only in a fixed-effect model. For FPA, however, eTSS did not seem to offer a significantly higher rate of GTR. These conclusions should be interpreted with caution because of the nature of the included non-comparative studies.

Predictors of nonfunctional arteriovenous access at hemodialysis initiation and timing of access creation: A registry-based study

PubMed Central

Metzger, Marie; Labeeuw, Michel; Ayav, Carole; Jacquelinet, Christian; Massy, Ziad A.; Stengel, Bénédicte

2017-01-01

Determinants of nonfunctional arteriovenous (AV) access, including timing of AV access creation, have not been sufficiently described. We studied 29 945 patients who had predialysis AV access placement and were included in the French REIN registry from 2005 through 2013. AV access was considered nonfunctional when dialysis began with a catheter. We estimated crude and adjusted odds ratio (OR) with 95% confidence intervals (CI) of nonfunctional versus functional AV access associated with case-mix, facility characteristics, and timing of AV access creation. Analyses were stratified by dialysis start condition (planned or as an emergency) and comorbidity profile. Overall, 18% patients had nonfunctional AV access at hemodialysis initiation. In the group with planned dialysis start, female gender (OR 1.43, 95% CI 1.32–1.56), diabetes (OR 1.28, 95% CI 1.15–1.44), and a higher number of cardiovascular comorbidities (OR 1.27, 95% CI 1.09–1.49, and 1.31, 1.05–1.64, for 3 and >3 cardiovascular comorbidities versus none, respectively) were independent predictors of nonfunctional AV access. A higher percentage of AV access creation at the region level was associated with a lower rate of nonfunctional AV access (OR 0.98, 95% CI 0.98–0.99 per 1% increase). The odds of nonfunctional AV access decreased as time from creation to hemodialysis initiation increased up to 3 months in nondiabetic patients with fewer than 2 cardiovascular comorbidities and 6 months in patients with diabetes or 2 or more such comorbidities. In conclusion, both patient characteristics and clinical practices may play a role in successful AV access use at hemodialysis initiation. Adjusting the timing of AV access creation to patients’ comorbidity profiles may improve functional AV access rates. PMID:28749967

Predictors of nonfunctional arteriovenous access at hemodialysis initiation and timing of access creation: A registry-based study.

PubMed

Alencar de Pinho, Natalia; Coscas, Raphael; Metzger, Marie; Labeeuw, Michel; Ayav, Carole; Jacquelinet, Christian; Massy, Ziad A; Stengel, Bénédicte

2017-01-01

Determinants of nonfunctional arteriovenous (AV) access, including timing of AV access creation, have not been sufficiently described. We studied 29 945 patients who had predialysis AV access placement and were included in the French REIN registry from 2005 through 2013. AV access was considered nonfunctional when dialysis began with a catheter. We estimated crude and adjusted odds ratio (OR) with 95% confidence intervals (CI) of nonfunctional versus functional AV access associated with case-mix, facility characteristics, and timing of AV access creation. Analyses were stratified by dialysis start condition (planned or as an emergency) and comorbidity profile. Overall, 18% patients had nonfunctional AV access at hemodialysis initiation. In the group with planned dialysis start, female gender (OR 1.43, 95% CI 1.32-1.56), diabetes (OR 1.28, 95% CI 1.15-1.44), and a higher number of cardiovascular comorbidities (OR 1.27, 95% CI 1.09-1.49, and 1.31, 1.05-1.64, for 3 and >3 cardiovascular comorbidities versus none, respectively) were independent predictors of nonfunctional AV access. A higher percentage of AV access creation at the region level was associated with a lower rate of nonfunctional AV access (OR 0.98, 95% CI 0.98-0.99 per 1% increase). The odds of nonfunctional AV access decreased as time from creation to hemodialysis initiation increased up to 3 months in nondiabetic patients with fewer than 2 cardiovascular comorbidities and 6 months in patients with diabetes or 2 or more such comorbidities. In conclusion, both patient characteristics and clinical practices may play a role in successful AV access use at hemodialysis initiation. Adjusting the timing of AV access creation to patients' comorbidity profiles may improve functional AV access rates.

In-frame seven amino-acid duplication in AIP arose over the last 3000 years, disrupts protein interaction and stability and is associated with gigantism

PubMed Central

Salvatori, Roberto; Radian, Serban; Diekmann, Yoan; Iacovazzo, Donato; David, Alessia; Gabrovska, Plamena; Grassi, Giorgia; Bussell, Anna-Marie; Stals, Karen; Weber, Astrid; Quinton, Richard; Crowne, Elizabeth C; Corazzini, Valentina; Metherell, Lou; Kearney, Tara; Du Plessis, Daniel; Sinha, Ajay Kumar; Baborie, Atik; Lecoq, Anne-Lise; Chanson, Philippe; Ansorge, Olaf; Ellard, Sian; Trainer, Peter J; Balding, David; Thomas, Mark G

2017-01-01

Objective Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events. Design and methods Observational, inferential and experimental study, including: AIP mutation testing; reconstruction of 14 AIP-region (8.3 Mbp) haplotypes; coalescent-based approximate Bayesian estimation of the time to most recent common ancestor (tMRCA) of the derived allele; forward population simulations to estimate current number of allele carriers; proposal of mutation mechanism; protein structure predictions; co-immunoprecipitation and cycloheximide chase experiments. Results Nine European-origin, unrelated c.805_825dup-positive pedigrees (four familial, five sporadic from the UK, USA and France) included 16 affected (nine gigantism/four acromegaly/two non-functioning pituitary adenoma patients and one prospectively diagnosed acromegaly patient) and nine unaffected carriers. All pedigrees shared a 2.79 Mbp haploblock around AIP with additional haploblocks privately shared between subsets of the pedigrees, indicating the existence of an evolutionarily recent common ancestor, the ‘English founder’, with an estimated median tMRCA of 47 generations (corresponding to 1175 years) with a confidence interval (9–113 generations, equivalent to 225–2825 years). The mutation occurred in a small tandem repeat region predisposed to slipped strand mispairing. The resulting seven amino-acid duplication disrupts interaction with HSP90 and leads to a marked reduction in protein stability. Conclusions The c.805_825dup allele, originating from a common ancestor, associates with a severe clinical phenotype and a high frequency of gigantism. The mutation is likely to be the result of slipped strand mispairing and affects protein–protein interactions and AIP protein stability. PMID:28634279

In-frame seven amino-acid duplication in AIP arose over the last 3000 years, disrupts protein interaction and stability and is associated with gigantism.

PubMed

Salvatori, Roberto; Radian, Serban; Diekmann, Yoan; Iacovazzo, Donato; David, Alessia; Gabrovska, Plamena; Grassi, Giorgia; Bussell, Anna-Marie; Stals, Karen; Weber, Astrid; Quinton, Richard; Crowne, Elizabeth C; Corazzini, Valentina; Metherell, Lou; Kearney, Tara; Du Plessis, Daniel; Sinha, Ajay Kumar; Baborie, Atik; Lecoq, Anne-Lise; Chanson, Philippe; Ansorge, Olaf; Ellard, Sian; Trainer, Peter J; Balding, David; Thomas, Mark G; Korbonits, Márta

2017-09-01

Mutations in the aryl hydrocarbon receptor-interacting protein ( AIP ) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events. Observational, inferential and experimental study, including: AIP mutation testing; reconstruction of 14 AIP -region (8.3 Mbp) haplotypes; coalescent-based approximate Bayesian estimation of the time to most recent common ancestor (tMRCA) of the derived allele; forward population simulations to estimate current number of allele carriers; proposal of mutation mechanism; protein structure predictions; co-immunoprecipitation and cycloheximide chase experiments. Nine European-origin, unrelated c.805_825dup-positive pedigrees (four familial, five sporadic from the UK, USA and France) included 16 affected (nine gigantism/four acromegaly/two non-functioning pituitary adenoma patients and one prospectively diagnosed acromegaly patient) and nine unaffected carriers. All pedigrees shared a 2.79 Mbp haploblock around AIP with additional haploblocks privately shared between subsets of the pedigrees, indicating the existence of an evolutionarily recent common ancestor, the 'English founder', with an estimated median tMRCA of 47 generations (corresponding to 1175 years) with a confidence interval (9-113 generations, equivalent to 225-2825 years). The mutation occurred in a small tandem repeat region predisposed to slipped strand mispairing. The resulting seven amino-acid duplication disrupts interaction with HSP90 and leads to a marked reduction in protein stability. The c.805_825dup allele, originating from a common ancestor, associates with a severe clinical phenotype and a high frequency of gigantism. The mutation is likely to be the result of slipped strand mispairing and affects protein-protein interactions and AIP protein stability. © 2017 The authors.

Pituitary disorders as a predictor of apathy and executive dysfunction in adult survivors of childhood brain tumors.

PubMed

Fox, Michelle E; King, Tricia Z

2016-11-01

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

Pituitary gigantism: Causes and clinical characteristics.

PubMed

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

2015-12-01

Acromegaly and pituitary gigantism are very rare conditions resulting from excessive secretion of growth hormone (GH), usually by a pituitary adenoma. Pituitary gigantism occurs when GH excess overlaps with the period of rapid linear growth during childhood and adolescence. Until recently, its etiology and clinical characteristics have been poorly understood. Genetic and genomic causes have been identified in recent years that explain about half of cases of pituitary gigantism. We describe these recent discoveries and focus on some important settings in which gigantism can occur, including familial isolated pituitary adenomas (FIPA) and the newly described X-linked acrogigantism (X-LAG) syndrome. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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:26186299

Interpretation of serum gonadotropin levels in hyperprolactinemia.

PubMed

Abbara, Ali; Clarke, Sophie A; Nesbitt, Alexander; Ali, Sabreen; Comninos, Alexander N; Hatfield, Emma; Martin, Niamh; Sam, Amir; Meeran, Karim; Dhillo, Waljit S

2018-04-16

Background/Aims: Hyperprolactinemia is a common cause of amenorrhea due to hypogonadotropic hypogonadism. Prolactin is hypothesized to impede the reproductive axis through an inhibitory action at the hypothalamus. However, limited data exists to aid the interpretation of serum gonadotropins in the context of hyperprolactinemia. Serum gonadotropin values were reviewed in 243 patients with elevated serum monomeric prolactin due to discrete etiologies at a tertiary reproductive endocrine centre between 2012 and 2015. The cause of hyperprolactinemia was categorized by an experienced endocrinologist / pituitary multidisciplinary team, unless superseded by histology. The most frequently encountered diagnoses were Microprolactinoma (n=88), Macroprolactinoma (n=46), Non-Functioning Pituitary Adenoma (NFPA) (n=72), Drug-Induced Hyperprolactinemia (DIH) (n=22) and Polycystic Ovarian Syndrome (PCOS) (n=15). In patients with prolactinoma and modestly raised serum prolactin levels (<4000 mU/L), increasingly FSH-predominant gonadotropin values were observed with rising prolactin level, consistent with a progressive reduction in hypothalamic GnRH pulsatility. Patients with prolactinoma and higher prolactin values (>4000 mU/L) were more likely to have a reduction in serum levels of both FSH and LH, consistent with direct pituitary gonadotrope dysfunction. Patients with macroadenoma and extremes of serum gonadotropin values (either serum FSH or LH >8 IU/L) were more likely to have NFPA than prolactinoma. Patients with polycystic ovarian syndrome (PCOS) and hyperprolactinemia had LH-predominant secretion in keeping with increased GnRH pulsatility despite a raised prolactin level. The pattern of gonadotropin secretion in patients may reflect the etiology of hyperprolactinemia.
. ©2018S. Karger AG, Basel.

Adjuvant or radical fractionated stereotactic radiotherapy for patients with pituitary functional and nonfunctional macroadenoma

PubMed Central

2011-01-01

Purpose To evaluate the efficacy and toxicity of stereotactic fractionated radiotherapy (SFRT) for patients with pituitary macroadenoma (PMA). Methods and Materials Between March 2000 and March 2009, 27 patients (male to female ratio, 1.25) with PMA underwent SFRT (median dose, 50.4 Gy). Mean age of the patients was 56.5 years (range, 20.3 - 77.4). In all but one patient, SFRT was administered for salvage treatment after surgical resection (transphenoidal resection in 23, transphenoidal resection followed by craniotomy in 2 and multiple transphenoidal resections in another patient). In 10 (37%) patients, the PMAs were functional (3 ACTH-secreting, 3 prolactinomas, 2 growth hormone-secreting and 2 multiple hormone-secretion). Three (11.1%) and 9 (33.3%) patients had PMA abutting and compressing the optic chiasm, respectively. Mean tumor volume was 2.9 ± 4.6 cm3. Eighteen (66.7%) patients had hypopituitarism prior to SFRT. The mean follow-up period after SFRT was 72.4 ± 37.2 months. Results Tumor size decreased for 6 (22.2%) patients and remained unchanged for 19 (70.4%) other patients. Two (7.4%) patients had tumor growth inside the prescribed treatment volume. The estimated 5-year tumor growth control was 95.5% after SFRT. Biochemical remission occurred in 3 (30%) patients with functional PMA. Two patients with normal anterior pituitary function before SFRT developed new deficits 25 and 65 months after treatment. The 5-year survival without new anterior pituitary deficit was thus 95.8%. Five patients with visual field defect had improved visual function and 1 patient with no visual defect prior to SFRT, but an optic chiasm abutting tumor, had a decline in visual function. The estimated 5-year vision and pituitary function preservation rates were 93.2% and 95.8%, respectively. Conclusions SFRT is a safe and effective treatment for patients with PMA, although longer follow-up is needed to evaluate long-term outcomes. In this study, approximately 1 patient with visual field defect out of two had an improved visual function. PMID:22152397

Hereditary pituitary hyperplasia with infantile gigantism.

PubMed

Gläsker, Sven; Vortmeyer, Alexander O; Lafferty, Antony R A; Hofman, Paul L; Li, Jie; Weil, Robert J; Zhuang, Zhengping; Oldfield, Edward H

2011-12-01

We report hereditary pituitary hyperplasia. The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. The study is a retrospective analysis of three cases from one family. The study was conducted at the National Institutes of Health, a tertiary referral center. A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. The condition was treated by total hypophysectomy. We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development.

Pituitary Medicine From Discovery to Patient-Focused Outcomes

PubMed Central

2016-01-01

Context: This perspective traces a pipeline of discovery in pituitary medicine over the past 75 years. Objective: To place in context past advances and predict future changes in understanding pituitary pathophysiology and clinical care. Design: Author's perspective on reports of pituitary advances in the published literature. Setting: Clinical and translational Endocrinology. Outcomes: Discovery of the hypothalamic-pituitary axis and mechanisms for pituitary control, have culminated in exquisite understanding of anterior pituitary cell function and dysfunction. Challenges facing the discipline include fundamental understanding of pituitary adenoma pathogenesis leading to more effective treatments of inexorably growing and debilitating hormone secreting pituitary tumors as well as medical management of non-secreting pituitary adenomas. Newly emerging pituitary syndromes include those associated with immune-targeted cancer therapies and head trauma. Conclusions: Novel diagnostic techniques including imaging genomic, proteomic, and biochemical analyses will yield further knowledge to enable diagnosis of heretofore cryptic syndromes, as well as sub classifications of pituitary syndromes for personalized treatment approaches. Cost effective personalized approaches to precision therapy must demonstrate value, and will be empowered by multidisciplinary approaches to integrating complex subcellular information to identify therapeutic targets for enabling maximal outcomes. These goals will be challenging to attain given the rarity of pituitary disorders and the difficulty in conducting appropriately powered prospective trials. PMID:26908107

The 2017 World Health Organization classification of tumors of the pituitary gland: a summary.

PubMed

Lopes, M Beatriz S

2017-10-01

The 4th edition of the World Health Organization (WHO) classification of endocrine tumors has been recently released. In this new edition, major changes are recommended in several areas of the classification of tumors of the anterior pituitary gland (adenophypophysis). The scope of the present manuscript is to summarize these recommended changes, emphasizing a few significant topics. These changes include the following: (1) a novel approach for classifying pituitary neuroendocrine tumors according to pituitary adenohypophyseal cell lineages; (2) changes to the histological grading of pituitary neuroendocrine tumors with the elimination of the term "atypical adenoma;" and (3) introduction of new entities like the pituitary blastoma and re-definition of old entities like the null-cell adenoma. This new classification is very practical and mostly based on immunohistochemistry for pituitary hormones, pituitary-specific transcription factors, and other immunohistochemical markers commonly used in pathology practice, not requiring routine ultrastructural analysis of the tumors. Evaluation of tumor proliferation potential, by mitotic count and Ki-67 labeling index, and tumor invasion is strongly recommended on individual case basis to identify clinically aggressive adenomas. In addition, the classification offers the treating clinical team information on tumor prognosis by identifying specific variants of adenomas associated with an elevated risk for recurrence. Changes in the classification of non-neuroendocrine tumors are also proposed, in particular those tumors arising in the posterior pituitary including pituicytoma, granular cell tumor of the posterior pituitary, and spindle cell oncocytoma. These changes endorse those previously published in the 2016 WHO classification of CNS tumors. Other tumors arising in the sellar region are also reviewed in detail including craniopharyngiomas, mesenchymal and stromal tumors, germ cell tumors, and hematopoietic tumors. It is hoped that the 2017 WHO classification of pituitary tumors will establish more biologically and clinically uniform groups of tumors, make it possible for practicing pathologists to better diagnose these tumors, and contribute to our understanding of clinical outcomes for patients harboring pituitary tumors.

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

PubMed

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

2008-06-01

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

Neuropsychiatric and metabolic aspects of dopaminergic therapy: perspectives from an endocrinologist and a psychiatrist

PubMed Central

Athanasoulia-Kaspar, Anastasia P; Popp, Kathrin H; Stalla, Gunter Karl

2018-01-01

The dopaminergic treatment represents the primary treatment in prolactinomas, which are the most common pituitary adenomas and account for about 40% of all pituitary tumours with an annual incidence of six to ten cases per million population. The dopaminergic treatment includes ergot and non-ergot derivatives with high affinity for the dopamine receptors D1 or/and D2. Through the activation of the dopaminergic pathway on pituitary lactotrophs, the dopamine agonists inhibit the prolactin synthesis and secretion, therefore normalizing the prolactin levels and restoring eugonadism, but they also lead to tumour shrinkage. Treatment with dopamine agonists has been associated – apart from the common side effects such as gastrointestinal symptoms, dizziness and hypotension – with neuropsychiatric side effects such as impulse control disorders (e.g. pathological gambling, compulsive shopping, hypersexuality and binge eating) and also with behavioral changes from low mood, irritability and verbal aggressiveness up to psychotic and manic symptoms and paranoid delusions not only in patients with prolactinomas but also in patients with Parkinson’s disease and restless leg syndrome. They usually have de novo onset after initiation of the dopaminergic treatment and have been mainly reported in patients with Parkinson’s disease, who are being treated with higher doses of dopamine agonists. Moreover, dopamine and prolactin seem to play an essential role in the metabolic pathway. Patients with hyperprolactinemia tend to have increased body weight and an altered metabolic profile with hyperinsulinemia and increased prevalence of diabetes mellitus in comparison to healthy individuals and patients with non-functioning pituitary adenomas. Treatment with dopamine agonists in these patients in short-term studies seems to lead to weight loss and amelioration of the metabolic changes. Together these observations provide evidence that dopamine and prolactin have a crucial role both in the regard and metabolic system, findings that merit further investigation in long-term studies. PMID:29378769

Endoscopic Endonasal Transsphenoidal Approach

PubMed Central

Cappabianca, Paolo; Alfieri, Alessandra; Colao, Annamaria; Ferone, Diego; Lombardi, Gaetano; de Divitiis, Enrico

1999-01-01

The outcome of endoscopic endonasal transsphenoidal surgery in 10 patients with pituitary adenomas was compared with that of traditional transnasal transsphenoidal approach (TTA) in 20 subjects. Among the 10 individuals subjected to “pure endoscopy,” 2 had a microadenoma, 1 an intrasellar macroadenoma, 4 had a macroadenoma with suprasellar expansion, 2 had a macroadenoma with supra-parasellar expansion, and 1 a residual tumor; 5 had acromegaly and 5 had a nonfunctioning adenoma (NFA). Among the patients subjected to TTA, 4 had a microadenoma, 2 had an intrasellar macroadenoma, 6 had a macroadenoma with suprasellar expansion, 4 had a macroadenoma with supra-parasellar expansion, and 4 had a residual tumor; 9 patients had acromegaly, 1 hyperprolactinemia, 1 Cushing's disease, and 9 a NFA. At the macroscopic evaluation, tumor removal was total (100%) after endoscopy in 9 patients and after TTA in 14 patients. Six months after surgery, magnetic resonance imaging (MRI) confirmed the total tumor removal in 21 of 23 patients (91.3%). Circulating growth hormone (GH) and insulin-like growth factor-I (IGF-I) significantly decreased 6 months after surgery in all 14 acromegalic patients: normalization of plasma IGF-I levels was obtained in 4 of 5 patients after the endoscopic procedure and in 4 of 9 patients after TTA. Before surgery, pituitary hormone deficiency was present in 14 out of 30 patients: pituitary function improved in 4 patients, remaining unchanged in the other 10 patients. Visual field defects were present before surgery in 4 patients, and improved in all. Early surgical results in the group of 10 patients who underwent endoscopic pituitary tumor removal were at least equivalent to those of standard TTA, with excellent postoperative course. Postsurgical hospital stay was significantly shorter (3.1 ± 0.4 vs. 6.2 ± 0.3 days, p < 0.001) after endoscopy as compared to TTA. ImagesFigure 1Figure 2 PMID:17171126

MRI features of growth hormone deficiency in children with short stature caused by pituitary lesions.

PubMed

Xu, Chao; Zhang, Xinxian; Dong, Lina; Zhu, Bin; Xin, Tao

2017-06-01

We verified the advantages of using magnetic resonance imaging (MRI) for improving the diagnostic quality of growth hormone deficiency (GHD) in children with short stature caused by pituitary lesions. Clinical data obtained from 577 GHD patients with short stature caused by pituitary lesions were retrospectively analyzed. There were 354 cases (61.3%) with anterior pituitary dysplasia; 45 cases (7.8%) of pituitary stalk interruption syndrome (PSIS); 15 cases (2.6%) of pituitary hyperplasia due to primary hypothyroidism; 38 cases (6.6%) of Rathke cleft cyst; 68 cases (11.8%) of empty sella syndrome; 16 cases (2.8%) of pituitary invasion from Langerhans cell histiocytosis; 2 cases (0.3%) of sellar regional arachnoid cyst and 39 cases (6.8%) of craniopharyngioma. MRI results showed that the height of anterior pituitary in patients was less than normal. Location, size and signals of posterior pituitary and pituitary stalk were normal in anterior pituitary dysplasia. In all cases pituitary hyperplasia was caused by hypothyroidism. MRI results showed that anterior pituitary was enlarged, and we detected upward apophysis and obvious homogeneous enhancement. There were no pituitary stalk interruption and abnormal signal. We also observed that after hormone replacement therapy the size of pituitary gland was reduced. Anterior pituitary atrophy was observed in Rathke cleft cyst, empty sella syndrome, sellar regional arachnoid cyst and craniopharyngioma. The microstructure of hypophysis and sellar region was studied with MRI. We detected pituitary lesions, and the characteristics of various pituitary diseases of GHD in children with short stature. It was concluded that in children with GHD caused by pituitary lesions, MRI was an excellent method for early diagnosis. This method offers clinical practicability and we believe it can be used for differential diagnosis and to monitor the therapeutic effects.

Insulin Rescues Impaired Spermatogenesis via the Hypothalamic-Pituitary-Gonadal Axis in Akita Diabetic Mice and Restores Male Fertility

PubMed Central

Schoeller, Erica L.; Albanna, Gabriella; Frolova, Antonina I.; Moley, Kelle H.

2012-01-01

The mechanism responsible for poor reproductive outcomes in type 1 diabetic males is not well understood. In light of new evidence that the Sertoli cells of the testis secrete insulin, it is currently unclear whether diabetic subfertility is the result of deficiency of pancreatic insulin, testicular insulin, or both. In this study, the Akita mouse diabetic model, which expresses a mutant, nonfunctional form of ins2 in testes and pancreas, was used to distinguish between systemic and local effects of insulin deficiency on the process of spermatogenesis and fertility. We determined that Akita homozygous male mice are infertile and have reduced testis size and abnormal morphology. Spermatogonial germ cells are still present but are unable to mature into spermatocytes and spermatids. Exogenous insulin treatment regenerates testes and restores fertility, but this plasma insulin cannot pass through the blood-testis barrier. We conclude that insulin does not rescue fertility through direct interaction with the testis; instead, it restores function of the hypothalamic-pituitary-gonadal axis and, thus, normalizes hormone levels of luteinizing hormone and testosterone. Although we show that the Sertoli cells of the testis secrete insulin protein, this insulin does not appear to be critical for fertility. PMID:22522616

Silent adenoma subtype 3 of the pituitary--immunohistochemical and ultrastructural classification: a review of 29 cases.

PubMed

Horvath, E; Kovacs, K; Smyth, H S; Cusimano, M; Singer, W

2005-01-01

The silent adenoma subtype 3 (SAS-3) of undetermined cellular derivation is a seemingly nonfunctioning aggressive pituitary tumor with a high recurrence rate. At the time of diagnosis SAS-3s are macro- or giant adenomas particularly aggressive in young individuals, especially women. They are usually associated with mild hyperprolactinemia and are unremarkable by histology. Immunohistochemistry, demonstrating scattered immunoreactivity mostly for GH, PRL, TSH, and alpha-subunit, is not diagnostic. Presently, only TEM permits conclusive diagnosis. Ultrastructurally, the large polar adenoma cells contain abundant RER, masses of SER, extensive multipolar Golgi apparatus, and unevenly clustered mitochondria, displaced by RER and SER, which may show close spatial relationship to RER. Cell membranes often form plexiform interdigitations. Nuclear pleomorphism and nuclear inclusions are common. The 100- to 200-nm secretory granules accumulate heavily in cell processes, which is a hallmark of glycoprotein hormone cell differentiation. The endothelial cells may contain tubuloreticular inclusions. Complete surgical removal of the large often invasive tumors is difficult necessitating postoperative treatment. SAS-3 is sensitive to conventional radiation. Some tumors express somatostatin receptors and respond well to somatostatin analogues, offering long-term control in patients with residual tumor. Possible derivation of SAS-3 from rostral thyrotrophs, a cell type presently known in rodents is contemplated.

Passive contribution of the rotator cuff to abduction and joint stability.

PubMed

Tétreault, Patrice; Levasseur, Annie; Lin, Jenny C; de Guise, Jacques; Nuño, Natalia; Hagemeister, Nicola

2011-11-01

The purpose of this study is to compare shoulder joint biomechanics during abduction with and without intact non-functioning rotator cuff tissue. A cadaver model was devised to simulate the clinical findings seen in patients with a massive cuff tear. Eight full upper limb shoulder specimens were studied. Initially, the rotator cuff tendons were left intact, representing a non-functional rotator cuff, as seen in suprascapular nerve paralysis or in cuff repair with a patch. Subsequently, a massive rotator cuff tear was re-created. Three-dimensional kinematics and force requirements for shoulder abduction were analyzed for each condition using ten abduction cycles in the plane of the scapula. Mediolateral displacements of the glenohumeral rotation center (GHRC) during abduction with an intact non-functioning cuff were minimal, but massive cuff tear resulted in significant lateral displacement of the GHRC (p < 0.013). Similarly, massive cuff tear caused increased superior migration of the GHRC during abduction compared with intact non-functional cuff (p < 0.01). From 5 to 30° of abduction, force requirements were significantly less with an intact non-functioning cuff than with massive cuff tear (p < 0.009). During abduction, an intact but non-functioning rotator cuff resulted in decreased GHRC displacement in two axes as well as lowered the force requirement for abduction from 5 to 30° as compared with the results following a massive rotator cuff tear. This provides insight into the potential biomechanical effect of repairing massive rotator cuff tears with a biological or synthetic "patch," which is a new treatment for massive cuff tear.

Hereditary Pituitary Hyperplasia with Infantile Gigantism

PubMed Central

Gläsker, Sven; Vortmeyer, Alexander O.; Lafferty, Antony R. A.; Hofman, Paul L.; Li, Jie; Weil, Robert J.; Zhuang, Zhengping

2011-01-01

Context: We report hereditary pituitary hyperplasia. Objective: The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. Design: The study is a retrospective analysis of three cases from one family. Setting: The study was conducted at the National Institutes of Health, a tertiary referral center. Patients: A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. Interventions: The condition was treated by total hypophysectomy. Main Outcome Measure(s): We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. Results: All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. Conclusions: This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development. PMID:21976722

The association of pituitary tumors and headache.

PubMed

Levy, Miles J

2011-04-01

Pituitary tumors may give rise to headache via numerous mechanisms. The traditional explanation for headache is dural stretch and cavernous sinus invasion, although this is not borne out by clinical studies. Certain functional pituitary tumors are associated with headache, notably growth hormone and prolactin-secreting tumors. The observation that somatostatin analogues can have a dramatic analgesic effect in acromegaly suggests that biochemical properties of the tumor may be important. The genetic predisposition of the patient to primary headache also determines whether headache occurs with pituitary tumors. This article attempts to outline the clinical features, management strategies, and key academic questions regarding the subject of pituitary tumors and headache.

Cytomegalovirus and BK-Virus co-infection of a clinically non-functioning adrenal adenoma: innocent bystanders or new pathogenetic agents?

PubMed

Pomara, G; Cappello, F; Barzon, L; Morelli, G; Rappa, F; Benvegna, L; Giannarini, G; Palù, G; Selli, C

2006-01-01

We report a case of a 64-year-old woman who underwent left adrenalectomy with removal of a 8,5 cm clinically non-functioning adrenocortical adenoma and a 4-cm myelolipoma. Molecular testing for viral infection demonstrated the presence of cytomegalovirus (CMV) DNA sequences in the adrenal adenoma, but not in the myelolipoma (confirmed by immunohistochemistry). Moreover, the adrenal adenoma was also positive for parvovirus B19, and both adrenal tumor samples were positive for polyomavirus BK (BKV) and adenovirus DNA sequences. This is the first report of co-infection of an adrenocortical adenoma by CMV and BKV. The role of these viruses in adrenal tumorigenesis was postulated.

Functional versus Nonfunctional Rehabilitation in Chronic Ischemic Stroke: Evidences from a Randomized Functional MRI Study

PubMed Central

Pelicioni, Maristela C. X.; Novaes, Morgana M.; Peres, Andre S. C.; Lino de Souza, Altay A.; Minelli, Cesar; Fabio, Soraia R. C.; Pontes-Neto, Octavio M.; Santos, Antonio C.; de Araujo, Draulio B.

2016-01-01

Motor rehabilitation of stroke survivors may include functional and/or nonfunctional strategy. The present study aimed to compare the effect of these two rehabilitation strategies by means of clinical scales and functional Magnetic Resonance Imaging (fMRI). Twelve hemiparetic chronic stroke patients were selected. Patients were randomly assigned a nonfunctional (NFS) or functional (FS) rehabilitation scheme. Clinical scales (Fugl-Meyer, ARA test, and modified Barthel) and fMRI were applied at four moments: before rehabilitation (P1) and immediately after (P2), 1 month after (P3), and three months after (P4) the end of rehabilitation. The NFS group improved significantly and exclusively their Fugl-Meyer scores at P2, P3, and P4, when compared to P1. On the other hand, the FS group increased significantly in Fugl-Meyer at P2, when compared to P1, and also in their ARA and Barthel scores. fMRI inspection at the individual level revealed that both rehabilitation schemes most often led to decreased activation sparseness, decreased activity of contralesional M1, increased asymmetry of M1 activity to the ipsilesional side, decreased perilesional activity, and decreased SMA activity. Increased M1 asymmetry with rehabilitation was also confirmed by Lateralization Indexes. Our clinical analysis revealed subtle differences between FS and NFS. PMID:26839716

Investigating the role of cortisol and growth hormone in fatty liver development: fatty liver index in patients with pituitary adenomas.

PubMed

Auer, Matthias K; Stalla, Günter K; Stieg, Mareike R

2016-10-01

Non-alcoholic fatty liver disease (NAFLD) is a hallmark of the metabolic syndrome and has been shown to be an independent predictor of cardiovascular mortality. Although glucocorticoids and growth hormone are known to be implicated in its pathophysiology, it has only rarely been investigated in the context of patients with pituitary insufficiency or former cortisol excess. Case-control study in patients with biochemically controlled Cushing's disease (CD; N = 33) and non-functioning pituitary adenomas (NFPA; N = 79). NAFLD was estimated by calculating the fatty liver index (FLI) including BMI, waist circumference, GGT and triglyceride levels. Although there was no difference in FLI between patients with NFPA and CD, we identified average daily hydrocortisone (HC) intake in those with adrenal insufficiency to be an independent predictor of FLI (β = 1.124; p = 0.017), even after adjusting for BMI and waist circumference. In line, those with a FLI > 60 were also taking in average significantly more HC per day than those with a score <60 (21.05 mg ± 5.9 vs. 17.9 mg ± 4.4; p = 0.01). FLI was also the best independent predictor for HbA1c and fasting glucose levels (both p = 0.001). Growth hormone deficiency and replacement therapy were not associated with FLI in either group. While HC dosage affects FLI as an estimate of NFLD in patients with CD and NFPA, the benefit of GH replacement still needs to be determined. In contrast to reports in CD patients with active disease, NAFLD in those with biochemical control was not different from NFPA patients.

Thyrotropin secreting pituitary adenoma accompanying a silent somatotropinoma.

PubMed

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

2011-01-01

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

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

PubMed

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

2016-01-01

Pituitary adenomas are uncommon, difficult to diagnose tumors whose heterogeneity and low incidence complicate large-scale studies. The Molecular Registry of Pituitary Adenomas (REMAH) was promoted by the Andalusian Society of Endocrinology and Nutrition (SAEN) in 2008 as a cooperative clinical-basic multicenter strategy aimed at improving diagnosis and treatment of pituitary adenomas by combining clinical, pathological, and molecular information. In 2010, the Spanish Society of Endocrinology and Nutrition (SEEN) extended this project to national level and established 6 nodes with common protocols and methods for sample and clinical data collection, molecular analysis, and data recording in a common registry (www.remahnacional.com). The registry combines clinical data with molecular phenotyping of the resected pituitary adenoma using quantitative real-time PCR of expression of 26 genes: Pituitary hormones (GH-PRL-LH-FSH-PRL-ACTH-CGA), receptors (somatostatin, dopamine, GHRH, GnRH, CRH, arginine-vasopressin, ghrelin), other markers (Ki67, PTTG1), and control genes. Until 2015, molecular information has been collected from 704 adenomas, out of 1179 patients registered. This strategy allows for comparative and relational analysis between the molecular profile of the different types of adenoma and the clinical phenotype of patients, which may provide a better understanding of the condition and potentially help in treatment selection. The REMAH is therefore a unique multicenter, interdisciplinary network founded on a shared database that provides a far-reaching translational approach for management of pituitary adenomas, and paves the way for the conduct of combined clinical-basic innovative studies on large patient samples. Copyright © 2016 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Silent Corticotroph Adenomas After Stereotactic Radiosurgery: A Case–Control Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Zhiyuan; Ellis, Scott; Lee, Cheng-Chia

Purpose: To investigate the safety and effectiveness of stereotactic radiosurgery (SRS) in patients with a silent corticotroph adenoma (SCA) compared with patients with other subtypes of non–adrenocorticotropic hormone staining nonfunctioning pituitary adenoma (NFA). Methods and Materials: The clinical features and outcomes of 104 NFA patients treated with SRS in our center between September 1994 and August 2012 were evaluated. Among them, 34 consecutive patients with a confirmatory SCA were identified. A control group of 70 patients with other subtypes of NFA were selected for review based on comparable baseline features, including sex, age at the time of SRS, tumor size, marginmore » radiation dose to the tumor, and duration of follow-up. Results: The median follow-up after SRS was 56 months (range, 6-200 months). No patients with an SCA developed Cushing disease during the follow-up. Tumor control was achieved in 21 of 34 patients (62%) in the SCA group, compared with 65 of 70 patients (93%) in the NFA group. The median progression-free survival (PFS) was 58 months in the SCA group. The actuarial PFS was 73%, 46%, and 31% in the SCA group and was 94%, 87%, and 87% in the NFA group at 3, 5, and 8 years, respectively. Silent corticotroph adenomas treated with a dose of ≥17 Gy exhibited improved PFS. New-onset loss of pituitary function developed in 10 patients (29%) in the SCA group, whereas it occurred in 18 patients (26%) in the NFA group. Eight patients (24%) in the SCA group experienced worsening of a visual field deficit or visual acuity attributed to the tumor progression, as did 6 patients (9%) in the NFA group. Conclusion: Silent corticotroph adenomas exhibited a more aggressive course with a higher progression rate than other subtypes of NFAs. Stereotactic radiosurgery is an important adjuvant treatment for control of tumor growth. Increased radiation dose may lead to improved tumor control in SCA patients.« less

Pulsatile GnRH Therapy May Restore Hypothalamus-Pituitary-Testis Axis Function in Patients With Congenital Combined Pituitary Hormone Deficiency: A Prospective, Self-Controlled Trial.

PubMed

Zheng, Junjie; Mao, Jiangfeng; Xu, Hongli; Wang, Xi; Huang, Bingkun; Liu, Zhaoxiang; Cui, Mingxuan; Xiong, Shuyu; Ma, Wanlu; Min, Le; Kaiser, Ursula B; Nie, Min; Wu, Xueyan

2017-07-01

The effectiveness of pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with congenital combined pituitary hormone deficiency (CCPHD) has not been investigated because of the limited number of patients, as well as these patients' presumed pituitary hypoplasia, poor gonadotrophic cell reserve, and impaired gonadotrophic response to GnRH. To assess the pituitary response to pulsatile GnRH therapy in men with CCPHD. Prospective, self-controlled, 3-month clinical trial. University endocrine clinic. Men with hypogonadotropic hypogonadism caused by CCPHD. Pulsatile GnRH was administered subcutaneously for 3 months. Primary endpoints were total serum testosterone, testicular volume, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Secondary endpoints included occurrence of spermatogenesis. A total of 40 men with CCPHD completed the study. Of these, 60% (24 of 40) showed a good response to pulsatile GnRH treatment (response group). At 3 months, their LH and FSH levels increased to within the normal range and their testosterone levels increased to 8.67 ± 4.83 nmol/L. Of the patients in the response group, 33.3% (8 of 24) of them achieved spermatogenesis. The remaining 40% (16 of 40) of patients had a poor response to pulsatile GnRH treatment. Magnetic resonance imaging (MRI) did not reveal any correlation between pituitary response and pituitary height and/or integrity of the pituitary stalk. This study suggests that gonadotrophs in patients with CCPHD can exist and be functional-even with MRI evidence of pituitary hypoplasia or dysplasia. Pulsatile GnRH therapy restored pituitary-testis axis function in 60% of patients with CCPHD. These results may directly guide the clinical therapeutic choice. Copyright © 2017 Endocrine Society

A case of coexistence of TSH/GH-secreting pituitary tumor and papillary thyroid carcinoma: Challenges in pathogenesis and management.

PubMed

Kiatpanabhikul, Phatharaporn; Shuangshoti, Shanop; Chantra, Kraisri; Navicharern, Patpong; Kingpetch, Kanaungnit; Houngngam, Natnicha; Snabboon, Thiti

2017-07-01

Co-existence of thyrotropin/growth hormone-secreting pituitary adenoma with differentiated thyroid carcinoma is exceedingly rare, with less than 15 cases having been reported. Its clinical presentation and treatment strategy are challenging. We report a case of pituitary macroadenoma, with clinical syndromes of acromegaly and hyperthyroidism, and a thyroid nodule, with cytologically confirmed to be a papillary thyroid carcinoma. Clinical implications, focusing on the strategy for proper management, and possible pathogenesis were discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diagnostic Accuracy of Perioperative Measurement of Basal Anterior Pituitary and Target Gland Hormones in Predicting Adrenal Insufficiency After Pituitary Surgery.

PubMed

Cerina, Vatroslav; Kruljac, Ivan; Radosevic, Jelena Marinkovic; Kirigin, Lora Stanka; Stipic, Darko; Pecina, Hrvoje Ivan; Vrkljan, Milan

2016-03-01

The insulin tolerance test (ITT) is the gold standard for diagnosing adrenal insufficiency (AI) after pituitary surgery. The ITT is unpleasant for patients, requires close medical supervision and is contraindicated in several comorbidities. The aim of this study was to analyze whether tumor size, remission rate, preoperative, and early postoperative baseline hormone concentrations could serve as predictors of AI in order to increase the diagnostic accuracy of morning serum cortisol. This prospective study enrolled 70 consecutive patients with newly diagnosed pituitary adenomas. Thirty-seven patients had nonfunctioning pituitary adenomas (NPA), 28 had prolactinomas and 5 had somatotropinomas. Thyroxin (T4), thyrotropin (TSH), prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and insulin-like growth factor 1 (IGF-I) were measured preoperatively and on the sixth postoperative day. Serum morning cortisol was measured on the third postoperative day (CORT3) as well as the sixth postoperative day (CORT6). Tumor mass was measured preoperatively and remission was assessed 3 months after surgery. An ITT was performed 3 to 6 months postoperatively. Remission was achieved in 48% of patients and AI occurred in 51%. Remission rates and tumor type were not associated with AI. CORT3 had the best predictive value for AI (area under the curve (AUC) 0.868, sensitivity 82.4%, specificity 83.3%). Tumor size, preoperative T4, postoperative T4, and TSH were also associated with AI in a multivariate regression model. A combination of all preoperative and postoperative variables (excluding serum cortisol) had a sensitivity of 75.0% and specificity of 77.8%. The predictive power of CORT3 substantially improved by adding those variables into the model (AUC 0.921, sensitivity 94.1%, specificity 78.3%, PPV 81.9%, NPV of 92.7%). In a subgroup analysis that included only female patients with NPA, LH had exactly the same predictive value as CORT3. The addition of baseline LH to CORT3, increased sensitivity to 100.0%, specificity to 88.9%, PPV to 90.4%, and NPV to 100.0%. Besides CORT3, tumor size, thyroid hormones, and gonadotropins can serve as predictors of AI. LH in postmenopausal female patients with NPA has similar diagnostic accuracy as CORT3. Further studies are needed in order to validate the scoring system proposed by this study.

Gene expression changes in subcutaneous adipose tissue due to Cushing's disease

PubMed Central

Hochberg, Irit; Harvey, Innocence; Tran, Quynh T; Stephenson, Erin J; Barkan, Ariel L; Saltiel, Alan R; Chandler, William F; Bridges, Dave

2015-01-01

Glucocorticoids have major effects on adipose tissue metabolism. To study tissue mRNA expression changes induced by chronic elevated endogenous glucocorticoids, we performed RNA sequencing on the subcutaneous adipose tissue from patients with Cushing's disease (n=5) compared to patients with nonfunctioning pituitary adenomas (n=11). We found a higher expression of transcripts involved in several metabolic pathways, including lipogenesis, proteolysis and glucose oxidation as well as a decreased expression of transcripts involved in inflammation and protein synthesis. To further study this in a model system, we subjected mice to dexamethasone treatment for 12 weeks and analyzed their inguinal (subcutaneous) fat pads, which led to similar findings. Additionally, mice treated with dexamethasone showed drastic decreases in lean body mass as well as increased fat mass, further supporting the human transcriptomic data. These data provide insight to transcriptional changes that may be responsible for the comorbidities associated with chronic elevations of glucocorticoids. PMID:26150553

[The relative analysis of clinical endocrine features and pathological types of pituitary microadenomas].

PubMed

Yan, Qing; Zhang, Hua-qiu; Wang, He-ping; Guo, Dong-sheng; Lei, Ting; Li, Ling

2010-06-15

To study the relationship between the clinical presentation, endocrinal findings and pathological types in patients with pituitary microadenomas, so as to improve the accuracy of clinical diagnosis and choose the best therapy strategy before the operation. From January 2007 to June 2009, the clinical data of 94 patients who were surgically removed pituitary microadenomas were obtained, including the clinical presentation, endocrinal findings and pathological diagnosis. The analysis was accomplished with Chi-square test. Hormonal symptoms were found in 86 patients (91.5%), it occurred more frequently in immunopositive patients (85/92, 92.4%) than in immunonegative patients (1/2, 50.0%) (P < 0.05). The coincidence of hormonal symptoms and immunohistochemistry diagnosis was 71.7%; 88.9% patients had the symptoms of amenorrhea, galactorrhea and sexual function diseases in prolactin (PRL) positive group and 28.1% patients had the symptoms of gigantism or acromegaly in growth hormone (GH) positive group. The coincidence of endocrinal findings and immunohistochemistry diagnosis was 69.0%; 87.7% patients had high level of blood PRL in PRL positive group and 21.9% patients had high level of blood GH in GH positive group. There is an obvious relationship between the clinical presentation, endocrinal findings and pathological diagnosis in patients with pituitary microadenomas, which may contribute to the clinical diagnosis and treatment of pituitary secreting microadenomas.

Associations between pituitary imaging abnormalities and clinical and biochemical phenotypes in children with congenital growth hormone deficiency: data from an international observational study.

PubMed

Deal, Cheri; Hasselmann, Caroline; Pfäffle, Roland W; Zimmermann, Alan G; Quigley, Charmian A; Child, Christopher J; Shavrikova, Elena P; Cutler, Gordon B; Blum, Werner F

2013-01-01

Magnetic resonance imaging (MRI) is used to investigate the etiology of growth hormone deficiency (GHD). This study examined relationships between MRI findings and clinical/hormonal phenotypes in children with GHD in the observational Genetics and Neuroendocrinology of Short Stature International Study, GeNeSIS. Clinical presentation, hormonal status and first-year GH response were compared between patients with pituitary imaging abnormalities (n = 1,071), patients with mutations in genes involved in pituitary development/GH secretion (n = 120) and patients with idiopathic GHD (n = 7,039). Patients with hypothalamic-pituitary abnormalities had more severe phenotypes than patients with idiopathic GHD. Additional hormonal deficiencies were found in 35% of patients with structural abnormalities (thyroid-stimulating hormone > adrenocorticotropic hormone > luteinizing hormone/follicle-stimulating hormone > antidiuretic hormone), most frequently in patients with septo-optic dysplasia (SOD). Patients with the triad [ectopic posterior pituitary (EPP), pituitary aplasia/hypoplasia and stalk defects] had a more severe phenotype and better response to GH treatment than patients with isolated abnormalities. The sex ratio was approximately equal for patients with SOD, but there was a significantly higher proportion of males (approximately 70%) in the EPP, pituitary hypoplasia, stalk defects, and triad categories. This large, international database demonstrates the value of classification of GH-deficient patients by the presence and type of hypothalamic-pituitary imaging abnormalities. This information may assist family counseling and patient management. Copyright © 2013 S. Karger AG, Basel.

Pituitary iron and volume predict hypogonadism in transfusional iron overload.

PubMed

Noetzli, Leila J; Panigrahy, Ashok; Mittelman, Steven D; Hyderi, Aleya; Dongelyan, Ani; Coates, Thomas D; Wood, John C

2012-02-01

Hypogonadism is the most common morbidity in patients with transfusion-dependent anemias such as thalassemia major. We used magnetic resonance imaging (MRI) to measure pituitary R2 (iron) and volume to determine at what age these patients develop pituitary iron overload and volume loss. We recruited 56 patients (47 with thalassemia major, five with chronically transfused thalassemia intermedia and four with Blackfan-Diamond syndrome) to have pituitary MRIs to measure pituitary R2 and volume. Hypogonadism was defined clinically based on the timing of secondary sexual characteristics or the need for sex hormone replacement therapy. Patients with transfusional iron overload begin to develop pituitary iron overload in the first decade of life; however, clinically significant volume loss was not observed until the second decade of life. Severe pituitary iron deposition (Z > 5) and volume loss (Z < -2.5) were independently predictive of hypogonadism. Pituitary R2 correlated significantly with serum ferritin as well as liver, pancreatic, and cardiac iron deposition by MRI. Log pancreas R2* was the best single predictor for pituitary iron, with an area under the receiving operator characteristic curve of 0.88, but log cardiac R2* and ferritin were retained on multivariate regression with a combined r(2) of 0.71. Pituitary iron overload and volume loss were independently predictive of hypogonadism. Many patients with moderate-to-severe pituitary iron overload retained normal gland volume and function, representing a potential therapeutic window. The subset of hypogonadal patients having preserved gland volumes may also explain improvements in pituitary function observed following intensive chelation therapy. Copyright © 2011 Wiley Periodicals, Inc.

Pituitary xanthogranulomas: clinical features, radiological appearances and post-operative outcomes.

PubMed

Ved, R; Logier, N; Leach, P; Davies, J S; Hayhurst, C

2018-06-01

Xanthogranulomas are inflammatory masses most commonly found at peripheral sites such as the skin. Sellar and parasellar xanthogranulomas are rare and present a diagnostic challenge as they are difficult to differentiate from other sellar lesions such as craniopharyngiomas and Rathke's cleft cysts pre-operatively. Their radiological imaging features are yet to be clearly defined, and clinical outcomes after surgery are also uncertain. This study reviews clinical presentation, radiological appearances, and clinical outcomes in a cohort of patients with pituitary xanthogranulomas. A prospectively maintained pituitary surgery database was screened for histologically confirmed pituitary xanthogranulomas between May 2011-December 2016. Retrospective case note assessments were then performed by three independent reviewers. Patient demographics, clinical presentations, imaging, and clinical outcomes were analysed. During the study period 295 endoscopic endonasal pituitary surgeries were performed. Six patients had confirmed pituitary xanthogranulomas (2%). Patients most commonly presented with visual field deficits and/or endocrine dysfunction. Common imaging features included: a cystic consistency, hyperintensity on T1-weighted MR images, and contrast enhancement either peripherally (n = 3) or homogenously (n = 3). The most common pre-operative endocrine deficits were hyperprolactinaemia and hypoadrenalism (at least one of which was identified in 4/6 patients; 66%). Thirty-three percent (2/6) of patients presented with diabetes insipidus. The most common post-operative endocrinological deficits were adrenocortical dysfunction (66%) and gonadotropin deficiency (66%). Visual assessments normalised in all six patients post-operatively. Gross total resection was achieved in all patients, and at median follow up of 33.5 months there were no cases of tumour recurrence. The prevalence of pituitary xanthogranulomas in our series is higher than that suggested in the literature. Surgery restored normal vision to all cases, however four patients (67%) required long-term hormonal replacement post-operatively. Imaging features such peripheral rim enhancement, a suprasellar tumour epicentre, and the absence of both calcification or cavernous sinus invasion were identified as potential indicators that together should alert clinicians to the possibility of pituitary xanthogranuloma when assessing patients with cystic sellar and parasellar tumours.

Clinical prevalence and outcome impact of pituitary dysfunction after aneurysmal subarachnoid hemorrhage: a systematic review with meta-analysis.

PubMed

Robba, Chiara; Bacigaluppi, Susanna; Bragazzi, Nicola; Lavinio, Andrea; Gurnell, Mark; Bilotta, Federico; Menon, David K

2016-10-01

Pituitary dysfunction is reported to be a common complication following aneurysmal subarachnoid hemorrhage (aSAH). The aim of this meta-analysis is to analyze the literature on clinical prevalence, risk factors and outcome impact of pituitary dysfunction after aSAH, and to assess the possible need for pituitary screening in aSAH patients. We performed a systematic review with meta-analysis based on a comprehensive search of four databases (PubMed/MEDLINE, ISI/Web of Science, Scopus and Google Scholar). A total of 20 papers met criteria for inclusion. The prevalence of pituitary dysfunction in the acute phase (within the first 6 months after aSAH) was 49.30 % (95 % CI 41.6-56.9), decreasing in the chronic phase (after 6 months from aSAH) to 25.6 % (95 % CI 18.0-35.1). Abnormalities in basal hormonal levels were more frequent when compared to induction tests, and the prevalence of a single pituitary hormone dysregulation was more frequent than multiple pituitary hormone dysregulation. Increasing age was associated with a lower prevalence of endocrine dysfunction in the acute phase, and surgical treatment of the aneurysm (clipping) was related to a higher prevalence of single hormone dysfunction. The prevalence of pituitary dysfunction did not correlate with the outcome of the patient. Neuroendocrine dysfunction is common after aSAH, but these abnormalities have not been shown to consistently impact outcome in the data available. There is a need for well-designed prospective studies to more precisely assess the incidence, clinical course, and outcome impact of pituitary dysfunction after aSAH.

Combined treatment with octreotide LAR and pegvisomant in patients with pituitary gigantism: clinical evaluation and genetic screening.

PubMed

Mangupli, Ruth; Rostomyan, Liliya; Castermans, Emilie; Caberg, Jean-Hubert; Camperos, Paul; Krivoy, Jaime; Cuauro, Elvia; Bours, Vincent; Daly, Adrian F; Beckers, Albert

2016-10-01

Pituitary gigantism is a rare condition caused by growth hormone secreting hypersecretion, usually by a pituitary tumor. Acromegaly and gigantism cases that have a genetic cause are challenging to treat, due to large tumor size and poor responses to some medical therapies (e.g. AIP mutation affected cases and those with X-linked acrogigantism syndrome). We performed a retrospective study to identify gigantism cases among 160 somatotropinoma patients treated between 1985 and 2015 at the University Hospital of Caracas, Venezuela. We studied clinical details at diagnosis, hormonal responses to therapy and undertook targeted genetic testing. Among the 160 cases, eight patients (six males; 75 %) were diagnosed with pituitary gigantism and underwent genetic analysis that included array comparative genome hybridization for Xq26.3 duplications. All patients had GH secreting pituitary macroadenomas that were difficult to control with conventional treatment options, such as surgery or primary somatostatin receptor ligand (SRL) therapy. Combined therapy (long-acting SRL and pegvisomant) as primary treatment or after pituitary surgery and radiotherapy permitted the normalization of IGF-1 levels and clinical improvement. Novel AIP mutations were the found in three patients. None of the patients had Xq26.3 microduplications. Treatment of pituitary gigantism is frequently challenging; delayed control increases the harmful effects of GH excess, such as, excessive stature and symptom burden, so early diagnosis and effective treatment are particularly important in these cases.

Spontaneous remission of acromegaly or gigantism due to subclinical apoplexy of pituitary growth hormone adenoma.

PubMed

Wang, Xian-Ling; Dou, Jing-Tao; Lü, Zhao-Hui; Zhong, Wen-Wen; Ba, Jian-Ming; Jin, Du; Lu, Ju-Ming; Pan, Chang-Yu; Mu, Yi-Ming

2011-11-01

Subclinical apoplexy of pituitary functional adenoma can cause spontaneous remission of hormone hypersecretion. The typical presence of pituitary growth hormone (GH) adenoma is gigantism and/or acromegaly. We investigated the clinical characteristics of patients with spontaneous partial remission of acromegaly or gigantism due to subclinical apoplexy of GH adenoma. Six patients with spontaneous remission of acromegaly or gigantism were enrolled. The clinical characteristics, endocrinological evaluation and imageological characteristics were retrospectively analyzed. In these cases, the initial clinical presences were diabetes mellitus or hypogonadism. No abrupt headache, vomiting, visual function impairment, or conscious disturbance had ever been complained of. The base levels of GH and insulin growth factor-1 (IGF-1) were normal or higher, but nadir GH levels were all still > 1 µg/L in 75 g oral glucose tolerance test. Magnetic resonance imaging detected enlarged sella, partial empty sella and compressed pituitary. The transsphenoidal surgery was performed in 2 cases, and the other patients were conservatively managed. All the patients were in clinical remission. When the clinical presences, endocrine evaluation, biochemical examination and imageology indicate spontaneous remission of GH hypersecretion in patients with gigantism or acromegaly, the diagnosis of subclinical apoplexy of pituitary GH adenoma should be presumed. To these patients, conservative therapy may be appropriate.

Acute hypopituitarism associated with periorbital swelling and cardiac dysfunction in a patient with pituitary tumor apoplexy: a case report.

PubMed

Ohara, Nobumasa; Yoneoka, Yuichiro; Seki, Yasuhiro; Akiyama, Katsuhiko; Arita, Masataka; Ohashi, Kazumasa; Suzuki, Kazuo; Takada, Toshinori

2017-08-24

Pituitary tumor apoplexy is a rare clinical syndrome caused by acute hemorrhage or infarction in a preexisting pituitary adenoma. It typically manifests as an acute episode of headache, visual disturbance, mental status changes, cranial nerve palsy, and endocrine pituitary dysfunction. However, not all patients present with classical symptoms, so it is pertinent to appreciate the clinical spectrum of pituitary tumor apoplexy presentation. We report an unusual case of a patient with pituitary tumor apoplexy who presented with periorbital edema associated with hypopituitarism. An 83-year-old Japanese man developed acute anterior hypopituitarism; he showed anorexia, fatigue, lethargy, severe bilateral periorbital edema, and mild cardiac dysfunction in the absence of headache, visual disturbance, altered mental status, and cranial nerve palsy. Magnetic resonance imaging showed a 2.5-cm pituitary tumor containing a mixed pattern of solid and liquid components indicating pituitary tumor apoplexy due to hemorrhage in a preexisting pituitary adenoma. Replacement therapy with oral hydrocortisone and levothyroxine relieved his symptoms of central adrenal insufficiency, central hypothyroidism, periorbital edema, and cardiac dysfunction. Common causes of periorbital edema include infections, inflammation, trauma, allergy, kidney or cardiac dysfunction, and endocrine disorders such as primary hypothyroidism. In the present case, the patient's acute central hypothyroidism was probably involved in the development of both periorbital edema and cardiac dysfunction. The present case highlights the need for physicians to consider periorbital edema as an unusual predominant manifestation of pituitary tumor apoplexy.

A rare case of multiple pituitary adenomas in an adolescent Cushing disease presenting as a vertebral compression fracture.

PubMed

Song, Ji-Yeon; Mun, Sue-Jean; Sung, Soon-Ki; Hwang, Jae-Yeon; Baik, Seung-Kug; Kim, Jee Yeon; Cheon, Chong-Kun; Kim, Su-Young; Kim, Yoo-Mi

2017-09-01

Cushing disease in children and adolescents, especially with multiple pituitary adenomas (MPAs), is very rare. We report 17-year-old boy with MPAs. He presented with a vertebral compression fracture, weight gain, short stature, headache, and hypertension. On magnetic resonance imaging (MRI), only a left pituitary microadenoma was found. After surgery, transient clinical improvement was observed but headache and hypertension were observed again after 3 months later. Follow-up MRI showed a newly developed right pituitary microadenoma 6 months after the surgery. The need for careful clinical and radiographic follow-up should be emphasized in the search for potential MPAs in patients with persistent Cushing disease.

OpenICE medical device interoperability platform overview and requirement analysis.

PubMed

Arney, David; Plourde, Jeffrey; Goldman, Julian M

2018-02-23

We give an overview of OpenICE, an open source implementation of the ASTM standard F2761 for the Integrated Clinical Environment (ICE) that leverages medical device interoperability, together with an analysis of the clinical and non-functional requirements and community process that inspired its design.

Hypopituitarism in the elderly: a narrative review on clinical management of hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes dysfunction.

PubMed

Curtò, L; Trimarchi, F

2016-10-01

Hypopituitarism is an uncommon and under-investigated endocrine disorder in old age since signs and symptoms are unspecific and, at least in part, can be attributed to the physiological effects of aging and related co-morbidities. Clinical presentation is often insidious being characterized by non-specific manifestations, such as weight gain, fatigue, low muscle strength, bradipsychism, hypotension or intolerance to cold. In these circumstances, hypopituitarism is a rarely life-threatening condition, but evolution may be more dramatic as a result of pituitary apoplexy, or when a serious condition of adrenal insufficiency suddenly occurs. Clinical presentation depends on the effects that each pituitary deficit can cause, and on their mutual relationship, but also, inevitably, it depends on the severity and duration of the deficit itself, as well as on the general condition of the patient. Indeed, indications and methods of hormone replacement therapy must include the need to normalize the endocrine profile without contributing to the worsening of intercurrent diseases, such as those of glucose and bone metabolism, and the cardiovascular system, or to the increasing cancer risk. Hormonal requirements of elderly patients are reduced compared to young adults, but a prompt diagnosis and appropriate treatment of pituitary deficiencies are strongly recommended, also in this age range.

Clinical polyomavirus BK variants with agnogene deletion are non-functional but rescued by trans-complementation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Myhre, Marit Renee; Olsen, Gunn-Hege; Gosert, Rainer

High-level replication of polyomavirus BK (BKV) in kidney transplant recipients is associated with the emergence of BKV variants with rearranged (rr) non-coding control region (NCCR) increasing viral early gene expression and cytopathology. Cloning and sequencing revealed the presence of a BKV quasispecies which included non-functional variants when assayed in a recombinant virus assay. Here we report that the rr-NCCR of BKV variants RH-3 and RH-12, both bearing a NCCR deletion including the 5' end of the agnoprotein coding sequence, mediated early and late viral reporter gene expression in kidney cells. However, in a recombinant virus they failed to produce infectiousmore » progeny despite large T-antigen and VP1 expression and the formation of nuclear virus-like particles. Infectious progeny was generated when the agnogene was reconstructed in cis or agnoprotein provided in trans from a co-existing BKV rr-NCCR variant. We conclude that complementation can rescue non-functional BKV variants in vitro and possibly in vivo.« less

Infrasellar pituitary gangliocytoma causing Cushing's syndrome.

PubMed

Domingue, Marie-Eve; Marbaix, Etienne; Do Rego, Jean-Luc; Col, Vincent; Raftopoulos, Christian; Duprez, Thierry; Vaudry, Hubert; Maiter, Dominique

2015-10-01

Pituitary gangliocytomas are uncommon neuronal tumours that may present with endocrine disorders, the most frequent being acromegaly caused by growth hormone hypersecretion. Cushing's syndrome is very rarely seen with gangliocytomas. We report the unique case of a 62 year-old woman whose clinical picture and endocrine testing clearly demonstrated adrenocorticotropin (ACTH)-dependent Cushing's syndrome. Pituitary magnetic resonance imaging showed a 12-mm homogeneous, infra- and retrosellar mass first diagnosed as pituitary macroadenoma. Transsphenoidal surgery was performed and allowed complete resection of the tumour with sparing of normal anterior pituitary. Very low postoperative serum cortisol and ACTH levels were observed in the early postoperative period and the patient is still in remission 18 months after surgery, thus demonstrating that the resected lesion was entirely responsible for the clinical picture. Histological and immunocytochemical analyses demonstrated a benign tumour composed of mature neuronal cells suggestive of a gangliocytoma, expressing both ACTH and corticotropin-releasing hormone (CRH). The tumour was surrounded by a rim of pituitary tissue containing ACTH-producing endocrine cells. Careful analysis of the resected lesion did not reveal any pituitary microadenoma. We search literature for similar cases and retraced only nine cases of gangliocytomas associated with Cushing's syndrome. In most of them, the tumour was combined with either pituitary corticotroph adenoma or hyperplasia. Our case represents a unique case of an infrasellar pituitary gangliocytoma which was able to cause Cushing's syndrome by both direct ACTH production and CRH-induced stimulation of neighbour normal corticotroph cells.

Modification of hormonal secretion in clinically silent pituitary adenomas.

PubMed

Daems, Tania; Verhelst, Johan; Michotte, Alex; Abrams, Pascale; De Ridder, Dirk; Abs, Roger

2009-01-01

Silent pituitary adenomas are a subtype of adenomas characterized by positive immunoreactivity for one or more hormones classically secreted by normal pituitary cells but without clinical expression, although in some occasions enhanced or changed secretory activity can develop over time. Silent corticotroph adenomas are the classical example of this phenomenon. A series of about 500 pituitary adenomas seen over a period of 20 years were screened for modification in hormonal secretion. Biochemical and immunohistochemical data were reviewed. Two cases were retrieved, one silent somatotroph adenoma and one thyrotroph adenoma, both without specific clinical features or biochemical abnormalities, which presented 20 years after initial surgery with evidence of acromegaly and hyperthyroidism, respectively. While the acromegaly was controlled by a combination of somatostatin analogs and growth hormone (GH) receptor antagonist therapy, neurosurgery was necessary to manage the thyrotroph adenoma. Immunohistochemical examination demonstrated an increase in the number of thyroid stimulating hormone (TSH)-immunoreactive cells compared to the first tissue. Apparently, the mechanisms responsible for the secretory modifications are different, being a change in secretory capacity in the silent somatotroph adenoma and a quantitative change in the silent thyrotroph adenoma. These two cases, one somatotroph and one thyrotroph adenoma, are an illustration that clinically silent pituitary adenomas may in rare circumstances evolve over time and become active, as previously demonstrated in silent corticotroph adenomas.

Anti-PIT-1 antibody syndrome; a novel clinical entity leading to hypopituitarism.

PubMed

Bando, Hironori; Iguchi, Genzo; Yamamoto, Masaaki; Hidaka-Takeno, Ryoko; Takahashi, Yutaka

2015-03-01

Various hypothalamic-pituitary diseases cause hypopituitarism. Inflammation related to autoimmunity also causes hypopituitarism. Hypophysitis is a representative disease caused by autoimmunity. Generally, anterior pituitary hormones are non-specifically impaired in this condition, but specific hormone defects have been reported in some cases. Anti-PIT-1 (pituitary-specific transcription factor 1) antibody syndrome is a novel clinical entity that presents an acquired combined pituitary hormone deficiency characterized by a specific defect in growth hormone, prolactin, and thyroid-stimulating hormone. Circulating anti-PIT-1 antibody along with various autoantibodies are detected with multiple endocrine organopathy, meeting the definition of autoimmune polyglandular syndrome. Mechanistically, cytotoxic T lymphocytes that specifically react with PIT-1 protein play an important role in the development of this syndrome.

Sellar and supra-sellar glioblastoma masquerading as a pituitary macroadenoma.

PubMed

Mahta, Ali; Buhl, Ralf; Huang, Hongguang; Jansen, Olav; Kesari, Santosh; Ulmer, Stephan

2013-04-01

A few number of suprasellar gliomas have been reported thus far of which, some of them developed several years after radiation therapy for pituitary adenomas or craniopharyngiomas. Herein, we report a case of sellar glioblastoma with suprasellar extension with no prior radiation history who mimicked clinical and radiologic findings of a pituitary macroadenoma.

A rare case of anasarca caused by infiltration of the pituitary gland by diffuse large B-cell lymphoma.

PubMed

Kumabe, Ayako; Kenzaka, Tsuneaki; Nishimura, Yoshioki; Aikawa, Masaki; Mori, Masaki; Matsumura, Masami

2015-03-25

Anasarca in patients with lymphoma is a rare symptom. We report a patient with DLBCL associated with pituitary gland infiltration that was diagnosed based on significant anasarca. A 72-year-old woman with a 10-year history of hypertension visited a local hospital presenting with anasarca and 15-kg weight gain in the past 3 months. we clinically diagnosed central hypothyroidism caused by pituitary gland infiltration of diffuse large B-cell lymphoma (DLBCL) (clinical stage IV in the Ann Arbor staging classification). The first course of chemotherapy improved anasarca remarkably and the patient's body weight returned to what it was 3 months before. We experienced a patient with remarkable anasarca caused by DLBCL infiltration of the pituitary gland. A pituitary gland lesion with central hypothyroidism should be considered as one of the differential diagnoses of edema. This case was very valuable because we could assess it by following the time course of symptoms (edema and delayed relaxation time of the Achilles tendon reflex), laboratory data, and imaging findings (swelling anterior pituitary lobe).

Thyroid-stimulating hormone pituitary adenomas.

PubMed

Clarke, Michelle J; Erickson, Dana; Castro, M Regina; Atkinson, John L D

2008-07-01

Thyroid-stimulating hormone (TSH)-secreting pituitary adenomas are rare, representing < 2% of all pituitary adenomas. The authors conducted a retrospective analysis of patients with TSH-secreting or clinically silent TSH-immunostaining pituitary tumors among all pituitary adenomas followed at their institution between 1987 and 2003. Patient records, including clinical, imaging, and pathological and surgical characteristics were reviewed. Twenty-one patients (6 women and 15 men; mean age 46 years, range 26-73 years) were identified. Of these, 10 patients had a history of clinical hyperthyroidism, of whom 7 had undergone ablative thyroid procedures (thyroid surgery/(131)I ablation) prior to the diagnosis of pituitary adenoma. Ten patients had elevated TSH preoperatively. Seven patients presented with headache, and 8 presented with visual field defects. All patients underwent imaging, of which 19 were available for imaging review. Sixteen patients had macroadenomas. Of the 21 patients, 18 underwent transsphenoidal surgery at the authors' institution, 2 patients underwent transsphenoidal surgery at another facility, and 1 was treated medically. Patients with TSH-secreting tumors were defined as in remission after surgery if they had no residual adenoma on imaging and had biochemical evidence of hypo-or euthyroidism. Patients with TSH-immunostaining tumors were considered in remission if they had no residual tumor. Of these 18 patients, 9 (50%) were in remission following surgery. Seven patients had residual tumor; 2 of these patients underwent further transsphenoidal resection, 1 underwent a craniotomy, and 4 underwent postoperative radiation therapy (2 conventional radiation therapy, 1 Gamma Knife surgery, and 1 had both types of radiation treatment). Two patients had persistently elevated TSH levels despite the lack of evidence of residual tumor. On pathological analysis and immunostaining of the surgical specimen, 17 patients had samples that stained positively for TSH, 8 for alpha-subunit, 10 for growth hormone, 7 for prolactin, 2 for adrenocorticotrophic hormone, and 1 for follicle-stimulating hormone/luteinizing hormone. Eleven patients (61%) ultimately required thyroid hormone replacement therapy, and 5 (24%) required additional pituitary hormone replacement. Of these, 2 patients required treatment for new anterior pituitary dysfunction as a complication of surgery, and 2 patients with preoperative partial anterior pituitary dysfunction developed complete panhypopituitarism. One patient had transient diabetes insipidus. The remainder had no change in pituitary function from their preoperative state. Thyroid-stimulating hormone-secreting pituitary lesions are often delayed in diagnosis, are frequently macroadenomas and plurihormonal in terms of their pathological characteristics, have a heterogeneous clinical picture, and are difficult to treat. An experienced team approach will optimize results in the management of these uncommon lesions.

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

Outcomes of kidney transplants from non-heart-beating deceased donors as reported to the Japan Organ Transplant Network from April 1995-December 2003: a multi-center report.

PubMed

Teraoka, S; Nomoto, K; Kikuchi, K; Hirano, T; Satomi, S; Hasegawa, A; Uchida, K; Akiyama, T; Tanaka, S; Babazona, T; Shindo, K; Nakamura, N

2004-01-01

Between April 1995-December 2003, 1,324 deceased donor kidney transplantations were performed in 139 transplant institutes in Japan. Of these, 45 transplants were from heart-beating and 1,279 transplants were from non-heart-beating deceased donors (NHBDD). Clinical outcomes for the 1,279 recipients of NHBDD kidney transplants were investigated. The overall 5-year patient and graft survival rates were 90% and 72%, respectively. A total of 112 NHBDD kidney grafts never functioned after transplantation and the recipients had to remain on dialysis. The causes of nonfunction were rejection, primary nonfunction, death, thrombosis and others in the order of the incidence. The major causes of graft loss were nonfunction, death, chronic rejection and acute rejection in that order. Major causes of recipient deaths were pneumonia, sepsis and CVA within 12 months, and heart diseases, sepsis, malignancy and pneumonia more than 12 months after transplantation. Kidneys from female donors, donors aged 15 or less or over age 60, donors with extrinsic causes of death other than head trauma, recipients over age 60 and those with diabetic nephropathy as their original disease were found to be at risk for poor graft survival. The lowest and last donor serum creatinine level did not influence the incidence of nonfunction or graft survival. However, graft survival was significantly poorer among recipients of older "expanded" donor kidneys than for recipients of younger grafts. The warm and total ischemia times should be kept shorter than 30 minutes (better 15 minutes), and 12 hours, respectively to minimize the incidence of nonfunction and early graft loss. It is especially important in cases with WIT over 30 minutes that the total ischemia should be kept within 12 hours. Cannulation before cardiac standstill was important to reduce the incidence of nonfunction and achieve high graft survival rates with NHBDD kidneys. The discontinuance of ventilator support also reduced the incidence of graft nonfunction. The combination of CsA or Tacrolimus and MMF as both the induction and maintenance regimen significantly improved graft survival. The use of either anti-T cell antibodies or basiliximab was also associated with significantly better graft survival for NHBDD kidneys. The combination of basiliximab, CsA and MMF resulted in a graft survival rate of 98% at one and 2 years.

Management of endocrine disease: pituitary tumour apoplexy.

PubMed

Capatina, Cristina; Inder, Warrick; Karavitaki, Niki; Wass, John A H

2015-05-01

Pituitary tumour apoplexy (PA) is a rare clinical syndrome that occurs as a result of acute haemorrhage and/or infarction within a frequently undiagnosed pituitary tumour. The sudden enlargement of the pituitary mass undergoing PA is responsible for a wide range of acute symptoms/signs (severe headache, visual loss, diplopia, hypopituitarism, impaired consciousness) which, together with the radiological evidence of a pituitary lesion, establish the diagnosis. The optimal care of PA requires involvement of a multidisciplinary team including endocrinologist, neurosurgeon, neuroophthalmologist and the management strategy that depends on the clinical manifestations, as well as the presence of co-morbidities. Prompt surgical decompression is initially indicated in cases with severe or progressive impairment of the visual acuity or the visual fields or with altered mental state and leads to visual and neurological recovery in most of the patients. The patients with mild, stable clinical picture (including those with isolated ocular palsies) can be managed conservatively (support of fluid and electrolyte balance and stress doses of steroids in most cases) with favourable visual and neurological outcome. Frequent reassessment is mandatory because the clinical course can be unpredictable; if progression of symptoms occurs, later elective surgery is indicated and is beneficial, especially in terms of visual outcome. The endocrinological outcome is less favourable, irrespective of the treatment option, with many patients remaining on long-term replacement therapy. Despite the above guidelines, clear proof of optimal outcomes in the form of randomised controlled trials is lacking. Regrowth of the pituitary tumour years after a PA episode is possible and patients require long-term surveillance. © 2015 European Society of Endocrinology.

Pituitary abscess: a case report and review of the literature

PubMed Central

Karagiannis, Apostolos K A; Dimitropoulou, Fotini; Papatheodorou, Athanasios; Lyra, Stavroula; Seretis, Andreas

2016-01-01

Summary Pituitary abscess is a rare life-threating entity that is usually misdiagnosed as a pituitary tumor with a definite diagnosis only made postoperatively. Over the last several decades, advances in healthcare have led to a significant decrease in morbidity and mortality due to pituitary abscess. We report a case of a 34-year-old woman who was admitted to our department for investigation of a pituitary mass and with symptoms of pituitary dysfunction, headaches and impaired vision. During her admission, she developed meningitis-like symptoms and was treated with antibiotics. She eventually underwent transsphenoidal surgery for excision of the pituitary mass. A significant amount of pus was evident intraoperatively; however, no pathogen was isolated. Six months later, the patient was well and had full recovery of the anterior pituitary function. Her menses returned, and she was only on treatment with desmopressin for diabetes insipidus that developed postoperatively. Learning points Pituitary abscess is a rare disease and the reported clinical features vary mimicking other pituitary lesions. The diagnosis of pituitary abscess is often very difficult to make and rarely included in the differential. The histological findings of acute inflammatory infiltration confirm the diagnosis of pituitary abscess. Medical and surgical treatment is usually recommended upon diagnosis of a pituitary abscess. PMID:27274845

Plurihormonal pituitary adenoma immunoreactive for thyroid-stimulating hormone, growth hormone, follicle-stimulating hormone, and prolactin.

PubMed

Luk, Cynthia T; Kovacs, Kalman; Rotondo, Fabio; Horvath, Eva; Cusimano, Michael; Booth, Gillian L

2012-01-01

To describe the case of a patient with an unusual plurihormonal pituitary adenoma with immunoreactivity for thyroid-stimulating hormone (TSH), growth hormone, follicle-stimulating hormone, prolactin, and α-subunit. We report the clinical, laboratory, imaging, and pathology findings of a patient symptomatic from a plurihormonal pituitary adenoma and describe her outcome after surgical treatment. A 60-year-old woman presented to the emergency department with headaches, blurry vision, fatigue, palpitations, sweaty hands, and weight loss. Her medical history was notable for hyperthyroidism, treated intermittently with methimazole. Magnetic resonance imaging disclosed a pituitary macroadenoma (2.3 by 2.2 by 2.0 cm), and preoperative blood studies revealed elevated levels of TSH at 6.11 mIU/L, free thyroxine at 3.6 ng/dL, and free triiodothyronine at 6.0 pg/mL. She underwent an uncomplicated transsphenoidal resection of the pituitary adenoma. Immunostaining of tumor tissue demonstrated positivity for not only TSH but also growth hormone, follicle-stimulating hormone, prolactin, and α-subunit. The Ki-67 index of the tumor was estimated at 2% to 5%, and DNA repair enzyme O6-methylguanine-DNA methyltransferase immunostaining was mostly negative. Electron microscopy showed the ultrastructural phenotype of a glycoprotein-producing adenoma. Postoperatively, her symptoms and hyperthyroidism resolved. Thyrotropin-secreting pituitary adenomas are rare. Furthermore, recent reports suggest that 31% to 36% of adenomas may show evidence of secretion of multiple pituitary hormones. This case emphasizes the importance of considering pituitary causes of thyrotoxicosis and summarizes the clinical and pathology findings in a patient with a plurihormonal pituitary adenoma.

Pituitary stalk compression by the dorsum sellae: possible cause for late childhood onset growth disorders.

PubMed

Taoka, Toshiaki; Iwasaki, Satoru; Okamoto, Shingo; Sakamoto, Masahiko; Nakagawa, Hiroyuki; Otake, Shoichiro; Fujioka, Masayuki; Hirohashi, Shinji; Kichikawa, Kimihiko

2006-06-01

The purpose of this study was to evaluate the relationship between pituitary stalk compression by the dorsum sellae and clinical or laboratory findings in short stature children. We retrospectively reviewed magnetic resonance images of the pituitary gland and pituitary stalk for 34 short stature children with growth hormone (GH) deficiency and 24 age-matched control cases. We evaluated the degree of pituitary stalk compression caused by the dorsum sellae. Body height, GH level, pituitary height and onset age of the short stature were statistically compared between cases of pituitary stalk compression with associated stalk deformity and cases without compression. Compression of the pituitary stalk with associated stalk deformity was seen in nine cases within the short stature group. There were no cases observed in the control group. There were no significant differences found for body height, GH level and pituitary height between the cases of pituitary stalk compression with associated stalk deformity and cases without compression. However, a significant difference was seen in the onset age between cases with and without stalk compression. Pituitary stalk compression with stalk deformity caused by the dorsum sellae was significantly correlated with late childhood onset of short stature.

Study of Efficacy and Safety of PDR001 in Patients With Advanced or Metastatic, Well-differentiated, Non-functional Neuroendocrine Tumors of Pancreatic, Gastrointestinal (GI), or Thoracic Origin or Poorly-differentiated Gastroenteropancreatic Neuroendocrine Carcinoma (GEP-NEC)

ClinicalTrials.gov

2017-11-15

Well-differentiated Non-functional NET of Thoracic Origin; Well-differentiated Non-functional NET of Gastrointestinal Origin; Well-differentiated Non-functional NET of Pancreatic Origin; Poorly-differentiated Gastroenteropancreatic Neuroendocrine Carcinoma

Detection of Pituitary Antibodies by Immunofluorescence: Approach and Results in Patients With Pituitary Diseases

PubMed Central

Ricciuti, Adriana; De Remigis, Alessandra; Landek-Salgado, Melissa A.; De Vincentiis, Ludovica; Guaraldi, Federica; Lupi, Isabella; Iwama, Shintaro; Wand, Gary S.; Salvatori, Roberto

2014-01-01

Context: Pituitary antibodies have been measured mainly to identify patients whose disease is caused or sustained by pituitary-specific autoimmunity. Although reported in over 100 publications, they have yielded variable results and are thus considered of limited clinical utility. Objectives: Our objectives were to analyze all publications reporting pituitary antibodies by immunofluorescence for detecting the major sources of variability, to experimentally test these sources and devise an optimized immunofluorescence protocol, and to assess prevalence and significance of pituitary antibodies in patients with pituitary diseases. Study Design and Outcome Measures: We first evaluated the effect of pituitary gland species, section fixation, autofluorescence quenching, blockade of unwanted antibody binding, and use of purified IgG on the performance of this antibody assay. We then measured cross-sectionally the prevalence of pituitary antibodies in 390 pituitary cases and 60 healthy controls, expressing results as present or absent and according to the (granular, diffuse, perinuclear, or mixed) staining pattern. Results: Human pituitary was the best substrate to detect pituitary antibodies and yielded an optimal signal-to-noise ratio when treated with Sudan black B to reduce autofluorescence. Pituitary antibodies were more common in cases (95 of 390, 24%) than controls (3 of 60, 5%, P = .001) but did not discriminate among pituitary diseases when reported dichotomously. However, when expressed according to their cytosolic staining, a granular pattern was highly predictive of pituitary autoimmunity (P < .0001). Conclusion: We report a comprehensive study of pituitary antibodies by immunofluorescence and provide a method and an interpretation scheme that should be useful for identifying and monitoring patients with pituitary autoimmunity. PMID:24606106

Stages of Pituitary Tumors

MedlinePlus

... ACTH . A clinical trial of stereotactic radiation surgery . Growth Hormone–Producing Pituitary Tumors Treatment may include the ... Drug therapy to stop the tumor from making growth hormone . Thyroid-Stimulating Hormone–Producing Tumors Treatment may ...

Pituitary function within the first year after traumatic brain injury or subarachnoid haemorrhage.

PubMed

Tölli, A; Borg, J; Bellander, B-M; Johansson, F; Höybye, C

2017-02-01

Reports on long-term variations in pituitary function after traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH) diverge. The aim of the current study was to evaluate the prevalence and changes in pituitary function during the first year after moderate and severe TBI and SAH and to explore the relation between pituitary function and injury variables. Adults with moderate and severe TBI or SAH were evaluated at 10 days, 3, 6 and 12 months post-injury/illness. Demographic, clinical, radiological, laboratory, including hormonal data were collected. A total of 91 adults, 56 (15 women/41 men) with TBI and 35 (27 women/8 men) with SAH were included. Perturbations in pituitary function were frequent early after the event but declined during the first year of follow-up. The most frequent deficiency was hypogonadotrope hypogonadism which was seen in approximately 25 % of the patients. Most of the variations were transient and without clinical significance. At 12 months, two patients were on replacement with hydrocortisone, four men on testosterone and one man on replacement with growth hormone. No relations were seen between hormonal levels and injury variables. Perturbations in pituitary function continue to occur during the first year after TBI and SAH, but only a few patients need replacement therapy. Our study could not identify a marker of increased risk of pituitary dysfunction that could guide routine screening. However, data demonstrate the need for systematic follow-up of pituitary function after moderate or severe TBI or SAH.

Anterior pituitary failure (panhypopituitarism) with balanced chromosome translocation 46,XY,t(11;22)(q24;q13).

PubMed

Yang, C Y; Chou, C W; Chen, S Y; Cheng, H M

2001-04-01

Hypopituitarism is the clinical syndrome that results from failure of the anterior pituitary gland to produce its hormones. Hypopituitarism can result from: (1) intrinsic or primary pituitary disease; (2) intrinsic hypothalamic or secondary pituitary disease; or (3) extrinsic extrasellar or parasellar disease. The etiologies of primary hypopituitarism are miscellaneous. The dominant clinical picture of hypopituitarism in the adult is that of hypogonadism. Reports have associated hypopituitarism with anti-pituitary-antibodies, hereditary syndrome and chromosome defects, but hypopituitarism has rarely been associated with balanced chromosome translocation (11;22)(q24;q13). Here, we describe a case of anterior pituitary failure with balanced chromosome translocation. A 19-year-old Chinese teenager presented with failure of pubertal development and sexual infantilism. On examination, the patient had the classic appearance of hypogonadism. Endocrine studies and three combined pituitary function tests revealed panhypopituitarism. A chromosomal study revealed 46,XY,t(11;22)(q24;q13), a balanced translocation between 11q24 and 22q13. Chest films showed delayed fusion of bilateral humeral head epiphyses and bilateral acromions. Scrotal sonography revealed testes were small bilaterally. Magnetic resonance imaging (MRI) of the sella revealed pituitary dwarfism. The patient received 19 months replacement therapy, including steroids (prednisolone 5 mg each day), L-thyroxine (Eltroxin 100 ug each day), and testosterone enanthate 250 mg every two weeks. His height increased 4 cm with secondary sexual characteristics developed, and muscle power increased.

Developmental abnormalities of the posterior pituitary gland.

PubMed

di Iorgi, Natascia; Secco, Andrea; Napoli, Flavia; Calandra, Erika; Rossi, Andrea; Maghnie, Mohamad

2009-01-01

While the molecular mechanisms of anterior pituitary development are now better understood than in the past, both in animals and in humans, little is known about the mechanisms regulating posterior pituitary development. The posterior pituitary gland is formed by the evagination of neural tissue from the floor of the third ventricle. It consists of the distal axons of the hypothalamic magnocellular neurones that shape the neurohypophysis. After its downward migration, it is encapsulated together with the ascending ectodermal cells of Rathke's pouch which form the anterior pituitary. By the end of the first trimester, this development is completed and vasopressin and oxytocin can be detected in neurohypophyseal tissue. Abnormal posterior pituitary migration such as the ectopic posterior pituitary lobe appearing at the level of median eminence or along the pituitary stalk have been reported in idiopathic GH deficiency or in subjects with HESX1, LHX4 and SOX3 gene mutations. Another intriguing feature of abnormal posterior pituitary development involves genetic forms of posterior pituitary neurodegeneration that have been reported in autosomal-dominant central diabetes insipidus and Wolfram disease. Defining the phenotype of the posterior pituitary gland can have significant clinical implications for management and counseling, as well as providing considerable insight into normal and abnormal mechanisms of posterior pituitary development in humans.

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

Mission Connect Mild TBI Translational Research Consortium

DTIC Science & Technology

2012-08-01

as they relate to functional outcome. At 6 months post injury, patients will be screened for anterior pituitary function 121 subjects have been...are indicative of anterior pituitary function, including somatomedin (IGF-1), thyroid stimulating hormone (TSH), thyroxine (Free T4), prolactin, and...incidence of single and multiple pituitary hormone deficiencies. The clinical characteristics, MRI imaging results, EEG and MEG results of the

Treatment Options for Pituitary Tumors

MedlinePlus

... ACTH . A clinical trial of stereotactic radiation surgery . Growth Hormone–Producing Pituitary Tumors Treatment may include the ... Drug therapy to stop the tumor from making growth hormone . Thyroid-Stimulating Hormone–Producing Tumors Treatment may ...

Treatment Option Overview (Pituitary Tumors)

MedlinePlus

... ACTH . A clinical trial of stereotactic radiation surgery . Growth Hormone–Producing Pituitary Tumors Treatment may include the ... Drug therapy to stop the tumor from making growth hormone . Thyroid-Stimulating Hormone–Producing Tumors Treatment may ...

[Molecular pathology of congenital pituitary hypothyroidism--discovery of new clinical entities].

PubMed

Tatsumi, K; Amino, N; Miyai, K

1993-05-01

Congenital pituitary hypothyroidism (pituitary cretinism) results in severe mental and growth retardation when it is not treated soon after birth. Since the introduction of neonatal mass screening of thyrotropin (TSH), most congenital hypothyroidism has been detected except for pituitary and hypothalamic hypothyroidism. In 1971, we reported the first familial case of congenital isolated TSH deficiency and thereafter began intensively investigating the molecular pathology of congenital pituitary hypothyroidism. After determining the entire structure of the human TSH beta gene, we identified the molecular pathology in this patient. Recently, we reported a familial case of congenital combined pituitary hormone deficiency (PIT1 abnormality). To examine the PIT1 gene, which encodes pituitary specific transcription factor, Pit-1/GHF-1, we determined its genomic structure. Sequence comparisons using PCR amplified PIT1 gene sequences revealed only one nonsense mutation in the patient, and established that this alteration caused the combined deficiencies of TSH, GH and PRL. We also discuss other recent progress in molecular pathology of congenital pituitary hypothyroidism.

[Granulomatosis with polyangiitis manifested as diabetes insipidus].

PubMed

Pátek, Ondřej; Horáčková, Miroslava; Vítová, Lenka; Horváth, Rudolf; Háček, Jaromír; Schück, Otto

The case report shows a surprising presentation of pulmonary granulomatosis with polyangiitis (GPA) through symptoms of diabetes insipidus (DI) with granulomatous infiltration of the pituitary gland. The pituitary hormonal dysfunction as a result of granulomatosis of the pituitary gland is rare. Several studies have demonstrated that the incidence of the pituitary dysfunction reaches approx. 1 % of the patients with GPA. However it is mostly presented in patients with the disease already diagnosed. The patient described by us had no clinical expressions of GPA in the respiratory tract. He presented with polyuria and polydipsia. It was not until a more detailed examination of these symptoms was performed that a focal lung disease was detected and diagnosed as GPA. diabetes insipidus - granulomatosis with polyangiitis - granulomatous infiltration of the pituitary gland - pituitary hormonal dysfunction.

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

PubMed Central

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

1989-01-01

Acidophilic pituitary adenomas commonly produce growth hormone (GH) or prolactin (PRL), according to studies employing immunohistochemical and ultrastructural methods. To examine this question, in situ hybridization with oligonucleotide probes was done on routinely processed tissues received in the pathology laboratory to analyze for the presence of GH and PRL messenger RNA (mRNA) in 4 normal pituitaries, 10 prolactinomas, and 16 GH-secreting adenomas. Most acidophilic cells in normal pituitaries expressed either GH or PRL hormone and the respective mRNAs, but GH mRNA and PRL hormone were also detected in some of the same cells. Patients with a clinical diagnosis of prolactinoma had cells with only PRL mRNA in their tumors, while most (14 of 16) patients with a clinical diagnosis of acromegaly or gigantism had both GH and PRL mRNAs in their tumors. The GH adenomas varied in these studies. In situ hybridization was helpful in characterizing the adenoma from a patient with acromegaly who had immunoreactive PRL, but no immunoreactive GH in the resected tumor; in situ hybridization analysis revealed mRNAs for both GH and PRL in the same tumor cells. Our findings indicate that pituitary adenomas from patients with acromegaly commonly express PRL mRNA. It is concluded that in situ hybridization provides new information about the clinical biology and the histopathologic classification of pituitary adenomas. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:2466405

Clinical characteristics of patients with thyrotropin-secreting pituitary adenoma.

PubMed

Wu, Yung-Yen; Chang, Hung-Yu; Lin, Jen-Der; Chen, Kwang-Wen; Huang, Yu-Yao; Jung, Shih-Ming

2003-03-01

Thyroid-stimulating hormone (thyrotropin, TSH)-secreting pituitary adenoma is a very rare cause of hyperthyroidism. Diagnosis of this condition is often delayed due to lack of availability of TSH radioimmunoassay (RIA), the failure to recognize the utility of RIA and the incorrect attribution of the condition to other causes of thyrotoxicosis. This retrospective study analyzed the clinical characteristics of patients with this disorder treated from 1991 to 2002. Seven patients (6 females, 1 male; mean age, 48 years; range, 33 to 72 years) with a diagnosis of TSHsecreting pituitary adenoma based on detectable TSH levels with high serum free thyroid hormone or triiodothyronine concentrations and pituitary lesions found on neuroimaging were included in this study. Patient records including clinical features, endocrine studies, immunohistochemistry studies, and response to treatment were reviewed. All 7 patients had hyperthyroidism, elevated free thyroxine or triiodothyronine levels, and unsuppressed levels of TSH. Imaging studies demonstrated a pituitary mass or lesion in all patients. Six patients had macroadenomas and 1 patient had a microadenoma. One of the patients had coexisting acromegalic features and hypersecretion of growth hormone was diagnosed. All of the patients had been treated with thionamides or thyroidectomy for presumed primary hyperthyroidism. Serum alpha-subunit level was uncharacteristically normal in 2 patients and elevated in 1 patient. Alpha-subunit/TSH molar ratios were elevated in 3 patients. Five patients underwent transsphenoidal adenomectomy but only one of them remained well-controlled at follow-up. Three patients received administration of somatostatin analogs and they achieved normalization of serum TSH and free thyroid hormones during the period of therapy. TSH immunoassay has an important role in the evaluation of hyperthyroid patients to determine the presence of inappropriate secretion. TSH-secreting pituitary adenoma exhibits heterogeneity in clinical presentation, hormonal expression and therapeutic response.

Molecular and Clinical Findings in Patients with LHX4 and OTX2 Mutations

PubMed Central

Tajima, Toshihiro; Ishizu, Katsura; Nakamura, Akie

2013-01-01

The pituitary gland produces hormones that play important roles in both the development and homeostasis of the body. Ontogeny of the anterior and posterior pituitary is orchestrated by inputs from neighboring tissues, cellular signaling molecules and transcription factors. Disruption of expression or function of these factors has been implicated in the etiology of combined pituitary hormone deficiency (CPHD). These include the transcription factors HESX1, PROP1, POU1F1, LHX3, LHX4, OTX2, SOX2, SOX3 and GLI2. This review focuses on summarizing most recent mutations in LHX4 and OTX2 responsible for pituitary hormone deficiency. In both genetic defects of LHX4 and OTX2, there is high variability in clinical manifestations even in the same family. In addition, there is no clear phenotype-genotype correlation. These findings indicate that the other genetic and/or environmental factors influence the phenotype. In addition, the variability might reflect a plasticity during pituitary development and maintenance. Over the past two decades, a genetic basis for pituitary hormone deficiency and the mechanism of pituitary development have been clarified. It should be kept in mind that this review is not comprehensive, and defects of other transcriptional factors have been described in patients with CPHD. Furthermore, the causes in many patients with CPHD have not yet been determined. Therefore, continuing efforts for the clarification of the etiology are necessary. PMID:23990694

Gene Expression Signature in Adipose Tissue of Acromegaly Patients

PubMed Central

Hochberg, Irit; Tran, Quynh T.; Barkan, Ariel L.; Saltiel, Alan R.; Chandler, William F.; Bridges, Dave

2015-01-01

To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly. PMID:26087292

Somatic GNAS Mutation Causes Widespread and Diffuse Pituitary Disease in Acromegalic Patients with McCune-Albright Syndrome

PubMed Central

Vortmeyer, Alexander O.; Gläsker, Sven; Mehta, Gautam U.; Abu-Asab, Mones S.; Smith, Jonathan H.; Zhuang, Zhengping; Collins, Michael T.

2012-01-01

Context: McCune-Albright syndrome (MAS) is caused by sporadic mutations of the GNAS. Patients exhibit features of acromegaly. In most patients, GH-secreting pituitary adenomas have been held responsible for this presentation. However, surgical adenomectomy rarely eliminates excess GH production. Objective: The aim of this study was to elucidate pituitary pathology in patients with MAS and to explain the basis of failure of adenomectomy to eliminate GH hypersecretion. Design and Setting: We conducted a case series at the National Institutes of Health. Intervention(s): Interventions included medical therapy and transsphenoidal surgery. Patients and Main Outcome Measures: We studied clinical and imaging features and the histology and molecular features of the pituitary of four acromegalic MAS patients. Results: We identified widespread and diffuse pituitary gland disease. The primary pathological changes were characterized by hyperplastic and neoplastic change, associated with overrepresentation of somatotroph cells in structurally intact tissue areas. Genetic analysis of multiple microdissected samples of any type of histological area consistently revealed identical GNAS mutations in individual patients. The only patient with remission after surgery received complete hypophysectomy in addition to removal of multiple GH-secreting tumors. Conclusions: These findings indicate developmental effects of GNAS mutation on the entire anterior pituitary gland. The pituitary of individual cases contains a spectrum of changes with regions of normal appearing gland, hyperplasia, and areas of fully developed adenoma formation, as well as transitional stages between these entities. The primary change underlying acromegaly in MAS patients is somatotroph hyperplasia involving the entire pituitary gland, with or without development of somatotroph adenoma. Thus, successful clinical management, whether it is medical, surgical, or via irradiation, must target the entire pituitary, not just the adenomas evident on imaging. PMID:22564667

AIP mutations and gigantism.

PubMed

Rostomyan, Liliya; Potorac, Iulia; Beckers, Pablo; Daly, Adrian F; Beckers, Albert

2017-06-01

AIP mutations are rare in sporadic acromegaly but they are seen at a higher frequency among certain specific populations of pituitary adenoma patients (pituitary gigantism cases, familial isolated pituitary adenoma (FIPA) kindreds, and patients with macroadenomas who are diagnosed ≤30 years). AIP mutations are most prevalent in patients with pituitary gigantism (29% of this group were found to have mutations in AIP gene). These data support targeted genetic screening for AIP mutations/deletions in these groups of pituitary adenoma patients. Earlier diagnosis of AIP-related acromegaly-gigantism cases enables timely clinical evaluation and treatment, thereby improving outcomes in terms of excessive linear growth and acromegaly comorbidities. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Clinical guidelines for management of diabetes insipidus and syndrome of inappropriate antidiuretic hormone secretion after pituitary surgery.

PubMed

Lamas, Cristina; del Pozo, Carlos; Villabona, Carles

2014-04-01

Changes in water metabolism and regulation of vasopressin (AVP) or antidiuretic hormone (ADH) are common complications of pituitary surgery. The scarcity of studies comparing different treatment and monitoring strategies for these disorders and the lack of prior clinical guidelines makes it difficult to provide recommendations following a methodology based on grades of evidence. This study reviews the pathophysiology of diabetes insipidus and inappropriate ADH secretion after pituitary surgery, and is intended to serve as a guide for their diagnosis, differential diagnosis, treatment, and monitoring. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

Diabetes insipidus is an unfavorable prognostic factor for response to glucocorticoids in patients with autoimmune hypophysitis.

PubMed

Lupi, Isabella; Cosottini, Mirco; Caturegli, Patrizio; Manetti, Luca; Urbani, Claudio; Cappellani, Daniele; Scattina, Ilaria; Martino, Enio; Marcocci, Claudio; Bogazzi, Fausto

2017-08-01

Autoimmune hypophysitis (AH) has a variable clinical presentation and natural history; likewise, its response to glucocorticoid therapy is often unpredictable. To identify clinical and radiological findings associated with response to glucocorticoids. 12 consecutive patients with AH, evaluated from 2008 to 2016. AH was the exclusion diagnosis after ruling out other pituitary masses and secondary causes of hypophysitis. Mean follow-up time was 30 ± 27 months (range 12-96 months). MRI identified two main patterns of presentation: global enlargement of the pituitary gland or panhypophysitis ( n  = 4, PH), and pituitary stalk abnormality only, or infundibulo-neuro-hypophysitis ( n  = 8, INH). Multiple tropin defects were more common in PH (100%) than those in INH (28% P  = 0.014), whereas diabetes insipidus was more common in INH (100%) than that in PH (50%; P  = 0.028). All 4 PH and 4 out of 8 INH were treated with glucocorticoids. Pituitary volume significantly reduced in all PH patients ( P  = 0.012), defective anterior pituitary function recovered only in the two patients without diabetes insipidus (50%) and panhypopituitarism persisted, along with diabetes insipidus, in the remaining 2 (50%). In all INH patients, either treated or untreated, pituitary stalk diameter reduced ( P  = 0.008) but diabetes insipidus persisted in all. Glucocorticoid therapy may improve anterior pituitary function in a subset of patients but has no effect on restoring posterior pituitary function. Diabetes insipidus appears as a negative prognostic factor for response to glucocorticoids. © 2017 European Society of Endocrinology.

Diagnosis and management of endocrine gland neoplasmas. Revision 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weller, R.E.

1994-03-01

Functional and nonfunctional neoplasms of the endocrine glands constitute some of the more challenging diagnostic and therapeutic problems in veterinary cancer medicine. This discussion will focus on the clinical signs and syndromes associated with neoplasms of the thyroid, adrenal, and parathyroid glands, and pancreas in companion animals and will concentrate on the mechanisms producing the clinical signs, diagnosis, staging, therapy and prognosis.

[Transsphenoidal endoscopic endonasal approach for the surgery of pituitary abscess].

PubMed

Yu, Huanxin; Liu, Gang

2014-01-01

To evaluate the effectiveness of transsphenoidal endoscopic endonasal approach for the surgery of pituitary abscess. Eighteen pathologically diagnosed pituitary abscess were resected through transsphenoidal endoscopic endonasal approach at Tianjing Huanhu hospital between January 2000 and December 2011.Retrospective analysis was done upon clinical presentations and imaging features. There were 6 males and 12 females. The average age was 48.5 years old and the average disease course was 5.8 years. The typical clinical manifestations included headache (13 cases), pituitary dysfunction (10 cases), Diabetes Insipidus (4 cases) visual interference (8 cases) and fever (4 cases). All cases were resected by transsphenoidal endoscopic endonasal approach with general anesthesia. The postoperative symptoms and follow-up results were recorded. All patients were followed up from 6 months to 6 years. Postoperatively, headache was recovered in 13 cases, visual was improved in 6 cases, hypopituitarism was relieved in 8 cases and polyuria was disappeared in 3 cases. One case was recurrent and cured by transsphenoidal endoscopic endonasal approach. Transsphenoidal endoscopic endonasal approach for the surgery of pituitary abscess is effective.

Pituitary apoplexy in a teenager--case report.

PubMed

Chao, Chen-Cheng; Lin, Chun-Ju

2014-06-01

Pituitary apoplexy is a rare clinical emergency which results from hemorrhage or infarction in the pituitary gland. We present a 14-year-old girl with pituitary apoplexy and review the literature. Our patient experienced blurred vision, nausea, and headache. Her best-corrected visual acuity was 20/200 and 20/20. Confrontation test visual field testing revealed bitemporal hemianopsia. Brain imaging demonstrated a suprasellar mass. The microscopic endonasal transsphenoidal approach only found 5-10 mL brownish fluid-like material. Pathology confirmed no malignancy. Pituitary apoplexy was diagnosed. Her nausea and headache gradually improved. Six months after operation, her best-corrected visual acuity had improved to 20/30 and 20/20. Although pituitary apoplexy is rare in pediatric patients, prompt evaluation including detailed ophthalmic examination, biochemical evaluation, endocrine workup, and image study are very important. Copyright © 2014 Elsevier Inc. All rights reserved.

Dynamic enhancement MRI of anterior lobe in pituitary dwarfism.

PubMed

Liu, H M; Li, Y W; Tsai, W Y; Su, C T

1995-08-01

We examined 23 patients with pituitary dwarfism by dynamic MRI; with a repetition time of 150 or 50 ms. The time-enhancement difference curves of selected regions in the anterior lobes were plotted. Another 48 patients with no definite clinical pituitary disfunction were examined with the same technique. We found that the intensity of maximum enhancement in both groups was similar, but the time to achieve maximum enhancement was delayed in pituitary dwarfism with or without stalk transection; the time seemed longest with stalk transection. There was little difference in enhancement between patients with multiple hormone deficiency or isolated growth hormone deficiency. Dynamic MRI of the anterior lobes may be an important functional imaging study, and our results imply that poor perfusion is a useful finding in pituitary dwarfism, especially in patients without stalk transection and normal pituitary height.

Mission Connect Mild TBI Translational Research Consortium

DTIC Science & Technology

2014-08-01

outcome. At 6 months post injury, patients will be screened for anterior pituitary function f the 61 mTBI subjects with IGF-1 results at the 6 month... anterior pituitary function, including somatomedin (IGF-1), thyroid stimulating hormone (TSH), thyroxine (Free T4), prolactin, and total cortisol in...resolution of PCS at six months after mTBI. We will also examine the incidence of single and multiple pituitary hormone deficiencies. The clinical

Mission Connect Mild TBI Translational Research Consortium

DTIC Science & Technology

2013-08-01

injury, patients will be screened for anterior pituitary function of the 56 mTBI subjects with IGF-1 results, of the 63 who completed the 6 month... anterior pituitary function, including somatomedin (IGF -1 ), thyroid stimulating hormone (TSH), thyroxine (Free T4), prolactin, and total cortisol in all...resolution of PCS at six months after mTBI. We will also examine the incidence of single and multiple pituitary hormone deficiencies. The clinical

MR of the pituitary in patients with Prader-Willi syndrome: size determination and imaging findings.

PubMed

Miller, L; Angulo, M; Price, D; Taneja, S

1996-01-01

Prader-Willi syndrome (PWS) is an unusual genetic disorder characterized by short stature, obesity, hypogonadism, hypotonia, cognitive impairment, and dysmorphic facies. There is an interstitial deletion of the proximal long arm of chromosome 15 in about 70 % of patients. Some of these clinical features suggest a central hypothalamic/pituitary dysfunction, and recent investigations have demonstrated a marked impairment in spontaneous growth hormone (GH) secretion. We studied 15 GH-deficient PWS patients by magnetic resonance imaging (MRI) to determine whether there was a diminution in the gross morphological size of the anterior pituitary gland, the site of GH synthesis. We also set out to catalog the pertinent imaging findings in this patient population. Our results indicate that this is the first report documenting pituitary size by MRI in PWS patients. No statistically significant difference was found in the height of the anterior pituitary gland in PWS patients compared with either normal children or children with isolated GH deficiency. An interesting imaging finding is that three of 15 patients (20 %) demonstrated complete absence of the posterior pituitary bright spot (PPBS), and a fourth patient demonstrated a small PPBS. These observations reflect an objective physiologic disturbance in the hypothalamus. The clinical and radiologic implications of these findings are discussed.

Abdominal aortic aneurysm with aorta-left renal vein fistula with left varicocele.

PubMed

Meyerson, S L; Haider, S A; Gupta, N; O'Dorsio, J E; McKinsey, J F; Schwartz, L B

2000-04-01

Abdominal aortic aneurysm with spontaneous aorto-left renal vein fistula is a rare but well-described clinical entity usually with abdominal pain, hematuria, and a nonfunctioning left kidney. This report describes a 44-year-old man with left-sided groin pain and varicocele who was treated with conservative measures only. The diagnosis was eventually made when he returned with microscopic hematuria, elevated serum creatinine level, and nonfunction of the left kidney; computed tomography scan demonstrated a 6-cm abdominal aortic aneurysm, a retroaortic left renal vein, and an enlargement of the left kidney. This patient represents the youngest to be reported with aorto-left renal vein fistula and the second case with a left-sided varicocele.

Pituitary gland imaging and outcome.

PubMed

Di Iorgi, Natascia; Morana, Giovanni; Gallizia, Anna Lisa; Maghnie, Mohamad

2012-01-01

Magnetic resonance imaging (MRI) allows a detailed and precise anatomical study of the pituitary gland by differentiating between the anterior and posterior pituitary lobes. The identification of posterior pituitary hyperintensity, now considered a marker of neurohypophyseal functional integrity, has been the most striking advance for the diagnosis and understanding of anterior and posterior pituitary diseases. The advent of MRI has in fact led to a significant improvement in the understanding of the pathogenesis of disorders that affect the hypothalamo-pituitary area. Today, there is convincing evidence to support the hypothesis that marked MRI differences in pituitary morphology indicate a diverse range of disorders which affect the organogenesis and function of the anterior pituitary gland with different prognoses. Furthermore, the association of extrapituitary malformations accurately defined by MRI has supported a better definition of several conditions linked to pituitary hormone deficiencies and midline defects. MRI is a very informative procedure that should be used to support a diagnosis of hypopituitarism. It is useful in clinical management, because it helps endocrinologists determine which patients to target for further molecular studies and genetic counselling, which ones to screen for additional hormone deficits, and which ones may need growth hormone replacement into adult life. Copyright © 2012 S. Karger AG, Basel.

Thickened Pituitary Stalk Associated with a Mass in the Sphenoidal Sinus: An Alarm to Suspect Hypophysitis by Immunoglobulin G4?

PubMed Central

Batista, Rafael Loch; Ramos, Luciano Silva; Cescato, Valter Angelo; Musolino, Nina Rosa Castro; Borba, Clarissa Groberio; Silva, Gilberto Ochman; Moreno, Lilian Hupfeld; Cunha Neto, Malebranche Bernardo Carneiro

2015-01-01

Introduction Hypophysitis is a chronic inflammation of the pituitary gland of complex and still incompletely defined pathogenesis. It belongs to the group of non-hormone-secreting sellar masses, sharing with them comparable clinical presentation and radiographic appearance. Objectives Describe the case of immunoglobulin G4 (IgG4)-related hypophysitis presenting as a mass in the sphenoid sinus. Resumed Report A 40-year-old Brazilian man had a diagnosis of central diabetes insipidus since 2001 associated with pituitary insufficiency. Pituitary magnetic resonance imaging revealed a centered pituitary stalk with focal nodular thickening and the presence of heterogeneous materials inside the sphenoid sinus. The patient was treated with testosterone replacement therapy. Laboratory results revealed increased IgG4 serum. Conclusion IgG4-related hypophysitis should be considered in patients with pituitary insufficiency associated with sellar mass and/or thickened pituitary stalk. IgG4 serum measurement for early diagnosis of IgG4-related hypophysitis should be performed. PMID:26157505

Clinical and diagnostic approach to patients with hypopituitarism due to traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and ischemic stroke (IS).

PubMed

Karamouzis, Ioannis; Pagano, Loredana; Prodam, Flavia; Mele, Chiara; Zavattaro, Marco; Busti, Arianna; Marzullo, Paolo; Aimaretti, Gianluca

2016-06-01

The hypothalamic-pituitary dysfunction attributable to traumatic brain injury (TBI), aneurysmal subarachnoid hemorrhage (SAH), and ischemic stroke (IS) has been lately highlighted. The diagnosis of TBI-induced-hypopituitarism, defined as a deficient secretion of one or more pituitary hormones, is made similarly to the diagnosis of classical hypopituitarism because of hypothalamic/pituitary diseases. Hypopituitarism is believed to contribute to TBI-associated morbidity and to functional and cognitive final outcome, and quality-of-life impairment. Each pituitary hormone must be tested separately, since there is a variable pattern of hormone deficiency among patients with TBI-induced-hypopituitarism. Similarly, the SAH and IS may lead to pituitary dysfunction although the literature in this field is limited. The drive to diagnose hypopituitarism is the suspect that the secretion of one/more pituitary hormone may be subnormal. This suspicion can be based upon the knowledge that the patient has an appropriate clinical context in which hypopituitarism can be present, or a symptom known as caused by hypopituitarism. Hypopituitarism should be diagnosed as a combination of low peripheral and inappropriately normal/low pituitary hormones although their basal evaluation may be not distinctive due to pulsatile, circadian, or situational secretion of some hormones. Evaluation of the somatotroph and corticotroph axes require dynamic stimulation test (ITT for both axes, GHRH + arginine test for somatotroph axis) in order to clearly separate normal from deficient responses.

Comparison of post-surgical MRI presentation of the pituitary gland and its hormonal function.

PubMed

Bladowska, Joanna; Sokolska, Violetta; Sozański, Tomasz; Bednarek-Tupikowska, Grażyna; Sąsiadek, Marek

2010-01-01

Post-surgical evaluation of the pituitary gland in MRI is difficult because of a change of anatomical conditions. It depends also on numerous other factors, including: size and expansion of a tumour before surgery, type of surgical access, quality and volume of filling material used and time of its resorption.The aim of the study was to compare MR image of the pituitary gland after surgery with clinical findings and to establish a correlation between MRI presentation of spared pituitary and its hormonal function. 124 patients after resection of pituitary adenomas - 409 MRI results in total - were studied. With a 1.5-T unit, T1-weighted sagittal and coronal, enhanced and unenhanced images were obtained. The pituitary gland seemed to be normal in MRI in 11 patients, 8 of them had completely regular pituitary function but in 3 of them we noticed a partial hypopituitarism. In 99 patients only a part of the pituitary gland was recognised, 53 of them had hypopituitarism but 46 of them were endocrinologically healthy. 14 patients seemed to have no persistent pituitary gland in MRI, in comparison to hormonal studies: there was panhypopituitarism in 6 and hypopituitarism in 8 cases. MRI presentation of post - surgical pituitary gland doesn't necessarily correlate with its hormonal function - there was a significant statistical difference. Some patients with partial pituitary seems normal hormonal function. In some cases the pituitary seem normal in MRI but these patients have hormonal disorders and need substitution therapy.

Treatment of Pituitary Carcinomas and Atypical Pituitary Adenomas: A Review

PubMed Central

HIROHATA, Toshio; ISHII, Yudo; MATSUNO, Akira

2014-01-01

Atypical pituitary adenomas (APAs) are aggressive tumors, harboring a Ki-67 (MIB-1) staining index of 3% or more, and positive immunohistochemical staining for p53 protein, according to the World Health Organization (WHO) classification in 2004. Pituitary carcinomas (PC) usually develop from progressive APAs and predominantly consist of hormone-generating tumors, defined by the presence of disseminations in the cerebrospinal system or systemic metastases. Most of the cases with these malignant pituitary adenomas underwent surgeries, irradiations and adjuvant medical treatments, nevertheless, the therapies are mainly palliative. Recently, the efficacy of temozolomide (TMZ), an orally administered alkylating agent, has been reported as an alternative medical treatment. However, some recent studies have demonstrated a significant recurrence rate after effective response to TMZ. Further clinical and pathological researches of malignant pituitary adenomas will be required to improve the outcome of patients with these tumors. PMID:25446382

Pituitary apoplexy.

PubMed

Bi, Wenya Linda; Dunn, Ian F; Laws, Edward R

2015-02-01

Pituitary apoplexy is a clinical syndrome of sudden headache and visual decline associated with acute hemorrhagic or ischemic change of an intrasellar mass, and comprises only a subset of hemorrhagic pituitary lesions. The most common presenting symptoms include headache, nausea, diminished visual acuity or visual field, ophthalmoplegia/paresis, and impaired mental status. Multiple risk factors have been reported, although the majority of cases have no identifiable precipitants. MRI is the most sensitive diagnostic modality, with specific imaging findings dependent on the timing post-hemorrhage. Early clinical suspicion is imperative to allow for corticosteroid replacement and hemodynamic stabilization when indicated. Transsphenoidal surgical decompression improves outcome in a majority of cases, although conservative management may be appropriate in select scenarios.

Constraints imposed by non-functional protein–protein interactions on gene expression and proteome size

PubMed Central

Zhang, Jingshan; Maslov, Sergei; Shakhnovich, Eugene I

2008-01-01

Crowded intracellular environments present a challenge for proteins to form functional specific complexes while reducing non-functional interactions with promiscuous non-functional partners. Here we show how the need to minimize the waste of resources to non-functional interactions limits the proteome diversity and the average concentration of co-expressed and co-localized proteins. Using the results of high-throughput Yeast 2-Hybrid experiments, we estimate the characteristic strength of non-functional protein–protein interactions. By combining these data with the strengths of specific interactions, we assess the fraction of time proteins spend tied up in non-functional interactions as a function of their overall concentration. This allows us to sketch the phase diagram for baker's yeast cells using the experimentally measured concentrations and subcellular localization of their proteins. The positions of yeast compartments on the phase diagram are consistent with our hypothesis that the yeast proteome has evolved to operate closely to the upper limit of its size, whereas keeping individual protein concentrations sufficiently low to reduce non-functional interactions. These findings have implication for conceptual understanding of intracellular compartmentalization, multicellularity and differentiation. PMID:18682700

Loss of ACTH expression in cultured human corticotroph macroadenoma cells is consistent with loss of the POMC gene signal sequence.

PubMed

Rees, D A; Hepburn, P J; McNicol, A M; Francis, K; Jasani, B; Lewis, M D; Farrell, W E; Lewis, B M; Scanlon, M F; Ham, J

2002-03-28

The proopiomelanocortin (POMC) gene is highly expressed in the pituitary gland where the resulting mRNA of 1200 base pairs (bp) gives rise to a full-length protein sequence. In peripheral tissues however both shorter and longer POMC variants have been described, these include for example placental tissue which contain 800 (truncated at the 5' end) and 1500 as well as the 1200 bp transcripts. The importance of the 800 bp transcript is unclear as the lack of a signal sequence renders the molecule to be non-functional. This transcript has not been previously demonstrated in the pituitary gland. In this report we show evidence of a 5' truncated POMC gene in human pituitary corticotroph macroadenoma cells (JE) maintained in primary culture for >1 year. The original tumour tissue and the derived cells during early passage (up to passage 4-5) immunostained for ACTH and in situ hybridisation confirmed the presence of the POMC gene in the cultured cells. These cells also secreted 15-40 pg/10(5) cells/24 h ACTH. In addition, as expected RT-PCR demonstrated the presence of all three POMC gene exons and is thus indicative of a full-length POMC gene. In late culture passages (passages 8-15) JE cells ceased to express ACTH and cell growth became very slow due presumably to cells reaching their Hayflick limit. ACTH immunostaining in these cells was undetectable and ACTH secretion was also at the detection limits of the assay and no greater than 10 pg/10(5) cells/24 h. ACTH precursor molecules were also undetectable. RT-PCR for the POMC gene in these late passage cells showed that only exon 3 was detectable, in contrast to early passage cells where all three exons were present. In summary we isolated in culture, human pituitary cells that possessed initially all three exons of the POMC gene and immunostained for ACTH. On further passaging these cells showed a loss of exons 1 and 2 in the POMC gene and a loss of ACTH immunostaining and secretion. We would like to suggest that the loss of ACTH peptide expression in these late passage cells is in part due to the loss of the POMC signal sequence. An alternative explanation for our findings is that there were originally two populations of corticotrophs in the cultures, one of which possessed the full-length POMC gene and the other only the 5' truncated POMC transcript and it is these latter cells which survived in culture. In either scenario this is the first report of the 5' truncated POMC gene occurring in pituitary cells.

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

PubMed

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

2017-04-01

The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients. © 2017 Society for Endocrinology.

[Pituitary apoplexy. Report of 25 patients].

PubMed

Khaldi, M; Ben Hamouda, K; Jemel, H; Kallel, J; Zemmel, I

2006-09-01

A series of 25 patients with a clinical diagnosis of pituitary apoplexy (PA) is reviewed. It included 14 men and 11 women aged between 20 to 79 years (mean age: 54 years). Twenty-two patients did not know that they had a pituitary tumor when the apoplexy occurred. A precipitating event was found in 3 cases. Symptoms and signs ranged from isolated ocular paresis to a deep coma. Seventeen patients experienced a decrease in their visual acuity. CTscan and MRI showed a pituitary adenoma in all cases, a hemorrhage was also present in 10 out of the 24 CTscans, and in all the 8 MRI performed. Twenty patients underwent surgery; 18 of them by a transsphenoidal approach. A complete recovery of visual acuity was observed in 75% of patients operated within the week following the onset of symptoms, and in 56% of patients operated later on. There was no case of complete visual recovery among the blind patients. Pituitary apoplexy is a clinical concept. It applies only to symptomatic cases. It is generally a complication of a pituitary adenoma which is in most cases unknown. There are different degrees of severity; PA can even be life-threatening. The principal aim of surgery in the acute phase is the improvement of visual prognosis. In our series, blind patients or those with a history of visual loss for more than a week or with a blindness had a poorer prognosis.

An unusual case of hypopituitarism and transient thyrotoxicosis following asymptomatic pituitary apoplexy.

PubMed

Yoshida, Masanori; Murakami, Miho; Ueda, Harumi; Miyata, Misaki; Takahashi, Norio; Oiso, Yutaka

2014-01-01

Although pituitary function is often impaired in pituitary apoplexy, the development of thyrotoxicosis is rare. We describe an unusual case of hypopituitarism due to pituitary apoplexy coexisting with transient hyperthyroidism. A 74-year-old woman presented with severe fatigue, palpitation, appetite loss, hypotension, and hyponatremia. Endocrine studies showed hyperthyroidism and anterior pituitary hormone deficiencies. A magnetic resonance imaging suggested recent-onset pituitary apoplexy in a pituitary tumor, although the patient had no apoplectic symptoms such as headache and visual disturbance. Thyrotoxicosis and adrenal insufficiency worsened her general condition. Glucocorticoid supplementation improved her clinical symptoms and hyponatremia. Serum anti-thyrotropin receptor and thyroid-stimulating antibody titers were negative, and her thyroid function was spontaneously normalized without antithyroid medication, suggesting painless thyroiditis. Thereafter, her thyroid function decreased because of central hypothyroidism and 75 µg of levothyroxine was needed to maintain thyroid function at the euthyroid stage. The pituitary mass was surgically removed and an old hematoma was detected in the specimen. Considering that painless thyroiditis develops as a result of an autoimmune process, an immune rebound mechanism due to adrenal insufficiency probably caused painless thyroiditis. Although the most common type of thyroid disorder in pituitary apoplexy is central hypothyroidism, thyrotoxicosis caused by painless thyroiditis should be considered even if the patient has pituitary deficiencies. Because thyrotoxicosis with adrenal insufficiency poses a high risk for a life-threatening adrenal crisis, prompt diagnosis and treatment are critical.

Top 100 Most-cited Articles on Pituitary Adenoma: A Bibliometric Analysis.

PubMed

Guo, Xiaopeng; Gao, Lu; Wang, Zihao; Feng, Chenzhe; Xing, Bing

2018-06-02

Many articles have been published on pituitary adenomas. Bibliometric analyses are helpful for determining the most impactful studies within a field. To identify the top 100 most-cited articles on pituitary adenomas using the bibliometric analysis method. We searched the Thomson Reuters Web of Science on March 31, 2018. Articles were listed in descending order by the total citation (TC) number, and the most-cited articles on pituitary adenomas were identified and analyzed. The most-cited articles were published between 1970 and 2014, with 1999 as the most prolific year. Growth hormone-secreting pituitary adenoma was the most commonly studied tumor subtype (43%), and in clinical studies, treatment options and follow-up were the most important research focuses (62%). The average number of TCs was 326, and the average number of annual citations (ACs) was 17. More review articles were published in the last decade, and the average number of ACs was higher for this decade than for previous decades. Twenty-one articles were recognized as "Citation Classics" with a TC number>400. Twenty-five journals published the top 100 works; the Journal of Clinical Endocrinology and Metabolism published the most articles (25%). The most articles (43%) were published in the United States. S. Melmed authored the greatest number of publications (14%). Departments of Medicine (32%) and Endocrinology (32%) contributed to the largest number of articles. This study identified the research focuses and trends regarding pituitary adenoma and provides key references for investigators in guiding future pituitary adenoma research. Copyright © 2018 Elsevier Inc. All rights reserved.

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

PubMed

Cheng, Jing; Fan, Yanqin; Cen, Bo

2017-09-01

The objective of this study was to investigate the effect of preserving an infiltrated pituitary stalk during the resection of craniopharyngioma of pituitary stalk origin on postoperative outcomes and thus provide a theoretical basis for microsurgical treatment and prognosis. We screened the clinical data of all 103 pediatric patients with craniopharyngioma undergoing surgical treatment at our department between January 2006 and January 2013 and conducted a retrospective analysis of 82 patients with craniopharyngioma originating in the pituitary stalk. The patients were followed up from 12 months to 8 years. We analyzed the effect of preserving the pituitary stalk on the early and persistent diabetes insipidus rates, postoperative relapse rate, and mortality. In the total resection group (n = 67), the early and persistent diabetes insipidus rates were significantly lower in the 46 patients (68.7%) with a pituitary stalk than in those whose pituitary stalk was removed (P < 0.05); no significant difference was observed in the relapse rate between the 2 subgroups (P > 0.05). In the subtotal resection group (n = 15), a significant difference was observed in the early and persistent diabetes insipidus rates (P < 0.05), but no significant difference was observed in the relapse rate between the patients with a pituitary stalk and those whose pituitary stalk was removed (P > 0.05). For children with craniopharyngioma of pituitary stalk origin, preserving the pituitary stalk has a significant effect on the early and persistent diabetes insipidus rates. When intraoperative exploration showed excessive adhesion between the tumor and pituitary stalk, we opted to preserve the pituitary stalk, which significantly reduced the early and persistent postoperative diabetes insipidus rates, without significantly increasing the relapse or mortality rate.

78 FR 255 - Resumption of the Population Estimates Challenge Program

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-03

... governmental unit. In those instances where a non-functioning county-level government or statistical equivalent...) A non-functioning county or statistical equivalent means a sub- state entity that does not function... represents a non-functioning county or statistical equivalent, the governor will serve as the chief executive...

[Staged transcranial and transsphenoidal surgery for giant pituitary adenomas: a retrospective study of 21 cases].

PubMed

Liao, D Y; Liu, Z Y; Zhang, J; Ren, Q Q; Liu, X Y; Xu, J G

2018-05-08

Objective: To investigate the effect of the second-stage transcranial and transsphenoidal approach for giant pituitary tumors. Methods: A retrospective review of 21 patients, who had undergone the transcranial surgery and then transsphenoidal surgery for giant pituitary adenomas from 2012 to 2015 in the neurosurgery department of West China Hospital, was performed. Visual findings, endocrine presentation, complications, and tumor types were collected. All data were based on clinical feature, MRI, and follow-up. Results: Among the 21 cases, gross total resection of tumor was achieved in 7 of all patients, subtotal in 11, and partial in 3. No intracranial hemorrhage or death occurred postoperatively. Postoperative infectionoccurred in one patient and cerebrospinal fluid leakage occurred in 3 patients. Four patients recovered after treatment. Conclusion: According to the clinical feature and MRI, it is safe and effective to choose the transcranial surgery and then transsphenoidal surgery for specific giant pituitary adenomas, which can improve treatment effects and reduce postoperative complications.

Primary and Central Hypothyroidism After Radiotherapy for Head-and-Neck Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhandare, Niranjan; Kennedy, Laurence; Malyapa, Robert S.

Purpose: To investigate the incidence of radiotherapy (RT)-induced central and primary hypothyroidism regarding total dose, fractionation, and adjuvant chemotherapy. Methods and Materials: We retrospectively reviewed the data from 312 patients treated with RT for extracranial head-and-neck tumors between 1964 and 2000. The cervical lymph nodes were irradiated in 197 patients. The radiation doses to the thyroid gland and hypothalamic-pituitary axis were estimated by reconstructing the treatment plans. Results: Clinical central hypothyroidism (CH) was observed in 17 patients (5.4%); the median clinical latency was 4.8 years. Clinical primary hypothyroidism (PH) was observed in 40 patients (20.3%); the median clinical latency wasmore » 3.1 years. Multivariate analysis of clinical CH revealed that fractionation, adjuvant chemotherapy, and total dose to the pituitary were not significant. Multivariate analysis of clinical PH revealed that the total dose to the thyroid (p = 0.043) was significant, but adjuvant chemotherapy, age, and gender were not. Of the patients tested for hypopituitarism, 14 (20.3%) of 69 demonstrated subclinical CH and 17 (27.4%) of 62 demonstrated subclinical PH. The 5-year and 10-year rates of freedom from clinical CH and PH were 97% and 87% and 68% and 67%, respectively. Of the patients tested, the 5-year and 10-year rates of freedom from subclinical CH and PH were 91% and 78% and 71% and 71%, respectively. Conclusion: Clinical and subclinical manifestations of late radiation toxicity were observed in the thyroid and hypothalamic-pituitary axis. Although CH did not indicate a dependence on fractionation, adjuvant chemotherapy, or total dose to the pituitary, PH showed a dependence on the total dose to the thyroid gland.« less

External dacryocystorhinostomy for the treatment of epiphora in patients with patent but non-functioning lacrimal systems.

PubMed

Peter, Neena M; Pearson, Andrew R

2010-02-01

To assess the outcome of external dacryocystorhinostomies (DCRs) in patients with patent but non-functional lacrimal drainage systems and to identify any preoperative clinical or dacryocystography (DCG) and lacrimal scintigraphy (LS) factors associated with successful surgery. A retrospective study of 46 DCRs with silicone intubation performed for patients with epiphora associated with a clinically patent lacrimal drainage system. All patients underwent preoperative DCG and LS which were evaluated for presence, site and severity of delayed clearance. DCGs were also evaluated for reflux and anatomical abnormalities. Postoperative success was determined by subjective resolution of epiphora. Patients with persistent symptoms were offered Lester Jones Tube (LJT) insertion after establishment of a patent anastomosis to syringing and normal ostium on nasal endoscopy. Statistical analysis was performed using the chi2 and Fisher exact tests to determine whether there was any association between surgical outcome and preoperative resistance to lacrimal syringing, DCG and LS findings. 29 cases (63%) reported subjective surgical success after 11 months' average follow-up. There was a statistically significant association between increased resistance to syringing preoperatively and successful DCR (p=0.012). Of the 17 eyes that failed, all had patent anastomoses, and seven went on to have LJT insertion with complete resolution of symptoms. The majority of patients with patent but non-functional lacrimal drainage systems will be helped by DCR surgery, with greater success rates in those with significant reflux on preoperative syringing. For patients with residual epiphora, functional success can reach 100% with subsequent LJT insertion.

Korsakoff syndrome from retrochiasmatic suprasellar lesions: rapid reversal after relief of cerebral compression in 4 cases.

PubMed

Savastano, Luis E; Hollon, Todd C; Barkan, Ariel L; Sullivan, Stephen E

2018-06-01

Korsakoff syndrome is a chronic memory disorder caused by a severe deficiency of thiamine that is most commonly observed in alcoholics. However, some have proposed that focal structural lesions disrupting memory circuits-in particular, the mammillary bodies, the mammillothalamic tract, and the anterior thalamus-can give rise to this amnestic syndrome. Here, the authors present 4 patients with reversible Korsakoff syndromes caused by suprasellar retrochiasmatic lesions compressing the mammillary bodies and adjacent caudal hypothalamic structures. Three of the patients were found to have large pituitary macroadenomas in their workup for memory deficiency and cognitive decline with minimal visual symptoms. These tumors extended superiorly into the suprasellar region in a retrochiasmatic position and caused significant mass effect in the bilateral mammillary bodies in the base of the brain. These 3 patients had complete and rapid resolution of amnestic problems shortly after initiation of treatment, consisting of resection in 1 case of nonfunctioning pituitary adenoma or cabergoline therapy in 2 cases of prolactinoma. The fourth patient presented with bizarre and hostile behavior along with significant memory deficits and was found to have a large cystic craniopharyngioma filling the third ventricle and compressing the midline diencephalic structures. This patient underwent cyst fenestration and tumor debulking, with a rapid improvement in his mental status. The rapid and dramatic memory improvement observed in all of these cases is probably due to a reduction in the pressure imposed by the lesions on structures contiguous to the third ventricle, rather than a direct destructive effect of the tumor, and highlights the essential role of the caudal diencephalic structures-mainly the mammillary bodies-in memory function. In summary, large pituitary lesions with suprasellar retrochiasmatic extension and third ventricular craniopharyngiomas can cause severe Korsakoff-like amnestic syndromes, probably because of bilateral pressure on or damage to mammillary bodies, anterior thalamic nuclei, or their major connections. Neuropsychiatric symptoms may rapidly and completely reverse shortly after initiation of therapy via surgical decompression of tumors or pharmacological treatment of prolactinomas. Early identification of these lesions with timely treatment can lead to a favorable prognosis for this severe neuropsychiatric disorder.

[Acromegaly and pregnancy: report of six new cases].

PubMed

Persechini, M-L; Gennero, I; Grunenwald, S; Vezzosi, D; Bennet, A; Caron, P

2014-11-01

Pregnancies in acromegalic women are rare. Data from the literature indicate absence of congenital malformation in newborns, an increase of pituitary adenoma volume rarely clinically symptomatic, an increased risk of gestational diabetes and gravid hypertension in women with non-controlled GH/IGF-1 hypersecretion before gestation. The changes of somatotroph function are rarely described. Report of six new pregnancies in five women with acromegaly. Before pregnancy three women had incomplete surgical resection of GH-secreting pituitary adenoma, all were treated with somatostatin analogues, and the medical treatment was withdrawal at the diagnosis of gestation. We studied clinical (blood pressure, headaches, visual field), biological (blood glucose concentration) signs, GH and IGF-1 levels were measured during each trimester of pregnancy as well as in post-partum and were compared with pregestational values, MRI of the pituitary performed during the second trimester and in the post-partum were compared with MRI examen before pregnancy. All those pregnancies were normal without gestational diabetes, gravid hypertension and pituitary tumor syndrome. Clinical signs of acromegaly improved in 50 % of the patients, and IGF-1 decreased (22 %) in comparison of pregestational value without significant change in GH levels. No newborn had congenital malformation. Pregnancies in those women with acromegaly are uneventful without obstetrical or foetal complication, but a maternal follow-up is necessary in order to diagnose gravid hypertension and gestational diabetes. On the other hand, a clinical monitoring of pituitary tumor syndrome is necessary in women with non-operated GH-secreting macroadenoma before pregnancy. During the first trimester of gestation, an improvement of acromegalic signs can be due to a decrease of IGF-1 levels related to hepatic GH-resistance state secondary to physiological secretion of estrogens during gestation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Pituitary dwarfism in Saarloos and Czechoslovakian wolfdogs is associated with a mutation in LHX3.

PubMed

Voorbij, A M W Y; Leegwater, P A; Kooistra, H S

2014-01-01

Pituitary dwarfism in German Shepherd Dogs is associated with autosomal recessive inheritance and a mutation in LHX3, resulting in combined pituitary hormone deficiency. Congenital dwarfism also is encountered in breeds related to German Shepherd Dogs, such as Saarloos and Czechoslovakian wolfdogs. To investigate whether Saarloos and Czechoslovakian wolfdog dwarfs have the same LHX3 mutation as do Germans Shepherd Dog dwarfs. A specific aim was to determine the carrier frequency among Saarloos and Czechoslovakian wolfdogs used for breeding. Two client-owned Saarloos wolfdogs and 4 client-owned Czechoslovakian wolfdogs with pituitary dwarfism, 239 clinically healthy client-owned Saarloos wolfdogs, and 200 client-owned clinically healthy Czechoslovakian wolfdogs. Genomic DNA was amplified using polymerase chain reaction (PCR). In the Saarloos and Czechoslovakian wolfdog dwarfs, PCR products were analyzed by sequencing. DNA fragment length analysis was performed on the samples from the clinically healthy dogs. Saarloos and Czechoslovakian wolfdog dwarfs have the same 7 bp deletion in intron 5 of LHX3 as do German Shepherd Dog dwarfs. The frequency of carriers of this mutation among clinically healthy Saarloos and Czechoslovakian wolfdogs used for breeding was 31% and 21%, respectively. An LHX3 mutation is associated with pituitary dwarfism in Saarloos and Czechoslovakian wolfdogs. The rather high frequency of carriers of the mutated gene in the 2 breeds emphasizes the need for screening before breeding. If all breeding animals were genetically tested for the presence of the LHX3 mutation and a correct breeding policy would be implemented, this disease could be eradicated completely. Copyright © 2014 by the American College of Veterinary Internal Medicine.

76 FR 25535 - Airworthiness Directives; Dassault-Aviation Model FALCON 7X Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-05

...-functioning] of the RAT when needed. * * * * * Non-functioning of the RAT could result in insufficient...], and the consequent * * * [non-functioning] of the RAT when needed. The purpose of this AD is to require a repetitive functional test of the RAT heater * * *. Non-functioning of the RAT could result in...

26 CFR 1.988-6 - Nonfunctional currency contingent payment debt instruments.

Code of Federal Regulations, 2010 CFR

2010-04-01

... accrued but unpaid interest is translated into functional currency at the same rate used, in each of the... 26 Internal Revenue 10 2010-04-01 2010-04-01 false Nonfunctional currency contingent payment debt... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Export Trade Corporations § 1.988-6 Nonfunctional currency...

UML Profiles for Design Decisions and Non-Functional Requirements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Liming; Gorton, Ian

2007-06-30

A software architecture is composed of a collection of design decisions. Each design decision helps or hinders certain Non-Functional Requirements (NFR). Current software architecture views focus on expressing components and connectors in the system. Design decisions and their relationships with non-functional requirements are often captured in separate design documentation, not explicitly expressed in any views. This disassociation makes architecture comprehension and architecture evolution harder. In this paper, we propose a UML profile for modeling design decisions and an associated UML profile for modeling non-functional requirements in a generic way. The two UML profiles treat design decisions and nonfunctional requirements asmore » first-class elements. Modeled design decisions always refer to existing architectural elements and thus maintain traceability between the two. We provide a mechanism for checking consistency over this traceability. An exemplar is given as« less

Silent pituitary macroadenoma co-secreting growth hormone and thyroid stimulating hormone.

PubMed

Sen, Orhan; Ertorer, M Eda; Aydin, M Volkan; Erdogan, Bulent; Altinors, Nur; Zorludemir, Suzan; Guvener, Nilgun

2005-04-01

Silent pituitary adenomas are a group of tumors showing heterogenous morphological features with no hormonal function observed clinically. To date no explanation has been provided as to why these tumors remain "silent". We report a case of a silent macroadenoma with both growth hormone (GH) and thyroid stimulating hormone (TSH) staining and secretion but with no clinical manifestations, in particular, the absence of features of acromegaly or hyperthyroidism. The relevant literature is reviewed.

Pituitary imaging findings in male patients with hypogonadotrophic hypogonadism.

PubMed

Hirsch, Dania; Benbassat, Carlos; Toledano, Yoel; S'chigol, Irena; Tsvetov, Gloria; Shraga-Slutzky, Ilana; Eizenberg, Yoav; Shimon, Ilan

2015-08-01

Data on pituitary imaging in adult male patients presenting with hypogonadotrophic hypogonadism (HH) and no known pituitary disease are scarce. To assess the usefulness of pituitary imaging in the evaluation of men presenting with HH after excluding known pituitary disorders and hyperprolactinemia. A historical prospective cohort of males with HH. Men who presented for endocrine evaluation from 2011 to 2014 with testosterone levels <10.4 nmol/L (300 ng/mL), normal LH and FSH levels and no known pituitary disease. Seventy-five men were included in the analysis. Their mean age and BMI were 53.4 ± 14.8 years and 30.7 ± 5.2 kg/m2, respectively. Mean total testosterone, LH, and FSH were 6.2 ± 1.7 nmol/L, 3.4 ± 2 and 4.7 ± 3.1 mIU/L, respectively. Prolactin level within the normal range was obtained in all men (mean 161 ± 61, range 41-347 mIU/L). Sixty-two men had pituitary MRI and 13 performed CT. In 61 (81.3%) men pituitary imaging was normal. Microadenoma was found in 8 (10.7%), empty sella and thickened pituitary stalk in one patient (1.3%) each. In other four patients (5.3%) a small or mildly asymmetric pituitary gland was noted. No correlation was found between testosterone level and the presence of pituitary anomalies. This study suggests that the use of routine hypothalamic-pituitary imaging in the evaluation of IHH, in the absence of clinical characteristics of other hormonal loss or sellar compression symptoms, will not increase the diagnostic yield of sellar structural abnormalities over that reported in the general population.

Evaluation of clinical hypothyroidism risk due to irradiation of thyroid and pituitary glands in radiotherapy of nasopharyngeal cancer patients.

PubMed

Lin, Zhixiong; Wang, Xiaoyan; Xie, Wenjia; Yang, Zhining; Che, Kaijun; Wu, Vincent W C

2013-12-01

Radiation-induced thyroid dysfunction after radiotherapy for nasopharyngeal cancer (NPC) has been reported. This study investigated the radiation effects of the thyroid and pituitary glands on thyroid function after radiotherapy for NPC. Sixty-five NPC patients treated with radiotherapy were recruited. Baseline thyroid hormone levels comprising free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) were taken before treatment and at 3, 6, 12 and 18 months. A seven-beam intensity-modulated radiotherapy plan was generated for each patient. Thyroid and pituitary gland dose volume histograms were generated, dividing the patients into four groups: high (>50 Gy) thyroid and pituitary doses (HTHP group); high thyroid and low pituitary doses (HTLP group); low thyroid and high pituitary doses; and low thyroid and pituitary doses. Incidence of hypothyroidism was analysed. Twenty-two (34%) and 17 patients (26%) received high mean thyroid and pituitary doses, respectively. At 18 months, 23.1% of patients manifested various types of hypothyroidism. The HTHP group showed the highest incidence (83.3%) of hypothyroidism, followed by the HTLP group (50%). NPC patients with high thyroid and pituitary gland doses carried the highest risk of abnormal thyroid physiology. The dose to the thyroid was more influential than the pituitary dose at 18 months after radiotherapy, and therefore more attention should be given to the thyroid gland in radiotherapy planning. © 2013 The Royal Australian and New Zealand College of Radiologists.

Spontaneous resolution of pituitary apoplexy in a giant boy under 10 years old.

PubMed

Chentli, Farida; Bey, Abderrahim; Belhimer, Faiza; Azzoug, Said

2012-01-01

Pituitary gigantism is a very rare condition; the occurrence of pituitary apoplexy in children younger than 10 years old is even rarer. The aim of our study is to report this exceptional association. A boy aged 9 years and 6 months was hospitalized for the first time in November 2011 for symptoms suggesting pituitary apoplexy. The onset of his disease was difficult to determine as his health record has been poorly maintained. On October 10, 2011, he presented to an emergency department with a sudden drop of visual acuity with diplopia and retro-orbital headaches. An ophthalmological exam found very low visual acuity (1/20) with papillary edema. An MRI of the patient's brain revealed a hemorrhagic pituitary process reaching the chiasma, which was compressed, especially on the right side. Thereafter, the patient's vision improved spontaneously. Clinical examination was normal except for gigantism (+5 SD compared to the target stature). Hormonal assessment argued for mixed secretion [growth hormone (GH) = 39 ng/mL, n ≤ 5, prolactin ( PRL) = 470 ng/mL, n < 15]. Other pituitary functions were normal. Visual acuity normalized after 2 months, and an MRI showed a spontaneous reduction of the pituitary tumor. This unusual observation is a model of symptomatic pituitary apoplexy with spontaneous resolution in a boy with pituitary gigantism: phenomenon quite exceptional and worth to be reported.

Assessment of pituitary micro-lesions using 3D sampling perfection with application-optimized contrasts using different flip-angle evolutions.

PubMed

Wang, Jing; Wu, Yue; Yao, Zhenwei; Yang, Zhong

2014-12-01

The aim of this study was to explore the value of three-dimensional sampling perfection with application-optimized contrasts using different flip-angle evolutions (3D-SPACE) sequence in assessment of pituitary micro-lesions. Coronal 3D-SPACE as well as routine T1- and dynamic contrast-enhanced (DCE) T1-weighted images of the pituitary gland were acquired in 52 patients (48 women and four men; mean age, 32 years; age range, 17-50 years) with clinically suspected pituitary abnormality at 3.0 T, retrospectively. The interobserver agreement of assessment results was analyzed with K-statistics. Qualitative analyses were compared using Wilcoxon signed-rank test. There was good interobserver agreement of the independent evaluations for 3D-SPACE images (k = 0.892), fair for routine MR images (k = 0.649). At 3.0 T, 3D-SPACE provided significantly better images than routine MR images in terms of the boundary of pituitary gland, definition of pituitary lesions, and overall image quality. The evaluation of pituitary micro-lesions using combined routine and 3D-SPACE MR imaging was superior to that using only routine or 3D-SPACE imaging. The 3D-SPACE sequence can be used for appropriate and successful evaluation of the pituitary gland. We suggest 3D-SPACE sequence to be a powerful supplemental sequence in MR examinations with suspected pituitary micro-lesions.

Altered Pituitary Gland Structure and Function in Posttraumatic Stress Disorder

PubMed Central

Bonert, Vivien; Moser, Franklin; Mirocha, James; Melmed, Shlomo

2017-01-01

Objectives: Posttraumatic stress disorder (PTSD) is associated with hypothalamus-pituitary-adrenal (HPA) axis response to stressors, but links to neurophysiological and neuroanatomical changes are unclear. The purpose of this study was to determine whether stress-induced cortisol alters negative feedback on pituitary corticotroph function and pituitary volume. Design: Prospective controlled study in an outpatient clinic. Methods: Subjects with PTSD and matched control subjects underwent pituitary volume measurement on magnetic resonance imaging, with pituitary function assessed by 24-hour urine free cortisol (UFC), 8:00 am cortisol, and adrenocorticotropic hormone (ACTH) levels, and ACTH levels after 2-day dexamethasone/corticotropin-releasing hormone test. Primary outcome was pituitary volume; secondary outcomes were ACTH area under the curve (AUC) and 24-hour UFC. Results: Thirty-nine subjects were screened and 10 subjects with PTSD were matched with 10 healthy control subjects by sex and age. Mean pituitary volume was 729.7 mm3 [standard deviation (SD), 227.3 mm3] in PTSD subjects vs 835.2 mm3 (SD, 302.8 mm3) in control subjects. ACTH AUC was 262.5 pg/mL (SD, 133.3 pg/mL) L in PTSD vs 244.0 pg/mL (SD, 158.3 pg/mL) in control subjects (P = 0.80). In PTSD subjects, UFC levels and pituitary volume inversely correlated with PTSD duration; pituitary volume correlated with ACTH AUC in control subjects (Pearson correlation coefficient, 0.88, P = 0.0009) but not in PTSD subjects. Conclusions: The HPA axis may be downregulated and dysregulated in people with PTSD, as demonstrated by discordant pituitary corticotroph function and pituitary volume vs intact HPA feedback and correlation of pituitary volume with ACTH levels in healthy control subjects. The results suggest a link between pituitary structure and function in PTSD, which may point to endocrine targeted therapeutic approaches. PMID:29264511

Hypopituitarism after traumatic brain injury.

PubMed

Bondanelli, Marta; Ambrosio, Maria Rosaria; Zatelli, Maria Chiara; De Marinis, Laura; degli Uberti, Ettore C

2005-05-01

Traumatic brain injury (TBI) is one of the main causes of death and disability in young adults, with consequences ranging from physical disabilities to long-term cognitive, behavioural, psychological and social defects. Post-traumatic hypopituitarism (PTHP) was recognized more than 80 years ago, but it was thought to be a rare occurrence. Recently, clinical evidence has demonstrated that TBI may frequently cause hypothalamic-pituitary dysfunction, probably contributing to a delayed or hampered recovery from TBI. Changes in pituitary hormone secretion may be observed during the acute phase post-TBI, representing part of the acute adaptive response to the injury. Moreover, diminished pituitary hormone secretion, caused by damage to the pituitary and/or hypothalamus, may occur at any time after TBI. PTHP is observed in about 40% of patients with a history of TBI, presenting as an isolated deficiency in most cases, and more rarely as complete pituitary failure. The most common alterations appear to be gonadotropin and somatotropin deficiency, followed by corticotropin and thyrotropin deficiency. Hyper- or hypoprolactinemia may also be present. Diabetes insipidus may be frequent in the early, acute phase post-TBI, but it is rarely permanent. Severity of TBI seems to be an important risk factor for developing PTHP; however, PTHP can also manifest after mild TBI. Accurate evaluation and long-term follow-up of all TBI patients are necessary in order to detect the occurrence of PTHP, regardless of clinical evidence for pituitary dysfunction. In order to improve outcome and quality of life of TBI patients, an adequate replacement therapy is of paramount importance.

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.

A descriptive study to find possible correlation between MRI findings of pituitary gland and serum prolactin level.

PubMed

Azeemuddin, Muhammad; Naqi, Rohana; Wasay, Mohammad

2013-06-01

To explore equation, if any, between findings of magnetic resonance imaging of pituitary gland and serum prolactin level. The retrospective, descriptive study was conducted at the Department of Radiology, Aga Khan University Hospital, Karachi, and related to patients' records from April 19, 2006 to April 23, 2009. Seventy patients underwent magnetic resonance imaging of brain for pituitary gland. Inclusion criteria were all patients referred with relevant clinical symptoms or deranged serum prolactin level. Patients who were claustrophobic or had a pacemaker, aneurysm clip, metallic foreign body in the orbit or with no laboratory investigation were excluded from the study. SPSS 19 was used for statistical analysis. Of the 70 patients, normal imaging was noted in 29 (41.4%) patients. Out of these, 18 (62.06%) patients had normal and 11 (37.93%) had raised serum prolactin levels. Microadenoma was found in 23 (32.8%) patients. Out of these, 10 (42.47%) had normal and 13 (56.52%) had raised prolactin levels. Macroadenoma was found in 16 (22.8 %). Out of these, 8 (50%) had normal and 8 (50%) had raised prolactin levels. Pituitary cyst was located in 2 (2.8 %) patients. Out of these, 1 (50%) had normal and 1 (50%) had raised serum prolactin levels. Magnetic resonance imaging of pituitary gland was not associated with serum prolactin levels in patients with clinical suspicion of pituitary abnormality. Therefore, regular monitoring of serum prolactin is suggested.

Association of craniopharyngioma and pituitary adenoma.

PubMed

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

2013-08-01

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

Development of pituitary adenoma in women with hyperprolactinaemia: clinical, endocrine, and radiological characteristics.

PubMed Central

Pontiroli, A E; Falsetti, L

1984-01-01

Sixty eight women referred for treatment of hyperprolactinaemia entered a three year follow up study to determine the clinical and endocrine course of the disease and its association with microadenoma of the pituitary. Details recorded before treatment included medical history, gonadotrophin and ovarian hormonal concentrations, and release of prolactin in response to protirelin (thyrotrophin releasing hormone), benserazide, cimetidine, and nomifensine. Sellar tomography was then performed yearly for three years in all women, 54 of them also undergoing computed coronal and sagittal tomography. At baseline evaluation 27 women showed radiological evidence of pituitary adenoma; at the end of the follow up period the number had increased to 41. Amenorrhoea, steady and raised serum prolactin concentrations, a low ratio of luteinising hormone to follicle stimulating hormone, a longer duration of disease, and low serum progesterone concentrations were more common in women with a final diagnosis of pituitary adenoma than in those whose sella remained normal. Tests for release of prolactin had yielded abnormal results from the outset in all 41 women with radiological evidence of pituitary adenoma and in about half of those whose sella had remained radiologically normal. Response to medical treatment (metergoline in 20 patients, bromocriptine in 21) was similar and showed no difference between patients with tumorous and non-tumorous hyperprolactinaemia. These findings suggest that a large proportion of women with hyperprolactinaemia may harbour a prolactin secreting pituitary adenoma which becomes apparent over a relatively short period. Amenorrhoea and steady and raised serum prolactin concentrations are more common in these women. Tests for release of prolactin are of predictive value in identifying women who will develop a pituitary adenoma. PMID:6421360

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

PubMed

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

2016-03-01

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

Clinical presentation and outcome of children with central diabetes insipidus associated with a self-limited or transient pituitary stalk thickening, diagnosed as infundibuloneurohypophysitis.

PubMed

Schaefers, J; Cools, M; De Waele, K; Gies, I; Beauloye, V; Lysy, P; Francois, I; Beckers, D; De Schepper, J

2017-08-01

Despite lymphocytic or autoimmune infundibuloneurohypophysitis (INH) is an increasingly recognized aetiology in children with central diabetes insipidus (CDI); clinical data on epidemiology (clinical evolution, predisposing factors, complications), diagnosis and management of this entity are limited and mostly based on published case reports. The aim of this study was to gain a broader insight in the natural history of this disease by analysing the clinical presentation, radiological pituitary stalk changes, associated autoimmunity and hormonal deficiencies in children with CDI and a self-limiting or transient stalk thickening (ST), diagnosed as autoimmune infundibuloneurohypophysitis, during the last 15 years in four Belgian university hospitals. The medical files of nine CDI patients with a ST at initial presentation and no signs of Langerhans cell histiocytosis or germinoma at presentation and/or during follow-up of more than 1.5 years were reviewed. Age at presentation ranged from 3 to 14 years. Two patients had a positive family history of autoimmunity. Three children presented with associated growth failure, two with nausea and one with long-standing headache. Median maximal diameter of the stalk was 4.6 mm (2.7-10 mm). Four patients had extra-pituitary brain anomalies, such as cysts. One patient had central hypothyroidism, and another had a partial growth hormone deficiency at diagnosis. Within a mean follow-up of 5.4 (1.5-15) years, stalk thickening remained unchanged in two patients, regressed in one and normalized in six children. CDI remained in all, while additional pituitary hormone deficiencies developed in only one patient. In this series of children INH with CDI as initial presentation, CDI was permanent and infrequently associated with anterior pituitary hormone deficiencies, despite a frequent association with nonstalk cerebral lesions. © 2017 The Authors. Clinical Endocrinology Published by John Wiley & Sons Ltd.

Detrimental Effects of Non-Functional Spermatozoa on the Freezability of Functional Spermatozoa from Boar Ejaculate

PubMed Central

Martinez-Alborcia, Maria J.; Valverde, Anthony; Parrilla, Inmaculada; Vazquez, Juan M.; Martinez, Emilio A.; Roca, Jordi

2012-01-01

In the present study, the impact of non-functional spermatozoa on the cryopreservation success of functional boar spermatozoa was evaluated. Fifteen sperm-rich ejaculate fractions collected from five fertile boars were frozen with different proportions of induced non-functional sperm (0 –native semen sample-, 25, 50 and 75% non-functional spermatozoa). After thawing, the recovery of motile and viable spermatozoa was assessed, and the functional of the spermatozoa was evaluated from plasma membrane fluidity and intracellular reactive oxygen species (ROS) generation upon exposure to capacitation conditions. In addition, the lipid peroxidation of the plasma membrane was assessed by the indirect measurement of malondialdehyde (MDA) generation. The normalized (with respect to a native semen sample) sperm motility (assessed by CASA) and viability (cytometrically assessed after staining with Hoechst 33342, propidium iodide and fluorescein-conjugated peanut agglutinin) decreased (p<0.01) as the proportion of functional spermatozoa in the semen samples before freezing decreased, irrespective of the semen donor. However, the magnitude of the effect differed (p<0.01) among boars. Moreover, semen samples with the largest non-functional sperm subpopulation before freezing showed the highest (p<0.01) levels of MDA after thawing. The thawed viable spermatozoa of semen samples with a high proportion of non-functional spermatozoa before freezing were also functionally different from those of samples with a low proportion of non-functional spermatozoa. These differences consisted of higher (p<0.01) levels of intracellular ROS generation (assessed with 5-(and-6) chloromethyl-20,70-dichlorodihydrofluorescein diacetate acetyl ester; CM-H2DCFDA) and increased (p<0.01) membrane fluidity (assessed with Merocyanine 540). These findings indicate that non-functional spermatozoa in the semen samples before freezing negatively influence the freezability of functional spermatozoa. PMID:22567165

AIP mutations in Brazilian patients with sporadic pituitary adenomas: a single-center evaluation

PubMed Central

Kasuki, Leandro; de Azeredo Lima, Carlos Henrique; Ogino, Liana; Camacho, Aline H S; Chimelli, Leila; Korbonits, Márta

2017-01-01

Aryl hydrocarbon receptor-interacting protein (AIP) gene mutations (AIPmut) are the most frequent germline mutations found in apparently sporadic pituitary adenomas (SPA). Our aim was to evaluate the frequency of AIPmut among young Brazilian patients with SPA. We performed an observational cohort study between 2013 and 2016 in a single referral center. AIPmut screening was carried out in 132 SPA patients with macroadenomas diagnosed up to 40 years or in adenomas of any size diagnosed until 18 years of age. Twelve tumor samples were also analyzed. Leukocyte DNA and tumor tissue DNA were sequenced for the entire AIP-coding region for evaluation of mutations. Eleven (8.3%) of the 132 patients had AIPmut, comprising 9/74 (12%) somatotropinomas, 1/38 (2.6%) prolactinoma, 1/10 (10%) corticotropinoma and no non-functioning adenomas. In pediatric patients (≤18 years), AIPmut frequency was 13.3% (2/15). Out of the 5 patients with gigantism, two had AIPmut, both truncating mutations. The Y268* mutation was described in Brazilian patients and the K273Rfs*30 mutation is a novel mutation in our patient. No somatic AIP mutations were found in the 12 tumor samples. A tumor sample from an acromegaly patient harboring the A299V AIPmut showed loss of heterozygosity. In conclusion, AIPmut frequency in SPA Brazilian patients is similar to other populations. Our study identified two mutations exclusively found in Brazilians and also shows, for the first time, loss of heterozygosity in tumor DNA from an acromegaly patient harboring the A299V AIPmut. Our findings corroborate previous observations that AIPmut screening should be performed in young patients with SPA. PMID:29074612

Social, educational and vocational outcomes in patients with childhood-onset and young-adult-onset growth hormone deficiency.

PubMed

Mitra, M Tanya; Jönsson, Peter; Åkerblad, Ann-Charlotte; Clayton, Peter; Kołtowska-Häggström, Maria; Korbonits, Márta; Toogood, Andy; Gleeson, Helena

2017-04-01

Hypopituitarism diagnosed in childhood, adolescence and young adulthood has the potential to affect growth and somatic development. Less is known about the impact of such a diagnosis on other aspects of development. An analysis of the KIMS database (Pfizer International Metabolic Database) was performed to explore social, educational and vocational outcomes of adult patients diagnosed in childhood, adolescence and young adulthood compared with adult-onset controls. A total of 2952 adult patients diagnosed with hypothalamic pituitary conditions before the age of 25 were divided into two groups: childhood-onset [<16 years (CO)] (n = 1782) and young-adult-onset [16 to <25 years (YAO)] (n = 1170). A total of 1617 adult patients diagnosed with a nonfunctioning pituitary adenoma at the age of 25 or older formed the adult-onset control group (AO). KIMS Patient Life Situation Form which provided information on social, educational and vocational outcomes. Compared with the AO control group, CO and YAO patients were between 4·5 and 8·0 times more likely to live with their parents in adulthood; CO and YAO patients were also less likely to live in partnership and to have children. The impact on educational and vocational outcomes was less marked than on social outcomes with no significant differences compared with the AO control group. Educational and vocational outcomes showed the lowest level in male and female CO and YAO patients who had been previously diagnosed with a brain tumour. Social outcomes were more affected than educational and vocational outcomes. Although CO patients are more adversely affected, YAO patients were also failing to achieve social milestones. This has consequences for the delivery of endocrine care in both paediatric and adult services. © 2016 John Wiley & Sons Ltd.

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

PubMed

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

2013-01-01

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

Testosterone replacement therapy: role of pituitary and thyroid in diagnosis and treatment

PubMed Central

Crawford, Megan

2016-01-01

Crosstalk among hormones characterizes endocrine function, and assessment of the hypogonadal man should take that into consideration. In men for whom testosterone deficiency is a concern, initial evaluation should include a thorough history and physical exam in which other endocrinopathies are being considered. Hypogonadism can be associated with both pituitary and thyroid dysfunction, for which appropriate biochemical evaluation should be undertaken in certain clinical scenarios. If low serum testosterone is confirmed measurement of luteinizing and follicle stimulating hormones (LH and FSH respectively) is essential to establish whether the hypogonadism is primary or secondary. In secondary hypogonadism measurement of prolactin is always necessary, and measurement of other pituitary hormones, along with pituitary imaging, may be indicated. Checking thyroid function may also be enlightening, and can raise additional therapeutic considerations. Correction of other pituitary axes may attenuate the need for testosterone replacement therapy in some cases. PMID:28078216

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

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

PubMed Central

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

2008-01-01

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

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.

Endosphenoidal coil for intraoperative magnetic resonance imaging of the pituitary gland during transsphenoidal surgery.

PubMed

Chittiboina, Prashant; Talagala, S Lalith; Merkle, Hellmut; Sarlls, Joelle E; Montgomery, Blake K; Piazza, Martin G; Scott, Gretchen; Ray-Chaudhury, Abhik; Lonser, Russell R; Oldfield, Edward H; Koretsky, Alan P; Butman, John A

2016-12-01

OBJECTIVE Pituitary MR imaging fails to detect over 50% of microadenomas in Cushing's disease and nearly 80% of cases of dural microinvasion. Surface coils can generate exceptionally high-resolution images of the immediately adjacent tissues. To improve imaging of the pituitary gland, a receive-only surface coil that can be placed within the sphenoid sinus (the endosphenoidal coil [ESC]) during transsphenoidal surgery (TSS) was developed and assessed. METHODS Five cadaver heads were used for preclinical testing of the ESC. The ESC (a double-turn, 12-mm-diameter surface coil made from 1-mm-diameter copper wire) was developed to obtain images in a 1.5-T MR scanner. The ESC was placed (via a standard sublabial TSS approach) on the anterior sella face. Clinical MR scans were obtained using the 8-channel head coil and ESC as the receiver coils. Using the ESC, ultra-high-resolution, 3D, balanced fast field echo (BFFE) and T1-weighted imaging were performed at resolutions of 0.25 × 0.25 × 0.50 mm 3 and 0.15 × 0.15 × 0.30 mm 3 , respectively. RESULTS Region-of-interest analysis indicated a 10-fold increase in the signal-to-noise ratio (SNR) of the pituitary when using the ESC compared with the 8-channel head coil. ESC-related improvements (p < 0.01) in the SNR were inversely proportional to the distance from the ESC tip to the anterior pituitary gland surface. High-resolution BFFE MR imaging obtained using ESC revealed a number of anatomical features critical to pituitary surgery that were not visible on 8-channel MR imaging, including the pituitary capsule, the intercavernous sinus, and microcalcifications in the pars intermedia. These ESC imaging findings were confirmed by the pathological correlation with whole-mount pituitary sections. CONCLUSIONS ESC can significantly improve SNR in the sellar region intraoperatively using current 1.5-T MR imaging platforms. Improvement in SNR can provide images of the sella and surrounding structures with unprecedented resolution. Clinical use of this ESC may allow for MR imaging detection of previously occult pituitary adenomas and identify microscopic invasion of the dura or cavernous sinus.

Endosphenoidal coil for intraoperative magnetic resonance imaging of the pituitary gland during transsphenoidal surgery

PubMed Central

Chittiboina, Prashant; Talagala, S. Lalith; Merkle, Hellmut; Sarlls, Joelle E.; Montgomery, Blake K.; Piazza, Martin G.; Scott, Gretchen; Ray-Chaudhury, Abhik; Lonser, Russell R.; Oldfield, Edward H.; Koretsky, Alan P.; Butman, John A.

2016-01-01

OBJECTIVE Pituitary MR imaging fails to detect over 50% of microadenomas in Cushing’s disease and nearly 80% of cases of dural microinvasion. Surface coils can generate exceptionally high-resolution images of the immediately adjacent tissues. To improve imaging of the pituitary gland, a receive-only surface coil that can be placed within the sphenoid sinus (the endosphenoidal coil [ESC]) during transsphenoidal surgery (TSS) was developed and assessed. METHODS Five cadaver heads were used for preclinical testing of the ESC. The ESC (a double-turn, 12-mm-diameter surface coil made from 1-mm-diameter copper wire) was developed to obtain images in a 1.5-T MR scanner. The ESC was placed (via a standard sublabial TSS approach) on the anterior sella face. Clinical MR scans were obtained using the 8-channel head coil and ESC as the receiver coils. Using the ESC, ultra–high-resolution, 3D, balanced fast field echo (BFFE) and T1-weighted imaging were performed at resolutions of 0.25 × 0.25 × 0.50 mm3 and 0.15 × 0.15 × 0.30 mm3, respectively. RESULTS Region-of-interest analysis indicated a 10-fold increase in the signal-to-noise ratio (SNR) of the pituitary when using the ESC compared with the 8-channel head coil. ESC-related improvements (p < 0.01) in the SNR were inversely proportional to the distance from the ESC tip to the anterior pituitary gland surface. High-resolution BFFE MR imaging obtained using ESC revealed a number of anatomical features critical to pituitary surgery that were not visible on 8-channel MR imaging, including the pituitary capsule, the intercavernous sinus, and microcalcifications in the pars intermedia. These ESC imaging findings were confirmed by the pathological correlation with whole-mount pituitary sections. CONCLUSIONS ESC can significantly improve SNR in the sellar region intraoperatively using current 1.5-T MR imaging platforms. Improvement in SNR can provide images of the sella and surrounding structures with unprecedented resolution. Clinical use of this ESC may allow for MR imaging detection of previously occult pituitary adenomas and identify microscopic invasion of the dura or cavernous sinus. PMID:26991390

MEN1, MEN4, and Carney Complex: Pathology and Molecular Genetics

PubMed Central

Schernthaner-Reiter, Marie Helene; Trivellin, Giampaolo; Stratakis, Constantine A.

2015-01-01

Pituitary adenomas are a common feature of a subset of endocrine neoplasia syndromes, which have otherwise highly variable disease manifestations. We provide here a review of the clinical features and human molecular genetics of multiple endocrine neoplasia type 1 and 4 (MEN1 and MEN4, respectively) and Carney complex (CNC). MEN1, MEN4 and CNC are hereditary autosomal dominant syndromes that can present with pituitary adenomas. MEN1 is caused by inactivating mutations in the MEN1 gene, whose product menin is involved in multiple intracellular pathways contributing to transcriptional control and cell proliferation. MEN1 clinical features include primary hyperparathyroidism, pancreatic neuroendocrine tumours and prolactinomas and other pituitary adenomas. A subset of patients with pituitary adenomas and other MEN1 features have mutations in the CDKN1B gene; their disease has been called MEN type 4 (MEN4). Inactivating mutations in the type 1α regulatory subunit of protein kinase A (PKA) (the PRKAR1A gene), that lead to dysregulation and activation of the PKA pathway, are the main genetic cause of CNC, which is clinically characterised by primary pigmented adrenocortical disease (PPNAD), spotty skin pigmentation (lentigines), cardiac and other myxomas and acromegaly due to somatotropinomas or somatotrope hyperplasia. PMID:25592387

Clinical profile and etiologies of children with central diabetes insipidus: a single-center experience from Turkey.

PubMed

Catli, Gonul; Abaci, Ayhan; Demir, Korcan; Ulusoy, Emel; Altincik, Ayca; Buyukgebiz, Atilla; Bober, Ece

2012-01-01

The aim of this study is to evaluate the clinical, anthropometric, hormonal, and radiological characteristics of children with central diabetes insipidus (DI). Case records of 34 children (22 boys and 12 girls) with documented central DI referred to the Pediatric Endocrinology and Adolescent Clinic of Dokuz Eylul University Faculty of Medicine were reviewed. The mean age at diagnosis was 6.4 +/- 5.6 years (range, 0.08-16 years). All patients underwent anterior pituitary function assessment and magnetic resonance imaging of pituitary at diagnosis. The median duration of follow-up was 7.9 +/- 4.5 years. The etiology of central DI was organic in 22 (64.7%) patients, trauma in 2 (5.9%) patients, and idiopathic in 10 (29.4%) patients. Organic causes consisted of craniopharyngioma in 7 patients, Langerhans cell histiocytosis in 4 patients, germinoma in 4 patients, holoprosencephaly in 3 patients, astrocytoma in 1 patient, cavernous hemangioma in 1 patient, Rathke's cleft cyst in 1 patient, and autoimmune polyendocrinopathy in 1 patient. Anterior pituitary hormone deficiencies were documented in 18 (53%) patients. Organic central DI group had a greater prevalence of anterior pituitary hormone deficiency when compared with the idiopathic group (66% and 10%, respectively; p = 0.007). The final height of patients with organic etiology were significantly lower than the idiopathic group (155 and 178, cm respectively; p = 0.021). Etiological diagnosis is possible in a significant proportion (70.6%) of children with central DI. Findings of this study suggest that accompanying anterior pituitary hormone deficiencies and short stature may be considered as indicators of organic etiology.

Diabetes insipidus in pediatric germinomas of the suprasellar region: characteristic features and significance of the pituitary bright spot.

PubMed

Kilday, John-Paul; Laughlin, Suzanne; Urbach, Stacey; Bouffet, Eric; Bartels, Ute

2015-01-01

The pituitary bright spot is acknowledged to indicate functional integrity of the posterior pituitary gland, whilst its absence supports a diagnosis of central diabetes insipidus (DI). This feature was evaluated, together with the incidence and clinical characteristics of DI in children with suprasellar/neurohypophyseal germinomas. We performed a review of all suprasellar (SS) or bifocal (BF) germinoma pediatric patients treated in Toronto since 2000. Demographics, symptomatology, treatment outcome and imaging were evaluated. Nineteen patients fulfilled inclusion criteria (10 SS, 9 BF; median age 12.5 years (6.2-16.8 years)). All remained alive at 6.4 years median follow-up (1.2-13.7 years) after receiving chemotherapy and radiotherapy (13 focal/ventricular, four whole brain, two neuraxis), with only one progression. All had symptoms of DI at presentation with a symptom interval above one year in eight cases (42 %). Desmopressin was commenced and maintained in 16 patients (84 %). The pituitary bright spot was lost in most diagnostic interpretable cases, but was appreciated in three patients (18 %) who had normal serum sodium values compared to 'absent' cases (p = 0.013). For two such cases, spots remained visible until last follow-up (range 0.4-3.3 years), with one still receiving desmopressin. No case of bright spot recovery was observed following therapy. Protracted symptom intervals for germinoma-induced central DI may reflect poor clinical awareness. Explanations for persistence of the pituitary bright spot in symptomatic patients remain elusive. Desmopressin seldom reverses the clinical features of germinoma-induced DI to allow discontinuation, nor does treatment cause bright spot recovery.

Magnetic Resonance Imaging Determination of Normal Pituitary Gland Dimensions in Zaria, Northwest Nigerian Population

PubMed Central

Ibinaiye, Philip Oluleke; Olarinoye-Akorede, Sefia; Kajogbola, Olugbenga; Bakari, Adamu Girei

2015-01-01

Objectives: To determine the dimensions of normal pituitary gland using T1-weighted magnetic resonance images (MRI) and to determine their relationship with age and sex. Materials and Methods: Cranial MRI scans of 100 individuals with clinically normal pituitary function (58 males and 42 females) and in the age range 14–82 years were reviewed in order to obtain volumetric measurements of the pituitary gland. The height, width, and depth of the pituitary were obtained from mid-sagittal and coronal planes, while the volume was calculated from these measured parameters. The data obtained were stratified based on age and sex for analysis. Statistical tests applied included Student's t-test and Pearson correlation. A minimum level of statistical significance was set at P < 0.05. Results: The mean pituitary volumes were 334.1 ± 145.8 mm3 and 328.1 ± 129.2 mm3 while the mean pituitary heights were 6.45 ± 1.7 mm and 6.46 ± 1.57 mm in males and females, respectively. Although there was no statistically significant difference between pituitary height and pituitary volume in both sexes, they correlated negatively with increasing age (r = −202, P = 0.04 and r = −410, P = 0.000, respectively). Both parameters were highest in pubertal subjects and declined steadily with age, with a second peak occurring only for pituitary height in the sixth decade. The mean pituitary widths (9.08 ± 2.59 mm and 9.21 ± 1.86 mm) and depths (10.59 ± 1.71 mm and 10.49 ± 1.57 mm) in males and females, respectively, did not show remarkable changes with age and sex in the individuals studied. Conclusion: With this study, we have provided reference values in Nigerian population for the dimensions of normal pituitary gland, in order to facilitate assessment and diagnosis in patients with abnormalities of the hypothalamic–pituitary axis. PMID:26167387

Effect of tertiary multileaf collimator (MLC) on foetal dose during three-dimensional conformal radiation therapy (3DCRT) of a brain tumour during pregnancy.

PubMed

Sharma, Dayananda S; Jalali, Rakesh; Tambe, Chandrashekhar M; Animesh; Deshpande, Deepak D

2004-01-01

The aim of this work was to measure the dose to foetus both in vivo and in vitro during three-dimensional conformal radiation therapy (3DCRT) in a pregnant patient with a pituitary adenoma. The study was then extended to assess the components contributing to the foetal dose such as collimator scatter, internal scatter, head leakage, wedge scatter and multileaf collimator (MLC) effect. A 30-year-old pregnant woman with a non-functioning pituitary macroadenoma was planned for 3DCRT with 6MV X-ray using four equally weighted MLC-shaped non-coplanar wedged portals. In vivo dosimetry was carried out using thermoluminescent (TL) phosphor powder, which was placed at different positions on the patient, corresponding to different locations in the uterus and also at external os. In vitro measurements were also performed on a simulated phantom using the same set-up parameters and beam arrangement to verify the in vivo measured dose. Experiments were carried out to measure the respective contributions of different components towards peripheral dose. In vitro measured dose to foetus was found to be slightly more than that of in vivo measurement with a maximum of 0.044% of the prescribed dose of 45Gy, which corresponded to 0.0199+/-0.0008Gy. Thermoluminescence dosimeter (TLD) kept at the external os of the patient showed a dose of 0.031% of the prescribed dose. Among the various components of the peripheral dose (foetal dose) measured, head leakage was found to be the leading cause contributing 52%, followed by wedge scatter (31%), collimator scatter (14%) and internal scatter (13%). The use of MLC reduced not only the volume of normal brain irradiation as compared to open fields but also the peripheral dose by 10%. Radiotherapy of brain tumours during pregnancy poses a unique clinical situation and decisions to deliver radiotherapy should be taken after detailed in vitro and in vivo dosimetric measurements. Our findings suggest that the beam arrangement using 3-4-fields generally used for 3DCRT of brain tumour with MLC for optimal coverage can be employed for pregnant patients even in early trimester. A possible increase in foetal dose from wedges to a large extent can be compensated with the use of MLC.

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

PubMed Central

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

2017-01-01

Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D2 receptors-agonist, have emerged as promising new approaches to treat pituitary adenomas. However, information on direct in vitro effects of BIM-23A760 in normal and tumoral pituitaries remains incomplete. The objective of this study was to analyze BIM-23A760 effects on functional parameters (Ca2+ signaling, hormone expression/secretion, cell viability and apoptosis) in pituitary adenomas (n = 74), and to compare with the responses of normal primate and human pituitaries (n = 3–5). Primate and human normal pituitaries exhibited similar sst2/sst5/D2 expression patterns, wherein BIM-23A760 inhibited the expression/secretion of several pituitary hormones (specially GH/PRL), which was accompanied by increased sst2/sst5/D2 expression in primates and decreased Ca2+ concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca2+ concentration, hormone secretion/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca2+ signaling and/or hormone secretion, which was associated with the relative somatostatin/dopamine-receptors levels, especially sst5 and sst5TMD4. The chimeric sst2/sst5/D2 compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D2 expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760. PMID:28181484

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

PubMed

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

2017-02-09

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

Response of Indian growth hormone deficient children to growth hormone therapy: association with pituitary size.

PubMed

Khadilkar, Vaman V; Prasad, Hemchand Krishna; Ekbote, Veena H; Rustagi, Vaishakhi T; Singh, Joshita; Chiplonkar, Shashi A; Khadilkar, Anuradha V

2015-05-01

To ascertain the impact of pituitary size as judged by Magnetic Resonance Imaging (MRI), on response to Growth Hormone (GH) therapy in GH deficient children. Thirty nine children (9.1 ± 2.7 y, 22 boys) with non-acquired GH deficiency (21 Isolated GH deficiency and 18 Combined pituitary hormone deficiency) were consecutively recruited and followed up for one year. Clinical, radiological (bone age and MRI) and biochemical parameters were studied. Children with hypoplastic pituitary (pituitary height < 3 mm) had more severe height deficit (height for age Z-score -6.0 vs. -5.0) and retardation of skeletal maturation (bone age chronological age ratio of 0.59 vs. 0.48) at baseline as compared to children with normal pituitary heights (p < 0.05 for both). After one year of GH therapy, height for age Z scores and percentage change in height for age Z scores were significantly higher in children with hypoplastic pituitaries (13.8 ± 3.6 and 28.7 % vs. 11.2 ± 4.1 and 21.4 %). Significant co-relation was observed between pituitary height and height for age Z-scores at baseline (r = 0.39, p < 0.05). The predicted adult height using Tanner Whitehouse-2 equations improved from 140.8 to 152.3 cm in children with hypoplastic pituitary when compared to an increase from 145.8 to 153.5 cm observed in children with normal pituitary height (p < 0.05). Indian growth hormone deficient children with hypoplastic pituitary respond better to therapy with GH in short term.

Pituitary Metastasis from Renal Cell Carcinoma: Description of a Case Report

PubMed Central

Wendel, Chloé; Campitiello, Marco; Plastino, Francesca; Eid, Nada; Hennequin, Laurent; Quétin, Philippe; Longo, Raffaele

2017-01-01

Patient: Male, 61 Final Diagnosis: Pituitary metastasis from renal cell carcinoma Symptoms: Deterioration of visual acuity and field • persisting headache • excess thirst • polyuria Medication: — Clinical Procedure: Total body CT-scan • brain MRI • trans-sphenoidal endoscopical surgery • radiotherapy • anti-angiogenic therapy Specialty: Oncology Objective: Rare disease Background: Pituitary metastasis is uncommon, breast and lung cancers being the most frequent primary tumors. Renal cell carcinoma (RCC) is a rare cause of pituitary metastases, with only a few cases described to date. Case Report: We report a case of a 61-year-old man who presented with a progressive deterioration of visual acuity and field associated with a bitemporal hemianopsia. Two years ago, he underwent radical right nephrectomy for a clear cell RCC (ccRCC). The biological tests showed pan-hypopituitarism and diabetes insipidus. Brain MRI revealed a large sellar tumor lesion bilaterally infiltrating the cavernous sinuses, which was surgically resected. Histology confirmed a ccRCC pituitary metastasis. The patient received post-surgical radiotherapy. Considering the presence of concomitant extra-pituitary metastases, treatment with sunitinib was started, followed by several lines of therapy with axitinib, everolimus, and sorafenib because of tumor progression. The patient also presented with a pituitary tumor recurrence, which was treated by stereotaxic radiotherapy. He died five years after the initial diagnosis of RCC and 30 months after the diagnosis of the pituitary metastasis. Conclusions: There are no standardized treatment guidelines for management of pituitary metastases. Pituitary surgery plays a role in symptom palliation, and it does not have any relevant impact on survival. Exclusive radiotherapy or stereotaxic radiotherapy could be an alternative to surgery in patients whose general condition is poor or who have concomitant extra-pituitary metastases. PMID:28044054

Three-dimensional magnetic resonance volumetry of the pituitary gland is effective in detecting short stature in children

PubMed Central

HAN, XUE; XIU, JIANJUN; HUANG, ZHAOQIN; ZHANG, JIE; ZHANG, ZHONGHE; DONG, YIN; YUAN, XIANSHUN; LIU, QINGWEI

2014-01-01

The aim of the present study was to obtain standard reference values for the pituitary gland volumes of healthy children and to analyze the potential diagnostic values of pituitary gland volumetry for growth hormone deficiency (GHD) and idiopathic short stature (ISS). The volume of the pituitary gland was measured using a thin-section three-dimensional (3D) magnetic resonance imaging (MRI) sequence of magnetization-prepared rapid gradient echo imaging with a section thickness of 1 mm. A group of 75 healthy children aged between 1 and 19 years were recruited to obtain normal volumetry values of the pituitary gland. These individuals demonstrated no evidence of abnormalities to the central nervous or endocrine systems prior to the study. An additional group of 55 children with GHD (n=32) or ISS (n=23) aged between 0 and 14 years were included in the measurement of pituitary gland volume and height. The Student’s t-test was used to evaluate the repetition test, while Pearson’s correlation coefficient and regression analyses were performed to examine the correlations between the volume and height of the pituitary glands. Pituitary gland volume and height demonstrated an increasing trend with age in the healthy children. In addition, the pituitary gland volume exhibited a growth spurt in the early teenage years (10–14 years-old), which was more prominent in females. The growth spurt was not observed for pituitary gland height. When compared with the healthy children, 65.6% of the children with GHD and 34.8% of the children with ISS had smaller pituitary gland volumes. Similarly, 37.5% of the children with GHD and 26.1% of the children with ISS had a smaller pituitary gland height compared with the healthy children. The pituitary gland volume performed significantly better compared with height with regard to the detection rate. Therefore, the results indicated that 3D MRI volumetry was useful for understanding the developmental characteristics of the pituitary gland in healthy children, and that the reference data provided by 3D MRI were effective in the diagnosis of short stature following associations with neuroimaging and clinical functional abnormalities of the pituitary gland. PMID:25009618

Three-dimensional magnetic resonance volumetry of the pituitary gland is effective in detecting short stature in children.

PubMed

Han, Xue; Xiu, Jianjun; Huang, Zhaoqin; Zhang, Jie; Zhang, Zhonghe; Dong, Yin; Yuan, Xianshun; Liu, Qingwei

2014-08-01

The aim of the present study was to obtain standard reference values for the pituitary gland volumes of healthy children and to analyze the potential diagnostic values of pituitary gland volumetry for growth hormone deficiency (GHD) and idiopathic short stature (ISS). The volume of the pituitary gland was measured using a thin-section three-dimensional (3D) magnetic resonance imaging (MRI) sequence of magnetization-prepared rapid gradient echo imaging with a section thickness of 1 mm. A group of 75 healthy children aged between 1 and 19 years were recruited to obtain normal volumetry values of the pituitary gland. These individuals demonstrated no evidence of abnormalities to the central nervous or endocrine systems prior to the study. An additional group of 55 children with GHD (n=32) or ISS (n=23) aged between 0 and 14 years were included in the measurement of pituitary gland volume and height. The Student's t-test was used to evaluate the repetition test, while Pearson's correlation coefficient and regression analyses were performed to examine the correlations between the volume and height of the pituitary glands. Pituitary gland volume and height demonstrated an increasing trend with age in the healthy children. In addition, the pituitary gland volume exhibited a growth spurt in the early teenage years (10-14 years-old), which was more prominent in females. The growth spurt was not observed for pituitary gland height. When compared with the healthy children, 65.6% of the children with GHD and 34.8% of the children with ISS had smaller pituitary gland volumes. Similarly, 37.5% of the children with GHD and 26.1% of the children with ISS had a smaller pituitary gland height compared with the healthy children. The pituitary gland volume performed significantly better compared with height with regard to the detection rate. Therefore, the results indicated that 3D MRI volumetry was useful for understanding the developmental characteristics of the pituitary gland in healthy children, and that the reference data provided by 3D MRI were effective in the diagnosis of short stature following associations with neuroimaging and clinical functional abnormalities of the pituitary gland.

Pre- and postoperative magnetic resonance imaging appearance of the normal residual pituitary gland following macroadenoma resection: Clinical implications

PubMed Central

Maio, Salvatore Di; Biswas, Arundhati; Vézina, Jean Lorrain; Hardy, Jules; Mohr, Gérard

2012-01-01

Background: To assess the relationship between the preoperative magnetic resonance imaging (MRI) appearance of the normal residual pituitary gland (NRPG) and pituitary functional outcome following transsphenoidal resection of pituitary macroadenomas. Methods: We retrospectively reviewed the medical records of 100 consecutive patients with a pituitary macroadenoma, who underwent transsphenoidal resection. The preoperative configuration of the displaced NRPG was stratified as superior, superolateral or lateral. The extent of postoperative restitution of the NRPG was divided into four groups: Group 1 — normal residual gland or almost normal; Group 2 — more than 50% restitution; Group 3 — less than 50% of the normal residual gland; and Group 4 — barely visible or absent residual gland. The pre- and postoperative NRPG appearance was correlated with pituitary functional status. Results: Preoperatively, the NRPG was identifiable in 79 patients, with extrasellar displacement in 53%. The displacement pattern was superior in 8%, superolateral in 32%, and lateral in 58% of the patients. If the NRPG was displaced laterally, the ipsilateral cavernous sinus was not invaded by the pituitary macroadenoma. Partial or complete pituitary function was lost in 6 / 23 (26.1%) patients with superior or superolateral displacement of the NRPG, compared to only 1 / 36 (2.8%) patients without superior displacement of the NRPG (P = 0.025). Progressive postoperative reconstitution of the NRPG was related to the preservation of the pituitary hormonal axis (Pearson Chi-Square P < 0.001). Conclusions: Progressive displacement of the NRPG preoperatively, and lack of restitution of the NRPG on postoperative MRI appeared to correlate with the postoperative pituitary functional loss. PMID:22754732

Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline.

PubMed

Fleseriu, Maria; Hashim, Ibrahim A; Karavitaki, Niki; Melmed, Shlomo; Murad, M Hassan; Salvatori, Roberto; Samuels, Mary H

2016-11-01

To formulate clinical practice guidelines for hormonal replacement in hypopituitarism in adults. The participants include an Endocrine Society-appointed Task Force of six experts, a methodologist, and a medical writer. The American Association for Clinical Chemistry, the Pituitary Society, and the European Society of Endocrinology co-sponsored this guideline. The Task Force developed this evidence-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the American Association for Clinical Chemistry, the Pituitary Society, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Using an evidence-based approach, this guideline addresses important clinical issues regarding the evaluation and management of hypopituitarism in adults, including appropriate biochemical assessments, specific therapeutic decisions to decrease the risk of co-morbidities due to hormonal over-replacement or under-replacement, and managing hypopituitarism during pregnancy, pituitary surgery, and other types of surgeries.

Prolactin-Producing Pituitary Carcinoma, Hypopituitarism, and Graves' Disease-Report of a Challenging Case and Literature Review.

PubMed

Bettencourt-Silva, Rita; Pereira, Josué; Belo, Sandra; Magalhães, Daniela; Queirós, Joana; Carvalho, Davide

2018-01-01

The diagnosis of pituitary carcinoma is very rare, requires the evidence of metastatic disease, and has a poor overall survival. Malignant prolactinoma frequently requires dopamine agonist therapy, pituitary surgery, radiotherapy, and even chemotherapy. A 19-year-old female presented with galactorrhea, primary amenorrhea, and left hemianopsia. Complementary study detected hyperprolactinemia and a pituitary macroadenoma with cavernous sinus invasion and suprasellar growth. She was treated with cabergoline and bromocriptine without clinical or analytical improvement. Resection of the pituitary lesion was programmed and a non-contiguous lesion of the nasal mucosa was detected during the approach. This metastasis led to the diagnosis of prolactin-producing pituitary carcinoma. After partial resection, the patient was submitted to radiotherapy for residual disease with persistent symptoms. She developed growth hormone deficiency, central hypothyroidism, hypogonadism, and permanent diabetes insipidus. Six years later she was admitted for the suspicion of secondary adrenal insufficiency and thyrotoxicosis. Physical findings, laboratory data, thyroid ultrasound, and scintigraphy achieved the diagnosis of Graves' disease and hypocortisolism. She was treated with hydrocortisone and methimazole, but central hypothyroidism recurred after antithyroid drug withdrawal. Nine years after the diagnosis of a pituitary carcinoma, she maintains treatment with bromocriptine, has a locally stable disease, with no metastases. This report highlights an unusual presentation of a prolactin-producing pituitary carcinoma in a young female. The patient had multiple hormone deficiencies due to a pituitary lesion and treatments. The posterior development of hyperthyroidism and adrenal insufficiency brought an additional difficulty to the approach.

Childhood maltreatment and adult psychopathology: pathways to hypothalamic-pituitary-adrenal axis dysfunction

PubMed Central

Mello, Marcelo F.; Faria, Alvaro A.; Mello, Andrea F.; Carpenter, Linda L.; Tyrka, Audrey R.; Price, Lawrence H.

2015-01-01

Objective The aim of this paper was to examine the relationship between childhood maltreatment and adult psychopathology, as reflected in hypothalamic-pituitary-adrenal axis dysfunction. Method A selective review of the relevant literature was undertaken in order to identify key and illustrative research findings. Results There is now a substantial body of preclinical and clinical evidence derived from a variety of experimental paradigms showing how early-life stress is related to hypothalamic-pituitary-adrenal axis function and psychological state in adulthood, and how that relationship can be modulated by other factors. Discussion The risk for adult psychopathology and hypothalamic-pituitary-adrenal axis dysfunction is related to a complex interaction among multiple experiential factors, as well as to susceptibility genes that interact with those factors. Although acute hypothalamic-pituitary-adrenal axis responses to stress are generally adaptive, excessive responses can lead to deleterious effects. Early-life stress alters hypothalamic-pituitary-adrenal axis function and behavior, but the pattern of hypothalamic-pituitary-adrenal dysfunction and psychological outcome in adulthood reflect both the characteristics of the stressor and other modifying factors. Conclusion Research to date has identified multiple determinants of the hypothalamic-pituitary-adrenal axis dysfunction seen in adults with a history of childhood maltreatment or other early-life stress. Further work is needed to establish whether hypothalamic-pituitary-adrenal axis abnormalities in this context can be used to develop risk endophenotypes for psychiatric and physical illnesses. PMID:19967199

A diagnostic pitfall in IgG4-related hypophysitis: infiltration of IgG4-positive cells in the pituitary of granulomatosis with polyangiitis.

PubMed

Bando, Hironori; Iguchi, Genzo; Fukuoka, Hidenori; Taniguchi, Masaaki; Kawano, Seiji; Saitoh, Miki; Yoshida, Kenichi; Matsumoto, Ryusaku; Suda, Kentaro; Nishizawa, Hitoshi; Takahashi, Michiko; Morinobu, Akio; Kohmura, Eiji; Ogawa, Wataru; Takahashi, Yutaka

2015-10-01

Immunoglobulin (Ig) G4-related hypophysitis is an emerging clinical entity, which is characterized by an elevated serum IgG4 concentration and infiltration of IgG4-positive plasma cells in the pituitary. Although some criteria for its diagnosis have been proposed, they have not been fully established. In particular, differential diagnosis from secondary chronic inflammation including granulomatosis with polyangiitis (GPA) is difficult in some cases. We describe central diabetes insipidus with pituitary swelling exhibiting infiltration of IgG4-positive cells. A 43-year-old woman in the remission stage of GPA presented with sudden-onset polyuria and polydipsia. Pituitary magnetic resonance imaging revealed swelling of the anterior and posterior pituitary and stalk, with heterogeneous gadolinium enhancement and disappearance of the high signal intensity of the posterior pituitary. Evaluation of biochemical markers for GPA suggested that the disease activity was well-controlled. Endocrinological examination revealed the presence of central diabetes insipidus and growth hormone deficiency. Pituitary biopsy specimen showed IgG4-positive cells, with a 43% IgG4(+)/IgG(+) ratio, which met the criteria for IgG4-related hypophysitis. However, substantial infiltration of polymorphonuclear neutrophils with giant cells was also noted, resulting in a final diagnosis of pituitary involvement of GPA. These results suggest that pituitary involvement of GPA should be taken into account for the differential diagnosis of IgG4-related hypophysitis.

Investigation of pituitary functions in patients with acute meningitis: a pilot study.

PubMed

Tanriverdi, F; Alp, E; Demiraslan, H; Dokmetas, H S; Unluhizarci, K; Doganay, M; Casanueva, F F; Kelestimur, F

2008-06-01

Although long-term pituitary consequences of tuberculous meningitis are well documented in the literature, there have been few case reports of pituitary dysfunction after acute bacterial or viral meningitis. In this preliminary study, we have assessed the pituitary functions in adult patients who had acute bacterial or viral meningitis. Fourteen patients (8 men, 6 women; mean age 35.3+/-13.3) were included in the study. The diagnosis of bacterial and viral meningitis was proven by clinical findings, cerebrospinal fluid (CSF) examination, gram staining, and blood and CSF cultures. Pituitary functions were evaluated ranging from 6 to 48 months (mean 20 months) after acute meningitis. GH deficiency was investigated by the GHRH+arginine stimulation test. Four of 14 patients (28.6%) had isolated GH deficiency. In GH-deficient patients, the earliest duration was 6 months and the latest duration was 48 months after the diagnosis of acute meningitis. Three of the GH-deficient patients had acute bacterial meningitis and 1 patient had acute viral meningitis. Pituitary magnetic resonance imaging revealed normal pituitary gland in the patients with GH deficiency. This is the first systematic study evaluating the anterior pituitary function long term after the diagnosis of acute meningitis. Based on the present study, it is tempting to speculate that pituitary dysfunction is a more common sequel of acute bacterial or viral meningitis than hitherto reported. Studies with high numbers of patients are warranted to ascertain the prevalence of meningitis-induced hypopituitarism.

GH and Pituitary Hormone Alterations After Traumatic Brain Injury.

PubMed

Karaca, Züleyha; Tanrıverdi, Fatih; Ünlühızarcı, Kürşad; Kelestimur, Fahrettin

2016-01-01

Traumatic brain injury (TBI) is a crucially important public health problem around the world, which gives rise to increased mortality and is the leading cause of physical and psychological disability in young adults, in particular. Pituitary dysfunction due to TBI was first described 95 years ago. However, until recently, only a few papers have been published in the literature and for this reason, TBI-induced hypopituitarism has been neglected for a long time. Recent studies have revealed that TBI is one of the leading causes of hypopituitarism. TBI which causes hypopituitarism may be characterized by a single head injury such as from a traffic accident or by chronic repetitive head trauma as seen in combative sports including boxing, kickboxing, and football. Vascular damage, hypoxic insult, direct trauma, genetic predisposition, autoimmunity, and neuroinflammatory changes may have a role in the development of hypopituitarism after TBI. Because of the exceptional structure of the hypothalamo-pituitary vasculature and the special anatomic location of anterior pituitary cells, GH is the most commonly lost hormone after TBI, and the frequency of isolated GHD is considerably high. TBI-induced pituitary dysfunction remains undiagnosed and therefore untreated in most patients because of the nonspecific and subtle clinical manifestations of hypopituitarism. Treatment of TBI-induced hypopituitarism depends on the deficient anterior pituitary hormones. GH replacement therapy has some beneficial effects on metabolic parameters and neurocognitive dysfunction. Patients with TBI without neuroendocrine changes and those with TBI-induced hypopituitarism share the same clinical manifestations, such as attention deficits, impulsion impairment, depression, sleep abnormalities, and cognitive disorders. For this reason, TBI-induced hypopituitarism may be neglected in TBI victims and it would be expected that underlying hypopituitarism would aggravate the clinical picture of TBI itself. Therefore, the diagnosis and treatment of unrecognized hypopituitarism due to TBI are very important not only to decrease morbidity and mortality due to hypopituitarism but also to alleviate the chronic sequelae caused by TBI. Copyright © 2016 Elsevier Inc. All rights reserved.

Cystic tumors of the pituitary infundibulum: seminal autopsy specimens (1899 to 1904) that allowed clinical-pathological craniopharyngioma characterization.

PubMed

Pascual, José M; Prieto, Ruth; Rosdolsky, Maria; Strauss, Sewan; Castro-Dufourny, Inés; Hofecker, Verena; Winter, Eduard; Carrasco, Rodrigo; Ulrich, Walter

2018-04-21

A heterogeneous group of epithelial cystic tumors developed at the infundibulum and the third ventricle disconcerted pathologists at the dawn of the twentieth century. Very little was known at that time about the physiological role played by the pituitary gland, and there was almost complete ignorance regarding the function of the hypothalamus. Acromegaly, or enlargement of acral body parts, described in 1886 by Pierre Marie, was the only disease linked to primary hypertrophies of the pituitary gland, known as "pituitary strumas". A growing number of young patients manifesting an unexplained combination of physical and mental symptoms, including absent or delayed sexual maturation, progressive obesity, abnormal somnolence, and dementia-like changes in behavior were reported to present large solid-cystic tumors which characteristically expanded within the infundibulum and third ventricle, above an anatomically intact pituitary gland. Between 1899 and 1904, five seminal autopsy studies from different countries thoroughly described the anatomical relationships and histological features of this newly recognized type of infundibular tumors. These cases were instrumental in fostering the systematic investigation of similar lesions by the Austrian pathologist Jakob Erdheim (1874-1937), who in 1904 was able to classify these infundibulo-tuberal cysts under the common category of hypophyseal duct tumors. The pioneering American neurosurgeon Harvey Cushing (1869-1939) unsuccessfully attempted to surgically remove one of these cysts, for the first time in history, in 1902. The term "craniopharyngioma", chosen by Cushing in 1929 to designate these lesions, would eventually prevail over Erdheim's more accurate denomination, which linked their origin to squamous cell remnants derived from the embryological structures that give rise to the pituitary gland. This paper presents a comprehensive, renewed account of the five clinical-pathological reports which laid the groundwork for the proper clinical diagnosis, topographic conceptualization and pathological categorization of craniopharyngiomas.

21 CFR 862.1625 - Prolactin (lactogen) test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test... anterior pituitary gland or of the hypothalamus portion of the brain. (b) Classification. Class I (general...

Surgical biopsies in patients with central diabetes insipidus and thickened pituitary stalks.

PubMed

Jian, Fangfang; Bian, Liuguan; Sun, Shouyue; Yang, Jun; Chen, Xiao; Chen, Yufan; Ma, Qinyun; Miao, Fei; Wang, Weiqing; Ning, Guang; Sun, Qingfang

2014-09-01

Thickened pituitary stalks (TPSs) on magnetic resonance imaging (MRI) result from diverse pathologies; therefore, it is essential to make specific diagnoses for clinical decision-making. The diagnoses and indications for surgical biopsies in patients with central diabetes insipidus (CDI) and TPSs are thoroughly discussed in this paper. Thirty-seven patients with CDI and TPSs were retrospectively reviewed. The mean age at the diagnosis of CDI was 29.0 ± 15.9 years (range 8.0-63.3), and the median duration of follow-up was 5.5 ± 2.8 years (range 0.7-13.0). Anterior pituitary hormone deficiencies were documented in 26 (70.3 %) patients. All patients had a TPS on MRI at the diagnosis of CDI, and 21 (56.8 %) patients exhibited radiological changes during the follow-up. Of these 21 patients, 11 exhibited increases in the thickness of the stalk, and two patients exhibited reversals of the TPSs. Involvements of the hypothalamus, pituitary gland, basal ganglia or supersellar, and pineal gland were found in four, three, one, and 1 patient, respectively. Ultimately, clear diagnoses were established in 17 patients who underwent biopsies, nine of whom had germinomas, six of whom had Langerhans cell histiocytosis, one of whom had a granular cell tumor, and one of whom had Erdheim-Chester disease. Patients with CDI and TPSs should submit to periodic clinic follow-ups with serial MRI assessments to establish anterior pituitary deficiencies and to detect radiological progressions that are appropriate for surgical biopsies. Endoscopic-assisted microsurgery via the supraorbital keyhole approach is a good choice for the biopsy of pituitary stalk lesions.

Clinical Investigation of Adrenal Incidentalomas in Japanese Patients of the Fukuoka Region with Updated Diagnostic Criteria for Sub-clinical Cushing's Syndrome.

PubMed

Abe, Ichiro; Sugimoto, Kaoru; Miyajima, Tetsumasa; Ide, Tomoko; Minezaki, Midori; Takeshita, Kaori; Takahara, Saori; Nakagawa, Midori; Fujimura, Yuki; Kudo, Tadachika; Miyajima, Shigero; Taira, Hiroshi; Ohe, Kenji; Ishii, Tatsu; Yanase, Toshihiko; Kobayashi, Kunihisa

2018-04-27

Objectives We retrospectively investigated the clinical and endocrinological characteristics of adrenal incidentalomas. Methods We studied 61 patients who had been diagnosed with adrenal incidentalomas and had undergone detailed clinical and endocrinological evaluations while hospitalized. We used common criteria to diagnose the functional tumors, but for sub-clinical Cushing's syndrome, we used an updated set of diagnosis criteria: serum cortisol ≥1.8 μg/dL after a positive response to a 1-mg dexamethasone suppression test if the patient has a low morning ACTH level (<10 pg/mL) and a loss of the diurnal serum cortisol rhythm. Results Of the 61 patients, none (0%) had malignant tumors, 8 (13.1%) had pheochromocytoma, and 15 (24.6%) had primary aldosteronism; when diagnosed by our revised criteria, 13 (21.3%) had cortisol-secreting adenomas (Cushing's syndrome and sub-clinical Cushing's syndrome), and 25 (41.0%) had non-functional tumors. Compared with the non-functional tumor group, the primary aldosteronism group and the cortisol-secreting adenoma group were significantly younger and had significantly lower rates of hypokalemia, whereas the pheochromocytoma group had significantly larger tumors and a significantly lower body mass index. Conclusion Our study found a larger percentage of functional tumors among adrenal incidentalomas than past reports, partly because we used a lower serum cortisol level after a dexamethasone suppression test to diagnose sub-clinical Cushing's syndrome and because all of the patients were hospitalized and could therefore receive more detailed examinations. Young patients with hypokalemia or lean patients with large adrenal tumors warrant particularly careful investigation.

Effects of active acromegaly on bone mRNA and microRNA expression patterns.

PubMed

Belaya, Zhanna; Grebennikova, Tatiana; Melnichenko, Galina; Nikitin, Alexey; Solodovnikov, Alexander; Brovkina, Olga; Grigoriev, Andrey; Rozhinskaya, Liudmila; Lutsenko, Alexander; Dedov, Ivan

2018-04-01

To evaluate the response of bone to chronic long-term growth hormone (GH) and insulin-like growth factor-1 (IGF1) excess by measuring the expression of selected mRNA and microRNA (miR) in bone tissue samples of patients with active acromegaly. Case-control study. Bone tissue samples were obtained during transsphenoidal adenomectomy from the sphenoid bone (sella turcica) from 14 patients with clinically and biochemically confirmed acromegaly and 10 patients with clinically non-functioning pituitary adenoma (NFPA) matched by sex and age. Expression of genes involved in the regulation of bone remodeling was studied using quantitative polymerase chain reaction (qPCR). Of the genes involved in osteoblast and osteoclast activity, only alkaline phosphatase (ALP) mRNA was 50% downregulated in patients with acromegaly. GH excess caused increased expression of the Wnt signaling antagonists ( DKK1) and agonists ( WNT10B) and changes in the levels of miR involved in mesenchymal stem cell commitment to chondrocytes (miR-199a-5p) or adipocytes (miR-27-5p, miR-125b-5p, miR-34a-5p, miR-188-3p) P  < 0.05; q  < 0.1. Relevant compensatory mechanisms were found through the changes in miR involved in osteoblastogenesis (miR-210-5p, miR-135a-5p, miR-211, miR-23a-3p, miR-204-5p), but the expression of TWIST1 was 50% downregulated and RUNX2 was unchanged. Acromegaly had minimal effects on tested mRNAs specific to osteoblast or osteoclast function except for downregulated ALP expression. The expressions of miR known to be involved in mesenchymal stem cell commitment and downregulated TWIST1 expression suggest acromegaly has a negative effect on osteoblastogenesis. © 2018 European Society of Endocrinology.

Assessment of Diverse Biological Indicators in Gulf War Illness: Are They Replicable Are They Related

DTIC Science & Technology

2016-04-01

compared to 50 healthy veteran controls in a protocol that includes physical and neuropsychological evaluations, neuroimaging (MRI, fMRI, DTI), adrenal...SUBJECT TERMS Gulf War illness, neuroimaging, neuropsychological testing, immune function, hypothalamic-pituitary-adrenal testing 16. SECURITY... neuropsychological evaluations, assessment of hypothalamic-pituitary-adrenal function, standard clinical diagnostic laboratory tests, and research

Case report of recurrent atrial fibrillation induced by thyrotropin-secreting pituitary adenoma with Graves' disease.

PubMed

Li, Jiaqi; Tan, Huiwen; Huang, Juan; Luo, Dan; Tang, Ying; Yu, Ruichao; Huang, Hui

2018-06-01

Thyrotropin-secreting adenoma (TSHoma) is rare. Even though the thyrotoxicosis is mild in patients with TSHoma, it is still a rare cause of arrhythmia, ignore of mild disfunction of thyroid function of TSHoma can lead to the delayed diagnosis of pituitary tumor or leading to recurring of complications. Graves' disease is an auto-immue endocrinological disorder. Association of TSHoma and Graves's disease is extremely rare. Coexistence of these two diseases made the diagnosis and treatment complicated. This patient was a 55-year-old man who had been referred to the department of endocrinology and metabolism of the West China Hospital due to recurrent atrial fibrillation (AF) and thyroxicosis. Examinations revealed pituitary thyrotropin-secreting macroadenoma with Graves' disease. We conducted transsphenoidal surgery. Thyrozol was used to treat the recurrence of Graves' disease after pituitary surgery. The TSHoma was successfully cured, and recurrent Graves' disease was controlled very well. The association of TSHoma and Graves' disease is extremely rare. Even though the clinical features of thyrotoxicosis are milder in patients with TSHoma, thyroid function tests are still important clinical assessment of patients with AF, which is an arrhythmia associated with hyperthyroidism. TSHoma is a rare cause of thyrotoxicosis; however, ignoring of the mild disfunction caused by TSHoma can lead to the delayed diagnosis of pituitary tumors or to recurring of complications of TSHoma.

Esthetic Outcomes of Immediately Loaded Locking Taper Implants in the Anterior Maxilla: A Case Series Study.

PubMed

Lombardo, Giorgio; Corrocher, Giovanni; Pighi, Jacopo; Mascellaro, Anna; Marincola, Mauro; Nocini, Per Francesco

2016-06-01

The purpose of this study was to evaluate the esthetic outcome of single-tooth locking taper connection implants placed in the anterior maxilla following a postextractive nonfunctional loading protocol. This preliminary clinical study involving 16 patients evaluated the results of 21 implants placed in areas with high esthetic value. For each implant the pink esthetic score, white esthetic score, cumulative survival rate, and health status of peri-implant tissues were evaluated. The cumulative survival rate was 100% 2 years after prosthetic loading, and the mean total pink esthetic score/white esthetic score was 16.9 ± 1.14 on a maximum value of 20. There was excellent plaque control in all patients, and inflammation indices were within the norm. Within the limits of this study, this immediate nonfunctional loading protocol seems to be a successful procedure esthetically and for the maintenance of peri-implant soft tissues.

[Identification and management of intra-operative suspicious tissues in 20 transsphenoidal surgery cases].

PubMed

Liu, Jun-Feng; Ke, Chang-Shu; Chen, Xi; Xu, Yu; Zhang, Hua-Qiu; Chen, Juan; Gan, Chao; Li, Chao-Xi; Lei, Ting

2013-05-01

To determine appropriate protocols for the identification and management of intra operative suspicious tissues during transsphenoidal surgery. Clinical data and pathological reports of 20 patients with intra-operative suspicious tissues during transsphenoidal surgeries were analyzed retrospectively. The methods for discriminating between adenoma and normal pituitary tissues were reviewed. The postoperative pathological reports revealed that adenoma and normal pituitary tissues coexisted in 9 samples, while 5 samples were identified as normal pituitary tissues, 2 as adenoma tissues, and 4 as other tissues. Adenomas were distinguished from normal pituitary tissues on the basis of intra-operative appearance, texture, blood supply and possible existence of boundary. If decisions are difficult to made during surgeries from the appearance of the suspicious tissues, pathological examinations are advised as a guidance for the next steps.

Pituitary Microsomal Autoantibodies in Patients with Childhood-Onset Combined Pituitary Hormone Deficiency: an Antigen Identification Attempt.

PubMed

Ziemnicka, Katarzyna; Gut, Paweł; Gołąb, Monika; Dworacki, Grzegorz; Wrotkowska, Elżbieta; Stajgis, Marek; Katulska, Katarzyna; Rabska-Pietrzak, Barbara; Obara-Moszyńska, Monika; Niedziela, Marek; Budny, Bartłomiej; Kałużna, Małgorzata; Waśko, Ryszard; Ruchała, Marek

2016-12-01

The role of autoimmunization in the pathogenesis of pituitary disorders is poorly understood. The presence of pituitary autoantibodies (APA) has been detected in various pituitary disorders. Their role, however, remains elusive. Childhood-onset combined pituitary hormone deficiency (CPHD) may be caused by environmental or genetic factors. In some of patients, causes of the disease remain unclear and contributions of autoimmune processes have been postulated. The aim of this study was to identify the microsomes-derived pituitary antigens (MPA) as potential immunogenic autoantigens in patients with hypopituitarism, therefore 62 CPHD patients, 100 healthy controls and five autoimmune polyglandular syndrome type II (APS II) patients were included in the study. The clinical evaluation included hormonal tests and magnetic resonance imaging of the pituitary. The sources of MPA were pituitary glands taken from autopsies. Isolated MPA were then separated on SDS-PAGE gel and incubated with sera obtained from patients and controls. Microsomal APA were detected using Western blot and radioimmunological method. In all CPHD and APS II patients and in 9 % individuals from control group marked immunoreactivity was detected against MPA. Antibodies showed high affinity to 67, 60, 50 and 36 kDa MPAs. Since the identified autoantigens were of unknown nature, an in silico exploration of UniProt database was applied and indicated their possible relationship with chaperones, golgins and already known autoantigens like GAD67. Reactivity against MPA indicates that these proteins certainly play a role in the processes undergoing within pituitary of CPHD patients. The identification and further detailed studies on their role in the pathogenesis of CPHD should be continued.

Acute Sheehan's syndrome presenting as central diabetes insipidus.

PubMed

Robalo, Raquel; Pedroso, Célia; Agapito, Ana; Borges, Augusta

2012-11-06

Sheehan's syndrome occurs as a result of ischaemic pituitary necrosis due to severe postpartum haemorrhage. Improvements in obstetrical care have significantly reduced its incidence in developed countries, but postpartum pituitary infarction remains a common cause of hypopituitarism in developing countries. We report a case of severe postpartum haemorrhage followed by headache, central diabetes insipidus and failure to lactate, which prompted us to investigate and identify both anterior and posterior pituitary deficiency compatible with Sheehan's syndrome. A timely diagnosis allowed us to implement an adequate treatment and follow-up plan, which are known to improve clinical status and patient outcome.

Two coexisting heterozygous frameshift mutations in PROP1 are responsible for a different phenotype of combined pituitary hormone deficiency.

PubMed

Ziemnicka, K; Budny, B; Drobnik, K; Baszko-Błaszyk, D; Stajgis, M; Katulska, K; Waśko, R; Wrotkowska, E; Słomski, R; Ruchała, M

2016-08-01

The role of genetic background in childhood-onset combined pituitary hormone deficiency (CPHD) has been extensively studied. The major contributors are the PROP1, POU1F1, LHX3, LHX4 and HESX1 genes coding transcription factors implicated in pituitary organogenesis. The clinical consequences of mutations encompass impaired synthesis of a growth hormone (GH) and one or more concurrent pituitary hormones (i.e. LH, FSH, TSH, PRL). Manifestation of the disorder may vary due to various mutation impacts on the final gene products or an influence of environmental factors during pituitary organogenesis. We describe the clinical and molecular characteristics of two brothers aged 47 and 39 years presenting an uncommon manifestation of congenital hypopituitarism. Sequencing of the PROP1, POU1F1, LHX3, LHX4 and HESX1 genes was performed to confirm the genetic origin of the disorder. A compound heterozygosity in the PROP1 gene has been identified for both probands. The first change represents a mutational hot spot (c.150delA, p.R53fsX164), whereas the second is a novel alteration (p.R112X) that leads to protein disruption. Based on precise genetic diagnosis, an in silico prediction of a p.R112X mutation on protein architecture was performed. The resulting clinical phenotype was surprisingly distinct compared to most patients with genetic alterations in PROP1 reported in the current literature. This may be caused by a residual activity of a newly identified p.R112X protein that preserves over 70 % of the homeodomain structure. This examination may confirm a key role of a DNA-binding homeodomain in maintaining PROP1 functionality and suggests a conceivable explanation of an unusual phenotype.

Sellar reconstruction without intrasellar packing after endoscopic surgery of pituitary macroadenomas is better than its reputation.

PubMed

Ismail, Mostafa; Fares, Abd Alla; Abdelhak, Balegh; D'Haens, Jean; Michel, Olaf

2016-01-01

Sellar reconstruction with intrasellar packing following endoscopic resection of pituitary macroadenomas remains a subject of clinical and radiological discussion particularly, when an intraoperative cerebrospinal fluid (CSF) leakage is absent. This study was conducted to contribute our experience with sellar reconstruction after a standard endoscopic surgery of pituitary macroadenomas without intraoperative CSF leakage to the ongoing discussion between techniques with and without intrasellar packing. A consecutive series of 47 pituitary macroadenomas undergoing excision via a standard endoscopic endonasal transsphenoidal surgery (EETS) without evident intraoperative CSF leakage were retrospectively evaluated over a 10-months mean follow-up period. According to the sellar reconstruction technique, three groups could be identified: Group A - with no intrasellar packing, Group B - with haemostatic materials packing, and Group C - with abdominal fat packing. Postoperative clinical and radiological assessments of the three groups were documented and analyzed for differences in outcome. Postoperative clinical assessment did not differ significantly between the three groups. In group A, postoperative CSF leakage, sphenoid sinusitis and empty sella syndrome were not observed. However, a significant difference in radiological assessment could be identified; the interpretation of sellar contents in postoperative MRI of group A succeeded earlier and more reliably than in other groups with intrasellar packing. There is no difference in the incidence of postoperative CSF leakage and empty sella syndrome among the various reconstructive techniques with and without intrasellar packing, irrespective of size and extension of the pituitary adenoma. Sellar reconstruction without intrasellar packing following a standard EETS is not inferior to other techniques with packing and even shows more radiological advantages, which made it our preferred technique, at least if no intraoperative CSF leakage is evident.

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

PubMed Central

Yakoushina, Tatiana V.; Lavi, Ehud; Hoda, R. S.

2010-01-01

Pituitary carcinoma (PC) is a very rare entity (0.2% of all pituitary tumors), with only about 140 cases reported in English literature. There are no reliable histological, immunohistochemical or ultrastructural features distinguishing pituitary adenoma (PA) from PC. By definition, a diagnosis of PC is made after a patient with PA develops non-contiguous central nervous system (CNS) or systemic metastases. To date, only three cases of PC have been reportedly diagnosed on fine needle aspiration (FNA). Two of the reported cases were diagnosed on FNA of the cervical lymph nodes and one on FNA of the vertebral bone lesion. Herein, we present a case of PC, diagnosed on FNA of the liver lesion. In this case, we describe cytologic features of PC and compare them to histologic features of the tumor in the pituitary. Clinical behavior of tumor, pathogenesis of metastasis and immunochemical and prognostic markers will also be described. PMID:20806088

Impaired Pituitary Axes Following Traumatic Brain Injury

PubMed Central

Scranton, Robert A.; Baskin, David S.

2015-01-01

Pituitary dysfunction following traumatic brain injury (TBI) is significant and rarely considered by clinicians. This topic has received much more attention in the last decade. The incidence of post TBI anterior pituitary dysfunction is around 30% acutely, and declines to around 20% by one year. Growth hormone and gonadotrophic hormones are the most common deficiencies seen after traumatic brain injury, but also the most likely to spontaneously recover. The majority of deficiencies present within the first year, but extreme delayed presentation has been reported. Information on posterior pituitary dysfunction is less reliable ranging from 3%–40% incidence but prospective data suggests a rate around 5%. The mechanism, risk factors, natural history, and long-term effect of treatment are poorly defined in the literature and limited by a lack of standardization. Post TBI pituitary dysfunction is an entity to recognize with significant clinical relevance. Secondary hypoadrenalism, hypothyroidism and central diabetes insipidus should be treated acutely while deficiencies in growth and gonadotrophic hormones should be initially observed. PMID:26239686

Rare presentation of Wegener's granulomatosis in the pituitary gland: Case report and literature review.

PubMed

Baird, Samantha M; Pratap, Upasna; McLean, Catriona; Law, Candice P; Maartens, Nicholas

2017-01-01

Wegener's granulomatosis (WG) is a systemic vasculitis that can affect a variety of organs including ear, nose and throat, lungs and kidneys. However WG is unusual in the pituitary and rare in the central nervous system. A 56-year-old male with likely WG presented with polyuria and polydipsia despite six months of conservative medical management. MRI scanning revealed an enlarging heterogeneously enhancing pituitary gland. Following endoscopic transsphenoidal pituitary biopsy and debulking, final tissue pathology was diagnostic for WG in the pituitary gland. Diagnosis remains difficult but most patients present with central diabetes insipidus (CDI) as well as varying degrees of hypopituitarism on a background of disease activity in other organs. Clinical judgment needs to balance the need for invasive surgical tissue diagnosis with increasing immunosuppressive therapy. It is important to consider this rare complication of WG to ensure timely diagnosis and management. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Pathophysiology of the Effects of Alcohol Abuse on the Endocrine System.

PubMed

Rachdaoui, Nadia; Sarkar, Dipak K

2017-01-01

Alcohol can permeate virtually every organ and tissue in the body, resulting in tissue injury and organ dysfunction. Considerable evidence indicates that alcohol abuse results in clinical abnormalities of one of the body's most important systems, the endocrine system. This system ensures proper communication between various organs, also interfacing with the immune and nervous systems, and is essential for maintaining a constant internal environment. The endocrine system includes the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-gonadal axis, the hypothalamic-pituitary-thyroid axis, the hypothalamic-pituitary-growth hormone/insulin-like growth factor-1 axis, and the hypothalamic-posterior pituitary axis, as well as other sources of hormones, such as the endocrine pancreas and endocrine adipose tissue. Alcohol abuse disrupts all of these systems and causes hormonal disturbances that may result in various disorders, such as stress intolerance, reproductive dysfunction, thyroid problems, immune abnormalities, and psychological and behavioral disorders. Studies in both humans and animal models have helped shed light on alcohol's effects on various components of the endocrine system and their consequences.

VARIATIONS IN CLINICAL AND IMAGING FINDINGS BY TIME OF DIAGNOSIS IN FEMALES WITH HYPOPITUITARISM ATTRIBUTED TO LYMPHOCYTIC HYPOPHYSITIS.

PubMed

Tirosh, Amit; Hirsch, Dania; Robenshtok, Eyal; Masri-Iraqi, Hiba; Yoel, Uri; Toledano, Yoel; Twito, Orit; Tsvetov, Gloria; Shimon, Ilan

2016-04-01

To describe the various patterns of presentation, including assisting analyses, associated with the timing of diagnosis of females with hypopituitarism and suspected clinical diagnosis of lymphocytic hypophysitis. A retrospective study of 9 consecutive females with pituitary dysfunction developed during or after pregnancy. All subjects were treated in our clinics between 2008 and 2014. Data were collected on clinical characteristics, pituitary hormone levels, and imaging findings. The study group included 9 patients with a mean age 33.7 ± 7.8 years at delivery. The probable cause of disease was lymphocytic hypophysitis. Headache or specific symptoms/signs of hypopituitarism appeared within 1 year of delivery. Five patients had headache, and 8 had difficulty breastfeeding or amenorrhea. Laboratory findings included central hypocortisolism (8/9 patients), hypogonadotropic hypogonadism (8/9), and central hypothyroidism (6/7). Insulin-like growth factor-1 (IGF-1) levels were low in 8/8 patients. Prolactin levels were low in 3/9 patients, and 1 patient had diabetes insipidus. Seven patients were diagnosed less than 1 year from symptom onset; 4 (57%) complained of headaches, and 5 (71%) had panhypopituitarism. Two patients were diagnosed later. Both had difficulty breastfeeding and amenorrhea, and one also had headaches. Both had panhypopituitarism and reduced pituitary volume. None of the patients fully recovered pituitary function. Normalization of the thyrotroph axis occurred in 3 patients, gonadotroph function in 3, the corticotroph axis in 2, and IGF-1 normalized in 1 subject. Hypopituitarism attributed to lymphocytic hypophysitis may present during pregnancy or early postpartum period with a clear clinical picture, or later, with indolent and nonspecific symptoms and signs.

Relationship between pituitary stalk (PS) visibility and the severity of hormone deficiencies: PS interruption syndrome revisited.

PubMed

Wang, Weiqing; Wang, Shuwei; Jiang, Yiran; Yan, Fuhua; Su, Tingwei; Zhou, Weiwei; Jiang, Lei; Zhang, Yifei; Ning, Guang

2015-09-01

Pituitary stalk interruption syndrome (PSIS) is a rare cause of combined pituitary hormone deficiency characterized by a triad shown in pituitary imaging, yet it has never been evaluated due to the visibility of pituitary stalk (PS) in imaging findings. The major objective of the study was to systematically describe the disease including clinical presentations, imaging findings and to estimate the severity of anterior pituitary hormone deficiency based on the visibility of the PS. This was a retrospective study including 74 adult patients with PSIS in Shanghai Clinical Center for Endocrine and Metabolic Diseases between January 2010 and June 2014. Sixty had invisible PS according to the findings on MRI, while the rest had a thin or intersected PS. Basic characteristics and hormonal status were compared. Of the 74 patients with PSIS, age at diagnosis was 25 (22-28) years. Absent pubertal development (97·3%) was the most common presenting symptom, followed by short stature. Insulin tolerance test (ITT) and gonadotrophin-releasing hormone (GnRH) stimulation test were used to evaluate the function of anterior pituitary. The prevalence of isolated deficiency in growth hormone (GH), gonadotrophins, corticotrophin and thyrotrophin were 100%, 97·2%, 88·2% and 70·3%, respectively. Although the ratio of each deficiency did not vary between patients with invisible PS and with visible PS, panhypopituitarism occurred significantly more frequent in patients with invisible PS. Patients with invisible PS had significantly lower levels of luteinizing hormone (LH), follicle stimulation hormone (FSH) and hormones from targeted glands including morning cortisol, 24-h urine free cortisol, free triiodothyronine (FT3), free thyroxine (FT4) and testosterone (T) in male than patients with visible PS. Moreover, patients with invisible PS had lower peak LH and FSH in GnRH stimulation test, and higher peak cortisol in ITT while peak GH remained unchanged between two groups. The prevalence of multiple anterior pituitary hormone deficiency was high in adult patients with PSIS. And more importantly, we found the visibility of PS shown on MRI might be an indication of the severity of PSIS. © 2015 John Wiley & Sons Ltd.

Radiotherapy-induced hypopituitarism: a review.

PubMed

Sathyapalan, Thozhukat; Dixit, Sanjay

2012-05-01

Hypopituitarism is a disorder caused by impaired hormonal secretions from the hypothalamic-pituitary axis. Radiotherapy is the most common cause of iatrogenic hypopituitarism. The hypothalamic-pituitary axis inadvertently gets irradiated in patients receiving prophylactic cranial radiotherapy for leukemia, total body irradiation and radiotherapy for intracranial, base skull, sinonasal and nasopharyngeal tumors. Radiation-induced hypopituitarism (RIH) is insidious, progressive and largely nonreversible. Mostly, RIH involves one hypothalamic-pituitary axis; however, multiple hormonal axes deficiency starts developing at higher doses. Although the clinical effects of the hypopituitarism are more profound in children and young adults, its implications in older adults are being increasingly recognized. The risk continues to persist or increase up to 10 years following radiation exposure. The clinical management of hypopituitarism is challenging both for the patients and healthcare providers. Here we have reviewed the scale of the problem, the risk factors and the management of RIH.

[Panhypopituitarism caused by an intrasellar cystic mass in late-onset hypogonadism clinic].

PubMed

Yamamoto, Yoshiyuki; Takada, Shingo; Kinjo, Takanori; Nonomura, Daichi; Yoneda, Suguru; Nomura, Hironori; Tei, Norihide; Matsumiya, Kiyomi; Okusu, Takahiro

2013-10-01

A 74-year-old man who was referred to our late onset hypogonadism clinic presented with sweating and loss of appetite. His aging males' symptoms (AMS) and international index of erectile function (IIEF-5) scores were 59 and 2, respectively. His hormonal examination revealed extremely low free testosterone values. The patient was started on androgen replacement therapy, but his symptoms did not improve. Additional hormonal examinations revealed low values for other anterior pituitary hormones. Magnetic resonance imaging revealed an intrasellar cystic mass with suprasellar extension. We considered this mass caused hypothalamic hypopituitarism. A load test for anterior pituitary hormones revealed panhypogonadism. His symptoms improved after administration of adrenal and thyroid hormones and androgen. Five months after start of drug administration, his AMS score improved to 29, but IIEF-5 score showed little change. As a matter of course, not only androgen but all pituitary-related hormones are needed for hypopituitarism patients.

Sellar Region Surgery in Croatia in the First Half of 20th Century

PubMed Central

Fatović Ferenčić, Stella; Gnjidić, Živko

2006-01-01

We reconstructed the historical development of surgical approaches to the pituitary gland, which were used in Croatia in the first half of the 20th century, on the basis of earliest clinical case reports and descriptions of initial surgical attempts. The first published case report on surgical treatment of acromegaly was described, as well as the review of 11 patients with pituitary disease admitted to the Ophthalmology Clinic in Zagreb in the period 1925-1927. The earliest 5 reports on pituitary surgery dating from 1925 were analyzed to reveal the circumstances that led to the development of transsphenoidal approach as a method of choice in Croatia, when this technique was becoming obsolete in other parts of the world. Frequent modifications of surgical approaches to sellar region have been shown a suitable historical-medical model for analysis of changes in surgical trends. PMID:16625698

Neuroendocrine abnormalities in patients with traumatic brain injury

NASA Technical Reports Server (NTRS)

Yuan, X. Q.; Wade, C. E.

1991-01-01

This article provides an overview of hypothalamic and pituitary alterations in brain trauma, including the incidence of hypothalamic-pituitary damage, injury mechanisms, features of the hypothalamic-pituitary defects, and major hypothalamic-pituitary disturbances in brain trauma. While hypothalamic-pituitary lesions have been commonly described at postmortem examination, only a limited number of clinical cases of traumatic hypothalamic-pituitary dysfunction have been reported, probably because head injury of sufficient severity to cause hypothalamic and pituitary damage usually leads to early death. With the improvement in rescue measures, an increasing number of severely head-injured patients with hypothalamic-pituitary dysfunction will survive to be seen by clinicians. Patterns of endocrine abnormalities following brain trauma vary depending on whether the injury site is in the hypothalamus, the anterior or posterior pituitary, or the upper or lower portion of the pituitary stalk. Injury predominantly to the hypothalamus can produce dissociated ACTH-cortisol levels with no response to insulin-induced hypoglycemia and a limited or failed metopirone test, hypothyroxinemia with a preserved thyroid-stimulating hormone response to thyrotropin-releasing hormone, low gonadotropin levels with a normal response to gonadotropin-releasing hormone, a variable growth hormone (GH) level with a paradoxical rise in GH after glucose loading, hyperprolactinemia, the syndrome of inappropriate ADH secretion (SIADH), temporary or permanent diabetes insipidus (DI), disturbed glucose metabolism, and loss of body temperature control. Severe damage to the lower pituitary stalk or anterior lobe can cause low basal levels of all anterior pituitary hormones and eliminate responses to their releasing factors. Only a few cases showed typical features of hypothalamic or pituitary dysfunction. Most severe injuries are sufficient to damage both structures and produce a mixed endocrine picture. Increased intracranial pressure, which releases vasopressin by altering normal hypothalamic anatomy, may represent a unique type of stress to neuroendocrine systems and may contribute to adrenal secretion by a mechanism that requires intact brainstem function. Endocrine function should be monitored in brain-injured patients with basilar skull fractures and protracted posttraumatic amnesia, and patients with SIADH or DI should be closely monitored for other endocrine abnormalities.

Neuropsychiatric Manifestations in a Patient with Panhypopituitarism

PubMed Central

Jeyakumar, Ajouka; Balakumar, Thyarapan; Raghu, Alyssa; Chang, Katherine I.; Soewono, Katarina; Gustave, Mario; Jolayemi, Ayodeji

2017-01-01

We present a case of an incidental diagnosis of panhypopituitarism in a 68-year-old African American man admitted to our psychiatric inpatient unit with symptoms suggestive of schizophrenia. The case was unusual as a first-episode psychosis given the patient's age. In the course of his admission, the patient's clinical condition deteriorated culminating in a sudden altered mental status which prompted a transfer to the medical floors and further investigations. A head CT scan and a pituitary MRI revealed a near total resection of the pituitary while laboratory investigations revealed hyponatremia and a grossly low hormone profile. The progression of these events casts doubts on our admitting diagnosis as the primary cause of the patient's symptoms. The patient's clinical condition improved only when his endocrinopathy was treated with hormone replacement, fluids, and electrolyte correction in addition to antipsychotics. An inability to verify the patient's psychiatric history and a remote history of pituitary resection several decades earlier, unknown to the treating team, added to the diagnostic conundrum. We revised the diagnosis to neuropsychiatric manifestations secondary to an organic brain syndrome due to a partial pituitary resection. The patient was discharged with no symptoms of psychosis, good insight, judgment, and good reality testing. PMID:28567321

Neuropsychiatric Manifestations in a Patient with Panhypopituitarism.

PubMed

Jegede, Oluwole; Jeyakumar, Ajouka; Balakumar, Thyarapan; Raghu, Alyssa; Chang, Katherine I; Soewono, Katarina; Gustave, Mario; Jolayemi, Ayodeji

2017-01-01

We present a case of an incidental diagnosis of panhypopituitarism in a 68-year-old African American man admitted to our psychiatric inpatient unit with symptoms suggestive of schizophrenia. The case was unusual as a first-episode psychosis given the patient's age. In the course of his admission, the patient's clinical condition deteriorated culminating in a sudden altered mental status which prompted a transfer to the medical floors and further investigations. A head CT scan and a pituitary MRI revealed a near total resection of the pituitary while laboratory investigations revealed hyponatremia and a grossly low hormone profile. The progression of these events casts doubts on our admitting diagnosis as the primary cause of the patient's symptoms. The patient's clinical condition improved only when his endocrinopathy was treated with hormone replacement, fluids, and electrolyte correction in addition to antipsychotics. An inability to verify the patient's psychiatric history and a remote history of pituitary resection several decades earlier, unknown to the treating team, added to the diagnostic conundrum. We revised the diagnosis to neuropsychiatric manifestations secondary to an organic brain syndrome due to a partial pituitary resection. The patient was discharged with no symptoms of psychosis, good insight, judgment, and good reality testing.

The pituitary gland in patients with Langerhans cell histiocytosis: a clinical and radiological evaluation.

PubMed

Kurtulmus, Neslihan; Mert, Meral; Tanakol, Refik; Yarman, Sema

2015-04-01

Langerhans cell histiocytosis (LCH) is a rare disease in which the most common endocrine manifestation is diabetes insipidus (DI). Data on anterior pituitary function in patients with LCH are limited. Thus, the present study investigated anterior pituitary function in LCH patients with DI via the evaluation of clinical and radiological findings at disease onset and during follow-up. The present study retrospectively evaluated nine patients with LCH (five males and four females). All diagnoses of LCH were made following histological and/or immunophenotypic analyses of tissue biopsies, bronchoalveolar lavage, or cerebrospinal fluid (CSF). Basal and, if necessary, dynamic pituitary function tests were used to assess anterior pituitary function, and magnetic resonance imaging (MRI) scans were used to image the pituitary. The LCH treatment modality was based on organ involvement. The mean age at onset of DI was 27.6 years (range 15-60 years). One patient (11%) exhibited single organ involvement, while eight patients (89%) displayed multisystem organ involvement. On admittance, one patient had hypogonadotropic hypogonadism, one patient exhibited panhypopituitarism [hypogonadotropic hypogonadism, central hypothyroidism, hypocortisolism, and growth hormone (GH) deficiency], and four patients (44%) displayed hyperprolactinemia. The MRI data revealed infundibular enlargement in seven patients (78%), a thalamic mass in one patient (11%), and the absence of the bright spot in all patients. A single patient (11%) showed a mass in the pons that had a partially empty sella. The patients were treated with radiation therapy (RT), chemotherapy (CT), or a combination of both (RT+CT) and were followed up for a median of 91.8 months (range 2-318 months). Seven patients were assessed during the follow-up period, of whom four patients (57.1%) developed anterior pituitary hormone deficiency, three (43%) were diagnosed with GH deficiency, and one (14%) exhibited gonadotropin deficiency. The gonadotropin deficiency in the patient, which was diagnosed on admittance, was resolved during the follow-up period. DI persisted in all patients, and the conditions of the seven patients who have remained on follow-up are stable. In the present study, patients with LCH exhibited altered function in the anterior pituitary as well as the posterior pituitary, which may be due to the natural course of the disease or the effects of treatment. The present findings indicate that anterior pituitary function should be assessed in LCH patients on admittance and during follow-up, especially in LCH patients with multisystem organ involvement.

Surgical Outcomes of Cavernous Sinus Syndrome in Pituitary Adenomas.

PubMed

Fu, Weilun; Duan, Lian; Geng, Sumin

2017-11-01

The type of pituitary adenoma with a manifestation that includes cavernous sinus syndrome is rare. Based on the clinical data of 70 patients, this study investigated the pathogenesis, imaging characteristics, and prognostic factors of pituitary adenoma with cavernous sinus syndrome. We conducted a retrospective analysis of the characteristics of patients with pituitary adenoma with cavernous sinus syndrome who received surgical treatment. The patients were classified into different prognosis groups according to the time required for them to recover from the cavernous sinus syndrome. Univariate analyses were conducted for the correlations between the prognosis and factors. Of the 3598 cases of pituitary adenomas, 70 (1.95%) presented cavernous sinus syndrome. Of the patients, 55.7% recovered within 2 weeks of surgery, 24.3% recovered from 2 weeks to 1 year after surgery, and 20% had not returned to normal after more than 1 year after surgery. Univariate analyses showed that shorter disease duration (P < 0.001), lower Knosp grade (P = 0.045), a transsphenoidal approach (P < 0.001), and associated pituitary apoplexy (P = 0.012) were predictive factors of early postoperative recovery. The prognosis of cavernous sinus syndrome differs depending on the mechanism of the syndrome. There was no significant difference in the prognosis between patients with total pituitary adenoma resection and subtotal resection. Timely surgery within 100 days of symptom occurrence, Knosp grade 0-2, and associated pituitary apoplexy are predictive factors of good prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

INITIAL SYMPTOMATIC PITUITARY METASTASIS IN A PATIENT WITH PROSTATE FOAMY GLAND CARCINOMA: TAILORING SAFE AND EFFECTIVE THERAPY.

PubMed

Prpić, Marin; Fröbe, Ana; Zadravec, Dijana; Pažanin, Leo; Jakšić, Blanka; Bolanča, Ante; Kusić, Zvonko

2015-06-01

Metastases to pituitary gland are unusual and mostly asymptomatic, presenting with local symptoms in one of ten patients, and only 3%-5% of them are of prostate origin. Here we report and evaluate the effectiveness and safety of multimodal treatment in a patient with pituitary metastasis of a prostate foamy gland carcinoma. A 78-year-old male patient presented with blurred vision and headache without a previous history of malignancy. Magnetic resonance imaging scans revealed a large sellar mass, with infiltration of the surrounding structures. Maximal transsphenoidal reduction of pituitary metastasis was performed, with a histologic finding of metastatic prostate foamy gland adenocarcinoma. Evaluation of the prostate specific antigen revealed a very high level (1461 ng/mL) and foamy gland carcinoma was found on prostate needle biopsy. The patient received 3D conformal external beam radiotherapy with 6 MV photons to the sellar and parasellar region with a tumor dose of 44 Gy, followed by androgen deprivation therapy. Follow up magnetic resonance imaging done after radiotherapy showed shrinkage of the tumor process, with rapid prostate specific antigen decline to 0.3 ng/mL. The visual function was fully established and headache resolved. On the last follow up 14 months after the diagnosis, the patient was alive and free from clinical signs of disease. Tailored treatment, including limited radiotherapy in a higher palliative dose, in a patient with foamy gland symptomatic pituitary metastatic disease resulted in good local and systemic control of the disease. In older male patients with clinical and/or radiologic characteristics suggestive of metastatic pituitary disease, the prostate specific antigen test should be included as part of the work-up.

Rare Frequency of Mutations in Pituitary Transcription Factor Genes in Combined Pituitary Hormone or Isolated Growth Hormone Deficiencies in Korea.

PubMed

Choi, Jin Ho; Jung, Chang Woo; Kang, Eungu; Kim, Yoon Myung; Heo, Sun Hee; Lee, Beom Hee; Kim, Gu Hwan; Yoo, Han Wook

2017-05-01

Congenital hypopituitarism is caused by mutations in pituitary transcription factors involved in the development of the hypothalamic-pituitary axis. Mutation frequencies of genes involved in congenital hypopituitarism are extremely low and vary substantially between ethnicities. This study was undertaken to compare the clinical, endocrinological, and radiological features of patients with an isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD). This study included 27 patients with sporadic IGHD and CPHD. A mutation analysis of the POU1F1, PROP1, LHX3, LHX4, and HESX1 genes was performed using genomic DNA from peripheral blood leukocytes. IGHD and CPHD were observed in 4 and 23 patients, respectively. Mean age at diagnosis was 8.28±7.25 years for IGHD and 13.48±10.46 years for CPHD (p=0.37). Serum insulin-like growth factor-1 and peak growth hormone (GH) levels following GH stimulation tests were significantly lower in patients with CPHD than in those with IGHD (p<0.05). Sellar MRI findings revealed structural abnormalities in 3 patients with IGHD (75%) and 21 patients with CPHD (91.3%) (p=0.62). A mutation analysis identified homozygous p.R109Q mutations in HESX1 in a patient with CPHD. Patients with CPHD had more severe GHD than those with IGHD. The frequency of defects in the genes encoding pituitary transcription factors was extremely low in Korean patients with congenital hypopituitarism. Environmental factors and the impact of other causative genes may contribute to this clinical phenotype. © Copyright: Yonsei University College of Medicine 2017

Rare Frequency of Mutations in Pituitary Transcription Factor Genes in Combined Pituitary Hormone or Isolated Growth Hormone Deficiencies in Korea

PubMed Central

Choi, Jin-Ho; Jung, Chang-Woo; Kang, Eungu; Kim, Yoon-Myung; Heo, Sun Hee; Lee, Beom Hee; Kim, Gu-Hwan

2017-01-01

Purpose Congenital hypopituitarism is caused by mutations in pituitary transcription factors involved in the development of the hypothalamic-pituitary axis. Mutation frequencies of genes involved in congenital hypopituitarism are extremely low and vary substantially between ethnicities. This study was undertaken to compare the clinical, endocrinological, and radiological features of patients with an isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD). Materials and Methods This study included 27 patients with sporadic IGHD and CPHD. A mutation analysis of the POU1F1, PROP1, LHX3, LHX4, and HESX1 genes was performed using genomic DNA from peripheral blood leukocytes. Results IGHD and CPHD were observed in 4 and 23 patients, respectively. Mean age at diagnosis was 8.28±7.25 years for IGHD and 13.48±10.46 years for CPHD (p=0.37). Serum insulin-like growth factor-1 and peak growth hormone (GH) levels following GH stimulation tests were significantly lower in patients with CPHD than in those with IGHD (p<0.05). Sellar MRI findings revealed structural abnormalities in 3 patients with IGHD (75%) and 21 patients with CPHD (91.3%) (p=0.62). A mutation analysis identified homozygous p.R109Q mutations in HESX1 in a patient with CPHD. Patients with CPHD had more severe GHD than those with IGHD. Conclusion The frequency of defects in the genes encoding pituitary transcription factors was extremely low in Korean patients with congenital hypopituitarism. Environmental factors and the impact of other causative genes may contribute to this clinical phenotype. PMID:28332357

A journey through the pituitary gland: Development, structure and function, with emphasis on embryo-foetal and later development.

PubMed

Musumeci, Giuseppe; Castorina, Sergio; Castrogiovanni, Paola; Loreto, Carla; Leonardi, Rosi; Aiello, Flavia Concetta; Magro, Gaetano; Imbesi, Rosa

2015-01-01

The pituitary gland and the hypothalamus are morphologically and functionally associated in the endocrine and neuroendocrine control of other endocrine glands. They therefore play a key role in a number of regulatory feedback processes that co-ordinate the whole endocrine system. Here we review the neuroendocrine system, from the discoveries that led to its identification to some recently clarified embryological, functional, and morphological aspects. In particular we review the pituitary gland and the main notions related to its development, organization, cell differentiation, and vascularization. Given the crucial importance of the factors controlling neuroendocrine system development to understand parvocellular neuron function and the aetiology of the congenital disorders related to hypothalamic-pituitary axis dysfunction, we also provide an overview of the molecular and genetic studies that have advanced our knowledge in the field. Through the action of the hypothalamus, the pituitary gland is involved in the control of a broad range of key aspects of our lives: the review focuses on the hypothalamic-pituitary-gonadal axis, particularly GnRH, whose abnormal secretion is associated with clinical conditions involving delayed or absent puberty and reproductive dysfunction. Copyright © 2015 Elsevier GmbH. All rights reserved.

Follicular thyroid carcinoma with metastases to the pituitary causing pituitary insufficiency.

PubMed

Vianello, Federica; Mazzarotto, Renzo; Taccaliti, Augusto; Lora, Ornella; Basso, Michela; Servodio, Oscar; Mian, Caterina; Sotti, Guido

2011-08-01

Pituitary metastases are found in about 1% of all pituitary resections. They often derive from breast, lung, and gastroenteric tract adenocarcinomas, very rarely from thyroid carcinoma. Presenting symptoms of thyroid carcinoma metastatic to the pituitary gland are usually chiasmatic with central neurological impairment due to space-occupying expansion in the parasellar region. Hypopituitarism is more often associated with papillary and medullary rather than follicular thyroid carcinoma (FTC). Here we describe a patient with pituitary metastasis from FTC who had hypopituitarism with thyrotropin (TSH) deficiency. A 61-year-old woman, who presented with visual deficits and pain to the right orbit, was found on magnetic resonance imaging to have a large mass involving the pituitary gland. She was found to have pituitary insufficiency based on corticotropin-releasing hormone and TSH-releasing hormone testing. Transnasopharyngeal biopsy of the mass revealed metastases from FTC. After total thyroidectomy, which confirmed widely invasive FTC, the patient underwent external beam radiation therapy of the metastases for progressive neurological symptoms and an increase in orbit pain. Since endogenous TSH production was insufficient, we used recombinant human TSH (rhTSH) as preparation for a series of radioiodine treatments. rhTSH administration, followed by 7.4 GBq of (131)I, was repeated seven times over a 10-year period. This was associated with a marked decrease in serum thyroglobulin levels accompanied by substantial clinical improvement, but after 7 years disease progression occurred. Seven patients with pituitary metastases from FTC have been reported. In all cases, some neurological signs and symptoms related to mass effect were reported, but no pituitary insufficiency was described. This may be the first case of FTC with metastases to the pituitary causing hypopituitarism. It seems likely that management of such cases could be limited to biopsy to confirm thyroid carcinoma, rather than more extensive surgery, and that this could be followed by multiple treatments with rhTSH followed by (131)I.

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

Functioning and nonfunctioning thyroid adenomas involve different molecular pathogenetic mechanisms.

PubMed

Tonacchera, M; Vitti, P; Agretti, P; Ceccarini, G; Perri, A; Cavaliere, R; Mazzi, B; Naccarato, A G; Viacava, P; Miccoli, P; Pinchera, A; Chiovato, L

1999-11-01

The molecular biology of follicular cell growth in thyroid nodules is still poorly understood. Because gain-of-function (activating) mutations of the thyroid-stimulating hormone receptor (TShR) and/or Gs alpha genes may confer TSh-independent growth advantage to neoplastic thyroid cells, we searched for somatic mutations of these genes in a series of hyperfunctioning and nonfunctioning follicular thyroid adenomas specifically selected for their homogeneous gross anatomy (single nodule in an otherwise normal thyroid gland). TShR gene mutations were identified by direct sequencing of exons 9 and 10 of the TShR gene in genomic DNA obtained from surgical specimens. Codons 201 and 227 of the Gs alpha gene were also analyzed. At histology, all hyperfunctioning nodules and 13 of 15 nonfunctioning nodules were diagnosed as follicular adenomas. Two nonfunctioning thyroid nodules, although showing a prevalent microfollicular pattern of growth, had histological features indicating malignant transformation (a minimally invasive follicular carcinoma and a focal papillary carcinoma). Activating mutations of the TShR gene were found in 12 of 15 hyperfunctioning follicular thyroid adenomas. In one hyperfunctioning adenoma, which was negative for TShR mutations, a mutation in codon 227 of the Gs alpha gene was identified. At variance with hyperfunctioning thyroid adenomas, no mutation of the TShR or Gs alpha genes was detected in nonfunctioning thyroid nodules. In conclusion, our findings clearly define a different molecular pathogenetic mechanism in hyperfunctioning and nonfunctioning follicular thyroid adenomas. Activation of the cAMP cascade, which leads to proliferation but maintains differentiation of follicular thyroid cells, typically occurs in hyperfunctioning thyroid adenomas. Oncogenes other than the TShR and Gs alpha genes are probably involved in nonfunctioning follicular adenomas.

Pituitary gigantism in a 31 month old girl: endocrine studies and successful response to hypophysectomy.

PubMed

Espiner, E A; Carter, T A; Abbott, G D; Wrightson, P

1981-01-01

A case of pituitary gigantism occurring in a 31 month old female child is reported. Growth records indicate that the disorder began early in the second yr of life. Apart from her size and history of excessive sweating, there were no characteristic clinical features of endocrinopathy. Elevated and autonomous secretion of GH (60-109 microgram/l) and prolactin were corrected by the removal of an eosinophilic pituitary adenoma. In the subsequent 6 yr, despite the presence of immunoreactive GH (4.6-17.3 microgram/l), plasma somatomedin was subnormal and the patient showed growth failure which responded normally to exogenous GH therapy. This case, which appears to be the youngest example of verified pituitary gigantism on record, illustrates that a successful outcome can be achieved by surgical ablative therapy.

Non-functional tricuspid valve disease

PubMed Central

2017-01-01

Only 75% of severe tricuspid regurgitation is classified as functional, or related primarily to pulmonary hypertension, right ventricular dysfunction, or a combination of both. Non-functional tricuspid regurgitation occurs when there is damage to the tricuspid leaflets, chordae, papillary muscles, or annulus, independent of right ventricular dysfunction or pulmonary hypertension. The entities that cause non-functional tricuspid regurgitation include rheumatic and myxomatous disease, acquired and genetic connective tissue disorders, endocarditis, sarcoid, pacing, RV biopsy, blunt trauma, radiation, carcinoid, ergot alkaloids, dopamine agonists, fenfluramine, cardiac tumors, atrial fibrillation, and congenital malformations. Over time, severe tricuspid regurgitation that is initially non-functional, can blend into functional tricuspid regurgitation, related to progressive right ventricular dysfunction. Symptoms and signs, including a falling right ventricular ejection fraction, cardiac cirrhosis, ascites, esophageal varices, and anasarca, may occur insidiously and late, but are associated with substantial morbidity and mortality. Attempted valve repair or replacement at late stages carries a high mortality. Crucial to following patients with severe non-functional tricuspid regurgitation is attention to echo quantification of the tricuspid regurgitation and right ventricular function, patient symptoms, and the physical examination. PMID:28706863

Non-functional tricuspid valve disease.

PubMed

Adler, Dale S

2017-05-01

Only 75% of severe tricuspid regurgitation is classified as functional, or related primarily to pulmonary hypertension, right ventricular dysfunction, or a combination of both. Non-functional tricuspid regurgitation occurs when there is damage to the tricuspid leaflets, chordae, papillary muscles, or annulus, independent of right ventricular dysfunction or pulmonary hypertension. The entities that cause non-functional tricuspid regurgitation include rheumatic and myxomatous disease, acquired and genetic connective tissue disorders, endocarditis, sarcoid, pacing, RV biopsy, blunt trauma, radiation, carcinoid, ergot alkaloids, dopamine agonists, fenfluramine, cardiac tumors, atrial fibrillation, and congenital malformations. Over time, severe tricuspid regurgitation that is initially non-functional, can blend into functional tricuspid regurgitation, related to progressive right ventricular dysfunction. Symptoms and signs, including a falling right ventricular ejection fraction, cardiac cirrhosis, ascites, esophageal varices, and anasarca, may occur insidiously and late, but are associated with substantial morbidity and mortality. Attempted valve repair or replacement at late stages carries a high mortality. Crucial to following patients with severe non-functional tricuspid regurgitation is attention to echo quantification of the tricuspid regurgitation and right ventricular function, patient symptoms, and the physical examination.

Walter E. Dandy: his contributions to pituitary surgery in the context of the overall Johns Hopkins Hospital experience

PubMed Central

Corsello, Andrea; Di Dalmazi, Giulia; Pani, Fabiana; Chalan, Paulina; Salvatori, Roberto

2017-01-01

Background Walter E. Dandy (1886–1946) was an outstanding neurosurgeon who spent his entire career at the Johns Hopkins Hospital. After graduating from medical school in 1910, he completed a research fellowship in the Hunterian laboratory with Harvey Cushing and then joined the Department of Surgery as resident, rising to the rank professor in 1931. Dandy made several contributions that helped building the neurosurgical specialty, most famously the introduction of pneumo-ventriculography to image brain lesions for which he received a Nobel prize nomination. He also performed many pituitary surgeries, although his role in this area is less known and overshadowed by that of Cushing’s. Purpose This retrospective cohort study was designed to unveil Dandy’s pituitary work and place it in the context of the overall pituitary surgeries performed at the Johns Hopkins Hospital. Methods Pituitary surgery data were obtained by screening the paper and electronic surgical pathology records of the Department of Pathology, as well as the general operating room log books of the Johns Hopkins Hospital housed in the Chesney Medical Archives. Results A total of 3211 pituitary surgeries associated with a pathological specimen were performed between February 1902 and July 2017 in 2847 patients. Most of the surgeries (2875 of 3211 89%) were done by 21 neurosurgeons. Dandy ranks 4th as number of surgeries, with 287 pituitary operations in 35 years of activity. He averaged 8 pituitary surgeries per year, a rate that positions him 6th among all Hopkins neurosurgeons. With the exception of his first operation done in July 1912 while Cushing was still at Hopkins, Dandy approached the pituitary gland transcranially, rather than transphenoidally. The majority of Dandy’s pituitary patients had a pathological diagnosis of pituitary adenomas, followed by craniopharyngiomas and sellar cysts. In the decades Dandy operated, pituitary surgeries represented 0.56% of the total Johns Hopkins surgeries, a percentage significantly greater (p < 0.001) than the 0.1% observed in modern days. Dandy’s pituitary clinical work was matched by important experimental studies done in the early stages of his career. Conclusions This study highlights the role of Dandy as an important contributor to advance our understanding of pathophysiology and treatment of pituitary diseases. PMID:28871375

Steroidogenic Factor 1, Pit-1, and Adrenocorticotropic Hormone: A Rational Starting Place for the Immunohistochemical Characterization of Pituitary Adenoma.

PubMed

McDonald, William C; Banerji, Nilanjana; McDonald, Kelsey N; Ho, Bridget; Macias, Virgilia; Kajdacsy-Balla, Andre

2017-01-01

-Pituitary adenoma classification is complex, and diagnostic strategies vary greatly from laboratory to laboratory. No optimal diagnostic algorithm has been defined. -To develop a panel of immunohistochemical (IHC) stains that provides the optimal combination of cost, accuracy, and ease of use. -We examined 136 pituitary adenomas with stains of steroidogenic factor 1 (SF-1), Pit-1, anterior pituitary hormones, cytokeratin CAM5.2, and α subunit of human chorionic gonadotropin. Immunohistochemical staining was scored using the Allred system. Adenomas were assigned to a gold standard class based on IHC results and available clinical and serologic information. Correlation and cluster analyses were used to develop an algorithm for parsimoniously classifying adenomas. -The algorithm entailed a 1- or 2-step process: (1) a screening step consisting of IHC stains for SF-1, Pit-1, and adrenocorticotropic hormone; and (2) when screening IHC pattern and clinical history were not clearly gonadotrophic (SF-1 positive only), corticotrophic (adrenocorticotropic hormone positive only), or IHC null cell (negative-screening IHC), we subsequently used IHC for prolactin, growth hormone, thyroid-stimulating hormone, and cytokeratin CAM5.2. -Comparison between diagnoses generated by our algorithm and the gold standard diagnoses showed excellent agreement. When compared with a commonly used panel using 6 IHC for anterior pituitary hormones plus IHC for a low-molecular-weight cytokeratin in certain tumors, our algorithm uses approximately one-third fewer IHC stains and detects gonadotroph adenomas with greater sensitivity.

System requirements for a computerised patient record information system at a busy primary health care clinic.

PubMed

Blignaut, P J; McDonald, T; Tolmie, C J

2001-05-01

A prototyping approach was used to determine the essential system requirements of a computerised patient record information system for a typical township primary health care clinic. A pilot clinic was identified and the existing manual system and business processes in this clinic was studied intensively before the first prototype was implemented. Interviews with users, incidental observations and analysis of actual data entered were used as primary techniques to refine the prototype system iteratively until a system with an acceptable data set and adequate functionalities were in place. Several non-functional and user-related requirements were also discovered during the prototyping period.

Dental Abnormalities in Pituitary Dwarfism: A Case Report and Review of the Literature

PubMed Central

Blasi, Sergio; Crippa, Rolando; Angiero, Francesca

2017-01-01

Hypopituitarism is a disorder caused by a reduced level of trophic hormones that may be consequent on different destructive processes. The clinical manifestations depend on the type of hormone involved. A deficiency of growth hormone (GH) in children causes the lack of growth known as pituitary dwarfism. The case is reported of a patient with pituitary dwarfism, multiple dental anomalies, functional prosthetic problems, and a revision of the literature. She was subjected to prosthetic rehabilitation without surgical intervention, using zirconium substructures, thus eliminating the potential complications that may require trauma surgery. The therapeutic approach adopted led to excellent results and restored an aesthetic smile. PMID:28458931

Macro- and microadenoma of thyrotropin secreting pituitary tumors--two clinical cases.

PubMed

Hubalewska-Hola, Alicja; Fröss, Katarzyna; Kostecka-Matyja, Marta; Sowa-Staszczak, Anna; Szybiński, Zbigniew; Huszno, Bohdan; Ptak, Marzena

2003-01-01

Thyrotropin secreting adenoma, thyrotropinoma (TSH-oma), is a rare cause of hyperthyroidism--called secondary hyperthyroidism. The hormonal profile in pituitary hyperthyroidism is characterized by a nonsuppressed TSH in the presence of high levels of free thyroid hormones (fT4, fT3) reflecting an abnormal feedback. The diagnosis of TSH-oma is often made at the stage of macroadenoma because of the aggressive nature of the tumor and due to the fact that patients are mistakenly treated for more common primary hyperthyroidism for a long time. Two cases of TSH-secreting adenoma were detected in Chair and Department of Endocrinology, Collegium Medicum of the Jagiellonian University in Krakow for the last twenty years. Case 1: 49 year old woman was admitted to the Clinic of Endocrinology in 1999 with recurring hyperthyroidism treated with surgical thyroid ablation in 1992 and thyreostatics for the previous nine years. On admission to the Clinic her thyroid panel presented with elevated free hormone levels (mainly fT3-14.8 pmol/l) and not suppressed TSH-0.7 mIU/l suggesting central hyperthyroidism. MRI scan of the pituitary gland revealed microadenoma of 5 mm in diameter. She was qualified to transsphenoidal resection of the tumor. Histopathology revealed acidophilic adenoma with positive TSH staining. Thyroid hormones 8 days after the operation suggested full effectiveness of the surgery. Case 2: 65 year old man treated for one year with L-Thyroxin because of elevated TSH (60 mIU/l) and then with thyreostatics for elevated fT3 and fT4 was admitted to the Clinic of Endocrinology in 2000 with suspected thyrotropinoma. On admission to the Clinic thyroid panel suggested hyperthyroidism with fT4-40 pmol/l, FT3-11.2 pmol/l without suppression of TSH 2.2 mIU/l. MRI scan revealed a pituitary tumor 20 x 18 x 20 mm, compressing the optic chiasm. He was administered octreotide as a preparation for the operation. The patient underwent trans-sphenoidal resection of the adenoma (histopathologically a chromophobic adenoma). The example of presented patients suggests that clinical course of the pituitary tumor producing TSH and the rate of the tumor growth may differ significantly. Surgical resection of TSH producing adenoma is the most effective therapy. It should be proceeded by octreotide administration in patients with macroadenoma.

Pituitary Antibodies in Women with Hashimoto's Thyroiditis: Prevalence in Diagnostic and Prediagnostic Sera

PubMed Central

Guaraldi, Federica; Landek-Salgado, Melissa A.; Hutfless, Susan; Samoni, Francesca; Talor, Monica V.; Matos, Peter G.; Salvatori, Roberto; Rose, Noel R.

2012-01-01

Background Pituitary antibodies have been reported with greater frequency in patients with Hashimoto's thyroiditis than in healthy controls, although there is significant variability in the strength of the association and the methodologies used. Methods We designed a nested case–control study to characterize the prevalence of pituitary antibodies at the time of the clinical diagnosis of Hashimoto's thyroiditis, as well as at 2, 5, and 7 years before diagnosis. Active component female service member cases (n=87) and matched female controls (n=107) were selected using the Defense Medical Surveillance System database (DMSSD) between January 1998 and December 2007. Pituitary antibodies were measured by immunofluorescence using human pituitary glands collected at autopsy as the substrate. Results At diagnosis, pituitary antibodies were present in 9% of cases with Hashimoto's (8 of 87) and 3% of controls (3 of 107). When the data were analyzed using a conditional logistic regression model, which takes into account the matching on age and work status, pituitary antibodies increased the odds of having Hashimoto's thyroiditis by sevenfold (95% confidence interval from 1.3 to 40.1, p=0.028), after adjusting for components of the DMSSD-category-termed race and for thyroperoxidase antibodies. Before diagnosis, pituitary antibodies were positive in 3 of the 11 subjects (2 cases and 1 control) at the −2-year time point, and negative in all 11 subjects at the −5- and −7-year time points. Conclusions In summary, using a nested case–control design, we confirm that pituitary antibodies are more common in Hashimoto's thyroiditis and suggest that they appear late during its natural history. PMID:22468943

Gigantism caused by growth hormone secreting pituitary adenoma.

PubMed

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

2014-06-01

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

Gigantism caused by growth hormone secreting pituitary adenoma

PubMed Central

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

2014-01-01

Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings. PMID:25077093

X-linked Acrogigantism (X-LAG) Syndrome: Clinical Profile and Therapeutic Responses

PubMed Central

Beckers, Albert; Lodish, Maya Beth; Trivellin, Giampaolo; Rostomyan, Liliya; Lee, Misu; Faucz, Fabio R; Yuan, Bo; Choong, Catherine S; Caberg, Jean-Hubert; Verrua, Elisa; Naves, Luciana Ansaneli; Cheetham, Tim D; Young, Jacques; Lysy, Philippe A; Petrossians, Patrick; Cotterill, Andrew; Shah, Nalini Samir; Metzger, Daniel; Castermans, Emilie; Ambrosio, Maria Rosaria; Villa, Chiara; Strebkova, Natalia; Mazerkina, Nadia; Gaillard, Stéphan; Barra, Gustavo Barcelos; Casulari, Luis Augusto; Neggers, Sebastian J.; Salvatori, Roberto; Jaffrain-Rea, Marie-Lise; Zacharin, Margaret; Santamaria, Beatriz Lecumberri; Zacharieva, Sabina; Lim, Ee Mun; Mantovani, Giovanna; Zatelli, Maria Chaira; Collins, Michael T; Bonneville, Jean-François; Quezado, Martha; Chittiboina, Prashant; Oldfield, Edward H.; Bours, Vincent; Liu, Pengfei; De Herder, Wouter; Pellegata, Natalia; Lupski, James R.; Daly, Adrian F.; Stratakis, Constantine A.

2015-01-01

X-linked acro-gigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and a microduplication in chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in 2 families was dominant with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2–3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight SDS score of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF-1 and prolactin, usually due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high somatostatin receptor subtype-2 expression in tumor tissue. Postoperative adjuvant pegvisomant achieved control of IGF-1 all 5 cases in which it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management. PMID:25712922

Anatomic Dissection of Arachnoid Membranes Encircling the Pituitary Stalk on Fresh, Non-Formalin-Fixed Specimens: Anatomoradiologic Correlations and Clinical Applications in Craniopharyngioma Surgery.

PubMed

Ciappetta, Pasqualino; Pescatori, Lorenzo

2017-12-01

The anatomy of the arachnoid membranes and cisternal spaces around the pituitary stalk has not been yet exhaustively described and understood. In this study, we performed a detailed anatomic study on fresh, non-formalin-fixed cadavers of the arachnoid membranes encircling the pituitary stalk and correlate our anatomic findings with magnetic resonance imaging (MRI). Ten fresh, non-formalin-fixed, non-silicon-injected adult cadaveric heads were analyzed in this study. The membrane and cisterns that were studied for our study were as follows: 1) the diaphragma sellae and its dural components; 2) the basal arachnoid membrane; 3) the Liliequist membrane with its diencephalic and mesencephalic portion; 4) the medial carotid membrane; 5) the chiasmatic cistern; and 6) the pituitary stalk. MRI examinations of the sellar region were performed in 15 healthy volunteers (9 men, mean age 40 years; and 6 women mean age, 37 years) to visualize the arachnoid membrane encircling the pituitary stalk. MRI examinations were performed with a 3-T unit. A 3-dimensional constructive interference in steady state pulse magnetic resonance sequence was used. All the membranes examined were visualized clearly in all the dissections performed. Their 3-dimensional organization around the pituitary stalk was clarified and confirmed by MRI. Our study gives a detailed description of the pituitary stalk arachnoid sheets on fresh, non-formalin-fixed cadavers. This technique allowed us to clearly identify a funnel-shaped arachnoid collar encircling the pituitary stalk and delimiting a distinct cisternal space belonging to the stalk itself. Copyright © 2017 Elsevier Inc. All rights reserved.

Central regulation of the hypothalamo-pituitary-thyroid (HPT) axis: focus on clinical aspects.

PubMed

Fliers, E; Boelen, A; van Trotsenburg, A S P

2014-01-01

The hypothalamus is the most prominent brain region involved in setpoint regulation of the thyroid axis. It generates the diurnal thyroid-stimulating hormone (TSH) rhythm, and it plays a central role in the adaptation of the thyroid axis to environmental factors such as caloric deprivation or infection. Many studies, including studies in human post-mortem tissue samples, have confirmed a key role for the thyrotropin-releasing hormone (TRH) neuron in the hypothalamic paraventricular nucleus (PVN) in thyroid axis regulation. In addition to their negative feedback action on TRH neurons in the hypothalamus, intrahypothalamic thyroid hormones can also modulate metabolism in adipose tissue and the liver via the autonomic nervous system. Congenital or acquired dysfunction of the hypothalamus or pituitary gland may result in central hypothyroidism (CeH). In the Netherlands, the prevalence of permanent congenital CeH as detected by neonatal screening is approximately 1 in 18000. In most neonates congenital CeH is accompanied by additional anterior pituitary hormone deficiencies, and many show clear morphological abnormalities such as a small anterior gland, a thin or absent pituitary stalk, or an ectopic posterior pituitary gland. Recently, a mutation in the immunoglobulin superfamily member 1 (IGSF1) gene was reported as a novel cause of X-linked, apparently isolated CeH occurring in neonates, children and adults. In adults, the most frequent cause of acquired CeH is a pituitary macroadenoma, usually accompanied by other pituitary hormone deficiencies. Central hyperthyroidism is a rare disorder, especially in children. In adults, it is mostly caused by a TSH-secreting pituitary adenoma. © 2014 Elsevier B.V. All rights reserved.

21 CFR 100.100 - Misleading containers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... nonfunctional slack-fill. Slack-fill is the difference between the actual capacity of a container and the volume of product contained therein. Nonfunctional slack-fill is the empty space in a package that is filled...

Influence of different cusp coverage methods for the extension of ceramic inlays on marginal integrity and enamel crack formation in vitro.

PubMed

Krifka, Stephanie; Stangl, Martin; Wiesbauer, Sarah; Hiller, Karl-Anton; Schmalz, Gottfried; Federlin, Marianne

2009-09-01

No information is available to date about cusp design of thin (1.0 mm) non-functional cusps and its influence upon (1) marginal integrity of ceramic inlays (CI) and partial ceramic crowns (PCC) and (2) crack formation of dental tissues. The aim of this in vitro study was to investigate the effect of cusp coverage of thin non-functional cusps on marginal integrity and enamel crack formation. CI and PCC preparations were performed on extracted human molars. Non-functional cusps were adjusted to 1.0-mm wall thickness and 1.0-mm wall thickness with horizontal reduction of about 2.0 mm. Ceramic restorations (Vita Mark II, Cerec3 System) were adhesively luted with Excite/Variolink II. The specimens were exposed to thermocycling and central mechanical loading. Marginal integrity was assessed by evaluating dye penetration after thermal cycling and mechanical loading. Enamel cracks were documented under a reflective-light microscope. The data were statistically analysed with the Mann-Whitney U test, the Fishers exact test (alpha = 0.05) and the error rates method. PCC with horizontal reduction of non-functional cusps showed statistically significant less microleakage than PCC without such a cusp coverage. Preparation designs with horizontal reduction of non-functional cusps showed a tendency to less enamel crack formation than preparation designs without cusp coverage. Thin non-functional cusp walls of adhesively bonded restorations should be completely covered or reduced to avoid enamel cracks and marginal deficiency.

[A case of GH and TSH secreting pituitary macroadenoma].

PubMed

Gołkowski, Filip; Buziak-Bereza, Monika; Stefańska, Agnieszka; Trofimiuk, Małgorzata; Pantofliński, Jacek; Huszno, Bohdan; Czepko, Ryszard; Adamek, Dariusz

2006-01-01

A case of GH and TSH secreting pituitary macroadenoma is reported. A 45-year-old female presented clinical features of acromegaly (the abnormal growth of the hands and feet, with lower jaw protrusion), diabetes mellitus, hypertension, nodular goiter and hyperthyroidism of unclear origin. NMR pituitary imaging revealed intra and extrasellar tumor. The laboratory examinations showed very high plasma levels of GH and IGF-1 and normal level of TSH coexisting with high plasma levels of free thyroid hormones. Pharmacological pretreatment with somatostatin analogues caused the substantial reduction of GH and TSH plasma levels. Histological and immunohistochemical examination of the tissue obtained at transsphenoidal surgery showed GH and TSH secreting adenoma. The laboratory examinations after surgery showed normal GH and IGF-1 plasma levels and reduced insulin requirement, what indicates radical operation. The very low plasma levels of TSH and free thyroid hormones after surgery and immunohistochemical examination suggest central hyperthyroidism due to TSH secreting pituitary tumor (thyrotropinoma).

Pituitary adenoma and unexpected sudden infant death: a case report.

PubMed

Matsuura, H; Kitazawa, Y; Tanaka, M; Morooka, K

1994-01-01

Pituitary adenomas can cause sudden death in adults, but they are quite rare during infancy. Herein we present an unusual case of sudden infant death associated with a pituitary adenoma. The clinical presentations were "quietness" complained of by the parents and probable gigantism with accelerated growth rate during the first 2 months of life. The female infants had been in good health until one day when, at the age of 3 months, she was found immobile in bed. Microscopic examination showed that the cells of the entire pituitary gland were replaced by bizarre undifferentiated tumor cells. There were no invasive lesions in the surrounding brain tissue. It was also found that the cortex of the adrenal glands was atrophic. No metastatic lesions were observed in any organ. While the mechanism leading our infant to death is both controversial and unknown, we speculated that insufficient secretion of steroid hormones might have caused cardiovascular collapse.

UK guidelines for the management of pituitary apoplexy.

PubMed

Rajasekaran, Senthil; Vanderpump, Mark; Baldeweg, Stephanie; Drake, Will; Reddy, Narendra; Lanyon, Marian; Markey, Andrew; Plant, Gordon; Powell, Michael; Sinha, Saurabh; Wass, John

2011-01-01

Classical pituitary apoplexy is a medical emergency and rapid replacement with hydrocortisone maybe life saving. It is a clinical syndrome characterized by the sudden onset of headache, vomiting, visual impairment and decreased consciousness caused by haemorrhage and/or infarction of the pituitary gland. It is associated with the sudden onset of headache accompanied or not by neurological symptoms involving the second, third, fourth and sixth cranial nerves. If diagnosed patients should be referred to a multidisciplinary team comprising, amongst others, a neurosurgeon and an endocrinologist. Apart from patients with worsening neurological symptoms in whom surgery is indicated, it is unclear currently for the majority of patients whether conservative or surgical management carries the best outcome. Post apoplexy, there needs to be careful monitoring for recurrence of tumour growth. It is suggested that further trials be carried out into the management of pituitary apoplexy to optimize treatment. © 2010 Blackwell Publishing Ltd.

High-Resolution DCE-MRI of the Pituitary Gland Using Radial k-Space Acquisition with Compressed Sensing Reconstruction.

PubMed

Rossi Espagnet, M C; Bangiyev, L; Haber, M; Block, K T; Babb, J; Ruggiero, V; Boada, F; Gonen, O; Fatterpekar, G M

2015-08-01

The pituitary gland is located outside of the blood-brain barrier. Dynamic T1 weighted contrast enhanced sequence is considered to be the gold standard to evaluate this region. However, it does not allow assessment of intrinsic permeability properties of the gland. Our aim was to demonstrate the utility of radial volumetric interpolated brain examination with the golden-angle radial sparse parallel technique to evaluate permeability characteristics of the individual components (anterior and posterior gland and the median eminence) of the pituitary gland and areas of differential enhancement and to optimize the study acquisition time. A retrospective study was performed in 52 patients (group 1, 25 patients with normal pituitary glands; and group 2, 27 patients with a known diagnosis of microadenoma). Radial volumetric interpolated brain examination sequences with golden-angle radial sparse parallel technique were evaluated with an ROI-based method to obtain signal-time curves and permeability measures of individual normal structures within the pituitary gland and areas of differential enhancement. Statistical analyses were performed to assess differences in the permeability parameters of these individual regions and optimize the study acquisition time. Signal-time curves from the posterior pituitary gland and median eminence demonstrated a faster wash-in and time of maximum enhancement with a lower peak of enhancement compared with the anterior pituitary gland (P < .005). Time-optimization analysis demonstrated that 120 seconds is ideal for dynamic pituitary gland evaluation. In the absence of a clinical history, differences in the signal-time curves allow easy distinction between a simple cyst and a microadenoma. This retrospective study confirms the ability of the golden-angle radial sparse parallel technique to evaluate the permeability characteristics of the pituitary gland and establishes 120 seconds as the ideal acquisition time for dynamic pituitary gland imaging. © 2015 by American Journal of Neuroradiology.

High-Resolution DCE-MRI of the Pituitary Gland Using Radial k-Space Acquisition with Compressed Sensing Reconstruction

PubMed Central

Rossi Espagnet, M.C.; Bangiyev, L.; Haber, M.; Block, K.T.; Babb, J.; Ruggiero, V.; Boada, F.; Gonen, O.; Fatterpekar, G.M.

2015-01-01

BACKGROUNDANDPURPOSE The pituitary gland is located outside of the blood-brain barrier. Dynamic T1 weighted contrast enhanced sequence is considered to be the gold standard to evaluate this region. However, it does not allow assessment of intrinsic permeability properties of the gland. Our aim was to demonstrate the utility of radial volumetric interpolated brain examination with the golden-angle radial sparse parallel technique to evaluate permeability characteristics of the individual components (anterior and posterior gland and the median eminence) of the pituitary gland and areas of differential enhancement and to optimize the study acquisition time. MATERIALS AND METHODS A retrospective study was performed in 52 patients (group 1, 25 patients with normal pituitary glands; and group 2, 27 patients with a known diagnosis of microadenoma). Radial volumetric interpolated brain examination sequences with golden-angle radial sparse parallel technique were evaluated with an ROI-based method to obtain signal-time curves and permeability measures of individual normal structures within the pituitary gland and areas of differential enhancement. Statistical analyses were performed to assess differences in the permeability parameters of these individual regions and optimize the study acquisition time. RESULTS Signal-time curves from the posterior pituitary gland and median eminence demonstrated a faster wash-in and time of maximum enhancement with a lower peak of enhancement compared with the anterior pituitary gland (P < .005). Time-optimization analysis demonstrated that 120 seconds is ideal for dynamic pituitary gland evaluation. In the absence of a clinical history, differences in the signal-time curves allow easy distinction between a simple cyst and a microadenoma. CONCLUSIONS This retrospective study confirms the ability of the golden-angle radial sparse parallel technique to evaluate the permeability characteristics of the pituitary gland and establishes 120 seconds as the ideal acquisition time for dynamic pituitary gland imaging. PMID:25953760

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, both groups experienced significant improvements in mental health (13%, p = 0.005) and vitality (15%, p = 0.037). By 1 year after surgery, patients improved significantly in mental health (14%, p = 0.03), role physical (14%, p = 0.036), social functioning (16%, p = 0.009), vitality (22%, p = 0.002), and SF-36 total (10%, p = 0.024) as compared with preoperative measures. There were no significant differences at any time point between the 2 groups for the total SF-36 or for any of the 8 subscales. CONCLUSIONS Patients who underwent either an endoscopic or a microscopic approach experienced the greatest nasal symptoms at 2 weeks postoperatively and exhibited similar time courses of recovery in nasal, headache, and quality of life assessments. Although patients who underwent endoscopic surgery experienced significantly fewer nasal symptoms during the first 8 weeks, by 1 year after surgery, there were no significant differences between the 2 groups.

Pituitary apoplexy precipitating diabetes insipidus after living donor liver transplantation.

PubMed

Matsusaki, Takashi; Morimatsu, Hiroshi; Matsumi, Junya; Matsuda, Hiroaki; Sato, Tetsufumi; Sato, Kenji; Mizobuchi, Satoshi; Yagi, Takahito; Morita, Kiyoshi

2011-02-01

Pituitary apoplexy occurring after surgery is a rare but life-threatening acute clinical condition that follows extensive hemorrhagenous necrosis within a pituitary adenoma. Pituitary apoplexy has been reported to occur spontaneously in the majority of cases or in association with various inducing factors. Reported is a case of pituitary apoplexy complicated by diabetes insipidus following living donor liver transplantation (LDLT). To the best of our knowledge, this has not been previously reported. A 56-year-old woman with nonalcoholic steatohepatitis underwent LDLT from her daughter. The patient also required dopamine support and transfusions because of massive intraoperative bleeding. Postoperatively, her coagulopathy continued, and she underwent a second laparotomy because of unknown bleeding on postoperative day 7, when she needed transfusions and dopamine support to maintain her vital signs. She complained of severe headache, excessive thirst, frequent urination, and diplopia from postoperative day 10. She also had polyuria greater than 300 ml/h and was diagnosed with pituitary apoplexy precipitating diabetes insipidus on postoperative day 13. She was treated conservatively without surgery because of the hormonally inactive status and slight mass effect of her tumor. It is important for anesthesiologists and critical care personnel in LDLT settings to take into consideration this complication as a differential diagnosis.

Radiation-induced ocular motor cranial nerve palsies in patients with pituitary tumor.

PubMed

Vaphiades, Michael S; Spencer, Sharon A; Riley, Kristen; Francis, Courtney; Deitz, Luke; Kline, Lanning B

2011-09-01

Radiation therapy is often used in the treatment of pituitary tumor. Diplopia due to radiation damage to the ocular motor cranial nerves has been infrequently reported as a complication in this clinical setting. Retrospective case series of 6 patients (3 men and 3 women) with pituitary adenoma, all of whom developed diplopia following transsphenoidal resection of pituitary adenoma with subsequent radiation therapy. None had evidence of tumor involvement of the cavernous sinus. Five patients developed sixth nerve palsies, 3 unilateral and 2 bilateral, and in 1 patient, a sixth nerve palsy was preceded by a fourth cranial nerve palsy. One patient developed third nerve palsy. Five of the 6 patients had a growth hormone-secreting pituitary tumor with acromegaly. Following transsphenoidal surgery in all 6 patients (2 had 2 surgeries), 4 had 2 radiation treatments consisting of either radiosurgery (2 patients) or external beam radiation followed by radiosurgery (2 patients). Patients with pituitary tumors treated multiple times with various forms of radiation therapy are at risk to sustain ocular motor cranial nerve injury. The prevalence of acromegalic patients in this study reflects an aggressive attempt to salvage patients with recalcitrant growth hormone elevation and may place the patient at a greater risk for ocular motor cranial nerve damage.

Hypopituitarism after acute brain injury.

PubMed

Urban, Randall J

2006-07-01

Acute brain injury has many causes, but the most common is trauma. There are 1.5-2.0 million traumatic brain injuries (TBI) in the United States yearly, with an associated cost exceeding 10 billion dollars. TBI is the most common cause of death and disability in young adults less than 35 years of age. The consequences of TBI can be severe, including disability in motor function, speech, cognition, and psychosocial and emotional skills. Recently, clinical studies have documented the occurrence of pituitary dysfunction after TBI and another cause of acute brain injury, subarachnoid hemorrhage (SAH). These studies have consistently demonstrated a 30-40% occurrence of pituitary dysfunction involving at least one anterior pituitary hormone following a moderate to severe TBI or SAH. Growth hormone (GH) deficiency is the most common pituitary hormone disorder, occurring in approximately 20% of patients when multiple tests of GH deficiency are used. Within 7-21 days of acute brain injury, adrenal insufficiency is the primary concern. Pituitary function can fluctuate over the first year after TBI, but it is well established by 1 year. Studies are ongoing to assess the effects of hormone replacement on motor function and cognition in TBI patients. Any subject with a moderate to severe acute brain injury should be screened for pituitary dysfunction.

Transcranial Evacuation of Atypical Progressive Supradiaphragmatic Hematoma After Transsphenoidal Complete Resection of Pituitary Adenoma.

PubMed

Metwali, Hussam; Fahlbusch, Rudolf

2017-06-01

Supradiaphragmatic hematoma is a type of hematoma that occurs after transsphenoidal (TS) resection of pituitary adenoma and requires special management. Two patients had symptomatic supradiaphragmatic hematomas after total TS resection of pituitary adenomas in the absence of vascular anomalies. Both patients also had hydrocephalus at the time of diagnosis of the hematoma. The initial endoscopic endonasal inspection showed no subdiaphragmatic bleeding. The hematoma was evacuated via a frontolateral approach after insertion of an external ventricular drain (EVD). The supradiaphragmatic hematoma could be clinically and radiologically distinguished. It presented early with visual deterioration without headache. The patients developed hydrocephalus, which was associated with deterioration of level of consciousness. Radiologically, the hematoma filled the suprasellar space and was associated with the extension of bleeding in the basal cisterns. Recovery was good in both patients. There were no permanent neurologic deficits. The EVD was removed in both patients. One patient required a ventriculoperitoneal shunt because of delayed hydrocephalus. Supradiaphragmatic hematoma can be clinically and radiologically distinguished from other types of hematoma occurring after TS resection of pituitary adenoma. Transcranial surgery should be performed to manage supradiaphragmatic hematoma, when symptomatic. Insertion of an EVD at the time of evacuation is mandatory to relax the brain and to alleviate the hydrocephalus. Copyright © 2017 Elsevier Inc. All rights reserved.

A Histologically Diagnosed Case with Infantile Osteopetrosis Complicated by Hypopituitarism

PubMed Central

Calkavur, Sebnem; Buyukinan, Muammer; Altay, Canan

2015-01-01

Malignant infantile osteopetrosis is a rarely seen severe disorder which appears early in life with general sclerosis of the skeleton. It is caused by functionally defective osteoclasts which fail to resorb bone. Affected infants can exhibit a wide spectrum of clinical manifestations including impaired hematopoiesis, hepatosplenomegaly, visual impairment, and hypocalcemia. With the exception of secondary hyperparathyroidism, involvement of the endocrine system seems to be quite rare. Hypopituitarism is defined as underproduction of the growth hormone in combination with deficiencies of other pituitary hormones. Any lesion that damages hypothalamus, pituitary stalk, or anterior pituitary can cause secondary hypopituitarism. In this report, we presented a rare combination of malignant infantile osteopetrosis and secondary hypopituitarism in a newborn who presented predominantly with endocrinological symptoms. This is the first case report of malignant infantile osteopetrosis accompanied by hypopituitarism secondary to sclerosis of the sella turcica. On the other hand, this is a very interesting case which was diagnosed based on histological examination of bone marrow biopsy specimens despite lack of any clinical suspicion. PMID:26576309

Polycystic ovary syndrome and prolactinoma association.

PubMed

Yavasoglu, Irfan; Kucuk, Mert; Coskun, Adil; Guney, Engin; Kadikoylu, Gurhan; Bolaman, Zahit

2009-01-01

Hyperprolactinemia is the most common pituitary hormone hypersecretion syndrome in both men and women. Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting 5%-10% of reproductive age women. Here, we present a patient with irregular menses, obesity, hirsutism and infertility, and hyperprolactinemia who was diagnosed as PCOS and prolactinoma and admitted to our clinic. Prolactinoma and PCOS association is a rare condition. This 33-year-old woman was admitted to the internal medicine outpatient clinic for irregular menses, obesity, hirsutism and infertility, and hyperprolactinemia. Her laboratory results were as follows: prolactin was 74 ng/mL (normal range:1.8-20.3 ng/mL). Pelvic ultrasonography was correlated with polycystic ovary syndrome. Pituitary MRI showed 6x8 mm microadenoma at left half. Bromocriptine was started with 1.25 mg/day and increased to 5 mg/day. After six months of bromocriptine treatment her prolactin level was normal and no adenoma was detected in pituitary MRI. PCOS and prolactinoma association should be taken into account in PCOS cases with mild hyperprolactinoma.

Short-term estriol administration modulates hypothalamo-pituitary function in patients with functional hypothalamic amenorrhea (FHA).

PubMed

Genazzani, Alessandro D; Podfigurna-Stopa, Agnieszka; Czyzyk, Adam; Katulski, Krzysztof; Prati, Alessia; Despini, Giulia; Angioni, Stefano; Simoncini, Tommaso; Meczekalski, Blazej

2016-01-01

To evaluate the influence of short-term estriol administration (10 d) on the hypothalamus-pituitary function and gonadotropins secretion in patients affected by functional hypothalamic amenorrhea (FHA). Controlled clinical study on patients with FHA (n = 12) in a clinical research environment. Hormonal determinations and gonadotropin (luteinizing hormone [LH] and FSH) response to a gonadotropin-releasing hormone (GnRH) bolus (10 μg) at baseline condition and after 10 d of therapy with 2 mg/d of estriol per os. Measurements of plasma LH, FSH, prolactin, estradiol, androstenedione, 17α-hydroxyprogesterone, insulin, cortisol, thyroid-stimulating hormone, free triiodothyronine, and free thyroxine. After treatment, the FHA patients showed a statistically significant increase of both LH and FSH plasma levels and the significant increase of their responses to the GnRH bolus. Estriol short-term therapy modulates within 10 d of administration the neuroendocrine control of the hypothalamus-pituitary unit and induces the recovery of both gonadotropins synthesis and secretion in hypogonadotropic patients with FHA.

Acromegaly and gigantism in the medical literature. Case descriptions in the era before and the early years after the initial publication of Pierre Marie (1886).

PubMed

de Herder, Wouter W

2009-01-01

In 1886 Pierre Marie used the term "acromegaly" for the first time and gave a full description of the characteristic clinical picture. However several others had already given clear clinical descriptions before him and sometimes had given the disease other names. After 1886, it gradually became clear that pituitary enlargement (caused by a pituitary adenoma) was the cause and not the consequence of acromegaly, as initially thought. Pituitary adenomas could be found in the great majority of cases. It also became clear that acromegaly and gigantism were the same disease but occurring at different stages of life and not different diseases as initially thought. At the end of the 19th and beginning of the 20th century most information was derived from case descriptions and post-mortem examinations of patients with acromegaly or (famous) patients with gigantism. The stage was set for further research into the pathogenesis, diagnosis and therapy of acromegaly and gigantism.

MEN1 and pituitary adenomas.

PubMed

Delemer, Brigitte

2012-04-01

MEN1 gene mutations predispose carriers to pituitary tumors. Molecular pathways involved in the development of these tumors seem different to what is known in sporadic tumors. Clinical studies showed that all types of adenomas can be found with a predominance of prolactinoma and macroadenoma compared to a control population. These MEN1 tumors seem more aggressive, invasive and resistant to treatment requiring a very careful long-life follow-up. Occurrence of these tumors can be described in the pediatric population and it can be the first and only manifestation of MEN1 for some years asking the question of the systematic screening for MEN1 gene mutation in pediatric population with pituitary adenoma. Copyright © 2012. Published by Elsevier Masson SAS.

A rare cause of hypophysitis: tuberculosis.

PubMed

Ates, Ihsan; Katipoglu, B; Copur, B; Yilmaz, N

2017-10-26

Hypophysitis is a heterogeneous inflammatory disease of pituitary gland. As it causes headache and visual defects, it mimics sellar tumors in clinical and radiological aspects. It may occur due to primary or secondary causes. Tuberculosis is one of the rare secondary causes of the hypophysitis. Subject and Results. A 30-year-old male patient presented with fatigue and headache. Panhypopituitarism was considered due to the results and the diagnostic magnetic resonance (MR) imaging revealed sagittal section diamater of pituitary gland higher than normal. Biopsy of the pituitary gland was concordant with the granulomatous hypophysitis. Other possible diagnosis was excluded. The tubercular hypophysitis, as a result of performed tests, is discussed hereby, in the case report.

Governor Pio Pico, the monster of California...no more: lessons in neuroendocrinology.

PubMed

Login, Ivan S; Login, Jessica

2010-01-01

We hypothesize that Pio Pico, the last Mexican Governor of California, had acromegaly between at least ages 43 to 57, from 1844 to 1858, before Pierre Marie published the clinical description of acromegaly in 1886. Pico's probable growth hormone-secreting pituitary tumor likely infarcted spontaneously after 1858. The tumor infarction resulted in burnt-out acromegaly and probably restored normal pituitary function. Pearce Bailey published the first account of pituitary tumor infarction only in 1898. Pico's undiagnosed, misunderstood, profoundly acromegalic appearance was widely misinterpreted, leading to pervasive, degrading, and highly prejudicial comments. This landmark case study in neuroendocrinology provides the opportunity to re-examine elements of 19th century California and American history.

[The incidence of the pituitary autoantibodies in Addison disease].

PubMed

Gut, Paweł; Kosowicz, Jerzy; Ziemnicka, Katarzyna; Baczyk, Maciej; Sowiński, Jerzy

2008-01-01

Addison disease (primary insufficience of adrenal cortex) characterized by clinical signs and symptoms associated with deficiency of adrenal hormones. The most frequent etiopathogenesis of Addison disease is related with autoimmunization. In sera of Addison patients are detectable autoantibodies against another endocrine glands. The aim of the study was evaluation of pituitary autoantibodies in Addison disease patients using immunoblotting methods. Studies were performed in 19 Addison disease patients, 16 women (age range: 28-63 yrs, median: 43.5 +/- 8.9) and 3 men (age range: 18-45 yrs, median: 30.6 +/- 9.8). All patients presented signs and symptoms typical of primary insufficiency of adrenal cortex. Sera of control subjects were obtained from 10 healthy blood donors, 7 women, 3 men (age range 21-45 yrs, median: 30.6 +/- 7.1). Incidence of pituitary autoantibodies was assessed by polyacrylamide electrophoresis gel and western-blotting. Pituitary microsomes were obtained from human pituitary tissues by ultracentrifugation and solubilisation in 1% desoxycholic acid. In 14 sera from 19 we detected autoantibodies against pituitary microsomal antigen 67 kDa, 12 sera were recting with 60 kDa and 10 sera with 55 kDa. It is important to note that 10 sera were reacting with 67 and 55 kDa, and 9 sera with 55, 60 and 67 kDa. In sera of Addison disease patients autoantibodies against pituitary microsomal antigens can be frequently detected. The most frequent are antibodies against 55, 60 and 67 kDa antigens.

Impact of the primary aetiology upon the clinical outcome of adults with childhood-onset GH deficiency.

PubMed

Hoybye, Charlotte; Jönsson, Peter; Monson, John P; Koltowska-Häggström, Maria; Hána, Václav; Geffner, Mitchell; Abs, Roger

2007-11-01

The impact of the aetiology of childhood-onset GH deficiency (CO-GHD) on the clinical presentation during adulthood and the response to GH replacement has been poorly defined. Our study aims to characterize CO-GHD in adults due to different aetiologies and evaluate the effect of 2 years of GH replacement therapy. Data from 353 adults with CO-GHD from Pfizer International Metabolic Database KIMS were retrospectively grouped according to GHD aetiology: non-organic disorder (n=147), organic pituitary disease (n=159), and brain tumour (n=47). Extent of pituitary dysfunction, IGF-I concentration, lipid concentrations and quality-of-life (QoL) were assessed at baseline and after 2 years of GH replacement. GHD was diagnosed at a later age in the organic pituitary group than in the other groups, resulting in a shorter duration of GH treatment during childhood. However, the final height was greater in the organic pituitary group. Panhypopituitarism was most common in the non-organic disorder and in the organic pituitary groups, while isolated GHD was more prominent in the brain tumour group. Serum IGF-I levels were the lowest in the non-organic group. QoL was the poorest in the brain tumour group. Lipid profile and QoL improved significantly during GH replacement. The adverse consequences of CO-GHD in adulthood vary between aetiologies, but improve similarly with GH treatment. It is, therefore, important to consider retesting all patients with CO-GHD in early adulthood and, if persistent severe GHD is confirmed, recommence GH replacement.

Reliability of magnetic resonance imaging for the detection of hypopituitarism in children with optic nerve hypoplasia.

PubMed

Ramakrishnaiah, Raghu H; Shelton, Julie B; Glasier, Charles M; Phillips, Paul H

2014-01-01

It is essential to identify hypopituitarism in children with optic nerve hypoplasia (ONH) because they are at risk for developmental delay, seizures, or death. The purpose of this study is to determine the reliability of neurohypophyseal abnormalities on magnetic resonance imaging (MRI) for the detection of hypopituitarism in children with ONH. Cross-sectional study. One hundred one children with clinical ONH who underwent MRI of the brain and orbits and a detailed pediatric endocrinologic evaluation. Magnetic resonance imaging studies were performed on 1.5-Tesla scanners. The imaging protocol included sagittal T1-weighted images, axial fast fluid-attenuated inversion-recovery/T2-weighted images, and diffusion-weighted images of the brain. Orbital imaging included fat-saturated axial and coronal images and high-resolution axial T2-weighted images. The MRI studies were reviewed by 2 pediatric neuroradiologists for optic nerve hypoplasia, absent or ectopic posterior pituitary, absent pituitary infundibulum, absent septum pellucidum, migration anomalies, and hemispheric injury. Medical records were reviewed for clinical examination findings and endocrinologic status. All patients underwent a clinical evaluation by a pediatric endocrinologist and a standardized panel of serologic testing that included serum insulin-like growth factor-1, insulin-like growth factor binding protein-3, prolactin, cortisol, adrenocorticotropic hormone, thyroid-stimulating hormone, and free thyroxine levels. Radiologists were masked to patients' endocrinologic status and funduscopic findings. Sensitivity and specificity of MRI findings for the detection of hypopituitarism. Neurohypophyseal abnormalities, including absent pituitary infundibulum, ectopic posterior pituitary bright spot, and absent posterior pituitary bright spot, occurred in 33 children. Magnetic resonance imaging disclosed neurohypophyseal abnormalities in 27 of the 28 children with hypopituitarism (sensitivity, 96%). A normal neurohypophysis occurred in 67 of 73 children with normal endocrinologic function (specificity, 92%). Neurohypophyseal abnormalities on MRI are sensitive and specific indicators of hypopituitarism in children with ONH. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

A patient with thyrotropinoma cosecreting growth hormone and follicle-stimulating hormone with low alpha-glycoprotein: a new subentity?

PubMed

Elhadd, Tarik A; Ghosh, Sujoy; Teoh, Wei Leng; Trevethick, Katy Ann; Hanzely, Zoltan; Dunn, Laurence T; Malik, Iqbal A; Collier, Andrew

2009-08-01

Thyrotropinomas are rare pituitary tumors. In 25 percent of cases there is autonomous secretion of a second pituitary hormone, adding to the clinical complexity. We report a patient with thyrotropin (TSH)-dependant hyperthyroidism along with growth hormone (GH) and follicle-stimulating hormone (FSH) hypersecretion but low alpha-glycoprotein (alpha-subunit) concentrations, a hitherto unique constellation of findings. A 67-year-old Scottish lady presented with longstanding ankle edema, paroxysmal atrial fibrillation, uncontrolled hypertension, fine tremors, warm peripheries, and agitation. Initial findings were a small goiter, elevated serum TSH of 7.37 mU/L (normal range, 0.30-6.0 mU/L), a free-thyroxine concentration of 34.9 pmol/L (normal range, 9.0-24.0 pmol/L), a flat TSH response to TSH-releasing hormone, and serum alpha-subunit of 3.1 IU/L (normal, <3.0 IU/L). There was no evidence of an abnormal thyroid hormone beta receptor by genotyping. Serum FSH was 56.8 U/L, but the luteinizing hormone (LH) was 23.6 U/L (postmenopausal FSH and LH reference ranges both >30 U/L) Basal insulin-like growth factor I was elevated to 487 microg/L with the concomitant serum GH being 14.1 mU/L, and subsequent serum GH values 30 minutes after 75 g oral glucose being 19.1 mU/L and 150 minutes later being 13.7 mU/L. An magnetic resonance imaging pituitary revealed a macroadenoma. Pituitary adenomectomy was performed with the histology confirming a pituitary adenoma, and the immunohistochemistry staining showed positive reactivity for FSH with scattered cells staining for GH and TSH. Staining for other anterior pituitary hormones was negative. After pituitary surgery she became clinically and biochemically euthyroid, the serum IFG-1 became normal, but the pattern of serum FSH and LH did not change. This case of plurihormonal thyrotropinoma is unique in having hypersecretion of TSH, GH, and FSH with low alpha-subunit. Such a combination may represent a new subentity of TSHomas.

Obsessive-compulsive disorder: a disorder of pessimal (non-functional) motor behavior.

PubMed

Zor, R; Keren, H; Hermesh, H; Szechtman, H; Mort, J; Eilam, D

2009-10-01

To determine whether in addition to repetitiveness, the motor rituals of patients with obsessive-compulsive disorder (OCD) involve reduced functionality due to numerous and measurable acts that are irrelevant and unnecessary for task completion. Comparing motor rituals of OCD patients with behavior of non-patient control individuals who were instructed to perform the same motor task. Obsessive-compulsive disorder behavior comprises abundant acts that were not performed by the controls. These acts seem unnecessary or even irrelevant for the task that the patients were performing, and therefore are termed 'non-functional'. Non-functional acts comprise some 60% of OCD motor behavior. Moreover, OCD behavior consists of short chains of functional acts bounded by long chains of non-functional acts. The abundance of irrelevant or unnecessary acts in OCD motor rituals represents reduced functionality in terms of task completion, typifying OCD rituals as pessimal behavior (antonym of optimal behavior).

Pituitary dysfunction following traumatic brain injury: clinical perspectives

PubMed Central

Tanriverdi, Fatih; Kelestimur, Fahrettin

2015-01-01

Traumatic brain injury (TBI) is a well recognized public health problem worldwide. TBI has previously been considered as a rare cause of hypopituitarism, but an increased prevalence of neuroendocrine dysfunction in patients with TBI has been reported during the last 15 years in most of the retrospective and prospective studies. Based on data in the current literature, approximately 15%–20% of TBI patients develop chronic hypopituitarism, which clearly suggests that TBI-induced hypopituitarism is frequent in contrast with previous assumptions. This review summarizes the current data on TBI-induced hypopituitarism and briefly discusses some clinical perspectives on post-traumatic anterior pituitary hormone deficiency. PMID:26251600

Thyroid abnormalities after therapeutic external radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hancock, S.L.; McDougall, I.R.; Constine, L.S.

1995-03-30

The thyroid gland is the largest pure endocrine gland in the body and one of the organs most likely to produce clinically significant abnormalities after therapeutic external radiation. Radiation doses to the thyroid that exceed approximately 26 Gy frequently produce hypothyroidism, which may be clinically overt or subclinical, as manifested by increased serum thyrotropin and normal serum-free thyroxine concentrations. Pituitary or hypothalamic hypothyroidism may arise when the pituitary region receives doses exceeding 50 Gy with conventional, 1.8-2 Gy fractionation. Direct irradiation of the thyroid may increase the risk of Graves` disease or euthyroid Graves` ophthalmopathy. Silent thyroiditis, cystic degeneration, benignmore » adenoma, and thyroid cancer have been observed after therapeutically relevant doses of external radiation. Direct or incidental thyroid irradiation increases the risk for well-differentiated, papillary, and follicular thyroid cancer from 15- to 53-fold. Thyroid cancer risk is highest following radiation at a young age, decreases with increasing age at treatment, and increases with follow-up duration. The potentially prolonged latent period between radiation exposure and the development of thyroid dysfunction, thyroid nodularity, and thyroid cancer means that individuals who have received neck or pituitary irradiation require careful, periodic clinical and laboratory evaluation to avoid excess morbidity. 39 refs.« less

[Clinical values of triptorelin stimulating test in assessing hypothalamus-pituitary-gonad axis function in male patients with hypothalamus-pituitary-gonad axis disorders].

PubMed

Wu, Xue-yan; Nie, Min; Lu, Shuang-yu; Mao, Jiang-feng

2011-03-15

To investigate the clinical values of luteinizing hormone-releasing hormone (LHRH) α (triptorelin) stimulating test in the differential diagnoses of hypothalamus-pituitary-gonad axis (HPGA) disorders. A total of 229 male patients with various HPGA disorders were recruited for triptorelin stimulating test. And all patients were followed up for 12 - 48 months until a definite diagnosis was made. The values of triptorelin stimulating test in the differential diagnoses of HPGA disorders were assessed by examining the close relationship between LHmax and the final clinical diagnosis. (1) LH levels rose steady after an intramuscular injection of triptorelin 100 µg and the time of LHmax appeared at 45 - 60 min. (2) LHmax < 4 U/L indicated the function of HPGA was not activated. LHmax in the range of 4 - 12 U/L indicated the patients might have constitutional delayed puberty development. LHmax > 12 U/L indicated the fulfilled puberty development. Triptorelin stimulating test can precisely evaluate the functions of HPGA in various HPGA disorders and provide valuable information for the differential diagnoses in constitutional delayed puberty development, hypogonadotropic hypogonadism, central and peripheral precocious puberty disorders.

Inhibition of NFkappaB reduces cellular viability in GH3 pituitary adenoma cells.

PubMed

Vender, John R; Laird, Melissa D; Dhandapani, Krishnan M

2008-05-01

Adenomas of the pituitary gland are among the most common types of tumors of the adult brain. Although adenomas are histologically benign, they may be associated with significant morbidity and mortality, mostly because of their invasive growth pattern and hormone hypersecretion. Current medical therapies are suppressive, acting at a receptor level. Thus, there is a need to identify novel cellular and molecular targets for pituitary tumors. We investigated the possible role of the NFkappaB transcription factor in pituitary tumor cell growth. The effect of NFkappaB pathway inhibition on cellular viability was studied in the GH3 pituitary adenoma cell line, a well-characterized rat cell line that secretes growth hormone and prolactin. Cells were treated with mechanistically diverse pharmacological NFkappaB pathway inhibitors or with molecular inhibitors that were overexpressed in tumor cells before the assessment of cellular viability. NFkappaB activity was also assessed in GH3 cells using deoxyribonucleic acid binding assays. GH3 cells exhibited constitutive NFkappaB activity, which contributed to increased cellular proliferation. Treatment with wedelolactone, an IkappaB kinase inhibitor, or overexpression of an IkappaB super-repressor reduced cell viability, further implicating NFkappaB in pituitary tumor cell growth. Pharmacological or molecular inhibition of Akt similarly reduced GH3 viability and NFkappaB binding, suggesting that constitutive activation of NFkappaB may be, at least in part, mediated by Akt. Directed targeting of the Akt and NFkappaB signaling pathways may be a useful adjunct in the clinical management of pituitary tumors. Further elucidation of this pathway may yield novel information regarding the behavior of pituitary tumors in humans.

Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis.

PubMed

Iwata, Naoko; Iwama, Shintaro; Sugimura, Yoshihisa; Yasuda, Yoshinori; Nakashima, Kohtaro; Takeuchi, Seiji; Hagiwara, Daisuke; Ito, Yoshihiro; Suga, Hidetaka; Goto, Motomitsu; Banno, Ryoichi; Caturegli, Patrizio; Koike, Teruhiko; Oshida, Yoshiharu; Arima, Hiroshi

2017-06-01

IgG4-related disease is a systemic inflammatory disease characterized by infiltration of IgG4-positive plasma cells into multiple organs, including the pituitary gland. Autoimmunity is thought to be involved in the pathogenesis of IgG4-related disease. The diagnosis of IgG4-related hypophysitis (IgG4-RH) is difficult because its clinical features, such as pituitary swelling and hypopituitarism, are similar to those of other pituitary diseases, including lymphocytic hypophysitis and sellar/suprasellar tumors. The presence and significance of anti-pituitary antibodies (APA) in IgG4-RH is unclear. In this case-control study, we used single indirect immunofluorescence on human pituitary substrates to assess the prevalence of serum APA in 17 patients with IgG4-RH, 8 control patients with other pituitary diseases (lymphocytic infundibulo-neurohypophysitis, 3; craniopharyngioma, 2; germinoma, 3), and 9 healthy subjects. We further analyzed the endocrine cells targeted by the antibodies using double indirect immunofluorescence. APA were found in 5 of 17 patients with IgG4-RH (29%), and in none of the pituitary controls or healthy subjects. The endocrine cells targeted by the antibodies in the 5 IgG4-RH cases were exclusively corticotrophs. Antibodies were of the IgG1 subclass, rather than IgG4, in all 5 cases, suggesting that IgG4 is not directly involved in the pathogenesis. Finally, antibodies recognized pro-opiomelanocortin in 2 of the cases. Our study suggests that autoimmunity is involved in the pathogenesis of IgG4-RH and that corticotrophs are the main antigenic target, highlighting a possible new diagnostic marker for this condition.

15 CFR 90.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... non-functioning county or statistical equivalent means a sub-state entity that does not function as an... program, an eligible governmental unit also includes the District of Columbia and non-functioning counties or statistical equivalents represented by a FSCPE member agency. ...

Equine pituitary pars intermedia dysfunction: current understanding and recommendations from the Australian and New Zealand Equine Endocrine Group.

PubMed

Secombe, C J; Bailey, S R; de Laat, M A; Hughes, K J; Stewart, A S; Sonis, J M; Tan, Rhh

2018-06-03

The purpose of this article is to provide a review of the current knowledge and opinions about the epidemiology, clinical findings (including sequelae), diagnosis, treatment and monitoring of equine pituitary pars intermedia dysfunction, particularly in the Australian context. This information and the recommendations provided will assist practitioners in making informed decisions regarding the diagnosis and management of this disorder. © 2018 Australian Veterinary Association.

Clinical characteristics, etiologies and pathophysiology of patients with severe short stature with severe GH deficiency: questionnaire study on the data registered with the foundation for growth science, Japan.

PubMed

Hanew, Kunihiko; Tachibana, Katsuhiko; Yokoya, Susumu; Fujieda, Kenji; Tanaka, Toshiaki; Igarashi, Yutaka; Shimatsu, Akira; Tanaka, Hiroyuki; Tanizawa, Takakuni; Teramoto, Akira; Nishi, Yoshikazu; Hasegawa, Yukihiro; Hizuka, Naomi; Hirano, Takeki; Fujita, Keinosuke

2006-04-01

In this study, we sent questionnaires to doctors treating severe short stature with severe GH deficiency (GHD) (height SDS (HtSDS) below -4 and all peak GH to provocative stimuli below 2 micro/L) (abbreviated as Severe Case), and obtained effective replies of 51 cases. The clinical characteristics, etiologies, and pathophysiology of these patients were examined. Among the 51 Severe Cases no consanguinity was observed, 44 were IGHD (24 males and 20 females), 3 were GH-1 gene deletion, 2 were Pit-1 gene mutation, and 2 were achondroplasia. HtSDS in these Severe Cases was already remarkably low at 12 (-3.0) and 24 months old (-3.9), while their birth weight and birth length were within normal ranges. Among 44 patients with IGHD, 12 were isolated GHD, and the remaining 32 were combined pituitary hormone deficiency (CPHD). Pituitary MRI was undergone in 25 idiopathic GHD, and abnormal findings (pituitary atrophy, interruption of stalk, and ectopic posterior lobe) were observed in 21 patients with CPHD. More than half of these patients had the history of breech delivery. Three patients with GH-1 gene mutation showed normal pituitary MRI, whereas one of two patients with Pit-1 mutation showed pituitary atrophy and narrowing of pituitary stalk. In conclusion, Severe Cases tended to have CPHD, and the incidence of Severe Case was only 0.6% of total IGHD. Although GHD due to genetic disorders is considered to be extremely rare (0.06% of total IGHD), the incidence reaches high levels (9.8%) among Severe Cases. Growth disorders in these Severe Cases seem to occur soon after delivery. Much earlier diagnosis and hGH treatment are desirable to attain better final height in the Severe Cases. GH-1 and Pit-1 gene analyses are crucial, when genetic abnormalities other than achondroplasia are suspected.

General Information about Pituitary Tumors

MedlinePlus

... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ... Twitter Instagram YouTube Google+ LinkedIn GovDelivery RSS CONTACT INFORMATION Contact Us LiveHelp Online Chat MORE INFORMATION About ...

X-linked acrogigantism syndrome: clinical profile and therapeutic responses.

PubMed

Beckers, Albert; Lodish, Maya Beth; Trivellin, Giampaolo; Rostomyan, Liliya; Lee, Misu; Faucz, Fabio R; Yuan, Bo; Choong, Catherine S; Caberg, Jean-Hubert; Verrua, Elisa; Naves, Luciana Ansaneli; Cheetham, Tim D; Young, Jacques; Lysy, Philippe A; Petrossians, Patrick; Cotterill, Andrew; Shah, Nalini Samir; Metzger, Daniel; Castermans, Emilie; Ambrosio, Maria Rosaria; Villa, Chiara; Strebkova, Natalia; Mazerkina, Nadia; Gaillard, Stéphan; Barra, Gustavo Barcelos; Casulari, Luis Augusto; Neggers, Sebastian J; Salvatori, Roberto; Jaffrain-Rea, Marie-Lise; Zacharin, Margaret; Santamaria, Beatriz Lecumberri; Zacharieva, Sabina; Lim, Ee Mun; Mantovani, Giovanna; Zatelli, Maria Chaira; Collins, Michael T; Bonneville, Jean-François; Quezado, Martha; Chittiboina, Prashant; Oldfield, Edward H; Bours, Vincent; Liu, Pengfei; W de Herder, Wouter; Pellegata, Natalia; Lupski, James R; Daly, Adrian F; Stratakis, Constantine A

2015-06-01

X-linked acrogigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological, and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and microduplication of chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in two families was dominant, with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2-3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight standard deviation scores (SDS) of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF1 and usually prolactin, due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection, but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high levels of expression of somatostatin receptor subtype-2 in tumor tissue. Postoperative use of adjuvant pegvisomant resulted in control of IGF1 in all five cases where it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management. © 2015 Society for Endocrinology.

Frostbite of the liver: an unrecognized cause of primary non-function?

PubMed

Potanos, Kristina; Kim, Heung Bae

2014-02-01

Appropriate hypothermic packaging techniques are an essential part of organ procurement. We present a case in which deviation from standard packaging practice may have caused sub-zero storage temperatures during transport, resulting in a clinical picture resembling PNF. An 18-month-old male with alpha-1-antitrypsin deficiency underwent liver transplant from a size-matched pediatric donor. Upon arrival at the recipient hospital, ice crystals were noted in the UW solution. The transplant proceeded uneventfully with short ischemia times. Surprisingly, transaminases, INR, and total bilirubin were markedly elevated in the postoperative period but returned to near normal by discharge. Follow-up of over five yr has demonstrated normal liver function. Upon review, it was discovered that organ packaging during recovery included storage in the first bag with only 400 mL of UW solution, and pure ice in the second bag instead of slush. This suggests that the postoperative delayed graft function was related to sub-zero storage of the graft during transport. This is the first report of sub-zero cold injury, or frostbite, following inappropriate packaging of an otherwise healthy donor liver. The clinical picture closely resembled PNF, perhaps implicating this mechanism in other unexpected cases of graft non-function. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Surgical Results of Pure Endoscopic Endonasal Transsphenoidal Surgery for 331 Pituitary Adenomas: A 15-Year Experience from a Single Institution.

PubMed

Jang, Ji Hwan; Kim, Kyu Hong; Lee, Young Min; Kim, Joon Soo; Kim, Young Zoon

2016-12-01

The aim of this study is to report the results of pure endoscopic endonasal transsphenoidal surgery (EETSS) for pituitary adenomas (PAs) and to evaluate the efficacy and safety of this procedure. In addition, we tried to determine the predicting factors for progression of PAs. We reviewed the medical records of 331 consecutive patients who underwent pure EETSS of newly diagnosed PAs between April 1998 and December 2014. Demographic, endocrinologic, and radiologic features and their outcomes, complications, and hospital stay durations were retrospectively assessed in these patients. There were 157 (47.4%) nonfunctioning adenomas and 174 (52.6%) hormone-secreting adenomas. Fifty-one (15.4%) complications were present in 39 patients postoperatively. The frequent complications were temporary and permanent diabetes insipidus (14 and 3 cases, respectively), syndrome of inappropriate antidiuretic hormone secretion (9 cases), and cerebrospinal fluid leaks (6 cases). There was only 1 death (0.3%) related to the procedure in this series. The patient's age (P = 0.047), the tumor size (P = 0.003), and the parasellar growth (P <0.001) were associated with the occurrence of complications on multivariate analysis. Progression occurred in 92 (27.8%) patients and the mean time-to-progression was 23.7 months (range, 3.7-52.4 months) after a mean follow-up period of 68.5 months. In the multivariate analysis, the tumor size (P = 0.021), the extent of surgery (P = 0.012), the Knosp classification (P = 0.002), and the MIB-1 index (P = 0.019) were associated with progression-free survival. The mean duration of hospitalization was 4.4 (±1.6) days. The pure EETSS of PA provides acceptable and reasonable results representing a safe alternative procedure to the traditional transsphenoidal microscopic approach. Copyright © 2016 Elsevier Inc. All rights reserved.

Single-surgeon fully endoscopic endonasal transsphenoidal surgery: outcomes in three-hundred consecutive cases.

PubMed

Mamelak, Adam N; Carmichael, John; Bonert, Vivien H; Cooper, Odelia; Melmed, Shlomo

2013-09-01

The objective of this study was to evaluate outcomes of endoscopic transsphenoidal surgery using a single-surgeon technique as an alternative to the more commonly employed two-surgeon, three-hand method. Three hundred consecutive endoscopic transsphenoidal procedures performed over a 5 year period from 2006 to 2011 were reviewed. All procedures were performed via a binasal approach utilizing a single surgeon two handed technique with a pneumatic endoscope holder. Expanded enodnansal cases were excluded. Surgical technique, biochemical and surgical outcomes, and complications were analyzed. 276 patients underwent 300 consecutive surgeries with a mean follow-up period of 37 ± 22 months. Non-functioning pituitary adenoma (NFPA) was the most common pathology (n = 152), followed by growth hormone secreting tumors (n = 41) and Rathke's cleft cysts (n = 30). Initial gross total cyst drainage based on radiologic criteria was obtained in 28 cases of Rathke's cleft cyst, with 5 recurrences. For NFPA and other pathologies (n = 173) gross total resection was obtained in 137 cases, with a 92% concordance rate between observed and expected extent of resection. For functional adenoma, remission rates were 30/41 (73%) for GH-secreting, 12/12 (100%) for ACTH-secreting, and 8/17 (47%) for prolactin-secreting tumors. Post-operative complications included transient (11%) and permanent (1.4%) diabetes insipidus, hyponatremia (13%), and new anterior pituitary hormonal deficits (1.4%). CSF leak occurred in 42 cases (15%), and four patients required surgical repair. Two carotid artery injuries occurred, both early in the series. Epistaxis and other rhinological complications were noted in 10% of patients, most of which were minor and diminished as surgical experience increased. Fully endoscopic single surgeon transsphenoidal surgery utilizing a binasal approach and a pneumatic endoscope holder yields outcomes comparable to those reported with a two-surgeon method. Endoscopic outcomes appear to be better than those reported in microscope-based series, regardless of a one or two surgeon technique.

Sir Victor Horsley: pioneer craniopharyngioma surgeon.

PubMed

Pascual, José M; Prieto, Ruth; Mazzarello, Paolo

2015-07-01

Sir Victor Horsley (1857-1916) is considered to be the pioneer of pituitary surgery. He is known to have performed the first surgical operation on the pituitary gland in 1889, and in 1906 he stated that he had operated on 10 patients with pituitary tumors. He did not publish the details of these procedures nor did he provide evidence of the pathology of the pituitary lesions operated on. Four of the patients underwent surgery at the National Hospital for Neurology and Neurosurgery (Queen Square, London), and the records of those cases were recently retrieved and analyzed by members of the hospital staff. The remaining cases corresponded to private operations whose records were presumably kept in Horsley's personal notebooks, most of which have been lost. In this paper, the authors have investigated the only scientific monograph providing a complete account of the pituitary surgeries that Horsley performed in his private practice, La Patologia Chirurgica dell'Ipofisi (Surgical Pathology of the Hypophysis), written in 1911 by Giovanni Verga, Italian assistant professor of anatomy at the University of Pavia. They have traced the life and work of this little-known physician who contributed to the preservation of Horsley's legacy in pituitary surgery. Within Verga's pituitary treatise, a full transcription of Horsley's notes is provided for 10 pituitary cases, including the patients' clinical symptoms, surgical techniques employed, intraoperative findings, and the outcome of surgery. The descriptions of the topographical and macroscopic features of two of the lesions correspond unmistakably to the features of craniopharyngiomas, one of the squamous-papillary type and one of the adamantinomatous type. The former lesion was found on necropsy after the patient's sudden death following a temporal osteoplastic craniectomy. Surgical removal of the lesion in the latter case, with the assumed nature of an adamantinomatous craniopharyngioma, was successful. According to the evidence provided in Giovanni Verga's monograph, it can be claimed that Sir Victor Horsley was not only the pioneer of pituitary gland surgery but also the pioneer of craniopharyngioma surgery.

Central diabetes insipidus in children and young adults: etiological diagnosis and long-term outcome of idiopathic cases.

PubMed

Di Iorgi, Natascia; Allegri, Anna Elsa Maria; Napoli, Flavia; Calcagno, Annalisa; Calandra, Erika; Fratangeli, Nadia; Vannati, Marianna; Rossi, Andrea; Bagnasco, Francesca; Haupt, Riccardo; Maghnie, Mohamad

2014-04-01

Central diabetes insipidus (CDI) is considered idiopathic in 20% to 50% of affected subjects. The purpose of this study was to determine whether a systematic diagnostic workup could achieve better etiologic diagnosis in children and adolescents presenting with polyuria and polydipsia. This is a prospective study conducted at a tertiary referral center. Patients underwent clinical and endocrine evaluations every 6 months and neuroimaging every 6 months for 2 years and yearly for 3 years. Endocrine function and neuroimaging were also reassessed after adult height achievement. A total of 85 consecutive patients with CDI were enrolled at a median age of 7.5 years; those with idiopathic CDI were stratified based on pituitary stalk thickness. To establish the etiology of CDI, we determined the time lag between its onset and the specific diagnosis, the long-term impact on pituitary function, and the overall long-term outcomes. Of the subjects, 24 (28.2%) received an etiologic diagnosis at presentation and 11 (13%) within 2.5 years (n = 7 germinomas and n = 4 Langerhans cell histiocytosis), 7 (8.2%) were lost to follow-up, and 43 (50.6%) were considered to have idiopathic disease and were followed until the median age of 17.3 years. Neuroimaging identified 40 of 43 patients with self-limited inflammatory/autoimmune pituitary stalk thickness within the first 6 months, the severity of which was significantly correlated to pituitary dysfunction. The probability of >10-year-survival without an anterior pituitary defect was related to the severity of pituitary stalk thickness, and 53% showed permanent anterior pituitary defects. Three patients developed Langerhans cell histiocytosis and 1 developed Hodgkin lymphoma after a median of 9 and 13 years, respectively. A diagnostic etiology was achieved in 96% of patients with CDI. Risk stratification based on the degree of pituitary stalk thickness is of prognostic value for long-term outcomes including permanent pituitary dysfunction. New guidance is provided for the management of these patients.

An Approach for Integrating the Prioritization of Functional and Nonfunctional Requirements

PubMed Central

Dabbagh, Mohammad; Lee, Sai Peck

2014-01-01

Due to the budgetary deadlines and time to market constraints, it is essential to prioritize software requirements. The outcome of requirements prioritization is an ordering of requirements which need to be considered first during the software development process. To achieve a high quality software system, both functional and nonfunctional requirements must be taken into consideration during the prioritization process. Although several requirements prioritization methods have been proposed so far, no particular method or approach is presented to consider both functional and nonfunctional requirements during the prioritization stage. In this paper, we propose an approach which aims to integrate the process of prioritizing functional and nonfunctional requirements. The outcome of applying the proposed approach produces two separate prioritized lists of functional and non-functional requirements. The effectiveness of the proposed approach has been evaluated through an empirical experiment aimed at comparing the approach with the two state-of-the-art-based approaches, analytic hierarchy process (AHP) and hybrid assessment method (HAM). Results show that our proposed approach outperforms AHP and HAM in terms of actual time-consumption while preserving the quality of the results obtained by our proposed approach at a high level of agreement in comparison with the results produced by the other two approaches. PMID:24982987

An approach for integrating the prioritization of functional and nonfunctional requirements.

PubMed

Dabbagh, Mohammad; Lee, Sai Peck

2014-01-01

Due to the budgetary deadlines and time to market constraints, it is essential to prioritize software requirements. The outcome of requirements prioritization is an ordering of requirements which need to be considered first during the software development process. To achieve a high quality software system, both functional and nonfunctional requirements must be taken into consideration during the prioritization process. Although several requirements prioritization methods have been proposed so far, no particular method or approach is presented to consider both functional and nonfunctional requirements during the prioritization stage. In this paper, we propose an approach which aims to integrate the process of prioritizing functional and nonfunctional requirements. The outcome of applying the proposed approach produces two separate prioritized lists of functional and non-functional requirements. The effectiveness of the proposed approach has been evaluated through an empirical experiment aimed at comparing the approach with the two state-of-the-art-based approaches, analytic hierarchy process (AHP) and hybrid assessment method (HAM). Results show that our proposed approach outperforms AHP and HAM in terms of actual time-consumption while preserving the quality of the results obtained by our proposed approach at a high level of agreement in comparison with the results produced by the other two approaches.

T3 receptors in human pituitary tumors.

PubMed

Machiavelli, Gloria A; Pauni, Micaela; Heredia Sereno, Gastón M; Szijan, Irene; Basso, Armando; Burdman, José A

2009-11-01

The purpose of this work was to investigate the synthesis of T3 receptors in human tumors of the anterior pituitary gland, its relationship with the hormone synthesized and/or secreted by the tumor and the post-surgical evolution of the patient. Patients were evaluated clinically and by magnetic nuclear resonance to classify the adenoma according to their size. Hormonal concentrations in sera were determined by radioimmunoassay. Immunohistochemistry of the pituitary hormones was performed in the tumors. Tumors were obtained at surgery and immediately frozen in ice, transported to the laboratory and stored at -70 degrees C. Reverse transcription was performed with purified RNA from the tumors. Out of 33 pituitary tumors, 29 had RNA for T3 receptors synthesis (88%). They were present in different histological specimens, the tumors were grades 1-4 according to their size, and there was no relationship between the size of the tumor and the presence of T3 receptor RNAs. The post-surgical evolution of the patient was mostly dependent on the size and not on the presence of T3 receptors. The presence of thyroid hormone receptors in pituitary tumors is in line with two important characteristics of these tumors: they are histologically benign and well differentiated.

Occurrence of primary lymphocytic hypophysitis in two horses and presence of scattered T-lymphocytes in the normal equine pituitary gland.

PubMed

Grau-Roma, Llorenç; Peckham, Robert; Paton, Jacqui; Stahel, Anina; de Brot, Simone

2017-01-01

The postmortem examination of a 14-y-old Appaloosa gelding with clinically diagnosed pituitary pars intermedia dysfunction showed a unique finding of moderate multifocal lymphocytic hypophysitis (LH). The pituitary glands of 24 horses submitted for postmortem examination were examined grossly and examined histologically for the presence of lymphocytes. Of these 23 horses, 1 additional case suffered from moderate LH. The 2 cases with LH tested negative for Equid herpesvirus 1 and 4 by polymerase chain reaction and immunohistochemistry (IHC), and no viral particles were observed by electron microscopy in 1 case examined. The cause of LH remains unknown, but based on the T-lymphocytic nature of the inflammation and the human literature, an immune-mediated origin is hypothesized. In addition, the review of 24 cases revealed that 10 horses had few and small multifocal lymphocytic infiltrates within the pituitary gland; the remaining 12 horses showed no evident lymphocytes when examined by hematoxylin and eosin. IHC for CD3 showed the presence of a small number of individual T-lymphocytes scattered through the gland in all examined horses, which appears therefore to be a normal feature of the pituitary gland in horses.

Development of two surgical approaches to the pituitary gland in the Horse.

PubMed

Carmalt, James L; Scansen, Brian A

2018-12-01

Current treatment of equine pituitary pars intermedia dysfunction (PPID) requires daily oral medication. Minimally invasive surgical palliation of this condition is appealing as a single treatment to alleviate the clinical signs of disease, dramatically improving the welfare of the horse. To develop a surgical approach to the equine pituitary gland, for subsequent treatment of PPID. A cadaver study to develop methodology and a terminal procedure under anaesthesia in the most promising techniques. Four surgical approaches to the pituitary gland were investigated in cadaver animals. A ventral trans-basispheniodal osteotomy and a minimally invasive intravenous approach via the ventral cavernous sinus progressed to live horse trials. Technical complications prevented the myeloscopic and trans-sphenopalatine sinus techniques from being successful. The ventral basisphenoidal osteotomy was repeatable and has potential if an intra-operative imaging guidance system could be employed. The minimally invasive approach was repeatable, atraumatic and relatively inexpensive. A minimally invasive surgical approach to the equine pituitary gland is possible and allows for needle placement within the target tissue. More work is necessary to determine what that treatment might be, but repeatable access to the gland has been obtained, which is a promising step.

Long-term effects of octreotide on pituitary gigantism: its analgesic action on cluster headache.

PubMed

Otsuka, Fumio; Mizobuchi, Satoshi; Ogura, Toshio; Sato, Kenji; Yokoyama, Masataka; Makino, Hirofumi

2004-10-01

We report the case of 19-year-old man with pituitary gigantism due to growth hormone-producing pituitary macroadenoma. The patient complained of recurrent headache and excessive growth spurt since age 15. Octreotide administration was initiated following transsphenoidal pituitary adenomectomy. Octreotide injection for 4 years efficaciously reduced the size of remnant adenoma as well as serum growth hormone levels. Notably, octreotide exhibited a potent analgesic effect on his intractable cluster headache that has continued even after reduction of the adenoma volume. The analgesic effect lasted 2 to 6 hours after each injection and no tachyphylaxis to octreotide appeared during 4-year treatment. To characterize the headache and the pain intensity, analgesic drugs including octreotide, lidocaine, morphine and thiopental were tested using a visual analogue scale (VAS) evaluation, with the result that octreotide exhibited a prompt and complete disappearance of the headache. Headache relief was in part reproduced by morphine injection (56% reduction) but not by lidocaine or thiopental. The present case suggests that the intractable headache associated with pituitary gigantism is possibly related to the endogenous opioid system. Thus, the headache control by octreotide is clinically helpful for continuation of the self-injection regimen.

Screening for genetic causes of growth hormone hypersecretion.

PubMed

Rostomyan, Liliya; Beckers, Albert

Growth hormone (GH) secreting pituitary tumors may be caused by genetic abnormalities in a variety of genes including AIP, MEN1, CDKN1B, and PRKAR1A. These can lead to GH secreting pituitary adenomas as an isolated occurrence (e.g. as aggressive sporadic adenomas or in familial isolated pituitary adenomas (FIPA)) or as part of syndromic conditions such as MEN1 or Carney complex. These tumors have more aggressive features than sporadic acromegaly, including a younger age at disease onset and larger tumor size, and they can be challenging to manage. In addition to mutations or deletions, copy number variation at the GPR101 locus may also lead to mixed GH and prolactin secreting pituitary adenomas in the setting of X-linked acrogigantism (X-LAG syndrome). In X-LAG syndrome and in McCune Albright syndrome, mosaicism for GPR101 duplications and activating GNAS1 mutations, respectively, contribute to the genetic pathogenesis. As only 5% of pituitary adenomas have a known cause, efficient deployment of genetic testing requires detailed knowledge of clinical characteristics and potential associated syndromic features in the patient and their family. Copyright © 2016 Elsevier Ltd. All rights reserved.

Panhypopituitarism presenting as life-threatening heart failure caused by an inherited microdeletion in 1q25 including LHX4.

PubMed

Filges, Isabel; Bischof-Renner, Andrea; Röthlisberger, Benno; Potthoff, Christian; Glanzmann, René; Günthard, Joëlle; Schneider, Jacques; Huber, Andreas R; Zumsteg, Urs; Miny, Peter; Szinnai, Gabor

2012-02-01

Clinical presentation of hypopituitarism in the neonate may be variable, ranging from absent to severe nonspecific symptoms and may be life-threatening in patients with adrenocorticotropic hormone deficiency. The LIM homeobox gene 4 (LHX4) transcription factor regulates early embryonic development of the anterior pituitary gland. Autosomal dominant mutations in LHX4 cause congenital hypopituitarism with variable combined pituitary hormone deficiency (CPHD). We report on a neonate with unexplained heart failure and minor physical anomalies, suggesting a midline defect. She was diagnosed with complete CPHD. Cardiac function was rescued by replacement with hydrocortisone and thyroxine; hypoglycaemia stopped under growth hormone therapy. Magnetic resonance imaging revealed a dysgenetic pituitary gland suggesting an early developmental defect. Array comparative genomic hybridization showed a maternally inherited 1.5-megabase microdeletion in 1q25.2q25.3, including the LHX4 gene. Haploinsufficiency of LHX4 likely explains the predominant pituitary phenotype in the proposita and we suggest variable intrafamilial penetrance of the inherited microdeletion. To the best of our knowledge, we are the first to report on heart failure as a rare nonspecific symptom of treatable CPHD in the newborn. Variably penetrant pituitary insufficiency, including this severe and atypical presentation, can be correlated with LHX4 insufficiency and highlights the role of LHX4 for pituitary development.

Early descriptions of acromegaly and gigantism and their historical evolution as clinical entities.

PubMed

Mammis, Antonios; Eloy, Jean Anderson; Liu, James K

2010-10-01

Giants have been a subject of fascination throughout history. Whereas descriptions of giants have existed in the lay literature for millennia, the first attempt at a medical description was published by Johannes Wier in 1567. However, it was Pierre Marie, in 1886, who established the term "acromegaly" for the first time and established a distinct clinical diagnosis with clear clinical descriptions in 2 patients with the characteristic presentation. Multiple autopsy findings revealed a consistent correlation between acromegaly and pituitary enlargement. In 1909, Harvey Cushing postulated a “hormone of growth" as the underlying pathophysiological trigger involved in pituitary hypersecretion in patients with acromegaly. This theory was supported by his observations of clinical remission in patients with acromegaly in whom he had performed hypophysectomy. In this paper, the authors present some of the early accounts of acromegaly and gigantism, and describe its historical evolution as a medical and surgical entity.

Alternative causes of hypopituitarism: traumatic brain injury, cranial irradiation, and infections.

PubMed

Pekic, Sandra; Popovic, Vera

2014-01-01

Hypopituitarism often remains unrecognized due to subtle clinical manifestations. Anterior pituitary hormone deficiencies may present as isolated or multiple and may be transient or permanent. Traumatic brain injury (TBI) is recognized as a risk factor for hypopituitarism, most frequently presenting with isolated growth hormone deficiency (GHD). Data analysis shows that about 15% of patients with TBI have some degree of hypopituitarism which if not recognized may be mistakenly ascribed to persistent neurologic injury and cognitive impairment. Identification of predictors for hypopituitarism after TBI is important, one of them being the severity of TBI. The mechanisms involve lesions in the hypothalamic-pituitary axis and inflammatory changes in the central nervous system (CNS). With time, hypopituitarism after TBI may progress or reverse. Cranial irradiation is another important risk factor for hypopituitarism. Deficiencies in anterior pituitary hormone secretion (partial or complete) occur following radiation damage to the hypothalamic-pituitary region, the severity and frequency of which correlate with the total radiation dose delivered to the region and the length of follow-up. These radiation-induced hormone deficiencies are irreversible and progressive. Despite numerous case reports, the incidence of hypothalamic-pituitary dysfunction following infectious diseases of the CNS has been underestimated. Hypopituitarism usually relates to the severity of the disease, type of causative agent (bacterial, TBC, fungal, or viral) and primary localization of the infection. Unrecognized hypopituitarism may be misdiagnosed as postencephalitic syndrome, while the presence of a sellar mass with suprasellar extension may be misdiagnosed as pituitary macroadenoma in a patient with pituitary abscess which is potentially a life-threatening disease. © 2014 Elsevier B.V. All rights reserved.

Diabetes Insipidus: An Unusual Presentation of Adenocarcinoma of the Lung in a Patient with no Identifiable Lung Mass.

PubMed

Gulati, Shuchi; Kiefer, Christoper; Karim, Nagla Abdel

2015-10-01

Lung cancers are known to metastasize to unusual sites. Despite this knowledge often times the diagnosis of a primary lung cancer gets delayed especially when the patient presents without respiratory symptoms. The patient discussed in our review is a 47-year-old female, smoker who had presented to several hospitals with months of headache, nausea and intermittent episodes of vomiting. She was noted to have hypernatremia due to diabetes insipidus and a pituitary lesion on her magnetic resonance images. The pituitary mass on biopsy was found to represent a metastatic focus from a primary lung adenocarcinoma. Clinicians should be aware of malignancies that are well known to metastasize to the posterior pituitary. Conversely, since not every patient presents with symptoms of metastasis, there is a need to recognize the clinical syndromes (e. g., diabetes insipidus-like symptoms or more subtle symptoms like cranial nerve palsies) associated with potential metastasis to the pituitary.

Diagnosis and Multimodality Management of Cushing's Disease: A Practical Review

PubMed Central

Zada, Gabriel

2013-01-01

Cushing's Disease is caused by oversecretion of ACTH from a pituitary adenoma and results in subsequent elevations of systemic cortisol, ultimately contributing to reduced patient survival. The diagnosis of Cushing's Disease frequently involves a stepwise approach including clinical, laboratory, neuroimaging, and sometimes interventional radiology techniques, often mandating multidisciplinary collaboration from numerous specialty practitioners. Pituitary microadenomas that do not appear on designated pituitary MRI or dynamic contrast protocols may pose a particularly challenging subset of this disease. The treatment of Cushing's Disease typically involves transsphenoidal surgical resection of the pituitary adenoma as a first-line option, yet may require the addition of adjunctive measures such as stereotactic radiosurgery or medical management to achieve normalization of serum cortisol levels. Vigilant long-term serial endocrine monitoring of patients is imperative in order to detect any recurrence that may occur, even years following initial remission. In this paper, a stepwise approach to the diagnosis, and various management strategies and associated outcomes in patients with Cushing's Disease are discussed. PMID:23401686

Folate receptor overexpression can be visualized in real time during pituitary adenoma endoscopic transsphenoidal surgery with near-infrared imaging.

PubMed

Lee, John Y K; Cho, Steve S; Zeh, Ryan; Pierce, John T; Martinez-Lage, Maria; Adappa, Nithin D; Palmer, James N; Newman, Jason G; Learned, Kim O; White, Caitlin; Kharlip, Julia; Snyder, Peter; Low, Philip S; Singhal, Sunil; Grady, M Sean

2017-08-25

OBJECTIVE Pituitary adenomas account for approximately 10% of intracranial tumors and have an estimated prevalence of 15%-20% in the general US population. Resection is the primary treatment for pituitary adenomas, and the transsphenoidal approach remains the most common. The greatest challenge with pituitary adenomas is that 20% of patients develop tumor recurrence. Current approaches to reduce recurrence, such as intraoperative MRI, are costly, associated with high false-positive rates, and not recommended. Pituitary adenomas are known to overexpress folate receptor alpha (FRα), and it was hypothesized that OTL38, a folate analog conjugated to a near-infrared (NIR) fluorescent dye, could provide real-time intraoperative visual contrast of the tumor versus the surrounding nonneoplastic tissues. The preliminary results of this novel clinical trial are presented. METHODS Nineteen adult patients who presented with pituitary adenoma were enrolled. Patients were infused with OTL38 2-4 hours prior to surgery. A 4-mm endoscope with both visible and NIR light capabilities was used to visualize the pituitary adenoma and its margins in real time during surgery. The signal-to-background ratio (SBR) was recorded for each tumor and surrounding tissues at various endoscope-to-sella distances. Immunohistochemical analysis was performed to assess the FRα expression levels in all specimens and classify patients as having either high or low FRα expression. RESULTS Data from 15 patients (4 with null cell adenomas, 1 clinically silent gonadotroph, 1 totally silent somatotroph, 5 with a corticotroph, 3 with somatotrophs, and 1 somatocorticotroph) were analyzed in this preliminary analysis. Four patients were excluded for technical considerations. Intraoperative NIR imaging delineated the main tumors in all 15 patients with an average SBR of 1.9 ± 0.70. The FRα expression level of the adenomas and endoscope-to-sella distance had statistically significant impacts on the fluorescent SBRs. Additional considerations included adenoma functional status and time from OTL38 injection. SBRs were 3.0 ± 0.29 for tumors with high FRα expression (n = 3) and 1.6 ± 0.43 for tumors with low FRα expression (n = 12; p < 0.05). In 3 patients with immunohistochemistry-confirmed FRα overexpression (2 patients with null cell adenoma and 1 patient with clinically silent gonadotroph), intraoperative NIR imaging demonstrated perfect classification of the tumor margins with 100% sensitivity and 100% specificity. In addition, for these 3 patients, intraoperative residual fluorescence predicted postoperative MRI results with perfect concordance. CONCLUSIONS Pituitary adenomas and their margins can be intraoperatively visualized with the preoperative injection of OTL38, a folate analog conjugated to NIR dye. Tumor-to-background contrast is most pronounced in adenomas that overexpress FRα. Intraoperative SBR at the appropriate endoscope-to-sella distance can predict adenoma FRα expression status in real time. This work suggests that for adenomas with high FRα expression, it may be possible to identify margins and to predict postoperative MRI findings.

Cushing disease revealed by bilateral atypical central serous chorioretinopathy: case report.

PubMed

Giovansili, Iama; Belange, Georeges; Affortit, Aude

2013-01-01

We report the case of a patient with Cushing disease revealed by bilateral central serous chorioretinopathy (CSCR). We present the clinical history, physical findings, laboratory results, and imaging studies of a 53-year-old Chinese woman with a Cushing disease revealed by bilateral CSCR. The association with CSCR and the pertinent literature are reviewed. A 53-year-old patient initially presented to the Department of Ophthalmology with a 4-week history of decreased vision in the left eye. Standard ophthalmologic examination and fluorescein angiography established the diagnosis of bilateral CSCR. Systemic clinical signs and biochemical analysis indicated hypercortisolism. Magnetic resonance imaging (MRI) of the pituitary gland showed a left-side lesion compatible with a microadenoma. The diagnosis of Adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome secondary to a pituitary microadenoma was selected. Endoscopic endonasal transsphenoidal surgery was performed and the pituitary adenoma was successfully removed. The histology confirmed the presence of ACTH-immunopositive pituitary adenoma. Early postoperative morning cortisol levels indicated early remission. At 6 weeks postoperatively, the patient's morning cortisol remains undetectable, and serous retinal detachments had regressed. CSCR is an uncommon manifestation of endogenous Cushing syndrome. It can be the first presentation of hypercortisolism caused by Cushing disease. CSCR should be considered when assessing patients with Cushing syndrome complaining of visual disorders. On the other hand, it is useful in patients with an atypical form of CSCR to exclude Cushing's syndrome.

The glucagon test in the diagnosis of growth hormone deficiency in children with short stature younger than 6 years.

PubMed

Secco, Andrea; di Iorgi, Natascia; Napoli, Flavia; Calandra, Erika; Ghezzi, Michele; Frassinetti, Costanza; Parodi, Stefano; Casini, Maria Rosaria; Lorini, Renata; Loche, Sandro; Maghnie, Mohamad

2009-11-01

Few studies have addressed the diagnostic role of the glucagon test in children with suspected GH deficiency (GHD). The objective of the study was to investigate the diagnostic value of the glucagon test as an alternative test to insulin tolerance test (ITT) and arginine in GHD children younger than 6 yr. This study was conducted in two pediatric endocrinology centers. Forty-eight children (median age 4.2 yr, median height -3.0 sd score) with GHD confirmed by a peak GH to ITT and arginine less than 10 microg/liter (median 4.7 and 3.4 microg/liter, respectively) underwent a glucagon stimulation test. Magnetic resonance imaging showed normal hypothalamic-pituitary anatomy in 24 children, isolated anterior pituitary hypoplasia in seven, and structural hypothalamic-pituitary abnormalities in 17. Median GH peak response to glucagon (13.5 microg/liter) was significantly higher than that observed after ITT and arginine (P < 0.0001). GH peak after glucagon was less than 10 microg/liter in 20 subjects (group 1) and greater than 10 microg/liter in 28 subjects (group 2) without significant clinical or biochemical differences between the two groups. Median GH peak after glucagon was similar between patients with multiple pituitary hormone deficiency and those with isolated GHD and between subjects with and without structural hypothalamic-pituitary abnormalities. The magnitude of the GH peak after glucagon was negatively correlated to age at diagnosis (rho = -0.636, P < 0.0001). This study shows that glucagon has an effective GH-releasing activity and can be used to evaluate somatotroph function in young children with short stature. Normative data for this test in young children need to be established before its use in clinical practice.

The value of prolactin in predicting prolactinοma in hyperprolactinaemic polycystic ovarian syndrome.

PubMed

Kyritsi, Eleni Magdalini; Dimitriadis, Georgios K; Angelousi, Anna; Mehta, Hiten; Shad, Amjad; Mytilinaiou, Maria; Kaltsas, Gregory; Randeva, Harpal S

2018-05-29

To identify a serum prolactin (PRL) cut-off value indicative of a PRL-producing adenoma in women with polycystic ovarian syndrome (PCOS) and hyperprolactinaemia and characterize such patients. In the present retrospective case-control study, the medical records of 528 PCOS women were reviewed. Pituitary magnetic resonance imaging (MRI) was performed in PCOS patients with PRL levels ≥94.0 ng/mL and/or symptoms suspicious of a pituitary adenoma (PA). Prolactinoma diagnosis was made in the presence of an MRI-identifiable PA with biochemical and radiological response to dopamine agonists. Receiver operating characteristic (ROC) curve analysis was performed to determine a serum PRL threshold that could identify hyperprolactinaemic PCOS subjects with prolactinomas. Clinical, metabolic and endocrine parameters were also analysed. Among 528 patients with PCOS, 60 (11.4%) had elevated PRL levels. Of 44 (73.3%) patients who had pituitary imaging, 19 had PAs, 18 normal MRI and 7 other abnormalities. Patients harbouring prolactinomas had significantly higher PRL levels compared to patients without adenomas (median PRL 95.4 vs 49.2 ng/mL, P < .0001). A PRL threshold of 85.2 ng/mL could distinguish patients with prolactinomas with 77% sensitivity and 100% specificity [Area Under the curve (AUC) (95%) 0.91(0.8-1.018), P = .0001]. PCOS women with prolactinomas were younger and had lower LH levels compared to women without prolactinomas. In women with PCOS, PRL levels exceeding 85.2 ng/mL are highly suggestive of a prolactinoma warranting pituitary imaging. Pituitary MRI could also be considered in young PCOS patients with milder PRL elevation and low LH levels. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

Efficacy, safety, and pharmacokinetics of sustained-release lanreotide (lanreotide Autogel) in Japanese patients with acromegaly or pituitary gigantism.

PubMed

Shimatsu, Akira; Teramoto, Akira; Hizuka, Naomi; Kitai, Kazuo; Ramis, Joaquim; Chihara, Kazuo

2013-01-01

The somatostatin analog lanreotide Autogel has proven to be efficacious for treating acromegaly in international studies and in clinical practices around the world. However, its efficacy in Japanese patients has not been extensively evaluated. We examined the dose-response relationship and long-term efficacy and safety in Japanese patients with acromegaly or pituitary gigantism. In an open-label, parallel-group, dose-response study, 32 patients (29 with acromegaly, 3 with pituitary gigantism) received 5 injections of 60, 90, or 120 mg of lanreotide Autogel over 24 weeks. Four weeks after the first injection, 41% of patients achieved serum GH level of <2.5 ng/mL and insulin-like growth factor-I (IGF-I) level was normalized in 31%. Values at Week 24 were 53% for GH and 44% for IGF-I. Dose-dependent decreases in serum GH and IGF-I levels were observed with dose-related changes in pharmacokinetic parameters. In an open-label, long-term study, 32 patients (30 with acromegaly, 2 with pituitary gigantism) received lanreotide Autogel once every 4 weeks for a total of 13 injections. Dosing was initiated with 90 mg and adjusted according to clinical responses at Weeks 16 and/or 32. At Week 52, 47% of patients had serum GH levels of <2.5 ng/mL and 53% had normalized IGF-I level. In both studies, acromegaly symptoms improved and treatment was generally well tolerated although gastrointestinal symptoms and injection site induration were reported. In conclusion, lanreotide Autogel provided early and sustained control of elevated GH and IGF-I levels, improved acromegaly symptoms, and was well tolerated in Japanese patients with acromegaly or pituitary gigantism.

Central nervous system abnormalities in Fanconi anaemia: patterns and frequency on magnetic resonance imaging

PubMed Central

Alston, Robert; Wright, Neville B; Chandler, Kate; Bonney, Denise; Wynn, Robert F; Will, Andrew M; Punekar, Maqsood; Loughran, Sean; Kilday, John-Paul; Schindler, Detlev; Patel, Leena; Meyer, Stefan

2015-01-01

Objective: Fanconi anaemia (FA) is an inherited disease associated with congenital and developmental abnormalities resulting from the disruption of a multigenic DNA damage response pathway. This study aimed to define the MRI appearances of the brain in patients with FA in correlation with their genetic and clinical features. Methods: A review of the brain MRI in 20 patients with FA was performed. Pituitary size and frequencies of the radiological findings of individuals with FA and age-matched controls were determined. Results: Abnormalities were identified in 18 (90%) patients with FA, the commonest being a small pituitary (68%, p < 0.01 females and p < 0.001 males). In five cases (25%, p = 0.02), the pituitary morphology was also abnormal. Posterior fossa abnormalities were seen in six cases (30%, p = 0.01) including Chiari I malformation (n = 3), Dandy–Walker variant (n = 2) and cerebellar atrophy (n = 2). Six patients (30%, p = 0.01) had morphological structural variation of the corpus callosum (CC). Conclusion: The incidence of central nervous system (CNS) abnormalities in FA is higher than previously reported, with a midline predominance that points to impact in the early stages of CNS development. MRI brain imaging is important for endocrine assessment and pre-transplant evaluation and can make an important contribution to clinical decision-making. Advances in knowledge: The incidence of brain structural abnormalities in FA is higher than previously reported, with abnormalities of the posterior fossa, CC and pituitary being common. There is an association with gender and reduction in pituitary size which does not strongly correlate with biochemically evident endocrine abnormality. PMID:26369989

Supplementation with a recombinant human chorionic gonadotropin microdose leads to similar outcomes in ovarian stimulation with recombinant follicle-stimulating hormone using either a gonadotropin-releasing hormone agonist or antagonist for pituitary suppression.

PubMed

Cavagna, Mario; Maldonado, Luiz Guilherme Louzada; de Souza Bonetti, Tatiana Carvalho; de Almeida Ferreira Braga, Daniela Paes; Iaconelli, Assumpto; Borges, Edson

2010-06-01

To compare the outcomes of protocols for ovarian stimulation with recombinant hCG microdose, with GnRH agonists and antagonists for pituitary suppression. Prospective nonrandomized clinical trial. A private assisted reproduction center. We studied 182 patients undergoing intracytoplasmic sperm injection (ICSI) cycles, allocated into two groups: GnRH agonist group, in which patients received a GnRH agonist (n = 73), and a GnRH antagonist group, in which patients were administered a GnRH antagonist for pituitary suppression (n = 109). Pituitary suppression with GnRH agonist or GnRH antagonist. Ovarian stimulation carried out with recombinant FSH and supplemented with recombinant hCG microdose. Total dose of recombinant FSH and recombinant hCG administered; E(2) concentrations and endometrial width on the day of hCG trigger; number of follicles aspirated, oocytes and mature oocytes retrieved; fertilization, pregnancy (PR), implantation, and miscarriage rates. The total dose of recombinant FSH and recombinant hCG administered were similar between groups, as were the E(2) concentrations and endometrial width. The number of follicles aspirated, oocytes, and metaphase II oocytes collected were also comparable. There were no statistically significant differences in fertilization, PR, implantation, and miscarriage rates in the GnRH agonist and GnRH antagonist groups. When using recombinant hCG microdose supplementation for controlled ovarian stimulation (COS), there are no differences in laboratory or clinical outcomes with the use of either GnRH antagonist or agonist for pituitary suppression. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Three endocrine neoplasms: an unusual combination of pheochromocytoma, pituitary adenoma, and papillary thyroid carcinoma.

PubMed

Sisson, James C; Giordano, Thomas J; Avram, Anca M

2012-04-01

Three endocrine neoplasms-bilateral pheochromocytomas, somatotrophic pituitary adenoma inducing acromegaly, and papillary carcinoma of the thyroid-occurred concurrently in a patient. A genetic mutation was hypothesized. Possible previously described genetic mutations were explored. Clinical assessments, laboratory data, images of tumors, histopathology, and immunohistochemistry of excised tissues documented the three neoplasms. Clinical assessment of the patient, family history, and a review of the literature sought a familial basis for the disorders. The methods confirmed the presence of three endocrine neoplasms. Each neoplasm was surgically excised and histologically verified. Surgical and (131)I treatments reduced the papillary carcinoma, but eventually this tumor progressed to a lethal degree. History, including that of nine siblings, uncovered no familial neoplasms. No similar case was found in the literature, but possible associations with germline mutations were considered. The concurrent development of pheochromocytomas, pituitary somatotrophic adenoma, and papillary thyroid carcinoma appears to be unique. Nevertheless, such tumors, particularly bilateral pheochromocytomas, strongly suggest a de novo germline mutation in a gene not previously associated with multiple endocrine neoplasia syndromes.

Harvey Cushing Treated the First Known Patient With Carney Complex.

PubMed

Tsay, Cynthia J; Stratakis, Constantine A; Faucz, Fabio Rueda; London, Edra; Stathopoulou, Chaido; Allgauer, Michael; Quezado, Martha; Dagradi, Terry; Spencer, Dennis D; Lodish, Maya

2017-10-01

Carney complex (CNC) is a syndrome characterized by hyperplasia of endocrine organs and may present with clinical features of Cushing syndrome and acromegaly due to functional adrenal and pituitary gland tumors. CNC has been linked to mutations in the regulatory subunit of protein kinase A type I-alpha ( PRKAR1A ) gene. Tissue samples were taken from the hypothalamus or thalamus or tumors of patients with pituitary adenomas seen and operated on by neurosurgeon Harvey Cushing between 1913 and 1932. Following DNA extraction, sequencing for genes of interest was attempted, including PRKAR1A , AIP , USP8 , GNAS1 , and GPR101 , to explore the possibility that these mutations associated with acromegaly, CNC, and Cushing syndrome have been conserved over time. We report a patient described by Dr. Cushing in 1914 with a clinical presentation and postmortem findings suggestive of CNC. Genetic sequencing of the hypothalamus and pituitary adenoma revealed a germline heterozygous p.Arg74His mutation in the PRKAR1A gene, a codon previously described as mutated in CNC, but with a novel amino acid change. This patient is, to our knowledge, the first molecularly confirmed individual with CNC. This case demonstrates the power of modern genetics in studying archived tissues and the importance of recording detailed clinical notes in the diagnosis of disease.

[Comparison of Alarelin and Triptorelin in the long-protocol ovulation induction in in vitro fertilization and embryo transfer].

PubMed

Duan, Jin-Liang; Jiang, Yuan-Hua; Liu, Ying; Zeng, Qiong-Fang; Huang, Ya-Dan

2010-07-01

To compare the pituitary down-regulatory effects of the two gonadotropin-releasing hormone agonists Alarelin and Triptorelin in the long protocol of ovulation induction in in vitro fertilization and embryo transfer (IVF-ET). We included in this study 122 patients aged 24-39 years treated by IVF-ET for secondary infertility, with 10-20 pre-antral follicles and obstruction of the fallopian tube. Seventy-eight of them received Alarelin, and the other 44 Triptorelin. Comparative analyses were made on the pituitary down-regulatory effects of the two gonadotropin-releasing hormone agonists and the clinical outcomes of IVF-ET. No premature LH surge and ovulation, nor severe hyperovarian stimulation syndrome was found in either group. There were no significant differences between the two groups in the mean dose and duration of gonodatropin treatment, the numbers of oocytes retrieved, mature oocytes and top-quality embryos, and the rates of 2PN, multi-sperm fertilization, cleavage, embryo transfer, embryo implantation, clinical pregnancy and early miscarriage (P > 0.05), but the rate of cancelled cycles was significantly higher in the Triptorelin than in the Alarelin group (P < 0.05). Alarelin and Triptorelin can achieve similar pituitary down-regulatory effects and clinical outcomes in IVF-ET when used in the long protocol of ovulation induction.

Two novel LHX3 mutations in patients with combined pituitary hormone deficiency including cervical rigidity and sensorineural hearing loss.

PubMed

Ramzan, Khushnooda; Bin-Abbas, Bassam; Al-Jomaa, Lolwa; Allam, Rabab; Al-Owain, Mohammed; Imtiaz, Faiqa

2017-03-16

Congenital combined pituitary hormone deficiency (CPHD) is a rare heterogeneous group of conditions. CPHD-type 3 (CPHD3; MIM# 221750) is caused by recessive mutations in LHX3, a LIM-homeodomain transcription factor gene. The isoforms of LHX3 are critical for pituitary gland formation and specification of the anterior pituitary hormone-secreting cell types. They also play distinct roles in the development of neuroendocrine and auditory systems. Here, we summarize the clinical, endocrinological, radiological and molecular features of three patients from two unrelated families. Clinical evaluation revealed severe CPHD coupled with cervical vertebral malformations (rigid neck, scoliosis), mild developmental delay and moderate sensorineural hearing loss (SNHL). The patients were diagnosed with CPHD3 based on the array of hormone deficiencies and other associated syndromic symptoms, suggestive of targeted LHX3 gene sequencing. A novel missense mutation c.437G > T (p. Cys146Phe) and a novel nonsense mutation c.466C > T (p. Arg156Ter), both in homozygous forms, were found. The altered Cys146 resides in the LIM2 domain of the encoded protein and is a phylogenetically conserved residue, which mediates LHX3 transcription factor binding with a zinc cation. The p. Arg156Ter is predicted to result in a severely truncated protein, lacking the DNA binding homeodomain. Considering genotype/phenotype correlation, we suggest that the presence of SNHL and limited neck rotation should be considered in the differential diagnosis of CPHD3 to facilitate molecular diagnosis. This report describes the first LHX3 mutations from Saudi patients and highlights the importance of combining molecular diagnosis with the clinical findings. In addition, it also expands the knowledge of LHX3-related CPHD3 phenotype and the allelic spectrum for this gene.

CENTRAL DIABETES INSIPIDUS: CLINICAL CHARACTERISTICS AND LONG-TERM COURSE IN A LARGE COHORT OF ADULTS.

PubMed

Masri-Iraqi, Hiba; Hirsch, Dania; Herzberg, Dana; Lifshitz, Avner; Tsvetov, Gloria; Benbassat, Carlos; Shimon, Ilan

2017-05-01

Central diabetes insipidus (CDI) is a rare heterogeneous condition with various underlying causes. This study sought to increase the still-limited data on the clinical characteristics and long-term course in adults diagnosed with CDI. Data on demographics, presentation, imaging findings, affected pituitary axes, treatment, and complications were collected retrospectively from the files of 70 adult patients with CDI followed at a referral endocrine clinic. Forty women and 30 men were included. Mean age was 46.8 ± 15 years at the time of this study and 29.3 ± 20 years at CDI diagnosis. Twenty-eight patients were diagnosed in childhood. Forty patients (57%) acquired CDI following surgery. Main sellar pathologies were: craniopharyngioma, 17 patients (11 diagnosed in childhood); Langerhans histiocytosis, 10 patients (5 diagnosed in childhood); 7 patients (all diagnosed as adults) had a growth hormone-secreting adenoma; 12 patients (17%; 6 diagnosed in childhood) had idiopathic CDI. At least one anterior pituitary axis was affected in 73% of the cohort: 59% had growth hormone deficiency, 56% hypogonadism, 55% central hypothyroidism, 44% adrenocorticotropic hormone-cortisol deficiency. Patients with postoperative/trauma CDI (n = 44) tended to have multiple anterior pituitary axes deficits compared to the nonsurgical group of patients. All patients were treated with vasopressin preparations, mostly nasal spray. Hyponatremia developed in 32 patients, more in women, and was severe (<125 mEq/L) in 10 patients. Hypernatremia (>150 mEq/L) was noticed in 5 patients. Overall, the calculated complication rate was 22 in 1,250 treatment-years. Most adult patients with CDI have anterior pituitary dysfunction. Stability is usually achieved with long-term treatment. Women were more susceptible to desmopressin complications, albeit with an overall relatively low complication rate. ACTH = adrenocorticotropic hormone CDI = central diabetes insipidus GH = growth hormone MRI = magnetic resonance imaging.

Pregnancy may favour the development of severe autoimmune central diabetes insipidus in women with vasopressin cell antibodies: description of two cases.

PubMed

Bellastella, Giuseppe; Bizzarro, Antonio; Aitella, Ernesto; Barrasso, Mariluce; Cozzolino, Domenico; Di Martino, Sergio; Esposito, Katherine; De Bellis, Annamaria

2015-03-01

Recently, an increased incidence of central diabetes insipidus (CDI) in pregnancy, and less frequently in the post partum period, has been reported, most probably favoured by some conditions occurring in pregnancy. This study was aimed at investigating the influence of pregnancy on a pre-existing potential/subclinical hypothalamic autoimmunity. We studied the longitudinal behaviour of arginine-vasopressin cell antibodies (AVPcAbs) and post-pituitary function in two young women with a positive history of autoimmune disease and presence of AVPcAbs, but without clinical CDI, and who became pregnant 5 and 7 months after our first observation. The behaviour of post-pituitary function and AVPcAbs (by immunofluorescence) was evaluated at baseline, during pregnancy and for 2 years after delivery. AVPcAbs, present at low/middle titres at baseline in both patients, showed a titre increase during pregnancy in one patient and after delivery in the other patient, with development of clinically overt CDI. Therapy with 1-deamino-8-d-arginine vasopressin (DDAVP) caused a prompt clinical remission. After a first unsuccessful attempt of withdrawal, the therapy was definitively stopped at the 6th and the 7th month of post partum period respectively, when AVPcAbs disappeared, accompanied by post-pituitary function recovery, persisting until the end of the follow-up. The determination of AVPcAbs is advisable in patients with autoimmune diseases planning their pregnancy, because they could be considered good predictive markers of gestational or post partum autoimmune CDI. The monitoring of AVPcAb titres and post-pituitary function during pregnancy in these patients may allow for an early diagnosis and an early replacement therapy, which could induce the disappearance of these antibodies with consequent complete remission of CDI. © 2015 European Society of Endocrinology.

Early Focal Segmental Glomerulosclerosis as a Cause of Renal Allograft Primary Nonfunction

PubMed Central

Griffin, Emma J.; Thomson, Peter C.; Kipgen, David; Clancy, Marc; Daly, Conal

2013-01-01

Background. Primary focal segmental glomerulosclerosis (FSGS) is one of the commonest causes of glomerular disease and if left untreated will often progress to established renal failure. In many cases the best treatment option is renal transplantation; however primary FSGS may rapidly recur in renal allografts and may contribute to delayed graft function. We present a case of primary nonfunction in a renal allograft due to biopsy-proven FSGS. Case Report. A 32-year-old man presented with serum albumin of 22 g/L, proteinuria quantified at 12 g/L, and marked peripheral oedema. Renal biopsy demonstrated tip-variant FSGS. Despite treatment, the patient developed progressive renal dysfunction and was commenced on haemodialysis. Cadaveric renal transplantation was undertaken; however this was complicated by primary nonfunction. Renal biopsies failed to demonstrate evidence of acute rejection but did demonstrate clear evidence of FSGS. The patient was treated to no avail. Discussion. Primary renal allograft nonfunction following transplantation is often due to acute kidney injury or acute rejection. Recurrent FSGS is recognised as a phenomenon that drives allograft dysfunction but is not traditionally associated with primary nonfunction. This case highlights FSGS as a potentially aggressive process that, once active in the allograft, may prove refractory to targeted treatment. Preemptive therapies in patients deemed to be at high risk of recurrent disease may be appropriate and should be considered. PMID:23781382

Pituitary tumor in a woman with a 47,XXX karyotype--case report.

PubMed

Witek, A; Skałba, P; Zieba, M

2001-01-01

The 47,XXX karyotype is a rare sex chromosome anomaly. This karyotype is usually not associated with a characteristic physical phenotype. In presented case a 47 triple X women with pituitary tumor and premature ovarian failure is identified. Diagnosis of a 47,XXX individual remains difficult because specific clinical criteria used to identify this condition are not available. The case described should attract attention to how difficult it is to diagnose properly a genetic disease in young women with correct phenotype.

The hypothalamus and pituitary in cerebral gigantism. A clinicopathologic and immunocytochemical study.

PubMed

Whitaker, M D; Scheithauer, B W; Hayles, A B; Okazaki, H

1985-07-01

Cerebral gigantism, or Sotos' disease, is a rare disorder of unknown cause characterized by the early onset of excessive growth, acromegalic features, and some degree of mental retardation. Although several endocrinologic abnormalities have been described in such patients, none has been specific or sufficient to explain the clinical features. Our report of the endocrinologic and pathologic aspects in a young woman with Sotos' disease includes the first microanatomic study of the hypothalamus and immunocytochemical examination of the pituitary gland in this disorder.

Treatment complexities of a young woman suffering psychosis and pituitary adenoma.

PubMed

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.

Familial gigantism

PubMed Central

de Herder, Wouter W.

2012-01-01

Familial GH-secreting tumors are seen in association with three separate hereditary clinical syndromes: multiple endocrine neoplasia type 1, Carney complex, and familial isolated pituitary adenomas. PMID:22584702

Third-space fluid shift in elderly patients undergoing gastrointestinal surgery: Part 1: Pathophysiological mechanisms.

PubMed

Redden, Maurine; Wotton, Karen

2002-06-01

Third-space fluid shift, the movement of body fluid to a non-functional space, is a frequently occurring and potentially fatal clinical phenomenon. Little published research exists however in medical or nursing journals concerning its incidence, significance and ramifications in elderly patients undergoing major gastrointestinal surgery. This initial article, part I, explores fluid movement between fluid compartments and uses these principles to discuss the pathophysiology of the two distinct phases of third-space fluid shift. Part II will examine the criteria nurses could use in the clinical assessment of patients in both first and second phases third-space fluid shift and discuss the clinical reliability of these criteria.

Medical treatment of Cushing's Disease.

PubMed

Cuevas-Ramos, Daniel; Fleseriu, Maria

2016-09-01

Cushing's Syndrome (CS) is a serious endocrine disease that results from the adverse clinical consequences of chronic exposure to high levels of glucocorticoids. Most patients with endogenous CS have an adrenocorticotropin (ACTH)-secreting pituitary corticotroph adenoma, i.e. Cushing's Disease (CD). The first-line therapy for CD is transsphenoidal pituitary surgery. If tumor removal is incomplete or unsuccessful, persistent hypercortisolism will require further treatment. Repeat surgery, medical therapy, radiation and bilateral adrenalectomy are all second line therapy options; however, medical therapy can be also used as first line therapy in patients who cannot undergo surgery, or to decrease cortisol values and/or improve co-morbidities. Medications used in the treatment of CD, classified into three groups: pituitary directed drugs, adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers, are reviewed. Future 'on the horizon' treatment options are also discussed.

26 CFR 1.1273-2 - Determination of issue price and issue date.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (a), money includes functional currency and, in certain circumstances, nonfunctional currency. See § 1.988-2(b)(2) for circumstances when nonfunctional currency is treated as money rather than as... debt instruments in the issue is sold for money. (b) Publicly traded debt instruments issued for...

26 CFR 1.1274-1 - Debt instruments to which section 1274 applies.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., see sections 404 and 467. For purposes of this paragraph (a), money includes functional currency and, in certain circumstances, nonfunctional currency. See § 1.988-2(b)(2) for circumstances when nonfunctional currency is treated as money rather than as property. (b) Exceptions—(1) Debt instrument with...

Advanced virtual endoscopy for endoscopic transsphenoidal pituitary surgery.

PubMed

Wolfsberger, Stefan; Neubauer, André; Bühler, Katja; Wegenkittl, Rainer; Czech, Thomas; Gentzsch, Stephan; Böcher-Schwarz, Hans-Gerd; Knosp, Engelbert

2006-11-01

Virtual endoscopy (vE) is the navigation of a camera through a virtual anatomical space that is computationally reconstructed from radiological image data. Inside this three-dimensional space, arbitrary movements and adaptations of viewing parameters are possible. Thereby, vE can be used for noninvasive diagnostic purposes and for simulation of surgical tasks. This article describes the development of an advanced system of vE for endoscopic transsphenoidal pituitary surgery and its application to teaching, training, and in the routine clinical setting. The vE system was applied to a series of 35 patients with pituitary pathology (32 adenomas, three Rathke's cleft cysts) operated endoscopically via the transsphenoidal route at the Department of Neurosurgery of the Medical University Vienna between 2004 and 2006. The virtual endoscopic images correlated well with the intraoperative view. For the transsphenoidal approach, vE improved intraoperative orientation by depicting anatomical landmarks and variations. For planning a safe and tailored opening of the sellar floor, transparent visualization of the pituitary adenoma and the normal gland in relation to the internal carotid arteries was useful. According to our experience, vE can be a valuable tool for endoscopic transsphenoidal pituitary surgery for training purposes and preoperative planning. For the novice, it can act as a simulator for endoscopic anatomy and for training surgical tasks. For the experienced pituitary surgeon, vE can depict the individual patient's anatomy, and may, therefore, improve intraoperative orientation. By prospectively visualizing unpredictable anatomical variations, vE may increase the safety of this surgical procedure.

Endocrine disorders among long-term survivors of childhood head and neck rhabdomyosarcoma.

PubMed

Clement, S C; Schoot, R A; Slater, O; Chisholm, J C; Abela, C; Balm, A J M; van den Brekel, M W; Breunis, W B; Chang, Y C; Davila Fajardo, R; Dunaway, D; Gajdosova, E; Gaze, M N; Gupta, S; Hartley, B; Kremer, L C M; van Lennep, M; Levitt, G A; Mandeville, H C; Pieters, B R; Saeed, P; Smeele, L E; Strackee, S D; Ronckers, C M; Caron, H N; van Santen, H M; Merks, J H M

2016-02-01

Head and neck rhabdomyosarcoma (HNRMS) survivors are at increased risk of developing pituitary dysfunction as an adverse event of radiotherapy. Our aim was to investigate the frequency and risk factors for pituitary dysfunction in these survivors. Secondly, we aimed to compare the prevalence of pituitary dysfunction between survivors treated with external beam radiation therapy (EBRT) and survivors treated with the ablative surgery, moulage technique after loading brachytherapy, and surgical reconstruction (AMORE) procedure. Eighty HNRMS survivors treated in London (EBRT based) and Amsterdam (AMORE based: AMORE if feasible, otherwise EBRT) in the period 1990-2010 and alive ≥ 2 years post-treatment were evaluated. Survivors were evaluated in multidisciplinary late-effects clinics, with measurement of linear growth, determination of thyroid function, and growth hormone parameters. Additional data, such as baseline characteristics, anthropometrics, pubertal stage, and the results of additional laboratory investigations, were retrieved from patient charts. Pituitary dysfunction was diagnosed in 24 in 80 (30%) survivors, after a median follow-up time of 11 years. Median time to develop pituitary dysfunction after HNRMS diagnosis was 3.0 years. Risk factors were EBRT-based therapy (odds ratio [OR] 2.06; 95% confidence interval [CI] 1.79-2.46), parameningeal tumour site (OR 1.83; 95% CI 1.60-2.17) and embryonal RMS histology (OR 1.49; 95% CI 1.19-1.90). Radiotherapy used for the treatment of HNRMS confers a significant risk of the development of pituitary dysfunction. AMORE-based treatment in children with HNRMS resulted in less pituitary dysfunction than treatment with conventional EBRT. Our findings underscore the importance of routine early endocrine follow-up in this specific population. Copyright © 2015 Elsevier Ltd. All rights reserved.

PITUITARY GIGANTISM--EXPERIENCE OF A SINGLE CENTER FROM WESTERN INDIA.

PubMed

Patt, Hiren P; Bothra, Nikita; Goel, Atul H; Kasaliwal, Rajeev; Lila, Anurag R; Bandgar, Tushar R; Shah, Nalini S

2015-06-01

Limited data are available on pituitary gigantism, as it is a rare disorder. This study was carried out to assess the clinical, hormonal, and radiologic profiles and management outcomes of patients with pituitary gigantism. We conduced a retrospective analysis of 14 patients with pituitary gigantism who presented to a single tertiary care institute from 1990 to 2014. Thirteen patients were male, and 1 was female. The mean age at diagnosis was 21.9 ± 6.1 years, with a mean lag period of 6.5 ± 5.6 years. The mean height SD score at the time of diagnosis was 3.2 ± 0.6. Symptoms of tumor mass effect were the chief presenting complaint in the majority (50%) of patients, while 2 patients were asymptomatic. Six patients had hyperprolactinemia. At presentation, the nadir PGGH (postglucose GH) and insulin-like growth factor (IGF 1)-ULN (× upper limit of normal) were 63.2 ± 94.9 ng/mL and 1.98 ± 0.5, respectively. All (except 1 with mild pituitary hyperplasia) had pituitary macroadenoma. Six patients had invasive pituitary adenoma. Transsphenoidal surgery (TSS) was the primary modality of treatment in 13/14 patients, and it achieved remission in 4/13 (30.76%) patients without recurrence over a median follow-up of 7 years. Post-TSS radiotherapy (RT) achieved remission in 3/5 (60%) patients over a median follow-up of 3.5 years. None of the patients received medical management at any point of time. Gigantism is more common in males, and remission can be achieved in the majority of the patients with the help of multimodality treatment (TSS and RT).

Determinants of surgical resection for pancreatic neuroendocrine tumors.

PubMed

Doi, Ryuichiro

2015-08-01

Pancreatic neuroendocrine tumors (pNETs) include functioning and non-functional tumors. Functioning tumors consist of tumors that produce a variety of hormones and their clinical effects. Therefore, determinants of resection of pNETs should be discussed for each group of tumors. Less than 10% of insulinomas are malignant, therefore more than 90% of the cases can be cured by surgical resection. Lymphadenectomy is generally not necessary in insulinoma operation. If preoperative localization of the insulinoma is completed, enucleation from the pancreatic body or tail, and distal pancreatectomy can be performed safely by laparoscopy. When preoperative localization of a sporadic insulinoma is not confirmed, surgical exploration is needed. Intraoperative localization of a tumor, intraoperative insulin sampling and frozen section are required. The crucial purpose of surgical resection is to control inappropriate insulin secretion by removing all insulinomas. Gastrinomas are usually located in the duodenum or pancreas, which secrete gastrin and cause Zollinger-Ellison syndrome (ZES). Duodenal gastrinomas are usually small, therefore they are not seen on preoperative imaging studies or endoscopic ultrasound, and can be found only at surgery if a duodenotomy is performed. In addition, lymph node metastasis is found in 40-60% of cases. Therefore, the experienced surgeons should direct operation for gastrinomas. Surgical exploration with duodenotomy should be performed at a laparotomy. Other functioning pNETs can occur in the pancreas or in other locations. Curative resection is always recommended whenever possible after optimal symptomatic control of the clinical syndrome by medical treatment. Indications for surgery depend on clinical symptom control, tumor size, location, extent, malignancy and presence of metastasis. A lot of non-functioning pNETs are found incidentally according to the quality improvement of imaging techniques. Localized, small, malignant non-functioning pNETs should be operated on aggressively, while in possibly benign tumors smaller than 2 cm the surgical risk-benefit ratio should be carefully weighted. Surgical liver resection is generally proposed in curative intent to all patients with operable metastases from G1 or G2 pNET. The benefits of surgical resection of liver metastases have been demonstrated in terms of overall survival and quality of life. Complete resection is associated with better long-term survival. © 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Pasireotide therapy in a rare and unusual case of plurihormonal pituitary macroadenoma.

PubMed

Rajendran, Rajesh; Naik, Sarita; Sandeman, Derek D; Nasruddin, Azraai B

2013-01-01

We report the use of pasireotide in a rare and unusual case of pituitary macroadenoma co-secreting GH, prolactin and ACTH. A 62-year-old Caucasian man presented with impotence. Clinically, he appeared acromegalic and subsequent investigations confirmed GH excess and hyperprolactinaemia. Magnetic resonance imaging (MRI) of pituitary revealed a large pituitary macroadenoma. He underwent trans-sphenoidal surgery and histology confirmed an adenoma with immunohistochemistry positive for ACTH, GH and prolactin. Acromegaly was not cured following surgery and inadequately controlled despite subsequent octreotide therapy. He underwent further debulking pituitary surgery, following which IGF1 levels improved but still high. This time adenoma cells showed immunohistochemistry positivity for ACTH only, following which subsequent investigations confirmed intermittent hypercortisolaemia compatible with pituitary Cushing's disease. We recommended radiotherapy, but in view of the pluripotential nature of the tumour, we proceeded with a trial of s.c. pasireotide therapy on the basis that it may control both his acromegaly and Cushing's disease. After 3 months of pasireotide therapy, his mean GH and IGF1 levels improved significantly, with improvement in his symptoms but intermittent hypercortisolaemia persists. His glycaemic control deteriorated requiring addition of new anti-diabetic medication. MRI imaging showed loss of contrast uptake within the tumour following pasireotide therapy but no change in size. We conclude that our patient has had a partial response to pasireotide therapy. Long-term follow-up studies are needed to establish its safety and efficacy in patients with acromegaly and/or Cushing's disease. Plurihormonal pituitary adenomas are rare and unusual.Patients with pituitary adenomas co-secreting ACTH and GH are more likely to present with acromegaly because GH excess can mask hypercortisolaemia.Pasireotide holds potential where conventional somatostatin analogues are not effective in acromegaly due to higher affinity for somatostatin receptor subtypes 1, 2, 3 and 5.Significant deterioration in glycaemic control remains a concern in the use of pasireotide.Currently, long-term safety and efficacy of pasireotide in patients with acromegaly and/or Cushing's disease are not fully clear.

[A Case of Central Diabetes Insipidus That Was Caused by Pituitary Metastasis of Lung Adenocarcinoma and Was Controlled by Radiation Therapy].

PubMed

Izumi, Yusuke; Masuda, Takeshi; Nabeshima, Shinji; Horimasu, Yasushi; Nakashima, Taku; Miyamoto, Shintaro; Iwamoto, Hiroshi; Fujitaka, Kazunori; Murakami, Yuji; Hamada, Hironobu; Nagata, Yasushi; Hattori, Noboru

2017-06-01

Pituitary metastasis of lung cancer is rare; however, it often causes diabetes insipidus. Although the majority of such patients are treated with radiation therapy, it remains unclear whether diabetes insipidus can be controlled by radiation therapy. A 72-year-old man was admitted to our hospital for hemosputum, headache, and polyuria. A chest CT scan showed a 3.0 cm mass in the left upper lobe of his lung. Bronchofiberscopy results confirmed the pathological diagnosis of lung adenocarcinoma. Based on the findings from PET-CT, head MRI, and endocrine tests, the diagnosis of lung adenocarcinoma( cT1bN0M1b, stage IV)accompanied with central diabetes insipidus caused by pituitary metastasis was made. Oral administration of desmopressin reduced urine volumes; however, chemotherapy for achieving stable disease in the primary tumor was ineffective in controlling the symptoms of diabetes insipidus. Chemotherapy was discontinued after 4 months because of severe hematological toxicity. During 2 months after the cessation of chemotherapy, polyuria worsened and, therefore, radiation therapy for pituitary metastasis was started. Following the radiation therapy, an apparent reduction in urine volume was observed. Our experience of this case suggests that radiation therapy for pituitary metastasis should be considered at the time when diabetes insipidus becomes clinically overt.

Genetic regulation of pituitary gland development in human and mouse.

PubMed

Kelberman, Daniel; Rizzoti, Karine; Lovell-Badge, Robin; Robinson, Iain C A F; Dattani, Mehul T

2009-12-01

Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke's pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans.

Genetic Regulation of Pituitary Gland Development in Human and Mouse

PubMed Central

Kelberman, Daniel; Rizzoti, Karine; Lovell-Badge, Robin; Robinson, Iain C. A. F.; Dattani, Mehul T.

2009-01-01

Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke’s pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans. PMID:19837867

Clinically guided genetic screening in a large cohort of italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas.

PubMed

Mannelli, Massimo; Castellano, Maurizio; Schiavi, Francesca; Filetti, Sebastiano; Giacchè, Mara; Mori, Luigi; Pignataro, Viviana; Bernini, Gianpaolo; Giachè, Valentino; Bacca, Alessandra; Biondi, Bernadette; Corona, Giovanni; Di Trapani, Giuseppe; Grossrubatscher, Erika; Reimondo, Giuseppe; Arnaldi, Giorgio; Giacchetti, Gilberta; Veglio, Franco; Loli, Paola; Colao, Annamaria; Ambrosio, Maria Rosaria; Terzolo, Massimo; Letizia, Claudio; Ercolino, Tonino; Opocher, Giuseppe

2009-05-01

The aim of the study was to define the frequency of hereditary forms and the genotype/phenotype correlations in a large cohort of Italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas. We examined 501 consecutive patients with pheochromocytomas and/or paragangliomas (secreting or nonsecreting). Complete medical and family histories, as well as the results of clinical, laboratory, and imaging studies, were recorded in a database. Patients were divided into different groups according to their family history, the presence of lesions outside adrenals/paraganglia considered syndromic for VHL disease, MEN2, and NF1, and the number and types of pheochromocytomas and/or paragangliomas. Germ-line mutations in known susceptibility genes were investigated by gene sequencing (VHL, RET, SDHB, SDHC, SDHD) or diagnosed according to phenotype (NF1). In 160 patients younger than 50 yr with a wild-type profile, multiplex ligation-dependent probe amplification assays were performed to detect genomic rearrangements. Germline mutations were detected in 32.1% of cases, but frequencies varied widely depending on the classification criteria and ranged from 100% in patients with associated syndromic lesions to 11.6% in patients with a single tumor and a negative family history. The types and number of pheochromocytomas/paragangliomas as well as age at presentation and malignancy suggest which gene should be screened first. Genomic rearrangements were found in two of 160 patients (1.2%). The frequency of the hereditary forms of pheochromocytoma/paraganglioma varies depending on the family history and the clinical presentation. A positive family history and an accurate clinical evaluation of patients are strong indicators of which genes should be screened first.

Prevalence of hypopituitarism after intracranial operations not directly associated with the pituitary gland.

PubMed

Fleck, Steffen Kristian; Wallaschofski, Henri; Rosenstengel, Christian; Matthes, Marc; Kohlmann, Thomas; Nauck, Matthias; Schroeder, Henry Werner Siegfried; Spielhagen, Christin

2013-11-04

Over the last few years, awareness and detection rates of hypopituitarism following traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) has steadily increased. Moreover, recent studies have found that a clinically relevant number of patients develop pituitary insufficiency after intracranial operations and radiation treatment for non-pituitary tumors. But, in a substantial portion of more than 40%, the hypopituitarism already exists before surgery. We sought to determine the frequency, pattern, and severity of endocrine disturbances using basal and advanced dynamic pituitary testing following non-pituitary intracranial procedures. 51 patients (29 women, 22 men) with a mean age of 55 years (range of 20 to 75 years) underwent prospective evaluation of basal parameters and pituitary function testing (combined growth hormone releasing hormone (GHRH)/arginine test, insulin tolerance test (ITT), low dose adrenocorticotropic hormone (ACTH) test), performed 5 to 168 months (median 47.2 months) after intracranial operation (4 patients had additional radiation and 2 patients received additional radiation combined with chemotherapy). We discovered an overall rate of hypopituitarism with distinct magnitude in 64.7% (solitary in 45.1%, multiple in 19.6%, complete in 0%). Adrenocorticotropic hormone insufficiency was found in 51.0% (partial in 41.2%, complete in 9.8%) and growth hormone deficiency (GHD) occurred in 31.4% (partial in 25.5%, severe in 5.9%). Thyrotropic hormone deficiency was not identified. The frequency of hypogonadism was 9.1% in men. Pituitary deficits were associated with operations both in close proximity to the sella turcica and more distant regions (p = 0.91). Age (p = 0.76) and gender (p = 0.24) did not significantly differ across patients with versus those without hormonal deficiencies. Groups did not significantly differ across pathology and operation type (p = 0.07). Hypopituitarism occurs more frequently than expected in patients who have undergone neurosurgical intracranial procedures for conditions other then pituitary tumors or may already exists in a neurosurgical population before surgery. Pituitary function testing and adequate substitution may be warranted for neurosurgical patients with intracranial pathologies at least if unexplained symptoms like fatigue, weakness, altered mental activity, and decreased exercise tolerance are present.

PITUITARY DEFICIENCY FOLLOWING TRAUMATIC BRAIN INJURY IN EARLY CHILDHOOD: A REVIEW OF THE LITERATURE.

PubMed

Soliman, A T; Adel, A; Soliman, N A; Elalaily, R; De Sanctis, V

2015-01-01

AIMS OF REVIEW: the intent of the current manuscript is to critically review the studies on pituitary gland dysfunction in early childhood following traumatic brain injury (TBI), in comparison with those in adults. Search of the literature: The MEDLINE database was accessed through PubMed in April 2015. Results were restricted to the past 15 years and English language of articles. Both transient and permanent hypopituitarisms are not uncommon after TBI. Early after the TBI, pituitary dysfunction/s differ than those occurring after few weeks and months. Growth hormone deficiency (GHD) and alterations in puberty are the most common. After the one to more years of TBI, pituitary dysfunction tends to improve in some patients but may deteriorate in others. GH deficiency as well as Hypogonadism and thyroid dysfunction are the most common permanent lesions. Many of the symptoms of these endocrine defects can pass unnoticed because of the psychomotor defects associated with the TBI like depression and apathy. Unfortunately pituitary dysfunction appear to negatively affect psycho-neuro-motor recovery as well as growth and pubertal development of children and adolescents after TBI. Therefore, the current review highlights the importance of closely following patients, especially children and adolescents for growth and other symptoms and signs suggestive of endocrine dysfunction. In addition, all should be screened serially for possible endocrine disturbances early after the TBI as well as few months to a year after the injury. Risk factors for pituitary dysfunction after TBI include relatively serious TBI (Glasgow Coma Scale score < 10 and MRI showing damage to the hypothalamic pituitary area), diffuse brain swelling and the occurrence of hypotensive and/or hypoxic episodes. There is a considerable risk of developing pituitary dysfunction after TBI in children and adolescents. These patients should be clinically followed and screened for these abnormalities according to an agreed protocol of investigations. Further multicenter and multidisciplinary prospective studies are required to explore in details the occurrence of permanent pituitary dysfunction after TBI in larger numbers of children with TBI. This requires considerable organisation and communication between many disciplines such as neurosurgery, neurology, endocrinology, rehabilitation and developmental paediatrics.

Non-functional Avionics Requirements

NASA Astrophysics Data System (ADS)

Paulitsch, Michael; Ruess, Harald; Sorea, Maria

Embedded systems in aerospace become more and more integrated in order to reduce weight, volume/size, and power of hardware for more fuel-effi ciency. Such integration tendencies change architectural approaches of system ar chi tec tures, which subsequently change non-functional requirements for plat forms. This paper provides some insight into state-of-the-practice of non-func tional requirements for developing ultra-critical embedded systems in the aero space industry, including recent changes and trends. In particular, formal requi re ment capture and formal analysis of non-functional requirements of avionic systems - including hard-real time, fault-tolerance, reliability, and per for mance - are exemplified by means of recent developments in SAL and HiLiTE.

Towards an Early Software Effort Estimation Based on Functional and Non-Functional Requirements

NASA Astrophysics Data System (ADS)

Kassab, Mohamed; Daneva, Maya; Ormandjieva, Olga

The increased awareness of the non-functional requirements as a key to software project and product success makes explicit the need to include them in any software project effort estimation activity. However, the existing approaches to defining size-based effort relationships still pay insufficient attention to this need. This paper presents a flexible, yet systematic approach to the early requirements-based effort estimation, based on Non-Functional Requirements ontology. It complementarily uses one standard functional size measurement model and a linear regression technique. We report on a case study which illustrates the application of our solution approach in context and also helps evaluate our experiences in using it.

A simple uniformity test for ultrasound phased arrays.

PubMed

Dudley, Nicholas J; Woolley, Darren J

2016-09-01

It is difficult to test phased array ultrasound transducers for non functioning elements. We aimed to modify a widely performed test to improve its ease and effectiveness for these arrays. A paperclip was slowly moved along the transducer array, with the scanner operating in M-mode, imaging at a fundamental frequency with automatic gain and grey scale adjustment disabled. Non-functioning elements are identified by a dark vertical line in the image. The test was repeated several times for each transducer, looking for consistency of results. 2 transducers, with faults already shown by electronic transducer testing, were used to validate the method. 23 transducers in clinical use were tested. The results of the modified test on the 2 faulty transducers agreed closely with electronic transducer testing results. The test indicated faults in 5 of the 23 transducers in clinical use: 3 with a single failed element and 2 with non-uniform sensitivity. 1 transducer with non-uniform sensitivity had undergone lens repair; the new lens was visibly non-uniform in thickness and further testing showed a reduction in depth of penetration and a loss of elevational focus in comparison with a new transducer. The modified test is capable of detecting non-functioning elements. Further work is required to provide a better understanding of more subtle faults. Copyright © 2016 Associazione Italiana di Fisica Medica. All rights reserved.

Clinical spectrum of hypopituitarism in India: A single center experience

PubMed Central

Gundgurthi, Abhay; Garg, M. K.; Bhardwaj, Reena; Brar, Karninder S.; Kharb, Sandeep; Pandit, Aditi

2012-01-01

Objectives: There is paucity of information regarding clinical profile of hypopituitarism from India. We report the clinical profile of hypopituitarism from a tertiary center in North India. Materials and Methods: This study was carried out in patients attending our endocrine center between January 2010 and December 2011. All new patients were studied prospectively and those registered before January 2010 retrospectively. Relevant clinical, hormonal, and imaging data were collected. Dynamic testing for pituitary functions was carried out as necessary. Hormonal deficiencies were defined as per prevailing recommendations. Results: This study included 113 subjects. The mean age was 38.6 ± 17.8 years (range, 4 – 76 years). There were 78 (69%) males and 35 females (31%). There were 22 subjects aged ≤18 years (childhood and adolescence) and 91 adults (>18 years). Visual disturbances were the most common presenting complaint (33%), though headache was the most common symptom (81%). Fifteen percent presented with pituitary apoplexy. Tumors comprised of 84% of cases. Hypogonadism (97%) was the most common abnormality seen followed by hypothyroidism (83.2%), hypoadrenalism (79.6%), growth hormone deficiency (88.1% of the 42 patients tested), and diabetes insipidus (13.3%). Panhypopituitarism was seen in 104 (92%) patients. There were no cases of hypopituitarism secondary to traumatic brain injury, subarachnoid hemorrhage, central nervous system infections, or cranial irradiation to extrasellar tumors. Conclusion: The most common cause of hypopituitarism at tertiary care center is pituitary tumors and the commonest presenting complaint is visual symptoms. Panhypopituitarism is present in 92% cases. PMID:23087868

Clinical characteristics of central diabetes insipidus in Taiwanese children.

PubMed

Liu, Shih-Yao; Tung, Yi-Ching; Lee, Cheng-Ting; Liu, Hon-Man; Peng, Shinn-Forng; Wu, Mu-Zon; Kuo, Meng-Fai; Tsai, Wen-Yu

2013-10-01

Data on the clinical features of children with central diabetes insipidus (CDI) are lacking in Taiwan. This study investigated the clinical manifestations and etiology of CDI in Taiwanese children. From 1983 to 2012, 62 children with permanent diabetes insipidus were enrolled in the study. They were diagnosed at the Department of Pediatrics of National Taiwan University Hospital. Their medical records were thoroughly reviewed and their clinical symptoms and signs, laboratory data, and etiologies were analyzed. The patients' median age at diagnosis was 10 years and the median interval between initial manifestations and diagnosis was 0.5 years. The most common symptoms and signs were polyuria, polydipsia, nocturia, and growth retardation. Most patients had low urine osmolality and elevated plasma osmolality on diagnosis. Absence of a posterior pituitary hyperintense signal and thickening of the pituitary stalk were common findings on magnetic resonance imaging. Approximately 80% of the patients had anterior pituitary hormone deficiency and all patients had growth hormone deficiency. Approximately 60% of patients had intracranial lesions, the most common causes of which were germ cell tumor and Langerhans cell histiocytosis. Two patients were initially believed to have idiopathic CDI but intracranial lesions were detected during the follow-up period. Because a delayed diagnosis of CDI is common in Taiwanese children, a high index of suspicion is important. The underlying etiology of CDI in children may not initially be obvious. Long-term surveillance is therefore necessary, especially for the early detection of evolving treatable intracranial lesions. Copyright © 2013. Published by Elsevier B.V.

Clinical manifestations and hormonal profile of two women with Cushing's disease and mild deficiency of 21-hydroxylase.

PubMed

Boronat, M; Carrillo, A; Ojeda, A; Estrada, J; Ezquieta, B; Marín, F; Nóvoa, F J

2004-06-01

The development of Cushing's disease among patients with deficiency of 21-hydroxylase has not been observed to date. The clinical manifestations and the hormonal profile of this exceptional association are herein described through the study of two cases. The first one was a 39-yr-old woman who had undergone non-curative transsphenoidal surgery for a pituitary-dependent Cushing's syndrome 12 yr before. She showed hypertension, central obesity, severe hirsutism, alopecia and hyperpigmentation. Urinary excretion of cortisol was normal, but ACTH levels were very high and hormonal dynamic studies (cortisol circadian rhythm, insulin-induced hypoglycemia and dexamethasone suppression tests) revealed the qualitative disturbances that characterize Cushing's disease. Serum concentrations of androstenedione, free testosterone and 17-hydroxyprogesterone were clearly increased. Reexamination of the tissue samples from previous surgery confirmed the presence of an ACTH-producing pituitary adenoma. CYP21 gene analysis found the splicing 655G mutation at intron 2 and the V281L mutation at exon 7. The second case was a 21-yr-old woman who was diagnosed with pituitary ACTH-dependent Cushing's syndrome according to unequivocal clinical and laboratory findings. However, hirsutism was particularly severe and both serum androgens and 17-hydroxyprogesterone were elevated. The patient was heterozygote for a large conversion of CYP21 gene. In these cases, the clinical and biochemical expression of Cushing's syndrome was determined by the different severity of 21-hydroxylase deficiency and the subsequent residual ability of adrenal cortex to synthesize cortisol.

From Consternation to Revelation: Discovery of a Role for IGSF1 in Pituitary Control of Thyroid Function.

PubMed

Bernard, Daniel J; Brûlé, Emilie; Smith, Courtney L; Joustra, Sjoerd D; Wit, Jan M

2018-03-01

Immunoglobulin superfamily, member 1 (IGSF1) is a transmembrane glycoprotein highly expressed in the mammalian pituitary gland. Shortly after its discovery in 1998, the protein was proposed to function as a coreceptor for inhibins (and was even temporarily renamed inhibin binding protein). However, subsequent investigations, both in vitro and in vivo , failed to support a role for IGSF1 in inhibin action. Research on IGSF1 nearly ground to a halt until 2011, when next-generation sequencing identified mutations in the X-linked IGSF1 gene in boys and men with congenital central hypothyroidism. IGSF1 was localized to thyrotrope cells, implicating the protein in pituitary control of the thyroid. Investigations in two Igsf1 knockout mouse models converged to show that IGSF1 deficiency leads to reduced expression of the receptor for thyrotropin-releasing hormone (TRH) and impaired TRH stimulation of thyrotropin secretion, providing a candidate mechanism for the central hypothyroidism observed in patients. Nevertheless, the normal functions of IGSF1 in thyrotropes and other cells remain unresolved. Moreover, IGSF1 mutations are also commonly associated with other clinical phenotypes, including prolactin and growth hormone dysregulation, and macroorchidism. How the loss of IGSF1 produces these characteristics is unknown. Although early studies of IGSF1 ran into roadblocks and blind alleys, armed with the results of detailed clinical investigations, powerful mouse models, and new reagents, the field is now poised to discover IGSF1's function in endocrine tissues, including the pituitary and testes.

Novel Mutations in HESX1 and PROP1 Genes in Combined Pituitary Hormone Deficiency.

PubMed

Avbelj Stefanija, Magdalena; Kotnik, Primož; Bratanič, Nina; Žerjav Tanšek, Mojca; Bertok, Sara; Bratina, Nataša; Battelino, Tadej; Trebušak Podkrajšek, Katarina

2015-01-01

The HESX1 gene is essential in forebrain development and pituitary organogenesis, and its mutations are the most commonly identified genetic cause of septo-optic dysplasia (SOD). The PROP1 gene is involved in anterior pituitary cell lineage specification and is commonly implicated in non-syndromic combined pituitary hormone deficiency (CPHD). We aimed to assess the involvement of HESX1 and PROP1 mutations in a cohort of patients with SOD and CPHD. Six patients with sporadic SOD and 16 patients with CPHD from 14 pedigrees were screened for mutations in HESX1 and PROP1 genes by exon sequencing. Half of the CPHD patients had variable associated clinical characteristics, such as hearing loss, orofacial cleft, kidney disorder or developmental delay. Novel variants were evaluated in silico and verified in SNP databases. A novel heterozygous p.Glu102Gly mutation in the HESX1 gene and a novel homozygous p.Arg121Thr mutation in the PROP1 gene were detected in 2 pedigrees with CPHD. A small previously reported deletion in PROP1 c.301_302delAG was detected in a separate patient with CPHD, in heterozygous state. No mutations were identified in patients with SOD. Our results expand the spectrum of mutations implicated in CPHD. The frequency of 15% of the PROP1 mutations in CPHD was low, likely due to the clinical heterogeneity of the cohort. © 2015 S. Karger AG, Basel.

Usefulness of an ad hoc questionnaire (Acro-CQ) for the systematic assessment of acromegaly comorbidities at diagnosis and their management at follow-up.

PubMed

Guaraldi, F; Gori, D; Beccuti, G; Prencipe, N; Giordano, R; Mints, Y; Di Giacomo, V S; Berton, A; Lorente, M; Gasco, V; Ghigo, E; Salvatori, R; Grottoli, S

2016-11-01

To determine the validity of a self-administered questionnaire (Acro-CQ) developed to systematically assess the presence, type and time of onset of acromegaly comorbidities. This is a cross-sectional study; 105 acromegaly patients and 147 controls with other types of pituitary adenoma, referred to a specialized Italian Center, autonomously compiled Acro-CQ in an outpatient clinical setting. To test its reliability in a different setting, Acro-CQ was administered via mail to 78 patients with acromegaly and 100 with other pituitary adenomas, referred to a specialized US Center. Data obtained from questionnaires in both settings were compared with medical records (gold standard). Demographics of patients and controls from both countries were similar. In both settings, >95 % of the questionnaires were completely filled; only one item was missed in the others. Concordance with medical record was excellent (k > 0.85) for most of the items, independently from the way of administration, patient age, gender and nationality, pituitary adenoma type and disease activity. Acro-CQ is an inexpensive, highly accepted from patients and reliable tool recommended to expedite systematic collection of relevant clinical data in acromegaly at diagnosis, to be replicated at follow-ups. This tool may guide a targeted, cost-effective management of complications. Moreover, it could be applied to retrieve data for survey studies in both acromegaly and other pituitary adenomas, as information is easily and rapidly accessible for statistical analysis.

A novel germline mutation in the aryl hydrocarbon receptor-interacting protein (AIP) gene in an Italian family with gigantism.

PubMed

Urbani, C; Russo, D; Raggi, F; Lombardi, M; Sardella, C; Scattina, I; Lupi, I; Manetti, L; Tomisti, L; Marcocci, C; Martino, E; Bogazzi, F

2014-10-01

Acromegaly usually occurs as a sporadic disease, but it may be a part of familial pituitary tumor syndromes in rare cases. Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene have been associated with a predisposition to familial isolated pituitary adenoma. The aim of the present study was to evaluate the AIP gene in a patient with gigantism and in her relatives. Direct sequencing of AIP gene was performed in fourteen members of the family, spanning among three generations. The index case was an 18-year-old woman with gigantism due to an invasive GH-secreting pituitary adenoma and a concomitant tall-cell variant of papillary thyroid carcinoma. A novel germline mutation in the AIP gene (c.685C>T, p.Q229X) was identified in the proband and in two members of her family, who did not present clinical features of acromegaly or other pituitary disorders. Eleven subjects had no mutation in the AIP gene. Two members of the family with clinical features of acromegaly refused either the genetic or the biochemical evaluation. The Q229X mutation was predicted to generate a truncated AIP protein, lacking the last two tetratricopeptide repeat domains and the final C-terminal α-7 helix. We identified a new AIP germline mutation predicted to produce a truncated AIP protein, lacking its biological properties due to the disruption of the C-terminus binding sites for both the chaperones and the client proteins of AIP.

Transnasal stereotactic surgery of pituitary adenomas concomitant with acromegaly.

PubMed

Metyolkina, L; Peresedov, V

1995-01-01

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

Advances in understanding hypopituitarism

PubMed Central

Stieg, Mareike R.; Renner, Ulrich; Stalla, Günter K.; Kopczak, Anna

2017-01-01

The understanding of hypopituitarism has increased over the last three years. This review provides an overview of the most important recent findings. Most of the recent research in hypopituitarism has focused on genetics. New diagnostic techniques like next-generation sequencing have led to the description of different genetic mutations causative for congenital dysfunction of the pituitary gland while new molecular mechanisms underlying pituitary ontogenesis have also been described. Furthermore, hypopituitarism may occur because of an impairment of the distinctive vascularization of the pituitary gland, especially by disruption of the long vessel connection between the hypothalamus and the pituitary. Controversial findings have been published on post-traumatic hypopituitarism. Moreover, autoimmunity has been discussed in recent years as a possible reason for hypopituitarism. With the use of new drugs such as ipilimumab, hypopituitarism as a side effect of pharmaceuticals has come into focus. Besides new findings on the pathomechanism of hypopituitarism, there are new diagnostic tools in development, such as new growth hormone stimulants that are currently being tested in clinical trials. Moreover, cortisol measurement in scalp hair is a promising tool for monitoring cortisol levels over time. PMID:28299199

Endoscopic endonasal pituitary adenomas surgery: the surgical experience of 178 consecutive patients and learning curve of two neurosurgeons.

PubMed

Shou, Xuefei; Shen, Ming; Zhang, Qilin; Zhang, Yichao; He, Wenqiang; Ma, Zengyi; Zhao, Yao; Li, Shiqi; Wang, Yongfei

2016-11-30

We aim to study surgical technique and analyze the related factors affecting tumor total removal and postoperative endocrinological remission for endoscopic endonasal pituitary adenomas surgery. We retrospectively analyzed 178 endoscopic endonasal pituitary adenomas surgery from March 2011 to May 2014. Endonasal approach included the routine transnasal-sphenoidal approach, transnasal- maxillary sinus approach in four cases and transnasal-clivus approach in one case. According to postoperative imaging data and endocrine examination results, total removal was achieved in 129 patients (72.5%), and endocrinological remission was achieved in 38 patients with functional adenomas (44.1%). Statistical analysis of the clinical data showed that total removal rate was much closely related to tumor volume (P = 0.006), and tumor invasiveness (P < 0.001). In this study, we found tumor sizes and invasion of cavernous sinus were related to total removal rate and endocrinological remission rate; the direction and degree of tumor invasion, and the surgeon's experience were the key influence factors of the endocrinological remission rate for invasive functional pituitary adenomas.

Case report of a pituitary thyrotropin-secreting macroadenoma with Hashimoto thyroiditis and infertility.

PubMed

Li, Jiaqi; Li, Jianwei; Jiang, Shu; Yu, Ruichao; Yu, Yerong

2018-01-01

Thyrotropin-secreting adenoma (TSHoma) is rare, diagnosis and treatment are often delayed if the condition coexists with Hashimoto thyroiditis. The enlarged pituitary adenoma may eventually induce panhypopituitarism, infertility, or the compression of optic nerves and optic chiasma. This patient was a 36-year-old man who had been referred to the pituitary disease multidisciplinary team (MDT) of the West China Hospital, due to infertility. Examinations revealed pituitary thyrotropin-secreting macroadenoma. We conducted trans-sphenoidal surgery. Human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) were used for reproductive reconstruction after surgery. This patient successfully fathered a child. To date, the multidisciplinary team treatment of TSHoma was rare, TSHomas are often misdiagnosed as macroadenomas, because the clinical features are varied and it often takes a long time to be diagnosed. So the purpose of this case report is to attract attention to the manifestation of increased thyroid stimulating hormone (TSH) concentration and discuss MDT treatment for TSH-secreting adenoma. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Inhibin at 90: From Discovery to Clinical Application, a Historical Review

PubMed Central

Makanji, Yogeshwar; Zhu, Jie; Mishra, Rama; Holmquist, Chris; Wong, Winifred P. S.; Schwartz, Neena B.; Mayo, Kelly E.

2014-01-01

When it was initially discovered in 1923, inhibin was characterized as a hypophysiotropic hormone that acts on pituitary cells to regulate pituitary hormone secretion. Ninety years later, what we know about inhibin stretches far beyond its well-established capacity to inhibit activin signaling and suppress pituitary FSH production. Inhibin is one of the major reproductive hormones involved in the regulation of folliculogenesis and steroidogenesis. Although the physiological role of inhibin as an activin antagonist in other organ systems is not as well defined as it is in the pituitary-gonadal axis, inhibin also modulates biological processes in other organs through paracrine, autocrine, and/or endocrine mechanisms. Inhibin and components of its signaling pathway are expressed in many organs. Diagnostically, inhibin is used for prenatal screening of Down syndrome as part of the quadruple test and as a biochemical marker in the assessment of ovarian reserve. In this review, we provide a comprehensive summary of our current understanding of the biological role of inhibin, its relationship with activin, its signaling mechanisms, and its potential value as a diagnostic marker for reproductive function and pregnancy-associated conditions. PMID:25051334

Clinical Guidelines for the Diagnosis and Treatment of Cushing's Disease in Korea

PubMed Central

Hur, Kyu Yeon; Kim, Jung Hee; Kim, Byung Joon; Kim, Min-Seon; Lee, Eun Jig

2015-01-01

Cushing's disease (CD) is a rare disorder characterized by the overproduction of adrenocorticotropic hormone due to a pituitary adenoma that ultimately stimulates excessive cortisol secretion from the adrenal glands. Prior to the detection of pituitary adenomas, various clinical signs of CD such as central obesity, moon face, hirsutism, and facial plethora are usually already present. Uncontrolled hypercortisolism is associated with metabolic, cardiovascular, and psychological disorders that result in increased mortality. Hence, the early detection and treatment of CD are not only important but mandatory. Because its clinical manifestations vary from patient to patient and are common in other obesity-related conditions, the precise diagnosis of CD can be problematic. Thus, the present set of guidelines was compiled by Korean experts in this field to assist clinicians with the screening, diagnoses, and treatment of patients with CD using currently available tests and treatment modalities. PMID:25827452

Analysis of Xylem Sap from Functional (Nonembolized) and Nonfunctional (Embolized) Vessels of Populus nigra: Chemistry of Refilling1[C][W][OA

PubMed Central

Secchi, Francesca; Zwieniecki, Maciej A.

2012-01-01

It is assumed that the refilling of drought-induced embolism requires the creation of an osmotic gradient between xylem parenchyma cells and vessel lumens to generate the water efflux needed to fill the void. To assess the mechanism of embolism repair, it is crucial to determine if plants can up-regulate the efflux of osmotically active substances into embolized vessels and identify the major components of the released osmoticum. Here, we introduce a new approach of sap collection designed to separate water from nonembolized (functional) and embolized (nonfunctional) vessels. This new approach made possible the chemical analysis of liquid collected from both types of vessels in plants subjected to different levels of water stress. The technique also allowed us to determine the water volumes in nonfunctional vessels as a function of stress level. Overall, with the increase of water stress in plants, the osmotic potential of liquid collected from nonfunctional vessels increased while its volume decreased. These results revealed the presence of both sugars and ions in nonfunctional vessels at elevated levels in comparison with liquid collected from functional vessels, in which only traces of sugars were found. The increased sugar concentration was accompanied by decreased xylem sap pH. These results provide new insight into the biology of refilling, underlining the role of sugar and sugar transporters, and imply that a large degree of hydraulic compartmentalization must exist in the xylem during the refilling process. PMID:22837359

Laparoscopic versus open distal pancreatectomy for nonfunctioning pancreatic neuroendocrine tumors: a large single-center study.

PubMed

Han, Sang Hyup; Han, In Woong; Heo, Jin Seok; Choi, Seong Ho; Choi, Dong Wook; Han, Sunjong; You, Yung Hun

2018-01-01

Pancreatic neuroendocrine tumors (PNETs) account for 1-2% of all pancreatic neoplasms. Nonfunctioning PNETs (NF-PNETs) account for 60-90% of all PNETs. Laparoscopic distal pancreatectomy (LDP) is becoming the treatment of choice for benign lesions in the body and tail of the pancreas. However, LDP has not yet been widely accepted as the gold standard for NF-PNETs. The purpose of this study is to evaluate the clinical and oncologic outcomes after laparoscopic versus open distal pancreatectomy (ODP) for NF-PNETs. Between April 1995 and September 2016, 94 patients with NF-PNETs underwent open or laparoscopic distal pancreatectomy at Samsung Medical Center. Patients were divided into two groups: those who underwent LDP and those who underwent ODP. Both groups were compared in terms of clinical and oncologic variables. LDP patients had a significantly shorter hospital stay compared with ODP patients, amounting to a mean difference of 2 days (p < 0.001). Overall complication rates did not differ significantly between the ODP and LDP groups (p = 0.379). The 3-year overall survival rates in the ODP and LDP groups were 93.7 and 100%, respectively (p = 0.069). In this study, LDP for NF-PNETs had similar oncologic outcomes compared with ODP. In addition, LDP was associated with a shorter hospital stay compared with ODP. Therefore, LDP is a safe and effective procedure for patients with NF-PNETs. A multicenter study and a randomized controlled trial are needed to better assess the clinical and oncologic outcomes.

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

Pituitary stalk interruption syndrome presenting as short stature: a case report.

PubMed

Ram, Nanik; Ali, Syed Ahsan; Hussain, Syed Zubair

2014-12-19

Pituitary stalk interruption syndrome is a rare congenital abnormality of the pituitary that is responsible for anterior pituitary deficiency. It is characterized by a classic triad of interrupted pituitary stalk, absent or ectopic posterior pituitary, and anterior pituitary hypoplasia or aplasia. Clinical presentation varies according to age. In adults it presents as short stature and anterior pituitary deficiency. Without early diagnosis and treatment, mortality and morbidity in these patients is high. Early diagnosis and treatment of this rare disease can prevent permanent short statue of the patient. We report the first case of pituitary stalk interruption syndrome from Pakistan. A 17-year-old Pakistani young man presented with short stature and underdeveloped secondary sexual characters. His siblings and parents were healthy, with normal height. An examination showed his blood pressure was 90/60 mmHg, and his height, weight, and body mass index were 142 cm, 34.5 kg, and 17.10 kg/m2, respectively. He had no hair growth on his face, axilla, or pubis. His testes were between 1 and 2 mL in size, with a 4 cm-at-stretch micropenis. His lab investigations showed that his thyroid stimulating hormone (TSH) was 8.58 uIU/mL (0.4 to 4.2), his free thyroid hormone level FT4 was 0.46 ng/dL (0.89 to 1.76), his prolactin was 21.1 ng/mL (3.0 to 14.7), and his baseline cortisol was 0.30 ug/dL (4.3 to 22.4). His cortisol level after 60 minutes of cosyntropin injection was 3.5 ug/dL (4.3 to 22.4), his insulin like growth factor IGF-1 was 31.56 ng/mL (247.3 to 481.7), his testosterone level was under 2.5 ng/dL (2 to 800), his follicle stimulating hormone FSH was 0.41 uIU/mL (0.0 to 10.0), and his leutinizing hormone LH was under 0.1 uIU/mL (1.2 to 7.8). His bone age was 10 years according to the Greulich and Pyle method, as shown by X-rays. The results from his pituitary magnetic resonance imaging scan were consistent with pituitary stalk interruption syndrome. We describe a young man who presented with short stature and was found to have pituitary stalk interruption syndrome. Despite the fact that this is a rare disorder, it should always be kept in the differential diagnosis of a patient presenting with short stature. Patients with this disease have an excellent opportunity to reach normal height if they present before the joining of epiphyses.

Pouch functional outcomes after restorative proctocolectomy with ileal-pouch reconstruction in patients with ulcerative colitis: Japanese multi-center nationwide cohort study.

PubMed

Uchino, Motoi; Ikeuchi, Hiroki; Sugita, Akira; Futami, Kitaro; Watanabe, Toshiaki; Fukushima, Kouhei; Tatsumi, Kenji; Koganei, Kazutaka; Kimura, Hideaki; Hata, Keisuke; Takahashi, Kenichi; Watanabe, Kazuhiro; Mizushima, Tsunekazu; Funayama, Yuji; Higashi, Daijiro; Araki, Toshimitsu; Kusunoki, Masato; Ueda, Takeshi; Koyama, Fumikazu; Itabashi, Michio; Nezu, Riichiro; Suzuki, Yasuo

2018-05-01

Although several complications capable of causing pouch failure may develop after restorative proctocolectomy (RPC) for ulcerative colitis (UC), the incidences and causes are conflicting and vary according to country, race and institution. To avoid pouch failure, this study aimed to evaluate the rate of pouch failure and its risk factors in UC patients over the past decade via a nationwide cohort study. We conducted a retrospective, observational, multicenter study that included 13 institutions in Japan. Patients who underwent RPC between January 2005 and December 2014 were included. The characteristics and backgrounds of the patients before and during surgery and their postoperative courses and complications were reviewed. A total of 2376 patients were evaluated over 6.7 ± 3.5 years of follow-up. Twenty-seven non-functional pouches were observed, and the functional pouch rate was 98.9% after RPC. Anastomotic leakage (odds ratio, 9.1) was selected as a risk factor for a non-functional pouch. The cumulative pouch failure rate was 4.2%/10 years. A change in diagnosis to Crohn's disease/indeterminate colitis (hazard ratio, 13.2) was identified as an independent risk factor for pouch failure. The significant risk factor for a non-functional pouch was anastomotic leakage. The optimal staged surgical procedure should be selected according to a patient's condition to avoid anastomotic failure during RPC. Changes in diagnosis after RPC confer a substantial risk of pouch failure. Additional cohort studies are needed to obtain an understanding of the long-standing clinical course of and proper treatment for pouch failure.

Retinoic acid as a novel medical therapy for Cushing's disease in dogs.

PubMed

Castillo, Victor; Giacomini, Damiana; Páez-Pereda, Marcelo; Stalla, Johanna; Labeur, Marta; Theodoropoulou, Marily; Holsboer, Florian; Grossman, Ashley B; Stalla, Günter K; Arzt, Eduardo

2006-09-01

Cushing's disease is almost always caused by an ACTH-secreting pituitary tumor, but effective medical therapy is currently limited. Because retinoic acid has been shown to be potentially useful in decreasing corticotroph secretion and proliferation in rodent models, we have studied its action in dogs with Cushing's disease. A randomized treatment with retinoic acid (n = 22) vs. ketoconazole (n = 20) in dogs with Cushing's disease was assigned for a period of 180 d. Clinical signs, plasma ACTH and alpha-MSH, the cortisol/creatinine urine ratio, and pituitary magnetic resonance imaging were assessed and compared at different time points. We recorded a significant reduction in plasma ACTH and alpha-MSH, and also in the cortisol/creatinine urine ratio, of the dogs treated with retinoic acid. Pituitary adenoma size was also significantly reduced at the end of retinoic acid treatment. Survival time and all the clinical signs evaluated showed an improvement in the retinoic-acid-treated dogs. No adverse events or signs of hepatotoxicity were observed, suggesting that the drug is not only effective but also safe. Retinoic acid treatment controls ACTH and cortisol hyperactivity and tumor size in dogs with ACTH-secreting tumors, leading to resolution of the clinical phenotype. This study highlights the possibility of using retinoic acid as a novel therapy in the treatment of ACTH-secreting tumors in humans with Cushing's disease.

Harvey Cushing Treated the First Known Patient With Carney Complex

PubMed Central

Tsay, Cynthia J.; Stratakis, Constantine A.; Faucz, Fabio Rueda; London, Edra; Stathopoulou, Chaido; Allgauer, Michael; Quezado, Martha; Dagradi, Terry; Spencer, Dennis D.

2017-01-01

Context: Carney complex (CNC) is a syndrome characterized by hyperplasia of endocrine organs and may present with clinical features of Cushing syndrome and acromegaly due to functional adrenal and pituitary gland tumors. CNC has been linked to mutations in the regulatory subunit of protein kinase A type I-alpha (PRKAR1A) gene. Design: Tissue samples were taken from the hypothalamus or thalamus or tumors of patients with pituitary adenomas seen and operated on by neurosurgeon Harvey Cushing between 1913 and 1932. Following DNA extraction, sequencing for genes of interest was attempted, including PRKAR1A, AIP, USP8, GNAS1, and GPR101, to explore the possibility that these mutations associated with acromegaly, CNC, and Cushing syndrome have been conserved over time. Results: We report a patient described by Dr. Cushing in 1914 with a clinical presentation and postmortem findings suggestive of CNC. Genetic sequencing of the hypothalamus and pituitary adenoma revealed a germline heterozygous p.Arg74His mutation in the PRKAR1A gene, a codon previously described as mutated in CNC, but with a novel amino acid change. Conclusions: This patient is, to our knowledge, the first molecularly confirmed individual with CNC. This case demonstrates the power of modern genetics in studying archived tissues and the importance of recording detailed clinical notes in the diagnosis of disease. PMID:29264456

Unususpected meningioma in a patient with pituitary gigantism. Case report with autopsy findings.

PubMed

Stock, J M; Ghatak, N R; Oppenheimer, J H

1975-06-01

A unique example of a clinically unsuspected large parasellar meningioma is described in a 36-yr-old pituitary giant who had been treated initially with conventional irradiation, subsequently by surgical excision of an acidophil adenoma, and ultimately with medroxyprogesterone acetate (MPA) prior to his demise. The patient died of increased intracranial pressure resulting from a combined mass effect of the meningioma and recurrent tumor. The relationship between radiation and the development of the meningioma is discussed, as well as the fine ultrastructure of a highly functioning acidophil adenoma.

Mixed pituitary adenoma/craniopharyngioma: clinical, morphological, immunohistochemical and ultrastructural study of a case, review of the literature, and pathogenetic and nosological considerations.

PubMed

Finzi, Giovanna; Cerati, Michele; Marando, Alessandro; Zoia, Cesare; Ferreli, Fabio; Tomei, Giustino; Castelnuovo, Paolo; La Rosa, Stefano; Capella, Carlo

2014-02-01

Mixed pituitary adenoma/craniopharyngiomas are very rare tumors. Their pathogenesis is still unclear and it is not known whether they are collision tumors derived from independent stem cells or whether they originate from a single stem cell undergoing divergent differentiation. The latter hypothesis is supported by the close commixture between the two tumor components with transition areas that has been previously described. However, "hybrid" cells with both pituitary adenoma and craniopharyngioma features have never been described. In this paper we report a case of mixed pituitary adenoma/craniopharyngioma observed in a 75-year-old woman presenting with diplopia and slight increase of serum prolactin, who underwent endoscopic endonasal trans-sphenoidal tumor resection. Histologically, the tumor was composed of a typical pituitary silent subtype 2 ACTH cell adenoma admixed with islands of adamantinomatous craniopharyngioma. Electron microscopy showed that, in addition to distinct silent subtype 2 ACTH and craniopharyngioma cells, there were "hybrid" cells, showing characteristics of both pituitary adenoma and craniopharyngioma, consisting of small dense secretory granules, bundles of cytoplasmic filaments, and desmosomes. This ultrastructural finding was also confirmed by the presence of cells showing nuclear p40 expression and chromogranin A immunoreactivity. The close commixture between the two components and the ultrastructural and immunohistochemical findings demonstrate a common histogenesis of the two components and support the classification of the neoplasm as a mixed tumor. The patient completely recovered and, 10 months after surgery, head MR confirmed the complete resection of the lesion.

Value of pituitary gland MRI at 7 T in Cushing's disease and relationship to inferior petrosal sinus sampling: case report.

PubMed

Law, Meng; Wang, Regina; Liu, Chia-Shang J; Shiroishi, Mark S; Carmichael, John D; Mack, William J; Weiss, Martin; Wang, Danny J J; Toga, Arthur W; Zada, Gabriel

2018-03-23

Cushing's disease is caused by adrenocorticotrophic hormone (ACTH)-secreting pituitary adenomas, which are often difficult to identify on standard 1.5-T or 3-T MRI, including dynamic contrast imaging. Inferior petrosal and cavernous sinus sampling remains the gold standard for MRI-negative Cushing's disease. The authors report on a 27-year-old woman with Cushing's disease in whom the results of standard 1.5-T and 3-T MRI, including 1.5-T dynamic contrast imaging, were negative. Inferior petrosal sinus sampling showed a high central-to-peripheral ACTH ratio (148:1) as well as a right-to-left ACTH gradient (19:1), suggesting a right-sided pituitary microadenoma. The patient underwent 7-T MRI, which showed evidence of a right-sided pituitary lesion with focal hypoenhancement not visualized on 1.5-T or 3-T MRI. The patient underwent an endoscopic endonasal transsphenoidal operation, with resection of a right-sided pituitary mass. Postoperatively, she developed clinical symptoms suggestive of adrenal insufficiency and a nadir cortisol level of 1.6 μg/dl on postoperative day 3, and hydrocortisone therapy was initiated. Permanent histopathology specimens showed Crooke's hyaline change and ACTH-positive cells suggestive of an adenoma. MRI at 7 T may be beneficial in identifying pituitary microadenoma location in cases of standard 1.5-T and 3-T MRI-negative Cushing's disease. In the future, 7-T MRI may preempt inferior petrosal sinus sampling and help in cases of standard and dynamic contrast 1.5-T and 3-T MRI-negative Cushing's disease.

Intraoperative indocyanine green videoangiography for identification of pituitary adenomas using a microscopic transsphenoidal approach.

PubMed

Sandow, N; Klene, W; Elbelt, U; Strasburger, C J; Vajkoczy, P

2015-10-01

Initial successful surgical treatment of pituitary adenomas is crucial to reach long-term remission. Indocyanine green (ICG) videoangiography (VA) is well established in vascular neurosurgery nowadays and several reports described ICG application in brain tumor surgery. We designed this study to evaluate the feasibility of intravenous application of ICG and visualisation of a pituitary lesion via the fluorescence mode of the operation microscope. 22 patients with pituitary adenomas were treated with transsphenoidal microsurgery and were included in this study. Intraoperatively 25 mg ICG was administered intravenously and visualized via the fluorescence mode of the operation microscope (Pentero/Zeiss). 22 patients qualified for transsphenoidal surgery presenting with different clinical symptoms (13 patients with acromegaly, 6 with M. Cushing and 3 with other symptoms like vision disorder or dizziness) and identification of a pituitary lesion (21 of 22 patients) in preoperative MR-imaging (mean diameter: 9 mm; SD 3.6; 6 macroadenomas, 15 microadenomas, 1 MR-negative). In all 22 patients ICG VA was performed during surgery. No technical failures or adverse events after drug administration occurred. Visualization was optimal approximately 2.4 min after intravenous application. In all patients the adenoma could be detected via two different types of visualization: direct visualization by fluorophore emission versus indirect detection of the adenoma by a lower ICG fluorescence compared to the surrounding tissue. Our data show that intraoperative ICG VA can be a useful and easily applicable additional diagnostic tool for visualization of pituitary lesions using the microscopic approach.

Pituitary abscess following transsphenoidal surgery: the experience of 12 cases from a single institution.

PubMed

Wang, Lei; Yao, Yong; Feng, Feng; Deng, Kan; Lian, Wei; Li, Guilin; Wang, Renzhi; Xing, Bing

2014-09-01

To explore possible reasons for the incidence of a pituitary abscess following transsphenoidal surgery and determine the most effective treatment. A series of 12 patients who had undergone transsphenoidal surgery in other hospitals before being treated at Peking Union Medical College Hospital were reviewed. The presence of a pituitary abscess was confirmed when pus was intraoperatively observed within the sella turcica. All patients were treated with debridement of the abscess, nine among whom through a transsphenoidal approach and the other three via a craniotomy, followed by antibiotic treatment and hormone replacement therapy. The mean follow-up time was 27.0 months (range from 3.0 to 79.0 months). Headache (92%), panhypopituitarism (58%) and visual disturbance (50%) were the most common clinical indicators of a pituitary abscess. Imaging tests demonstrated a pituitary mass in all patients, with seven (58%) manifested with typical magnetic resonance features of an abscess. Ten patients (83%) were correctly diagnosed preoperatively. During surgical exploration, six presented with severe inflammation or an abscess within the sphenoidal sinus. Causative organisms were identified in five patients (42%). After surgical and antibiotic therapies, all patients fully recovered except for two presenting with severe visual impairment. Six patients (50%) required hormone replacement therapy. Retrograde infection from the sphenoid sinus may be a vital mechanism underlying the formation of a pituitary abscess following transsphenoidal surgery. Debridement of the abscess through surgical approaches combined with antibiotic treatment has been found to yield positive outcomes. Copyright © 2014 Elsevier B.V. All rights reserved.

A Case Study of Non-Functional Requirements and Continuous Improvement at a National Communications System Contractor

ERIC Educational Resources Information Center

Douglas, Volney L. R.

2010-01-01

National communications systems (NCS) are critical elements of a government's infrastructure. Limited improvements to the non-functional requirements (NFR) of NCS have caused issues during national emergencies such as 9/11 and Hurricane Katrina. The literature indicates that these issues result from a deficiency in understanding the roles NFRs and…

The NERV Methodology: Non-Functional Requirements Elicitation, Reasoning and Validation in Agile Processes

ERIC Educational Resources Information Center

Domah, Darshan

2013-01-01

Agile software development has become very popular around the world in recent years, with methods such as Scrum and Extreme Programming (XP). Literature suggests that functionality is the primary focus in Agile processes while non-functional requirements (NFR) are either ignored or ill-defined. However, for software to be of good quality both…

[Clinical study on the postburn change in the hypothalamus-pituitary-adrenal hormones in severely burned patients].

PubMed

Li, Hong-mian; Liang, Zi-qian; Luo, Zuo-jie

2003-06-01

To investigate the postburn dynamic changes in the hypothalamus-pituitary-adrenal hormones in severely burned patients. Fifty burn patients were enrolled in the study. The plasma contents of total GC (cortisol), ACTH and aldosterone (ALDO) and urinary contents of 17-OHO and 17-KS were determined with radio-immunological assay (RIA) method after burn injury to compare with the normal values which were well established clinically. The postburn plasma and urinary contents of the above indices were increased evidently with two peak values in shock and infectious stages, whilst the majority of he indices were lower than the normal values after 6 postburn weeks (PBWs). The values of these hormones were the lowest in dying patients. On the other hand, the values approached normal levels in those patients whose burn wounds were healing. Increases of the plasma and urinary levels of hypothalamus-pituitary -adrenal hormones in severely burned patients were constantly seen. Burn shock and infection seemed to be the two major factors in inducing postburn stress reaction in burn victims. Abrupt decrease of the hormone levels in plasma and or urine indicated adrenal failure predicting a poor prognosis of the burn patients.

Pituitary response to thyrotropin releasing hormone in children with overweight and obesity.

PubMed

Rijks, Jesse; Penders, Bas; Dorenbos, Elke; Straetemans, Saartje; Gerver, Willem-Jan; Vreugdenhil, Anita

2016-08-03

Thyroid stimulating hormone (TSH) concentrations in the high normal range are common in children with overweight and obesity, and associated with increased cardiovascular disease risk. Prior studies aiming at unravelling the mechanisms underlying these high TSH concentrations mainly focused on factors promoting thyrotropin releasing hormone (TRH) production as a cause for high TSH concentrations. However, it is unknown whether TSH release of the pituitary in response to TRH is affected in children with overweight and obesity. Here we describe TSH release of the pituitary in response to exogenous TRH in 73 euthyroid children (39% males) with overweight or (morbid) obesity. Baseline TSH concentrations (0.9-5.5 mU/L) were not associated with BMI z score, whereas these concentrations were positively associated with TSH concentrations 20 minutes after TRH administration (r(2) = 0.484, p < 0.001) and the TSH incremental area under the curve during the TRH stimulation test (r(2) = 0.307, p < 0.001). These results suggest that pituitary TSH release in response to TRH stimulation might be an important factor contributing to high normal serum TSH concentrations, which is a regular finding in children with overweight and obesity. The clinical significance and the intermediate factors contributing to pituitary TSH release need to be elucidated in future studies.

Nelfinavir induces radiation sensitization in pituitary adenoma cells

PubMed Central

Zeng, Jing; See, Alfred P.; Aziz, Khaled; Thiyagarajan, Saravanan; Salih, Tarek; Gajula, Rajendra P.; Armour, Michael; Phallen, Jillian; Terezakis, Stephanie; Kleinberg, Lawrence; Redmond, Kristen; Hales, Russell K.; Salvatori, Roberto; Quinones-Hinojosa, Alfredo; Tran, Phuoc T.; Lim, Michael

2017-01-01

Pituitary adenomas with local invasion and high secretory activity remain a therapeutic challenge. The HIV protease inhibitor nelfinavir is a radiosensitizer in multiple tumor models. We tested nelfinavir as a radiosensitizer in pituitary adenoma cells in vitro and in vivo. We examined the effect of nelfinavir with radiation on in vitro cell viability, clonogenic survival, apoptosis, prolactin secretion, cell cycle distribution and the PI3K-AKT-mTOR pathway. We evaluated tumor growth delay and confirmed nelfinavir’s effect on the PI3K-AKT-mTOR pathway in a hind-flank model. Nelfinavir sensitized pituitary adenoma cells to ionizing radiation as shown by viability assays and clonogenic assay with an enhancement ratio of 1.2 (p < 0.05). There is increased apoptotic cell death, as determined by annexin-V expression and cleaved caspase-3 levels. Nelfinavir does not affect prolactin secretion or cell cycle distribution. In vivo, untreated tumors reached 4-fold volume in 12 d, 17 d with nelfinavir treatment, 27 d with radiation 6 Gy, and 41 d with nelfinavir plus radiation (one-way ANOVA p < 0.001). Decreased phospho-S6 on protein gel blotting in vitro and immunohistochemistry in vivo demonstrated nelfinavir inhibition of the PI3K-AKT-mTOR pathway. Our data suggests a promising combination therapy with nelfinavir plus radiation in pituitary adenomas, which should be investigated in clinical studies. PMID:21811091

Nelfinavir induces radiation sensitization in pituitary adenoma cells.

PubMed

Zeng, Jing; See, Alfred P; Aziz, Khaled; Thiyagarajan, Saravanan; Salih, Tarek; Gajula, Rajendra P; Armour, Michael; Phallen, Jillian; Terezakis, Stephanie; Kleinberg, Lawrence; Redmond, Kristen; Hales, Russell K; Salvatori, Roberto; Quinones-Hinojosa, Alfredo; Tran, Phuoc T; Lim, Michael

2011-10-01

Pituitary adenomas with local invasion and high secretory activity remain a therapeutic challenge. The HIV protease inhibitor nelfinavir is a radiosensitizer in multiple tumor models. We tested nelfinavir as a radiosensitizer in pituitary adenoma cells in vitro and in vivo. We examined the effect of nelfinavir with radiation on in vitro cell viability, clonogenic survival, apoptosis, prolactin secretion, cell cycle distribution, and the PI3K-AKT-mTOR pathway. We evaluated tumor growth delay and confirmed nelfinavir's effect on the PI3K-AKT-mTOR pathway in a hind-flank model. Nelfinavir sensitized pituitary adenoma cells to ionizing radiation as shown by viability assays and clonogenic assay with an enhancement ratio of 1.2 (p < 0.05). There is increased apoptotic cell death, as determined by annexin-V expression and cleaved caspase-3 levels. Nelfinavir does not affect prolactin secretion or cell cycle distribution. In vivo, untreated tumors reached 4-fold volume in 12 days, 17 days with nelfinavir treatment, 27 days with radiation 6 Gy, and 41 days with nelfinavir plus radiation (one-way ANOVA p < 0.001). Decreased phospho-S6 on Western blotting in vitro and immunohistochemistry in vivo demonstrated nelfinavir inhibition of the PI3K-AKT-mTOR pathway. Our data suggests a promising combination therapy with nelfinavir plus radiation in pituitary adenomas, which should be investigated in clinical studies.

Pituitary response to thyrotropin releasing hormone in children with overweight and obesity

PubMed Central

Rijks, Jesse; Penders, Bas; Dorenbos, Elke; Straetemans, Saartje; Gerver, Willem-Jan; Vreugdenhil, Anita

2016-01-01

Thyroid stimulating hormone (TSH) concentrations in the high normal range are common in children with overweight and obesity, and associated with increased cardiovascular disease risk. Prior studies aiming at unravelling the mechanisms underlying these high TSH concentrations mainly focused on factors promoting thyrotropin releasing hormone (TRH) production as a cause for high TSH concentrations. However, it is unknown whether TSH release of the pituitary in response to TRH is affected in children with overweight and obesity. Here we describe TSH release of the pituitary in response to exogenous TRH in 73 euthyroid children (39% males) with overweight or (morbid) obesity. Baseline TSH concentrations (0.9–5.5 mU/L) were not associated with BMI z score, whereas these concentrations were positively associated with TSH concentrations 20 minutes after TRH administration (r2 = 0.484, p < 0.001) and the TSH incremental area under the curve during the TRH stimulation test (r2 = 0.307, p < 0.001). These results suggest that pituitary TSH release in response to TRH stimulation might be an important factor contributing to high normal serum TSH concentrations, which is a regular finding in children with overweight and obesity. The clinical significance and the intermediate factors contributing to pituitary TSH release need to be elucidated in future studies. PMID:27485208

Optic nerve size evaluated by magnetic resonance imaging in children with optic nerve hypoplasia, multiple pituitary hormone deficiency, isolated growth hormone deficiency, and idiopathic short stature.

PubMed

Birkebaek, Niels Holtum; Patel, Leena; Wright, Neville Bryce; Grigg, John Russell; Sinha, Smeeta; Hall, Catherine Margaret; Price, David Anthony; Lloyd, Ian Christopher; Clayton, Peter Ellis

2004-10-01

To objectively define criteria for intracranial optic nerve (ON) size in ON hypoplasia (ONH) on magnetic resonance imaging (MRI) scans. Intracranial ON sizes from MRI were compared between 46 children with ONH diagnosed by ophthalmoscopy (group 1, isolated ONH, 8 children; and group 2, ONH associated with abnormalities of the hypothalamic-pituitary axis and septum pellucidum, 38 children) and children with multiple pituitary hormone deficiency (group 3, multiple pituitary hormone deficiency, 14 children), isolated growth hormone deficiency (group 4, isolated growth hormone deficiency, 15 children), and idiopathic short stature (group 5, idiopathic short stature, 10 children). Intracranial ON size was determined by the cross-sectional area, calculated as [pi x (1/2) height x (1/2) width]. Groups 1 and 2 had lower intracranial ON size than did groups 3, 4, and 5 (P < .001). No patients in groups 3 through 5 who had MRI after 12 months of age (when 95% adult size of ONs is attained) had ONs <2.9 mm 2 . Visual acuity correlated significantly with ON size (P < .01). Magnetic resonance imaging of the ONs with cross-sectional area <2.9 mm 2 in a short child more than 12 months of age, with or without hypothalamic-pituitary axis abnormalities, confirms the clinical diagnosis of ONH.

[Dwarfism due to familial panhypopituitarism].

PubMed

Cos Welsh, J; Espinosa de los Monteros, A; de la Luz Ajuria, M; Morillo Almao, E

1977-01-01

Three sisters of 27 7/12, 13 8/12 and 9 1/12 years of age, respectively, with proportionate dwarfism, high pitched voice and lack of sexual development are described. All the patients had very low serum levels of immunoreactive growth hormone (GH), as well as of LH and FSH. Hypoglycemia induced by insulin and arginine infusion failed to increase GH levels, and the administration of the hypothalamic LH-FSH releasing hormone (LH-RH) did not elicit any response in the secretion of gonadotropins. The oldest sister developed hypothyroidism in recent years, since the I131 thyroid uptake was normal ten years before; her serum TSH was low and did not change with TRH stimulation. In addition, a low pituitary ACTH reserve was demonstrated by the hypoglycemia and metirapone tests. Case 2 showed partial pituitary TSH and ACTH reserve, whereas the youngest child only had low TSH pituitary reserve. These patients had all the clinical and laboratory characteristics of familial panhypopituitarism, with normal sella turcica. Genetic transmission in this cases is consistent with the autosomal recessive form, which is the most frequent type of inheritance of this entity. Consanguinity can not be ruled out. The results of the hypothalamic-pituitary functional tests apparently suggest that the primary defect could be located at the pituitary level. It is also possible that the pathological process may have a progressive evolution.

A membranous structure separating the adenohypophysis and neurohypophysis: an anatomical study and its clinical application for craniopharyngioma.

PubMed

Lu, Yun-Tao; Qi, Song-Tao; Xu, Jia-Ming; Pan, Jun; Shi, Jin

2015-06-01

OBJECT This study aimed to identify the membranous septation between the adeno- and neurohypophysis. The clinical impact of this septation in the surgical removal of infradiaphragmatic craniopharyngioma (Id-CP) is also clarified. METHODS The sellar regions from 8 fetal and 6 adult cadavers were dissected. After staining first with H & E and then with picro-Sirius red, the membranous structures were observed and measured under normal light and polarization microscopy. The pre- and postsurgical images and intraoperative procedures in 28 cases of childhood Id-CP were reviewed and analyzed. RESULTS There is a significant membranous septation (termed the adenoneurohypophysis septation [ANHS]) lying behind the intermediate lobe to separate the adeno- and neurohypophysis. The average thicknesses are 21.9 ± 16.9 μm and 79.1 ± 43.2 μm in fetal and adult heads, respectively. The median segment of the septation is significantly thicker than the upper and lower segments. The ANHS extends from the suprasellar pars tuberalis to the sellar floor, where it is fused with the pituitary capsule. During Id-CP surgery performed via a transcranial approach, the ANHS can be identified to reserve the neurohypophysis. Moreover, by understanding the anatomy of this membrane, the pituitary stalk was preserved in 3 patients (10.7%). CONCLUSIONS There is a significant membrane separating the anterior and posterior lobes of the pituitary gland, which lies behind the intermediate lobe. Understanding the anatomy of this septation is important for identifying and preserving the neurohypophysis and pituitary stalk during Id-CP surgery.

A thyrotropin-secreting macroadenoma with positive growth hormone and prolactin immunostaining: A case report and literature review.

PubMed

Kuzu, F; Bayraktaroğlu, T; Zor, F; G N, B D; Salihoğlu, Y S; Kalaycı, M

2015-01-01

Thyrotropin (thyroid stimulating hormone [TSH]) secreting pituitary adenomas (TSHoma) are rare adenomas presenting with hyperthyroidism due to impaired negative feedback of thyroid hormone on the pituitary and inappropriate TSH secretion. This article presents a case of TSH-secreting macroadenoma without any clinical hyperthyroidism symptoms accompanying immunoreaction with growth hormone (GH) and prolactin. A 36-year-old female patient was admitted with complaints of irregular menses and blurred vision. On physical exam, she had bitemporal hemianopsia defect. Magnetic resonance imaging (MRI) evaluation showed suprasellar macroadenoma measuring 33 mm × 26 mm × 28 mm was detected on pituitary MRI. She had no hyperthyroidism symptoms clinically. Although free T4 and free T3 levels were elevated, TSH level was inappropriately within the upper limit of normal. Response to T3 suppression and thyrotropin releasing hormone-stimulation test was inadequate. Other pituitary hormones were normal. Transsphenoidal adenomectomy was performed due to parasellar compression findings. Immunohistochemically widespread reaction was observed with TSH, GH and prolactin in the adenoma. The patient underwent a second surgical procedure 2 months later due to macroscopic residual tumor, bitemporal hemianopsia and a suprasellar homogenous uptake with regular borders on indium-111 octreotide scintigraphy. After second surgery; due to ongoing symptoms and residual tumor, she was managed with octreotide and cabergoline treatment. On her follow-up with medical treatment, TSH and free T4 values were within normal limits. Although silent TSHomas are rare, they may arise with compression symptoms as in our case. The differential diagnosis of secondary hyperthyroidism should include TSHomas and thyroid hormone receptor resistance syndrome.

Introducing AgilePQ DCM (Digital Conversion Module) - Video Text Version

Science.gov Websites

monolith. There's not one thing you do to make things digitally secure. We talk in terms of confidentiality enable these nonfunctional attributes. There's not, as I said, one thing you can do to satisfy the whole subject of cyber security. And there's not one thing you can do to fully enable these nonfunctional

Radioimmunoassay of human homologous prolactin in serum with commercially available reagents. [/sup 125/I tracer technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kao, P.C.; Jiang, N.S.; Abboud, C.F.

A clinically useful and reproducible radioimmunoassay for human homologous prolactin, established with commercially available reagents, was studied and validated. We present detailed conditions for iodination and purification of labeled prolactin and the optimal conditions for the assay. By the method, we found values (..mu..g/liter) as follows for serum prolactin: normal men, 8.9 +- 5.2 (mean +- SD); normal women, 11.8 +- 5.5; normal women taking contraceptive pills, 9.2 +- 5.0; pregnant women in the third trimester, 188 +- 69.5; patients with various diseases other than of the hypothalamic-pituitary axis, 9.3 +- 6.3; in some patients with amenorrhea and galactorrhea ofmore » diverse origin, 78.2 +- 87.4; and in some patients with surgically proven pituitary tumor, 1414 +- 1980. Results under provocative testing are also presented for a patient with normal hypothalamic-pituitary function.« less

Abscess inside craniopharyngioma: diagnostic and management implications.

PubMed

Bhaisora, Kamlesh Singh; Prasad, Surya Nandan; Das, Kuntal Kanti; Lal, Hira

2018-02-03

Abscess inside the pituitary fossa is very rare. Such abscess can be primary, occurring in an otherwise healthy pituitary gland, or secondary, developing inside a diseased gland (ie, harbouring craniopharyngioma, Rathke's cleft cyst, etc). Secondary pituitary abscess inside a craniopharyngioma remains an extremely rare occurrence. Our literature search revealed only six such cases reported so far. In this report, we present the seventh case of craniopharyngioma with abscess in a 38-year-old woman. We describe the uniqueness of the clinical presentation of our case, the radiological pointers to the possible diagnosis and the management issues in our patient. A review of literature is also included to provide a comprehensive picture of this rare condition to the readers. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Overlap of Post-obstructive Diuresis and Unmasked Diabetes Insipidus in a Case of IgG4-related Retroperitoneal Fibrosis and Tuberoinfundibular Hypophysitis: A Case Report and Review of the Literature

PubMed Central

Sasaki Yatabe, Midori; Watanabe, Kimio; Hayashi, Yoshimitsu; Yatabe, Junichi; Morimoto, Satoshi; Ichihara, Atsuhiro; Nakayama, Masaaki; Watanabe, Tsuyoshi

2017-01-01

The clinical picture of IgG4-related disease (IgG4-RD) is diverse because various organs can be affected. We describe the case of a 56-year-old man with acute renal failure and tuberoinfundibular hypophysitis due to IgG4-RD. Steroid therapy lowered the serum IgG4 level and ameliorated renal dysfunction, bilateral hydronephrosis and retroperitoneal fibrosis. However, polyuria from post-obstructive diuresis and unmasked central diabetes insipidus ensued. The patient's polyuria continued despite the administration of a therapeutic dose of glucocorticoid; the patient's pituitary swelling and anterior pituitary dysfunction were partially ameliorated. The pituitary swelling recurred seven months later. In patients with IgG4-RD, the manifestation of polyuria after steroid therapy should prompt suspicion of post-obstructive diuresis and the unmasking of central diabetes insipidus. PMID:28049999

Overlap of Post-obstructive Diuresis and Unmasked Diabetes Insipidus in a Case of IgG4-related Retroperitoneal Fibrosis and Tuberoinfundibular Hypophysitis: A Case Report and Review of the Literature.

PubMed

Sasaki Yatabe, Midori; Watanabe, Kimio; Hayashi, Yoshimitsu; Yatabe, Junichi; Morimoto, Satoshi; Ichihara, Atsuhiro; Nakayama, Masaaki; Watanabe, Tsuyoshi

The clinical picture of IgG4-related disease (IgG4-RD) is diverse because various organs can be affected. We describe the case of a 56-year-old man with acute renal failure and tuberoinfundibular hypophysitis due to IgG4-RD. Steroid therapy lowered the serum IgG4 level and ameliorated renal dysfunction, bilateral hydronephrosis and retroperitoneal fibrosis. However, polyuria from post-obstructive diuresis and unmasked central diabetes insipidus ensued. The patient's polyuria continued despite the administration of a therapeutic dose of glucocorticoid; the patient's pituitary swelling and anterior pituitary dysfunction were partially ameliorated. The pituitary swelling recurred seven months later. In patients with IgG4-RD, the manifestation of polyuria after steroid therapy should prompt suspicion of post-obstructive diuresis and the unmasking of central diabetes insipidus.

Dogs with macroadenomas have lower body temperature and heart rate than dogs with microadenomas.

PubMed

Benchekroun, Ghita; Desquilbet, Loic; Herrtage, Michael E; Jeffery, Nick D; Rosenberg, Dan; Granger, Nicolas

2017-09-01

Pituitary macroadenomas compress the hypothalamus, which partly regulates heart rate and body temperature. The aim of this study was to investigate whether heart rate and/or body temperature could aid in clinically differentiating dogs with macroadenomas from dogs with microadenomas (i.e. small non-compressive pituitary mass). Two groups of dogs diagnosed with pituitary-dependent hyperadrenocorticism (i.e. Cushing's disease) were included. Heart rate and body temperature were collected on initial presentation before any procedure. Dogs with macroadenoma had a significantly lower heart rate and body temperature (P<0.01) compared to dogs with microadenoma. We suggest that the combined cut-off values of 84 beats per minutes and 38.3°C in dogs with Cushing's disease, especially with vague neurological signs (nine of 12 dogs=75%), might help to suspect the presence of a macroadenoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

Severe peripheral neuropathy and elevated plantar pressures causing foot ulceration in pituitary gigantism.

PubMed

Jennings, A M; Robinson, A; Kandler, R H; Betts, R P; Ryder, R E; Cullen, D R

1993-07-01

We report two patients with treated pituitary gigantism and peripheral neuropathy, one of whom has chronic foot ulceration. Detailed neurophysiological assessment was performed on both patients. The patient with foot ulceration had clinical and neurophysiological evidence of severe neuropathy, whereas the patient without ulceration had only neurophysiological abnormalities. The sweating response to acetylcholine was markedly impaired in the feet of both patients, suggesting pedal autonomic denervation. Neither patient had evidence of diabetes mellitus and detailed investigation failed to reveal an alternative cause of peripheral neuropathy. Optical pedobarography revealed abnormally high pressure (> 10 kg/cm2) under the metatarsal heads of both patients, one such area coinciding with the area of ulceration. Thus in pituitary gigantism elevated plantar pressures may contribute to the development of foot ulceration when severe peripheral neuropathy is present. Furthermore, as in diabetes mellitus, impaired sweating may also increase the risk of ulceration as the resultant dry skin may develop fissures.

Central hypothyroidism and its role for cardiovascular risk factors in hypopituitary patients.

PubMed

Feldt-Rasmussen, Ulla; Klose, Marianne

2016-10-01

Hypothyroidism is characterized by hypometabolism, and may be seen as a part of secondary failure due to pituitary insufficiency or tertiary due to hypothalamic disease. Secondary and tertiary failures are also referred to as central hypothyroidism. Whereas overt primary hypothyroidism has a well-known affection on the heart and cardiovascular system, and may result in cardiac failure, cardiovascular affection is less well recognized in central hypothyroidism. Studies on central hypothyroidism and cardiovascular outcome are few and given the rarity of the diseases often small. Further, there are several limitations given vast difficulties in diagnosing the condition correctly biochemically, and difficulties monitoring the treatment because normal thyroid-pituitary feedback interrelationships are disrupted. The present review summarizes available studies of central adult hypothyroidism and its possible influence on the cardiovascular system, describe differences from primary thyroid failure and seek evidence for performing guidelines for clinical management of this particular thyroid and hypothalamo-pituitary disorder.

Pasireotide therapy in a rare and unusual case of plurihormonal pituitary macroadenoma

PubMed Central

Rajendran, Rajesh; Naik, Sarita; Sandeman, Derek D; Nasruddin, Azraai B

2013-01-01

Summary We report the use of pasireotide in a rare and unusual case of pituitary macroadenoma co-secreting GH, prolactin and ACTH. A 62-year-old Caucasian man presented with impotence. Clinically, he appeared acromegalic and subsequent investigations confirmed GH excess and hyperprolactinaemia. Magnetic resonance imaging (MRI) of pituitary revealed a large pituitary macroadenoma. He underwent trans-sphenoidal surgery and histology confirmed an adenoma with immunohistochemistry positive for ACTH, GH and prolactin. Acromegaly was not cured following surgery and inadequately controlled despite subsequent octreotide therapy. He underwent further debulking pituitary surgery, following which IGF1 levels improved but still high. This time adenoma cells showed immunohistochemistry positivity for ACTH only, following which subsequent investigations confirmed intermittent hypercortisolaemia compatible with pituitary Cushing's disease. We recommended radiotherapy, but in view of the pluripotential nature of the tumour, we proceeded with a trial of s.c. pasireotide therapy on the basis that it may control both his acromegaly and Cushing's disease. After 3 months of pasireotide therapy, his mean GH and IGF1 levels improved significantly, with improvement in his symptoms but intermittent hypercortisolaemia persists. His glycaemic control deteriorated requiring addition of new anti-diabetic medication. MRI imaging showed loss of contrast uptake within the tumour following pasireotide therapy but no change in size. We conclude that our patient has had a partial response to pasireotide therapy. Long-term follow-up studies are needed to establish its safety and efficacy in patients with acromegaly and/or Cushing's disease. Learning points Plurihormonal pituitary adenomas are rare and unusual.Patients with pituitary adenomas co-secreting ACTH and GH are more likely to present with acromegaly because GH excess can mask hypercortisolaemia.Pasireotide holds potential where conventional somatostatin analogues are not effective in acromegaly due to higher affinity for somatostatin receptor subtypes 1, 2, 3 and 5.Significant deterioration in glycaemic control remains a concern in the use of pasireotide.Currently, long-term safety and efficacy of pasireotide in patients with acromegaly and/or Cushing's disease are not fully clear. PMID:24616766

Prevalence of hypopituitarism after intracranial operations not directly associated with the pituitary gland

PubMed Central

2013-01-01

Background Over the last few years, awareness and detection rates of hypopituitarism following traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) has steadily increased. Moreover, recent studies have found that a clinically relevant number of patients develop pituitary insufficiency after intracranial operations and radiation treatment for non-pituitary tumors. But, in a substantial portion of more than 40%, the hypopituitarism already exists before surgery. We sought to determine the frequency, pattern, and severity of endocrine disturbances using basal and advanced dynamic pituitary testing following non-pituitary intracranial procedures. Methods 51 patients (29 women, 22 men) with a mean age of 55 years (range of 20 to 75 years) underwent prospective evaluation of basal parameters and pituitary function testing (combined growth hormone releasing hormone (GHRH)/arginine test, insulin tolerance test (ITT), low dose adrenocorticotropic hormone (ACTH) test), performed 5 to 168 months (median 47.2 months) after intracranial operation (4 patients had additional radiation and 2 patients received additional radiation combined with chemotherapy). Results We discovered an overall rate of hypopituitarism with distinct magnitude in 64.7% (solitary in 45.1%, multiple in 19.6%, complete in 0%). Adrenocorticotropic hormone insufficiency was found in 51.0% (partial in 41.2%, complete in 9.8%) and growth hormone deficiency (GHD) occurred in 31.4% (partial in 25.5%, severe in 5.9%). Thyrotropic hormone deficiency was not identified. The frequency of hypogonadism was 9.1% in men. Pituitary deficits were associated with operations both in close proximity to the sella turcica and more distant regions (p = 0.91). Age (p = 0.76) and gender (p = 0.24) did not significantly differ across patients with versus those without hormonal deficiencies. Groups did not significantly differ across pathology and operation type (p = 0.07). Conclusion Hypopituitarism occurs more frequently than expected in patients who have undergone neurosurgical intracranial procedures for conditions other then pituitary tumors or may already exists in a neurosurgical population before surgery. Pituitary function testing and adequate substitution may be warranted for neurosurgical patients with intracranial pathologies at least if unexplained symptoms like fatigue, weakness, altered mental activity, and decreased exercise tolerance are present. PMID:24188166

Pituitary genomic expression profiles of steers are altered by grazing of high vs. low endophyte-infected tall fescue forages.

PubMed

Li, Qing; Hegge, Raquel; Bridges, Phillip J; Matthews, James C

2017-01-01

Consumption of ergot alkaloid-containing tall fescue grass impairs several metabolic, vascular, growth, and reproductive processes in cattle, collectively producing a clinical condition known as "fescue toxicosis." Despite the apparent association between pituitary function and these physiological parameters, including depressed serum prolactin; no reports describe the effect of fescue toxicosis on pituitary genomic expression profiles. To identify candidate regulatory mechanisms, we compared the global and selected targeted mRNA expression patterns of pituitaries collected from beef steers that had been randomly assigned to undergo summer-long grazing (89 to 105 d) of a high-toxic endophyte-infected tall fescue pasture (HE; 0.746 μg/g ergot alkaloids; 5.7 ha; n = 10; BW = 267 ± 14.5 kg) or a low-toxic endophyte tall fescue-mixed pasture (LE; 0.023 μg/g ergot alkaloids; 5.7 ha; n = 9; BW = 266 ± 10.9 kg). As previously reported, in the HE steers, serum prolactin and body weights decreased and a potential for hepatic gluconeogenesis from amino acid-derived carbons increased. In this manuscript, we report that the pituitaries of HE steers had 542 differentially expressed genes (P < 0.001, false discovery rate ≤ 4.8%), and the pattern of altered gene expression was dependent (P < 0.001) on treatment. Integrated Pathway Analysis revealed that canonical pathways central to prolactin production, secretion, or signaling were affected, in addition to those related to corticotropin-releasing hormone signaling, melanocyte development, and pigmentation signaling. Targeted RT-PCR analysis corroborated these findings, including decreased (P < 0.05) expression of DRD2, PRL, POU1F1, GAL, and VIP and that of POMC and PCSK1, respectively. Canonical pathway analysis identified HE-dependent alteration in signaling of additional pituitary-derived hormones, including growth hormone and GnRH. We conclude that consumption of endophyte-infected tall fescue alters the pituitary transcriptome profiles of steers in a manner consistent with their negatively affected physiological parameters.

TSH-induced hyperthyroidism caused by a pituitary tumor.

PubMed

Beck-Peccoz, Paolo; Persani, Luca

2006-09-01

A 45-year-old man presented with frontal headache and visual disturbances to our clinic. For the previous 5 years, he had been receiving treatment for long-lasting mild hyperthyroidism with antithyroid therapy, but therapy had not been carefully followed. During the last 2 years he had also complained of erectile dysfunction and loss of libido. On physical examination, he had a small goiter, normal skin, no Graves' ophthalmopathy, normal BMI, and reduced testis volume and pubic hair. Serum levels of free T3 and T4, serum prolactin, testosterone, serum gonadotropins, insulin-like growth factor 1, adrenocorticotropic hormone, and cortisol were measured. MRI scan, TSH-releasing hormone test, and T3 suppression test were carried out. Levels of pituitary glycoprotein hormone alpha-subunit and sex-hormone-binding protein were also measured. Hyperthyroidism caused by a mixed pituitary adenoma that secretes prolactin and TSH. Trans-sphenoidal resection of the pituitary tumor. After surgery, T3 suppression test failed to completely suppress TSH secretion, which suggested a persistence of residual adenomatous cells. Hyperthyroidism and hypogonadism recurred after 5 years, therefore, treatment with lanreotide was initiated, and resulted in complete resolution of signs and symptoms of the disease.

Decreased expression of SFRP2 promotes development of the pituitary corticotroph adenoma by upregulating Wnt signaling

PubMed Central

Sun, Yuhao; Pan, Sijian; Gu, Changwei; Chen, Xiao; Wang, Weiqing; Ning, Guang; Bian, Liuguan; Sun, Qingfang

2018-01-01

Cushing's disease is primarily caused by pituitary adrenocorticotropin-secreting adenoma. However, its pathogenesis has remained obscure. In the present study, whole transcriptome analysis was performed by RNA sequencing (RNA-Seq) and expression of secreted frizzled-related protein 2 (SFRP2) was decreased in corticotroph tumors compared with normal pituitary glands. Furthermore, the RNA-Seq results were validated and the expression of SFRP2 in tumor tissues was analyzed by comparing another cohort of 23 patients with Cushing's disease and 3 normal human pituitary samples using reverse transcription-quantitative polymerase chain reaction, western blot and immunohistochemistry staining. Clinically, there was an association between lower SFRP2 expression and aggressive adenoma characteristics, including larger size and invasiveness. Conversely, SFRP2 overexpression reduced the ability of AtT20 cells to proliferate and migrate, and reduced production of the adrenocorticotrophic hormone in vitro. Mechanistically, overexpressed SFRP2 reduced the level of β-catenin in the cytoplasm and nucleus, and decreased Wnt signaling activity in AtT20 cells. Therefore, SFRP2 appears to act as a tumor suppressor in Cushing's disease by regulating the activity of the Wnt signaling pathway. PMID:29620167

Anterior hypopituitarism is rare and autoimmune disease is common in adults with idiopathic central diabetes insipidus.

PubMed

Hannon, M J; Orr, C; Moran, C; Behan, L A; Agha, A; Ball, S G; Thompson, C J

2012-05-01

Central diabetes insipidus is a rare clinical condition with a heterogenous aetiology. Up to 40% of cases are classified as idiopathic, although many of these are thought to have an autoimmune basis. Published data have suggested that anterior hypopituitarism is common in childhood-onset idiopathic diabetes insipidus. We aimed to assess the incidence of anterior hypopituitarism in a cohort of adult patients with idiopathic diabetes insipidus. We performed a retrospective review of the databases of two pituitary investigation units. This identified 39 patients with idiopathic diabetes insipidus. All had undergone magnetic resonance imaging scanning and dynamic pituitary testing (either insulin tolerance testing or GHRH/arginine and short synacthen testing) to assess anterior pituitary function. One patient had partial growth hormone deficiency; no other anterior pituitary hormonal deficits were found. Thirty-three percent had at least one autoimmune disease in addition to central diabetes insipidus. Our data suggest that anterior hypopituitarism is rare in adult idiopathic diabetes insipidus. Routine screening of these patients for anterior hypopituitarism may not, therefore, be indicated. The significant prevalence of autoimmune disease in this cohort supports the hypothesis that idiopathic diabetes insipidus may have an autoimmune aetiology. © 2012 Blackwell Publishing Ltd.

Application of intraoperative magnetic resonance imaging in large invasive pituitary adenoma surgery.

PubMed

Li, Jie; Cong, Zixiang; Ji, Xueman; Wang, Xiaoliang; Hu, Zhigang; Jia, Yue; Wang, Handong

2015-07-01

To investigate the clinical application value of intraoperative magnetic resonance imaging (iMRI) in large invasive pituitary adenoma surgery. A total of 30 patients with large pituitary adenoma underwent microscopic tumor resection under the assistance of an iMRI system; 26 cases received surgery through the nasal-transsphenoidal approach, and the remaining four cases received surgery through the pterion approach. iMRI was performed one or two times depending on the need of the surgeon. If a residual tumor was found, further resection was conducted under iMRI guidance. iMRI revealed residual tumors in 12 cases, among which nine cases received further resection. Of these nine cases, iMRI rescanning confirmed complete resection in six cases, and subtotal resection in the remaining three. Overall, 24 cases of tumor were totally resected, and six cases were subtotally resected. The total resection rate of tumors increased from 60% to 80%. iMRI can effectively determine the resection extent of pituitary adenomas. In addition, it provides an objective basis for real-time judgment of surgical outcome, subsequently improving surgical accuracy and safety, and increasing the total tumor resection rate. Copyright © 2015. Published by Elsevier Taiwan.

[Correlations between the hypothalamo-pituitary-adrenal axis and the metabolic syndrome].

PubMed

Góth, Miklós; Hubina, Erika; Korbonits, Márta

2005-01-09

The metabolic syndrome has several similarities with Cushing's syndrome (impaired glucose tolerance, hypertension, dyslipidemia, central obesity) suggesting that abnormalities in the regulation of the hypothalamic-pituitary-adrenal axis may have a link with the metabolic syndrome. Several studies suggested an association between the clinical signs of the metabolic syndrome and the increased hypothalamic-pituitary-adrenal axis activity based on increased cortisol concentration at 09.00 a.m. and increased cortisol response to corticotropin. According to the Barker hypothesis the fetal malnutrition could determine adult cardiovascular diseases (coronary heart disease, hypertension), some endocrine and metabolic disorders (obesity, type 2 diabetes and hyperlipidemia). The suggested mechanism of the phenomenon is that the suboptimal fetal nutrition results in glucocorticoid overproduction. The 11beta-hydroxysteroid dehydrogenase (converts biological inactive cortisone to cortisol and vice versa) is an important enzyme in cortisol metabolism. The increased expression of 11beta-hydroxysteroid dehydrogenase type 1 in fat tissue could lead to central obesity and impaired glucose tolerance. The hypothesis that increased corticotropin-releasing hormone production drives the overactive hypothalamo-pituitary-adrenal axis was not proven. Further investigations are needed to identify additional pathogenetic factors and to find new therapeutic possibilities.

Growth hormone-secreting macroadenoma of the pituitary gland successfully treated with the radiolabeled somatostatin analog (90)Y-DOTATATE: case report.

PubMed

Waligórska-Stachura, Joanna; Gut, Paweł; Sawicka-Gutaj, Nadia; Liebert, Włodzimierz; Gryczyńska, Maria; Baszko-Błaszyk, Daria; Blanco-Gangoo, Al Ricardo; Ruchała, Marek

2016-08-01

Pituitary tumors causing acromegaly are usually macroadenomas at the time of diagnosis, and they can grow aggressively, infiltrating surrounding tissues. Difficulty in achieving complete tumor removal at surgery can lead toward a strong tendency for recurrence, making it necessary to consider a means of treatment other than those currently used such as somatostatin analogs (SSAs), growth hormone (GH) receptor antagonist, surgical removal, and radiotherapy. The purpose of this paper is to describe a patient diagnosed with an aggressive, giant GH-secreting tumor refractory to medical therapy but ultimately treated with the radiolabeled somatostatin analog (90)Y-DOTATATE. A 26-year-old male with an invasive macroadenoma of the pituitary gland (5.6 × 2.5 × 3.6 cm) and biochemically confirmed acromegaly underwent 2 partial tumor resections: the first used the transsphenoidal approach and the second used the transcranial method. The patient received SSAs pre- and postoperatively. Because of the progression in pituitary tumor size, he underwent classic irradiation of the tumor (50 Gy). One and a half years later, the patient presented with clinically and biochemically active disease, and the tumor size was still 52 mm in diameter (height). Two neurosurgeons disqualified him from further surgical procedures. After confirming the presence of somatostatin receptors in the pituitary tumor by using (68)Ga-DOTATATE PET/CT, we treated the patient 4 times with an SSA bound with (90)Y-DOTATATE. After this treatment, the patient attained partial biochemical remission and a reduction in the tumor mass for the first time. Treatment with an SSA bound with (90)Y-DOTATATE may be a promising option for some aggressive GH-secreting pituitary adenomas when other methods have failed.

The Utility of Magnetic Resonance Imaging in Assessing Patients With Pituitary Tumors Compressing the Anterior Visual Pathway.

PubMed

Ryu, Won Hyung A; Starreveld, Yves; Burton, Jodie M; Liu, Junjie; Costello, Fiona

2017-09-01

Pituitary tumors are one of the most common types of intracranial neoplasms, and can cause progressive visual loss. An ongoing challenge in the management of patients with pituitary tumors is the cost, availability, and reliability of current magnetic resonance imaging (MRI) techniques to capture clinically significant incremental tumor growth. The purpose of this study was to evaluate the various MRI-based structural analyses and to explore the relationship between measures of structure and function in the afferent visual pathway of patients with pituitary tumors. We performed a critical review of literature on MRI-based structural analyses of pituitary adenomas using PubMed, Embase, Cochrane Library, and Google Scholar. In addition, preoperative structural characteristics of the optic apparatus, optic nerve compression, and optic chiasm elevation identified as important in the literature review, were examined in 18 of our patients from October 2010 to January 2014. In our review of literature, a total of 443 citations were obtained from our search strategy and review of bibliographies. Eight of these studies met inclusion/exclusion criteria and were retrieved for critical review. Of the 8 included studies, only 2 studies examined the relationship between MRI-based structural measurements and postoperative visual recovery. In our small case-series, MRI analysis of chiasm elevation, severity of optic nerve compression, chiasm position, height of chiasm, tumor height, and tumor volume failed to differentiate patients with postoperative visual dysfunction vs those with visual recovery (P > 0.05). Although MRI-based structural analysis is an important and useful tool for managing patients with pituitary tumors, there are limited objective measures shown to be predictive of postoperative visual recovery.

Clinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients.

PubMed

Rostomyan, Liliya; Daly, Adrian F; Petrossians, Patrick; Nachev, Emil; Lila, Anurag R; Lecoq, Anne-Lise; Lecumberri, Beatriz; Trivellin, Giampaolo; Salvatori, Roberto; Moraitis, Andreas G; Holdaway, Ian; Kranenburg-van Klaveren, Dianne J; Chiara Zatelli, Maria; Palacios, Nuria; Nozieres, Cecile; Zacharin, Margaret; Ebeling, Tapani; Ojaniemi, Marja; Rozhinskaya, Liudmila; Verrua, Elisa; Jaffrain-Rea, Marie-Lise; Filipponi, Silvia; Gusakova, Daria; Pronin, Vyacheslav; Bertherat, Jerome; Belaya, Zhanna; Ilovayskaya, Irena; Sahnoun-Fathallah, Mona; Sievers, Caroline; Stalla, Gunter K; Castermans, Emilie; Caberg, Jean-Hubert; Sorkina, Ekaterina; Auriemma, Renata Simona; Mittal, Sachin; Kareva, Maria; Lysy, Philippe A; Emy, Philippe; De Menis, Ernesto; Choong, Catherine S; Mantovani, Giovanna; Bours, Vincent; De Herder, Wouter; Brue, Thierry; Barlier, Anne; Neggers, Sebastian J C M M; Zacharieva, Sabina; Chanson, Philippe; Shah, Nalini Samir; Stratakis, Constantine A; Naves, Luciana A; Beckers, Albert

2015-10-01

Despite being a classical growth disorder, pituitary gigantism has not been studied previously in a standardized way. We performed a retrospective, multicenter, international study to characterize a large series of pituitary gigantism patients. We included 208 patients (163 males; 78.4%) with growth hormone excess and a current/previous abnormal growth velocity for age or final height >2 s.d. above country normal means. The median onset of rapid growth was 13 years and occurred significantly earlier in females than in males; pituitary adenomas were diagnosed earlier in females than males (15.8 vs 21.5 years respectively). Adenomas were ≥10 mm (i.e., macroadenomas) in 84%, of which extrasellar extension occurred in 77% and invasion in 54%. GH/IGF1 control was achieved in 39% during long-term follow-up. Final height was greater in younger onset patients, with larger tumors and higher GH levels. Later disease control was associated with a greater difference from mid-parental height (r=0.23, P=0.02). AIP mutations occurred in 29%; microduplication at Xq26.3 - X-linked acrogigantism (X-LAG) - occurred in two familial isolated pituitary adenoma kindreds and in ten sporadic patients. Tumor size was not different in X-LAG, AIP mutated and genetically negative patient groups. AIP-mutated and X-LAG patients were significantly younger at onset and diagnosis, but disease control was worse in genetically negative cases. Pituitary gigantism patients are characterized by male predominance and large tumors that are difficult to control. Treatment delay increases final height and symptom burden. AIP mutations and X-LAG explain many cases, but no genetic etiology is seen in >50% of cases. © 2015 Society for Endocrinology.

Primary Endoscopic Transnasal Transsphenoidal Surgery for Giant Pituitary Adenoma.

PubMed

Kuo, Chao-Hung; Yen, Yu-Shu; Wu, Jau-Ching; Chang, Peng-Yuan; Chang, Hsuan-Kan; Tu, Tsung-Hsi; Huang, Wen-Cheng; Cheng, Henrich

2016-07-01

Giant pituitary adenoma (>4 cm) remains challenging because the optimal surgical approach is uncertain. Consecutive patients with giant pituitary adenoma who underwent endoscopic transnasal transsphenoidal surgery (ETTS) as the first and primary treatment were retrospectively reviewed. Inclusion criteria were tumor diameter ≥4 cm in at least 1 direction, and tumor volume ≥10 cm(3). Exclusion criteria were follow-ups <2 years and diseases other than pituitary adenoma. All the clinical and radiologic outcomes were evaluated. A total of 38 patients, average age 50.8 years, were analyzed with a mean follow-up of 72.9 months. All patients underwent ETTS as the first and primary treatment, and 8 (21.1%) had complete resection without any evidence of recurrence at the latest follow-up. Overall, mean tumor volume decreased from 29.7 to 3.2 cm(3) after surgery. Residual and recurrent tumors (n = 30) were managed with 1 of the following: Gamma Knife radiosurgery (GKRS), reoperation (redo ETTS), both GKRS and ETTS, medication, conventional radiotherapy, or none. At last follow-up, most of the patients had favorable outcomes, including 8 (21.1%) who were cured and 29 (76.3%) who had a stable residual condition without progression. Only 1 (2.6%) had late recurrence at 66 months after GKRS. The overall progression-free rate was 97.4%, with few complications. In this series of giant pituitary adenoma, primary (ie, the first) ETTS yielded complete resection and cure in 21.1%. Along with adjuvant therapies, including GKRS, most patients (97.4%) were stable and free of disease progression. Therefore, primary ETTS appeared to be an effective surgical approach for giant pituitary adenoma. Copyright © 2016 Elsevier Inc. All rights reserved.

Atlanto-axial malformation and instability in dogs with pituitary dwarfism due to an LHX3 mutation.

PubMed

Voorbij, A M W Y; Meij, B P; van Bruggen, L W L; Grinwis, G C M; Stassen, Q E M; Kooistra, H S

2015-01-01

Canine pituitary dwarfism or combined pituitary hormone deficiency (CPHD) in shepherd dogs is associated with an LHX3 mutation and can lead to a wide range of clinical manifestations. Some dogs with CPHD have neurological signs that are localized to the cervical spine. In human CPHD, caused by an LHX3 mutation, anatomical abnormalities in the atlanto-axial (C1-C2) joint have been described. To evaluate the presence of atlanto-axial malformations in dogs with pituitary dwarfism associated with an LHX3 mutation and to investigate the degree of similarity between the atlanto-axial anomalies found in canine and human CPHD patients with an LHX3 mutation. Three client-owned Czechoslovakian wolfdogs and 1 client-owned German shepherd dog, previously diagnosed with pituitary dwarfism caused by an LHX3 mutation, with neurological signs indicating a cervical spinal disorder. Radiography, computed tomography, and magnetic resonance imaging of the cranial neck and skull, necropsy, and histology. Diagnostic imaging identified abnormal positioning of the dens axis and incomplete ossification of the suture lines between the ossification centers of the atlas with concurrent atlanto-axial instability and dynamic compression of the spinal cord by the dens axis. The malformations and aberrant motion at C1-C2 were confirmed at necropsy and histology. The atlanto-axial abnormalities of the dwarf dogs resemble those encountered in human CPHD patients with an LHX3 mutation. These findings suggest an association between the LHX3 mutation in dogs with CPHD and atlanto-axial malformations. Consequently, pituitary dwarfs should be monitored closely for neurological signs. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

21 CFR 520.1705 - Pergolide.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 2 micrograms/kilograms (µ/kg) once daily. Dosage may be adjusted to effect, not to exceed 4 µg/kg daily. (2) Indications for use. For the control of clinical signs associated with Pituitary Pars...

21 CFR 520.1705 - Pergolide.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 2 micrograms/kilograms (µ/kg) once daily. Dosage may be adjusted to effect, not to exceed 4 µg/kg daily. (2) Indications for use. For the control of clinical signs associated with Pituitary Pars...

21 CFR 520.1705 - Pergolide.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 2 micrograms/kilograms (µ/kg) once daily. Dosage may be adjusted to effect, not to exceed 4 µg/kg daily. (2) Indications for use. For the control of clinical signs associated with Pituitary Pars...

A step by step approach in differential diagnosing of adrenal incidentaloma (epinephroma), (with comments on the new Clinical Practice Guidelines of the European Society of Endocrinology).

PubMed

Farrugia, Frederick-Anthony; Misiakos, Evangelos; Martikos, Georgios; Tzanetis, Panagiotis; Charalampopoulos, Anestis; Zavras, Nicolaos; Sotiropoulos, Dimitrios; Koliakos, Nikolaos

2017-12-01

To present a step by step approach for the diagnosis of adrenal incidentaloma (AI). An extensive review of the literature was conducted, searching the Pub-Med and Google Scholar using the Mesh terms; Adrenal; Incidentaloma; Adrenal tumours; Radiology; Diagnosis. We also did a cross-referencing search of the literature. Comments on the new European guidelines are presented. The majority of the tumours are non-functioning benign adenomas. The most important radiological characteristic of an adrenal incidentaloma is the radiation attenuation coefficient. Wash out percentage and the imaging characteristics of the tumour may help in diagnosis. Density less than 10 HU is in most cases characteristic of a lipid rich benign adenoma. More than 10 HU or/and history of malignancy raise the possibility for cancer. 1 mg dexamethasone test and plasma metanephrines should be done in all patients. If there is history of hypokalemia and/or resistant hypertension we test the plasma aldosterone to plasma renin ratio (ARR). Newer studies have shown that tumours even nonfunctioning and less than 4 cm may increase the metabolic risks so we may consider surgery at an earlier stage.

[A Case of Von Hippel-Lindau Disease with Nonfunctioning Pancreatic Neuroendocrine Tumors Treated by Duodenum-Preserving Resection of the Head of the Pancreas and Spleen-Preserving Resection of the Tail of the Pancreas].

PubMed

Umehara, Yutaka; Umehara, Minoru; Tokura, Tomohisa; Yachi, Takafumi; Takahashi, Kenichi; Morita, Takayuki; Hakamada, Kenichi

2015-10-01

A 26-year-old woman presented to our department with a diagnosis of multiple nonfunctioning pancreatic neuroendocrine tumors. She had a family history of pheochromocytoma and a medical history of bilateral adrenalectomy for pheochromocytoma at the age of 25 years. During follow-up treatment for adrenal insufficiency after the surgery, highly enhanced tumors in the pancreas were detected on contrast-enhanced CT. Other examinations found that the patient did not satisfy the clinical criteria for von Hippel-Lindau (VHL) disease. Considering her age and risk of developing multiple heterotopic and heterochronous tumors, we performed a duodenum-preserving resection of the head of the pancreas and spleen-preserving resection of the tail of the pancreas with informed consent. The histopathological findings revealed that all of the tumors were NET G1. She underwent genetic testing postoperatively and was diagnosed with VHL disease. This diagnosis meant that we were able to create an optimal treatment plan for the patient. If a tumor predisposition syndrome is suspected, VHL disease should be borne in mind and genetic testing after genetic counseling should be duly considered.

Non-functioning parathyroid cystic tumour: malignant or not? Report of a case

PubMed Central

COCORULLO, G.; SCERRINO, G.; MELFA, G.; RASPANTI, C.; ROTOLO, G.; MANNINO, V.; RICHIUSA, P.; CABIBI, D.; GIANNONE, A.G.; PORRELLO, C.; GULOTTA, G.

2017-01-01

Parathyroid carcinoma (PC) is a very rare endocrine tumour, usually characterized by symptoms such as a neck mass, dysphonia, severe hypercalcemia exceeding 140 mg/L and elevated serum parathyroid hormone levels, even more than 5 times the upper limit of normal. Non-functioning parathyroid cancer is extremely rare and, in this case, its pre-operative diagnosis is often difficult. A 54-year old female patient, referring dysphagia and dysphonia, underwent neck ultrasound and neck CT. A left thyroid nodule, probably cystic, was found. It presented caudal extent on anterior mediastinum causing compression of the left lateral wall of the trachea. The preoperative calcemia was into the normal range. The patient underwent left thyroid lobectomy. Histological exam showed a cystic lesion, immunohistochemically originating from parathyroid that oriented for carcinoma. The 18 months follow-up did not show a residual-recurrent disease. The parathyroid origin of a neck lesion could not be suspected before surgery when specific laboratory tests are not available and clinical effects of hyperparathyroidism syndrome are not present. Histological features are not always sufficient for the differential diagnosis between the parathyroid adenoma and carcinoma. The immunohistochemistry is an useful tool that can aid to reach the definite diagnosis. PMID:29280705

Non-functioning parathyroid cystic tumour: malignant or not? Report of a case.

PubMed

Cocorullo, G; Scerrino, G; Melfa, G; Raspanti, C; Rotolo, G; Mannino, V; Richiusa, P; Cabibi, D; Giannone, A G; Porrello, C; Gulotta, G

2017-01-01

Parathyroid carcinoma (PC) is a very rare endocrine tumour, usually characterized by symptoms such as a neck mass, dysphonia, severe hypercalcemia exceeding 140 mg/L and elevated serum parathyroid hormone levels, even more than 5 times the upper limit of normal. Non-functioning parathyroid cancer is extremely rare and, in this case, its pre-operative diagnosis is often difficult. A 54-year old female patient, referring dysphagia and dysphonia, underwent neck ultrasound and neck CT. A left thyroid nodule, probably cystic, was found. It presented caudal extent on anterior mediastinum causing compression of the left lateral wall of the trachea. The preoperative calcemia was into the normal range. The patient underwent left thyroid lobectomy. Histological exam showed a cystic lesion, immunohistochemically originating from parathyroid that oriented for carcinoma. The 18 months follow-up did not show a residual-recurrent disease. The parathyroid origin of a neck lesion could not be suspected before surgery when specific laboratory tests are not available and clinical effects of hyperparathyroidism syndrome are not present. Histological features are not always sufficient for the differential diagnosis between the parathyroid adenoma and carcinoma. The immunohistochemistry is an useful tool that can aid to reach the definite diagnosis.

Pancreatic non-functioning neuroendocrine tumor: a new entity genetically related to Lynch syndrome

PubMed Central

Serracant Barrera, Anna; Serra Pla, Sheila; Blázquez Maña, Carmen María; Salas, Rubén Carrera; García Monforte, Neus; Bejarano González, Natalia; Romaguera Monzonis, Andreu; Andreu Navarro, Francisco Javier; Bella Cueto, Maria Rosa

2017-01-01

Some pancreatic neuroendocrine tumors (P-NETs) are associated with hereditary syndromes. An association between Lynch syndrome (LS) and P-NETs has been suggested, however it has not been confirmed to date. We describe the first case associating LS and P-NETs. Here we report a 65-year-old woman who in the past 20 years presented two colorectal carcinomas (CRC) endometrial carcinoma (EC), infiltrating ductal breast carcinoma, small intestine adenocarcinoma, two non-functioning P-NETs and sebomatricoma. With the exception of one P-NET, all these conditions were associated with LS, as confirmed by immunohistochemistry (IHC) and polymerase chain reaction (PCR). LS is caused by a mutation of a mismatch repair (MMR) gene which leads to a loss of expression of its protein. CRC is the most common tumor, followed by EC. Pancreatic tumors have also been associated with LS. Diagnosis of LS is based on clinical criteria (Amsterdam II and Bethesda) and genetic study (MMR gene mutation). The association between LS and our patient’s tumors was confirmed by IHC (loss of expression of proteins MLH1 and its dimer PMS2) and the detection of microsatellite instability (MSI) using PCR. PMID:29184699

Massive pleural and pericardial effusion due to hypothyroidism in a patient with a surgically treated thyroid-stimulating hormone-producing pituitary adenoma.

PubMed

Lee, Ji-Hoon; Park, MinA; Park, Myung Jae; Jo, Yong Suk

2018-05-14

Hypothyroidism is relatively rare etiology of serositis with effusion, but massive pleural effusion is very unusual. This is a report of massive pleural effusion in patient taking methimazole after surgical resection of thyroid-stimulating hormone (TSH)-producing pituitary adenoma (TSHoma). The patient was clinically and biochemically hypothyroid and responded well to discontinuation of methimazole and thyroid hormone replacement therapy. When assessing patients with pleural effusion, we should not rely on laboratory test results alone, as a detailed medical history and thorough physical examination could be more useful.

Spontaneous ovarian hyperstimulation syndrome and pituitary hyperplasia mimicking macroadenoma associated with primary hypothyroidism

PubMed Central

Kanza, Rene Epunza; Gagnon, Sylvain; Villeneuve, Helene; Laverdiere, David; Rousseau, Isabelle; Bordeleau, Edith; Berube, Michel

2013-01-01

We report an unusual case of spontaneous ovarian hyperstimulation syndrome and pituitary hyperplasia mimicking macroadenoma in an adult, non-pregnant woman. Her condition was triggered by unrecognized primary hypothyroidism, which regressed after thyroid hormone replacement therapy. This case highlights the need for clinicians and radiologists to familiarize themselves with the clinical and imaging features detected in case of these complications of primary hypothyroidism, which are not well known in the medical and radiological profession. Such improved knowledge will help avoid delays in diagnosis, progression to life-threatening complications, and unnecessary surgery. PMID:23494012

Accelerated Telomere Shortening in Acromegaly; IGF-I Induces Telomere Shortening and Cellular Senescence.

PubMed

Matsumoto, Ryusaku; Fukuoka, Hidenori; Iguchi, Genzo; Odake, Yukiko; Yoshida, Kenichi; Bando, Hironori; Suda, Kentaro; Nishizawa, Hitoshi; Takahashi, Michiko; Yamada, Shozo; Ogawa, Wataru; Takahashi, Yutaka

2015-01-01

Patients with acromegaly exhibit reduced life expectancy and increased prevalence of age-related diseases, such as diabetes, hypertension, and cardiovascular disease. However, the underlying mechanism has not been fully elucidated. Telomere shortening is reportedly associated with reduced life expectancy and increased prevalence of these age-related diseases. We measured telomere length in patients with acromegaly using quantitative PCR method. The effect of GH and IGF-I on telomere length and cellular senescence was examined in human skin fibroblasts. Patients with acromegaly exhibited shorter telomere length than age-, sex-, smoking-, and diabetes-matched control patients with non-functioning pituitary adenoma (0.62 ± 0.23 vs. 0.75 ± 0.35, respectively, P = 0.047). In addition, telomere length in acromegaly was negatively correlated with the disease duration (R2 = 0.210, P = 0.003). In vitro analysis revealed that not GH but IGF-I induced telomere shortening in human skin fibroblasts. Furthermore, IGF-I-treated cells showed increased senescence-associated β-galactosidase activity and expression of p53 and p21 protein. IGF-I-treated cells reached the Hayflick limit earlier than GH- or vehicle-treated cells, indicating that IGF-I induces cellular senescence. Shortened telomeres in acromegaly and cellular senescence induced by IGF-I can explain, in part, the underlying mechanisms by which acromegaly exhibits an increased morbidity and mortality in association with the excess secretion of IGF-I.

Coexisting diseases modifying each other’s presentation - lack of growth failure in Turner syndrome due to the associated pituitary gigantism.

PubMed

Dragović, Tamara; Đuran, Zorana; Jelić, Svetlana; Marinković, Dejan; Kiković, Saša; Kuzmić-Janković, Snežana; Hajduković, Zoran

2016-10-01

Turner syndrome presents with one of the most frequent chromosomal aberrations in female, typically presented with growth retardation, ovarian insufficiency, facial dysmorphism, and numerous other somatic stigmata. Gigantism is an extremely rare condition resulting from an excessive growth hormone (GH) secretion that occurs during childhood before the fusion of epiphyseal growth plates. The major clinical feature of gigantism is growth acceleration, although these patients also suffer from hypogonadism and soft tissue hypertrophy. We presented a girl with mosaic Turner syndrome, delayed puberty and normal linear growth for the sex and age, due to the simultaneous GH hypersecretion by pituitary tumor. In the presented case all the typical phenotypic stigmata related to Turner syndrome were missing. Due to excessive pituitary GH secretion during the period while the epiphyseal growth plates of the long bones are still open, characteristic stagnation in longitudinal growth has not been demonstrated. The patient presented with delayed puberty and primary amenorrhea along with a sudden appearance of clinical signs of hypersomatotropinism, which were the reasons for seeking medical help at the age of 16. Physical examination of children presenting with delayed puberty but without growth arrest must include an overall hormonal and genetic testing even in the cases when typical clinical presentations of genetic disorder are absent. To the best of our knowledge, this is the first reported case of simultaneous presence of Turner syndrome and gigantism in the literature.

An assessment of functioning and non-functioning distractors in multiple-choice questions: a descriptive analysis.

PubMed

Tarrant, Marie; Ware, James; Mohammed, Ahmed M

2009-07-07

Four- or five-option multiple choice questions (MCQs) are the standard in health-science disciplines, both on certification-level examinations and on in-house developed tests. Previous research has shown, however, that few MCQs have three or four functioning distractors. The purpose of this study was to investigate non-functioning distractors in teacher-developed tests in one nursing program in an English-language university in Hong Kong. Using item-analysis data, we assessed the proportion of non-functioning distractors on a sample of seven test papers administered to undergraduate nursing students. A total of 514 items were reviewed, including 2056 options (1542 distractors and 514 correct responses). Non-functioning options were defined as ones that were chosen by fewer than 5% of examinees and those with a positive option discrimination statistic. The proportion of items containing 0, 1, 2, and 3 functioning distractors was 12.3%, 34.8%, 39.1%, and 13.8% respectively. Overall, items contained an average of 1.54 (SD = 0.88) functioning distractors. Only 52.2% (n = 805) of all distractors were functioning effectively and 10.2% (n = 158) had a choice frequency of 0. Items with more functioning distractors were more difficult and more discriminating. The low frequency of items with three functioning distractors in the four-option items in this study suggests that teachers have difficulty developing plausible distractors for most MCQs. Test items should consist of as many options as is feasible given the item content and the number of plausible distractors; in most cases this would be three. Item analysis results can be used to identify and remove non-functioning distractors from MCQs that have been used in previous tests.

The diagnosis of children with central diabetes insipidus.

PubMed

Ghirardello, Stefano; Garrè, Maria-Luisa; Rossi, Andrea; Maghnie, Mohamad

2007-03-01

Central diabetes insipidus is the end result of a number of different diseases that affect the hypothalamic-neurohypophyseal system. In many patients, especially children and young adults, it is caused by the destruction or degeneration of neurons that originate in the supraoptic and paraventricular nuclei of the hypothalamus. The known causes of these lesions include germinoma or craniopharyngioma; Langerhans cell histiocytosis; local inflammatory, autoimmune or vascular diseases; trauma resulting from surgery or an accident; sarcoidosis; metastases; and midline cerebral and cranial malformations. In rare cases, genetic defects in AVP synthesis that are inherited as autosomal dominant, autosomal recessive or X-linked recessive traits are the underlying cause. Accurate diagnostic differentiation is essential for both safe and effective disease management. Proper etiological diagnosis can be achieved via a series of steps that start with clinical observations and then progress, as needed, to more sophisticated methods. Indeed, magnetic resonance imaging (MRI) represents the examination method of choice for evaluating hypothalamic-pituitary-related endocrine diseases due to its ability to provide strongly-contrasted high-resolution multi-planar and spatial images. Specifically, MRI allows a detailed and precise anatomical study of the pituitary gland by differentiating between the anterior and posterior pituitary lobes. MRI identification of pituitary hyperintensity in the posterior part of the sella, now considered to be a clear marker of neurohypophyseal functional integrity, together with careful analysis of pituitary stalk shape and size, have provided the most striking recent findings contributing to the diagnosis and understanding of some forms of 'idiopathic' central diabetes insipidus.

Trade-Off Analysis between Concerns Based on Aspect-Oriented Requirements Engineering

NASA Astrophysics Data System (ADS)

Laurito, Abelyn Methanie R.; Takada, Shingo

The identification of functional and non-functional concerns is an important activity during requirements analysis. However, there may be conflicts between the identified concerns, and they must be discovered and resolved through trade-off analysis. Aspect-Oriented Requirements Engineering (AORE) has trade-off analysis as one of its goals, but most AORE approaches do not actually offer support for trade-off analysis; they focus on describing concerns and generating their composition. This paper proposes an approach for trade-off analysis based on AORE using use cases and the Requirements Conflict Matrix (RCM) to represent compositions. RCM shows the positive or negative effect of non-functional concerns over use cases and other non-functional concerns. Our approach is implemented within a tool called E-UCEd (Extended Use Case Editor). We also show the results of evaluating our tool.

Functional and nonfunctional testing of ATM networks

NASA Astrophysics Data System (ADS)

Ricardo, Manuel; Ferreira, M. E. P.; Guimaraes, Francisco E.; Mamede, J.; Henriques, M.; da Silva, Jorge A.; Carrapatoso, E.

1995-02-01

ATM network will support new multimedia services that will require new protocols, those services and protocols will need different test strategies and tools. In this paper, the concepts of functional and non-functional testers of ATM networks are discussed, a multimedia service and its requirements are presented and finally, a summary description of an ATM network and of the test tool that will be used to validate it are presented.

Chronic hypopituitarism is uncommon in survivors of aneurysmal subarachnoid haemorrhage.

PubMed

Hannon, M J; Behan, L A; O'Brien, M M; Tormey, W; Javadpour, M; Sherlock, M; Thompson, C J

2015-01-01

The incidence of hypopituitarism after aneurysmal subarachnoid haemorrhage (SAH) is unclear from the conflicting reports in the literature. As routine neuroendocrine screening for hypopituitarism for all patients would be costly and logistically difficult, there is a need for precise data on the frequency of hypopituitarism and on factors which might predict the later development of pituitary dysfunction. We aimed to: (i) Establish the incidence of long-term hypopituitarism in patients with aneurysmal SAH. (ii) Determine whether data from patients' acute admission with SAH could predict the occurrence of long-term hypopituitarism. One hundred patients were studied prospectively from the time of presentation with acute SAH. Plasma cortisol, plasma sodium and a variety of clinical and haemodynamic parameters were sequentially measured for the first 12 days of their acute admission. Forty-one patients then underwent dynamic pituitary testing at median 15 months following SAH (range 7-30 months), with insulin tolerance test (ITT) or, if contraindicated, a glucagon stimulation test (GST) plus short synacthen test (SST). If symptoms of cranial diabetes insipidus (CDI) were present, a water deprivation test was also performed. Forty-one patients attended for follow-up dynamic pituitary testing. Although 14 of 100 had acute glucocorticoid deficiency immediately following SAH, only two of 41 had long-term adrenocorticotrophic hormone (ACTH) deficiency and four of 41 had growth hormone (GH) deficiency. None were hypothyroid or gonadotrophin deficient. None had chronic CDI or hyponatraemia. There was no association between acute glucocorticoid deficiency, acute CDI or acute hyponatraemia and long-term pituitary dysfunction. Both anterior and posterior hypopituitarism are very uncommon following SAH and are not predicted by acute clinical, haemodynamic or endocrinological parameters. Routine neuroendocrine screening is not justified in SAH patients. © 2014 John Wiley & Sons Ltd.

Craniopharyngeal canal and its spectrum of pathology.

PubMed

Abele, T A; Salzman, K L; Harnsberger, H R; Glastonbury, C M

2014-04-01

The craniopharyngeal canal is a rare, well-corticated defect through the midline of the sphenoid bone from the sellar floor to the anterosuperior nasopharyngeal roof. We reviewed a series of craniopharyngeal canals to determine a system of classification that might better our understanding of this entity, highlight the range of associated pathologic conditions, and optimize patient treatment. Available MR imaging, CT, and clinical data (from 1989-2013) of 29 patients (10 female, 15 male, 4 unknown; median age, 4 years; age range, 1 day-65 years) with craniopharyngeal canals were retrospectively examined. Qualitative assessment included orthotopic or ectopic adenohypophysis and the presence of a tumor and/or cephalocele. The midpoint anteroposterior diameter was measured. Clinical and imaging data were evaluated for pituitary dysfunction and accompanying anomalies. Craniopharyngeal canals were qualitatively separated into 3 types: incidental canals (type 1); canals with ectopic adenohypophysis (type 2); and canals containing cephaloceles (type 3A), tumors (type 3B), or both (type 3C), including pituitary adenoma, craniopharyngioma, dermoid, teratoma, and glioma. Quantitative evaluation showed a significant difference (P < .0001) in the anteroposterior diameters of type 1 canals (median, 0.8; range, 0.7-1.1 mm), type 2 canals (median, 3.9, range, 3.5-4.4 mm), and type 3 canals (median, 9.0; range, 5.9-31.0 mm) imparting small, medium, and large descriptors. Canals with cephaloceles all contained an ectopic adenohypophysis. The craniopharyngeal canals were associated with pituitary dysfunction (6/29) and congenital anomalies (8/29). Accurate diagnosis and classification of craniopharyngeal canals are valuable to characterize lesions requiring surgery, identify patients with potential pituitary dysfunction, and avoid iatrogenic hypopituitarism or CSF leak during surgical resection of nasopharyngeal masses.

High resolution pituitary gland MRI at 7.0 tesla: a clinical evaluation in Cushing's disease.

PubMed

de Rotte, Alexandra A J; Groenewegen, Amy; Rutgers, Dik R; Witkamp, Theo; Zelissen, Pierre M J; Meijer, F J Anton; van Lindert, Erik J; Hermus, Ad; Luijten, Peter R; Hendrikse, Jeroen

2016-01-01

To evaluate the detection of pituitary lesions at 7.0 T compared to 1.5 T MRI in 16 patients with clinically and biochemically proven Cushing's disease. In seven patients, no lesion was detected on the initial 1.5 T MRI, and in nine patients it was uncertain whether there was a lesion. Firstly, two readers assessed both 1.5 T and 7.0 T MRI examinations unpaired in a random order for the presence of lesions. Consensus reading with a third neuroradiologist was used to define final lesions in all MRIs. Secondly, surgical outcome was evaluated. A comparison was made between the lesions visualized with MRI and the lesions found during surgery in 9/16 patients. The interobserver agreement for lesion detection was good at 1.5 T MRI (κ = 0.69) and 7.0 T MRI (κ = 0.62). In five patients, both the 1.5 T and 7.0 T MRI enabled visualization of a lesion on the correct side of the pituitary gland. In three patients, 7.0 T MRI detected a lesion on the correct side of the pituitary gland, while no lesion was visible at 1.5 T MRI. The interobserver agreement of image assessment for 7.0 T MRI in patients with Cushing's disease was good, and lesions were detected more accurately with 7.0 T MRI. Interobserver agreement for lesion detection on 1.5 T MRI was good; Interobserver agreement for lesion detection on 7.0 T MRI was good; 7.0 T enabled confirmation of unclear lesions at 1.5 T; 7.0 T enabled visualization of lesions not visible at 1.5 T.

Pituitary block with gonadotrophin-releasing hormone antagonist during intrauterine insemination cycles: a systematic review and meta-analysis of randomised controlled trials.

PubMed

Vitagliano, A; Saccone, G; Noventa, M; Borini, A; Coccia, M E; Nardelli, G B; Saccardi, C; Bifulco, G; Litta, P S; Andrisani, A

2018-06-03

Several randomised controlled trials (RCTs) have investigated the usefulness of pituitary block with gonadotrophin-releasing hormone (GnRH) antagonists during intrauterine insemination (IUI) cycles, with conflicting results. The aim of the present systematic review and meta-analysis of RCTs was to evaluate the effectiveness of GnRH antagonist administration as an intervention to improve the success of IUI cycles. Electronic databases (MEDLINE, Scopus, EMBASE, Sciencedirect) and clinical registers were searched from their inception until October 2017. Randomised controlled trials of infertile women undergoing one or more IUI stimulated cycles with GnRH antagonists compared with a control group. The primary outcomes were ongoing pregnancy/live birth rate (OPR/LBR) and clinical pregnancy rate (CPR). Pooled results were expressed as odds ratio (OR) or mean differences with 95% confidence interval (95% CI). Sources of heterogeneity were investigated through sensitivity and subgroups analysis. The body of evidence was rated using GRADE methodology. Publication bias was assessed with funnel plot, Begg's and Egger's tests. Fifteen RCTs were included (3253 IUI cycles, 2345 participants). No differences in OPR/LBR (OR 1.14, 95% CI 0.82-1.57, P = 0.44) and CPR (OR 1.28, 95% CI 0.97-1.69, P = 0.08) were found. Sensitivity and subgroup analyses did not provide statistical changes in pooled results. The body of evidence was rated as low (GRADE 2/4). No publication bias was detected. Pituitary block with GnRH antagonists does not improve OPR/LBR and CPR in women undergoing IUI cycles. Pituitary block with GnRH antagonists does not improve the success of IUI cycles. © 2018 Royal College of Obstetricians and Gynaecologists.

Transsphenoidal Surgery for Mixed Pituitary Gangliocytoma-Adenomas.

PubMed

Shepard, Matthew J; Elzoghby, Mohamed A; Ghanim, Daffer; Lopes, M Beatriz S; Jane, John A

2017-12-01

Most sellar gangliocytomas are discovered with a concurrent pituitary adenoma, also known as a mixed gangliocytoma-adenoma (MGA). MGAs are rare, with fewer than 100 cases reported in the literature to date and only 1 previously documented surgical series. Because MGAs are radiologically indistinguishable from pituitary adenomas, they are often diagnosed after surgery. Combined with the paucity of clinical outcome data for these tumors, this makes their diagnosis and management challenging. Here we describe the clinical presentation and outcomes of 10 individuals who were diagnosed with a MGA at a single institution. This retrospective case series study included patients diagnosed with a combined sellar MGA between 1993 and 2016. This series comprised 10 patients, mean age of 44 years (range, 28-63 years) diagnosed with an MGA. The mean tumor size was 1.6 cm (range, 0.4-2.4 cm). Five patients presented with acromegaly, and 1 patient had recurrent Cushing disease. Transsphenoidal surgery was performed in all cases, and gross total resection was achieved in 7 patients (70%). Histologically, 9 of the 10 MGAs were identified as mixed somatotroph adenoma-gangliocytomas. The median duration of follow-up was 74 months (range, 2-180 months). Following adjuvant treatment (n = 3), all patients with acromegaly (n = 4) achieved biochemical remission, and no patient experienced recurrence of the pituitary tumor with a median radiographic follow-up of 48 months. MGAs are often associated with a hypersecretory adenoma. Transsphenoidal surgery is well tolerated by most patients, and when performed in combination with adjuvant therapy, a low rate of recurrence and reversal of preoperative endocrinopathy can be expected. Copyright © 2017 Elsevier Inc. All rights reserved.

Observational Study to Assess the Therapeutic Value of Four Ovarian Hyperstimulation Protocols in IVF After Pituitary Suppression with GnRH Antagonists in Normally Responding Women.

PubMed

Ana, Monzó; Vicente, Montañana; María, Rubio José; Trinidad, García-Gimeno; Alberto, Romeu

2011-02-22

To compare the clinical results of four different protocols of COH for IVF-ICSI in normovulatory women, using in all cases pituitary suppression with GnRH antagonists. A single center, open label, parallel-controlled, prospective, post-authorization study under the approved conditions for use where 305 normal responders women who were candidates to COH were assigned to r-FSH +hp-hMG (n = 51, Group I), hp-hMG (n = 61, Group II), fixed-dose r-FSH (n = 118, Group III), and r-FSH with potential dose adjustment (n = 75, Group IV) to subsequently undergo IVF-ICSI. During stimulation, Group IV needed significantly more days of stimulation as compared to Group II [8.09 ± 1.25 vs. 7.62 ± 1.17; P < 0.05], but was the group in which more oocytes were recovered [Group I: 9.43 ± 4.99 vs. Group II: 8.96 ± 4.82 vs. Group III: 8.78 ± 3.72 vs. Group IV: 11.62 ± 5.80; P < 0.05]. No significant differences were seen between the groups in terms of clinical and ongoing pregnancy, but among patients in whom two embryos with similar quality parameters (ASEBIR) were transferred, the group treated with hp-hMG alone achieved a significantly greater clinical pregnancy rate as compared to all other groups [Group I: 31.6%, Group II: 56.4%, Group III: 28.7%, Group IV: 32.7%; P < 0.05]. Although randomized clinical trials should be conducted to achieve a more reliable conclusion, these observations support the concept that stimulation with hp-hMG could be beneficial in normal responders women undergoing pituitary suppression with GnRH antagonists.

[How to choose appropriate surgical approach in removal of the eyeball].

PubMed

Ye, Juan; Ning, Qingyao

2014-08-01

We often consult patients with non-functional eye caused by trauma, intraocular malignancy, absolute stage of glaucoma and other diseases who need to remove the eyeball in our clinical work. Eye removal is an irreversibly destructive procedure, which mainly include enucleation and evisceration. There are various surgical techniques which are still controversial. Both of the two procedures have their own advantages, disadvantages, indications and contraindications. The ophthalmologists should comprehensively consider the disease situations, medical conditions and the requirements of the patients when choosing appropriate surgical approach to remove the eyeball.

Clinical and endocrine responses to pituitary radiotherapy in pediatric Cushing's disease: an effective second-line treatment.

PubMed

Storr, Helen L; Plowman, P Nicholas; Carroll, Paul V; François, Inge; Krassas, Gerasimos E; Afshar, Farhad; Besser, G Michael; Grossman, Ashley B; Savage, Martin O

2003-01-01

Transsphenoidal surgery (TSS) is considered first-line treatment for Cushing's disease (CD). Options for treatment of postoperative persisting hypercortisolemia are pituitary radiotherapy (RT), repeat TSS, or bilateral adrenalectomy. From 1983 to 2001, we treated 18 pediatric patients (age, 6.4-17.8 yr) with CD. All underwent TSS, and 11 were cured (postoperative serum cortisol, <50 nM). Seven (39%) had 0900-h serum cortisol of 269-900 nM during the immediate postoperative period (2-20 d), indicating lack of cure. These patients (6 males and 1 female; mean age, 12.8 yr; range, 6.4-17.8 yr; 4 prepubertal; 3 pubertal) received external beam RT to the pituitary gland, using a 6-MV linear accelerator, with a dose of 45 Gy in 25 fractions over 35 d. Until the RT became effective, hypercortisolemia was controlled with ketoconazole (dose, 200-600 mg/d) (n = 4) and metyrapone (750 mg-3 g/d) +/- aminoglutethimide (1 g/d) or o'p'DDD (mitotane, 3 mg/d) (n = 3). All patients were cured after pituitary RT. The mean interval from RT to cure (mean serum cortisol on 5-point day curve, <150 nM) was 0.94 yr (0.25-2.86 yr). Recovery of pituitary-adrenal function (mean cortisol, 150-300 nM) occurred at mean 1.16 yr (0.40-2.86 yr) post RT. At 2 yr post RT, puberty occurred early in one male patient (age, 9.8 yr) but was normal in the others. GH secretion was assessed at 0.6-2.5 yr post RT in all patients: six had GH deficiency (peak on glucagon/insulin provocation, <1.0-17.9 mU/liter) and received human GH replacement. Follow-up of pituitary function 7.6 and 9.5 yr post RT in two patients showed normal gonadotropin secretion and recovery of GH peak to 29.7 and 19.2 mU/liter. The seven patients were followed for mean 6.9 yr (1.4-12.0 yr), with no evidence of recurrence of CD. In conclusion, pituitary RT is an effective and relatively rapid-onset treatment for pediatric CD after failure of TSS. GH deficiency occurred in 86% patients. Long-term follow-up suggests some recovery of GH secretion and preservation of other anterior pituitary function.

Cushing Syndrome: Diagnostic Workup and Imaging Features, With Clinical and Pathologic Correlation.

PubMed

Wagner-Bartak, Nicolaus A; Baiomy, Ali; Habra, Mouhammed Amir; Mukhi, Shalini V; Morani, Ajaykumar C; Korivi, Brinda R; Waguespack, Steven G; Elsayes, Khaled M

2017-07-01

Cushing syndrome (CS) is a constellation of clinical signs and symptoms resulting from chronic exposure to excess cortisol, either exogenous or endogenous. Exogenous CS is most commonly caused by administration of glucocorticoids. Endogenous CS is subdivided into two types: adrenocorticotropic hormone (ACTH) dependent and ACTH independent. Cushing disease, which is caused by a pituitary adenoma, is the most common cause of ACTH-dependent CS for which pituitary MRI can be diagnostic, with bilateral inferior petrosal sinus sampling useful in equivocal cases. In ectopic ACTH production, which is usually caused by a tumor in the thorax (e.g., small cell lung carcinoma, bronchial and thymic carcinoids, or medullary thyroid carcinoma) or abdomen (e.g., gastroenteropancreatic neuroendocrine tumors or pheochromocytoma), CT, MRI, and nuclear medicine tests are used for localizing the source of ACTH. In ACTH-independent CS, which is caused by various adrenal abnormalities, adrenal protocol CT or MRI is usually diagnostic.

[Diagnosis of congenital endocrinological disease in newborns with prolonged jaundice and hypoglycaemia].

PubMed

Braslavsky, D; Keselman, A; Chiesa, A; Bergadá, I

2012-03-01

The association of prolonged neonatal jaundice and hypoglycaemia may be secondary to an endocrinological disease. Pituitary insufficiency and primary adrenal insufficiency are the most likely endocrine diseases that need to be ruled out. We retrospectively analysed the clinical and laboratory characteristics of thirteen patients referred to the Hospital de Niños Ricardo Gutiérrez between years 2003 and 2008 due to prolonged neonatal jaundice and hypoglycaemia secondary to pituitary insufficiency in twelve patients, and in one secondary to primary adrenal insufficiency. All patients had a history of neonatal hypoglycaemia. Ten patients had conjugated hyperbilirubinaemia and six also had elevated transaminases. Combined pituitary hormone deficiency was observed in the twelve hypopituitarism patients. Hormonal replacement normalised liver function and resolved the prolonged jaundice in all the patients. None of them underwent liver biopsy. Hypoglycaemia also remitted after hormonal therapy. Prolonged or cholestatic jaundice associated with neonatal hypoglycaemia is highly likely to be due to pituitary hormone deficiency or primary adrenal insufficiency. Early diagnosis and treatment of these children reverts the prolonged jaundice and prevents morbidity and mortality due to recurrent hypoglycaemia and hormone deficiencies. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Effect of dopamine agonist withdrawal after long-term therapy in prolactinomas. Studies with high-definition computerised tomography.

PubMed

Johnston, D G; Hall, K; Kendall-Taylor, P; Patrick, D; Watson, M; Cook, D B

1984-07-28

The clinical, radiological, and biochemical effects of dopamine agonist withdrawal after long-term treatment were investigated in seven women and eight men who had been treated for prolactinomas for 1.5 to 7 (mean 3.7) years. Before treatment, serum prolactin concentrations were 1473 to 115 000 mU/l, all patients had abnormal radiological findings, and six had suprasellar extensions of pituitary tumours. Treatment with either bromocriptine or pergolide relieved symptoms and suppressed prolactin secretion in most patients. The size of the residual tumour was defined by doing fourth generation computerised tomographic scans immediately before termination of therapy, and evidence of tumour re-expansion was sought on scans repeated 5-39 weeks later. After discontinuation of treatment, symptoms recurred in 13 of 15 patients and hyper-prolactinaemia redeveloped in 14. Other pituitary function tests remained unchanged or improved. In 13 of 15 patients tumour or gland size did not change after withdrawal of treatment. One man had a marginal increase in tumour size, while in another the pituitary tumour shrank. Thus, although cessation of long-term dopamine agonist therapy leads to recurrence of symptoms and hyperprolactinaemia, rapid tumour regrowth is uncommon and of small extent, and other pituitary function is not altered in the short term.

Genetics, gene expression and bioinformatics of the pituitary gland.

PubMed

Davis, Shannon W; Potok, Mary Anne; Brinkmeier, Michelle L; Carninci, Piero; Lyons, Robert H; MacDonald, James W; Fleming, Michelle T; Mortensen, Amanda H; Egashira, Noboru; Ghosh, Debashis; Steel, Karen P; Osamura, Robert Y; Hayashizaki, Yoshihide; Camper, Sally A

2009-04-01

Genetic cases of congenital pituitary hormone deficiency are common and many are caused by transcription factor defects. Mouse models with orthologous mutations are invaluable for uncovering the molecular mechanisms that lead to problems in organ development and typical patient characteristics. We are using mutant mice defective in the transcription factors PROP1 and POU1F1 for gene expression profiling to identify target genes for these critical transcription factors and candidates for cases of pituitary hormone deficiency of unknown aetiology. These studies reveal critical roles for Wnt signalling pathways, including the TCF/LEF transcription factors and interacting proteins of the groucho family, bone morphogenetic protein antagonists and targets of notch signalling. Current studies are investigating the roles of novel homeobox genes and pathways that regulate the transition from proliferation to differentiation, cell adhesion and cell migration. Pituitary adenomas are a common human health problem, yet most cases are sporadic, necessitating alternative approaches to traditional Mendelian genetic studies. Mouse models of adenoma formation offer the opportunity for gene expression profiling during progressive stages of hyperplasia, adenoma and tumorigenesis. This approach holds promise for the identification of relevant pathways and candidate genes as risk factors for adenoma formation, understanding mechanisms of progression, and identifying drug targets and clinically relevant biomarkers. Copyright 2009 S. Karger AG, Basel.

Bilateral inferior petrosal sinus sampling

PubMed Central

Grossrubatscher, Erika; Dalino Ciaramella, Paolo; Boccardi, Edoardo

2016-01-01

Simultaneous bilateral inferior petrosal sinus sampling (BIPSS) plays a crucial role in the diagnostic work-up of Cushing’s syndrome. It is the most accurate procedure in the differential diagnosis of hypercortisolism of pituitary or ectopic origin, as compared with clinical, biochemical and imaging analyses, with a sensitivity and specificity of 88–100% and 67–100%, respectively. In the setting of hypercortisolemia, ACTH levels obtained from venous drainage of the pituitary are expected to be higher than the levels of peripheral blood, thus suggesting pituitary ACTH excess as the cause of hypercortisolism. Direct stimulation of the pituitary corticotroph with corticotrophin-releasing hormone enhances the sensitivity of the procedure. The procedure must be undertaken in the presence of hypercortisolemia, which suppresses both the basal and stimulated secretory activity of normal corticotrophic cells: ACTH measured in the sinus is, therefore, the result of the secretory activity of the tumor tissue. The poor accuracy in lateralization of BIPSS (positive predictive value of 50–70%) makes interpetrosal ACTH gradient alone not sufficient for the localization of the tumor. An accurate exploration of the gland is recommended if a tumor is not found in the predicted area. Despite the fact that BIPSS is an invasive procedure, the occurrence of adverse events is extremely rare, particularly if it is performed by experienced operators in referral centres. PMID:27352844

Bilateral inferior petrosal sinus sampling.

PubMed

Zampetti, Benedetta; Grossrubatscher, Erika; Dalino Ciaramella, Paolo; Boccardi, Edoardo; Loli, Paola

2016-07-01

Simultaneous bilateral inferior petrosal sinus sampling (BIPSS) plays a crucial role in the diagnostic work-up of Cushing's syndrome. It is the most accurate procedure in the differential diagnosis of hypercortisolism of pituitary or ectopic origin, as compared with clinical, biochemical and imaging analyses, with a sensitivity and specificity of 88-100% and 67-100%, respectively. In the setting of hypercortisolemia, ACTH levels obtained from venous drainage of the pituitary are expected to be higher than the levels of peripheral blood, thus suggesting pituitary ACTH excess as the cause of hypercortisolism. Direct stimulation of the pituitary corticotroph with corticotrophin-releasing hormone enhances the sensitivity of the procedure. The procedure must be undertaken in the presence of hypercortisolemia, which suppresses both the basal and stimulated secretory activity of normal corticotrophic cells: ACTH measured in the sinus is, therefore, the result of the secretory activity of the tumor tissue. The poor accuracy in lateralization of BIPSS (positive predictive value of 50-70%) makes interpetrosal ACTH gradient alone not sufficient for the localization of the tumor. An accurate exploration of the gland is recommended if a tumor is not found in the predicted area. Despite the fact that BIPSS is an invasive procedure, the occurrence of adverse events is extremely rare, particularly if it is performed by experienced operators in referral centres. © 2016 The authors.

Genetics, Gene Expression and Bioinformatics of the Pituitary Gland

PubMed Central

Davis, Shannon W; Potok, Mary Anne; Brinkmeier, Michelle L; Carninci, Piero; Lyons, Robert H; MacDonald, James W.; Fleming, Michelle T; Mortensen, Amanda H; Egashira, Noboru; Ghosh, Debashis; Steel, Karen P.; Osamura, Robert Y; Hayashizaki, Yoshihide; Camper, Sally A

2011-01-01

Genetic cases of congenital pituitary hormone deficiency are common and many are caused by transcription factor defects. Mouse models with orthologous mutations are invaluable for uncovering the molecular mechanisms that lead to problems in organ development and typical patient characteristics. We are using mutant mice defective in the transcription factors PROP1 and POU1F1 for gene expression profiling to identify target genes for these critical transcription factors and candidates for cases of pituitary hormone deficiency of unknown etiology. These studies reveal critical roles for Wnt signalling pathways including the TCF/LEF transcription factors and interacting proteins of the groucho family, bone morphogenetic proteins antagonists, and targets of notch signalling. Current studies are investigating roles of novel homeobox genes and pathways that regulate the transition from proliferation to differentiation, cell adhesion and cell migration. Pituitary adenomas are a common human health problem, yet most cases are sporadic, necessitating alternative approaches to traditional Mendelian genetic studies. Mouse models of adenoma formation offer the opportunity for gene expression profiling during progressive stages of hyperplasia, adenoma and tumorigenesis. This approach holds promise for identification of relevant pathways and candidate genes as risk factors for adenoma formation, understanding mechanisms of progression, and identifying drug targets and clinically relevant biomarkers. PMID:19407506

[Germinoma responsible for central diabetes insipidus].

PubMed

Bakoto, N; Strivay, M

2009-01-01

We report the case of a 20-year-old woman who presented with sudden onset of polydipsia and polyuria. A diagnosis of diabetes insipidus was confirmed and the MRI showed a pituitary stalk enlargement. The patient was treated with Minirin. Two years later, she developed a panhypopituitarism. The MRI showed an intrasellar mass with an enlargement of the pituitary gland. A biopsy confirmed a germinoma. The patient was treated with radiotherapy with a partial response as only a part of the mass disappeared. This case highlights the importance of the clinical and radiological follow-up of central diabetes insipidus, especially when it is of unknown origin. The differential diagnosis will be reviewed.

Hypogonadism: Its Prevalence and Diagnosis.

PubMed

Ross, Anna; Bhasin, Shalender

2016-05-01

Hypogonadism is a clinical syndrome, which results from the failure of the testes to produce physiologic levels of testosterone and a normal number of spermatozoa due to defects at one or more levels of the hypothalamic-pituitary-gonadal axis. Primary hypogonadism results from malfunction at the level of the testes due to a genetic cause, injury, inflammation, or infection. Hypothalamic and/or pituitary failure leads to secondary hypogonadism, most often as a result of genetic defects, neoplasm, or infiltrative disorders. The signs and symptoms of hypogonadism depend on the age of onset, severity of androgen deficiency, and underlying cause of androgen deficiency. Copyright © 2016 Elsevier Inc. All rights reserved.

[Prolonged desensitization pretreatment for in vitro fertilization in women with polycystic ovary].

PubMed

Kuczyński, W; Czech, R; Redźko, S; Wasilewski, T; Mrugacz, G; Wołczyński, S; Pietrewicz, P; Grochowski, D; Szamatowicz, M

2000-09-01

To analyse the outcome of intracytoplasmic sperm injection (ICSI) in women with severe polycystic ovary disease (PCD), stimulated after prolonged pituitary desensitization in comparison with regular long protocol therapy. The results of controlled ovarian hyperstimulation (COH), fertilization rate, early embryo development parameters and clinical pregnancy rates were compared depending on the duration of pituitary desensitization before gonadotropin administration. A total of 60 patients with severe PCOD were desensitized with GnRH agonist up to 30 days before COH. The results were compared with the group of 213 patients with mild PCOD treated with regular long protocol (control). We observed a slightly higher rate of mature oocytes MII as well as the number of embryos obtained in the control group, however the pregnancy rate in the group with prolonged desensitization was significantly higher (50%) in comparison to the control group (33.8%). The prolonged pituitary desensitization before controlled ovarian hyperstimulation gives better chance for obtaining pregnancy in patients with severe PCOD. It could be recommended facing previous treatment failure.

Development of syndrome of inappropriate antidiuretic hormone secretion (SIADH) after Onyx embolisation of a cavernous carotid fistula

PubMed Central

Chen, Tsinsue; Kalani, M Yashar S; Ducruet, Andrew F; Albuquerque, Felipe C; McDougall, Cameron G

2016-01-01

Patients with cavernous carotid fistulas (CCFs) can present with pituitary hypoperfusion and hypopituitarism; however, there are no previous reports of pituitary or hormonal abnormalities developing after CCF embolisation in an asymptomatic patient. We describe a patient with no hormonal abnormalities who developed syndrome of inappropriate antidiuretic hormone (SIADH) secretion after CCF embolisation. The patient had bilateral indirect CCFs, which were completely embolised via a transvenous approach, and was neurologically stable postoperatively and discharged. In the subsequent 2 weeks the patient was readmitted twice for acute hyponatraemia and a tonic-clonic seizure. Laboratory studies revealed severe SIADH. Clinical status and sodium levels improved after treatment. One year later the patient was weaned off all medications and remained neurologically stable. SIADH may be a delayed phenomenon after CCF embolisation. Given the proximity of embolised vessels to the pituitary's vascular supply, CCF treatment may result in flow disturbance, ischaemia and hormonal abnormalities. PMID:27001597

Sustained remission of Cushing's disease with mitotane and pituitary irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schteingart, D.E.; Tsao, H.S.; Taylor, C.I.

1980-05-01

Low doses of mitotane were given orally to 36 patients with Cushing's disease, concurrently with or after pituitary cobalt irradiation. Clinical and biochemical remission occurred in 29. The response to treatment occurred early in 17 patients and late in 12. The different pattern of response to mitotane was not related to the dose given or to its serum level. Early biochemical indicators of adrenal suppression with mitotane were a sharp decrease in adrenal response to the infusion of ACTH and in plasma levels of dehydroepiandrosterone sulfate. Although mitotane was given together with pituitary irradiation, initial remission was due mainly tomore » the adrenal effect of mitotane. Plasma ACTH levels were still elevated when cortisol had returned to normal. In seventeen of the 29 patients who responded to treatment drug therapy has been discontinued, and they remain in remission of Cushing's syndrome. Side-effects have been dose dependent, with anorexia, nausea, decreased memory, and gynecomastia in men being the commonest.« less

Hypersomatotropism induced secondary polycythaemia leading to spontaneous pituitary apoplexy resulting in cure of acromegaly and remission of polycythaemia: 'The virtuous circle'.

PubMed

Patra, Shinjan; Biswas, Sugata Narayan; Datta, Joydip; Chakraborty, Partha Pratim

2017-12-07

A young man with subtle clinical features suggestive of hypersomatotropism presented with acute-onset severe headache. Relevant investigations confirmed polycythaemia and growth hormone (GH)-secreting pituitary macroadenoma with apoplexy. Secondary polycythaemia and myeloproliferative disorders were ruled out. At follow-up after 3 months, resolution of polycythaemia and acromegaly was observed, evident on normal haemoglobin levels, a normocellular marrow, and normal insulin-like growth factor-1 (IGF-1) with glucose-suppressed GH levels. Direct mitogenic properties of GH-IGF-1 axis on bone marrow progenitor cells may very rarely lead to erythroid hyperplasia and subsequent polycythaemia, reversible with successful therapy of acromegaly. In this case, polycythaemia secondary to hypersomatotropism likely resulted in pituitary apoplexy with subsequent remission of both acromegaly and resultant polycythaemia. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Refractory Cushing's disease caused by multinodular ACTH-cell hyperplasia.

PubMed

McKeever, P E; Koppelman, M C; Metcalf, D; Quindlen, E; Kornblith, P L; Strott, C A; Howard, R; Smith, B H

1982-09-01

A patient with pituitary-dependent hypercortisolism, unresponsive to resection of nodules in the anterior lobe, is described. Histochemical stains of the nodules showed multiple, focal, cellular expansions of the fibrovascular stroma. Transitions between normal and expanded adenohypophysial acini were present. Immunoperoxidase stains for ACTH and other pituitary hormones revealed that these multiple foci contained an excess of ACTH-positive cells. Less than 10% of the cells in these foci were negative for ACTH and positive for other hormones. Serial sections showed that these foci of predominantly ACTH-producing acini were not connected. Clinical, morphological, and immunohistochemical data indicated that ACTH-cell hyperplasia caused Crushing's disease in this patient. Pathologic study of individual cases should concentrate on determining whether hyperplasia or adenoma exist at the time of surgical exploration of the pituitary gland, since this determination is important to proper treatment. Tentative criteria to recognize ACTH-cell hyperplasia are: 1. Multiple foci of ACTH laden cells. 2. A minor subpopulation of cells of alternate hormone series. 3. Expansion without destruction of acini in the adenohypophysis.

Computerized tomography versus magnetic resonance imaging: a comparative study in hypothalamic-pituitary and parasellar pathology.

PubMed

Webb, S M; Ruscalleda, J; Schwarzstein, D; Calaf-Alsina, J; Rovira, A; Matos, G; Puig-Domingo, M; de Leiva, A

1992-05-01

We wished to analyse the relative value of computerized tomography and magnetic resonance in patients referred for evaluation of pituitary and parasellar lesions. We performed a separate evaluation by two independent neuroradiologists of computerized tomography and magnetic resonance images ordered numerically and anonymously, with no clinical data available. We studied 40 patients submitted for hypothalamic-pituitary study; 31 were carried out preoperatively, of which histological confirmation later became available in 14. The remaining nine patients were evaluated postoperatively. Over 40 parameters relating to the bony margins, cavernous sinuses, carotid arteries, optic chiasm, suprasellar cisterns, pituitary, pituitary stalk and extension of the lesion were evaluated. These reports were compared with the initial ones offered when the scans were ordered, and with the final diagnosis. Concordance between initial computerized tomography and magnetic resonance was observed in 27 cases (67.5%); among the discordant cases computerized tomography showed the lesion in two, magnetic resonance in 10, while in the remaining case reported to harbour a microadenoma on computerized tomography the differential diagnosis between a true TSH-secreting microadenoma and pituitary resistance to thyroid hormones is still unclear. Both neuroradiologists coincided in their reports in 32 patients (80%); when the initial report was compared with those of the neuroradiologists, concordance was observed with at least one of them in 34 instances (85%). Discordant results were observed principally in microadenomas secreting ACTH or PRL and in delayed puberty. In the eight patients with Cushing's disease (histologically confirmed in six) magnetic resonance was positive in five and computerized tomography in two; the abnormal image correctly identified the side of the lesion at surgery. In patients referred for evaluation of Cushing's syndrome or hyperprolactinaemia (due to microadenomas) or after surgery, magnetic resonance is clearly preferable to computerized tomography. In macroadenomas both scans are equally diagnostic but magnetic resonance offers more information on pituitary morphology and neighbouring structures. Nevertheless, there are cases in which the results of computerized tomography and magnetic resonance will complement each other, since different parameters are analysed with each examination and discordant results are encountered.

Pathology of excessive production of growth hormone.

PubMed

Scheithauer, B W; Kovacs, K; Randall, R V; Horvath, E; Laws, E R

1986-08-01

Since its clinical description in the last century, much progress has been made in our understanding of acromegaly. From an initial description of pituitary enlargement as just another manifestation of generalized visceromegaly, the pituitary abnormality has come to be recognized, in most instances, as the underlying aetiological factor. Gigantism and acromegaly are manifestations of disordered pituitary physiology, but the lesion responsible may be hypothalamic, adenohypophyseal or ectopic in location. The best known pathological hypothalamic basis for acromegaly is represented by a neuronal malformation or 'gangliocytoma'. It usually takes the form of an intrasellar gangliocytoma or, more rarely, a hypothalamic hamartoma. The neuronal elaboration of GHRH may play a role in the development of a growth hormone adenoma; the pituitary process may pass through an intermediate stage of somatotropic hyperplasia. When acromegaly has its basis in a pituitary abnormality, the lesion is almost exclusively an adenoma; the non-tumorous adenohypophysis shows no evidence of coexistent hyperplasia. Surprisingly, such tumours are more often engaged in the formation of multiple hormones rather than GH alone. They frequently produce not only GH and prolactin, the products characteristics of cells of the acidophil line, but also glycoprotein hormones, usually TSH. The spectrum of adenomas also varies in its degree of differentiation from a histogenetically primitive lesion, the acidophil stem cell adenoma, to well-differentiated tumours of varying cellular composition and hormone content. Each adenoma type has its clinicopathological, histochemical, immunocytological and ultrastructural characteristics. The isolation and characterization of GHRH has permitted the identification of neuroendocrine tumours, most of foregut origin, elaborating this releasing hormone. Such functional tumours induce hyperplasia of pituitary somatotrophs and may, on occasion, result in the formation of growth hormone adenomas. Resection of these GHRH-producing neoplasms results in reversal of endocrinological and sellar abnormalities. Future efforts should be directed toward the elucidation of the aetiology of pituitary adenomas, specifically whether they represent a proliferative process having its origin in endocrinological imbalance, presumably a hypothalamic abnormality, or whether it has a 'de novo' origin in the 'usual process of neoplastic transformation'.

Hypophysopexy technique for radiosurgical treatment of cavernous sinus pituitary adenoma.

PubMed

Couldwell, William T; Rosenow, Joshua M; Rovit, Richard L; Benzil, Deborah L

2002-01-01

Stereotactic radiosurgery is being used with increased frequency in the treatment of residual or recurrent pituitary adenomas. The major risk associated with radiosurgical treatment of residual or recurrent pituitary tumor adjacent to normal functional pituitary gland is radiation of the pituitary, which frequently leads to the development of hypopituitarism. The authors describe a technique of pituitary transposition to reduce the radiation dose to the normal pituitary gland in cases of planned radiosurgical treatment of residual pituitary adenoma within the cavernous sinus. A sellar exploration for tumor resection is performed, the pituitary gland is transposed from the region of the cavernous sinus, and a fat and fascia graft is interposed between the normal pituitary gland and the residual tumor in the cavernous sinus. The residual tumor may then be treated with stereotactic radiosurgery. The increased distance between the normal pituitary gland and the residual tumor facilitates treatment of the tumor with radiosurgery and reduces the radiation to the normal pituitary gland. An illustrative case of a young female with recurrent acromegaly and a pituitary adenoma invading the cavernous sinus is described.

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

PubMed Central

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

2014-01-01

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

The infundibulo-tuberal syndrome caused by craniopharyngiomas: clinicopathological evidence from an historical French cohort (1705-1973).

PubMed

Castro-Dufourny, Inés; Carrasco, Rodrigo; Prieto, Ruth; Barrios, Laura; Pascual, José M

2015-10-01

Infundibulo-tuberal syndrome groups endocrine, metabolic and behavioral disturbances caused by lesions involving the upper neurohypophysis (median eminence) and adjacent basal hypothalamus (tuber cinereum). It was originally described by Henri Claude and Jean Lhermitte in 1917, in a patient with a craniopharyngioma. This study investigates the clinical, pathological and surgical evidence verifying the infundibulo-tuberal syndrome caused by craniopharyngiomas (CPs). A systematic retrospective review of craniopharyngiomas reported in French literature between 1705 and 1973 was conducted. A total of 128 well described reports providing a comprehensive clinical and pathological description of the tumors were selected. This series represents the historical French cohort of CPs reported in the pre-CT/MRI era. Three major syndromes caused by CPs were categorized: pituitary syndrome (35%), infundibulo-tuberal syndrome (52%) and hypothalamic syndrome (49%). CP topography was significantly related to the type of syndrome described (p < 0.001). Infundibulo-tuberal syndrome occurred in CPs which replaced or invaded the third ventricle floor. In contrast, the majority of sellar/suprasellar CPs growing below the third ventricle showed a pituitary syndrome (82%). Cases with hypothalamic syndrome were characterized by anatomical integrity of the pituitary gland and stalk (p = 0.033) and occurred predominantly in adults older than 41 years old (p < 0.005). Among infundibulo-tuberal symptoms, abnormal somnolence was not related with the presence of hydrocephalus. All squamous-papillary CPs presented psychiatric disturbances (p < 0.001). This historical CP cohort evidences a clinical-topographical correlation between the patient's type of syndrome and the anatomical structures involved by the tumor along the hypophysial-hypothalamic axis.

Clinical predictors of advanced sellar masses.

PubMed

Rambaldini, Gloria M; Butalia, Sonia; Ezzat, Shereen; Kucharczyk, Walter; Sawka, Anna M

2007-10-01

To identify clinical variables associated with the presence of a structurally advanced sellar mass (ASM). We performed a retrospective study of patients referred for evaluation of suspected new pituitary disease or sellar mass to the Endocrine Oncology Unit of Mount Sinai Hospital in Toronto, Ontario, Canada. By multivariate analysis, we examined predictors of a structurally ASM (a sellar lesion with any of the following characteristics: diameter of >or=1 cm on magnetic resonance imaging [MRI], optic chiasmal compression on MRI, or clinical or biochemical evidence of hypopituitarism). Data from 152 patients were analyzed. Of the 152 sellar masses, 142 (93%) were pituitary adenomas. An ASM was noted in 85 of the 152 patients (56%). In the final multivariate model, male sex (odds ratio [OR], 6.23; 95% confidence interval [CI], 2.84 to 13.56; P<0.001) and self-reported visual field defect (OR, 3.62; 95% CI, 1.07 to 12.25; P = 0.039) were significantly independently associated with the presence of an ASM. The presence of new or changed headaches also tended to be associated with an ASM (OR, 2.11; 95% CI, 0.96 to 4.64; P = 0.063). Age and self-reported galactorrhea were not independently associated with the presence of an ASM and were conditionally removed from the final model. In patients with suspected sellar or pituitary disease, male sex and self-reported visual field defects independently predict the presence of an ASM. New or changed headaches also tend to be related to the presence of an ASM. The presence of predictors of an ASM should prompt expedited sellar MRI and biochemical evaluation.

Cushing's syndrome: from physiological principles to diagnosis and clinical care.

PubMed

Raff, Hershel; Carroll, Ty

2015-02-01

The physiological control of cortisol synthesis in the adrenal cortex involves stimulation of adrenocorticotrophic hormone (ACTH) by hypothalamic corticotrophin-releasing hormone (CRH) and then stimulation of the adrenal by ACTH. The control loop of the hypothalamic-pituitary-adrenal (HPA) axis is closed by negative feedback of cortisol on the hypothalamus and pituitary. Understanding this system is required to master the diagnosis, differential diagnosis and treatment of endogenous hypercortisolism--Cushing's syndrome. Endogenous Cushing's syndrome is caused either by excess ACTH secretion or by autonomous cortisol release from the adrenal cortex. Diagnosis of cortisol excess exploits three physiological principles: failure to achieve the normal nadir in the cortisol diurnal rhythm, loss of sensitivity of ACTH-secreting tumours to cortisol negative feedback, and increased excretion of free cortisol in the urine. Differentiating a pituitary source of excess ACTH (Cushing's disease) from an ectopic source is accomplished by imaging the pituitary and sampling for ACTH in the venous drainage of the pituitary. With surgical removal of ACTH or cortisol-secreting tumours, secondary adrenal insufficiency ensues because of the prior suppression of the HPA axis by glucocorticoid negative feedback. Medical therapy is targeted to the anatomical location of the dysregulated component of the HPA axis. Future research will focus on new diagnostics and treatments of Cushing's syndrome. These are elegant examples of translational research: understanding basic physiology informs the development of new approaches to diagnosis and treatment. Appreciating pathophysiology generates new areas for inquiry of basic physiological and biochemical mechanisms. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Clinical outcomes in male patients with lactotroph adenomas who required pituitary surgery: a retrospective single center study.

PubMed

Liu, Winnie; Zahr, Roula Shraiky; McCartney, Shirley; Cetas, Justin S; Dogan, Aclan; Fleseriu, Maria

2018-06-23

Lactotroph adenomas (LA) are the most frequently encountered pituitary tumors. Although more frequently observed in women, LAs in men were recently included in a more aggressive category regardless of histological grading, by the WHO. We aimed to perform a rigorous retrospective review of a single center's pre-operative evaluation, patient characteristics and outcomes of male LAs patients requiring pituitary surgery. A retrospective review, over 11 years, of patients who underwent resection of a pituitary adenoma at a single center was conducted. Predictors of persistent disease in male LAs patients along with a comparison to predictors of silent corticotroph adenomas (SCAs) patients who also underwent surgery at the center was also conducted. Thirty-one male patients with LAs were identified. When compared to SCAs patients, LAs male patients were younger (41 vs. 50 years of age, p = 0.01). Men with LAs had more invasive tumors (75% vs. 44.7% p = 0.02). More LAs in men had residual tumor after surgery than patients with SCA (92.6% vs. 42.1%, p < 0.001). Male patients with LAs and patients with SCA had similar rates of requiring additional surgery (28.9% vs. 24.1%, p = NS) and radiation therapy (18.4% vs. 19.4%, p = NS). High rates of DA resistance, invasive tumors and postoperative residual disease in male patients with LA who required surgery are shown. Surgery improved optic chiasm compression, PRL level and central hypogonadism but, not surprisingly, failed to normalize other pituitary hormones and/or eliminate need for DA therapy.

Prospective investigation of anterior pituitary function in the acute phase and 12 months after pediatric traumatic brain injury.

PubMed

Ulutabanca, Halil; Hatipoglu, Nihal; Tanriverdi, Fatih; Gökoglu, Abdülkerim; Keskin, Mehmet; Selcuklu, Ahmet; Kurtoglu, Selim; Kelestimur, Fahrettin

2014-06-01

Although head trauma is common in childhood, there is no enough prospective study investigating both acute phase and 12 months after injury. Therefore, a prospective clinical trial was planned to evaluate the pituitary function in childhood in the acute and chronic phase after traumatic brain injury (TBI). Forty-one children (27 boys and 14 girls, mean age 7 ± 4.3), who were admitted to neurosurgery intensive care unit due to head trauma, were included. Twenty-one (51.2 %) patients had mild, 10 (24.4 %) had moderate, and 10 (24.4 %) had severe TBI. Twenty-two of them were reevaluated 12 months after TBI. Basal pituitary hormone levels were measured during acute (first 24 h) and chronic phase of TBI. Additionally, in the chronic phase, GHRH-arginine test was used for the diagnosis of growth hormone (GH) deficiency. In the acute phase, 10 patients (24.4 %) had ACTH deficiency, and the overall 44.3 % of patients had at least one pituitary hormone dysfunction. All the pituitary hormone deficiencies during the acute phase were recovered after 12 months. Two patients (9.1 %) had new-onset GH deficiency in the chronic phase, and in one of them, ACTH deficiency was also present. Present prospective data clearly demonstrated that most of the hormonal changes in the early acute phase were transient, suggesting an adaptive response, and these changes did not predict the hormone deficiencies after 1 year. In the chronic phase, although GH deficiency was present, the frequency of TBI-induced hypopituitarism was clearly lower than the adult patients.

Iron overload detection using pituitary and hepatic MRI in thalassemic patients having short stature and hypogonadism.

PubMed

Mousa, Amany A; Ghonem, Mohamed; Elhadidy, El Hadidy M; Azmy, Emad; Elbackry, Magda; Elbaiomy, Azza A; Elzehery, Rasha R; Shaker, Gehan A; Saleh, Omyma

2016-05-01

to assess the growth and pubertal development among a group of patients with β-Thalassemia Major (β-TM) and to evaluate the role of the pituitary gland and liver MRI signal intensity (SI) reduction in assessing and predicting the clinical severity of growth and pubertal dysfunctions. Thirty-eight patients with β-TM were examined and divided into two groups: Group I patients were of normal height and puberty and Group II patients had short statures and hypogonadism. Laboratory investigations included serum ferritin, LH, FSH, prolactin, TSH, and basal and dynamic growth hormones. Pituitary and liver MRIs were performed to assess the pituitary to fat (P/F) and liver to muscle (L/M) signal intensities (SI), respectively. Fifteen healthy and sex- and age-matched subjects were included as controls. Both patient groups had significantly elevated serum ferritin and significantly decreased prolactin and IGF1 compared to control subjects. Group II showed a significant reduction in LH, FSH, and IGF1 and a significant increase in ferritin in comparison with Group I and the control group, and it had a highly significant reduction in both P/F and L/M SI in comparison with Group I (p<0.001 and 0.008, respectively). The reduced P/F ratio was significantly correlated with FSH and LH, and a cutoff for a P/F ratio ≥0.94 was obtained to differentiate between Group I and II. MRI in conjunction with the P/F signal intensity ratio is a useful and noninvasive tool for the early diagnosis of pituitary iron overload.

Budget impact of everolimus for the treatment of progressive, well-differentiated, non-functional neuroendocrine tumors of gastrointestinal or lung origin that are advanced or metastatic.

PubMed

Rose, Darya B; Nellesen, Dave; Neary, Maureen P; Cai, Beilei

2017-04-01

Advanced neuroendocrine tumors (NETs) are a rare malignancy with considerable need for effective therapies. Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2016 for treatment of adults with progressive, well-differentiated, non-functional NETs of gastrointestinal (GI) or lung origin that are unresectable, locally advanced, or metastatic. To assess the 3-year budget impact for a typical US health plan following availability of everolimus for treatment of GI and lung NETs. Methods An economic model was developed that considered two perspectives: an entire health plan and a pharmacy budget. The total budget impact included costs of drug therapies, administration, hospitalizations, physician visits, monitoring, and adverse events (AEs). The pharmacy model only considered drug costs. In a US health plan with 1 million members, the model estimated 66 patients with well-differentiated, non-functional, and advanced or metastatic GI NETs and 20 with lung NETs undergoing treatment each year. Total budget impact in the first through third year after FDA approval ranged from $0.0568-$0.1443 per member per month (PMPM) for GI NETs and from $0.0181-$0.0355 PMPM for lung NETs. The total budget impact was lower than the pharmacy budget impact because it included cost offsets from administration and AE management for everolimus compared with alternative therapies (e.g. chemotherapies). Because GI and lung NETs are rare diseases with limited published data, several assumptions were made that may influence interpretation of results. The budget impact for everolimus was minimal in this rare disease area with a high unmet need, largely due to low disease prevalence. These results should be considered in the context of significant clinical benefits potentially provided by everolimus, including significantly longer progression-free survival (PFS) for advanced GI and lung NET patients.

Randomized controlled trial of ionization and photoelectric smoke alarm functionality.

PubMed

Mueller, B A; Sidman, E A; Alter, H; Perkins, R; Grossman, D C

2008-04-01

To compare functionality, reasons for non-function, and nuisance alarm levels of two common types of smoke alarms after installation in low- to mid-level income households in King County, Washington. Randomized controlled trial of 761 households. An ionization or photoelectric smoke alarm was installed between June 1, 2000 and July 31, 2002. Main outcome measures were: percentage of study alarms that were working, observed reasons for non-functional status, and self-reported frequency of nuisance alarms at 9 and 15 months of follow-up. At 9 months after installation, 20% of ionization, vs 5% of photoelectric alarms were non-functional, a difference that persisted at 15 months, with the most common reasons for both types being a disconnected or absent battery. The risk ratio for ionization, relative to photoelectric alarms, being non-functional or removed was 2.7 (95% CI 1.8 to 4.1) at 15 months of follow-up. These findings were not altered by educational level, or the presence of smokers, children <5 years, or adults > or =65 years. Burn prevention efforts are geared towards increasing smoke alarm ownership and improving maintenance of functional status. Results suggest that the selective use of photoelectric alarms by fire injury prevention programs or consumers may provide longer-term protection in similar populations. Designing smoke alarms that minimize nuisance alarming may also result in longer term functionality.

Effect of central and ovarian endocrine disturbances on the female genital tract--clinical signs and symptoms.

PubMed

Sillem, M; Rabe, T; Runnebaum, B

1997-01-01

Disorders of the female genital tract caused by endocrine disturbances commonly lead to two presenting complaints: dysfunctional uterine bleeding and infertility. In oestrogen deficiency, sequelae of vaginal atrophy may also be present. The common pathogenic "turntable" of these clinical signs is an impaired ovarian function, for which primary (i.e. intraovarian) and secondary (i.e. resulting from dysfunctions of other endocrine systems) causes are known. Primary ovarian failure can be the result of gonadal dysgenesis or premature menopause. Secondary ovarian dysfunction may be caused by hypothalamic-pituitary dysregulation, hyperprolactinaemia, thyroid disorders, and hyperandrogenaemia, which often also has an intraovarian component. For clinical considerations, several severities of ovarian dysfunction can be distinguished, ranging from corpus luteum insufficiency which is only relevant for the selection of infertility treatment to the complete absence of ovarian steroidogenesis leading to severe long term sequelae of the skeletal, cardiovascular and probably central nervous systems. Diagnosis and differential diagnosis are made by clinical examination, vaginal ultrasound, hormone assays, curettage and laparoscopy. Rarely, additional techniques like magnetic resonance imaging of the pituitary or the adrenals, or sequential catheterization of the inferior vena cava are needed.

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

PubMed

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

2015-08-01

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

The Value of Intraoperative Magnetic Resonance Imaging in Endoscopic and Microsurgical Transsphenoidal Pituitary Adenoma Resection.

PubMed

Pal'a, Andrej; Knoll, Andreas; Brand, Christine; Etzrodt-Walter, Gwendolin; Coburger, Jan; Wirtz, Christian Rainer; Hlaváč, Michal

2017-06-01

The routine use of intraoperative magnetic resonance imaging (iMRI) helps to achieve gross total resection in transsphenoidal pituitary surgery. We compared the added value of iMRI for extent of resection in endoscopic versus microsurgical transsphenoidal adenomectomy. A total of 96 patients with pituitary adenoma were included. Twenty-eight consecutive patients underwent endoscopic transsphenoidal tumor resection. For comparison, we used a historic cohort of 68 consecutive patients treated microsurgically. We evaluated the additional resection after conducting iMRI using intraoperative and late postoperative volumetric tumor analysis 3 months after surgery. Demographic data, clinical symptoms, and complications as well as pituitary function were evaluated. We found significantly fewer additional resections after conducting iMRI in the endoscopic group (P = 0.042). The difference was even more profound in Knosp grade 0-2 adenomas (P = 0.029). There was no significant difference in Knosp grade 3-4 adenomas (P = 0.520). The endoscopic approach was associated with smaller intraoperative tumor volume (P = 0.023). No significant difference was found between both techniques in postoperative tumor volume (P = 0.228). Satisfactory results of pituitary function were significantly more often associated with an endoscopic approach in the multiple regression analysis (P = 0.007; odds ratio, 17.614; confidence interval 95%, 2.164-143.396). With the endoscopic approach, significantly more tumor volume reduction was achieved before conducting iMRI, decreasing the need for further resection. This finding was even more pronounced in adenomas graded Knosp 0-2. In the case of extensive and invasive adenomas with infiltration of cavernous sinus and suprasellar or parasellar extension, additional tumor resection and increase in the extent of resection was achieved with iMRI in both groups. The endoscopic approach seems to result in better endocrine outcomes, especially in Knosp grade 0-2 pituitary adenomas. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative inhibition of the GH/IGF-I axis obtained with either the targeted secretion inhibitor SXN101959 or the somatostatin analog octreotide in growing male rats.

PubMed

Somm, Emmanuel; Bonnet, Nicolas; Zizzari, Philippe; Tolle, Virginie; Toulotte, Audrey; Jones, Richard; Epelbaum, Jacques; Martinez, Alberto; Hüppi, Petra S; Aubert, Michel L

2013-11-01

Abnormally high GH/IGF-I levels, most often caused by adenomas arising from pituitary somatotrophs, generate deleterious effects. We recently described a targeted secretion inhibitor (SXN101742) comprising a GHRH domain and the endopeptidase domain of botulinum toxin serotype D (GHRH-light chain endopeptidase type D domain [LC/D] associated to a heavy chain translocation domain [HN]) able to down-regulate the GH/IGF-I axis. In the present study, we compared the effect of a single iv bolus of a related molecule developed for clinical studies (SXN101959, 1 mg/kg) with a sc infusion of the somatostatin analog octreotide (SMS201-995, 10 μg/kg · h) to lower GH/IGF-I activity in growing male rats. Ten days after administration of SXN101959 or initiation of the octreotide infusion, body and pituitary weights, body length, GH peaks, and IGF-I production were reduced by both treatments but to a greater extent with SXN101959. In contrast to unaltered GH gene expression and increased GH storage in pituitaries from octreotide-treated rats, the inhibition of GH secretion was associated with a collapse of both GH mRNA and protein level in pituitaries from SXN101959-treated rats, in line with a specific decrease in hypothalamic GHRH production, not observed with octreotide. SXN101959 did not induce major apoptotic events in anterior pituitary and exhibited a reversible mode of action with full recovery of somatotroph cell functionality 30 days after treatment. Octreotide infusion permanently decreased ghrelin levels, whereas SXN101959 only transiently attenuated ghrelinemia. Both treatments limited bone mass acquisition and altered specifically tissues development. In conclusion, SXN101959 exerts a powerful and reversible inhibitory action on the somatotropic axis. Specific features of SXN101959, including long duration of action coupled to a strong inhibition of pituitary GH synthesis, represent advantages when treating overproduction of GH.

Growth hormone-secreting pituitary adenomas in childhood and adolescence: features and results of transnasal surgery.

PubMed

Abe, T; Tara, L A; Lüdecke, D K

1999-07-01

Pituitary tumors causing gigantism are rare in childhood and adolescence. In a review of 2367 patients with pituitary adenomas who were treated between 1970 and 1997, we found 15 cases (0.63%, 9 male and 6 female patients) of growth hormone-secreting pituitary adenomas in patients who were less than 20 years of age at the time of surgery, and we compared their characteristics with those of adenomas in an adult group. Patients were grouped according to their ages at the first operation, with five patients (33.3%) in the prepubescent group (0-11 yr), eight (53.3%) in the pubescent group (12-17 yr), and two (13.3%) in the postpubescent group (18-19 yr). All 15 patients exhibited the typical symptoms of growth hormone oversecretion. The incidence of hyperprolactinemia among patients with prepubescent onset was 66.7%. Radiological examinations demonstrated microadenomas in 4 patients (26.7%) and macroadenomas in 11 patients (73.3%). The mean follow-up period was 73.5 months. Direct transnasal explorations were performed for all patients. Tumor invasion into the cavernous sinus was observed in six patients (40%). Radical tumor resection was performed for four patients (80%) in the prepubescent group, for five patients (62.5%) in the pubescent group, and for neither patient in the postpubescent group. Surgical morbidity was caused by permanent diabetes insipidus in three patients (20%). Rapid growth was postoperatively improved in 80% of the prepubescent age group. The recurrence rate was 13.3% (2 of 15 patients). Transnasal pituitary surgery was found to be as safe in pediatric patients with gigantism as in adults. Growth hormone-secreting pituitary adenomas in childhood and adolescence were more likely to be invasive or aggressive than were those in adulthood. The clinical biological characteristics for children were different from those for adults.