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https://www.readbyqxmd.com/read/28522647/prkar1a-mutation-causing-pituitary-dependent-cushing-disease-in-a-patient-with-carney-complex
#1
Florian W Kiefer, Yvonne Winhofer, Donato Iacovazzo, Marta Korbonits, Stefan Wolfsberger, Engelbert Knosp, Franz Trautinger, Romana Höftberger, Michael Krebs, Anton Luger, Alois Gessl
CONTEXT: Carney complex (CNC) is an autosomal dominant condition caused, in most cases, by an inactivating mutation of the PRKAR1A gene, which encodes for the type 1 alpha regulatory subunit of protein kinase A. CNC is characterized by the occurrence of endocrine overactivity, myxomas and typical skin manifestations. Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine disease observed in CNC. CASE DESCRIPTION: Here we describe the first case of a patient with CNC and adrenocorticotropic hormone (ACTH)-dependent Cushing disease due to a pituitary corticotroph adenoma...
May 18, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28516968/preliminary-experience-with-4k-ultra-high-definition-endoscope-analysis-of-pros-and-cons-in-skull-base-surgery
#2
M Rigante, G La Rocca, L Lauretti, G Q D'Alessandris, A Mangiola, C Anile, A Olivi, G Paludetti
During the last two decades endoscopic skull base surgery observed a continuous technical and technological development 3D endoscopy and ultra High Definition (HD) endoscopy have provided great advances in terms of visualisation and spatial resolution. Ultra-high definition (UHD) 4K systems, recently introduced in the clinical practice, will shape next steps forward especially in skull base surgery field. Patients were operated on through transnasal transsphenoidal endoscopic approaches performed using Olympus NBI 4K UHD endoscope with a 4 mm 0° Ultra Telescope, 300 W xenon lamp (CLV-S400) predisposed for narrow band imaging (NBI) technology connected through a camera head to a high-quality control unit (OTV-S400 - VISERA 4K UHD) (Olympus Corporation, Tokyo, Japan)...
June 2017: Acta Otorhinolaryngologica Italica
https://www.readbyqxmd.com/read/28512418/cushing-s-syndrome-cortisol-and-cognitive-competency-a-case-report
#3
Neil Oronsky, Bennett Thilagar, Carolyn M Ray, Scott Caroen, Michelle M C Lybeck, Lindsey Ferry, Ronald A Voves, Bryan Oronsky
Glucocorticoids are associated with immunosuppression and neuropsychiatric complications. We describe the case of a carcinoid patient with Cushing's syndrome (CS) and neurocognitive impairment due to ectopic ACTH production who developed sepsis and died because of his family's decision to withdraw antibiotic treatment. This report is presented to illustrate the importance of advanced-care planning in patients with CS.
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28512417/a-case-of-paraneoplastic-cushing-syndrome-presenting-as-hyperglycemic-hyperosmolar-nonketotic-syndrome
#4
Christina E Brzezniak, Nicole Vietor, Patricia E Hogan, Bryan Oronsky, Bennett Thilagar, Carolyn M Ray, Scott Caroen, Michelle Lybeck, Neil Oronsky, Corey A Carter
Carcinoid tumors are neuroendocrine tumors that mainly arise in the gastrointestinal tract, lungs, and bronchi. Bronchopulmonary carcinoids have been associated with Cushing syndrome, which results from ectopic adrenocorticotrophic hormone (ACTH) secretion. We report the case of a 65-year-old man, a colonel in the US Air Force, with metastatic bronchopulmonary carcinoid tumors treated on a clinical trial who was hospitalized for complaints of increasing thirst, polydipsia, polyuria, weakness, and visual changes...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28512117/the-interaction-of-mc3r-and-mc4r-with-mrap2-acth-%C3%AE-msh-and-agrp-in-chickens
#5
Jiannan Zhang, Xin Li, Yawei Zhou, Lin Cui, Jing Li, Chenlei Wu, Yiping Wan, Juan Li, Yajun Wang
The interaction of melanocortin-4 (MC4R) and melanocortin-3 (MC3R) receptors with proopiomelanocortin (POMC)-derived peptides (e.g. α-MSH), agouti-related protein (AgRP), and melanocortin-2 receptor accessory protein 2 (MRAP2) is suggested to play critical roles in energy balance of vertebrates. However, evidence on their interaction in birds remains scarce. Our study aims to reveal their interaction in chickens and the results showed that: 1) chicken (c-)MC3R and cMC4R expressed in CHO cells can be activated by α-MSH and ACTH1-39 equipotently, monitored by a pGL3-CRE-luciferase reporter system; 2) cMC3R and cMC4R, when co-expressed with cMRAP2 (or cMRAP, a cMRAP2 homolog), show increased sensitivity to ACTH treatment and thus likely act as ACTH-preferring receptors, and the interaction between cMC3R/cMC4R and cMRAP2 was demonstrated by co-immunoprecipitation assay; 3) both cMC3R and cMC4R display constitutive activity when expressed in CHO cells, as monitored by Dual-luciferase reporter assay, and cMRAP2 (and cMRAP) can modulate their constitutive activity; 4) AgRP inhibits the constitutive activity of cMC3R/cMC4R, and it also antagonizes ACTH/α-MSH action on cMC4R/cMC3R, indicating that AgRP functions as the inverse agonist and antagonist for both receptors...
May 16, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28511913/the-non-peptide-crh1-antagonist-cp-154-526-elicits-a-paradoxical-route-dependent-activation-of-the-hpa-axis
#6
Dmitry V Zaretsky, Maria V Zaretskaia, Sumit Sarkar, Daniel E Rusyniak, Joseph A DiMicco
The corticotropin-releasing hormone (CRH) plays an important role in mediating physiological response to stress and is thought to be involved in the development of various psychiatric disorders. In this paper we compare the differences between the effect of intraperitoneal (i.p.) and intraarterial (i.a.) administration of the non-peptide CRH1 antagonist CP-154,526 (CP) (10 and 20mg/kg) on plasma adrenocorticotropic hormone levels (ACTH), heart rate, MAP, and c-Fos expression in the paraventricular nucleus of the hypothalamus...
May 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28511160/features-of-some-clinical-examination-parameters-in-patients-with-psoriatic-arthritis
#7
Оrysya Syzon, Iryna Voznyak, Marianna Dashko
INTRODUCTION: The relationship of cause-and-effect mechanisms of exacerbation and progressing with defining of the role of stress reaction in the psoriatic arthritis (PA) development has been examined in the article by analyzing the characteristics of medical history, current dynamics as well as clinical, instrumental and laboratory examinations. The objective was to study the role of basic indices of laboratory examinations of patients used clarify their role in the pathogenesis of PA...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28505327/histone-deacetylase-inhibitor-saha-is-a-novel-promising-treatment-for-cushing-s-disease
#8
Jie Lu, Grégoire P Chatain, Alejandro Bugarini, Xiang Wang, Dragan Maric, Stuart Walbridge, Zhengping Zhuang, Prashant Chittiboina
Context: Remission failure following transsphenoidal surgery in Cushing's disease (CD) from pituitary corticotroph tumors (CtT) remains clinically challenging. Histone deacetylase (HDAC) inhibitors are antitumor drugs approved for oral clinical use, with potential to affect adrenocorticotropin (ACTH) hypersecretion by inhibiting proopiomelanocortin (POMC) transcription. Objective: Testing efficacy of suberolyl hydroxamic acid (SAHA) on human and murine ACTH-secreting tumor cells...
May 12, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28505279/somatic-usp8-gene-mutations-are-a-common-cause-of-pediatric-cushing-disease
#9
Fabio R Faucz, Amit Tirosh, Christina Tatsi, Annabel Berthon, Laura C Hernández-Ramírez, Nikolaos Settas, Anna Angelousi, Ricardo Correa, Georgios Z Papadakis, Prashant Chittiboina, Martha Quezado, Nathan Pankratz, John Lane, Aggeliki Dimopoulos, James L Mills, Maya Lodish, Constantine A Stratakis
Context: Somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have been recently identified as the most common genetic alteration in patients with Cushing disease (CD). However, the frequency of these mutations in the pediatric population has not been extensively assessed. Objective: We investigated the status of the USP8 gene at the somatic level in a cohort of pediatric patients with corticotroph adenomas. Design and Methods: The USP8 gene was fully sequenced in both germline and tumor DNA samples from 42 pediatric CD patients...
May 12, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28504317/adrenal-cortex-reactivity-in-dairy-cows-differs-between-lactational-stages-and-between-different-feeding-levels
#10
J J Gross, R S Zbinden, F Dohme-Meier, R M Bruckmaier
Changes in ACTH challenge test characteristics in dairy cows changing their physiological status at different lactational stages and different feeding levels were not investigated in terms of repeatability yet. In 23 multiparous Holstein cows (10 cows fed a sole fresh herbage diet without concentrate, 13 cows fed with concentrate), three ACTH challenge tests were performed: once during pregnancy shortly prior to drying off (T1), and in week 3 (T2) and 8 (T3) after parturition. Test characteristics were correlated to performance and metabolic parameters: DMI, BW, energy balance (EB), plasma concentrations of free fatty acids (NEFA) and beta-hydroxybutyrate (BHB)...
May 15, 2017: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/28500827/psychological-vulnerability-to-stress-in-carriers-of-congenital-adrenal-hyperplasia-due-to-21-hydroxylase-deficiency
#11
Eleni-Magdalini Kyritsi, Georgia Koltsida, Ioanna Farakla, Aikaterini Papanikolaou, Elena Critselis, Emilia Mantzou, Emmanouil Zoumakis, Gerasimos Kolaitis, George P Chrousos, Evangelia Charmandari
OBJECTIVE: Carriers of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) demonstrate increased secretion of cortisol precursors following ACTH stimulation, suggestive of impaired cortisol production and compensatory increases in hypothalamic corticotropin-releasing hormone (CRH) secretion. Both cortisol and CRH have behavioral effects, and hypothalamic CRH hypersecretion has been associated with chronic states of anxiety and depression. We performed an endocrinologic and psychological evaluation in carriers of 21-OHD and matched control subjects...
January 2017: Hormones: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28499989/melanocortin-receptor-accessory-proteins-mraps-functions-in-the-melanocortin-system-and-beyond
#12
REVIEW
Alix A J Rouault, Dinesh K Srinivasan, Terry C Yin, Abigail A Lee, Julien A Sebag
G-protein coupled receptors (GPCRs) are regulated by numerous proteins including kinases, G-proteins, β-arrestins and accessory proteins. Several families of GPCR accessory proteins like Receptor Activity Modifying Proteins, Receptor Transporting Proteins and Melanocortin Receptor Accessory Proteins (MRAPs) have been identified as regulator of receptor trafficking, signaling and ligand specificity. The MRAP family contains two members, MRAP1 and MRAP2, responsible for the formation of a functional ACTH receptor and for the regulation of energy homeostasis respectively...
May 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28495271/the-melanocortin-2-receptor-of-the-rainbow-trout-identifying-a-role-for-critical-positions-in-transmembrane-domain-4-extracellular-loop2-and-transmembrane-domain-5-in-the-activation-of-rainbow-trout-mc2r
#13
Liang Liang, Perry V Davis, Michael R Dores, Robert M Dores
The activation of either teleost or tetrapod melanocortin-2 receptor (MC2R) orthologs requires interaction between the HFRW motif and R/KKRRP motif in the primary sequence of ACTH, and two corresponding sites on the melanocortin 2 receptor. While the HFRW contact site on MC2R appears to involve residues in TM2, TM3, and TM6, several studies on human MC2R point to the EC2/TM5 region of MC2R as a possible location for the R/KKRRP contact site. In this study nineteen single-alanine mutants of rainbow trout (rt) MC2R were made beginning at V(153) in TM4, at all positions in EC2 (extracellular loop 2), to F(175) in TM5...
May 8, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28492512/aldosterone-and-mineralocorticoid-receptors-physiology-and-pathophysiology
#14
John W Funder
Aldosterone is a uniquely terrestrial hormone, first appearing in lungfish, which have both gills and lungs. Mineralocorticoid receptors (MRs), on the other hand, evolved much earlier, and are found in cartilaginous and bony fish, presumptive ligand cortisol. MRs have equivalent high affinity for aldosterone, progesterone, and cortisol; in epithelia, despite much higher cortisol circulating levels, aldosterone selectively activates MRs by co-expression of the enzyme 11β-hydroxysteroid dehydrogenase, Type 11...
May 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28487882/identification-of-a-novel-rasd1-somatic-mutation-in-a-usp8-mutated-corticotroph-adenoma
#15
Andrew V Uzilov, Khadeen C Cheesman, Marc Y Fink, Leah C Newman, Chetanya Pandya, Yelena Lalazar, Marco Hefti, Mary Fowkes, Gintaras Deikus, Chun Yee Lau, Aye S Moe, Yayoi Kinoshita, Yumi Kasai, Micol Zweig, Arpeta Gupta, Daniela Starcevic, Milind Mahajan, Eric E Schadt, Kalmon D Post, Michael J Donovan, Robert Sebra, Rong Chen, Eliza B Geer
Cushing's disease (CD) is caused by pituitary corticotroph adenomas that secrete excess adrenocorticotropic hormone (ACTH). In these tumors, somatic mutations in the gene USP8 have been identified as recurrent and pathogenic and are the sole known molecular driver for CD. Although other somatic mutations were reported in these studies, their contribution to the pathogenesis of CD remains unexplored. No molecular drivers have been established for a large proportion of CD cases and tumor heterogeneity has not yet been investigated using genomics methods...
May 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28487631/activation-of-brain-somatostatin-signaling-suppresses-crf-receptor-mediated-stress-response
#16
REVIEW
Andreas Stengel, Yvette F Taché
Corticotropin-releasing factor (CRF) is the hallmark brain peptide triggering the response to stress and mediates-in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA) axis-other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a broader anti-stress effect by blunting the endocrine, autonomic, behavioral (with a focus on food intake) and visceral gastrointestinal motor responses through the involvement of distinct somatostatin receptor subtypes...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28487303/female-phenotype-with-male-karyotype-a-clinical-enigma
#17
Suja Sukumar, Pavan Uppula, Santosh Kumar, Anil Bhansali
Development of gonadal and phenotypic sex during embryogenesis invariably corresponds to the genotypic sex. However, some disorders of sex development are associated with discordance between the chromosomal, gonadal or phenotypic sex which include complete androgen insensitivity syndrome, 46XY complete gonadal dysgenesis (Swyer syndrome) and, rarely, congenital adrenal hyperplasia due to CYP 17A1 (17α-hydroxylase) deficiency. The enzyme CYP17A1 includes 17α-hydroxylase and 17,20-lyase which are required for the synthesis of cortisol and sex steroids, respectively...
May 9, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28472507/a-case-report-of-hypoglycemia-and-hypogammaglobulinemia-david-syndrome-in-a-patient-with-a-novel-nfkb2-mutation
#18
Rayhan A Lal, Laura K Bachrach, Andrew R Hoffman, Jingga Inlora, Shannon Rego, Michael P Snyder, David B Lewis
Context: DAVID syndrome (Deficient Anterior pituitary with Variable Immune Deficiency) is a rare disorder in which children present with symptomatic ACTH deficiency preceded by hypogammaglobulinemia from B-cell dysfunction with recurrent infections, termed common variable immunodeficiency (CVID). Subsequent whole exome sequencing studies have revealed germline heterozygous C-terminal mutations of NFKB2 as either a cause of DAVID syndrome or of CVID without clinical hypopituitarism. However, to the best of our knowledge there have been no cases in which the endocrinopathy has presented in the absence of a prior clinical history of CVID...
May 3, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28471529/reduced-steroidogenesis-in-patients-with-pcdh19-female-limited-epilepsy
#19
Marina Trivisano, Chiara Lucchi, Cecilia Rustichelli, Alessandra Terracciano, Raffaella Cusmai, Grazia Maria Ubertini, Germana Giannone, Enrico Silvio Bertini, Federico Vigevano, Jozef Gecz, Giuseppe Biagini, Nicola Specchio
Patients affected by protocadherin 19 (PCDH19)-female limited epilepsy (PCDH19-FE) present a remarkable reduction in allopregnanolone blood levels. However, no information is available on other neuroactive steroids and the steroidogenic response to hormonal stimulation. For this reason, we evaluated allopregnanolone, pregnanolone, and pregnenolone sulfate by liquid chromatographic procedures coupled with electrospray tandem mass spectrometry in 12 unrelated patients and 15 age-matched controls. We also tested cortisol, estradiol, progesterone, and 17OH-progesterone using standard immunoassays...
May 4, 2017: Epilepsia
https://www.readbyqxmd.com/read/28468567/expression-of-star-and-key-genes-regulating-cortisol-biosynthesis-in-near-term-ovine-fetal-adrenocortical-cells-effects-of-long-term-hypoxia
#20
Vladimir E Vargas, Dean A Myers, Kanchan M Kaushal, Charles A Ducsay
We previously demonstrated decreased expression of key genes regulating cortisol biosynthesis in long-term hypoxic (LTH) sheep fetal adrenals compared to controls. We also showed that inhibition of the extracellular signal-regulated kinases (ERKs) with the mitogen-activated protein kinase (MEK)/ERK inhibitor UO126 limited adrenocorticotropic (ACTH)-induced cortisol production in ovine fetal adrenocortical cells (FACs), suggesting a role for ERKs in cortisol synthesis. This study was designed to determine whether the previously observed decrease in LTH cytochrome P45011A1/cytochrome P450c17 (CYP11A1/CYP17) in adrenal glands was maintained in vitro, and whether ACTH alone with or without UO126 treatment had altered the expression of CYP11A1, CYP17, and steroidogenic acute regulatory protein (StAR) in control versus LTH FACs...
January 1, 2017: Reproductive Sciences
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