37 results on '"Marija Pfeifer"'
Search Results
2. Adult growth hormone deficiency in CEE region: Heterogeneity of the patient pathway
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Artur Bossowski, Jana Kollerova, Roy Gomez, Marija Pfeifer, Iveta Dzivite-Krisane, Nikolette Szũcs, Vaclav Hana, Emil Natchev, Ilan Shimon, Corin P Badiu, Mirjana Doknic, and J. Hey-Hadavi
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Adult ,0301 basic medicine ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Hypopituitarism ,Patient pathway ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Adult growth hormone deficiency ,Humans ,Medicine ,Dwarfism, Pituitary ,Reimbursement ,Human Growth Hormone ,business.industry ,Standard of Care ,Exercise capacity ,3. Good health ,Eastern european ,030104 developmental biology ,Family medicine ,Practice Guidelines as Topic ,Critical Pathways ,business ,hormones, hormone substitutes, and hormone antagonists ,Healthcare system - Abstract
Objectives Adult growth hormone deficiency (AGHD) is a rare disease characterised by abnormal body composition, reduced strength and exercise capacity and impaired psychological wellbeing. An advisory board of leading Central and Eastern European (CEE) endocrinologists was assembled to gain insights into the status of AGHD care in the CEE region. Topics of discussion included the position of adult hypopituitarism/AGHD in health system priorities, availability and affordability of treatments, awareness of AGHD, practice guidelines used in CEE countries and provisions for long-term care of patients. Design Prior to the meeting, the advisors were asked to summarise, using an itemised survey questionnaire, the usual standards of care for patients with AGHD in their country. At the meeting, the panel of experts discussed the findings and thereby elucidated similarities and differences among CEE countries; these were compared with international guideline-recommended practices for AGHD. Results All CEE countries involved reported having some type of infrastructure in place for care of patients with GHD transitioning from adolescence to adulthood. Most countries reported having at least one specialist centre for patients with AGHD. The main variations across the region included initial entry into healthcare systems, tests required to confirm AGHD diagnosis and medication reimbursement by health authorities. Most CEE countries relied on international society-led guidelines, while some countries have developed national guidelines. Conclusion The CEE Adult Endocrinology Advisory Board meeting recognised considerable diversity in the care and patient pathways for AGHD across CEE countries. Additional work is needed to optimise care of patients with AGHD in the CEE region. more...
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- 2019
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Catalog
3. Adrenal failure and antiphospholipid syndrome
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Aleš Ambrožič, Marija Pfeifer, Mojca Jensterle, and Katarina Mlekus Kozamernik
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Medicine (General) ,Pediatrics ,medicine.medical_specialty ,pulmonary embolism ,Fever ,adrenocorticotropic hormone ,Signs and symptoms ,Case Report ,Adrenocorticotropic hormone ,Newly diagnosed ,030204 cardiovascular system & hematology ,Biochemistry ,Primary Adrenal Insufficiency ,03 medical and health sciences ,plasma renin activity ,R5-920 ,0302 clinical medicine ,systemic lupus erythematosus ,Antiphospholipid syndrome ,Adrenal insufficiency ,medicine ,Humans ,Lupus Erythematosus, Systemic ,030203 arthritis & rheumatology ,Adrenal failure ,business.industry ,hyponatraemia ,Biochemistry (medical) ,Cell Biology ,General Medicine ,medicine.disease ,Antiphospholipid Syndrome ,Pulmonary embolism ,Hypotension ,business - Abstract
We herein report two cases of primary adrenal insufficiency (AI) associated with antiphospholipid syndrome (APS). In both patients, the main finding that led to the diagnosis was hyponatraemia. The major difference between the two cases was the time at which AI evolved during the course of APS. In the first patient, AI developed acutely along with other presenting features of APS. In the second patient, the AI was unmasked during a stressful situation induced by severe inflammation that occurred 7 years after the first APS manifestation and had probably evolved slowly during the previous few years. These cases emphasise the importance of considering AI in patients with either suspected or newly diagnosed APS as well as in patients who have long been known to have APS. The symptoms and signs alerting the clinician to possible AI are general abdominal complaints, fever, hypotension, and hyponatraemia. Conversely, patients with primary AI should be questioned about the signs and symptoms of APS. more...
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- 2020
4. Vitamin D Supplementation During the COVID-19 Pandemic
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Bojana Pinter, Darko Siuka, and Marija Pfeifer
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2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Pneumonia, Viral ,Global Health ,Article ,Betacoronavirus ,Risk Factors ,Pandemic ,medicine ,Global health ,Humans ,Vitamin D ,Pandemics ,biology ,Vitamin d supplementation ,Viral Epidemiology ,business.industry ,SARS-CoV-2 ,COVID-19 ,General Medicine ,Vitamins ,medicine.disease ,biology.organism_classification ,Vitamin D Deficiency ,Virology ,Pneumonia ,Dietary Supplements ,business ,Coronavirus Infections - Published
- 2020
5. Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors
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Stefan Zschiedrich, Nicole Reisch, Ursula Ploeckinger, Joanne Ngeow, Raymond H. Kim, William F. Young, Dmitry Beltsevich, Francesca Schiavi, Umit Ugurlu, Madson Q. Almeida, Taweesak Wannachalee, Gabriela Sanso, Mònica Recasens, Angelica Malinoc, Roman Petrov, Luis Robles Diaz, Andrzej Januszewicz, Jochen Seufert, Holger Amthauer, Svetlana Yaremchuk, Karl-Heinrich Link, Ulrich F. Wellner, Timm Denecke, Jens Aberle, Nalini S. Shah, Xiao-Ping Qi, Marina Y. Yukina, Zheiwei Zhang, Ernst von Dobschuetz, Marta Barontini, Maria Candida Barisson Villares Fragoso, Andrey Kvachenyuk, Laura von Duecker, Giuseppe Opocher, Swati S Jadhav, Roland Därr, Birke Bausch, Merav Fraenkel, Viacheslav I. Egorov, Staffan Welin, Özer Makay, Sirinart Sirinvaravong, Rene Eduardo Diaz, Garrett Bullivant, Matthias Schott, Ana Rosa Pinto Quidute, Ekaterina Kuchinskaya, Camilla Schalin-Jäntti, Charis Eng, Martin K. Walz, Ana O. Hoff, Barbara Jarzab, Tobias B. Huber, Thera P. Links, Nikolaus Tiling, Kornelia Hasse-Lazar, Eric Jonasch, Gianmaria Pennelli, Per Hellman, Maria Adelaide Albergaria Pereira, Nelson Wohllk, Tada Kunavisarut, Attila Patócs, Dirk Bausch, Juri Ruf, Hartmut P. H. Neumann, Alice Helena Dutra Violante, Simona Grozinsky-Glasberg, Stefania Zovato, Oliver Gimm, Alfonso Massimiliano Ferrara, Delmar Munir Lourenço, Mariola Pęczkowska, Marija Pfeifer, Irina Bancos, Tobias Krauss, Karina Villar Gómez de las Heras, Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Guided Treatment in Optimal Selected Cancer Patients (GUTS) more...
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Oncology ,INVOLVEMENT ,Cancer Research ,Endocrinology, Diabetes and Metabolism ,Medizin ,Disease ,Neuroendocrine tumors ,PanNET ,0302 clinical medicine ,Endocrinology ,management recommendations ,CRITERIA ,Registries ,Child ,Islet cell tumors ,Middle Aged ,GA-68-DOTATOC ,3. Good health ,Tumor Burden ,Neuroendocrine Tumors ,030220 oncology & carcinogenesis ,survival ,von Hippel–Lindau disease ,GROWTH ,Adult ,medicine.medical_specialty ,Adolescent ,PET/CT ,030209 endocrinology & metabolism ,03 medical and health sciences ,Young Adult ,Internal medicine ,SURVEILLANCE ,medicine ,Humans ,Von Hippel–Lindau disease ,Preventive healthcare ,Aged ,PET-CT ,business.industry ,JAPANESE PATIENTS ,CLINICAL-FEATURES ,von Hippel-Lindau disease ,medicine.disease ,Pancreatic Neoplasms ,ISLET-CELL TUMORS ,Mutation ,business - Abstract
Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel–Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10–75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P P = 0.001). All metastatic tumors were ≥2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off ≥2.8 cm, 44% and 91% for TVDT cut-off of ≤24 months). In 117 of 273 patients, PanNETs >1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs P = 0.020; 80% vs 50% at 10 years; P = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs. more...
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- 2018
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6. The impact of testosterone replacement therapy on glycemic control, vascular function, and components of the metabolic syndrome in obese hypogonadal men with type 2 diabetes
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Kristina Groti, Ivan Žuran, Marija Pfeifer, Lidija Foršnarič, and Blaž Antonič
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Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Hormone Replacement Therapy ,030232 urology & nephrology ,030209 endocrinology & metabolism ,Type 2 diabetes ,Cardiovascular System ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Double-Blind Method ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Testosterone ,Obesity ,Aged ,Glycemic ,Glycated Hemoglobin ,Metabolic Syndrome ,business.industry ,Hypogonadism ,Testosterone (patch) ,Middle Aged ,medicine.disease ,Endocrinology ,Diabetes Mellitus, Type 2 ,Intima-media thickness ,Glycemic Index ,Transgender hormone therapy ,Androgens ,Geriatrics and Gerontology ,Metabolic syndrome ,business - Abstract
This study set out to assess effects of testosterone replacement therapy (TRT) on parameters of metabolic syndrome and vascular function in obese hypogonadal males with type 2 diabetes mellitus (DM2).Fifty-five obese hypogonadal diabetic males on oral hypoglycemic treatment were enrolled into this one-year, double-blind, randomized, placebo-controlled clinical study. Group T (n = 28) was treated with testosterone undecanoate (1000 mg i.m. every 10 weeks) while group P (n = 27) received placebo.Anthropometrical and vascular measurements - flow-mediated dilatation (FMD) and intima media thickness (IMT) - biochemical and hormonal blood sample analyses were performed at the start of the study and after one year. Derived parameters (BMI, HOMA-IR, calculated free testosterone (cFT) and bioavailable testosterone (BT)) were calculated.TRT resulted in reduction of HOMA-IR by 4.64 ± 4.25 (p .001), HbA1c by 0.94 ± 0.88% points (p .001), and an increase in FMD by 2.40 ± 4.16% points (p = .005).TRT normalized serum testosterone levels, improved glycemic control and endothelial function while exerting no ill effects on the study population. more...
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- 2018
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7. MOD-4023, a long-acting carboxy-terminal peptide-modified human growth hormone: results of a Phase 2 study in growth hormone-deficient adults
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Eyal Fima, L'udmila Trejbalová, Laszlo Bajnok, Ronit Koren, Leanne Amitzi, Christian J. Strasburger, Miklós Góth, Janos Vadasz, Juraj Payer, Peter Vanuga, Marija Pfeifer, Martin Bidlingmaier, Gili Hart, Veˇra Olšovská, Beverly M. K. Biller, Oren Hershkovitz, and Vera Popovic more...
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Antineoplastic Agents, Hormonal ,Hormone Replacement Therapy ,Endocrinology, Diabetes and Metabolism ,Phases of clinical research ,030209 endocrinology & metabolism ,Hypopituitarism ,Gastroenterology ,Drug Administration Schedule ,law.invention ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Randomized controlled trial ,Pharmacokinetics ,law ,Internal medicine ,Humans ,Medicine ,Dosing ,Hormone replacement therapy ,Insulin-Like Growth Factor I ,Adverse effect ,Dose-Response Relationship, Drug ,Human Growth Hormone ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Treatment Outcome ,030104 developmental biology ,Growth Hormone ,Pharmacodynamics ,Clinical Study ,Female ,business - Abstract
Objective Growth hormone (GH) replacement therapy currently requires daily injections, which may cause distress and low compliance. C-terminal peptide (CTP)-modified growth hormone (MOD-4023) is being developed as a once-weekly dosing regimen in patients with GH deficiency (GHD). This study’s objective is to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of MOD-4023 administered once-weekly in GHD adults. Design 54 adults with GHD currently treated with daily GH were normalized and randomized into 4 weekly dosing cohorts of MOD-4023 at 18.5%, 37%, 55.5% or 123.4% of individual cumulative weekly molar hGH dose. The study included 2 stages: Stage A assessed the effectiveness and PK/PD profiles of the 4 dosing regimens of MOD-4023. Stage B was an extension period of once-weekly MOD-4023 administration (61.7% molar hGH content) to collect further safety data and confirm the results from Stage A. Results Dose-dependent response was observed for both PK and PD data of weekly MOD-4023 treatment. Insulin-like growth factor I (IGF-I) SDS levels were maintained within normal range. The 18.5% cohort was discontinued due to low efficacy. MOD-4023 was well tolerated and exhibited favorable safety profile in all dose cohorts. The reported adverse events were consistent with known GH-related side effects. Conclusions Once-weekly MOD-4023 administration in GHD adults was found to be clinically effective while maintaining a favorable safety profile and may obviate the need for daily injections. Weekly GH injections may improve compliance and overall outcome. The promising results achieved in this Phase 2 study led to a pivotal Phase 3 trial, which is currently ongoing. more...
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- 2017
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8. DIAGNOSIS OF ENDOCRINE DISEASE: Drug-induced endocrinopathies and diabetes: a combo-endocrinology overview
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Alexander D. Miras, Eleni A Kandaraki, Vera Popovic, D Rachoń, George Mastorakos, Leonidas H. Duntas, S Nader, Eva Kassi, T Tzotzas, Marija Pfeifer, R Poladian, George Kanakis, Constantine Tsigos, Ilias Migdalis, T Tsilchorozidou, Niki Karavitaki, Evanthia Diamanti-Kandarakis, Alexandra Bargiota, Olga Papalou, Stelios Tigas, and Sarantis Livadas more...
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Drug ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,media_common.quotation_subject ,030209 endocrinology & metabolism ,Context (language use) ,Endocrine System ,Endocrine System Diseases ,Androgen deprivation therapy ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Intervention (counseling) ,medicine ,Diabetes Mellitus ,Endocrine system ,Animals ,Humans ,media_common ,Polypharmacy ,Endocrine disease ,business.industry ,General Medicine ,medicine.disease ,3. Good health ,business ,030217 neurology & neurosurgery ,Hormone - Abstract
In the currently overwhelming era of polypharmacy, the balance of the dynamic and delicate endocrine system can easily be disturbed by interfering pharmaceutical agents like medications. Drugs can cause endocrine abnormalities via different mechanisms, including direct alteration of hormone production, changes in the regulation of the feedback axis, on hormonal transport, binding and signaling, as well as similar changes to counter-regulatory hormone systems. Furthermore, drugs can interfere with the hormonal assays, leading to erroneous laboratory results that disorientate clinicians from the right diagnosis. The purpose of this review is to cover a contemporary topic, the drug-induced endocrinopathies, which was presented in the monothematic annual Combo Endo Course 2018. This challenging part of endocrinology is constantly expanding particularly during the last decade, with the new oncological therapeutic agents, targeting novel molecular pathways in the process of malignancies. In this new context of drug-induced endocrine disease, clinicians should be aware that drugs can cause endocrine abnormalities via different mechanisms and mimic a variety of clinical scenarios. Therefore, it is extremely important for clinicians not only to promptly recognize drug-induced hormonal and metabolic abnormalities, but also to address the therapeutic issues for timely intervention. more...
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- 2019
9. 65 YEARS OF THE DOUBLE HELIX: Genetics informs precision practice in the diagnosis and management of pheochromocytoma
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Giuseppe Opocher, Helena Leijon, Martin K. Walz, Frederic Castinetti, Nelson Wohllk, Juri Ruf, Hartmut P. H. Neumann, Gianmaria Pennelli, Carsten Christof Boedeker, Ernst von Dobschuetz, Mariola Pęczkowska, Charis Eng, Attila Patócs, Harald Groeben, Jean-Pierre Bayley, William F. Young, Delmar M. Lourenço, Francesca Schiavi, Oliver Gimm, Dmitry Beltsevich, Birke Bausch, Tobias Krauss, Karina Villar Gómez de las Heras, Amit Tirosh, Marija Pfeifer, Thera P. Links, Arthur S. Tischler, Özer Makay, Joanne Ngeow, Nalini S. Shah, Albert-Ludwigs-Universität Freiburg, Mayo Clinic [Rochester], University of Freiburg [Freiburg], Universiteit Leiden, Familial Cancer Clinic, Veneto Institute of Oncology, IRCCS & Department of Medical and Surgical Sciences, Università degli Studi di Padova = University of Padua (Unipd), Tel Aviv University (TAU), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Kliniken Essen-Mitte, Gall, Valérie, Leiden University, Lee Kong Chian School of Medicine (LKCMedicine), Universita degli Studi di Padova, Tel Aviv University [Tel Aviv], HUSLAB, Department of Pathology, Medicum, Clinicum, University of Helsinki, and Ege Üniversitesi more...
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0301 basic medicine ,Cancer Research ,von Hippel-Lindau Disease ,Endocrinology, Diabetes and Metabolism ,Medizin ,NEUROFIBROMATOSIS TYPE-1 ,TUMOR-SUPPRESSOR GENE ,Bioinformatics ,0302 clinical medicine ,Endocrinology ,RENAL-CELL CARCINOMA ,Paraganglioma ,lipid metabolism ,oxidative stress ,Precision Medicine ,ENDOCRINE NEOPLASIA TYPE-2 ,Syndrome ,3. Good health ,SUCCINATE-DEHYDROGENASE ,Oncology ,030220 oncology & carcinogenesis ,Brown Adipose Tissue ,GERMLINE MUTATION CARRIERS ,medicine.medical_specialty ,Neurofibromatosis 1 ,ADRENAL-SPARING SURGERY ,3122 Cancers ,Context (language use) ,CASE SERIES ,Pheochromocytoma ,[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics ,HIPPEL-LINDAU-DISEASE ,03 medical and health sciences ,Germline mutation ,white adipose tissue ,Molecular genetics ,brown adipose tissue ,Endocrine Gland Neoplasms ,Genetic Predisposition to Disease ,Germ-Line Mutation ,Humans ,medicine ,RET PROTOONCOGENE ,Medicine [Science] ,Von Hippel–Lindau disease ,business.industry ,medicine.disease ,Precision medicine ,Lipid Metabolism ,Review article ,030104 developmental biology ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,business - Abstract
WOS: 000439200100008, PubMed ID: 29794110, Although the authors of the present review have contributed to genetic discoveries in the field of pheochromocytoma research, we can legitimately ask whether these advances have led to improvements in the diagnosis and management of patients with pheochromocytoma. The answer to this question is an emphatic Yes! In the field of molecular genetics, the well-established axiom that familial (genetic) pheochromocytoma represents 10% of all cases has been overturned, with >35% of cases now attributable to germline disease-causing mutations. Furthermore, genetic pheochromocytoma can now be grouped into five different clinical presentation types in the context of the ten known susceptibility genes for pheochromocytoma-associated syndromes. We now have the tools to diagnose patients with genetic pheochromocytoma, identify germline mutation carriers and to offer gene-informed medical management including enhanced surveillance and prevention. Clinically, we now treat an entire family of tumors of the paraganglia, with the exact phenotype varying by specific gene. In terms of detection and classification, simultaneous advances in biochemical detection and imaging localization have taken place, and the histopathology of the paraganglioma tumor family has been revised by immunohistochemical-genetic classification by gene-specific antibody immunohistochemistry. Treatment options have also been substantially enriched by the application of minimally invasive and adrenal-sparing surgery. Finally and most importantly, it is now widely recognized that patients with genetic pheochromocytoma/paraganglioma syndromes should be treated in specialized centers dedicated to the diagnosis, treatment and surveillance of this rare neoplasm. more...
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- 2018
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10. Preoperative medical treatment in Cushing's syndrome: frequency of use and its impact on postoperative assessment: data from ERCUSYN
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Elena Valassi, Holger Franz, Thierry Brue, Richard A Feelders, Romana Netea-Maier, Stylianos Tsagarakis, Susan M Webb, Maria Yaneva, Martin Reincke, Michael Droste, Irina Komerdus, Dominique Maiter, Darko Kastelan, Philippe Chanson, Marija Pfeifer, Christian J Strasburger, Miklós Tóth, Olivier Chabre, Michal Krsek, Carmen Fajardo, Marek Bolanowski, Alicia Santos, Peter J Trainer, John A H Wass, Antoine Tabarin, A Ambrogio, G Aranda, M Arosio, M Balomenaki, P Beck-Peccoz, C Berr-Kirmair, J Bollerslev, D Carvalho, F Cavagnini, E Christ, F Demtröder, J Denes, C Dimopoulou, A Dreval, T Dusek, E Erdinc, J A Evang, J Fazel, S Fica, E Ghigo, M Goth, Y Greenman, V Greisa, I Halperin, FA Hanzu, A Hermus, G Johannsson, P Kamenicky, A Kasperlik-Zaluska, J Kirchner, I Kraljevic, A Kruszynska, I Lambrescu, S Lang, A Luger, N Marpole, S Martin, M Martinie, O Moros, J Newell-Price, M Orbetzova, I Paiva, F Pecori Giraldi, A M Pereira, J Pickel, V Pirags, O Ragnarsson, A D Reghina, P Riesgo, M Roberts, S Roerink, O Roig, C Rowan, P Rudenko, M A Sahnoun, J Salvador, HA Sigurjonsdottir, T Skoric Polovina, R Smith, B Stachowska, G Stalla, J Tőke, E Ubina, S Vinay, M Wagenmakers, S Werner, J Young, P Zdunowski, K Zopf, S Zopp, I Zosin, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Internal Medicine, UCL - (SLuc) Service d'endocrinologie et de nutrition, and UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition more...
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Male ,Databases, Factual ,Endocrinology, Diabetes and Metabolism ,Cushing syndrome ,0302 clinical medicine ,Endocrinology ,Quality of life ,Interquartile range ,Adrenal Glands ,030212 general & internal medicine ,Postoperative Period ,Cushing Syndrome ,Medical treatment ,General Medicine ,Middle Aged ,3. Good health ,Adult ,Aged ,Europe ,Female ,Humans ,Ketoconazole ,Metyrapone ,Paraneoplastic Endocrine Syndromes ,Pituitary Gland ,Postoperative Care ,Quality of Life ,Treatment Outcome ,Diabetes and Metabolism ,medicine.drug ,medicine.medical_specialty ,Frequency of use ,030209 endocrinology & metabolism ,Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] ,03 medical and health sciences ,Databases ,All institutes and research themes of the Radboud University Medical Center ,Internal medicine ,medicine ,Factual ,S syndrome ,business.industry ,medicine.disease ,Surgery ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,business - Abstract
Background Surgery is the definitive treatment of Cushing’s syndrome (CS) but medications may also be used as a first-line therapy. Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial. Objective (1) Evaluate how frequently PMT is given to CS patients across Europe; (2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery and (3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS). Patients and methods 1143 CS patients entered into the ERCUSYN database from 57 centers in 26 countries. Sixty-nine percent had PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS) and 1% were classified as having CS from other causes (OTH-CS). Results Twenty per cent of patients took PMT. ECT-CS and PIT-CS were more likely to receive PMT compared to ADR-CS (P P P P Conclusions PMT may confound the interpretation of immediate postoperative outcome. Follow-up is recommended to definitely evaluate surgical results. more...
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- 2018
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11. The penetrance of MEN2 pheochromocytoma is not only determined by
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Frederic, Castinetti, Ana Luiza, Maia, Mariola, Peczkowska, Marta, Barontini, Kornelia, Hasse-Lazar, Thera P, Links, Rodrigo A, Toledo, Sarka, Dvorakova, Caterina, Mian, Maria Joao, Bugalho, Stefania, Zovato, Maria, Alevizaki, Andrei, Kvachenyuk, Birke, Bausch, Paola, Loli, Simona R, Bergmann, Attila, Patocs, Marija, Pfeifer, Josefina Biarnes, Costa, Ernst, von Dobschuetz, Claudio, Letizia, Gerlof, Valk, Marcin, Barczynski, Malgorzata, Czetwertynska, John T M, Plukker, Paola, Sartorato, Tomas, Zelinka, Petr, Vlcek, Svetlana, Yaremchuk, Georges, Weryha, Letizia, Canu, Nelson, Wohllk, Frederic, Sebag, Martin K, Walz, Charis, Eng, and Hartmut P H, Neumann more...
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Adult ,Aged, 80 and over ,Male ,Adolescent ,Proto-Oncogene Proteins c-ret ,Adrenal Gland Neoplasms ,Multiple Endocrine Neoplasia Type 2a ,Penetrance ,Exons ,Pheochromocytoma ,Middle Aged ,Young Adult ,Mutation ,Humans ,Female ,Child ,Aged - Published
- 2017
12. Diagnostic tests for Cushing's syndrome differ from published guidelines: data from ERCUSYN
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Elena Valassi, Holger Franz, Thierry Brue, Richard A Feelders, Romana Netea-Maier, Stylianos Tsagarakis, Susan M Webb, Maria Yaneva, Martin Reincke, Michael Droste, Irina Komerdus, Dominique Maiter, Darko Kastelan, Philippe Chanson, Marija Pfeifer, Christian J Strasburger, Miklós Tóth, Olivier Chabre, Antoine Tabarin, Michal Krsek, Carmen Fajardo, Marek Bolanowski, Alicia Santos, John A H Wass, Peter J Trainer, and Internal Medicine more...
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Adult ,Male ,medicine.medical_specialty ,Hydrocortisone ,Endocrinology, Diabetes and Metabolism ,Statistics as Topic ,030209 endocrinology & metabolism ,Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] ,Diagnostic tools ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Adrenocorticotropic Hormone ,Internal medicine ,Urinary free cortisol ,medicine ,Humans ,In patient ,Registries ,Cushing Syndrome ,Salivary cortisol ,Aged ,S syndrome ,Diagnostic Tests, Routine ,business.industry ,Diagnostic test ,General Medicine ,Middle Aged ,Europe ,030220 oncology & carcinogenesis ,Dexamethasone suppression test ,Practice Guidelines as Topic ,Female ,business ,Serum cortisol - Abstract
Objective To evaluate which tests are performed to diagnose hypercortisolism in patients included in the European Registry on Cushing’s syndrome (ERCUSYN), and to examine if their use differs from the current guidelines. Patients and methods We analyzed data on the diagnostic tests performed in 1341 patients with Cushing’s syndrome (CS) who have been entered into the ERCUSYN database between January 1, 2000 and January 31, 2016 from 57 centers in 26 European countries. Sixty-seven percent had pituitary-dependent CS (PIT-CS), 24% had adrenal-dependent CS (ADR-CS), 6% had CS from an ectopic source (ECT-CS) and 3% were classified as having CS from other causes (OTH-CS). Results Of the first-line tests, urinary free cortisol (UFC) test was performed in 78% of patients, overnight 1 mg dexamethasone suppression test (DST) in 60% and late-night salivary cortisol (LSaC) in 25%. Use of LSaC increased in the last five years as compared with previous years (P P P Conclusions Use of diagnostic tests for CS varies across Europe and partly differs from the currently available guidelines. It would seem pertinent that a European consensus be established to determine the best diagnostic approach to CS, taking into account specific inter-country differences with regard to the availability of diagnostic tools. more...
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- 2017
13. Short-term intervention with liraglutide improved eating behavior in obese women with polycystic ovary syndrome
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Marija Pfeifer, Andrej Janez, Tomaz Kocjan, Nika Aleksandra Kravos, and Mojca Jensterle
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Adult ,Blood Glucose ,medicine.medical_specialty ,Waist ,Adipose tissue ,Intra-Abdominal Fat ,Body Mass Index ,Young Adult ,Endocrinology ,Intervention (counseling) ,Internal medicine ,medicine ,Humans ,Hypoglycemic Agents ,Insulin ,Obesity ,Liraglutide ,business.industry ,Body Weight ,digestive, oral, and skin physiology ,Feeding Behavior ,General Medicine ,medicine.disease ,Polycystic ovary ,Metformin ,Eating behavior ,Female ,Waist Circumference ,business ,Polycystic Ovary Syndrome ,medicine.drug - Abstract
Glucagon-like peptide 1 receptor agonists (GLP-1 RA) stimulate satiety leading to reductions in food intake and body weight. The effects of long- acting GLP-1 RA liraglutide on eating behavior of women with PCOS have not been investigated yet.Thirty-six obese women with PCOS (mean ± SD, aged 31.2 ± 7.8 years, with BMI 38.7 ± 0.1 kg/m(2)), pretreated with metformin (1000 mg BID) were switched to liraglutide 1.2 mg QD sc for 12 weeks. Adiposity parameters and eating behavior as assessed by Three-Factor Eating Questionnaire (TFEQ-R18) were examined at baseline and after 12 weeks.Subjects treated with liraglutide lost on average 3.8 ± 0.1 kg (p 0.001). Significant reductions of waist circumference and visceral adipose tissue (VAT) mass, volume and area were demonstrated from liraglutide induction to the end of the study. TFEQ-R18 scores were significantly different pre- and post-liraglutide intervention. After treatment with liraglutide the uncontrolled eating (UE) score decreased from 36.8 ± 24.5 to 19.6 ± 18.4 (p 0.001) and emotional eating (EE) score decreased from 49.9 ± 33.3 to 28.5 ± 26.9 (p 0.001). Scores for cognitive restraint (CR) were not changed.Short-term liraglutide treatment was associated with weight loss and significantly improved eating behavior in obese women with PCOS. more...
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- 2014
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14. Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin
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Nika Aleksandra Kravos, Marija Pfeifer, Andrej Janez, Mojca Jensterle Sever, and Tomaz Kocjan
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Adult ,medicine.medical_specialty ,Waist ,Nausea ,Endocrinology, Diabetes and Metabolism ,Glucagon-Like Peptide-1 Receptor ,Endocrinology ,Glucagon-Like Peptide 1 ,Weight loss ,Internal medicine ,Weight Loss ,Receptors, Glucagon ,medicine ,Humans ,Obesity ,Prospective cohort study ,Liraglutide ,business.industry ,Body Weight ,General Medicine ,medicine.disease ,Polycystic ovary ,Metformin ,Clinical Study ,Female ,Waist Circumference ,medicine.symptom ,business ,medicine.drug - Abstract
ObjectiveThe effect of metformin on weight reduction in polycystic ovary syndrome (PCOS) is often unsatisfactory. In this study, we investigated the potential add-on effect of treatment with the glucagon-like peptide-1 receptor agonist liraglutide on weight loss in obese nondiabetic women with PCOS who had lost MethodsA total of 40 obese women with PCOS, who had been pretreated with metformin for at least 6 months, participated in a 12-week open-label, prospective study. They were randomized to one of three treatment arms: metformin (MET) arm 1000 mg BID, liraglutide (LIRA) arm 1.2 mg QD s.c., or combined MET 1000 mg BID and LIRA (COMBI) 1.2 mg QD s.c. Lifestyle intervention was not actively promoted. The primary outcome was change in body weight.ResultsThirty six patients (aged 31.3±7.1 years, BMI 37.1±4.6 kg/m2) completed the study: 14 on MET, 11 on LIRA, and 11 on combined treatment. COMBI therapy was superior to LIRA and MET monotherapy in reducing weight, BMI, and waist circumference. Subjects treated with COMBI lost on average 6.5±2.8 kg compared with a 3.8±3.7 kg loss in the LIRA group and a 1.2±1.4 kg loss in the MET group (PPP=0.029). Subjects treated with liraglutide experienced more nausea than those treated with metformin, but severity of nausea decreased over time and did not correlate with weight loss.ConclusionsShort-term combined treatment with liraglutide and metformin was associated with significant weight loss and decrease in waist circumference in obese women with PCOS who had previously been poor responders regarding weight reduction on metformin monotherapy. more...
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- 2014
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15. Variations inPROKR2, But NotPROK2, Are Associated With Hypopituitarism and Septo-optic Dysplasia
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Philippe Rondard, Oualid Sbai, Marija Pfeifer, Carles Gaston-Massuet, Yasufumi Shigeyoshi, Mehul T. Dattani, Louise C. Gregory, Tony Hulse, Mark J. McCabe, Nelly Pitteloud, Koh-hei Masumoto, Kyriaki S. Alatzoglou, Mamoru Nagano, Charles R. Buchanan, Vaitsa Tziaferi, and Juan Pedro Martinez-Barbera more...
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Male ,Kallmann syndrome ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Hypopituitarism ,Biochemistry ,Receptors, G-Protein-Coupled ,Cohort Studies ,Mice ,0302 clinical medicine ,Endocrinology ,Septo-Optic Dysplasia ,Child ,Mice, Knockout ,0303 health sciences ,JCEM Online: Advances in Genetics ,Homozygote ,Pedigree ,3. Good health ,Phenotype ,Child, Preschool ,Female ,medicine.symptom ,Heterozygote ,Hypothalamo-Hypophyseal System ,medicine.medical_specialty ,Genotype ,Receptors, Peptide ,Anosmia ,Context (language use) ,Biology ,Gastrointestinal Hormones ,03 medical and health sciences ,Hypogonadotropic hypogonadism ,Internal medicine ,medicine ,Animals ,Humans ,Genetic Testing ,030304 developmental biology ,Neuropeptides ,Biochemistry (medical) ,Infant, Newborn ,Infant ,Heterozygote advantage ,Septo-optic dysplasia ,Kallmann Syndrome ,medicine.disease ,HEK293 Cells ,Dysplasia ,030217 neurology & neurosurgery - Abstract
Context: Loss-of-function mutations in PROK2 and PROKR2 have been implicated in Kallmann syndrome (KS), characterized by hypogonadotropic hypogonadism and anosmia. Recent data suggest overlapping phenotypes/genotypes between KS and congenital hypopituitarism (CH), including septo-optic dysplasia (SOD). Objective: We screened a cohort of patients with complex forms of CH (n = 422) for mutations in PROK2 and PROKR2. Results: We detected 5 PROKR2 variants in 11 patients with SOD/CH: novel p.G371R and previously reported p.A51T, p.R85L, p.L173R, and p.R268C—the latter 3 being known functionally deleterious variants. Surprisingly, 1 patient with SOD was heterozygous for the p.L173R variant, whereas his phenotypically unaffected mother was homozygous for the variant. We sought to clarify the role of PROKR2 in hypothalamopituitary development through analysis of Prokr2−/− mice. Interestingly, these revealed predominantly normal hypothalamopituitary development and terminal cell differentiation, with the exception of reduced LH; this was inconsistent with patient phenotypes and more analogous to the healthy mother, although she did not have KS, unlike the Prokr2−/− mice. Conclusions: The role of PROKR2 in the etiology of CH, SOD, and KS is uncertain, as demonstrated by no clear phenotype-genotype correlation; loss-of-function variants in heterozygosity or homozygosity can be associated with these disorders. However, we report a phenotypically normal parent, homozygous for p.L173R. Our data suggest that the variants identified herein are unlikely to be implicated in isolation in these disorders; other genetic or environmental modifiers may also impact on the etiology. Given the phenotypic variability, genetic counseling may presently be inappropriate. more...
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- 2013
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16. The European Registry on Cushing's syndrome: 2-year experience. Baseline demographic and clinical characteristics
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Elena, Valassi, Alicia, Santos, Maria, Yaneva, Miklós, Tóth, Christian J, Strasburger, Philippe, Chanson, John A H, Wass, Olivier, Chabre, Marija, Pfeifer, Richard A, Feelders, Stylianos, Tsagarakis, Peter J, Trainer, Holger, Franz, Kathrin, Zopf, Sabina, Zacharieva, Steven W J, Lamberts, Antoine, Tabarin, Susan M, Webb, I, Zosin, and Internal Medicine more...
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Visual analogue scale ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Adrenal Gland Neoplasms ,Cohort Studies ,Fractures, Bone ,Endocrinology ,SDG 3 - Good Health and Well-being ,Internal medicine ,Prevalence ,medicine ,Humans ,Pituitary Neoplasms ,Prospective Studies ,Registries ,Prospective cohort study ,Cushing Syndrome ,hirsutism ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Retrospective cohort study ,General Medicine ,Middle Aged ,medicine.disease ,Europe ,Bone Diseases, Metabolic ,Quality of Life ,Etiology ,Female ,medicine.symptom ,business ,Weight gain ,Cohort study - Abstract
ObjectiveThe European Registry on Cushing's syndrome (ERCUSYN) is designed to collect prospective and follow-up data at EU level on Cushing's syndrome (CS).Design and methodsBaseline data on 481 CS patients (390 females, 91 males; mean age (±s.d.): 44±14 years) collected from 36 centres in 23 countries, including new patients from 2008 and retrospective cases since 2000. Patients were divided into four major aetiologic groups: pituitary-dependent CS (PIT-CS) (66%), adrenal-dependent CS (ADR-CS) (27%), CS from an ectopic source (ECT-CS) (5%) and CS from other aetiologies (2%).ResultsProportion of men in the ECT-CS group was higher than in the other groups (PPPPPPPPPPPPConclusionsThe ERCUSYN project demonstrates a heterogeneous clinical presentation of CS at a European level, depending on gender and aetiology. more...
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- 2011
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17. XbaI polymorphism of the estrogen receptor alpha gene influences the effect of raloxifene on the endothelial function
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Branka Žegura, Marija Pfeifer, Janja Marc, Andrej Zavratnik, and Janez Preželj
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Selective Estrogen Receptor Modulators ,medicine.medical_specialty ,medicine.drug_class ,Estrogen receptor ,General Biochemistry, Genetics and Molecular Biology ,Internal medicine ,medicine ,Humans ,Raloxifene ,Prospective Studies ,Vascular Diseases ,Estrogen receptor beta ,Aged ,Polymorphism, Genetic ,business.industry ,Estrogen Receptor alpha ,Obstetrics and Gynecology ,Middle Aged ,Intercellular Adhesion Molecule-1 ,medicine.disease ,Vasodilation ,Menopause ,Endocrinology ,Selective estrogen receptor modulator ,Estrogen ,Raloxifene Hydrochloride ,Osteoporosis ,Female ,Endothelium, Vascular ,E-Selectin ,business ,XX Genotype ,Estrogen receptor alpha ,medicine.drug - Abstract
Objectives Cardiovascular disease is the leading cause of death in postmenopausal women and estrogen deficiency may be an important factor in its development. The selective estrogen receptor modulator, raloxifene, exerts a part of its actions through the estrogen receptor alpha (ESR1) activation. We explored if polymorphisms of the ESR1 modify the effects of 6 months raloxifene treatment on endothelial function. Methods A total of 53 postmenopausal women, mean age 59.7 ± 6.2, finished the prospective clinical trial. The PvuII, XbaI, and P325P polymorphisms of the ESR1 gene were analyzed. In all subjects endothelium-dependent flow mediated dilatation (FMD) and cell adhesion molecules (CAM) ICAM-1, VCAM-1 and E-selectin were measured before and after 6 months of raloxifene treatment. Results There was no difference in FMD between the ESR1 genotypes, at baseline. After raloxifene treatment, the FMD was significantly greater in subjects with XX genotype of XbaI polymorphism compared to xx (p = 0.03) and borderline greater when compared to Xx genotype (p = 0.053). The FMD increased significantly with raloxifene treatment in women with Xx genotype of XbaI and Pp genotype of PvuII polymorphisms (p = 0.027 and p = 0.034, respectively). The P325P polymorphism did not influence the FMD after raloxifene. None of the ESR1 gene polymorphisms had any impact on the levels of CAM before or after the treatment. When analysing the whole group, a significant decrease in E-selectin (p more...
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- 2010
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18. Impact of metformin and rosiglitazone treatment on glucose transporter 4 mRNA expression in women with polycystic ovary syndrome
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Janja Marc, Mojca Jensterle, Marija Pfeifer, Janez Prezelj, Barbara Mlinar, and Andrej Janez
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Adult ,medicine.medical_specialty ,Time Factors ,Adolescent ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Gene Expression ,Adipose tissue ,Biology ,Rosiglitazone ,chemistry.chemical_compound ,Endocrinology ,Insulin resistance ,Internal medicine ,Adipocyte ,medicine ,Humans ,Hypoglycemic Agents ,RNA, Messenger ,Analysis of Variance ,Glucose Transporter Type 4 ,Reverse Transcriptase Polymerase Chain Reaction ,Insulin ,General Medicine ,medicine.disease ,Polycystic ovary ,Metformin ,chemistry ,Androgens ,biology.protein ,Female ,Thiazolidinediones ,Insulin Resistance ,GLUT4 ,Polycystic Ovary Syndrome ,medicine.drug - Abstract
ObjectiveThe insulin-resistant state of the polycystic ovary syndrome (PCOS) was found to be associated with a decreased glucose transporter GLUT4 expression in the insulin target tissues. This study was performed to explore whether the well-known clinical, hormonal and metabolic efficacy of metformin or rosiglitazone treatment is reflected in the modulation of adipocyte GLUT4 mRNA expression in patients with PCOS.MethodsWe enrolled 35 women with PCOS. They received either metformin or rosiglitazone for 6 months. A history, blood samples for the measurement of androgens and s.c. adipose tissue samples were taken at baseline and end point. Quantification of GLUT4 mRNA expression in adipose tissue was performed using real-time quantitative PCR. Homeostasis model assessment (HOMAIR) score calculation was applied as a measure for insulin resistance (IR).ResultsGLUT4 mRNA expression in adipose tissue increased significantly in both groups (PP=0.040). There was a statistically significant improvement of HOMAIRin both groups (P=0.008). After treatment, frequencies of menstrual bleeding were significantly higher (PP=0.001).ConclusionsA 6-month therapy with insulin sensitizers resulted in marked improvement in adipose tissue GLUT4 mRNA expression in PCOS patients, rosiglitazone being more effective when compared with metformin. The augmentation of the insulin signal transduction was accompanied by a significant improvement of HOMAIR, menstrual pattern and androgen profile. more...
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- 2008
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19. Decreased Androgen Levels and Improved Menstrual Pattern after Angiotensin II Receptor Antagonist Telmisartan Treatment in Four Hypertensive Patients with Polycystic Ovary Syndrome: Case Series
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Bojan Vrtovec, Helena Meden-Vrtovec, Marija Pfeifer, Tomaz Kocjan, Andrej Janez, Janez Prezelj, and Mojca Jensterle
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Adult ,Blood Glucose ,medicine.medical_specialty ,medicine.drug_class ,Case Report ,Blood Pressure ,Angiotensin II receptor antagonist ,Benzoates ,Body Mass Index ,chemistry.chemical_compound ,Dehydroepiandrosterone sulfate ,Insulin resistance ,Internal medicine ,medicine ,Humans ,Obesity ,Telmisartan ,Testosterone ,business.industry ,Fasting ,General Medicine ,Androgen ,medicine.disease ,Polycystic ovary ,Menstruation ,Treatment Outcome ,Blood pressure ,Endocrinology ,chemistry ,Hypertension ,Androgens ,Benzimidazoles ,Female ,business ,Angiotensin II Type 1 Receptor Blockers ,Polycystic Ovary Syndrome ,medicine.drug - Abstract
We describe 4 consecutive hypertensive women with polycystic ovary syndrome, classified according to the National Institute of Child Health and Human Development (NICHD) criteria, treated with telmisartan 40 mg/d for six months. Blood pressure, menstrual pattern, body mass index (BMI), homeostasis model assessment of insulin resistance, testosterone, dehydroepiandrosterone sulfate (DHEAS), and androstenedione were recorded and measured before and after telmisartan treatment. Obese hypertensive polycystic ovary syndrome patients had a decrease in systolic blood pressure. Marked drop-off in serum androgen concentrations was observed in all four patients. Three patients improved their menstrual cyclicity. The improvements were independent of changes in weight. The reduction of androgen concentrations and improvement in menstrual pattern was achieved despite a non-significant change of fasting insulin levels in patients, who were not considered severely insulin resistant at baseline. These findings may provide a new basis for a proper choice of the antihypertensive drug in hypertensive women with polycystic ovary syndrome. more...
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- 2007
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20. Comparison of different methods investigating functional and morphological markers of early atherogenesis in obese women with polycystic ovary syndrome
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Mateja K, Jezovnik, Mojca, Jensterle Sever, Andrej, Janez, Marija, Pfeifer, Ana, Spirkoska, Nika A, Kravos, and Pavel, Poredos
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Adult ,Carotid Artery Diseases ,Brachial Artery ,Manometry ,Hemodynamics ,Pulse Wave Analysis ,Prognosis ,Carotid Intima-Media Thickness ,Vasodilation ,Peripheral Arterial Disease ,Young Adult ,Carotid Arteries ,Early Diagnosis ,Vascular Stiffness ,Predictive Value of Tests ,Regional Blood Flow ,Vasoconstriction ,Humans ,Female ,Endothelium, Vascular ,Obesity ,Blood Flow Velocity ,Polycystic Ovary Syndrome - Abstract
The prognostic importance of preclinical markers of atherosclerosis and their interrelationship are inconclusive. In this study interrelationship between different methods investigating endothelial function and intima media thickness (IMT) was investigated in patients with polycystic ovary syndrome (PCOS).Endothelial function was assessed by endothelium-dependent flow-mediated dilation (FMD), nitrate-mediated dilation (NMD), low-flow-mediated constriction (L-FMC) and peripheral arterial tonometry (PAT). Arterial stiffness was determined by pulse wave velocity (PWV) and the Augmentation Index (AI). The IMT of carotid arteries was measured.Twenty-eight obese women were recruited with the diagnosis of PCOS, mean age 27±7.2 years and Body Mass Index 38.8±6.3 kg/m2. A relationship between FMD and NMD (r=0.44, P=0.02) was shown. FMD as well as NMD of the brachial artery were not correlated with L-FMC or PAT. The AI and PWV, indicators of arterial stiffness were not interrelated with FMD, and there was no significant interrelationship between IMT and FMD or NMD. The AI was related only to IMT (r=0.45, P=0.30).The relationship between available methods for evaluation of endothelial function/dysfunction is weak in PCOS. This indicates that different methods investigate different mechanisms and various sections of the circulatory system. more...
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- 2015
21. Identifying the Deleterious Effect of Rare LHX4 Allelic Variants, a Challenging Issue
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Frederic Castinetti, Alain Enjalbert, Alexandru Saveanu, Marija Pfeifer, Claire Rochette, Emmanuelle Caldagues, Thierry Brue, Debora Braslavsky, Nicolas Jullien, James P. Herman, Ignacio Bergadá, Anne Barlier, Rachel Reynaud, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'endocrinologie moléculaire, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Department of pediatric endocrinology, Centre hospitalier universitaire de Nantes (CHU Nantes), Centro de Investigaciones Endocrinologicas (CEDIE), Hospital de Ninos Ricardo Guttierrez, Department Endocrinology, and Univ med center Ljubjana more...
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Male ,Heterozygote ,Mutant ,LIM-Homeodomain Proteins ,lcsh:Medicine ,Thyrotropin ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Biology ,HYPOPITUITARISM ,medicine.disease_cause ,Adrenocorticotropic Hormone ,medicine ,Consensus sequence ,Humans ,Allele ,lcsh:Science ,Child ,Gene ,MUTATION ,Alleles ,Genetics ,Mutation ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Multidisciplinary ,Point mutation ,lcsh:R ,Wild type ,Infant ,Promoter ,Molecular biology ,GENE ,HEK293 Cells ,Child, Preschool ,Growth Hormone ,SURVIVAL ,PITUITARY-HORMONE DEFICIENCY ,lcsh:Q ,Female ,PROP1 ,Transcription Factors ,Research Article - Abstract
International audience; LHX4 is a LIM homeodomain transcription factor involved in the early steps of pituitary ontogenesis. To date, 8 heterozygous LHX4 mutations have been reported as responsible of combined pituitary hormone deficiency (CPHD) in Humans. We identified 4 new LHX4 heterozygous allelic variants in patients with congenital hypopituitarism: W204X, delK242, N271S and Q346R. Our objective was to determine the role of LHX4 variants in patients' phenotypes. Heterologous HEK293T cells were transfected with plasmids encoding for wild-type or mutant LHX4. Protein expression was analysed by Western Blot, and DNA binding by electro-mobility shift assay experiments. Target promoters of LHX4 were cotransfected with wild type or mutant LHX4 to test the transactivating abilities of each variant. Our results show that the W204X mutation was associated with early GH and TSH deficiencies and later onset ACTH deficiency. It led to a truncated protein unable to bind to alpha-Gsu promoter binding consensus sequence. W204X was not able to activate target promoters in vitro. Cotransfection experiments did not favour a dominant negative effect. In contrast, all other mutants were able to bind the promoters and led to an activation similar as that observed with wild type LHX4, suggesting that they were likely polymorphisms. To conclude, our study underlines the need for functional in vitro studies to ascertain the role of rare allelic variants of LHX4 in disease phenotypes. It supports the causative role of the W204X mutation in CPHD and adds up childhood onset ACTH deficiency to the clinical spectrum of the various phenotypes related to LHX4 mutations. more...
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- 2015
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22. A 12-week treatment with the long-acting glucagon-like peptide 1 receptor agonist liraglutide leads to significant weight loss in a subset of obese women with newly diagnosed polycystic ovary syndrome
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Andrej Janez, Marija Pfeifer, Nika Aleksandra Kravos, Mojca Jensterle, and Tomaz Kocjan
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Adult ,Blood Glucose ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Incretins ,Body Mass Index ,Young Adult ,Weight loss ,Internal medicine ,Diabetes mellitus ,Weight Loss ,medicine ,Humans ,Hypoglycemic Agents ,Obesity ,Glucagon-like peptide 1 receptor ,Liraglutide ,business.industry ,Body Weight ,nutritional and metabolic diseases ,General Medicine ,medicine.disease ,Polycystic ovary ,Metformin ,Endocrinology ,Treatment Outcome ,Female ,Metabolic syndrome ,medicine.symptom ,business ,Body mass index ,medicine.drug ,Polycystic Ovary Syndrome - Abstract
The long-acting glucagon-like peptide 1 receptor agonist liraglutide is linked to progressive and sustained weight loss in obese people with diabetes. However, its efficacy and safety in women with polycystic ovary syndrome (PCOS) has not yet been addressed.Thirty-two obese women (aged 27.6±7.2 years, BMI 39.5±6.2 kg/m(2)) with newly diagnosed PCOS were randomized to receive either liraglutide 1.2 mg QD sc (n=17) or metformin 1000 mg BID po (n=15) for 12 weeks; 28 patients completed the study (14 on liraglutide and 14 on metformin). The main outcome was change in body weight.Intention-to-treat analysis showed significant BMI (-0.98 kg/m(2); p0.001), body weight (-2.52 kg; p0.001), waist circumference (-3.38 cm; p0.001) and whole-body fat mass (-1.26%; p0.001) reduction in both treatment arms without significant differences between therapeutic groups. However, in a subgroup of patients (n=9) with insulin resistance (HOMA(IR)2), severe obesity and higher odds ratio for the metabolic syndrome (OR=3.9), the patients fared much better with liraglutide than with metformin (mean BMI decreased 2.13 kg/m(2) vs. 0.62 kg/m(2), respectively).Short-term liraglutide treatment was associated with significant weight loss in a subset of obese patients with newly diagnosed PCOS and a higher metabolic risk profile. more...
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- 2015
23. The polycystic ovary syndrome: a position statement from the European Society of Endocrinology
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Alessandra Gambineri, Michel Pugeat, Djuro Macut, Bulent O. Yildiz, Marija Pfeifer, Gerard S. Conway, Héctor F. Escobar-Morreale, Didier Dewailly, Evanthia Diamanti-Kandarakis, Stephen Franks, Fahrettin Kelestimur, Renato Pasquali, Dragan Micic, Duarte Pignatelli, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Conway, Gerard, Dewailly, Didier, Diamanti-Kandarakis, Evanthia, Escobar-Morreale, Héctor F, Franks, Stephen, Gambineri, Alessandra, Kelestimur, Fahrettin, Macut, Djuro, Micic, Dragan, Pasquali, Renato, Pfeifer, Marija, Pignatelli, Duarte, Pugeat, Michel, Yildiz, Bulent O., İç Hastalıkları, Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA) more...
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endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Concept Formation ,[SDV]Life Sciences [q-bio] ,Ovarian Disorder ,Bariatric Surgery ,Type 2 diabetes ,Gonadal Steroid Hormone ,Androgen ,0302 clinical medicine ,Endocrinology ,Cardiovascular Disease ,Glucose/metabolism ,Testosterone ,Gonadal Steroid Hormones ,Ultrasonography ,Polycystic Ovary ,Cardiovascular Diseases/*etiology/metabolism/prevention & control ,Female/*etiology/metabolism/therapy ,030219 obstetrics & reproductive medicine ,Medicine (all) ,General Medicine ,Polycystic ovary ,female genital diseases and pregnancy complications ,3. Good health ,Obesity/complications/*etiology/metabolism/therapy ,Phenotype ,Cardiovascular Diseases ,Androgens ,Body Composition ,Female ,Gonadal Steroid Hormones/metabolism ,Infertility, Female ,Human ,Polycystic Ovary Syndrome ,medicine.medical_specialty ,Ovary/*metabolism/*pathology/ultrasonography ,030209 endocrinology & metabolism ,Hypoglycemic Agents/therapeutic use ,Endocrinology & Metabolism ,03 medical and health sciences ,Insulin resistance ,Quality of life (healthcare) ,Testosterone/*metabolism ,Internal medicine ,Glucose Intolerance ,medicine ,Hypoglycemic Agents ,Humans ,Obesity ,Androgens/*metabolism ,Hypoglycemic Agent ,business.industry ,Genetic heterogeneity ,Ovary ,Biomarker ,medicine.disease ,Glucose Intolerance/etiology/metabolism ,Syndrome/complications/diagnosis/etiology/metabolism/psychology/therapy ,Glucose ,Clinical research ,Infertility ,Quality of Life ,Lipid Peroxidation ,Insulin Resistance ,business ,Risk Reduction Behavior ,Biomarkers ,Biomarkers/blood - Abstract
International audience; Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS. more...
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- 2014
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24. European survey of diagnosis and management of the polycystic ovary syndrome: results of the ESE PCOS Special Interest Group's Questionnaire
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Alessandra Gambineri, Fahrettin Kelestimur, Renato Pasquali, Duarte Pignatelli, Djuro Macut, Steven Franks, Marija Pfeifer, Gerard S. Conway, Dragan Micic, Evanthia Diamanti-Kandarakis, Bulent O. Yildiz, Didier Dewailly, Michel Pugeat, Héctor F. Escobar-Morreale, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), İç Hastalıkları, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Conway, Gerard, Dewailly, Didier, Diamanti-Kandarakis, Evanthia, Escobar-Morreale, Hector F, Franks, Steven, Gambineri, Alessandra, Kelestimur, Fahrettin, Macut, Djuro, Micic, Dragan, Pasquali, Renato, Pfeifer, Marija, Pignatelli, Duarte, Pugeat, Michel, and Yildiz, Bulent O. more...
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Male ,Hirsutism ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,[SDV]Life Sciences [q-bio] ,Type 2 diabetes ,Practice Patterns ,Androgen ,0302 clinical medicine ,Endocrinology ,Surveys and Questionnaires ,Diagnosis ,Surveys and Questionnaire ,Testosterone ,Practice Patterns, Physicians' ,hirsutism ,Menstruation Disturbances ,Societies, Medical ,030219 obstetrics & reproductive medicine ,Medicine (all) ,Oral/administration & dosage ,Contraceptives ,General Medicine ,Middle Aged ,Polycystic ovary ,female genital diseases and pregnancy complications ,Metformin ,3. Good health ,Europe ,Androgens ,Physicians'/*statistics & numerical data ,Female ,Human ,medicine.drug ,Polycystic Ovary Syndrome ,Infertility ,Adult ,medicine.medical_specialty ,Menstruation Disturbance ,education ,Hirsutism/*etiology ,030209 endocrinology & metabolism ,Hypoglycemic Agents/therapeutic use ,Female/therapeutic use ,Fertility Agents ,Clomiphene ,Diagnosis, Differential ,03 medical and health sciences ,Endocrinology & Metabolism ,Internal medicine ,Medical ,medicine ,Menstruation Disturbances/*etiology ,Humans ,Hypoglycemic Agents ,Metformin/therapeutic use ,Polycystic Ovary Syndrome/blood/*diagnosis/*therapy ,Clomiphene/therapeutic use ,Hypoglycemic Agent ,Free androgen index ,business.industry ,Hyperandrogenism/blood/*etiology ,Hyperandrogenism ,Biomarker ,Fertility Agents, Female ,medicine.disease ,Obesity ,Health Care Survey ,Androgens/blood ,Health Care Surveys ,Differential ,business ,Societies ,Testosterone/blood ,Risk Reduction Behavior ,Biomarkers/blood ,Biomarkers ,Contraceptives, Oral - Abstract
BackgroundThere is evidence for differences between endocrinologists and other specialists in their approach to diagnosis and management of the polycystic ovary syndrome (PCOS).ObjectiveA mailed survey consisting of a simple questionnaire aiming to understand current practice for diagnosis and management of the PCOS by specialists across Europe.MethodsThe questionnaire consisted of 23 questions grouped to achieve information on i) the general characteristics of the respondents, ii) patients with PCOS seen by endocrinologists, iii) the main diagnostic criteria, iv) biochemical parameters used in the differential diagnosis of hyperandrogenism, v) long-term concerns, and, finally vi) treatment choices. A total of 357 questionnaires representing 13.3% of the members of European Society of Endocrinology (ESE) were available for final analysis; 93% of the respondents were endocrinologistsResultsIn relation to the diagnostic criteria, respondents were most likely to select menstrual irregularity as the most frequent criteria used for the diagnosis of PCOS although very high rates were achieved for the use of hirsutism and biochemical hyperandrogenism. It therefore appears that the NIH criteria were followed by the majority of respondents. The most frequent biochemical parameters in the differential diagnosis of hyperandrogenism were total testosterone or free androgen index. Obesity and type 2 diabetes were regarded as the principal long-term concerns for PCOS. The most common treatments for patients with PCOS were metformin (33%), lifestyle modification (25%), and oral contraceptives (22%). More direct treatments of infertility include clomiphene citrate alone or in combination with metformin, prescribed by 9 and 23%, respectively, whereas only 6% used other methods for induction of ovulation.ConclusionThe survey produced by ESE is a good start for evaluating the perspective in the diagnosis and treatment of PCOS by endocrinologists in Europe. more...
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- 2014
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25. Outcomes of adrenal-sparing surgery or total adrenalectomy in phaeochromocytoma associated with multiple endocrine neoplasia type 2: an international retrospective population-based study
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Luigi Petramala, Thera P. Links, Josefina Biarnes Costa, Sergio P. A. Toledo, Thomas Cuny, Petr Vlcek, Maria Alevizaki, Ana Luiza Maia, Károly Rácz, Martin K. Walz, Mariola Pęczkowska, Nelson Wohllk, Bernard Conte-Devolx, Xiao Ping Qi, Paola Loli, Hans H G Verbeek, Marcin Barczyński, Michael Brauckhoff, Maria João Bugalho, Andrzej Januszewicz, Charis Eng, Giuseppe Opocher, Oleg Kollyukh, Francesca Schiavi, Thierry Brue, Gabriela Sanso, Nalini S. Shah, Dmitry Zabolotnyi, Lea Demarquet, Mònica Recasens, Paola Sartorato, Ernst von Dobschuetz, Marija Pfeifer, Kornelia Hasse-Lazar, Attila Patócs, Birke Bausch, Massimo Mannelli, Marta Barontini, Caterina Mian, Débora Rodrigues Siqueira, Hartmut P. H. Neumann, Georges Weryha, Özer Makay, Flavia L. Coutinho, Svetlana Yaremchuk, John T. M. Plukker, Jean François Henry, Letizia Canu, Frederic Castinetti, Malgorzata Szperl, Simona R Bergmann, Małgorzata Czetwertyńska, M. Umit Ugurlu, Barbara Jarzab, Rodrigo A. Toledo, Gerlof D. Valk, Tomáš Zelinka, Claudio Letizia, Sarka Dvorakova, Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Guided Treatment in Optimal Selected Cancer Patients (GUTS) more...
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Male ,endocrine system diseases ,MEDULLARY-THYROID CARCINOMA ,medicine.medical_treatment ,Adrenal Gland Neoplasms ,Multiple Endocrine Neoplasia Type 2a ,Medicina Clínica ,Kaplan-Meier Estimate ,DISEASE ,Endocrinología y Metabolismo ,Child ,Multiple endocrine neoplasia ,media_common ,Aged, 80 and over ,education.field_of_study ,Adrenalectomy ,GERMLINE MUTATIONS ,Adrenal Sparing ,Middle Aged ,Prophylactic Surgery ,Treatment Outcome ,Oncology ,Female ,Adult ,medicine.medical_specialty ,CIENCIAS MÉDICAS Y DE LA SALUD ,Adolescent ,Population ,Multiple endocrine neoplasia type 2 ,Pheochromocytoma ,Disease-Free Survival ,Young Adult ,RET PROTOONCOGENE ,MANAGEMENT ,medicine ,Adrenal insufficiency ,Humans ,media_common.cataloged_instance ,European union ,education ,2A ,Aged ,Retrospective Studies ,business.industry ,medicine.disease ,Surgery ,Pheocromocythoma ,business - Abstract
Background The prevention of medullary thyroid cancer in patients with multiple endocrine neoplasia type 2 syndrome has demonstrated the ability of molecular diagnosis and prophylactic surgery to improve patient outcomes. However, the other major neoplasia associated with multiple endocrine neoplasia type 2, phaeochromocytoma, is not as well characterised in terms of occurrence and treatment outcomes. In this study, we aimed to systematically characterise the outcomes of management of phaeochromocytoma associated with multiple endocrine neoplasia type 2. Methods This multinational observational retrospective population-based study compiled data on patients with multiple endocrine neoplasia type 2 from 30 academic medical centres across Europe, the Americas, and Asia. Patients were included if they were carriers of germline pathogenic mutations of the RET gene, or were first-degree relatives with histologically proven medullary thyroid cancer and phaeochromocytoma. We gathered clinical information about patients' RET genotype, type of treatment for phaeochromocytoma (ie, unilateral or bilateral operations as adrenalectomy or adrenal-sparing surgery, and as open or endoscopic operations), and postoperative outcomes (adrenal function, malignancy, and death). The type of surgery was decided by each investigator and the timing of surgery was patient driven. The primary aim of our analysis was to compare disease-free survival after either adrenal-sparing surgery or adrenalectomy. Findings 1210 patients with multiple endocrine neoplasia type 2 were included in our database, 563 of whom had phaeochromocytoma. Treatment was adrenalectomy in 438 (79%) of 552 operated patients, and adrenal-sparing surgery in 114 (21%). Phaeochromocytoma recurrence occurred in four (3%) of 153 of the operated glands after adrenal-sparing surgery after 6–13 years, compared with 11 (2%) of 717 glands operated by adrenalectomy (p=0·57). Postoperative adrenal insufficiency or steroid dependency developed in 292 (86%) of 339 patients with bilateral phaeochromocytoma who underwent surgery. However, 47 (57%) of 82 patients with bilateral phaeochromocytoma who underwent adrenal-sparing surgery did not become steroid dependent. Interpretation The treatment of multiple endocrine neoplasia type 2-related phaeochromocytoma continues to rely on adrenalectomies with their associated Addisonian-like complications and consequent lifelong dependency on steroids. Adrenal-sparing surgery, a highly successful treatment option in experienced centres, should be the surgical approach of choice to reduce these complications. Funding European Union, German Cancer Foundation, Arthur Blank Foundation, Italian Government, Charles University, Czech Ministry of Health, Nanjing Military Command, National Science Centre Poland, National Research Council for Scientific and Technological Development, and State of São Paulo Research Foundation Fil: Sanso, Elsa Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina Fil: Barontini, Marta Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina more...
- Published
- 2014
26. Growth hormone (GH) andatherosclerosis: changes in morphology and function of major arteries during GH treatment
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Marija Pfeifer, Renata Verhovec, and Zizek B
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Adult ,Male ,medicine.medical_specialty ,Brachial Artery ,Arteriosclerosis ,Endocrinology, Diabetes and Metabolism ,Hypopituitarism ,Growth hormone deficiency ,Endocrinology ,Risk Factors ,medicine.artery ,Internal medicine ,medicine ,Humans ,Longitudinal Studies ,cardiovascular diseases ,Common carotid artery ,Brachial artery ,Human Growth Hormone ,business.industry ,Vascular disease ,Middle Aged ,medicine.disease ,Vasodilation ,Growth hormone treatment ,Intima-media thickness ,Hemorheology ,cardiovascular system ,Endothelium, Vascular ,business - Abstract
Patients with hypopituitarism have increased carotid artery intima-media thickness and reduced arterial distensibility. The effect of 2 years of growth hormone (GH) replacement therapy on these parameters was studied in 11 GH-deficient men (age range, 24-49 years) with hypopituitarism and compared with 12 healthy, age-matched men with no evidence of pituitary or vascular disease. Before treatment the intima-media of the common carotid arteries and the carotid bifurcations were significantly thicker in patients (P < 0.001) than in the control group. Treatment with GH normalized the intima-media thickness of the common carotid artery within 6 months and of the carotid bifurcation within 3 months. The changes in intima-media thickness of the carotid artery were negatively correlated with changes in serum levels of insulin-like growth factor I during treatment. There was a significant improvement in flow-mediated, endothelium-dependent dilation of the brachial artery at 3 months, which was sustained at 6, 18 and 24 months of GH treatment (P < 0.05). Thus, GH replacement therapy in GH-deficient men reverses early morphological and functional atherosclerotic changes in major arteries, and may reduce rates of vascular morbidity and mortality. more...
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- 1999
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27. Cardiovascular risk and subclinical cardiovascular disease in polycystic ovary syndrome
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Katica, Bajuk Studen, Mojca, Jensterle Sever, and Marija, Pfeifer
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Adult ,Sleep Apnea, Obstructive ,Adolescent ,Coronary Artery Disease ,Middle Aged ,Atherosclerosis ,Carotid Intima-Media Thickness ,Incretins ,Metformin ,Postmenopause ,Renin-Angiotensin System ,Weight Reduction Programs ,Vascular Stiffness ,Cardiovascular Diseases ,Risk Factors ,Hypertension ,Humans ,Androstenes ,Female ,Thiazolidinediones ,Obesity ,Insulin Resistance ,Life Style ,Polycystic Ovary Syndrome - Abstract
In addition to its effects on reproductive health, it is now well recognized that polycystic ovary syndrome (PCOS) is a metabolic disorder, characterized by decreased insulin sensitivity which leads to an excess lifetime risk of type 2 diabetes and cardiovascular disease. PCOS patients are often obese, hypertensive, dyslipidemic and insulin resistant; they have obstructive sleep apnea and have been reported to have higher aldosterone levels in comparison to normal healthy controls. These are all components of an adverse cardiovascular risk profile. Many studies exploring subclinical atherosclerosis using different methods (flow-mediated dilatation, intima media thickness, arterial stiffness, coronary artery calcification) as well as assessing circulating cardiovascular risk markers, point toward an increased cardiovascular risk and early atherogenesis in PCOS. The risk and early features of subclinical atherosclerosis can be reversed by non-medical (normalization of weight, healthy lifestyle) and medical (metformin, thiazolidinediones, spironolactone, and statins) interventions. However, the long-term risk for cardiovascular morbidity and mortality as well as the clinical significance of different interventions still need to be properly addressed in a large prospective study. more...
- Published
- 2013
28. Influence of spironolactone treatment on endothelial function in non-obese women with polycystic ovary syndrome
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Marija Pfeifer, Janez Prezelj, Miran Sebestjen, and Katica Bajuk Studen
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Adult ,medicine.medical_specialty ,Endothelium ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Spironolactone ,chemistry.chemical_compound ,Young Adult ,Endocrinology ,Mineralocorticoid receptor ,Internal medicine ,Renin ,medicine ,Humans ,Testosterone ,Endothelial dysfunction ,Aldosterone ,Triglycerides ,business.industry ,Dehydroepiandrosterone Sulfate ,Androstenedione ,Endothelial Cells ,Androgen Antagonists ,General Medicine ,medicine.disease ,Androgen ,Polycystic ovary ,Lipids ,Lipoproteins, LDL ,medicine.anatomical_structure ,chemistry ,Androgens ,Potassium ,Female ,business ,Body mass index ,Lipoprotein ,Polycystic Ovary Syndrome - Abstract
ObjectiveAccumulating evidence connects polycystic ovary syndrome (PCOS) with increased risk of cardiovascular disease. Endothelial dysfunction is present in PCOS and represents an early, reversible marker of cardiovascular damage. As androgens and renin–angiotensin–aldosterone system are implicated in the atherogenesis process of PCOS, we tested the hypothesis that treatment with spironolactone, an androgen and mineralocorticoid receptor blocking drug, might reverse endothelial dysfunction in PCOS.PatientsA total of 30 non-obese PCOS patients, compared with 20 body mass index matched control subjects, were evaluated. PCOS patients were given spironolactone 100 mg daily in 21-day long intervals followed by a 7-day pause, for 6 months.MeasurementsFlow-mediated dilatation (FMD), glyceryl trinitrate-induced dilatation, free testosterone, androstenedione, DHEA-sulfate, total, low-density lipoprotein (LDL)-, high-density lipoprotein-cholesterol, and triglycerides were determined at baseline and after 6 months.ResultsResults are expressed as median (25–75th percentile). At baseline, FMD was significantly lower in PCOS patients than in controls: 6.0 (0.0–11.7) vs 10.2 (6.8–15.9) %, P=0.018. This difference disappeared after 6 months of spironolactone treatment, as FMD in PCOS patients significantly increased to 8.3 (5.7–10.3) %, P=0.034, and was no longer different from controls. In PCOS patients, serum androgen levels did not change during treatment, while total and LDL-cholesterol decreased significantly from 4.8 (4.1–5.1) mmol/l to 4.4 (3.9–4.8) mmol/l and from 2.5 (2.1–3.1) to 2.2. (2.1–2.5) mmol/l, PPConclusionTreatment with spironolactone normalized endothelial function and improved cholesterol levels in non-obese PCOS patients. more...
- Published
- 2010
29. Expression of 11β-hydroxysteroid dehydrogenase type 1 in visceral and subcutaneous adipose tissues of patients with polycystic ovary syndrome is associated with adiposity
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Marija Pfeifer, Barbara Mlinar, Aleš Jerin, Eda Vrtačnik Bokal, Janja Marc, and Mojca Jensterle
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Adult ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Subcutaneous Fat ,Adipose tissue ,Intra-Abdominal Fat ,Biochemistry ,Body Mass Index ,Endocrinology ,Insulin resistance ,11β-hydroxysteroid dehydrogenase type 1 ,Internal medicine ,Biopsy ,11-beta-Hydroxysteroid Dehydrogenase Type 1 ,medicine ,Humans ,Molecular Biology ,Adiposity ,Lipoprotein lipase ,medicine.diagnostic_test ,Adiponectin ,biology ,business.industry ,nutritional and metabolic diseases ,Cell Biology ,medicine.disease ,Polycystic ovary ,biology.protein ,Molecular Medicine ,Female ,Insulin Resistance ,Waist Circumference ,business ,GLUT4 ,Polycystic Ovary Syndrome - Abstract
Polycystic ovary syndrome (PCOS) is characterized by insulin resistance (IR) and central obesity. The impact of adipose tissue cortisol reactivation by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) on markers of obesity and IR was assessed in PCOS patients. Eighty-five PCOS patients and 43 controls were enrolled for subcutaneous adipose tissue biopsy; 25/85 patients and 29/43 controls underwent also visceral adipose tissue biopsy. HSD11B1 gene expression and expression of lipid metabolism genes were measured in subcutaneous and visceral adipose tissues. Anthropometric and biochemical markers of IR and PCOS were also assessed. HSD11B1 expression in visceral and subcutaneous adipose tissue was increased in PCOS patients compared to controls (p more...
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- 2010
30. Decreased lipin 1 beta expression in visceral adipose tissue is associated with insulin resistance in polycystic ovary syndrome
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Barbara Mlinar, Marija Pfeifer, Janja Marc, Eda Vrtačnik-Bokal, and Mojca Jensterle
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Adult ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Phosphatidate Phosphatase ,Adipose tissue ,Intra-Abdominal Fat ,Young Adult ,Endocrinology ,Insulin resistance ,Internal medicine ,Biopsy ,Medicine ,Humans ,Lipoprotein lipase ,medicine.diagnostic_test ,Adiponectin ,business.industry ,Nuclear Proteins ,General Medicine ,medicine.disease ,Polycystic ovary ,medicine.anatomical_structure ,Gene Expression Regulation ,Female ,Insulin Resistance ,business ,Body mass index ,Subcutaneous tissue ,Polycystic Ovary Syndrome - Abstract
ObjectiveIn polycystic ovary syndrome (PCOS), insulin resistance (IR) appears with high prevalence and represents the major cause of cardiometabolic complications. Lipin 1β regulates lipid metabolism and augments insulin sensitivity. The impact of lipin 1β expression in visceral and subcutaneous adipose tissue of PCOS patients on IR was studied for the first time.MethodsEighty-five PCOS patients and 44 controls were enrolled for subcutaneous tissue biopsy, of whom 25 patients and 30 controls also underwent visceral adipose tissue biopsy. Gene expression of lipin 1β was measured, together with that of peroxisome proliferator-activated receptor γ, lipoprotein lipase, hormone-sensitive lipase, adiponectin and glucose transporter 4 in subcutaneous and visceral adipose tissue. Markers of obesity, IR and PCOS were also measured.ResultsIn PCOS patients, lipin 1β expression in both adipose depots was lower than in controls: 0.76 (0.67–0.84) vs 1.16 (0.90–1.43) for visceral and 0.91 (0.73–1.10) vs 1.30 (1.03–1.57) for s.c. depot (both P−4). The difference remained significant after adjustment for body mass index (BMI) and also when comparing only lean patients with lean controls. In PCOS patients, visceral adipose lipin 1β expression correlated negatively with homeostasis model assessment–IR (r=−0.474, P=0.017), BMI (r=−0.511, P=0.009) and waist circumference (r=−0.473, P=0.017), waist circumference remaining significant (P=0.027) in multiple regression. Subcutaneous lipin 1β expression in PCOS correlated negatively with BMI, waist circumference and plasma triglycerides, and positively with high density lipoprotein-cholesterol. Subcutaneous, but not visceral lipin 1β expression, correlated positively with the studied genes.ConclusionsLipin 1β appears to be involved in the pathogenesis of IR in PCOS. more...
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- 2008
31. Improvement of endothelial function with metformin and rosiglitazone treatment in women with polycystic ovary syndrome
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Miran Sebestjen, Tomaz Kocjan, Mojca Jensterle, Janez Prezelj, Andrej Janez, Marija Pfeifer, and Irena Keber
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medicine.medical_specialty ,Endothelium ,Brachial Artery ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Rosiglitazone ,Endocrinology ,Insulin resistance ,Internal medicine ,medicine.artery ,medicine ,Homeostasis ,Humans ,Hypoglycemic Agents ,Brachial artery ,Menstrual Cycle ,business.industry ,Insulin ,General Medicine ,medicine.disease ,Polycystic ovary ,Lipids ,Metformin ,Vasodilation ,medicine.anatomical_structure ,C-Reactive Protein ,Cardiovascular Diseases ,Androgens ,Female ,Thiazolidinediones ,Endothelium, Vascular ,Insulin Resistance ,business ,medicine.drug ,Polycystic Ovary Syndrome - Abstract
ObjectiveThere is evidence of preclinical cardiovascular disease even in young women with polycystic ovary syndrome (PCOS). The aim of our study was to assess and compare the effects of metformin (MET) and rosiglitazone (ROSI) on endothelial function in PCOS patients.MethodsFor 6 months, 26 women with PCOS received either MET or ROSI. Blood samples for assessment of androgens, lipids, and high-sensitive C-reactive protein were taken at baseline and at endpoint. Endothelium-dependent flow-mediated dilation (FMD) and glyceryl trinitrate-induced endothelium-independent dilation of brachial artery were studied before and after treatment. Homeostasis model assessment (HOMAIR) calculation was applied as a measure of insulin resistance (IR).ResultsWith treatment, FMD of brachial artery improved significantly from 4.2±6.6 to 10.2±5.9% in MET group (P=0.036) and from 2.9±3.2 to 7.6±4.9% in ROSI group (P=0.026), MET being as effective as ROSI (P=0.70). The endothelium-independent dilation did not change. Additionally, administration of MET was associated with a significant decrease in HOMAIR (P=0.003), serum total and serum-free testosterone (P=0.045 and P=0.008 respectively) and significantly higher frequencies of menstrual bleeding (P=0.006).ConclusionsA 6-month therapy with insulin sensitizers, MET and ROSI, resulted in marked improvement of endothelial function in young PCOS patients without clinically evident atherosclerosis who were not severely insulin resistant. Neither drug was superior to the other. We conclude that therapeutic intervention with either insulin sensitizer may reverse the atherosclerotic process in PCOS patients at its early stage. more...
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- 2008
32. Assessment of insulin resistance in young women with polycystic ovary syndrome
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Andrej Janez, Mojca Jensterle, Marija Pfeifer, Andreas Pfützner, Marc Weber, and Janez Prezelj
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Adult ,medicine.medical_specialty ,endocrine system diseases ,medicine.medical_treatment ,Adipokine ,Insulin resistance ,Internal medicine ,medicine ,Homeostasis ,Humans ,Resistin ,Proinsulin ,Adiponectin ,business.industry ,Insulin ,nutritional and metabolic diseases ,Obstetrics and Gynecology ,General Medicine ,medicine.disease ,Polycystic ovary ,Endocrinology ,Homeostatic model assessment ,Female ,Insulin Resistance ,business ,hormones, hormone substitutes, and hormone antagonists ,Polycystic Ovary Syndrome - Abstract
To determine whether serum levels of potential markers could detect insulin resistance (IR) in young women with polycystic ovary syndrome (PCOS).Serum levels of fasting glucose, insulin, intact proinsulin, resistin, and adiponectin were measured in 50 women with PCOS and known homeostatic model assessment (HOMA)-IR values (or=2 indicating IR). The women were all younger than 25 years.Of the 50 women, 49 had undetectable levels of resistin, 50 had intact proinsulin levels within the normal range, and 50 had adiponectin levels of 8.4+/-3.3 mg/L, just below the normal range. When groups were compared, however, the 26 women (52%) with IR (HOMA-IR valuesor=2) had significantly higher intact proinsulin levels (3.2+/-2.0 pmol/L vs 1.8+/-1.0 pmol/L; P0.005) and significantly lower adiponectin levels (7.2+/-2.9 mg/L vs 9.7+/-3.3 mg/L; P0.01), than the 24 women (48%) without IR.Serum levels of intact proinsulin, resistin, or adiponectin were not detectors of IR in individual young women with PCOS. more...
- Published
- 2007
33. Molecular mechanisms of insulin resistance and associated diseases
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Andrej Janez, Janja Marc, Barbara Mlinar, and Marija Pfeifer
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medicine.medical_specialty ,Lipodystrophy ,medicine.medical_treatment ,Clinical Biochemistry ,Adipose tissue ,Biochemistry ,Insulin resistance ,Internal medicine ,Diabetes mellitus ,medicine ,Animals ,Humans ,Obesity ,Metabolic Syndrome ,biology ,Adiponectin ,Insulin ,Biochemistry (medical) ,General Medicine ,medicine.disease ,Polycystic ovary ,Endocrinology ,Diabetes Mellitus, Type 2 ,biology.protein ,Female ,Metabolic syndrome ,Insulin Resistance ,GLUT4 ,Polycystic Ovary Syndrome - Abstract
Insulin resistance is a state in which higher than normal concentrations of insulin are required for normal response. The most common underlying cause is central obesity, although primary insulin resistance in normal-weight individuals is also possible. Excess abdominal adipose tissue has been shown to release increased amounts of free fatty acids which directly affect insulin signalling, diminish glucose uptake in muscle, drive exaggerated triglyceride synthesis and induce gluconeogenesis in the liver. Other factors presumed to play the role in insulin resistance are tumour necrosis factor alpha, adiponectin, leptin, IL-6 and some other adipokines. Hyperinsulinaemia which accompanies insulin resistance may be implicated in the development of many pathological states, such as hypertension and hyperandrogenaemia. Insulin resistance underlies metabolic syndrome and is further associated with polycystic ovary syndrome and lipodystrophies. When beta-cells fail to secrete the excess insulin needed, diabetes mellitus type 2 emerges, which is, besides coronary heart disease, the main complication of insulin resistance and associated diseases. more...
- Published
- 2006
34. Intracytoplasmic sperm injection as a complement to gonadotrophin treatment in infertile men with hypogonadotrophic hypogonadism
- Author
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Branko, Zorn, Marija, Pfeifer, Irma, Virant-Klun, and Helena, Meden-Vrtovec
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Adult ,Male ,Treatment Outcome ,Hypogonadism ,Testis ,Humans ,Sperm Injections, Intracytoplasmic ,Spermatogenesis ,Chorionic Gonadotropin - Abstract
In this study we sought to determine whether intracytoplasmic sperm injection (ICSI) could improve the efficacy of treatment with gonadotrophins in gonadotrophin-deficient men in terms of pregnancy. A series of six adult men (aged 26-47 years) with hypogonadotrophic hypogonadism (HH) is reported: four men with prepubertal isolated idiopathic HH (IIHH) and two adult-onset HH, as part of hypopituitarism secondary to surgical treatment of a pituitary tumour. All were azoospermic. To restore spermatogenesis, all received hormonal treatment with intramuscular human menopausal gonadotrophins (HMG) and human chorionic gonadotrophin (HCG) for 2 to 23 months. High basal serum inhibin B was predictive of rapid and complete recovery of spermatogenesis. In the two adult-onset HH, a natural pregnancy was achieved within 3 months. The four men with IIHH underwent ICSI because of poor sperm quality. ICSI using fresh or frozen-thawed ejaculated spermatozoa was performed after 6-23 months of gonadotrophin treatment. ICSI provided good clinical results in terms of fertilization and embryo quality, and resulted in three pregnancies that ended in three term deliveries. In men with oligozoospermia related to prepubertal IIHH, ICSI shortens the hormonal treatment and enhances the chances of pregnancy. more...
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- 2005
35. Endothelial dysfunction in endocrine disease
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Tarik Elhadd, Tarig A. M. Abdu, Richard N. Clayton, and Marija Pfeifer
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medicine.medical_specialty ,Endothelium ,Endocrinology, Diabetes and Metabolism ,Hypopituitarism ,Thrombomodulin ,Endocrine System Diseases ,Coronary artery disease ,Endocrinology ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Obesity ,Endothelial dysfunction ,Endocrine disease ,business.industry ,Hyperparathyroidism ,medicine.disease ,Polycystic ovary ,Thyroid Diseases ,medicine.anatomical_structure ,Cardiovascular Diseases ,Acromegaly ,Cardiology ,Female ,Endothelium, Vascular ,Insulin Resistance ,business ,Polycystic Ovary Syndrome - Abstract
In addition to diabetes mellitus and obesity, acromegaly, Cushing's syndrome, hypopituitarism, hypo- and hyperthyroidism, hyperparathyroidism and polycystic ovary syndrome are associated with either increased mortality from, or increased prevalence of, cardiovascular disease (CVD). Recently, endothelial dysfunction has been identified as an early marker of CVD and has been shown to predict future coronary artery disease, before atherosclerotic changes appear in arteries. Thus, measurement of endothelial function might identify at-risk individuals early and be a useful means of assessing response to treatment aimed at reducing long-term morbidity and/or mortality from CVD. Such studies are being undertaken in hypopituitarism and other endocrinopathies, and are reviewed herein. Endothelial function in large vessels can be measured noninvasively by ultrasound measurement of flow-mediated endothelium-dependent dilation (FMD). Serum markers of endothelial function, such as von Willebrand's factor, thrombomodulin, E-selectin and intercellular adhesion molecule 1, could be increased and be useful for evaluation of treatment, because they correlate inversely with FMD. more...
- Published
- 2001
36. Effect of growth hormone (GH) therapy on endothelial function in GH-deficient adults
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Marija Pfeifer, Zizek B, and Pavel Poredos
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Adult ,medicine.medical_specialty ,Endothelium ,business.industry ,Human Growth Hormone ,Endocrinology, Diabetes and Metabolism ,Biochemistry (medical) ,Clinical Biochemistry ,Growth hormone ,Biochemistry ,Vasodilation ,Endocrinology ,medicine.anatomical_structure ,Text mining ,Internal medicine ,Growth Hormone ,Medicine ,Humans ,Endothelium, Vascular ,Ultrasonography ,business ,Function (biology) - Published
- 2001
37. Oncogene-induced senescence in pituitary adenomas and carcinomas
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Ashley B. Grossman, Daniel M. Berney, Mohammed Munayem Khan, Suzanne Jordan, Krystallenia I Alexandraki, Márta Korbonits, Philippe Caron, Harvinder Chahal, Marija Pfeifer, Vera Popovic, Nadezhda Dalantaeva, and Giampaolo Trivellin more...
- Subjects
Adenoma ,Cyclin-Dependent Kinase Inhibitor p21 ,Senescence ,Aging ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Biology ,Malignancy ,Adrenocorticotropic Hormone ,Pituitary adenoma ,Internal medicine ,medicine ,Humans ,Pituitary Neoplasms ,Prolactinoma ,Cyclin-Dependent Kinase Inhibitor p16 ,Messenger RNA ,General Medicine ,beta-Galactosidase ,medicine.disease ,Immunohistochemistry ,Real-time polymerase chain reaction ,Endocrinology ,Growth Hormone ,Pituitary Gland ,Pituitary carcinoma - Abstract
OBJECTIVE: The model of "oncogene-induced senescence" (OIS), resulting in cell-proliferation arrest, has recently been suggested as a possible explanation for the non-progression of pituitary tumours to malignancy. The aim of the study was to compare the expression of β-galactosidase as a molecular marker of OIS, and p21/p16 as additional markers involved in mediating OIS, in pituitary adenomas, carcinomas and normal pituitary tissue. DESIGN: We performed: a) semi-quantitative immunohistochemistry (β-galactosidase, p16, p21) in 41 pituitary adenomas [(11 GH-secreting, 9 PRL-secreting, 10 ACTH-secreting, 11 non-functioning (NFPAs)], 6 carcinomas (3 multihormonal: PRL/ACTH/GH, PRL/ACTH, PRL/GH/FSH; 1 non-functioning; 2 ACTH-secreting) and 7 normal pituitary tissues; b) quantitative PCR of mRNA (p16 and p21) in 6 GH-secreting, 6 NFPAs and 6 normal pituitary tissues. RESULTS: β-galactosidase was significantly increased in GH-secreting tumours (P=0.002), NFPAs (P=0.04), macroadenomas (P=0.03) and carcinomas (P=0.02), as compared to normal pituitary tissue. We found that p16 expression was significantly lower in all tumours (both adenomas and carcinomas) probably secondary to reduced transcription, at least for NFPAs; p21 showed a different biological behaviour, implying that p21 and p16 may play different roles in the senescence of each individual type of adenoma. CONCLUSIONS: β-galactosidase was significantly over-expressed in GH-secreting and NFPAs, and unexpectedly also in carcinomas. We speculate that the senescence pathway, which may explain the rarity of malignant progression to carcinomas in GH-secreting and NFPAs, might not be universal but cell-type specific. more...
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