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A Rehfeld Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Denmark
Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), University of Copenhagen, Rigshospitalet, Denmark

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D L Egeberg Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), University of Copenhagen, Rigshospitalet, Denmark

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K Almstrup Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), University of Copenhagen, Rigshospitalet, Denmark

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J H Petersen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), University of Copenhagen, Rigshospitalet, Denmark
Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark

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S Dissing Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

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N E Skakkebæk Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), University of Copenhagen, Rigshospitalet, Denmark

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Human sperm cell function must be precisely regulated to achieve natural fertilization. Progesterone released by the cumulus cells surrounding the egg induces a Ca2+ influx into human sperm cells via the CatSper Ca2+-channel and thereby controls sperm function. Multiple chemical UV filters have been shown to induce a Ca2+ influx through CatSper, thus mimicking the effect of progesterone on Ca2+ signaling. We hypothesized that these UV filters could also mimic the effect of progesterone on sperm function. We examined 29 UV filters allowed in sunscreens in the US and/or EU for their ability to affect acrosome reaction, penetration, hyperactivation and viability in human sperm cells. We found that, similar to progesterone, the UV filters 4-MBC, 3-BC, Meradimate, Octisalate, BCSA, HMS and OD-PABA induced acrosome reaction and 3-BC increased sperm penetration into a viscous medium. The capacity of the UV filters to induce acrosome reaction and increase sperm penetration was positively associated with the ability of the UV filters to induce a Ca2+ influx. None of the UV filters induced significant changes in the proportion of hyperactivated cells. In conclusion, chemical UV filters that mimic the effect of progesterone on Ca2+ signaling in human sperm cells can similarly mimic the effect of progesterone on acrosome reaction and sperm penetration. Human exposure to these chemical UV filters may impair fertility by interfering with sperm function, e.g. through induction of premature acrosome reaction. Further studies are needed to confirm the results in vivo.

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Clara Lundetoft Clausen Center of Research & Disruption of Infectious Diseases, Department of Infectious Diseases, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark

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Trine Holm Johannsen Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Niels Erik Skakkebæk Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Hanne Frederiksen Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Anders Juul Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Thomas Benfield Center of Research & Disruption of Infectious Diseases, Department of Infectious Diseases, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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In the context of severe coronavirus disease 2019 (COVID-19) illness, we examined endogenous glucocorticoid concentrations, steroidogenic enzyme activity, and their correlation with inflammation and patient outcomes. This observational study included 125 hospitalized COVID-19 patients and 101 healthy individuals as a reference group. We utilized LC-MS to assess serum concentrations of 11-deoxycortisol, cortisol, and cortisone, as well as activities of steroidogenic enzymes (11β-hydroxylase and 11β-hydroxysteroid-dehydrogenase type 1). Cox proportional hazards regression analysis and competing risk analysis were employed to analyze associations between glucocorticoid concentrations and outcomes, adjusting for relevant factors. In patients with COVID-19, cortisol concentrations were higher and cortisone concentrations were lower compared to the reference group, while 11-deoxycortisol concentrations were similar. Steroidogenic enzyme activity favored cortisol production. Correlations between glucocorticoid concentrations and inflammatory markers were low. A doubling in concentrations cortisol, was associated with increased 90-day mortality and mechanical ventilation (HR: 2.40 95% CI: (1.03–5.59) , P = 0.042 and HR: 3.83 (1.19–12.31), P = 0.024). A doubling in concentrations of 11-deoxycortisol was also associated to mortality (HR: 1.32 (1.05–1.67), P = 0.018), whereas concentrations of cortisone were associated with mechanical ventilation (HR: 5.09 (1.49–17.40), P = 0.009). In conclusion, serum concentrations of glucocorticoid metabolites were altered in patients hospitalized with severe COVID-19, and steroidogenic enzyme activity resulting in the conversion of cortisone to biologically active cortisol was preserved, thus not favoring critical-illness-related corticosteroid insufficiency at the enzymatic level. Glucocorticoid release did not counterbalance the hyperinflammatory state in patients with severe COVID-19. High serum concentrations of 11-deoxycortisol and cortisol were associated with 90-day mortality, and high serum concentrations of cortisol and cortisone were associated with mechanical ventilation.

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Lukas Plachy Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Lenka Petruzelkova Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Petra Dusatkova Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Klara Maratova Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Dana Zemkova Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Lenka Elblova Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Vit Neuman Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Stanislava Kolouskova Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Barbora Obermannova Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Marta Snajderova Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Zdenek Sumnik Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Jan Lebl Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Stepanka Pruhova Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Introduction Familial short stature (FSS) is a term commonly used in clinical practice to describe the vertical transmission of a growth disorder. A short child is classified as having FSS if at least one of his/her parents is also short

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Rossella Cannarella Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Andrea Crafa Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Sandro La Vignera Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Rosita A Condorelli Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Aldo E Calogero Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Introduction The acromegaly levels of insulin-like growth factor 1 (IGF1) that occur in healthy children in pubertal age have led to the speculation that this hormone may stimulate the function of the hypothalamus–pituitary–testicular (HPT

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Huma Qamar Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada
Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada

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Nandita Perumal Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada
Department of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

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Eszter Papp Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada

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Alison D Gernand Department of Nutritional Sciences, Pennsylvania State University, University Park, Pennsylvania, USA

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Abdullah Al Mahmud Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research (icddr,b), Dhaka, Bangladesh

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Daniel E Roth Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada
Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada
Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada

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Introduction Intrauterine growth restriction (IUGR), or inadequate fetal growth, is associated with short- and long-term adverse health outcomes ( 1 , 2 , 3 , 4 , 5 ). Low birthweight (LBW), defined as birthweight less than 2500 g, and

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R Solomon-Zemler Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

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L Basel-Vanagaite Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Raphael Recanati Genetic Institute, Rabin Medical Center – Beilinson Hospital, Petach Tikva, Israel
Felsenstein Medical Research Center, Petach Tikva, Israel
Pediatric Genetics, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

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D Steier Day Hospitalization Department, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

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S Yakar David B. Kriser Dental Center, Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, New York, USA

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E Mel Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

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M Phillip Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

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L Bazak Raphael Recanati Genetic Institute, Rabin Medical Center – Beilinson Hospital, Petach Tikva, Israel

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D Bercovich Tel-Hai College, Tel-Hai, Israel

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H Werner Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Shalom and VardaYoran Institute for Human Genome Research, Tel Aviv University, Tel Aviv, Israel

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L de Vries Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

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Introduction Growth retardation in children is multifactorial. While most conditions associated with growth impairment are amenable to genetic and molecular analyses, a significant portion of the cases is classified as idiopathic because no

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Morten Ruge Center for Clinical Research and Disease Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark

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Tea Skaaby Center for Clinical Research and Disease Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark

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Anna-Maria Andersson Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Allan Linneberg Center for Clinical Research and Disease Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark
Department of Clinical Experimental Research, Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Background

Reduced total hours of sleep and low quality of sleep have been suggested to be associated with low levels of male hormones. Few studies have examined the association between excessive sleep and male reproductive hormones.

Objective

To investigate the association of total hours of sleep and quality of sleep with serum levels of total, bioavailable and free testosterone (tT, bT and fT), sex hormone-binding globulin (SHBG) and dehydroepiandrosteron-sulfate (DHEAS).

Methods

Serum levels of tT, SHBG and DHEAS were measured with immunoassays in a cross-sectional population-based study of 2095 males. bT and fT were calculated in accordance with Vermeulens method. Information on total hours of sleep and sleep quality was obtained by questionnaire. Linear regression was used to calculate hormones according to total hours of sleep and the results were expressed as β-estimates and 95% confidence intervals (CI). The adjustment in the multivariable models was constructed taking age, BMI, smoking, alcohol intake and physical activity into account.

Results

Excessive sleep (>9 h) compared to 7–9 h of sleep was significantly associated with lower tT, bT and fT, but not with SHBG or DHEAS, after multivariable adjustment. These significant associations were also found in our analyses with hormones as continuous variables but no associations were found in our general additive model analyses.

Conclusions

In this cross-sectional study in men, excessive sleep associated with lower levels of male reproductive hormones. Longitudinal studies are needed to determine the causal direction of the observed association between excessive sleep and lower male reproductive hormones levels.

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María L Bacigalupo Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Química y Fisicoquímica Biológicas, Buenos Aires, Argentina

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Verónica G Piazza Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Química y Fisicoquímica Biológicas, Buenos Aires, Argentina

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Nadia S Cicconi Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Química y Fisicoquímica Biológicas, Buenos Aires, Argentina

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Pablo Carabias Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Química y Fisicoquímica Biológicas, Buenos Aires, Argentina

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Andrzej Bartke Department of Internal Medicine, Geriatrics Research, Southern Illinois University School of Medicine, Springfield, Illinois, USA

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Yimin Fang Department of Internal Medicine, Geriatrics Research, Southern Illinois University School of Medicine, Springfield, Illinois, USA

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Ana I Sotelo Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Química y Fisicoquímica Biológicas, Buenos Aires, Argentina

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Gabriel A Rabinovich Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, and Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina

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María F Troncoso Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Química y Fisicoquímica Biológicas, Buenos Aires, Argentina

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Johanna G Miquet Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Química y Fisicoquímica Biológicas, Buenos Aires, Argentina

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Maria Cristina De Martino Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy

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Richard A Feelders Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

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Claudia Pivonello Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy

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Chiara Simeoli Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy

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Fortuna Papa Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy

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Annamaria Colao Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy

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Rosario Pivonello Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy

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Leo J Hofland Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

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involved in tumor cell growth and/or tumor vascular supply, leading to major advances in oncology ( 4 , 5 ). Targeted drugs include compounds interfering with growth factor receptors and their related signaling pathways. Mammalian target of rapamycin

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Stefan M Constantinescu Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Brussels, Belgium

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Thierry Duprez Department of Radiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium

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Edward Fomekong Department of Neurosurgery, Cliniques Universitaires Saint-Luc, Brussels, Belgium

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Christian Raftopoulos Department of Neurosurgery, Cliniques Universitaires Saint-Luc, Brussels, Belgium

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Orsalia Alexopoulou Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Brussels, Belgium

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Dominique Maiter Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Brussels, Belgium

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-related tumor growth, younger age, hormone or visual deficits, as well as unremitting headache are recognized indications for surgery, although they need to be discussed on a case by case basis by a specialized multidisciplinary pituitary team ( 6 ). When

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