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  • Abstract: Adrenal x
  • Abstract: Adrenaline x
  • Abstract: Androgens x
  • Abstract: Catecholamines x
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  • Abstract: Glucocorticoids x
  • Abstract: Medulla x
  • Abstract: Noradrenaline x
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Magdalena Lech Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK

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Ruvini Ranasinghe Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Royce P Vincent Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK
Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK

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David R Taylor Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Lea Ghataore Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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James Luxton Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Fannie Lajeunesse-Trempe Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
Quebec Heart and Lung Institute, Laval University, Quebec, Canada

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Pia Roser Department of Endocrinology and Diabetes, University Medical Centre Hamburg Eppendorf, Hamburg, Germany

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Eftychia E Drakou Department of Clinical Oncology, Guy's Cancer Centre - Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London, UK

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Ling Ling Chuah Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Ashley B Grossman Green Templeton College, University of Oxford, Oxford, UK
Barts and the London School of Medicine, Centre for Endocrinology, William Harvey Institute, London, UK
Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK

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Simon J B Aylwin Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Georgios K Dimitriadis Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
Obesity, Type 2 Diabetes and Immunometabolism Research Group, School of Cardiovascular and Metabolic Medicine & Sciences, Faculty of Life Course Sciences, King’s College London, London, UK
Division of Reproductive Health, Warwick Medical School, University of Warwick, Coventry, UK

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Introduction

Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex. Whilst surgery is the preferred treatment, adjunctive therapy with mitotane may be offered post-surgically to minimise the risk of recurrence or, in the absence of surgery, to attenuate progression.

Aim

The objective was to evaluate the effects of mitotane treatment on serum protein concentrations in patients treated for ACC with mitotane therapy and compare this to patients with other adrenal neoplasms and a normal pregnant cohort.

Methods

Serum cortisol, thyroid function tests, adrenocorticotrophic hormone (ACTH), cortisol-binding globulin (CBG), thyroxine-binding globulin (TBG), gonadotrophins and androgens were measured on plasma and serum samples. Thirty-five patients with ACC were included, and mitotane levels were noted to be sub-/supra-therapeutic. Data were tested for normality, reported as mean ± s.d., and compared to other two cohorts using paired-sample t-test with a 5% P-value for significance and a 95% CI.

Results

Patients on mitotane therapy had a higher mean serum CBG concentration compared to the adrenal neoplasm group (sub-therapeutic: 79.5 (95% CI: 33.6, 125.4 nmol/L), therapeutic: 85.3 (95% CI: 37.1–133.6 nmol/L), supra-therapeutic: 75.7 (95% CI: −19.3, 170.6 nmol/L) and adrenal neoplasm: 25.5 (95% CI: 17.5, 33.5 nmol/L). Negative correlations between serum cortisol and CBG concentration were demonstrated within the supra-therapeutic plasma mitotane and adrenal neoplasm groups.

Conclusion

Patients with ACC and therapeutic plasma mitotane concentrations had higher serum CBG concentrations compared to those with adrenal neoplasms or pregnant women, and higher serum cortisol. Whilst there was no direct correlation with cortisol and mitotane level, the negative correlation of cortisol with CBG may suggest that the direct effect of mitotane in increasing cortisol may also reflect that mitotane has a direct adrenolytic effect.

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R Walia Department of Endocrinology, Postgraduate Institute of Medical Education & Research, Chandigarh, India

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M Singla Department of Endocrinology, Postgraduate Institute of Medical Education & Research, Chandigarh, India

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K Vaiphei Department of Histopathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India

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S Kumar Department of Urology, Postgraduate Institute of Medical Education & Research, Chandigarh, India

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A Bhansali Department of Endocrinology, Postgraduate Institute of Medical Education & Research, Chandigarh, India

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Objective

To study the clinical profile and the management of patients with disorders of sex development (DSD).

Design and setting

Retrospective study from a tertiary care hospital of North India.

Methods and patients

One hundred ninety-four patients of DSD registered in the Endocrine clinic of Postgraduate Institute of Medical Education and Research, Chandigarh between 1995 and 2014 were included.

Results

One hundred and two patients (52.5%) had 46,XY DSD and seventy-four patients (38.1%) had 46,XX DSD. Sex chromosome DSD was identified in seven (3.6%) patients. Of 102 patients with 46,XY DSD, 32 (31.4%) had androgen insensitivity syndrome and 26 (25.5%) had androgen biosynthetic defect. Of the 74 patients with 46,XX DSD, 52 (70.27%) had congenital adrenal hyperplasia (CAH) and eight (10.8%) had ovotesticular DSD. Five patients with sex chromosome DSD had mixed gonadal dysgenesis. Excluding CAH, majority of the patients (90%) presented in the post-pubertal period. One-fourth of the patients with simple virilising CAH were reared as males because of strong male gender identity and behaviour and firm insistence by the parents. Corrective surgeries were performed in twenty patients (20%) of 46,XY DSD without hormonal evaluation prior to the presentation.

Conclusion

Congenital adrenal hyperplasia is the most common DSD in the present series. Most common XY DSD is androgen insensitivity syndrome, while CAH is the most common XX DSD. Delayed diagnosis is a common feature, and corrective surgeries are performed without seeking a definite diagnosis.

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Karim Gariani Service of Endocrinology, Diabetes, Nutrition and Therapeutic Patient Education, Geneva University Hospitals and Geneva University, Geneva, Switzerland

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François R Jornayvaz Service of Endocrinology, Diabetes, Nutrition and Therapeutic Patient Education, Geneva University Hospitals and Geneva University, Geneva, Switzerland
Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland

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Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. NAFLD encompasses a whole spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. The latter can lead to hepatocellular carcinoma. Furthermore, NASH is the most rapidly increasing indication for liver transplantation in western countries and therefore represents a global health issue. The pathophysiology of NASH is complex and includes multiple parallel hits. NASH is notably characterized by steatosis as well as evidence of hepatocyte injury and inflammation, with or without fibrosis. NASH is frequently associated with type 2 diabetes and conditions associated with insulin resistance. Moreover, NASH may also be found in many other endocrine diseases such as polycystic ovary syndrome, hypothyroidism, male hypogonadism, growth hormone deficiency or glucocorticoid excess, for example. In this review, we will discuss the pathophysiology of NASH associated with different endocrinopathies.

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Rachel K Rowe Phoenix Veterans Affairs Health Care System, Phoenix, Arizona, USA
BARROW Neurological Institute at Phoenix Children’s Hospital, Phoenix, Arizona, USA
Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, Arizona, USA

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Benjamin M Rumney BARROW Neurological Institute at Phoenix Children’s Hospital, Phoenix, Arizona, USA
Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, Arizona, USA
Department of Biology and Biochemistry, University of Bath, UK

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Hazel G May BARROW Neurological Institute at Phoenix Children’s Hospital, Phoenix, Arizona, USA
Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, Arizona, USA
Department of Biology and Biochemistry, University of Bath, UK

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Paska Permana Phoenix Veterans Affairs Health Care System, Phoenix, Arizona, USA

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P David Adelson BARROW Neurological Institute at Phoenix Children’s Hospital, Phoenix, Arizona, USA
Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, Arizona, USA
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, USA

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S Mitchell Harman Phoenix Veterans Affairs Health Care System, Phoenix, Arizona, USA

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Jonathan Lifshitz Phoenix Veterans Affairs Health Care System, Phoenix, Arizona, USA
BARROW Neurological Institute at Phoenix Children’s Hospital, Phoenix, Arizona, USA
Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, Arizona, USA

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Theresa C Thomas Phoenix Veterans Affairs Health Care System, Phoenix, Arizona, USA
BARROW Neurological Institute at Phoenix Children’s Hospital, Phoenix, Arizona, USA
Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, Arizona, USA

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As many as 20–55% of patients with a history of traumatic brain injury (TBI) experience chronic endocrine dysfunction, leading to impaired quality of life, impaired rehabilitation efforts and lowered life expectancy. Endocrine dysfunction after TBI is thought to result from acceleration–deceleration forces to the brain within the skull, creating enduring hypothalamic and pituitary neuropathology, and subsequent hypothalamic–pituitary endocrine (HPE) dysfunction. These experiments were designed to test the hypothesis that a single diffuse TBI results in chronic dysfunction of corticosterone (CORT), a glucocorticoid released in response to stress and testosterone. We used a rodent model of diffuse TBI induced by midline fluid percussion injury (mFPI). At 2months postinjury compared with uninjured control animals, circulating levels of CORT were evaluated at rest, under restraint stress and in response to dexamethasone, a synthetic glucocorticoid commonly used to test HPE axis regulation. Testosterone was evaluated at rest. Further, we assessed changes in injury-induced neuron morphology (Golgi stain), neuropathology (silver stain) and activated astrocytes (GFAP) in the paraventricular nucleus (PVN) of the hypothalamus. Resting plasma CORT levels were decreased at 2months postinjury and there was a blunted CORT increase in response to restraint induced stress. No changes in testosterone were measured. These changes in CORT were observed concomitantly with altered complexity of neuron processes in the PVN over time, devoid of neuropathology or astrocytosis. Results provide evidence that a single moderate diffuse TBI leads to changes in CORT function, which can contribute to the persistence of symptoms related to endocrine dysfunction. Future experiments aim to evaluate additional HP-related hormones and endocrine circuit pathology following diffuse TBI.

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Anne-Sophie C A M Koning Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Philippe C Habets Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Marit Bogaards Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Jan Kroon Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Hanneke M van Santen Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
Department of Pediatric Neuro-Oncology, Prinses Máxima Centrum, Utrecht, The Netherlands

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Judith M de Bont Department of Pediatric Neuro-Oncology, Prinses Máxima Centrum, Utrecht, The Netherlands

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Onno C Meijer Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Background

Synthetic glucocorticoids like dexamethasone can cause severe neuropsychiatric effects. They preferentially bind to the glucocorticoid receptor (GR) over the mineralocorticoid receptor (MR). High dosages result in strong GR activation but likely also result in lower MR activation based on GR-mediated negative feedback on cortisol levels. Therefore, reduced MR activity may contribute to dexamethasone-induced neuropsychiatric symptoms.

Objective

In this single case study, we evaluate whether dexamethasone leads to reduced MR activation in the human brain. Brain tissue of an 8-year-old brain tumor patient was used, who suffered chronically from dexamethasone-induced neuropsychiatric symptoms and deceased only hours after a high dose of dexamethasone.

Main outcome measures

The efficacy of dexamethasone to induce MR activity was determined in HEK293T cells using a reporter construct. Subcellular localization of GR and MR was assessed in paraffin-embedded hippocampal tissue from the patient and two controls. In hippocampal tissue from the patient and eight controls, mRNA of MR/GR target genes was measured.

Results

In vitro, dexamethasone stimulated MR with low efficacy and low potency. Immunofluorescence showed the presence of both GR and MR in the hippocampal cell nuclei after dexamethasone exposure. The putative MR target gene JDP2 was consistently expressed at relatively low levels in the dexamethasone-treated brain samples. Gene expression showed substantial variation in MR/GR target gene expression in two different hippocampus tissue blocks from the same patient.

Conclusions

Dexamethasone may induce MR nuclear translocation in the human brain. Conclusions on in vivo effects on gene expression in the brain await the availability of more tissue of dexamethasone-treated patients.

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Theodoros Karampitsakos Third Department of Obstetrics and Gynecology, ATTIKON University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
Unit of Endocrinology, Diabetes Mellitus and Metabolism, ARETAIEION University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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Fotini Kanouta Unit of Endocrinology, Diabetes Mellitus and Metabolism, First Department of Obstetrics and Gynecology, ALEXANDRA University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
Unit of Endocrinology, Diabetes Mellitus and Metabolism, ARETAIEION University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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Christos Chatzakis Second Department of Obstetrics and Gynecology, IPPOKRATEIO General Hospital of Thessaloniki, Aristotle, University of Thessaloniki, Athens, Greece

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Vassilios Bakoulas Athens, Greece

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Alexandros Gryparis Department of Speech and Language Therapy, University of Ioannina, Ioannina, Greece
Unit of Endocrinology, Diabetes Mellitus and Metabolism, ARETAIEION University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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Petros Drakakis Third Department of Obstetrics and Gynecology, ATTIKON University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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Djuro Macut Department of Endocrinology, Diabetes and Diseases of Metabolism, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Unit of Endocrinology, Diabetes Mellitus and Metabolism, ARETAIEION University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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George Mastorakos Unit of Endocrinology, Diabetes Mellitus and Metabolism, ARETAIEION University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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Introduction

To investigate whether synthetic (s) glucocorticoids (GCs) administered between the 24th and the 34th gestational weeks in pre-term labor might precipitate labor, studies on sGCs administration were reviewed. The physiology of endogenous glucocorticoid-related increase in fetal–maternal circulation and its association with labor, followed by a scoping review of studies on exogenous sGCs administered for fetal lung maturation and the timing of labor, were included.

Materials and methods

The methodology of systematic reviews was followed. MEDLINE, Cochrane Library, and Google Scholar databases were searched until October 2023, for original studies investigating the administration of sGCs in pregnancies risking pre-term labor. Duplicates were removed, and 1867 abstracts were excluded as irrelevant. Six controlled and four non-controlled studies were included. The index group consisted of 6001 subjects and 7691 controls in the former, while in the latter, the index group consisted of 2069 subjects.

Results

In three out of the six controlled studies, gestational age at labor was significantly lower in sGC-treated women than in controls, while in three studies, gestational age at labor was lower in sGC-treated women than in controls, with a trend toward statistical significance. In one study, gestational age at labor was significantly lower in controls than in sGC-treated women. In the non-controlled studies, the majority of women delivered less than 1 week from the day of sGC administration.

Conclusions

In this scoping review, studies lack homogeneity. However, in the controlled studies, a pattern of earlier labor emerges among sGC-treated pregnant women. The use of multiple courses of antenatal sGCs appears to be associated with precipitated labor. Their use should be carefully weighed. Carefully designed trials should examine this ongoing scientific query.

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Robert I Menzies The University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh, UK

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Xin Zhao The University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh, UK

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Linda J Mullins The University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh, UK

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John J Mullins The University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh, UK

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Carolynn Cairns The University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh, UK

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Nicola Wrobel The University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh, UK

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Donald R Dunbar The University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh, UK

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Matthew A Bailey The University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh, UK

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Christopher J Kenyon The University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh, UK

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Chronic ACTH exposure is associated with adrenal hypertrophy and steroidogenesis. The underlying molecular processes in mice have been analysed by microarray, histological and immunohistochemical techniques. Synacthen infused for 2 weeks markedly increased adrenal mass and plasma corticosterone levels. Microarray analysis found greater than 2-fold changes in expression of 928 genes (P < 0.001; 397 up, 531 down). These clustered in pathways involved in signalling, sterol/lipid metabolism, cell proliferation/hypertrophy and apoptosis. Signalling genes included some implicated in adrenal adenomas but also upregulated genes associated with cyclic AMP and downregulated genes associated with aldosterone synthesis. Sterol metabolism genes were those promoting cholesterol supply (Scarb1, Sqle, Apoa1) and disposal (Cyp27a1, Cyp7b1). Oil red O staining showed lipid depletion consistent with reduced expression of genes involved in lipid synthesis. Genes involved in steroidogenesis (Star, Cyp11a1, Cyp11b1) were modestly affected (P < 0.05; <1.3-fold). Increased Ki67, Ccna2, Ccnb2 and Tk1 expression complemented immunohistochemical evidence of a 3-fold change in cell proliferation. Growth arrest genes, Cdkn1a and Cdkn1c, which are known to be active in hypertrophied cells, were increased >4-fold and cross-sectional area of fasciculata cells was 2-fold greater. In contrast, genes associated with apoptosis (eg Casp12, Clu,) were downregulated and apoptotic cells (Tunel staining) were fewer (P < 0.001) and more widely distributed throughout the cortex. In summary, long-term steroidogenesis with ACTH excess is sustained by genes controlling cholesterol supply and adrenal mass. ACTH effects on adrenal morphology and genes controlling cell hypertrophy, proliferation and apoptosis suggest the involvement of different cell types and separate molecular pathways.

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Kate E Lines Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital, Headington, Oxford, UK

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Mahsa Javid Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital, Headington, Oxford, UK

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Anita A C Reed Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital, Headington, Oxford, UK

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Gerard V Walls Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital, Headington, Oxford, UK

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Mark Stevenson Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital, Headington, Oxford, UK

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Michelle Simon MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus, Oxfordshire, UK

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Kreepa G Kooblall Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital, Headington, Oxford, UK

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Sian E Piret Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital, Headington, Oxford, UK

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Paul T Christie Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital, Headington, Oxford, UK

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Paul J Newey Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital, Headington, Oxford, UK

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Ann-Marie Mallon MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus, Oxfordshire, UK

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Rajesh V Thakker Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital, Headington, Oxford, UK

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Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder caused by MEN1 germline mutations, is characterised by parathyroid, pancreatic and pituitary tumours. MEN1 mutations also cause familial isolated primary hyperparathyroidism (FIHP), a milder condition causing hyperparathyroidism only. Identical mutations can cause either MEN1 or FIHP in different families, thereby implicating a role for genetic modifiers in altering phenotypic expression of tumours. We therefore investigated the effects of genetic background and potential for genetic modifiers on tumour development in adult Men1+/- mice, which develop tumours of the parathyroids, pancreatic islets, anterior pituitary, adrenal cortex and gonads, that had been backcrossed to generate C57BL/6 and 129S6/SvEv congenic strains. A total of 275 Men1+/- mice, aged 5–26 months were macroscopically studied, and this revealed that genetic background significantly influenced the development of pituitary, adrenal and ovarian tumours, which occurred in mice over 12 months of age and more frequently in C57BL/6 females, 129S6/SvEv males and 129S6/SvEv females, respectively. Moreover, pituitary and adrenal tumours developed earlier, in C57BL/6 males and 129S6/SvEv females, respectively, and pancreatic and testicular tumours developed earlier in 129S6/SvEv males. Furthermore, glucagon-positive staining pancreatic tumours occurred more frequently in 129S6/SvEv Men1+/- mice. Whole genome sequence analysis of 129S6/SvEv and C57BL/6 Men1+/- mice revealed >54,000 different variants in >300 genes. These included, Coq7, Dmpk, Ccne2, Kras, Wnt2b, Il3ra and Tnfrsf10a, and qRT-PCR analysis revealed that Kras was significantly higher in pituitaries of male 129S6/SvEv mice. Thus, our results demonstrate that Kras and other genes could represent possible genetic modifiers of Men1.

Open access
Kerry V Fanson Wildlife Reproductive Centre, School of Life and Environmental Sciences, School of Agriculture and Food Sciences, Taronga Conservation Society Australia, Dubbo, New South Wales, Australia
Wildlife Reproductive Centre, School of Life and Environmental Sciences, School of Agriculture and Food Sciences, Taronga Conservation Society Australia, Dubbo, New South Wales, Australia

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Tamara Keeley Wildlife Reproductive Centre, School of Life and Environmental Sciences, School of Agriculture and Food Sciences, Taronga Conservation Society Australia, Dubbo, New South Wales, Australia
Wildlife Reproductive Centre, School of Life and Environmental Sciences, School of Agriculture and Food Sciences, Taronga Conservation Society Australia, Dubbo, New South Wales, Australia

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Benjamin G Fanson Wildlife Reproductive Centre, School of Life and Environmental Sciences, School of Agriculture and Food Sciences, Taronga Conservation Society Australia, Dubbo, New South Wales, Australia

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In the context of reproduction, glucocorticoids (GCs) are generally considered to have negative effects. However, in well-studied model species, GCs fluctuate predictability across the estrous cycles, and short-term increases promote healthy ovarian function. Reproductive challenges have plagued captive elephant populations, which are not currently self-sustaining. Efforts to understand reproductive dysfunction in elephants have focused on the suppressive effects of cortisol, but the potential permissive or stimulatory effects of cortisol are unknown. In this study, we provide a detailed examination of cortisol patterns across the estrous cycle in Asian elephants (Elephas maximus). Time series analysis was used to analyze cortisol and progesterone data for a total of 73 cycles from eight females. We also compared cortisol profiles between females that successfully conceived and females that failed to conceive despite repeated mating attempts. Our results revealed that cortisol fluctuates predictably across the estrous cycle, with a peak during the second half of the follicular phase followed by low levels throughout the luteal phase. Furthermore, this pattern was significantly altered in nulliparous females; cortisol concentrations did not decline during the luteal phase to the same extent as in parous females. This study highlights the complexity of cortisol signaling and suggests future directions for understanding the role of cortisol in reproductive dysfunction.

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Yue-Yue Wang Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

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Qian Wu Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

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Lu Chen Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

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Wen Chen Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

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Tao Yang Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

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Xiao-Quan Xu Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

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Fei-Yun Wu Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

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Hao Hu Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

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Huan-Huan Chen Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

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Purpose

To evaluate the value of MRI-based texture analysis of extraocular muscle (EOM) and orbital fat (OF) in monitoring and predicting the response to glucocorticoid (GC) therapy in patients with thyroid-associated ophthalmopathy (TAO).

Methods

Thirty-seven active and moderate-to-severe TAO patients (responders, n = 23; unresponders, n = 14) were retrospectively enrolled. MRI-based texture parameters (entropy, uniformity, skewness and kurtosis) of EOM and OF were measured before and after GC therapy, and compared between groups. Correlations between the changes of clinical activity score (CAS) and imaging parameters before and after treatment were assessed. Receiver operating characteristic curves were used to evaluate the predictive value of identified variables.

Results

Responsive TAOs showed significantly decreased entropy and increased uniformity at EOM and OF after GC therapy (P < 0.01), while unresponders showed no significance. Changes of entropy and uniformity at EOM and OF were significantly correlated with changes of CAS before and after treatment (P < 0.05). Responders showed significantly lower entropy and higher uniformity at EOM than unresponders before treatment (P < 0.01). Entropy and uniformity of EOM and disease duration were identified as independent predictors for responsive TAOs. Combination of all three variables demonstrated optimal efficiency (area under curve, 0.802) and sensitivity (82.6%), and disease duration alone demonstrated optimal specificity (100%) for predicting responsive TAOs.

Conclusion

MRI-based texture analysis can reflect histopathological heterogeneity of orbital tissues. It could be useful for monitoring and predicting the response to GC in TAO patients.

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