Abstract：
:Glucocorticoids (GC) such as cortisol regulate multiple physiological functions, notably those involved in development, metabolism, inflammatory processes and stress, and exert their effects upon binding to the glucocorticoid receptor (GR, encoded by NR3C1 gene in humans). GC signaling follows several consecutive steps leading to target gene transactivation, including ligand binding, nuclear translocation of ligand-activated GR complexes, DNA binding, and recruitment of functional transcriptional machinery. Generalized glucocorticoid resistance syndrome, due to GR loss-of-function mutations, may be related to the impairment of one of the GC signaling steps. To date, 31 NR3C1 loss-of-function mutations have been reported in patients presenting with various clinical signs such as hypertension, adrenal hyperplasia, hirsutism or metabolic disorders associated with biological hypercortisolism but without Cushing syndrome signs and no negative regulatory feedback loop on the hypothalamic-pituitary-adrenal axis. Functional characterization of GR loss-of-function mutations often demonstrates GR haploinsufficiency and a decrease of GR target gene induction in relevant cell types. The main signs at presentation are very variable from resistant hypertension, bilateral adrenal hyperplasia likely related to increased ACTH levels but not exclusively, hirsutism to isolated renin-angiotensin-aldosterone system abnormalities in a context of 11βHSD2 deficiency. Some mutated GR patients are obese or overweight together with a healthier metabolic profile that remains to be further explored in future studies. Deciphering the molecular mechanisms altered by GR mutations should enhance our knowledge on GR signaling and ultimately facilitate management of GC-resistant patients. This review also focuses on the criteria facilitating identification of novel NR3C1 mutations in selected patients.
journal_name
Eur J Endocrinoljournal_title
European journal of endocrinologyauthors
Vitellius G,Lombes Mdoi
10.1530/EJE-19-0811subject
Has Abstractpub_date
2020-02-01 00:00:00pages
R15-R27issue
2eissn
0804-4643issn
1479-683Xpii
EJE-19-0811journal_volume
182pub_type
杂志文章,评审abstract：:Sex steroids are important for the growth and maintenance of both the female and the male skeleton. However, the relative contribution of androgens versus estrogens in the regulation of the male skeleton is unclear. Experiments using mice with inactivated sex steroid receptors demonstrated that both activation of the ...
journal_title：European journal of endocrinology
pub_type： 杂志文章,评审
doi：10.1530/EJE-09-0118
更新日期：2009-06-01 00:00:00
abstract：OBJECTIVE:In the last decade, surgery of primary hyperparathyroidism (HPT) due to a solitary adenoma has moved on from the traditional wide bilateral neck exploration (BNE) to more limited approaches such as unilateral neck exploration and minimally invasive parathyroidectomy. DESIGN:To define the role of intraoperati...
journal_title：European journal of endocrinology
pub_type： 临床试验,杂志文章
doi：10.1530/eje.0.1490007
更新日期：2003-07-01 00:00:00
abstract：:123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy scanning is commonly used in the imaging of phaeochromocytoma (and paraganglioma) to confirm the site of disease and whether any spread has occurred. However, 123I-MIBG imaging is negative in 15% of cases of benign phaeochromocytoma and around 50% of cases of malig...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/EJE-07-0369
更新日期：2007-10-01 00:00:00
abstract：OBJECTIVE:Smaller size at birth has been associated with an increased risk of metabolic and cardiovascular disorders in adult life. Fetal programming of the hypothalamic-pituitary-adrenal axis has been suggested as a possible explanation. Fetal glucocorticoid (GC) overexposure has effects that suggest a role of GCs in ...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/EJE-10-0718
更新日期：2010-12-01 00:00:00
abstract：:The recent discovery that functional brown adipose tissue (BAT) persists in adult humans has enkindled a renaissance in metabolic research, with a view of harnessing its thermogenic capacity to combat obesity. This review focuses on the advances in the regulation and the metabolic significance of BAT in humans. BAT ac...
journal_title：European journal of endocrinology
pub_type： 杂志文章,评审
doi：10.1530/EJE-15-1217
更新日期：2016-07-01 00:00:00
abstract：OBJECTIVE:Non-thyroidal illness (NTI) is associated with alterations in thyroid hormone metabolism. Whether morphological changes of the thyroid gland accompany NTI is unknown. The aim of the present study was to describe thyroid morphology in patients with lethal non-thyroidal disease. DESIGN:In an autopsy study 267 ...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/eje.0.1440221
更新日期：2001-03-01 00:00:00
abstract：OBJECTIVE:An increased tendency towards thromboembolic events is observed in patients with Cushing's syndrome. There are much fewer publications available about thromboembolic complications in patients with subclinical Cushing's syndrome (SCS). Therefore, a question arises whether hemostatic disturbances appear in this...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/EJE-11-0535
更新日期：2011-12-01 00:00:00
abstract：OBJECTIVE:Increased reverse tritiodothyronine (T(3)) used to be described as a part of euthyroid sick syndrome (ESS). It was demonstrated to be associated with increased mortality in acutely ill patients. It can also be found with low or normal T(3) in non-severely ill subjects but its significance remains unclear. PA...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/EJE-08-0519
更新日期：2009-02-01 00:00:00
abstract：OBJECTIVE:Iodine deficiency has re-emerged in New Zealand, while selenium status has improved. The aim of this study was to investigate the effects of excess iodine intake as iodate on thyroid and selenium status. METHODS:In a randomized controlled trial on older people (mean±s.d. 73±4.8 years; n=143), two groups rece...
journal_title：European journal of endocrinology
pub_type： 杂志文章,随机对照试验
doi：10.1530/EJE-11-0575
更新日期：2011-11-01 00:00:00
abstract：OBJECTIVE:Adrenocortical tumors may originate from the zona glomerulosa, zona fasciculata, or zona reticularis and be associated with syndromes due to overproduction of mineralocorticoids, glucocorticoids, or androgens respectively. We report an unusual case of recurrent adrenocortical carcinoma (ACC), which seems to c...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/eje.1.02011
更新日期：2005-11-01 00:00:00
abstract：:To assess the metabolic effects of thyroid disease, body composition was determined by bioimpedance analysis (BIA) in 72 patients with untreated hyperthyroidism (mean age 48.7 +/- 1.9 years) and 26 patients with untreated hypothyroidism (63.8 +/- 3.4 years). Bioelectrical whole body resistance (R) and reactance (Xc) w...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/eje.0.1360493
更新日期：1997-05-01 00:00:00
abstract：:The objective was to compare the changes in prostaglandin synthesis and metabolism occurring within the fetal membranes that are associated with the onset of parturition and to study the effect of steroid hormones on prostaglandin metabolism. A tissue explant study was made of discs of amnion and chorion obtained from...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/eje.0.1330527
更新日期：1995-11-01 00:00:00
abstract：OBJECTIVE:Adiponectin and resistin have been linked to inflammation, endothelial dysfunction, and/or insulin secretion or resistance. It remains to be elucidated which of these adipokines is associated primarily with biomarkers of all or only some of these categories, i.e. biomarkers of inflammation, endothelial dysfun...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/EJE-09-0555
更新日期：2010-02-01 00:00:00
abstract：:Endogenous pathologic hypercortisolism, or Cushing's syndrome, is associated with poor quality of life, morbidity, and increased mortality. Early diagnosis may mitigate against this natural history of the disorder. The clinical presentation of Cushing's syndrome varies, in part related to the extent and duration of co...
journal_title：European journal of endocrinology
pub_type： 杂志文章,评审
doi：10.1530/EJE-15-0464
更新日期：2015-10-01 00:00:00
abstract：BACKGROUND:Sleep behavior is changing toward shorter sleep duration and a later chronotype. It results in a sleep debt that is acquitted on work-free days, inducing a small but recurrent sleep misalignment each week, referred to as "social jetlag". These sleep habits could affect health through misalignment with circad...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/EJE-16-0188
更新日期：2016-11-01 00:00:00
abstract：OBJECTIVE:Late diagnosis hinders proper management of small intestine neuroendocrine carcinoma (SI-NEC) patients. The olfactory receptor, family 51, subfamily E, member 1 (OR51E1) has been reported as a potential novel SI-NEC marker, without protein expression recognition. Thus, we further studied whether the encoded p...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/EJE-12-0814
更新日期：2013-01-17 00:00:00
abstract：OBJECTIVE:The intrarenal renin-angiotensin system (RAS) activation plays a pivotal role in immunoglobulin A nephropathy (IgAN) pathogenesis, which is still largely undefined. Recently, vasopressin (AVP) has been advocated to contribute to the genesis and progression of chronic kidney diseases (CKD) directly, and indire...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/EJE-11-0512
更新日期：2011-10-01 00:00:00
abstract：OBJECTIVE:Glucocorticoid-induced osteoporosis is the most frequent cause of secondary osteoporosis. Nevertheless, limited data are available on bone status in patients with endogenous cortisol excess. This study is aimed at investigating the role of sex steroids and severity of hypercortisolism on bone mineral density ...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/EJE-07-0137
更新日期：2007-09-01 00:00:00
abstract：:The recent onslaught of mass spectrometry (MS) to measurements of steroid hormones, including demands that they should be the only acceptable method, has confused clinicians and scientists who have relied for more than 40 years on a variety of immunoassay (IA) methods in steroid hormone measurements. There is little d...
journal_title：European journal of endocrinology
pub_type： 杂志文章,评审
doi：10.1530/EJE-15-0338
更新日期：2015-08-01 00:00:00
abstract：OBJECTIVE:To compare baseline characteristics in adult patients with growth hormone (GH) deficiency (GHD) who had previously been treated for Cushing's disease or acromegaly with data from patients with GHD of other aetiologies. To study the effects of GH therapy in those patients who had completed at least 6 months of...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/eje.0.1460067
更新日期：2002-01-01 00:00:00
abstract：CONTEXT:Steroidogenic acute regulatory (STAR) gene mutations lead to adrenal and gonadal failure. Interesting, though as yet unexplained, features are the formation of ovarian cysts and the potential presence of CNS findings. OBJECTIVE:To report biochemical, genetic, and long-term clinical data in five Greek patients ...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/EJE-12-0600
更新日期：2013-02-15 00:00:00
abstract：:Glucose transporter-1 (GLUT1) has been found in high abundance in human placentas. The purpose of this study was to analyze the changes in the level of GLUT1 during pregnancy. We have analyzed the gestational changes in human placental GLUT1 by [3H]cytochalasin B binding assay, immunoblot analysis and Northern blot an...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/eje.0.1320206
更新日期：1995-02-01 00:00:00
abstract：OBJECTIVE:To assess the performance of current clinical recommendations for the evaluation of an adrenal incidentaloma. DESIGN AND METHODS LITERATURE REVIEW: Electronic databases (Pubmed, Ovid and citation searches from key articles) from 1980 to 2008 were searched. Eligible studies were those deemed most applicable to...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/EJE-09-0234
更新日期：2009-10-01 00:00:00
abstract：OBJECTIVE:Adult height deficit seen in Turner syndrome (TS) originates, in part, from growth retardation in utero and throughout the first 3 years of life. Earlier diagnosis enables earlier therapeutic intervention, such as with recombinant human GH (r-hGH), which may help to prevent growth retardation. In this open-la...
journal_title：European journal of endocrinology
pub_type： 杂志文章,多中心研究
doi：10.1530/EJE-10-1048
更新日期：2011-06-01 00:00:00
abstract：:Amiodarone (AMD) is a powerful anti-arrhythmic drug used for the treatment of a wide variety of cardiac arrhythmias and its most striking feature is its high iodine content. Thyroid dysfunction is a limiting side-effect of the drug and both AMD-induced hypothyroidism (AIH) and AMD-induced thyrotoxicosis (AIT) are repo...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/eje.0.1400241
更新日期：1999-03-01 00:00:00
abstract：:Pituitary adenomas are frequently occurring neoplasms that produce clinically significant disease in 1:1000 of the general population. The pathogenesis of pituitary tumors is a matter of interest as it could help to improve diagnosis and treatment. Until recently, however, disruptions in relatively few genes were know...
journal_title：European journal of endocrinology
pub_type： 杂志文章,评审
doi：10.1530/EJE-19-0602
更新日期：2019-12-01 00:00:00
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journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/EJE-15-1081
更新日期：2016-04-01 00:00:00
abstract：:We investigated the ontogeny of melatonin synthesis during fetal maturation by measuring the melatonin (MLT) and 6-hydroxymelatonin sulfate (MLTS) excretion in the urine of male infants aged 2-7 days and gestational age 26-42 weeks. We found a negative correlation between advancing gestational age and the MLT and MLTS...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/eje.0.1350184
更新日期：1996-08-01 00:00:00
abstract：BACKGROUND:Survival rates among childhood cancer survivors (CCS) have enormously increased in the last 40 years. However, this improvement has been achieved at the expense of serious late effects that frequently involve the endocrine system. AIM:To evaluate the cumulative incidence of endocrine diseases in a cohort of...
journal_title：European journal of endocrinology
pub_type： 杂志文章
doi：10.1530/EJE-12-1043
更新日期：2013-02-20 00:00:00
abstract：:Endocrine complications are frequently observed in childhood cancer survivors (CCS). One of two CCS will experience at least one endocrine complication during the course of his/her lifespan, most commonly as a late-effect of cancer treatments, especially radiotherapy and alkylating agent chemotherapy. Endocrine late-e...
journal_title：European journal of endocrinology
pub_type： 杂志文章,评审
doi：10.1530/EJE-17-0054
更新日期：2017-04-01 00:00:00
