Endocrine reviews最新文献

{"title":"Common and Uncommon Mouse Models of Growth Hormone Deficiency.","authors":"Edward O List, Reetobrata Basu, Darlene E Berryman, Silvana Duran-Ortiz, Gabriel Á Martos-Moreno, John J Kopchick","doi":"10.1210/endrev/bnae017","DOIUrl":"10.1210/endrev/bnae017","url":null,"abstract":"<p><p>Mouse models of growth hormone deficiency (GHD) have provided important tools for uncovering the various actions of GH. Nearly 100 years of research using these mouse lines has greatly enhanced our knowledge of the GH/IGF-1 axis. Some of the shared phenotypes of the 5 \"common\" mouse models of GHD include reduced body size, delayed sexual maturation, decreased fertility, reduced muscle mass, increased adiposity, and enhanced insulin sensitivity. Since these common mouse lines outlive their normal-sized littermates-and have protection from age-associated disease-they have become important fixtures in the aging field. On the other hand, the 12 \"uncommon\" mouse models of GHD described herein have tremendously divergent health outcomes ranging from beneficial aging phenotypes (similar to those described for the common models) to extremely detrimental features (such as improper development of the central nervous system, numerous sensory organ defects, and embryonic lethality). Moreover, advancements in next-generation sequencing technologies have led to the identification of an expanding array of genes that are recognized as causative agents to numerous rare syndromes with concomitant GHD. Accordingly, this review provides researchers with a comprehensive up-to-date collection of the common and uncommon mouse models of GHD that have been used to study various aspects of physiology and metabolism associated with multiple forms of GHD. For each mouse line presented, the closest comparable human syndromes are discussed providing important parallels to the clinic.</p>","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":" ","pages":"818-842"},"PeriodicalIF":22.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Challenges and Future Directions in the Assessment of Glucocorticoid Status.","authors":"Sophie A Clarke, Pei Chia Eng, Alexander N Comninos, Katharine Lazarus, Sirazum Choudhury, Christie Tsang, Karim Meeran, Tricia M Tan, Waljit S Dhillo, Ali Abbara","doi":"10.1210/endrev/bnae016","DOIUrl":"10.1210/endrev/bnae016","url":null,"abstract":"<p><p>Glucocorticoid (GC) hormones are secreted in a circadian and ultradian rhythm and play a critical role in maintaining physiological homeostasis, with both excess and insufficient GC associated with adverse effects on health. Current assessment of GC status is primarily clinical, often in conjunction with serum cortisol values, which may be stimulated or suppressed depending on the GC disturbance being assessed. In the setting of extreme perturbations in cortisol levels ie, markedly low or high levels, symptoms and signs of GC dysfunction may be overt. However, when disturbances in cortisol GC status values are less extreme, such as when assessing optimization of a GC replacement regimen, signs and symptoms can be more subtle or nonspecific. Current tools for assessing GC status are best suited to identifying profound disturbances but may lack sensitivity for confirming optimal GC status. Moreover, single cortisol values do not necessarily reflect an individual's GC status, as they are subject to inter- and intraindividual variation and do not take into account the pulsatile nature of cortisol secretion, variation in binding proteins, or local tissue concentrations as dictated by 11beta-hydroxysteroid dehydrogenase activity, as well as GC receptor sensitivity. In the present review, we evaluate possible alternative methods for the assessment of GC status that do not solely rely on the measurement of circulating cortisol levels. We discuss the potential of changes in metabolomic profiles, micro RNA, gene expression, and epigenetic and other novel biomarkers such as growth differentiating factor 15 and osteocalcin, which could in the future aid in the objective classification of GC status.</p>","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":" ","pages":"795-817"},"PeriodicalIF":22.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11581704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Teprotumumab for the Treatment of Thyroid Eye Disease.","authors":"Shoaib Ugradar, Emil Malkhasyan, Raymond S Douglas","doi":"10.1210/endrev/bnae018","DOIUrl":"10.1210/endrev/bnae018","url":null,"abstract":"<p><p>Thyroid eye disease (TED) is the most common extra thyroidal manifestation of Graves' disease (GD). It may also present in those who are hypothyroid or euthyroid. The characteristic clinical manifestations of TED, chemosis, lid swelling, proptosis, and diplopia, are driven by a combination of inflammation and extracellular matrix modification. It has recently emerged that 1 of the major drivers of this molecular signature is the overexpression of the IGF-1 receptor [IGF-1R]) on key effector cells in TED pathogenesis. The overexpression of the IGF-1R is coupled with a dysregulation of the IGF-1R axis, which links other pathways that modulate inflammation, such as fibrosis and extracellular matrix organization, in patients with TED. This overexpression is also found to persist from the acute stage into the chronic phase. Teprotumumab, a fully human IgG1 monoclonal antibody that inhibits the IGF-1R, recently gained approval in the United States for the treatment of TED. In phase 2 and phase 3 clinical studies, teprotumumab showed efficacy in reducing inflammation, proptosis, diplopia, and burden on quality of life in patients who were treated. Postintroduction studies have confirmed the results of the phase 2 and phase 3 studies. Since 2020, more than 5800 patients have been treated with teprotumumab, and it appears to be well tolerated. The American Thyroid Association and the European Thyroid Association have recommended it as first-line therapy for patients with moderate to severe TED who display features of proptosis and diplopia.</p>","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":" ","pages":"843-857"},"PeriodicalIF":22.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risks of Iodine Excess.","authors":"Seo Young Sohn, Kosuke Inoue, Connie M Rhee, Angela M Leung","doi":"10.1210/endrev/bnae019","DOIUrl":"10.1210/endrev/bnae019","url":null,"abstract":"<p><p>Iodine is a micronutrient that is required for thyroid hormone synthesis. The iodide cycle in thyroid hormone synthesis consists of a series of transport, oxidation, organification, and binding/coupling steps in thyroid follicular cells. Common sources of iodine include the consumption of an iodine-rich diet or iodine-fortified foods, the administration of amiodarone, iodine-containing supplements, or iodinated contrast media, and other miscellaneous sources. Methods to assess population iodine status include the measurement of urinary iodine concentrations, blood thyroglobulin levels, prevalence of elevated neonatal thyrotropin levels, and thyroid volume. Although excessive iodine intake or exposure is generally well tolerated, an acute iodine load may result in thyroid dysfunction (hypothyroidism or hyperthyroidism) in certain susceptible individuals due to the failure to escape from the Wolff-Chaikoff effect and to the Jod-Basedow phenomenon, respectively. In this review, we discuss the associations between excessive iodine intake or exposure, with particular focus on iodinated contrast media as a common source of excess iodine in health care settings, and risks of incident thyroid dysfunction. We also summarize the risks of iodine excess in vulnerable populations and review current guidelines regarding the screening and monitoring of iodinated contrast-induced thyroid dysfunction. Finally, we discuss the long-term potential nonthyroidal health risks associated with iodine excess and suggest the need for more data to define safe upper limits for iodine intake, particularly in high-risk populations.</p>","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":" ","pages":"858-879"},"PeriodicalIF":22.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement.","authors":"Niki Karavitaki,Jeffrey J Bettinger,Nienke Biermasz,Mirjam Christ-Crain,Monica R Gadelha,Warrick J Inder,Elena Tsourdi,Sarah E Wakeman,Maria Zatelli","doi":"10.1210/endrev/bnae023","DOIUrl":"https://doi.org/10.1210/endrev/bnae023","url":null,"abstract":"The use and misuse of opioids are a growing global problem. Although the effects of these drugs on the human endocrine system have been studied for decades, attention on their related clinical consequences, particularly on the hypothalamic-pituitary system and bone health, has intensified over recent years. This Statement appraises research data related to the impact of opioids on the gonadal and adrenal function. Whereas hypogonadism is well recognized as a side effect of opioids, the significance of their inhibitory actions on the hypothalamic-pituitary-adrenal system and the occurrence of clinically relevant adrenal insufficiency is not fully elucidated. The often-inconsistent results of studies investigating how opioids affect the secretion of GH, prolactin, arginine vasopressin, and oxytocin are assessed. The accumulating evidence of opioid actions on bone metabolism and their negative sequelae on bone mineral density and risk of fracture are also reviewed. In each section, available data on diagnostic and management approaches for opioid endocrine sequelae are described. This Statement highlights a plethora of gaps in research associated with the effects and clinical consequences of opioids on the endocrine system. It is anticipated that addressing these gaps will improve the care of people using or misusing opioids worldwide. The Statement is not intended to serve as a guideline or dictate treatment decisions.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"79 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Insulin-like Growth Factor System and Aging.","authors":"Cheryl A Conover,Claus Oxvig","doi":"10.1210/endrev/bnae029","DOIUrl":"https://doi.org/10.1210/endrev/bnae029","url":null,"abstract":"There is strong evidence that insulin-like growth factor (IGF) signaling is involved in fundamental aspects of the aging process. However, the extracellular part of the IGF system is complex with various receptors, ligand effectors, high affinity IGF binding proteins, proteinases and endogenous inhibitors that all, along with their biological context, must be considered. The IGF system components are evolutionarily conserved, underscoring the importance of understanding this system in physiology and pathophysiology. This review will briefly describe the different components of the IGF system and then discuss past and current literature regarding the IGFs and aging, with a focus on cellular senescence, model organisms of aging, centenarian genetics, and three age-related diseases - pulmonary fibrosis, Alzheimer's disease, and macular degeneration - in appropriate murine models and in humans. Commonalities in mechanism suggest conditions where IGF system components may be disease drivers and potential targets in promoting healthy aging in humans.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"11 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142447976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows.","authors":"Andrea Giustina, John P Bilezikian, Robert A Adler, Giuseppe Banfi, Daniel D Bikle, Neil C Binkley, Jens Bollerslev, Roger Bouillon, Maria Luisa Brandi, Felipe F Casanueva, Luigi di Filippo, Lorenzo M Donini, Peter R Ebeling, Ghada El-Hajj Fuleihan, Angelo Fassio, Stefano Frara, Glenville Jones, Claudio Marcocci, Adrian R Martineau, Salvatore Minisola, Nicola Napoli, Massimo Procopio, René Rizzoli, Anne L Schafer, Christopher T Sempos, Fabio Massimo Ulivieri, Jyrki K Virtanen","doi":"10.1210/endrev/bnae009","DOIUrl":"10.1210/endrev/bnae009","url":null,"abstract":"<p><p>The 6th International Conference, \"Controversies in Vitamin D,\" was convened to discuss controversial topics, such as vitamin D metabolism, assessment, actions, and supplementation. Novel insights into vitamin D mechanisms of action suggest links with conditions that do not depend only on reduced solar exposure or diet intake and that can be detected with distinctive noncanonical vitamin D metabolites. Optimal 25-hydroxyvitamin D (25(OH)D) levels remain debated. Varying recommendations from different societies arise from evaluating different clinical or public health approaches. The lack of assay standardization also poses challenges in interpreting data from available studies, hindering rational data pooling and meta-analyses. Beyond the well-known skeletal features, interest in vitamin D's extraskeletal effects has led to clinical trials on cancer, cardiovascular risk, respiratory effects, autoimmune diseases, diabetes, and mortality. The initial negative results are likely due to enrollment of vitamin D-replete individuals. Subsequent post hoc analyses have suggested, nevertheless, potential benefits in reducing cancer incidence, autoimmune diseases, cardiovascular events, and diabetes. Oral administration of vitamin D is the preferred route. Parenteral administration is reserved for specific clinical situations. Cholecalciferol is favored due to safety and minimal monitoring requirements. Calcifediol may be used in certain conditions, while calcitriol should be limited to specific disorders in which the active metabolite is not readily produced in vivo. Further studies are needed to investigate vitamin D effects in relation to the different recommended 25(OH)D levels and the efficacy of the different supplementary formulations in achieving biochemical and clinical outcomes within the multifaced skeletal and extraskeletal potential effects of vitamin D.</p>","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":" ","pages":"625-654"},"PeriodicalIF":22.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11405507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140851958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Cell Senescence and Senolytics: Novel Interventions for Age-Related Endocrine Dysfunction.","authors":"Masayoshi Suda, Karl H Paul, Utkarsh Tripathi, Tohru Minamino, Tamara Tchkonia, James L Kirkland","doi":"10.1210/endrev/bnae010","DOIUrl":"10.1210/endrev/bnae010","url":null,"abstract":"<p><p>Multiple changes occur in hormonal regulation with aging and across various endocrine organs. These changes are associated with multiple age-related disorders and diseases. A better understanding of responsible underling biological mechanisms could help in the management of multiple endocrine disorders over and above hormone replacement therapy (HRT). Cellular senescence is involved in multiple biological aging processes and pathologies common in elderly individuals. Cellular senescence, which occurs in many older individuals but also across the lifespan in association with tissue damage, acute and chronic diseases, certain drugs, and genetic syndromes, may contribute to such endocrine disorders as osteoporosis, metabolic syndrome, and type 2 diabetes mellitus. Drugs that selectively induce senescent cell removal, \"senolytics,\", and drugs that attenuate the tissue-destructive secretory state of certain senescent cells, \"senomorphics,\" appear to delay the onset of or alleviate multiple diseases, including but not limited to endocrine disorders such as diabetes, complications of obesity, age-related osteoporosis, and cancers as well as atherosclerosis, chronic kidney disease, neurodegenerative disorders, and many others. More than 30 clinical trials of senolytic and senomorphic agents have already been completed, are underway, or are planned for a variety of indications. Targeting senescent cells is a novel strategy that is distinct from conventional therapies such as HRT, and thus might address unmet medical needs and can potentially amplify effects of established endocrine drug regimens, perhaps allowing for dose decreases and reducing side effects.</p>","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":" ","pages":"655-675"},"PeriodicalIF":22.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11405506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Genetic Pathophysiology and Clinical Management of the TADopathy, X-Linked Acrogigantism.","authors":"Adrian F Daly, Albert Beckers","doi":"10.1210/endrev/bnae014","DOIUrl":"10.1210/endrev/bnae014","url":null,"abstract":"<p><p>Pituitary gigantism is a rare manifestation of chronic growth hormone (GH) excess that begins before closure of the growth plates. Nearly half of patients with pituitary gigantism have an identifiable genetic cause. X-linked acrogigantism (X-LAG; 10% of pituitary gigantism) typically begins during infancy and can lead to the tallest individuals described. In the 10 years since its discovery, about 40 patients have been identified. Patients with X-LAG usually develop mixed GH and prolactin macroadenomas with occasional hyperplasia that secrete copious amounts of GH, and frequently prolactin. Circulating GH-releasing hormone is also elevated in a proportion of patients. X-LAG is caused by constitutive or sporadic mosaic duplications at chromosome Xq26.3 that disrupt the normal chromatin architecture of a topologically associating domain (TAD) around the orphan G-protein-coupled receptor, GPR101. This leads to the formation of a neo-TAD in which GPR101 overexpression is driven by ectopic enhancers (\"TADopathy\"). X-LAG has been seen in 3 families due to transmission of the duplication from affected mothers to sons. GPR101 is a constitutively active receptor with an unknown natural ligand that signals via multiple G proteins and protein kinases A and C to promote GH/prolactin hypersecretion. Treatment of X-LAG is challenging due to the young patient population and resistance to somatostatin analogs; the GH receptor antagonist pegvisomant is often an effective option. GH, insulin-like growth factor 1, and prolactin hypersecretion and physical overgrowth can be controlled before definitive adult gigantism occurs, often at the cost of permanent hypopituitarism.</p>","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":" ","pages":"737-754"},"PeriodicalIF":22.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140851959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relative Energy Deficiency in Sport (REDs): Endocrine Manifestations, Pathophysiology and Treatments.","authors":"Angeliki M Angelidi, Konstantinos Stefanakis, Sharon H Chou, Laura Valenzuela-Vallejo, Konstantina Dipla, Chrysoula Boutari, Konstantinos Ntoskas, Panagiotis Tokmakidis, Alexander Kokkinos, Dimitrios G Goulis, Helen A Papadaki, Christos S Mantzoros","doi":"10.1210/endrev/bnae011","DOIUrl":"10.1210/endrev/bnae011","url":null,"abstract":"<p><p>Research on lean, energy-deficient athletic and military cohorts has broadened the concept of the Female Athlete Triad into the Relative Energy Deficiency in Sport (REDs) syndrome. REDs represents a spectrum of abnormalities induced by low energy availability (LEA), which serves as the underlying cause of all symptoms described within the REDs concept, affecting exercising populations of either biological sex. Both short- and long-term LEA, in conjunction with other moderating factors, may produce a multitude of maladaptive changes that impair various physiological systems and adversely affect health, well-being, and sport performance. Consequently, the comprehensive definition of REDs encompasses a broad spectrum of physiological sequelae and adverse clinical outcomes related to LEA, such as neuroendocrine, bone, immune, and hematological effects, ultimately resulting in compromised health and performance. In this review, we discuss the pathophysiology of REDs and associated disorders. We briefly examine current treatment recommendations for REDs, primarily focusing on nonpharmacological, behavioral, and lifestyle modifications that target its underlying cause-energy deficit. We also discuss treatment approaches aimed at managing symptoms, such as menstrual dysfunction and bone stress injuries, and explore potential novel treatments that target the underlying physiology, emphasizing the roles of leptin and the activin-follistatin-inhibin axis, the roles of which remain to be fully elucidated, in the pathophysiology and management of REDs. In the near future, novel therapies leveraging our emerging understanding of molecules and physiological axes underlying energy availability or lack thereof may restore LEA-related abnormalities, thus preventing and/or treating REDs-related health complications, such as stress fractures, and improving performance.</p>","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":" ","pages":"676-708"},"PeriodicalIF":22.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}