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Current Opinion in Endocrinology,... Feb 2018To summarize the recent developments in endocrine disorders associated with Down syndrome. (Review)
Review
PURPOSE OF REVIEW
To summarize the recent developments in endocrine disorders associated with Down syndrome.
RECENT FINDINGS
Current research regarding bone health and Down syndrome continues to show an increased prevalence of low bone mass and highlights the importance of considering short stature when interpreting dual energy x-ray absorptiometry. The underlying cause of low bone density is an area of active research and will shape treatment and preventive measures. Risk of thyroid disease is present throughout the life course in individuals with Down syndrome. New approaches and understanding of the pathophysiology and management of subclinical hypothyroidism continue to be explored. Individuals with Down syndrome are also at risk for other autoimmune conditions, with recent research revealing the role of the increased expression of the Autoimmune Regulatory gene on 21st chromosome. Lastly, Down-syndrome-specific growth charts were recently published and provide a better assessment of growth.
SUMMARY
Recent research confirms and expands on the previously known endocrinopathies in Down syndrome and provides more insight into potential underlying mechanisms.
Topics: Down Syndrome; Endocrine System Diseases; Female; Humans; Prevalence; Thyroid Diseases
PubMed: 29135488
DOI: 10.1097/MED.0000000000000382 -
Endocrine Reviews Nov 2022More than 2.1 million age-related fractures occur in the United States annually, resulting in an immense socioeconomic burden. Importantly, the age-related deterioration... (Review)
Review
More than 2.1 million age-related fractures occur in the United States annually, resulting in an immense socioeconomic burden. Importantly, the age-related deterioration of bone structure is associated with impaired bone healing. Fracture healing is a dynamic process which can be divided into four stages. While the initial hematoma generates an inflammatory environment in which mesenchymal stem cells and macrophages orchestrate the framework for repair, angiogenesis and cartilage formation mark the second healing period. In the central region, endochondral ossification favors soft callus development while next to the fractured bony ends, intramembranous ossification directly forms woven bone. The third stage is characterized by removal and calcification of the endochondral cartilage. Finally, the chronic remodeling phase concludes the healing process. Impaired fracture healing due to aging is related to detrimental changes at the cellular level. Macrophages, osteocytes, and chondrocytes express markers of senescence, leading to reduced self-renewal and proliferative capacity. A prolonged phase of "inflammaging" results in an extended remodeling phase, characterized by a senescent microenvironment and deteriorating healing capacity. Although there is evidence that in the setting of injury, at least in some tissues, senescent cells may play a beneficial role in facilitating tissue repair, recent data demonstrate that clearing senescent cells enhances fracture repair. In this review, we summarize the physiological as well as pathological processes during fracture healing in endocrine disease and aging in order to establish a broad understanding of the biomechanical as well as molecular mechanisms involved in bone repair.
Topics: Humans; Fracture Healing; Bony Callus; Osteogenesis; Fractures, Bone; Cellular Senescence; Aging; Endocrine System Diseases
PubMed: 35182420
DOI: 10.1210/endrev/bnac008 -
Nature Reviews. Endocrinology May 2020With the ageing of the global population, interest is growing in the 'geroscience hypothesis', which posits that manipulation of fundamental ageing mechanisms will delay... (Review)
Review
With the ageing of the global population, interest is growing in the 'geroscience hypothesis', which posits that manipulation of fundamental ageing mechanisms will delay (in parallel) the appearance or severity of multiple chronic, non-communicable diseases, as these diseases share the same underlying risk factor - namely, ageing. In this context, cellular senescence has received considerable attention as a potential target in preventing or treating multiple age-related diseases and increasing healthspan. Here we review mechanisms of cellular senescence and approaches to target this pathway therapeutically using 'senolytic' drugs that kill senescent cells or inhibitors of the senescence-associated secretory phenotype (SASP). Furthermore, we highlight the evidence that cellular senescence has a causative role in multiple diseases associated with ageing. Finally, we focus on the role of cellular senescence in a number of endocrine diseases, including osteoporosis, metabolic syndrome and type 2 diabetes mellitus, as well as other endocrine conditions. Although much remains to be done, considerable preclinical evidence is now leading to the initiation of proof-of-concept clinical trials using senolytics for several endocrine and non-endocrine diseases.
Topics: Aging; Animals; Cellular Senescence; Endocrine System Diseases; Humans; Risk Factors
PubMed: 32161396
DOI: 10.1038/s41574-020-0335-y -
Frontiers in Endocrinology 2022It is estimated that more and more couples suffer from fertility and pregnancy maintenance disorders. It is associated with impaired androgen secretion, which is... (Review)
Review
It is estimated that more and more couples suffer from fertility and pregnancy maintenance disorders. It is associated with impaired androgen secretion, which is influenced by many factors, ranging from genetic to environmental. It is also important to remember that fertility disorders can also result from abnormal anatomy of the reproductive male and female organ (congenital uterine anomalies - septate, unicornuate, bicornuate uterus; acquired defects of the uterus structure - fibroids, polyps, hypertrophy), disturbed hormonal cycle and obstruction of the fallopian tubes resulting from the presence of adhesions due to inflammation, endometriosis, and surgery, abnormal rhythm of menstrual bleeding, the abnormal concentration of hormones. There are many relationships between the endocrine organs, leading to a chain reaction when one of them fails to function properly. Conditions in which the immune system is involved, including infections and autoimmune diseases, also affect fertility. The form of treatment depends on infertility duration and the patient's age. It includes ovulation stimulation with clomiphene citrate or gonadotropins, metformin use, and weight loss interventions. Since so many different factors affect fertility, it is important to correctly diagnose what is causing the problem and to modify the treatment regimen if necessary. This review describes disturbances in the hormone secretion of individual endocrine organs in the context of fertility and the maintenance of pregnancy.
Topics: Pregnancy; Male; Female; Humans; Fertility; Reproduction; Infertility; Uterus; Clomiphene; Leiomyoma; Endocrine System Diseases
PubMed: 36733805
DOI: 10.3389/fendo.2022.970439 -
The Lancet. Diabetes & Endocrinology Oct 2014The term sarcopenia refers to the loss of muscle mass that occurs with ageing. On the basis of study results showing that muscle mass is only moderately related to... (Review)
Review
The term sarcopenia refers to the loss of muscle mass that occurs with ageing. On the basis of study results showing that muscle mass is only moderately related to functional outcomes, international working groups have proposed that loss of muscle strength or physical function should also be included in the definition. Irrespective of how sarcopenia is defined, both low muscle mass and poor muscle strength are clearly highly prevalent and important risk factors for disability and potentially mortality in individuals as they age. Many chronic diseases, in addition to ageing, could also accelerate decrease of muscle mass and strength, and this effect could be a main underlying mechanism by which chronic diseases cause physical disability. In this Review, we address both age-related and disease-related muscle loss, with a focus on diabetes and obesity but including other disease states, and potential common mechanisms and treatments. Development of treatments for age-related and disease-related muscle loss might improve active life expectancy in older people, and lead to substantial health-care savings and improved quality of life.
Topics: Diabetes Complications; Endocrine System Diseases; Humans; Male; Obesity; Sarcopenia
PubMed: 24731660
DOI: 10.1016/S2213-8587(14)70034-8 -
Nature Reviews. Endocrinology Mar 2017Anorexia nervosa is a psychiatric disorder characterized by altered body image, persistent food restriction and low body weight, and is associated with global endocrine... (Review)
Review
Anorexia nervosa is a psychiatric disorder characterized by altered body image, persistent food restriction and low body weight, and is associated with global endocrine dysregulation in both adolescent girls and women. Dysfunction of the hypothalamic-pituitary axis includes hypogonadotropic hypogonadism with relative oestrogen and androgen deficiency, growth hormone resistance, hypercortisolaemia, non-thyroidal illness syndrome, hyponatraemia and hypooxytocinaemia. Serum levels of leptin, an anorexigenic adipokine, are suppressed and levels of ghrelin, an orexigenic gut peptide, are elevated in women with anorexia nervosa; however, levels of peptide YY, an anorexigenic gut peptide, are paradoxically elevated. Although most, but not all, of these endocrine disturbances are adaptive to the low energy state of chronic starvation and reverse with treatment of the eating disorder, many contribute to impaired skeletal integrity, as well as neuropsychiatric comorbidities, in individuals with anorexia nervosa. Although 5-15% of patients with anorexia nervosa are men, only limited data exist regarding the endocrine impact of the disease in adolescent boys and men. Further research is needed to understand the endocrine determinants of bone loss and neuropsychiatric comorbidities in anorexia nervosa in both women and men, as well as to formulate optimal treatment strategies.
Topics: Adipokines; Anorexia Nervosa; Disease Management; Endocrine System Diseases; Female; Growth Hormone; Humans; Hypothalamo-Hypophyseal System; Leptin; Male; Pituitary-Adrenal System
PubMed: 27811940
DOI: 10.1038/nrendo.2016.175 -
Toxicology Jan 2022Per- and poly-fluoroalkyl substances (PFAS) are widespread environmental contaminants frequently detected in drinking water supplies worldwide that have been linked to a... (Review)
Review
Per- and poly-fluoroalkyl substances (PFAS) are widespread environmental contaminants frequently detected in drinking water supplies worldwide that have been linked to a variety of adverse reproductive health outcomes in women. Compared to men, reproductive health effects in women are generally understudied while global trends in female reproduction rates are declining. Many factors may contribute to the observed decline in female reproduction, one of which is environmental contaminant exposure. PFAS have been used in home, food storage, personal care and industrial products for decades. Despite the phase-out of some legacy PFAS due to their environmental persistence and adverse health effects, alternative, short-chain and legacy PFAS mixtures will continue to pollute water and air and adversely influence women's health. Studies have shown that both long- and short-chain PFAS disrupt normal reproductive function in women through altering hormone secretion, menstrual cyclicity, and fertility. Here, we summarize the role of a variety of PFAS and PFAS mixtures in female reproductive tract dysfunction and disease. Since these chemicals may affect reproductive tissues directly or indirectly through endocrine disruption, the role of PFAS in breast, thyroid, and hypothalamic-pituitary-gonadal axis function are also discussed as the interplay between these tissues may be critical in understanding the long-term reproductive health effects of PFAS in women. A major research gap is the need for mechanism of action data - the targets for PFAS in the female reproductive and endocrine systems are not evident, but the effects are many. Given the global decline in female fecundity and the ability of PFAS to negatively impact female reproductive health, further studies are needed to examine effects on endocrine target tissues involved in the onset of reproductive disorders of women.
Topics: Endocrine Disruptors; Endocrine System Diseases; Environmental Exposure; Environmental Pollutants; Female; Fertility; Humans; Hydrocarbons, Fluorinated; Infertility, Female; Menstrual Cycle; Pregnancy; Pregnancy Complications; Prognosis; Reproduction; Risk Assessment; Risk Factors
PubMed: 34774661
DOI: 10.1016/j.tox.2021.153031 -
Blood Sep 2011The purpose of this article is to set forth our approach to diagnosing and managing the thalassemias, including β-thalassemia intermedia and β-thalassemia major. The... (Review)
Review
The purpose of this article is to set forth our approach to diagnosing and managing the thalassemias, including β-thalassemia intermedia and β-thalassemia major. The article begins by briefly describing recent advances in our understanding of the pathophysiology of thalassemia. In the discussion on diagnosing the condition, we cover the development of improved diagnostic tools, including the use of very small fetal DNA samples to detect single point mutations with great reliability for prenatal diagnosis of homozygous thalassemia. In our description of treatment strategies, we focus on how we deal with clinical manifestations and long-term complications using the most effective current treatment methods for β-thalassemia. The discussion of disease management focuses on our use of transfusion therapy and the newly developed oral iron chelators, deferiprone and deferasirox. We also deal with splenectomy and how we manage endocrinopathies and cardiac complications. In addition, we describe our use of hematopoietic stem cell transplantation, which has produced cure rates as high as 97%, and the use of cord blood transplantation. Finally, we briefly touch on therapies that might be effective in the near future, including new fetal hemoglobin inducers and gene therapy.
Topics: Algorithms; Cardiovascular Diseases; Endocrine System Diseases; Humans; Incidence; Models, Biological; Thalassemia
PubMed: 21813448
DOI: 10.1182/blood-2010-08-300335 -
Medical Sciences (Basel, Switzerland) Jun 2021Hepatocrinology is defined as a bidirectional, complex relationship between hepatic physiology and endocrine function, hepatic disease and endocrine dysfunction,... (Review)
Review
Hepatocrinology is defined as a bidirectional, complex relationship between hepatic physiology and endocrine function, hepatic disease and endocrine dysfunction, hepatotropic drugs and endocrine function, and endocrine drugs and hepatic health. The scope of hepatocrinology includes conditions of varied etiology (metabolic, infectious, autoimmune, and invasive) that we term as hepato-endocrine syndromes. This perspective shares the definition, concept, and scope of hepatocrinology and shares insight related to this aspect of medicine. It is hoped that this communication will encourage further attention and research in this critical field.
Topics: Endocrine System Diseases; Humans; Liver Diseases; Liver Transplantation; Pharmaceutical Preparations
PubMed: 34205986
DOI: 10.3390/medsci9020039 -
Endocrine Reviews Jun 2009There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer... (Review)
Review
There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor gamma, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness.
Topics: Animals; Cardiovascular Diseases; Disease Models, Animal; Endocrine Disruptors; Endocrine System Diseases; Female; Humans; Male; Neoplasms; Public Health; Reproductive Medicine
PubMed: 19502515
DOI: 10.1210/er.2009-0002