{"title":"Hypoparathyroidism: diagnosis, management and emerging therapies","authors":"Sarah Khan, Aliya A. Khan","doi":"10.1038/s41574-024-01075-8","DOIUrl":"https://doi.org/10.1038/s41574-024-01075-8","url":null,"abstract":"<p>Hypoparathyroidism is characterized by inadequate parathyroid hormone (PTH) secretion or action and results in hypocalcaemia, and can lead to hyperphosphataemia and hypercalciuria. Most cases of hypoparathyroidism occur as a complication of surgery, with the remainder due to causes including autoimmune disease, genetic causes, infiltrative diseases, mineral deposition or due to abnormalities in serum levels of magnesium. Hypoparathyroidism can cause multisystem disease, with long-term complications resulting from ectopic calcification as well as renal complications with nephrocalcinosis, nephrolithiasis and renal impairment in addition to respiratory, cardiac or neurological manifestations. Conventional therapy consists of oral calcium salts and active vitamin D but it has limitations, including fluctuations in serum levels of calcium and a high pill burden, and can increase the risk of long-term complications. By contrast, PTH replacement therapy can effectively achieve normal serum levels of calcium, and lower serum levels of phosphate. The long-acting PTH analogue, palopegteriparatide, has been shown to normalize urine levels of calcium. In addition, PTH replacement therapy reduces the pill burden. Palopegteriparatide is also associated with improved quality of life in comparison to conventional therapy. This Review summarizes current recommendations regarding the pathophysiology, evaluation and management of hypoparathyroidism and also references the 2022 international hypoparathyroidism guidelines. Palopegteriparatide has now been approved as PTH replacement therapy for hypoparathyroidism. Emerging therapies will also be presented in this Review.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"11 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124437","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 effects of type 1 and type 2 diabetes mellitus on bone health in chronic kidney disease","authors":"Jasna Aleksova, Peter Ebeling, Grahame Elder","doi":"10.1038/s41574-024-01083-8","DOIUrl":"https://doi.org/10.1038/s41574-024-01083-8","url":null,"abstract":"<p>Fracture is an under-recognized but common complication of diabetes mellitus, with an incidence approaching twofold in type 2 diabetes mellitus (T2DM) and up to sevenfold in type 1 diabetes mellitus (T1DM) compared with that in the general population. Both T1DM and T2DM induce chronic hyperglycaemia, leading to the accumulation of advanced glycosylation end products that affect osteoblast function, increased collagen crosslinking and a senescence phenotype promoting inflammation. Together with an increased incidence of microvascular disease and an increased risk of vitamin D deficiency, these factors reduce bone quality, thereby increasing bone fragility. In T1DM, reduced anabolic stimuli as well as the presence of autoimmune conditions might also contribute to reduced bone mass and increased fragility. Diabetes mellitus is the most common cause of kidney failure, and fracture risk is exacerbated when chronic kidney disease (CKD)-related mineral and bone disorders are superimposed on diabetic changes. Microvascular pathology, cortical thinning and trabecular deterioration are particularly prominent in patients with T1DM and CKD, who suffer more fragility fractures than do other patients with CKD. This Review explores the pathophysiology of bone fragility in patients with diabetes mellitus and CKD and discusses techniques to predict fracture and pharmacotherapy that might reduce fracture risk.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"53 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986015","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":"Exploring the functions of the myokine feimin","authors":"Claire Greenhill","doi":"10.1038/s41574-025-01086-z","DOIUrl":"10.1038/s41574-025-01086-z","url":null,"abstract":"","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"21 3","pages":"133-133"},"PeriodicalIF":31.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981175","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":"Management, biomarkers and prognosis in people developing endocrinopathies associated with immune checkpoint inhibitors","authors":"Shintaro Iwama, Tomoko Kobayashi, Hiroshi Arima","doi":"10.1038/s41574-024-01077-6","DOIUrl":"https://doi.org/10.1038/s41574-024-01077-6","url":null,"abstract":"<p>Immune-related adverse events (irAEs), including endocrine irAEs, can occur in response to cancer immunotherapy using immune checkpoint inhibitors (ICIs). Of the endocrine irAEs, pituitary and thyroid irAEs are most frequently observed, followed by primary adrenal insufficiency, type 1 diabetes mellitus and hypoparathyroidism. Notably, pituitary irAEs and type 1 diabetes mellitus can be lethal if overlooked, potentially leading to adrenal crisis and diabetic ketoacidosis, respectively. On the other hand, pituitary and thyroid irAEs are reported to be associated with more favourable prognoses in some cancers if treated appropriately with hormone-replacement therapies. It would be useful to identify those people who are likely to develop endocrine irAEs before initiating therapy with ICIs. Anti-pituitary antibodies and thyroid autoantibodies have been identified as potential biomarkers for the development of pituitary and thyroid irAEs, respectively. This Review elaborates on the clinical characteristics and management strategies of several endocrine irAEs, using the latest research findings and guidelines published by several academic societies.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"1 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936994","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":"Bile acid metabolism in type 2 diabetes mellitus","authors":"Marti Cadena Sandoval, Rebecca A. Haeusler","doi":"10.1038/s41574-024-01067-8","DOIUrl":"https://doi.org/10.1038/s41574-024-01067-8","url":null,"abstract":"<p>Type 2 diabetes mellitus is a complex disorder associated with insulin resistance and hyperinsulinaemia that is insufficient to maintain normal glucose metabolism. Changes in insulin signalling and insulin levels are thought to directly explain many of the metabolic abnormalities that occur in diabetes mellitus, such as impaired glucose disposal. However, molecules that are directly affected by abnormal insulin signalling might subsequently go on to cause secondary metabolic effects that contribute to the pathology of type 2 diabetes mellitus. In the past several years, evidence has linked insulin resistance with the concentration, composition and distribution of bile acids. As bile acids are known to regulate glucose metabolism, lipid metabolism and energy balance, these findings suggest that bile acids are potential mediators of metabolic distress in type 2 diabetes mellitus. In this Review, we highlight advances in our understanding of the complex regulation of bile acids during insulin resistance, as well as how bile acids contribute to metabolic control.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"3 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929522","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}
Ravi Savarirayan, Julie Hoover-Fong, Keiichi Ozono, Philippe Backeljauw, Valérie Cormier-Daire, Kristen DeAndrade, Penny Ireland, Melita Irving, Juan Llerena Junior, Mohamad Maghnie, Margaret Menzel, Nadia Merchant, Klaus Mohnike, Susana Noval Iruretagoyena, Keita Okada, Svein Otto Fredwall
{"title":"International consensus guidelines on the implementation and monitoring of vosoritide therapy in individuals with achondroplasia","authors":"Ravi Savarirayan, Julie Hoover-Fong, Keiichi Ozono, Philippe Backeljauw, Valérie Cormier-Daire, Kristen DeAndrade, Penny Ireland, Melita Irving, Juan Llerena Junior, Mohamad Maghnie, Margaret Menzel, Nadia Merchant, Klaus Mohnike, Susana Noval Iruretagoyena, Keita Okada, Svein Otto Fredwall","doi":"10.1038/s41574-024-01074-9","DOIUrl":"https://doi.org/10.1038/s41574-024-01074-9","url":null,"abstract":"<p>Achondroplasia is the most common genetic form of short-limbed skeletal dysplasia (dwarfism). Clinical manifestations and complications can affect individuals across the lifespan, including the need for adaptations for activities of daily living, which can affect quality of life. Current international guidelines focus on symptomatic management, with little discussion regarding potential medication, as therapeutic options were limited at the time of their publication. Vosoritide is the first pharmacological, precision treatment for achondroplasia; it was approved for use in 2021, creating a need for vosoritide treatment guidelines to support clinicians. An international collaborative of leading experts and patient advocates was formed to develop this Consensus Statement. The group developed the guideline scope and topics during a hybrid meeting in November 2023; guideline statements were subsequently ratified via Delphi methodology using a predefined consensus threshold. These statements provide recommendations across the treatment pathway, from starting treatment with vosoritide through ongoing monitoring and evaluation, to stopping vosoritide and ongoing monitoring following cessation. These guidelines recommend a minimum set of requirements and a practical framework for professionals and health services worldwide regarding the use of vosoritide to treat infants, children and young people with achondroplasia. This Consensus Statement is a supplement to already established consensus guidelines for management and care of individuals with achondroplasia.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"34 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929479","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":"Enhancing adipose tissue plasticity: progenitor cell roles in metabolic health","authors":"Simon Lecoutre, Clémentine Rebière, Salwan Maqdasy, Mélanie Lambert, Sébastien Dussaud, Jimon Boniface Abatan, Isabelle Dugail, Emmanuel L. Gautier, Karine Clément, Geneviève Marcelin","doi":"10.1038/s41574-024-01071-y","DOIUrl":"https://doi.org/10.1038/s41574-024-01071-y","url":null,"abstract":"<p>Adipose tissue demonstrates considerable plasticity and heterogeneity, enabling metabolic, cellular and structural adaptations to environmental signals. This adaptability is key for maintaining metabolic homeostasis. Impaired adipose tissue plasticity can lead to abnormal adipose tissue responses to metabolic cues, which contributes to the development of cardiometabolic diseases. In chronic obesity, white adipose tissue undergoes pathological remodelling marked by adipocyte hypertrophy, chronic inflammation and fibrosis, which are linked to local and systemic insulin resistance. Research data suggest that the capacity for healthy or unhealthy white adipose tissue remodelling might depend on the intrinsic diversity of adipose progenitor cells (APCs), which sense and respond to metabolic cues. This Review highlights studies on APCs as key determinants of adipose tissue plasticity, discussing differences between subcutaneous and visceral adipose tissue depots during development, growth and obesity. Modulating APC functions could improve strategies for treating adipose tissue dysfunction and metabolic diseases in obesity.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"36 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929375","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":"Illuminating the metabolic effects of circadian misalignment","authors":"Ioannis G. Lempesis","doi":"10.1038/s41574-024-01085-6","DOIUrl":"https://doi.org/10.1038/s41574-024-01085-6","url":null,"abstract":"Circadian misalignment affects physiology and metabolism and increases the risk of developing cardiometabolic disease. A pivotal study by Frank Scheer’s team provided clear evidence that misaligned sleep–wake cycles and fasting–eating cycles impair glucose tolerance, insulin sensitivity and blood pressure, highlighting the importance of synchronizing lifestyles with our internal biological clocks.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"5 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929398","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}