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Abstract Disclosure: I.A. Bacila: None. R. Welch: None. S. Adam: None. S.F. Ahmed: None. M. Alimussina: None. E. Chinnasamy: None. E.C. Crowne: None. J.H. Davies: None. A. Davis: None. J. Davis: None. M. Debono: None. S. Elford: None. Y. Elhassan: None. G. Gazdagh: None. H. Gleeson: None. L. James: None. M. Korbonits: None. S. Llanaha: None. J.M. Lynch: None. S. McGeoch: None. A. Mitchell: None. R.D. Murray: None. S. Nedelcu: None. G. Okoro: None. M.W. O'Reilly: None. A. Rees: None. R. Scott: None. R.H. Stimson: None. A. Thankamony: None. J.W. Tomlinson: None. B. Vaidya: None. N.P. Krone: None. Background: Congenital adrenal hyperplasia (CAH) is one of the commonest forms of primary adrenal insufficiency with an incidence of about 1 in 15,000. Previous studies have highlighted the suboptimal health status and care provision in adults with CAH and these were associated with significant co-morbidities. In 2023, we implemented CaHASE2 (https://www.endocrinology.org/clinical-practice/research-projects/cahase-2/) to develop a strategy for prospective collection of longitudinal data. Our recent CAH service evaluation suggested significant differences in the approach to CAH patients. Aim: To identify specific unmet needs in the care of people living with CAH, through standardised phenotyping across all participating centres. Methods: In September 2023, PIs agreed a minimal dataset for the collection of real-world data for participating centres. The data is collected using the international CAH registry (I-CAH; https://sdmregistries.org/). CaHASE2 was launched in November 2023. Results: To date, 351 adults (213 females, 138 males) with CAH have been recruited and 1213 clinic visits were available for analysis. There is a preponderance of younger to middle-aged adults in the currently available datasets (median age 42 years, range 23-88). Preliminary analysis suggests a temporal change in glucocorticoid choice over time with an increased use of hydrocortisone and a decreased use of prednisolone. Analysis of 17OHP concentrations shows that a significant proportion of patients are overtreated. A significant proportion of patients are overweight or obese. Currently 18 centres are actively recruiting and 5 are awaiting local approval to use the I-CAH registry. The data will be analysed in 12-month cycles, to assess the current level of care provision and inform the development of CAH standards. In addition, we will establish a report that will provide centres with information about their local care provision in relation to other centres. Conclusions: The CaHASE2 project will provide important information about the health status of adults with CAH and how this might be related to differences in health care provision. Ultimately, such data should lead to a higher degree of equality of service provision in all parts of the UK and Ireland. Presentation: Saturday, July 12, 2025

\"For over a century, we've accepted the scientific consensus that cancer results from genetic disease due to chromosomal damage in cell nuclei. But what if cancer isn't a genetic disease after all? What if scientists are chasing a flawed paradigm, and cancer isn't a disease of damaged DNA but rather of defective metabolism as a result of mitochondrial dysfunction? What if that [theory] could revolutionize our understanding of other diseases as well--and show us a radical new path to optimal health?\"-- Provided by publisher.

Abstract Artificial intelligence (AI) holds the promise of addressing many of the numerous challenges healthcare faces, which include a growing burden of illness, an increase in chronic health conditions and disabilities due to aging and epidemiological changes, higher demand for health services, overworked and burned-out clinicians, greater societal expectations, and rising health expenditures. While technological advancements in processing power, memory, storage, and the abundance of data have empowered computers to handle increasingly complex tasks with remarkable success, AI introduces a variety of meaningful risks and challenges. Among these are issues related to accuracy and reliability, bias and equity, errors and accountability, transparency, misuse, and privacy of data. As AI systems continue to rapidly integrate into healthcare settings, it is crucial to recognize the inherent risks they bring. These risks demand careful consideration to ensure the responsible and safe deployment of AI in healthcare.

ObjectiveTo update the “Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline,” published by the Endocrine Society in 2009.ParticipantsThe participants include an Endocrine Society–appointed task force of nine experts, a methodologist, and a medical writer.EvidenceThis evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies.Consensus ProcessGroup meetings, conference calls, and e-mail communications enabled consensus. Endocrine Society committees, members and cosponsoring organizations reviewed and commented on preliminary drafts of the guidelines.ConclusionGender affirmation is multidisciplinary treatment in which endocrinologists play an important role. Gender-dysphoric/gender-incongruent persons seek and/or are referred to endocrinologists to develop the physical characteristics of the affirmed gender. They require a safe and effective hormone regimen that will (1) suppress endogenous sex hormone secretion determined by the person’s genetic/gonadal sex and (2) maintain sex hormone levels within the normal range for the person’s affirmed gender. Hormone treatment is not recommended for prepubertal gender-dysphoric/gender-incongruent persons. Those clinicians who recommend gender-affirming endocrine treatments—appropriately trained diagnosing clinicians (required), a mental health provider for adolescents (required) and mental health professional for adults (recommended)—should be knowledgeable about the diagnostic criteria and criteria for gender-affirming treatment, have sufficient training and experience in assessing psychopathology, and be willing to participate in the ongoing care throughout the endocrine transition. We recommend treating gender-dysphoric/gender-incongruent adolescents who have entered puberty at Tanner Stage G2/B2 by suppression with gonadotropin-releasing hormone agonists. Clinicians may add gender-affirming hormones after a multidisciplinary team has confirmed the persistence of gender dysphoria/gender incongruence and sufficient mental capacity to give informed consent to this partially irreversible treatment. Most adolescents have this capacity by age 16 years old. We recognize that there may be compelling reasons to initiate sex hormone treatment prior to age 16 years, although there is minimal published experience treating prior to 13.5 to 14 years of age. For the care of peripubertal youths and older adolescents, we recommend that an expert multidisciplinary team comprised of medical professionals and mental health professionals manage this treatment. The treating physician must confirm the criteria for treatment used by the referring mental health practitioner and collaborate with them in decisions about gender-affirming surgery in older adolescents. For adult gender-dysphoric/gender-incongruent persons, the treating clinicians (collectively) should have expertise in transgender-specific diagnostic criteria, mental health, primary care, hormone treatment, and surgery, as needed by the patient. We suggest maintaining physiologic levels of gender-appropriate hormones and monitoring for known risks and complications. When high doses of sex steroids are required to suppress endogenous sex steroids and/or in advanced age, clinicians may consider surgically removing natal gonads along with reducing sex steroid treatment. Clinicians should monitor both transgender males (female to male) and transgender females (male to female) for reproductive organ cancer risk when surgical removal is incomplete. Additionally, clinicians should persistently monitor adverse effects of sex steroids. For gender-affirming surgeries in adults, the treating physician must collaborate with and confirm the criteria for treatment used by the referring physician. Clinicians should avoid harming individuals (via hormone treatment) who have conditions other than gender dysphoria/gender incongruence and who may not benefit from the physical changes associated with this treatment.Gender affirmation is multidisciplinary treatment. Gender-dysphoric/gender-incongruent persons seek and/or are referred to endocrinologists to develop the physical characteristics of the affirmed gender.

Abstract Background Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain. Objective To develop clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing. Methods A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 14 clinically relevant questions related to the use of vitamin D and 25(OH)D testing to lower the risk of disease. The panel prioritized randomized placebo-controlled trials in general populations (without an established indication for vitamin D treatment or 25[OH]D testing), evaluating the effects of empiric vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined “empiric supplementation” as vitamin D intake that (a) exceeds the Dietary Reference Intakes (DRI) and (b) is implemented without testing for 25(OH)D. Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated perspectives from a patient representative and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. The process to develop this clinical guideline did not use a risk assessment framework and was not designed to replace current DRI for vitamin D. Results The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections; for those aged 75 years and older because of its potential to lower the risk of mortality; for those who are pregnant because of its potential to lower the risk of preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for those with high-risk prediabetes because of its potential to reduce progression to diabetes. Because the vitamin D doses in the included clinical trials varied considerably and many trial participants were allowed to continue their own vitamin D–containing supplements, the optimal doses for empiric vitamin D supplementation remain unclear for the populations considered. For nonpregnant people older than 50 years for whom vitamin D is indicated, the panel suggests supplementation via daily administration of vitamin D, rather than intermittent use of high doses. The panel suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years. No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, nor in those with obesity or dark complexion, and there was no clear evidence defining the optimal target level of 25(OH)D required for disease prevention in the populations considered; thus, the panel suggests against routine 25(OH)D testing in all populations considered. The panel judged that, in most situations, empiric vitamin D supplementation is inexpensive, feasible, acceptable to both healthy individuals and health care professionals, and has no negative effect on health equity. Conclusion The panel suggests empiric vitamin D for those aged 1 to 18 years and adults over 75 years of age, those who are pregnant, and those with high-risk prediabetes. Due to the scarcity of natural food sources rich in vitamin D, empiric supplementation can be achieved through a combination of fortified foods and supplements that contain vitamin D. Based on the absence of supportive clinical trial evidence, the panel suggests against routine 25(OH)D testing in the absence of established indications. These recommendations are not meant to replace the current DRIs for vitamin D, nor do they apply to people with established indications for vitamin D treatment or 25(OH)D testing. Further research is needed to determine optimal 25(OH)D levels for specific health benefits.

Hyperferritinaemia is a common laboratory finding that is often associated with metabolic dysfunction and fatty liver. Metabolic hyperferritinaemia reflects alterations in iron metabolism that facilitate iron accumulation in the body and is associated with an increased risk of cardiometabolic and liver diseases. Genetic variants that modulate iron homeostasis and tissue levels of iron are the main determinants of serum levels of ferritin in individuals with metabolic dysfunction, raising the hypothesis that iron accumulation might be implicated in the pathogenesis of insulin resistance and the related organ damage. However, validated criteria for the non-invasive diagnosis of metabolic hyperferritinaemia and the staging of iron overload are still lacking, and there is no clear evidence of a benefit for iron depletion therapy. Here, we provide an overview of the literature on the relationship between hyperferritinaemia and iron accumulation in individuals with metabolic dysfunction, and on the associated clinical outcomes. We propose an updated definition and a provisional staging system for metabolic hyperferritinaemia, which has been agreed on by a multidisciplinary global panel of expert researchers. The goal is to foster studies into the epidemiology, genetics, pathophysiology, clinical relevance and treatment of metabolic hyperferritinaemia, for which we provide suggestions on the main unmet needs, optimal design and clinically relevant outcomes.This Consensus Statement discusses the relationship between hyperferritinaemia and iron accumulation in individuals with metabolic dysfunction. The authors propose an updated definition and a provisional staging system for metabolic hyperferritinaemia, highlight research gaps and provide suggestions for the design and outcome measures for future studies.