Explore the vast range of titles available.

25(OH)D = 25-hydroxyvitamin D; BMD = bone mineral density; CV = cardiovascular; GI = gastrointestinal; IOM = Institute of Medicine; PTH = parathyroid hormone; RCT = randomized controlled trial; αTF = α-tocopherol; ucOC = undercarboxylated osteocalcin; VKA = vitamin K antagonist; WHI = Women's Health Initiative.

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.

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.

The possibility of other types of diabetes should be considered in the child who has negative diabetes-associated autoantibodies and (B): an autosomal dominant family history of diabetes (maturity-onset diabetes of the young [MODY]) age less than 12 months and especially in first 6 months of life (NDM [neonatal diabetes mellitus]) mild-fasting hyperglycemia (5.5-8.5 mmol [100-150 mg/dL]), especially if young, non-obese, and asymptomatic a prolonged honeymoon period over 1 year or an unusually low requirement for insulin of ≤0.5 U/kg/day after 1 year of diabetes associated conditions such as deafness, optic atrophy, or syndromic features (mitochondrial disease) a history of exposure to drugs known to be toxic to β-cells or cause insulin resistance (eg, immunosuppressive drugs such as tacrolimus or cyclosporin; gluocorticoids or some antidepressants). While type 1 diabetes remains the most common form of diabetes in young people in many populations, especially those of European background, type 2 diabetes has become an increasingly important public health concern globally among children in high risk ethnic populations as well as in those with severe obesity, see ISPAD guideline on type 2 diabetes . Diabetes in young people usually presents with characteristic symptoms such as polyuria, polydipsia, nocturia, enuresis, weight loss—which may be accompanied by polyphagia, behavioral disturbance including reduced school performance, and blurred vision. Glycated hemoglobin (HbA1c) can be used as a diagnostic test for diabetes providing that stringent quality assurance tests are in place and assays are standardized to criteria aligned to the international reference values, and there are no conditions present which preclude its accurate measurement. [...]the validity of HbA1c as a measure of average glucose is complicated in the context of hemoglobinopathies, certain forms of anemia, or any other condition that affects normal red blood cell turnover.

Recommendations: Regular self-monitoring of glucose (using accurate fingerstick blood glucose [BG] measurements, with or without continuous glucose monitoring [CGM] or intermittently scanned CGM [isCGM]), is essential for diabetes management for all children and adolescents with diabetes (A). ○ Each child should have access to technology and materials for self-monitoring of glucose measurements to test enough to optimize diabetes care (B). ○ Diabetes center personnel should advocate to nations, states, and health care funders to ensure that children and adolescents with diabetes have adequate glucose monitoring supplies (E). ○ When fingerstick BGs are used, testing may need to be performed 6 to 10 times per day to optimize intensive control. For children, adolescents, and young adults aged ≤25 years we recommend individualized targets, aiming for the lowest achievable HbA1c without undue exposure to severe hypoglycemia balanced with quality of life and burden of care (E). For children, adolescents, and young adults ≤25 years who have access to comprehensive care a target of HbA1c of <53 mmol/mol (7.0%) is recommended (E). ○ A higher HbA1c goal (in most cases <58 mmol/mol [7.5%]) is appropriate in the following contexts: inability to articulate symptoms of hypoglycemia, hypoglycemia unawareness/history of severe hypoglycemia, lack of access to analog insulins, advanced insulin delivery technology, ability to regularly check BG, and CGM (E), and individuals who are “high glycators,” in whom an at-target HbA1c would reflect a significantly lower mean glucose than 8.6 mmoL/L (155 mg/dL) (E). ○ A lower goal (6.5%) or 47.5 mmol/mol may be appropriate if achievable without excessive hypoglycemia, impairment of quality of life, and undue burden of care (E). ○ A lower goal may be appropriate during the honeymoon phase of type 1 diabetes (E). ○ For patients who have elevated HbA1c, a step-wise approach to improve glycemic control is advised including individualized attention to: dose adjustments (E), personal factors limiting achievement of the target (E), assessment of the psychological effect of goal setting on the individual (E), and incorporation of available technology to improve glucose monitoring and insulin delivery modalities (E). Importantly, recent data suggest that lowering HbA1c targets is associated with a decreased mean HbA1c on a population and individual level without an increased frequency of severe hypoglycemia, even in children who achieve HbA1c levels <53 mmol/mol (7.0%).

Thyroid nodules are detected in up to 50 to 60% of healthy subjects. Most nodules do not cause clinically significant symptoms, and as a result, the main challenge in their management is to rule out malignancy, with ultrasonography (US) and fine-needle aspiration (FNA) biopsy serving as diagnostic cornerstones. The key issues discussed in these guidelines are as follows: (1) US-based categorization of the malignancy risk and indications for US-guided FNA (henceforth, FNA), (2) cytologic classification of FNA samples, (3) the roles of immunocytochemistry and molecular testing applied to thyroid FNA, (4) therapeutic options, and (5) follow-up strategy. Thyroid nodule management during pregnancy and in children are also addressed. On the basis of US features, thyroid nodules may be categorized into 3 groups: low-, intermediate-and high-malignancy risk. FNA should be considered for nodules ≤10 mm diameter only when suspicious US signs are present, while nodules ≤5 mm should be monitored rather than biopsied. A classification scheme of 5 categories (nondiagnostic, benign, indeterminate, suspicious for malignancy, or malignant) is recommended for the cytologic report. Indeterminate lesions are further subdivided into 2 subclasses to more accurately stratify the risk of malignancy. At present, no single cytochemical or genetic marker can definitely rule out malignancy in indeterminate nodules. Nevertheless, these tools should be considered together with clinical data, US signs, elastographic pattern, or results of other imaging techniques to improve the management of these lesions. Most thyroid nodules do not require any treatment, and levothyroxine (LT4) suppressive therapy is not recommended. Percutaneous ethanol injection (PEI) should be the first-line treatment option for relapsing, benign cystic lesions, while US-guided thermal ablation treatments may be considered for solid or mixed symptomatic benign thyroid nodules. Surgery remains the treatment of choice for malignant or suspicious nodules. The present document updates previous guidelines released in 2006 and 2010 by the American Association of Clinical Endocrinologists (AACE), American College of Endocrinology (ACE) and Associazione Medici Endocrinologi (AME).

Urinary glucose screening in Japanese and Taiwanese adolescents may be a unique situation with demonstrated cost-effectiveness (A) Testing to identify clinical cases of diabetes should be considered in children and adolescents after the onset of puberty or after 10 years of age, whichever occurs earlier, who have risk factors for diabetes (obesity, intrauterine growth retardation with rapid infant weight gain, first-degree family history of T2DM, maternal history of diabetes or gestational diabetes during child's gestation, high-risk ethnicity, polycystic ovary syndrome). (A) Clinical testing for dysglycemia in obese at-risk youth should occur in the setting of clinical assessment of other obesity-related comorbidities (non-alcoholic fatty liver disease [NAFLD], dyslipidemia, elevated blood pressure [BP], polycystic ovary syndrome) that are more prevalent than dysglycemia (A) Diagnosis and determination of diabetes type T2DM in youth should be diagnosed using American Diabetes Association (ADA) criteria (A) Diagnosis can be made based on fasting glucose, or 2-hour glucose concentration during an oral glucose tolerance test (OGTT) or hemoglobin A1c (HbA1c) (B) In the absence of symptoms, testing should be confirmed with a repeat test on a different day Clinicians should be aware of the weaknesses of each diagnostic test Diabetes autoantibody testing should be considered in all pediatric patients with the clinical diagnosis of diabetes because of the high frequency of islet cell autoimmunity in otherwise “typical” T2DM (B) Pre-pubertal children are unlikely to have T2DM even if obese (A) Antibodies will indicate the diagnosis of T1DM and an earlier need for insulin (A) Antibodies will indicate the need to consider the presence of other associated autoimmune disorders (A) Diabetes autoantibody testing should be considered in overweight/obese pubertal children with a clinical picture of T1DM (A) The presence of clinically relevant comorbidities should be assessed at the time of diagnosis (A), including hypertension, dyslipidemia, elevation of liver enzymes, and elevated urine albumin/creatinine ratio (ACR) Patients should be screened for obstructive sleep apnea (OSA), depression/anxiety, eating disorders, and impairment of cognition at the time of diagnosis (E). (B) If repeat fasting LDL-C > 130 mg/dL (>3.4 mmol/L): begin medication with an initial goal of <130 mg/dL (<3.4 mmol/L): and an ideal target of <100 mg/dL (2.6 mmol/L (B) Statin therapy has been shown to be safe and effective in adolescents (A) The risks of pregnancy should be re-emphasized Triglycerides If triglycerides are >400 mg/dL fasting (>5.6 mmol/L) or >1000 mg/dL (>11.3 mmol/L) non-fasting: begin medication with a goal of <400 mg/dL (>5.6 mmol/L) fasting (to reduce risk for pancreatitis) (C) Fibrates are the preferred medication category for hypertriglyceridemia and have been shown to be safe and effective in adolescents (A) Retinal examination should be performed at diagnosis and annually thereafter (A) Evaluation for NAFLD and non-alcoholic Steatohepatitis (NASH) by measuring ALT and AST should be done at diagnosis and annually thereafter (A) Interpretation of ALT should be based upon sex-specific upper limits of normal in children (22 U/L for girls and 26 U/L for boys) and not individual laboratory upper limits of normal. [...]the prevalence of prediabetes, defined in adults as a state of high-risk for progression to diabetes, is increasing quickly in some developing countries with the increase of overweight and obesity. Because of the relatively recent emergence of the problem in children and adolescents, there has been a limited evidence base leading to unique challenges in the diagnosis, management, and monitoring of these individuals.

Recommendations Commence screening for microvascular complications at age 11 years (formerly 10 years) Screening for microvascular disease should be performed preconception and during each trimester of pregnancy Screen for lipid abnormalities in the non-fasting state Screen for renal disease by first morning albumin creatinine ratio as the preferred method Recommendations—Screening for and prevention of complications Prevention Intensive education and treatment should be used in children and adolescents to prevent or delay the onset and progression of vascular complications. E Because of potential worsening of retinopathy for patients with longstanding poor glycemic control when control is rapidly improved, ophthalmological monitoring is recommended before initiation of intensive treatment and at three monthly intervals for 6 to 12 months thereafter, particularly if retinopathy is moderate non-proliferative stage or worse at the time of intensification. Screening methods Risk factors Nephropathy 11 years with 2-5 years diabetes duration Urinary albumin/creatinine ratio Hyperglycaemia High BP Lipid abnormalities Smoking Retinopathy 11 years with 2-5 years diabetes duration Fundal photography or mydriatic ophthalmoscopy Hyperglycemia High BP Lipid abnormalities Higher BMI Neuropathy 11 years with 2-5 years diabetes duration History Physical examination Clinical tests Hyperglycemia Higher BMI Age Diabetes duration Genetics Macrovascular disease 11 years with 2-5 years diabetes duration Lipid profile every 2 years, BP annually Hyperglycemia High BP Lipid abnormalities Higher BMI Smoking Other ocular conditions A comprehensive initial eye examination should also be considered to detect cataracts, major refractive errors, or other ocular disorders. B Recommended threshold values for different parameters for intervention and primary prevention of microvascular and CVD in children and adolescents with type 1 diabetes Threshold value Type of intervention BP >90th percentile for age, gender and height Lifestyle intervention: exercise, less screen time and diet BP >90th percentile despite lifestyle intervention ACE inhibitor or other BP lowering agent If microalbuminuria is present: ACE inhibitor or ARB BP >95th percentile for age, gender and height Lifestyle intervention and ACE inhibitor or other BP lowering agent If microalbuminuria is present: ACE inhibitor or ARB LDL cholesterol >2.6 mmol/L (100 mg/dL) Dietary and lifestyle intervention LDL cholesterol >3.4 mmol/L (130 mg/dL) Statins Lipids Screening for dyslipidemia should be performed soon after diagnosis (when diabetes stabilized) in all children with type 1 diabetes from age 11 years E. If normal results are obtained, this should be repeated every 5 years.

Matching of insulin dose to carbohydrate intake on intensive insulin regimens allows greater flexibility in carbohydrate intake and meal-times, with improvements in glycemic control and quality of life (A). The use of the glycemic index provides additional benefit to glycemic control over that observed when total carbohydrate is considered alone (B). The impact of diabetes on eating behavior must not be underestimated and may cause psychological disturbance. [...]experienced professionals should facilitate dietary and lifestyle changes. Achieve a balance between food intake, metabolic requirements, energy expenditure, and insulin action profiles to attain optimum glycemic control.

Depression and diabetes distress Disordered eating behaviors Cognitive functioning and school performance Parental distress, coping, and demographic factors Stress and coping Factors affecting quality of life, including resiliency Psychosocial and behavioral intervention studies to improve glycemic control, diabetes management behaviors, and psychosocial functioning EXECUTIVE SUMMARY AND RECOMMENDATIONS The following summary and recommendations build upon the previous ISPAD Guidelines and are consistent with the latest statements and guidelines issued by the American Diabetes Association, Australia (APEG—Clinical Practice Guidelines, ), Canada and the United Kingdom ). Young people with diabetes are at increased risk for mild decrements in general cognitive ability, information processing skills, executive functions, and academic achievement, especially if there is a background of early diabetes onset, severe hypoglycemia or chronic hyperglycemia (B). [...]it is recommended that assessment of developmental progress in all domains of functioning (ie, physical, intellectual, academic, emotional and social development) should be conducted on a routine basis (A, B, E). Identification of overall psychosocial well-being and diabetes-specific quality of life, as well as psychosocial adjustment problems, depression, eating disorders, diabetes distress, and other psychiatric disorders should be performed at planned intervals and by appropriately trained mental health professionals (B, E). Family conflict is associated with lower regimen adherence and poor glycemic control (B, C). [...]the interdisciplinary team should assess general family functioning (conflict, cohesion, adaptability, parental psychopathology) and diabetes-related functioning (communication, parental involvement and support, roles and responsibilities for self-management behaviors) especially during periods of transition (eg, at diagnosis, at start of a new treatment plan, early adolescence) and when there is an evidence of cultural, language or family problems or difficulties in adjustment to diabetes (A, B, E).