American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity

Objective: Development of these guidelines is mandated by the American Association of Clinical Endocrinologists (AACE) Board of Directors and the American College of Endocrinology (ACE) Board of Trustees and adheres to published AACE protocols for the standardized production of clinical practice guidelines (CPGs).Methods: Recommendations are based on diligent review of clinical evidence with transparent incorporation of subjective factors.Results: There are 9 broad clinical questions with 123 recommendation numbers that include 160 specific statements (85 [53.1%] strong [Grade A], 48 [30.0%] intermediate [Grade B], and 11 [6.9%] weak [Grade C], with 16 [10.0%] based on expert opinion [Grade D]) that build a comprehensive medical care plan for obesity. There were 133 (83.1%) statements based on strong (best evidence level [BEL] 1 = 79 [49.4%]) or intermediate (BEL 2 = 54 [33.7%]) levels of scientific substantiation. There were 34 (23.6%) evidence-based recommendation grades (Grades A-C = 144) that were adjusted based on subjective factors. Among the 1,788 reference citations used in this CPG, 524 (29.3%) were based on strong (evidence level [EL] 1), 605 (33.8%) were based on intermediate (EL 2), and 308 (17.2%) were based on weak (EL 3) scientific studies, with 351 (19.6%) based on reviews and opinions (EL 4).Conclusion: The final recommendations recognize that obesity is a complex, adiposity-based chronic disease, where management targets both weight-related complications and adiposity to improve overall health and quality of life. The detailed evidence-based recommendations allow for nuanced clinical decision-making that addresses real-world medical care of patients with obesity, including screening, diagnosis, evaluation, selection of therapy, treatment goals, and individualization of care. The goal is to facilitate high-quality care of patients with obesity and provide a rational, scientific approach to management that optimizes health outcomes and safety.Abbreviations:A1C = hemoglobin A1cAACE = American Association of Clinical EndocrinologistsACE = American College of EndocrinologyAMA = American Medical AssociationBEL = best evidence levelBMI = body mass indexCCO = Consensus Conference on ObesityCPG = clinical practice guidelineCSS = cross-sectional studyCVD = cardiovascular diseaseEL = evidence levelFDA = Food and Drug AdministrationGERD = gastroesophageal reflux diseaseHDL-c = high-density lipoprotein cholesterolIFG = impaired fasting glucoseIGT = impaired glucose toleranceLDL-c = low-density lipoprotein cholesterolMNRCT = meta-analysis of non-randomized prospective or case-controlled trialsNE = no evidencePCOS = polycystic ovary syndromeRCT = randomized controlled trialSS = surveillance studyU.S = United States     

American Association of Clinical Endocrinologists/American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis— 2020 Update Executive Summary

Objective: The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs).Methods: Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols.Results: The Executive Summary of this 2020 updated guideline contains 52 recommendations: 21 Grade A (40%), 24 Grade B (46%), 7 Grade C (14%), and no Grade D (0%). These detailed, evidence-based recommendations allow for nuance-based clinical decision-making that addresses multiple aspects of real-world care of patients. The evidence base presented in the subsequent Appendix provides relevant supporting information for the Executive Summary recommendations. This update contains 368 citations: 123 (33.5%) evidence level (EL) 1 (highest), 132 (36%) EL 2 (intermediate), 20 (5.5%) EL 3 (weak), and 93 (25%) EL 4 (lowest). New or updated topics in this CPG include: clarification of the diagnosis of osteoporosis, stratification of the patient according to high-risk and very-high-risk features, a new dual-action therapy option, and transitions from therapeutic options.Conclusion: This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of post-menopausal osteoporosis.     

American Association Of Clinical Endocrinologists And American College Of Endocrinology Position Statement On Thyroid Dysfunction Case Finding

Hypothyroidism and hyperthyroidism can be readily diagnosed and can be treated in a safe, cost-effective manner. Professional organizations have given guidance on how and when to employ thyroid-stimulating hormone testing for the detection of thyroid dysfunction. Most recently, the United States Preventive Services Task Force did not endorse screening for thyroid dysfunction based on a lack of proven benefit and potential harm of treating those with thyroid dysfunction, which is mostly subclinical disease. The American Association of Clinical Endocrinologists (AACE) is concerned that this may discourage physicians from testing for thyroid dysfunction when clinically appropriate. Given the lack of specificity of thyroid-associated symptoms, the appropriate diagnosis of thyroid disease requires biochemical confirmation. The Thyroid Scientific Committee of the AACE has produced this White Paper to highlight the important difference between screening and case-based testing in the practice of clinical medicine. We recommend that thyroid dysfunction should be frequently considered as a potential etiology for many of the nonspecific complaints that physicians face daily. The application and success of safe and effective interventions are dependent on an accurate diagnosis. We, therefore, advocate for an aggressive case-finding approach, based on identifying those persons most likely to have thyroid disease that will benefit from its treatment.Abbreviations:AACE = American Association of Clinical EndocrinologistsATA = American Thyroid AssociationFT4 = free thyroxineIHD = ischemic heart diseaseTSH = thyroid-stimulating hormoneUSPSTF = United States Preventive Services Task Force     

American Association of Clinical Endocrinologists and American College of Endocrinology Guidelines for Management of Growth Hormone Deficiency in Adults and Patients Transitioning from Pediatric to Adult Care

Objective: The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPG).Methods: Recommendations are based on diligent reviews of clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols.Results: The Executive Summary of this 2019 updated guideline contains 58 numbered recommendations: 12 are Grade A (21%), 19 are Grade B (33%), 21 are Grade C (36%), and 6 are Grade D (10%). These detailed, evidence-based recommendations allow for nuance-based clinical decision-making that addresses multiple aspects of real-world care of patients. The evidence base presented in the subsequent Appendix provides relevant supporting information for the Executive Summary recommendations. This update contains 357 citations of which 51 (14%) are evidence level (EL) 1 (strong), 168 (47%) are EL 2 (intermediate), 61 (17%) are EL 3 (weak), and 77 (22%) are EL 4 (no clinical evidence).Conclusion: This CPG is a practical tool that practicing endocrinologists and regulatory bodies can refer to regarding the identification, diagnosis, and treatment of adults and patients transitioning from pediatric to adult-care services with growth hormone deficiency (GHD). It provides guidelines on assessment, screening, diagnostic testing, and treatment recommendations for a range of individuals with various causes of adult GHD. The recommendations emphasize the importance of considering testing patients with a reasonable level of clinical suspicion of GHD using appropriate growth hormone (GH) cut-points for various GH–stimulation tests to accurately diagnose adult GHD, and to exercise caution interpreting serum GH and insulin-like growth factor-1 (IGF-1) levels, as various GH and IGF-1 assays are used to support treatment decisions. The intention to treat often requires sound clinical judgment and careful assessment of the benefits and risks specific to each individual patient. Unapproved uses of GH, long-term safety, and the current status of long-acting GH preparations are also discussed in this document.LAY ABSTRACTThis updated guideline provides evidence-based recommendations regarding the identification, screening, assessment, diagnosis, and treatment for a range of individuals with various causes of adult growth-hormone deficiency (GHD) and patients with childhood-onset GHD transitioning to adult care. The update summarizes the most current knowledge about the accuracy of available GH–stimulation tests, safety of recombinant human GH (rhGH) replacement, unapproved uses of rhGH related to sports and aging, and new developments such as long-acting GH preparations that use a variety of technologies to prolong GH action. Recommendations offer a framework for physicians to manage patients with GHD effectively during transition to adult care and adulthood. Establishing a correct diagnosis is essential before consideration of replacement therapy with rhGH. Since the diagnosis of GHD in adults can be challenging, GH–stimulation tests are recommended based on individual patient circumstances and use of appropriate GH cut-points. Available GH–stimulation tests are discussed regarding variability, accuracy, reproducibility, safety, and contraindications, among other factors. The regimen for starting and maintaining rhGH treatment now uses individualized dose adjustments, which has improved effectiveness and reduced reported side effects, dependent on age, gender, body mass index, and various other individual characteristics. With careful dosing of rhGH replacement, many features of adult GHD are reversible and side effects of therapy can be minimized. Scientific studies have consistently shown rhGH therapy to be beneficial for adults with GHD, including improvements in body composition and quality of life, and have demonstrated the safety of short- and long-term rhGH replacement.Abbreviations: AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; AHSG = alpha-2-HS-glycoprotein; AO-GHD = adult-onset growth hormone deficiency; ARG = arginine; BEL = best evidence level; BMD = bone mineral density; BMI = body mass index; CI = confidence interval; CO-GHD = childhood-onset growth hormone deficiency; CPG = clinical practice guideline; CRP = C-reactive protein; DM = diabetes mellitus; DXA = dual-energy X-ray absorptiometry; EL = evidence level; FDA = Food and Drug Administration; FD-GST = fixed-dose glucagon stimulation test; GeNeSIS = Genetics and Neuroendocrinology of Short Stature International Study; GH = growth hormone; GHD = growth hormone deficiency; GHRH = growth hormone–releasing hormone; GST = glucagon stimulation test; HDL = high-density lipoprotein; HypoCCS = Hypopituitary Control and Complications Study; IGF-1 = insulin-like growth factor-1; IGFBP = insulin-like growth factor–binding protein; IGHD = isolated growth hormone deficiency; ITT = insulin tolerance test; KIMS = Kabi International Metabolic Surveillance; LAGH = long-acting growth hormone; LDL = low-density lipoprotein; LIF = leukemia inhibitory factor; MPHD = multiple pituitary hormone deficiencies; MRI = magnetic resonance imaging; P-III-NP = procollagen type-III amino-terminal pro-peptide; PHD = pituitary hormone deficiencies; QoL = quality of life; rhGH = recombinant human growth hormone; ROC = receiver operating characteristic; RR = relative risk; SAH = subarachnoid hemorrhage; SDS = standard deviation score; SIR = standardized incidence ratio; SN = secondary neoplasms; T3 = triiodothyronine; TBI = traumatic brain injury; VDBP = vitamin D-binding protein; WADA = World Anti-Doping Agency; WB-GST = weight-based glucagon stimulation test     

Transculturalization Recommendations For Developing Latin American Clinical Practice Algorithms In Endocrinology Proceedings Of The 2015 Pan-American Workshop By The American Association Of Clinical Endocrinologists And American College Of Endocrinology

The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) convened their first Workshop for recommendations to optimize Clinical Practice Algorithm (CPA) development for Latin America (LA) in diabetes (focusing on glycemic control), obesity (focusing on weight loss), thyroid (focusing on thyroid nodule diagnostics), and bone (focusing on postmenopausal osteoporosis) on February 28, 2015, in San Jose, Costa Rica. A standardized methodology is presented incorporating various transculturalization factors: resource availability (including imaging equipment and approved pharmaceuticals), health care professional and patient preferences, lifestyle variables, socio-economic parameters, web-based global accessibility, electronic implementation, and need for validation protocols. A standardized CPA template with node-specific recommendations to assist the local transculturalization process is provided. Participants unanimously agreed on the following five overarching principles for LA: (1) there is only one level of optimal endocrine care, (2) hemoglobin A1C should be utilized at every level of diabetes care, (3) nutrition education and increased pharmaceutical options are necessary to optimize the obesity care model, (4) quality neck ultrasound must be part of an optimal thyroid nodule care model, and (5) more scientific evidence is needed on osteoporosis prevalence and cost to justify intervention by governmental health care authorities. This 2015 AACE/ACE Workshop marks the beginning of a structured activity that assists local experts in creating culturally sensitive, evidence-based, and easy-to-implement tools for optimizing endocrine care on a global scale.Abbreviations:A1C = glycated hemoglobinAACE = American Association of Clinical EndocrinologistsACE = American College of EndocrinologyBG = blood glucoseBMI = body mass indexCPA = Clinical Practice AlgorithmCPG = Clinical Practice GuidelineCVD = cardiovascular diseaseDXA = dual-energy X-ray absorptiometryEDC = endocrine-disrupting compoundFBG = fasting blood glucoseFNA = fine-needle aspirationHCP = health care professionalLA = Latin AmericaPAACE = Pan-American AACESU = sulfonylureaT2D = type 2 diabetestDNA = transcultural Diabetes Nutrition AlgorithmTSH = thyroid-stimulating hormoneWC = waist circumferenceWHO = World Health Organization     

Application Of The Aace/Ace Advanced Framework For The Diagnosis Of Obesity And Cardiometabolic Disease Staging In A General Population From 3 Regions Of Venezuela: The Vemsols Study Results

Objective: To determine the prevalence of obesity according to the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) framework based on a complications-centric model with further application of the Cardiometabolic Disease Staging (CMDS) system in a Venezuelan population.Methods: A total of 1,320 adults were randomly selected from 3 regions. The AACE/ACE framework definitions were as follows: overweight, body mass index (BMI) 25 to 29.9 kg/m² and no obesity-related complications (ORC); obesity stage 0, BMI ≥30 and no ORC; stage 1, BMI ≥25 and 1 or more mild-to-moderate ORC; and stage 2, BMI ≥25 and 1 or more severe ORC. CMDS definitions were as follows: stage 0, no metabolic syndrome (MS) components; stage 1, 1 to 2 MS components without impaired fasting glucose (IFG); stage 2, IFG or ≥3 MS components but without IFG; stage 3, IFG and MS; and stage 4, type 2 diabetes (T2D) or cardiovascular disease.Results: The mean age was 44.8 ± 0.4 years, and 68.5% were female. The prevalence of obesity according to the AACE/ACE framework was 63.1%: overweight 3.0% (95% confidence interval &lsqb;CI]: 2.1–3.9); obesity stage 0: 0.1% (0.07–0.27); obesity stage 1: 26.6% (24.2–29.0); and obesity stage 2: 36.4% (33.8–39.0). Most subjects with a BMI <25 were CMDS 0 or 1. In those with BMI ≥ 25, only 4.6% were CMDS 0. The prevalence of obesity according to the World Health Organization (WHO, BMI ≥30) was 29.3% (24.7–33.7).Conclusion: In a general population study, applying the AACE/ACE framework for obesity and CMDS increased the detection of ORC and therefore higher risk subjects compared to classic anthropometric measurements.Abbreviations: AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; BMI = body mass index; CMDS = Cardiometabolic Disease Staging; DALY = disability-adjusted life years; LA = Latin America; MS = metabolic syndrome; ORC = obesity-related complications; WC = waist circumference; WHO = World Health Organization     

Clinical Practice Guidelines For The Perioperative Nutritional,Metabolic, And Nonsurgical Support Of The Bariatric Surgery Patient2013 Update: Cosponsored By American Association Of Clinical Endocrinologists,The Obesity Society,And American Society For Metabolic & Bariatric Surgery

The development of these updated guidelines was commissioned by the AACE, TOS, and ASMBS Board of Directors and adheres to the AACE 2010 protocol for standardized production of clinical practice guidelines (CPG). Each recommendation was re-evaluated and updated based on the evidence and subjective factors per protocol. Examples of expanded topics in this update include: the roles of sleeve gastrectomy, bariatric surgery in patients with type-2 diabetes, bariatric surgery for patients with mild obesity, copper deficiency, informed consent, and behavioral issues. There are 74 recommendations (of which 56 are revised and 2 are new) in this 2013 update, compared with 164 original recommendations in 2008. There are 403 citations, of which 33 (8.2%) are EL 1, 131 (32.5%) are EL 2, 170 (42.2%) are EL 3, and 69 (17.1%) are EL 4. There is a relatively high proportion (40.4%) of strong (EL 1 and 2) studies, compared with only 16.5% in the 2008 AACETOS-ASMBS CPG. These updated guidelines reflect recent additions to the evidence base. Bariatric surgery remains a safe and effective intervention for select patients with obesity. A team approach to perioperative care is mandatory with special attention to nutritional and metabolic issues.     

Patients' Perception On Clinical Outcome And Quality Of Life After A Diagnosis Of Cushing Syndrome

Objective: Excess cortisol production (Cushing syndrome, CS) is a chronic disease affecting many organ systems and impacting quality of life (QoL). This study analyzed factors associated with self-reported QoL, including aspects related to the diagnosis and treatment modalities of CS.Methods: In collaboration with the Cushing's Support and Research Foundation (CSRF), surveys using a validated QoL instrument were sent to CSRF members. Data were analyzed for associations between QoL and demographic, treatment, and disease factors.Results: A total of 269 patients completed the survey. Respondents were 89.9% female, and the mean age was 48 years (SD 12, range 16–76). Respondents visited a median of 4 physicians (range 1–40) prior to the diagnosis of CS, with a median of 5 years (mean 7, SD 5, range 1–30) to obtain a diagnosis, showing a statistically significant negative correlation (P<.001). In one-quarter of cases, someone other than a physician suggested the diagnosis. Multiple regression analysis demonstrated that remission status, time to diagnosis, radiation therapy, and hypopituitarism were significant predictors of QoL. There was no association between QoL and patient's sex, age, replacement steroid use, having follow-up with an endocrinologist, or surgical approach.Conclusion: This is one of the largest QoL studies of CS patients and provides information for treatment and education goals. It is notable that early diagnosis and treatment was the major predictor of better QoL after achieving remission from disease, highlighting the need for awareness about the disorder. Patients in remission had better QoL, emphasizing the importance of disease control.Abbreviations:CD = Cushing diseaseCS = Cushing syndromeCSRF = Cushing's Support and Research FoundationQoL = quality of life     

ACTN3 Gene R577X Polymorphism Associated with High-Density Lipoprotein Cholesterol and Adiponectin in Rugby Players

Objective: To determine the relationship between the R577X polymorphism of the α-actinin-3 (ACTN3), which may play a role in the individual differences observed in the effects of exercise on health benefits and antiatherogenic markers (i.e., high-density lipoprotein cholesterol [HDL-C] and adiponectin) in athletes.Methods: Seventy-six male rugby players (mean age 19.8 years) were enrolled in this study. Genomic DNA was extracted from peripheral blood samples, and restriction fragment length polymorphism-polymerase chain reactions were conducted to assess ACTN3 genotypes. Body mass index (BMI), waist circumference, serum lipids including HDL-C, and adiponectin levels were measured. Current smoking and alcohol intake habits were evaluated with a questionnaire. All of the parameters were compared between 2 groups displaying frequently observed genotypes: one group consisting of patients having either the R/R or R/X genotype and a second group with the X/X genotype.Results: The frequency of the X allele was 0.55 and the distribution of the genotypes was 35.5% (n = 27) for X/X, 39.5% (n = 30) for R/X, and 25.0% (n = 19) for R/R. Serum HDL-C and adiponectin levels were significantly higher in X/X genotype compared to the R/R or R/X genotype (HDL-C 1.6 ± 0.3 [SD] vs. 1.4 ± 0.2 mmol/L; P<.01, adiponectin 8.8 ± 2.6 vs. 6.9 ± 2.3 μg/mL; P<.01), even after adjustments for confounders (P<.01).Conclusion: There may be a relationship between the ACTN3 genotype and HDL-C and adiponectin levels in rugby players. This may be useful information when determining the individual responses of antiatherogenic markers to exercise.Abbreviations:ACTN3 = α-actinin-3BMI = body mass indexCVD = cardiovascular diseaseHDL-C = high-density lipoprotein cholesterolLDL-C = low-density lipoprotein cholesterolR = arginine (R) at amino acid position 577 of the ACTN3 proteinTC = total cholesterolTG = triglycerideX = truncation at amino acid position 577 of the ACTN3 protein     

Potential Place of SGLT2 Inhibitors in Treatment Paradigms for type 2 Diabetes Mellitus

Objective: Following the first Food and Drug Administration (FDA) approval in 2013, sodium glucose cotransporter 2 (SGLT2) inhibitors have generated much interest among physicians treating patients with type 2 diabetes mellitus (T2DM). Here, the role in treatment with this drug class is considered in the context of T2DM treatment paradigms.Methods: The clinical trials for the SGLT2 inhibitors are examined with a focus on canagliflozin, dapagliflozin, and empagliflozin.Results: Evidence from clinical trials in patients with T2DM supports the use of SGLT2 inhibitors either as monotherapy or in addition to other glucose-lowering treatments as adjuncts to diet and exercise, and we have gained significant clinical experience in a relatively short time.Conclusion: The drugs appear to be useful in a variety of T2DM populations, contingent primarily on renal function. Most obviously, SGLT2 inhibitors appear to be well suited for patients with potential for hypoglycemia or weight gain. In clinical trials, patients treated with SGLT2 inhibitors have experienced moderate weight loss and a low risk of hypoglycemic events except when used in combination with an insulin secretagogue. In addition, SGLT2 inhibitors have been shown to reduce blood pressure, so they may be beneficial in patients with T2DM complicated by hypertension. SGLT2 inhibitors were incorporated into the 2015 American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) position statement on the management of hyperglycemia and received an even more prominent position in the American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) comprehensive diabetes management guidelines and algorithm.Abbreviations: AE = adverse event A1C = glycated hemoglobin CI = confidence interval CKD = chronic kidney disease DKA = diabetic ketoacidosis DPP-4 = dipeptidyl peptidase 4 eGFR = estimated glomerular filtration rate FDA = Food and Drug Administration FPG = fasting plasma glucose GLP-1 = glucagon-like peptide 1 HDL-C = high-density lipoprotein cholesterol HR = hazard ratio LADA = late-onset autoimmune diabetes of adulthood LDL-C = low-density lipoprotein cholesterol MACE = major adverse cardiovascular events SGLT1 = sodium glucose cotransporter 1 SGLT2 = sodium glucose cotransporter 2 T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus UACR = urine albumin to creatinine ratio     

Asymmetric Dimethylarginine Levels and Atherosclerosis Markers in Cushing Syndrome

Objective: As a consequence of hypercortisolism, Cushing syndrome (CS) is frequently observed with other diseases that are associated with atherosclerosis, including diabetes mellitus, dyslipidemia, hypertension, and obesity. Cardiovascular disease (CVD) is the primary cause of mortality and morbidity in CS. We investigate CVD risk markers such as asymmetric dimethylarginine (ADMA), lipoprotein-associated phospholipase A2 (Lp-PLA2), highsensitive C-reactive protein (hsCRP), homocysteine, lipid levels, ankle-brachial index (ABI), and carotid intimamedia thickness (CIMT) in CS.Methods: Our study included 27 patients with CS and 27 age-, sex-, body mass index (BMI)-, and comorbid disease–matched control subjects.Results: Plasma ADMA levels were significantly lower in the CS group than the control group (P = .013). Total cholesterol, low-density lipoprotein, triglycerides, high-density lipoprotein, and apolipoprotein A1 and apolipoprotein B levels were higher in patients with CS than the control group (P<.05). We did not find any statistically significant differences in levels of hsCRP, Lp-PLA2, or homocysteine or CIMT and ABI measurements between the CS group and comorbidity-matched control group (P>.05).Conclusion: We found that ADMA levels were lower in CS, the finding that should be further investigated. Levels of hsCRP, Lp-PLA2, and homocysteine levels and CIMT and ABI measurements were similar between the CS group and comorbidity-matched control group. None of these markers was prominent to show an increased risk of CVD in CS, independent of the comorbidities of CS.Abbreviations:ABI = ankle-brachial indexApo = apolipoproteinADMA = asymmetric dimethylarginineBMI = body mass indexCVD = cardiovascular diseaseCIMT = carotid intima-media thicknessCS = Cushing syndromeDM = diabetes mellitusDDAH = dimethylarginine dimethylaminohydrolaseELISA = enzyme-linked immunosorbent assayHDL = high-density lipoproteinhsCRP = high-sensitive C-reactive proteinHOMA-IR = homeostatic model assessment of insulin resistanceHT = hypertensionLDL = low-density lipoproteinLp-PLA2 = lipoprotein-associated phospholipase A2Lp-a = lipoprotein aNO = nitric oxide     

American Association of Clinical Endocrinologists and American College of Endocrinology Protocol for Standardized Production of Clinical Practice Guidelines,Algorithms, and Checklists - 2014 Update and the AACE G4G Program

In 2010, the American Association of Clinical Endocrinologists (AACE) published an update to the original 2004 guidelines. This update hybridized strict evidence-based medicine methods with subjective factors and improved the efficiency of clinical practice guidelines (CPG) production, clinical applicability, and usefulness. Current and persistent shortcomings involving suboptimal implementation and protracted development timelines are addressed in the current 2014 update. The major advances include 1) formulation of an organizational educational strategy, represented by the AACE Council on Education, to address relevant teaching and decision-making tools for clinical endocrinologists, and to generate specific clinical questions to drive CPG, clinical algorithm (CA), and clinical checklist (CC) development; 2) creation and prioritization of printed and online CAs and CCs with a supporting evidence base; 3) focus on clinically relevant and question-oriented topics; 4) utilization of "cascades," where there can be more than 1 recommendation for 1 clinical question; and 5) incorporation of performance metrics to validate, optimize, and effectively update CPG, CAs, and CCs. Efforts continue to translate these clinical tools to electronic formats that can be integrated into a paperless healthcare delivery system, as well as applying them to diverse clinical settings by incorporating transcultural factors. (Endocr Pract. 2014;20:000-000)     

American Association of Clinical Endocrinologists and American College of Endocrinology Position Statement on the Association of SGLT-2 Inhibitors and Diabetic Ketoacidosis

Abbreviations:AACE = American Association of Clinical EndocrinologistsACE = American College of EndocrinologyDKA = diabetic ketoacidosisEMA = European Medicines AgencyFDA = U.S. Food and Drug AdministrationSGLT-2 = sodium glucosecotransporter 2T1D = type 1 diabetesT2D = type 2 diabetes     

American Association of Clinical Endocrinologists and American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis — 2016--Executive Summary

Abbreviations:AACE = American Association of Clinical EndocrinologistsAFF = atypical femur fractureASBMR = American Society for Bone and Mineral ResearchBEL = best evidence levelBMD = bone mineral densityBTM = bone turnover markerCBC = complete blood countCI = confidence intervalDXA = dual-energy X-ray absorptiometryEL = evidence levelFDA = U.S. Food and Drug AdministrationFLEX = Fracture Intervention Trial (FIT) Long-term ExtensionFRAX® = Fracture Risk Assessment ToolGFR = glomerular filtration rateGI = gastrointestinalHORIZON = Health Outcomes and Reduced Incidence with Zoledronic Acid Once YearlyIOF = International Osteoporosis FoundationISCD = International Society for Clinical DensitometryIU = international unitsIV = intravenousLSC = least significant changeNBHA = National Bone Health AllianceNOF = National Osteoporosis Foundation25(OH)D = 25-hydroxy vitamin DONJ = osteonecrosis of the jawPINP = serum carboxy-terminal propeptide of type I collagenPTH = parathyroid hormoneR = recommendationRANK = receptor activator of nuclear factor kappa-BRANKL = receptor activator of nuclear factor kappa-B ligandRCT = randomized controlled trialRR = relative riskS-CTX = serum C-terminal telopeptideSQ = subcutaneousVFA = vertebral fracture assessmentWHO = World Health Organization     

Transcultural Diabetes Care in The United States – A Position Statement by the American Association of Clinical Endocrinologists

The American Association of Clinical Endocrinologists (AACE) has created a transculturalized diabetes chronic disease care model that is adapted for patients across a spectrum of ethnicities and cultures. AACE has conducted several transcultural activities on global issues in clinical endocrinology and completed a 3-city series of conferences in December 2017 that focused on diabetes care for ethnic minorities in the U.S. Proceedings from the “Diabetes Care Across America” series of transcultural summits are presented here. Information from community leaders, practicing health care professionals, and other stakeholders in diabetes care is analyzed according to biological and environmental factors. Four specific U.S. ethnicities are detailed: African Americans, Latino/Hispanics, Asian Americans, and Native Americans. A core set of recommendations to culturally adapt diabetes care is presented that emphasizes culturally appropriate terminology, transculturalization of white papers, culturally adapting clinic infrastructure, flexible office hours, behavioral medicine—especially motivational interviewing and building trust—culturally competent nutritional messaging and health literacy, community partnerships for care delivery, technology innovation, clinical trial recruitment and retention of ethnic minorities, and more funding for scientific studies on epigenetic mechanisms of cultural impact on disease expression. It is hoped that through education, research, and clinical practice enhancements, diabetes care can be optimized in terms of precision and clinical outcomes for the individual and U.S. population as a whole.Lay AbstractThe American Association of Clinical Endocrinologists (AACE) has created a diabetes care model for patients of different backgrounds. AACE led meetings in New York, Houston, and Miami with health care professionals and community leaders to improve diabetes care. Information from these meetings looked at biological and environmental diabetes risks. Four American patient groups were studied: African Americans, Latinos, Asian Americans, and Native Americans. Diabetes care should use culturally appropriate language and search for better ways to apply science and clinic design. Talking to patients more clearly can improve their diabetes control. There are many other needed changes in the American health care system discussed in this paper. It is hoped that through better education, research, and practice, diabetes care can be improved for the entire U.S. population. This means that important differences among patients' ethnic and cultural backgrounds are addressed.Executive Summary

• Cultural adaptation of evidence-based recommendations is a necessary component of optimal diabetes care.
• Biological factors that contribute to the pathophysiology of diabetes vary according to race and ethnicity and can be affected by social determinants that vary with culture.
• The “Transcultural Diabetes Nutrition Algorithm” was developed in 2010 to optimize diabetes nutrition care globally and represents a validated methodology where evidence-based recommendations from a source culture can be adapted and implemented in a different culture using a toolkit.
• The 2015 AACE Pan-American Workshop examined diabetes care in 9 Latin American nations and concluded that there should only be one level of diabetes care for a population and that level should be “excellent;” also, that A1C measurements should be utilized and that more educational and nutritional options are needed to optimize diabetes care.
• The “Diabetes Care Across America – A Series of Transcultural Summits” was an AACE program conducted in 2017 in New York, Houston, and Miami to examine cultural factors that influence diabetes care domestically; the findings of this program are presented here.
• The African American, Hispanic/Latino, Asian American, and Native American populations are each comprised of different ancestries, anthropometrics/body compositions and physical appearances, and cultures and degrees of acculturation, with a significant evidence base that associates specific gene variants with specific phenotypic traits affecting diabetes care.
• For each ethno-cultural population, health messaging and diabetes care will need to consider issues of potential distrust of health care professionals, history of discrimination, religious practices, food preferences, attitudes toward physical activity, and despite the full range of socio-economics, the impact of poverty on engagement, self-monitoring, adherence with lifestyle and medical recommendations, and recruitment for clinical trials.
• Diabetes care should be as precise as possible, incorporating clinical trial evidence that best reflects the ethno-cultural attributes of a specific patient, with particular emphasis on cardiovascular disease risk mitigation, technology to assess the effects of eating patterns on glycemic status, adjusting traditional eating patterns to more healthy options that are still acceptable to the patient, flexibility in lifestyle and medication recommendations that take into account cultural factors, and the utilization of community-based resources to improve implementation.
• Pragmatic first steps to prepare a diabetes practice for an ethno-culturally diverse patient population include: learning more about biological-cultural interactions; gaining experience with lifestyle and behavioral medicine, especially motivational interviewing; creating a safe and immersive clinical environment; incorporating translation services, social prescribing, wearable technologies, web-based resources, and community engagement; and establishing referral networks with clinical trialists in diabetes research to improve recruitment of different populations.

ABSTRACTAbbreviations: A1C = hemoglobin A1c; AACE = American Association of Clinical Endocrinologists; ABCD = adiposity-based chronic disease; BMI = body mass index; CPA = clinical practice algorithm; CPG = clinical practice guideline; DBCD = dysglycemia-based chronic disease; DPP = Diabetes Prevention Program; GWAS = genome-wide association study; HCP = health care professional(s); IHS = Indian Health Service; LDL = low-density lipoprotein; MetS = metabolic syndrome; T2D = type 2 diabetes mellitus; tDNA = transcultural Diabetes Nutrition Algorithm; TG = triglyceride; WC = waist circumference     

SGLT-2 Inhibitor Therapy Added to GLP-1 Agonist Therapy in the Management of T2DM

Objective: To assess the real-world efficacy and safety of canagliflozin therapy added to type 2 diabetes mellitus (T2DM) patients who have received a minimum 1 year of glucagon-like peptide-1 (GLP-1) agonist therapy.Methods: This pre-post observational study assessed the efficacy and safety of canagliflozin in a group of T2DM patients from a community endocrinology practice who received GLP-1 agonist therapy for a minimum of 12 months. The primary study outcome was change in mean glycated hemoglobin (HbA1c) level from baseline. Secondary endpoints included changes in average weight, and comparison of the percentage of patients obtaining an HbA1c <7%.Results: A total of 75 patients met all the study criteria. Baseline patient characteristics were as follows: average age, 58 ± 9 years; mean duration of T2DM, 14 ± 6 years; 56% male; 92% Caucasian; baseline body mass index (BMI), 39.4 ± 9.4 kg/m²; and mean baseline HbA1c, 7.94 ± 0.69%. HbA1c and weight were significantly reduced by 0.39% and 4.6 kg, respectively. Adverse effects were reported by 13 (17.3%) patients, including 4 (5.3%) who discontinued canagliflozin because of adverse reactions.Conclusion: Canagliflozin was generally well tolerated and significantly further reduced mean HbA1c levels and body weight in patients with T2DM when added to GLP-1 regimen.Abbreviations:BP = blood pressureBUN = blood urea nitrogenCANTATA = Canagliflozin Treatment and Trial AnalysisDBP = diastolic blood pressureDKA = diabetic ketoacidosisDPP-4 = dipeptidyl peptidase-4EMR = electronic medical recordFDA = Food and Drug AdministrationGFR = glomerular filtration rateGLP-1 = glucagon-like peptide-1HbA1c = glycated hemoglobinHDL-C = high-density lipoprotein cholesterolLDL-C = low-density lipoprotein cholesterolSCr = serum creatinineSGLT-2 = sodium glucose cotransporter 2T2DM = type 2 diabetes mellitusTZD = thiazolidinedioneUTI = urinary tract infection     

Predictors Of Biochemical Remission And Recurrence After Surgical And Radiation Treatments Of Cushing Disease: A Systematic Review And Meta-Analysis

Objective: We conducted a systematic review and meta-analysis to synthesize the evidence about predictors that may affect biochemical remission and recurrence after transsphenoidal surgery (TSS), radiosurgery (RS), and radiotherapy (RT) in Cushing disease.Methods: We searched multiple databases through December 2014 including original controlled and uncontrolled studies that enrolled patients with Cushing disease who received TSS (first-line), RS, or RT. We extracted data independently, in duplicates. Outcomes of interest were biochemical remission and recurrence. A meta-analysis was conducted using the random-effects model to estimate event rates with 95% confidence intervals (CIs).Results: First-line TSS was associated with high remission (76% &lsqb;95% CI, 72 to 79%]) and low recurrence rates (10% &lsqb;95% CI, 6 to 16%]). Remission after TSS was higher in patients with microadenomas or positive–adrenocorticotropic hormone tumor histology. RT was associated with a high remission rate (RS, 68% &lsqb;95% CI, 61 to 77%]; RT, 66% &lsqb;95% CI, 58 to 75%]) but also with a high recurrence rate (RS, 32% &lsqb;95% CI, 16 to 60%]; RT, 26% &lsqb;95% CI, 14 to 48%]). Remission after RS was higher at short-term follow-up (≤2 years) and with high-dose radiation, while recurrence was higher in women and with lower-dose radiation. Remission was after RT in adults who received TSS prior to RT, and with lower radiation doses. There was heterogeneity (nonstandardization) in the criteria and cutoff points used to define biochemical remission and recurrence.Conclusion: First-line TSS is associated with high remission and low recurrence, while RS and RT are associated with reasonable remission rates but important recurrence rates. The current evidence warrants low confidence due to the noncomparative nature of the studies, high heterogeneity, and imprecision.Abbreviations:ACTH = adrenocorticotropic hormoneMRI = magnetic resonance imagingRS = radiosurgeryRT = radiotherapySC = serum cortisolTSS = transsphenoidal surgeryUFC = urinary free cortisol     

An Italian Survey of Compliance With Major Guidelines for L-Thyroxine of Primary Hypothyroidism

Objective: The adherence by endocrinologists to guideline regarding levothyroxine (LT4) therapy and the compliance of patients may impact the management of hypothyroidism. The aim of this study was to compare the adherence of Italian endocrinologists to the ATA/AACE and ETA guidelines on the management of newly diagnosed primary hypothyroidism and to validate the Italian version of the Morisky-Green Medical Adherence Scale-8 (MMAS-8) questionnaire as applied to the evaluation of the adherence of patients with hypothyroidism to LT4 treatment.Methods: This was an observational, longitudinal, multicenter, cohort study, involving 12 Italian Units of Endocrinology.Results: The study enrolled 1,039 consecutive outpatients (mean age 48 years; 855 women, 184 men). The concordance of Italian endocrinologists with American Association of Clinical Endocrinologists/American Thyroid Association (AACE/ATA) and European Thyroid Association (ETA) recommendations was comparable (77.1% and 71.7%) and increased (86.7 and 88.6%) after the recommendations on LT4 dose were excluded, considering only the remaining recommendations on diagnosis, therapy, and follow-up. The MMAS-8 was filled out by 293 patients. The mean score was 6.71 with 23.9% low (score <6), 38.6% medium (6 to <8), 37.5% highly (= 8) adherers; the internal validation coefficient was 0.613. Highly adherent patients were not more likely to have good control of hypothyroidism compared with either medium (69% versus 72%, P = .878) or low (69% versus 43%, P = .861) adherers.Conclusion: Clinical management of hypothyroidism in Italy demonstrated an observance of international guidelines by Italian endocrinologists. Validation of the Italian version of the MMAS-8 questionnaire provides clinicians with a reliable and simple tool for assessing the adherence of patients to LT4 treatment.Abbreviations: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; EDIPO = Endotrial SIE: DIagnosis and clinical management of Primitive hypothyrOidism in Italy; eCRF = electronic case report form; ETA = European Thyroid Association; fT3 = free triiodothyronine; fT4 = free thyroxine; LT4 = levothyroxine; MMAS-8 = Morisky-Green Medical Adherence Scale-8; PH = primary hypothyroidism; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone; US = ultrasonography