Faculty Bibliography

OBJECTIVE:The development of these guidelines is mandated 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 document contains 87 recommendations of which 45 are Grade A (51.7%), 18 are Grade B (20.7%), 15 are Grade C (17.2%), and 9 (10.3%) are Grade D. These detailed, evidence-based recommendations allow for nuance-based clinical decision-making that addresses multiple aspects of real-world medical care. The evidence base presented in the subsequent Appendix provides relevant supporting information for Executive Summary Recommendations. This update contains 695 citations of which 203 (29.2 %) are EL 1 (strong), 137 (19.7%) are EL 2 (intermediate), 119 (17.1%) are EL 3 (weak), and 236 (34.0%) are EL 4 (no clinical evidence). CONCLUSION/CONCLUSIONS:This CPG is a practical tool that endocrinologists, other health care professionals, health-related organizations, and regulatory bodies can use to reduce the risks and consequences of dyslipidemia. It provides guidance on screening, risk assessment, and treatment recommendations for a range of individuals with various lipid disorders. The recommendations emphasize the importance of treating low-density lipoprotein cholesterol (LDL-C) in some individuals to lower goals than previously endorsed and support the measurement of coronary artery calcium scores and inflammatory markers to help stratify risk. Special consideration is given to individuals with diabetes, familial hypercholesterolemia, women, and youth with dyslipidemia. Both clinical and cost-effectiveness data are provided to support treatment decisions. ABBREVIATIONS/BACKGROUND:4S = Scandinavian Simvastatin Survival Study A1C = glycated hemoglobin AACE = American Association of Clinical Endocrinologists AAP = American Academy of Pediatrics ACC = American College of Cardiology ACE = American College of Endocrinology ACS = acute coronary syndrome ADMIT = Arterial Disease Multiple Intervention Trial ADVENT = Assessment of Diabetes Control and Evaluation of the Efficacy of Niaspan Trial AFCAPS/TexCAPS = Air Force/Texas Coronary Atherosclerosis Prevention Study AHA = American Heart Association AHRQ = Agency for Healthcare Research and Quality AIM-HIGH = Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides trial ASCVD = atherosclerotic cardiovascular disease ATP = Adult Treatment Panel apo = apolipoprotein BEL = best evidence level BIP = Bezafibrate Infarction Prevention trial BMI = body mass index CABG = coronary artery bypass graft CAC = coronary artery calcification CARDS = Collaborative Atorvastatin Diabetes Study CDP = Coronary Drug Project trial CI = confidence interval CIMT = carotid intimal media thickness CKD = chronic kidney disease CPG(s) = clinical practice guideline(s) CRP = C-reactive protein CTT = Cholesterol Treatment Trialists CV = cerebrovascular CVA = cerebrovascular accident EL = evidence level FH = familial hypercholesterolemia FIELD = Secondary Endpoints from the Fenofibrate Intervention and Event Lowering in Diabetes trial FOURIER = Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects With Elevated Risk trial HATS = HDL-Atherosclerosis Treatment Study HDL-C = high-density lipoprotein cholesterol HeFH = heterozygous familial hypercholesterolemia HHS = Helsinki Heart Study HIV = human immunodeficiency virus HoFH = homozygous familial hypercholesterolemia HPS = Heart Protection Study HPS2-THRIVE = Treatment of HDL to Reduce the Incidence of Vascular Events trial HR = hazard ratio HRT = hormone replacement therapy hsCRP = high-sensitivity CRP IMPROVE-IT = Improved Reduction of Outcomes: Vytorin Efficacy International Trial IRAS = Insulin Resistance Atherosclerosis Study JUPITER = Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin LDL-C = low-density lipoprotein cholesterol Lp-PLA2 = lipoprotein-associated phospholipase A2 MACE = major cardiovascular events MESA = Multi-Ethnic Study of Atherosclerosis MetS = metabolic syndrome MI = myocardial infarction MRFIT = Multiple Risk Factor Intervention Trial NCEP = National Cholesterol Education Program NHLBI = National Heart, Lung, and Blood Institute PCOS = polycystic ovary syndrome PCSK9 = proprotein convertase subtilisin/kexin type 9 Post CABG = Post Coronary Artery Bypass Graft trial PROSPER = Prospective Study of Pravastatin in the Elderly at Risk trial QALY = quality-adjusted life-year ROC = receiver-operator characteristic SOC = standard of care SHARP = Study of Heart and Renal Protection T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus TG = triglycerides TNT = Treating to New Targets trial VA-HIT = Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial VLDL-C = very low-density lipoprotein cholesterol WHI = Women's Health Initiative.

ABBREVIATIONS/BACKGROUND:= Fracture Risk Assessment Tool GFR = glomerular filtration rate GI = gastrointestinal HORIZON = Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly IOF = International Osteoporosis Foundation ISCD = International Society for Clinical Densitometry IU = international units IV = intravenous LSC = least significant change NBHA = National Bone Health Alliance NOF = National Osteoporosis Foundation 25(OH)D = 25-hydroxy vitamin D ONJ = osteonecrosis of the jaw PINP = serum carboxy-terminal propeptide of type I collagen PTH = parathyroid hormone R = recommendation RANK = receptor activator of nuclear factor kappa-B RANKL = receptor activator of nuclear factor kappa-B ligand RCT = randomized controlled trial RR = relative risk S-CTX = serum C-terminal telopeptide SQ = subcutaneous VFA = vertebral fracture assessment WHO = World Health Organization.

ABBREVIATIONS/BACKGROUND:AACE = American Association of Clinical Endocrinologists AFF = atypical femur fracture ASBMR = American Society for Bone and Mineral Research BEL = best evidence level BMD = bone mineral density BTM = bone turnover marker CBC = complete blood count CI = confidence interval DXA = dual-energy X-ray absorptiometry EL = evidence level FDA = U.S. Food and Drug Administration FLEX = Fracture Intervention Trial (FIT) Long-term Extension FRAX(®) = Fracture Risk Assessment Tool GFR = glomerular filtration rate GI = gastrointestinal HORIZON = Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly IOF = International Osteoporosis Foundation ISCD = International Society for Clinical Densitometry IU = international units IV = intravenous LSC = least significant change NBHA = National Bone Health Alliance NOF = National Osteoporosis Foundation 25(OH)D = 25-hydroxy vitamin D ONJ = osteonecrosis of the jaw PINP = serum carboxy-terminal propeptide of type I collagen PTH = parathyroid hormone R = recommendation RANK = receptor activator of nuclear factor kappa-B RANKL = receptor activator of nuclear factor kappa-B ligand RCT = randomized controlled trial RR = relative risk S-CTX = serum C-terminal telopeptide SQ = subcutaneous VFA = vertebral fracture assessment WHO = World Health Organization.

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 A1c AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology AMA = American Medical Association BEL = best evidence level BMI = body mass index CCO = Consensus Conference on Obesity CPG = clinical practice guideline CSS = cross-sectional study CVD = cardiovascular disease EL = evidence level FDA = Food and Drug Administration GERD = gastroesophageal reflux disease HDL-c = high-density lipoprotein cholesterol IFG = impaired fasting glucose IGT = impaired glucose tolerance LDL-c = low-density lipoprotein cholesterol MNRCT = meta-analysis of non-randomized prospective or case-controlled trials NE = no evidence PCOS = polycystic ovary syndrome RCT = randomized controlled trial SS = surveillance study U.S = United States.

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 1,790 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 353 (19.7%) based on reviews and opinions (EL 4). CONCLUSION/CONCLUSIONS: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/BACKGROUND:A1C = hemoglobin A1c AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology ACSM = American College of Sports Medicine ADA = American Diabetes Association ADAPT = Arthritis, Diet, and Activity Promotion Trial ADHD = attention-deficit hyperactivity disorder AHA = American Heart Association AHEAD = Action for Health in Diabetes AHI = apnea-hypopnea index ALT = alanine aminotransferase AMA = American Medical Association ARB = angiotensin receptor blocker ART = assisted reproductive technology AUC = area under the curve BDI = Beck Depression Inventory BED = binge eating disorder BEL = best evidence level BLOOM = Behavioral Modification and Lorcaserin for Overweight and Obesity Management BLOSSOM = Behavioral Modification and Lorcaserin Second Study for Obesity Management BMI = body mass index BP = blood pressure C-SSRS = Columbia Suicidality Severity Rating Scale CAD = coronary artery disease CARDIA = Coronary Artery Risk Development in Young Adults CBT = cognitive behavioral therapy CCO = Consensus Conference on Obesity CHF = congestive heart failure CHO = carbohydrate CI = confidence interval COR-I = Contrave Obesity Research I CPG = clinical practice guideline CV = cardiovascular CVD = cardiovascular disease DASH = Dietary Approaches to Stop Hypertension DBP = diastolic blood pressure DEXA = dual-energy X-ray absorptiometry DPP = Diabetes Prevention Program DSE = diabetes support and education EL = evidence level ED = erectile dysfunction ER = extended release EWL = excess weight loss FDA = Food and Drug Administration FDG = 18F-fluorodeoxyglucose GABA = gamma-aminobutyric acid GERD = gastroesophageal reflux disease GI = gastrointestinal GLP-1 = glucagon-like peptide 1 HADS = Hospital Anxiety and Depression Scale HDL-c = high-density lipoprotein cholesterol HR = hazard ratio HTN = hypertension HUNT = Nord-Trøndelag Health Study ICSI = intracytoplasmic sperm injection IFG = impaired fasting glucose IGT = impaired glucose tolerance ILI = intensive lifestyle intervention IVF = in vitro fertilization LAGB = laparoscopic adjustable gastric banding LDL-c = low-density lipoprotein cholesterol LES = lower esophageal sphincter LSG = laparoscopic sleeve gastrectomy LV = left ventricle LVH = left ventricular hypertrophy LVBG = laparoscopic vertical banded gastroplasty MACE = major adverse cardiovascular events MAOI = monoamine oxidase inhibitor MI = myocardial infarction MNRCT = meta-analysis of non-randomized prospective or case-controlled trials MRI = magnetic resonance imaging MUFA = monounsaturated fatty acid NAFLD = nonalcoholic fatty liver disease NASH = nonalcoholic steatohepatitis NES = night eating syndrome NHANES = National Health and Nutrition Examination Surveys NHLBI = National Heart, Lung, and Blood Institute NHS = Nurses' Health Study NICE = National Institute for Health and Care Excellence OA = osteoarthritis OGTT = oral glucose tolerance test OR = odds ratio OSA = obstructive sleep apnea PHQ-9 = Patient Health Questionnaire PCOS = polycystic ovary syndrome PCP = primary care physician POMC = pro-opiomelanocortin POWER = Practice-Based Opportunities for Weight Reduction PPI = proton pump inhibitor PRIDE = Program to Reduce Incontinence by Diet and Exercise PSA = prostate specific antigen QOL = quality of life RA = receptor agonist RCT = randomized controlled trial ROC = receiver operator characteristic RR = relative risk RYGB = Roux-en-Y gastric bypass SAD = sagittal abdominal diameter SBP = systolic blood pressure SCOUT = Sibutramine Cardiovascular Outcome Trial SG = sleeve gastrectomy SHBG = sex hormonebinding globulin SIEDY = Structured Interview on Erectile Dysfunction SNRI = serotonin-norepinephrine reuptake inhibitors SOS = Swedish Obese Subjects SS = surveillance study SSRI = selective serotonin reuptake inhibitors STORM = Sibutramine Trial on Obesity Reduction and Maintenance TCA = tricyclic antidepressant TONE = Trial of Nonpharmacologic Intervention in the Elderly TOS = The Obesity Society T2DM = type 2 diabetes mellitus UKPDS = United Kingdom Prospective Diabetes Study U.S = United States VAT = visceral adipose tissue VLDL = very low-density lipoprotein WC = waist circumference WHO = World Health Organization WHR = waist-hip ratio WHtR = waist-to-height ratio WMD = weighted mean difference WOMAC = Western Ontario and McMaster Universities osteoarthritis index XENDOS = XEnical in the Prevention of Diabetes in Obese Subjects.

Adrenal diseases, including Cushing syndrome (CS), primary aldosteronism (PA), pheochromocytoma, and adrenocortical carcinoma, are uncommon in pregnancy; a high degree of clinical suspicion must exist. Physiologic changes to the hypothalamus-pituitary-adrenal axis in a normal pregnancy result in increased cortisol, renin, and aldosterone levels, making the diagnosis of CS and PA in pregnancy challenging. However, catecholamines are not altered in pregnancy and allow a laboratory diagnosis of pheochromocytoma that is similar to that of the nonpregnant state. Although adrenal tumors in pregnancy result in significant maternal and fetal morbidity, and sometimes mortality, early diagnosis and appropriate treatment often improve outcomes.

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.

BACKGROUND:Pregnant woman are at increased risk for iodine deficiency, which may induce thyroid insufficiency and have damaging effects not only on the mother but also the fetus. We hypothesize that iodine supplementation during pregnancy reduces the risk for iodine deficiency. METHODS:Cross-sectional study to assess iodine levels in random urine specimens during pregnancy in New York City. One hundred eighty-two women visited a clinic where free iodine supplementation was offered (150 μg of potassium iodide daily; Group A), and 183 women were seen at a practice at which no supplementation was offered (Group B). RESULTS:Overall, more than one out of two pregnant women in New York City were at risk for iodine deficiency with a spot urinary iodine (UI) level less than 150 μg/L and could be defined as at risk for iodine deficiency. The median urine iodine concentration for the entire group was 152.5 μg/L, but there was considerable variation from 10.9 to 1210 μg/L. The median UI level of the supplemented Group A (169.8 μg/L) was significantly greater than that of Group B (128.4 μg/L; p<0.01). Based on World Health Organization (WHO) guidelines, 38.9% of Group B women were at risk for mild, moderate, or severe iodine deficiency, compared with 22.8% of Group A women. CONCLUSIONS:New York City pregnant women were significantly less prone to iodine deficiency when provided with iodine supplementation. Nevertheless, when spot UI levels were used to estimate iodine sufficiency, more than 20% of supplemented women were still at risk for iodine deficiency according to WHO guidelines, suggesting that current supplementation practices remain insufficient.