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Showing papers in "The Journal of Clinical Endocrinology and Metabolism in 2012"


Journal ArticleDOI
TL;DR: It is recommended that MEN1 patients and their families should be cared for by multidisciplinary teams comprising relevant specialists with experience in the diagnosis and treatment of patients with endocrine tumors.
Abstract: Objective: The aim was to provide guidelines for evaluation, treatment, and genetic testing for multiple endocrine neoplasia type 1 (MEN1). Participants: The group, which comprised 10 experts, including physicians, surgeons, and geneticists from international centers, received no corporate funding or remuneration. Process: Guidelines were developed by reviews of peer-reviewed publications; a draft was prepared, reviewed, and rigorously revised at several stages; and agreed-upon revisions were incorporated. Conclusions: MEN1 is an autosomal dominant disorder that is due to mutations in the tumor suppressor gene MEN1, which encodes a 610-amino acid protein, menin. Thus, the finding of MEN1 in a patient has important implications for family members because first-degree relatives have a 50% risk of developing the disease and can often be identified by MEN1 mutational analysis. MEN1 is characterized by the occurrence of parathyroid, pancreatic islet, and anterior pituitary tumors. Some patients may also develo...

1,028 citations


Journal ArticleDOI
TL;DR: This evidence-based guideline provides recommendations for practical, achievable, and safe glycemic targets and describes protocols, procedures, and system improvements required to facilitate the achievement of glycemic goals in patients with hyperglycemia and diabetes admitted in non-critical care settings.
Abstract: Objective: The aim was to formulate practice guidelines on the management of hyperglycemia in hospitalized patients in the non-critical care setting. Participants: The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, six additional experts, and a methodologist. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Endocrine Society members, American Diabetes Association, American Heart Association, American Association of Diabetes Educators, European Society of Endocrinology, and the Society of Hospital Medicine reviewed and commented on preliminary drafts of this guideline. Conclusions: Hyperglycemia is a common, serious, and costly health care problem in hospitalized ...

931 citations


Journal ArticleDOI
TL;DR: Dapagliflozin reduces TBW, predominantly by reducing FM, VAT and SAT in T2DM inadequately controlled with metformin and establishes through body composition measurements whether weight loss is accounted for by changes in fat or fluid components.
Abstract: Context: Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion, and weight loss is a consistent associated finding. Objectives: Our objectives were to confirm weight loss with dapagliflozin and establish through body composition measurements whether weight loss is accounted for by changes in fat or fluid components. Design and Setting: This was a 24-wk, international, multicenter, randomized, parallel-group, double-blind, placebo-controlled study with ongoing 78-wk site- and patient-blinded extension period at 40 sites in five countries. Patients: Included were 182 patients with T2DM (mean values: women 63.3 and men 58.6 yr of age; hemoglobin A1c 7.17%, body mass index 31.9 kg/m2, and body weight 91.5 kg) inadequately controlled on metformin. Intervention: Dapagliflozin 10 mg/d or placebo was added to open-label metformin for 24 wk. Main Outcome Measures: Primary endpoint w...

667 citations


Journal ArticleDOI
TL;DR: In this paper, the authors developed clinical practice guidelines on hypertriglyceridemia based on systematic reviews of evidence, e-mail discussion, conference calls, and one in-person meeting.
Abstract: Objective: The aim was to develop clinical practice guidelines on hypertriglyceridemia. Participants: The Task Force included a chair selected by The Endocrine Society Clinical Guidelines Subcommittee (CGS), five additional experts in the field, and a methodologist. The authors received no corporate funding or remuneration. Consensus Process: Consensus was guided by systematic reviews of evidence, e-mail discussion, conference calls, and one in-person meeting. The guidelines were reviewed and approved sequentially by The Endocrine Society's CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments. Conclusions: The Task Force recommends that the diagnosis of hypertriglyceridemia be based on fasting levels, that mild and moderate hypertriglyceridemia (triglycerides of 150–999 mg/dl) be diagnosed to aid in the evaluation of cardiovascular risk, and that severe and very se...

632 citations


Journal ArticleDOI
TL;DR: The prevalence of familial hypercholesterolemia appears to be higher than commonly perceived in a general population of white Danish individuals, with at least half of affected subjects not receiving cholesterol-lowering medication.
Abstract: Context: The diagnosis of familial hypercholesterolemia (FH) can be made using the Dutch Lipid Clinic Network criteria. This employs the personal and family history of premature coronary artery disease and hypercholesterolemia and the presence of a pathogenic mutation in the low-density lipoprotein receptor (LDLR) and apolipoprotein B (APOB) genes. Objective: We employed this tool to investigate the prevalence of FH and the associations between FH and coronary artery disease and cholesterol-lowering medication in the Copenhagen General Population Study. Setting: The study was of an unselected, community-based population comprising 69,016 participants. Main Outcome Measures: FH (definite/probable) was defined as a Dutch Lipid Clinic Network score higher than 5. Coronary artery disease was myocardial infarction or angina pectoris. Results: The prevalence of FH was 0.73% (one in 137). Of participants with FH, 20% had an LDLR or APOB mutation. The prevalence of coronary artery disease among FH participants wa...

539 citations


Journal ArticleDOI
TL;DR: Boston University School of Medicine (M.H.F.H.), Boston, Massachusetts 02118-2526; Osteoporosis Research Program (N.C.G.), Childrens Hospital, Boston,achusetts 02115; Division of Endocrinology and Metabolism (D.A.M.W.), Purdue University, West Lafayette, Indiana 47907.
Abstract: Boston University School of Medicine (M.F.H.), Boston, Massachusetts 02118-2526; Osteoporosis Research Program (N.C.B.), University of Wisconsin, Madison, Wisconsin 53706; Department of Rheumatology and Institute for Physical Medicine (H.A.B.-F.), University Hospital Zurich, 8091 Zurich, Switzerland; Divisions of Adolescent Medicine and Endocrinology (C.M.G.), Childrens Hospital, Boston, Massachusetts 02115; Division of Endocrinology and Metabolism (D.A.H.), Health Science Centre, University of Calgary Faculty of Medicine (R.P.H.), Calgary, Canada AB T2N 4N1; Creighton University (R.P.H.), Omaha, Nebraska 68131; Division of Preventative, Occupational, and Aerospace Medicine Mayo Clinic (M.H.M.), Rochester, Minnesota 55905; and Department of Foods and Nutrition (C.M.W.), Purdue University, West Lafayette, Indiana 47907

519 citations


Journal ArticleDOI
TL;DR: Members of the Institute of Medicine committee respond to aspects of The Endocrine Society guideline that are not well supported and in need of reconsideration on target serum 25-hydroxyvitamin D levels and the definition of vitamin D deficiency.
Abstract: In early 2011, a committee convened by the Institute of Medicine issued a report on the Dietary Reference Intakes for calcium and vitamin D. The Endocrine Society Task Force in July 2011 published a guideline for the evaluation, treatment, and prevention of vitamin D deficiency. Although these reports are intended for different purposes, the disagreements concerning the nature of the available data and the resulting conclusions have caused confusion for clinicians, researchers, and the public. In this commentary, members of the Institute of Medicine committee respond to aspects of The Endocrine Society guideline that are not well supported and in need of reconsideration. These concerns focus on target serum 25-hydroxyvitamin D levels, the definition of vitamin D deficiency, and the question of who constitutes a population at risk vs. the general population.

497 citations


Journal ArticleDOI
TL;DR: Metabolically healthy obese participants were not at increased risk of CVD and all-cause mortality over 7 yr, and metabolic health/obesity categories with mortality were examined.
Abstract: Context: Previous studies have identified an obese phenotype without the burden of adiposity-associated cardiometabolic risk factors, although the health effects remain unclear. Objective: We examined the association between metabolically healthy obesity and risk of cardiovascular disease (CVD) and all-cause mortality. Design and Setting: This was an observational study with prospective linkage to mortality records in community-dwelling adults from the general population in Scotland and England. Participants: A total of 22,203 men and women [aged 54.1 (SD 12.7 yr), 45.2% men] without known history of CVD at baseline. Interventions: Based on blood pressure, high-density lipoprotein-cholesterol, diabetes diagnosis, waist circumference, and low-grade inflammation (C-reactive protein ≥ 3 mg/liter), participants were classified as metabolically healthy (0 or 1 metabolic abnormality) or unhealthy (two or more metabolic abnormalities). Obesity was defined as a body mass index of 30 kg/m2 or greater. Main Outcome...

482 citations


Journal ArticleDOI
TL;DR: Osteoporosis in men causes significant morbidity and mortality and Pharmacological treatment is recommended for men aged 50 or older who have had spine or hip fractures, those with T-scores of -2.5 or below, and men at high risk of fracture based on low bone mineral density and/or clinical risk factors.
Abstract: Objective: The aim was to formulate practice guidelines for management of osteoporosis in men. Evidence: We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and evidence quality. Consensus Process: Consensus was guided by systematic evidence reviews, one in-person meeting, and multiple conference calls and e-mails. Task Force drafts were reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee and Clinical Affairs Core Committee; representatives of ASBMR, ECTS, ESE, ISCD; and members at large. At each stage, the Task Force received written comments and incorporated needed changes. The reviewed document was approved by The Endocrine Society Council before submission for peer review. Conclusions: Osteoporosis in men causes significant morbidity and mortality. We recommend testing higher risk men [aged ≥70 and men aged 50–69 who have risk factors (e.g. low body weight, prior fracture as an adult, s...

466 citations


Journal ArticleDOI
TL;DR: In an observational cohort of men withLow testosterone levels, testosterone treatment was associated with decreased mortality compared with no testosterone treatment, and large, randomized clinical trials are needed to better characterize the health effects of testosterone treatment in older men with low testosterone levels.
Abstract: Context: Low testosterone levels in men have been associated with increased mortality. However, the influence of testosterone treatment on mortality in men with low testosterone levels is not known. Objective: The objective of the study was to examine the association between testosterone treatment and mortality in men with low testosterone levels. Design: This was an observational study of mortality in testosterone-treated compared with untreated men, assessed with time-varying, adjusted Cox proportional hazards regression models. Effect modification by age, diabetes, and coronary heart disease was tested a priori. Setting: The study was conducted with a clinical database that included seven Northwest Veterans Affairs medical centers. Patients: Patients included a cohort of 1031 male veterans, aged older than 40 yr, with low total testosterone [≤250 ng/dl (8.7 nmol/liter)] and no history of prostate cancer, assessed between January 2001 and December 2002 and followed up through the end of 2005. Main Outco...

409 citations


Journal ArticleDOI
TL;DR: A negative impact of excision of endometriomas on ovarian reserve is suggested as evidenced by a significant postoperative fall in circulating AMH.
Abstract: Context: Endometriomas are mainly treated surgically. However, there has been concern over the potential damaging effect of this surgery on ovarian reserve. Objective: The aim of this meta-analysis was to investigate the impact of surgery for endometriomas on ovarian reserve as determined by serum anti-Mullerian hormone (AMH). Data Sources: MEDLINE, PubMed, and Embase were searched electronically. Study Selection: All prospective cohort studies that analyzed changes of serum AMH concentrations after surgical treatment of endometriomas were eligible. Twenty-one studies were identified, of which eight were selected for meta-analysis. Data Extraction: Two reviewers performed the data extraction independently. Data Synthesis: Pooled analysis of 237 patients showed a statistically significant decrease in serum AMH concentration after ovarian cystectomy (weighted mean difference −1.13 ng/ml; 95% confidence interval −0.37 to −1.88), although heterogeneity was high. Sensitivity analysis for studies with a preoper...

Journal ArticleDOI
TL;DR: Mifepristone produced significant clinical and metabolic improvement in patients with CS with an acceptable risk-benefit profile during 6 months of treatment, and had significant improvement in clinical status.
Abstract: Context: Cushing's syndrome (CS) is a disorder associated with significant morbidity and mortality due to prolonged exposure to high cortisol concentrations. Objective: Our objective was to evaluate the safety and efficacy of mifepristone, a glucocorticoid receptor antagonist, in endogenous CS. Design and Setting: We conducted a 24-wk multicenter, open-label trial after failed multimodality therapy at 14 U.S. academic medical centers and three private research centers. Participants: Participants included 50 adults with endogenous CS associated with type 2 diabetes mellitus/impaired glucose tolerance (C-DM) or a diagnosis of hypertension alone (C-HT). Intervention: Mifepristone was administered at doses of 300-1200 mg daily. Main Outcome Measures: We evaluated change in area under the curve for glucose on 2-h oral glucose test for C-DM and change in diastolic blood pressure from baseline to wk 24 for C-HT. Results: In the C-DM cohort, an area under the curve for glucose (AUCglucose) response was seen in 60...

Journal ArticleDOI
TL;DR: The rich dataset of the T1D Exchange registry provides an opportunity to address numerous issues of relevance to clinicians and patients, including assessments of associations between patient characteristics and diabetes management factors with outcomes.
Abstract: Context: The T1D Exchange includes a clinic-based registry, a patient-centric web site called Glu, and a biobank. Objective: The aim of the study was to describe the T1D Exchange clinic registry and provide an overview of participant characteristics. Design: Data obtained through participant completion of a questionnaire and chart extraction include diabetes history, management, and monitoring; general health; lifestyle; family history; socioeconomic factors; medications; acute and chronic diabetic complications; other medical conditions; and laboratory results. Setting: Data were collected from 67 endocrinology centers throughout the United States. Patients: We studied 25,833 adults and children with presumed autoimmune type 1 diabetes (T1D). Results: Participants ranged in age from less than 1 to 93 yr, 50% were female, 82% were Caucasian, 50% used an insulin pump, 6% used continuous glucose monitoring, and 16% had a first-degree family member with T1D. Glycosylated hemoglobin at enrollment averaged 8.3...


Journal ArticleDOI
TL;DR: Significant dysregulation of seven candidate microRNAs has been found to be associated with risks involved in the manifestation of metabolic syndrome and six of them were identified as potential contributors of dyslipidemia in metabolic syndrome.
Abstract: Context: Coordinated interplay of dysregulated microRNAs in isolated metabolic disorder is implicated in the pathogenesis of metabolic syndrome. Objective: The objective of the study was to characterize microRNA expression in the blood and exosomes of individuals with metabolic syndrome and compare them with those manifesting one of the metabolic vascular risk factors (type 2 diabetes, hypercholesterolemia, or hypertension). Research Design/Setting/Participants: A total of 265 participants were recruited in a health screening and characterized into distinct groups as follows: 1) healthy controls (n = 46); 2) metabolic syndrome (n = 50); 3) type 2 diabetes (n = 50); 4) hypercholesterolemia (n = 89); and 5) hypertension (n = 30). Total RNA was subjected to microRNA profiling, and a panel of significantly dysregulated microRNAs was validated using quantitative PCR. Main Outcome Measures: Analysis of profiling data characterized unique pools of miRNAs that could categorize the different risk factors of metabo...

Journal ArticleDOI
TL;DR: Several themes emerged in the statement, including a need for basic science, population-based, translational and health services studies to explore underlying mechanisms contributing to endocrine health disparities, suggesting that population interventions targeting weight loss may favorably impact a number of endocrine disorders.
Abstract: Objective: The aim was to provide a scholarly review of the published literature on biological, clinical, and nonclinical contributors to race/ethnic and sex disparities in endocrine disorders and to identify current gaps in knowledge as a focus for future research needs. Participants in Development of Scientific Statement: The Endocrine Society's Scientific Statement Task Force (SSTF) selected the leader of the statement development group (S.H.G.). She selected an eight-member writing group with expertise in endocrinology and health disparities, which was approved by the Society. All discussions regarding the scientific statement content occurred via teleconference or written correspondence. No funding was provided to any expert or peer reviewer, and all participants volunteered their time to prepare this Scientific Statement. Evidence: The primary sources of data on global disease prevalence are from the World Health Organization. A comprehensive literature search of PubMed identified U.S. population-ba...

Journal ArticleDOI
TL;DR: BPA was positively associated with generalized obesity, abdominal obesity, and insulin resistance in middle-aged and elderly Chinese adults.
Abstract: Context: Bisphenol A (BPA) is one of the world's highest-volume chemicals in use today. Previous studies have suggested BPA disturbs body weight regulation and promotes obesity and insulin resistance. But epidemiological data in humans were limited. Objective: Our objective was to determine whether BPA associates with obesity and insulin resistance. Design, Setting, and Participants: This cross-sectional study included 3390 adults aged 40 yr or older, in Songnan Community, Baoshan District, Shanghai, China. Main Outcome Measures: Questionnaire, clinical and biochemical measurements, and urinary BPA concentration were determined. Generalized overweight was defined as body mass index (BMI) of 24 to less than 28 kg/m2 and obesity was defined as BMI of 28 kg/m2 or higher. Abdominal obesity was defined as waist circumference at least 90 cm for men and at least 85 cm for women. Insulin resistance was defined as the index of homeostasis model assessment of insulin resistance higher than 2.50. Results: The partic...

Journal ArticleDOI
TL;DR: Despite carrying a minimal risk of adrenal vein rupture and at variance with the guidelines, AVS is not used systematically at major referral centers worldwide, representing an argument for defining guidelines for this clinically important but technically demanding procedure.
Abstract: Context: In patients who seek surgical cure of primary aldosteronism (PA), The Endocrine Society Guidelines recommend the use of adrenal vein sampling (AVS), which is invasive, technically challenging, difficult to interpret, and commonly held to be risky. Objective: The aim of this study was to determine the complication rate of AVS and the ways in which it is performed and interpreted at major referral centers. Design and Settings: The Adrenal Vein Sampling International Study is an observational, retrospective, multicenter study conducted at major referral centers for endocrine hypertension worldwide. Participants: Eligible centers were identified from those that had published on PA and/or AVS in the last decade. Main Outcome Measure: The protocols, interpretation, and costs of AVS were measured, as well as the rate of adrenal vein rupture and the rate of use of AVS. Results: Twenty of 24 eligible centers from Asia, Australia, North America, and Europe participated and provided information on 2604 AVS ...

Journal ArticleDOI
TL;DR: The prospects of effective anabolic therapy for osteoporosis are indeed bright, and the two main osteoanabolic pathways identified as of today are PTH, the only anabolic drug currently on the market; and activation of canonical Wnt signaling through inhibition of the endogenous inhibitors sclerostin and dickkopf1.
Abstract: Osteoporosis is defined as low bone mineral density associated with skeletal fractures secondary to minimal or no trauma, most often involving the spine, the hip, and the forearm. The decrease in bone mineral density is the consequence of an unbalanced bone remodeling process, with higher bone resorption than bone formation. Osteoporosis affects predominantly postmenopausal women, but also older men. This chronic disease represents a considerable medical and socioeconomic burden for modern societies. The therapeutic options for the treatment of osteoporosis have so far comprised mostly antiresorptive drugs, in particular bisphosphonates and more recently denosumab, but also calcitonin and, for women, estrogens or selective estrogen receptor modulators. These drugs have limitations, however, in particular the fact that they lead to a low turnover state where bone formation decreases with the decrease in bone-remodeling activity. In this review, we discuss the alternative class of osteoporosis drugs, i.e. b...

Journal ArticleDOI
TL;DR: Human baseline β-cell population and appropriate association with other islet cell types is established before 5 yr of age, and a close association of neurons to pancreatic islets was noted developmentally and retained throughout adulthood.
Abstract: Context: Insulin resistance can be compensated by increased functional pancreatic β-cell mass; otherwise, diabetes ensues. Such compensation depends not only on environmental and genetic factors but also on the baseline β-cell mass from which the expansion originates. Objective: Little is known about assembly of a baseline β-cell mass in humans. Here, we examined formation of β-cell populations relative to other pancreatic islet cell types and associated neurons throughout the normal human lifespan. Design and Methods: Human pancreatic sections derived from normal cadavers aged 24 wk premature to 72 yr were examined by immunofluorescence. Insulin, glucagon, and somatostatin were used as markers for β-, α-, and δ-cells, respectively. Cytokeratin-19 marked ductal cells, Ki67 cell proliferation, and Tuj1 (neuronal class III β-tubulin) marked neurons. Results: Most β-cell neogenesis was observed preterm with a burst of β-cell proliferation peaking within the first 2 yr of life. Thereafter, little indication o...

Journal ArticleDOI
TL;DR: The course of disease in a large cohort of hypoparathyroid patients identified via a clinical patient data registry was characterized, finding that chronic kidney disease stage 3 or higher were 2- to 17-fold greater than age-appropriate norms.
Abstract: Context: Despite tremendous interest in hypoparathyroidism, large cohort studies describing typical treatment patterns, laboratory parameters, and rates of complications are lacking. Objective: Our objective was to characterize the course of disease in a large cohort of hypoparathyroid patients. Design and Setting: We conducted a chart review of patients with permanent hypoparathyroidism identified via a clinical patient data registry. Patients were seen at a Boston tertiary-care hospital system between 1988 and 2009. Patients: We identified 120 patients. Diagnosis was confirmed by documented hypocalcemia with a simultaneous low or inappropriately normal PTH level for at least 1 yr. Mean age at the end of the observation period was 52 ± 19 (range 2–87) yr, and the cohort was 73% female. Main Outcome Measure: We evaluated serum and urine laboratory results and renal and brain imaging. Results: We calculated time-weighted average serum calcium measurements for all patients. The time-weighted average for cal...

Journal ArticleDOI
TL;DR: Current practices in the management of GD diverge in some areas from recently published guidelines; these differences should be assessed serially to determine the impact of the guidelines on future clinical practice.
Abstract: Context: More than two decades have passed since members from the American Thyroid Association (ATA), European Thyroid Association, and Japan Thyroid Association were surveyed on management practices for patients with hyperthyroidism due to Graves' disease (GD). Objective: We sought to document current practices in the management of GD and compare these results both to those documented in earlier surveys and to practice recommendations made in the 2011 ATA/American Association of Clinical Endocrinologists (AACE) hyperthyroidism practice guidelines. Lastly, we sought to examine differences in GD management among international members of U.S.-based endocrine societies. Methods: Members of The Endocrine Society (TES), ATA, and AACE were invited to participate in a web-based survey dealing with testing, treatment preference, and modulating factors in patients with GD. Results: A total of 730 respondents participated in the survey, 696 of whom completed all sections. Respondents included 641 TES members, 330 A...

Journal ArticleDOI
TL;DR: Examination of brain activation after sleep and sleep deprivation in response to images of food provides evidence that acute sleep loss enhances hedonic stimulus processing in the brain underlying the drive to consume food, independent of plasma glucose levels.
Abstract: Context: There is growing recognition that a large number of individuals living in Western society are chronically sleep deprived. Sleep deprivation is associated with an increase in food consumption and appetite. However, the brain regions that are most susceptible to sleep deprivation-induced changes when processing food stimuli are unknown. Objective: Our objective was to examine brain activation after sleep and sleep deprivation in response to images of food. Intervention: Twelve normal-weight male subjects were examined on two sessions in a counterbalanced fashion: after one night of total sleep deprivation and one night of sleep. On the morning after either total sleep deprivation or sleep, neural activation was measured by functional magnetic resonance imaging in a block design alternating between high- and low-calorie food items. Hunger ratings and morning fasting plasma glucose concentrations were assessed before the scan, as were appetite ratings in response to food images after the scan. Main O...

Journal ArticleDOI
TL;DR: Differences in efficacy across drugs are small; therefore, patients and clinicians need to consider their associated harms and costs.
Abstract: Context: Osteoporosis and osteopenia are associated with increased fracture incidence. Objective: The aim of this study was to determine the comparative effectiveness of different pharmacological agents in reducing the risk of fragility fractures. Data Sources: We searched multiple databases through 12/9/2011. Study Selection: Eligible studies were randomized controlled trials enrolling individuals at risk of developing fragility fractures and evaluating the efficacy of bisphosphonates, teriparatide, selective estrogen receptor modulators, denosumab, or calcium and vitamin D. Data Extraction: Reviewers working independently and in duplicate determined study eligibility and collected descriptive, methodological quality, and outcome data. Data Synthesis: This network meta-analysis included 116 trials (139,647 patients; median age, 64 yr; 86% females and 88% Caucasians; median follow-up, 24 months). Trials were at low to moderate risk of bias. Teriparatide had the highest risk reduction of fractures (odds ra...

Journal ArticleDOI
TL;DR: Aging is associated with increased serum TSH concentrations, with no change in free T(4) concentrations, and the largest TSH increase is in people with the lowest TSH at baseline, which suggests that the T SH increase arises from age-related alteration in the TSH set point or reduced TSH bioactivity rather than occult thyroid disease.
Abstract: Context: In cross-sectional studies, serum TSH concentrations increase with age. This has not been examined longitudinally, and it is uncertain whether the TSH increase reflects healthy aging or occult thyroid failure. Methods: We measured serum TSH, free T4, thyroid peroxidase, and thyroglobulin antibodies in 1100 participants in the 1981 and 1994 Busselton Health Surveys and derived a reference group of 908 individuals without thyroid disease or thyroid antibodies. We examined changes in thyroid function longitudinally and, in 781 participants, explored associations with the CAPZB polymorphism rs10917469. Results: At 13 yr follow-up, mean serum TSH increased from 1.49 to 1.81 mU/liter, a change in mean TSH (ΔTSH) of 0.32 mU/liter [95% confidence interval (CI) 0.27, 0.38, P < 0.001], whereas mean free T4 concentration was unchanged (16.6 vs. 16.6 pmol/liter, P = 0.7). The TSH increase was most marked in the elderly, such that gender-adjusted ΔTSH increased by 0.08 mU/liter (95% CI 0.04, 0.11) for each de...

Journal ArticleDOI
TL;DR: Compared with conventional TID, OD provided a sustained serum cortisol profile 0-4 h after the morning intake and reduced the late afternoon and the 24-h cortisol exposure, and glucose metabolism improved in patients with concomitant DM.
Abstract: Context: Patients with treated adrenal insufficiency (AI) have increased morbidity and mortality rate. Our goal was to improve outcome by developing a once-daily (OD) oral hydrocortisone dual-relea ...

Journal ArticleDOI
TL;DR: Circulating sclerostin is increased in T2DM independently of gender and age, and its relationship with bone metabolism and calciotropic hormones, bone turnover markers, bone mineral density (BMD), and morphometric vertebral fractures is analyzed.
Abstract: Context: Diabetes mellitus is a risk factor for osteoporotic fractures. Sclerostin is an inhibitor of bone formation. However, there are no data about sclerostin levels in type 2 diabetes mellitus (T2DM). Objectives: The aims were to evaluate serum sclerostin in T2DM patients and to analyze its relationship with bone metabolism. Design, Setting, and Patients: This was a cross-sectional study. We compared serum sclerostin in the T2DM group (n = 74) and control group (n = 50), and we analyzed its relationship with calciotropic hormones, bone turnover markers, bone mineral density (BMD), and morphometric vertebral fractures. Results: Sclerostin levels were significantly higher in T2DM patients than control subjects (P < 0.001) and in T2DM males than in T2DM females (P < 0.001). Serum sclerostin was positively correlated with age in males T2DM (P = 0.031). In linear regression analysis, gender, study group, and age were predictive of sclerostin levels (P < 0.05). Sclerostin concentrations were positively asso...

Journal ArticleDOI
TL;DR: Data support the existence of a syndrome of LOH in only a minority of aging men, especially those with T below 8 nmol/liter, and LOH is associated with multiple end-organ deficits compatible with androgen deficiency.
Abstract: Context: Late-onset hypogonadism (LOH) has been defined as a syndrome in middle-aged and elderly men reporting symptoms in the presence of low testosterone (T). Objective: The objective of the study was to seek objective biochemical and end-organ evidence of androgen deficiency in men classified as having LOH according to our previously published criteria. Design, Setting, and Participants: The design of the study included cross-sectional data from the European Male Aging Study on 2966 community-dwelling men aged 40–79 years in eight European countries. Main Outcome Measure(s): Waist circumference, body mass index, muscle mass, estimated heel bone mineral density (eBMD), hemoglobin, insulin sensitivity, physical activity, metabolic syndrome, insulin resistance index, and cardiovascular disease were measured. Results: Sixty-three men (2.1%) were classified as having LOH: 36 moderate and 27 severe. They were older and more obese than eugonadal men and had, in proportion to the graded T deficiency, lower mus...

Journal ArticleDOI
TL;DR: Mortality rates were increased in this population of adults treated as children with recombinant GH, particularly in those who had received the highest doses, highlighting the need for additional studies of long-term mortality and morbidity after GH treatment in childhood.
Abstract: Context: Little is known about the long-term health of subjects treated with GH in childhood, and Safety and Appropriateness of Growth hormone treatments in Europe (SAGhE) is a study addressing this question. Objective: The objective of the study was to evaluate the long-term mortality of patients treated with recombinant GH in childhood in France. Design: This was a population-based cohort study. Setting: The setting of the study was a French population-based register. Participants: A total of 6928 children with idiopathic isolated GH deficiency (n = 5162), neurosecretory dysfunction (n = 534), idiopathic short stature (n = 871), or born short for gestational age (n = 335) who started treatment between 1985 and 1996 participated in the study. Follow-up data on vital status were available in September 2009 for 94.7% of the patients. Main outcome measures: All-cause and cause-specific mortality was measured in the study. Results: All-cause mortality was increased in treated subjects [standardized mortality...

Journal ArticleDOI
TL;DR: A multicenter, randomized, double-blind trial to determine efficacy and safety of three doses of i.v. methylprednisolone for Graves' orbitopathy, finding that the 7.47-g dose provides short-term advantages over lower doses, but this benefit is transient and associated with slightly greater toxicity.
Abstract: BACKGROUND: Optimal doses of i.v. glucocorticoids for Graves' orbitopathy (GO) are undefined. METHODS: We carried out a multicenter, randomized, double-blind trial to determine efficacy and safety of three doses of i.v. methylprednisolone in 159 patients with moderate to severe and active GO. Patients were randomized to receive a cumulative dose of 2.25, 4.98, or 7.47 g in 12 weekly infusions. Efficacy was evaluated objectively at 12 wk by blinded ophthalmologists and subjectively by blinded patients (using a GO specific quality of life questionnaire). Adverse events were recorded at each visit. RESULTS: Overall ophthalmic improvement was more common using 7.47 g (52%) than 4.98 g (35%; P = 0.03) or 2.25 g (28%; P = 0.01). Compared with lower doses, the high-dose regimen led to the most improvement in objective measurement of ocular motility and in the Clinical Activity Score. The Clinical Activity Score decreased in all groups and to the least extent with 2.25 g. Quality of life improved most in the 7.47-g group, although not reaching statistical significance. No significant differences occurred in exophthalmos, palpebral aperture, soft tissue changes, and subjective diplopia score. Dysthyroid optic neuropathy developed in several patients in all groups. Because of this, differences among the three groups were no longer apparent at the exploratory 24-wk visit. Major adverse events were slightly more frequent using the highest dose but occurred also using the lowest dose. Among patients whose GO improved at 12 wk, 33% in the 7.47-group, 21% in the 4.98-group, and 40% in the 2.25-group had relapsing orbitopathy after glucocorticoid withdrawal at the exploratory 24-wk visit. CONCLUSIONS: The 7.47-g dose provides short-term advantages over lower doses. However, this benefit is transient and associated with slightly greater toxicity. The use of a cumulative dose of 7.47 g of methylprednisolone provides short-term advantage over lower doses. This may suggest that an intermediate-dose regimen be used in most cases and the high-dose regimen be reserved to most severe cases of GO.