Showing papers in "The Journal of Clinical Endocrinology and Metabolism in 2014"
TL;DR: This evidence-based guideline recommends minimally invasive adrenalectomy for most pheochromocytomas with open resection for most paragangliomas and suggests personalized management with evaluation and treatment by multidisciplinary teams with appropriate expertise to ensure favorable outcomes.
Abstract: Objective: The aim was to formulate clinical practice guidelines for pheochromocytoma and paraganglioma (PPGL). Participants: The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), seven experts in the field, and a methodologist. The authors received no corporate funding or remuneration. 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. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, European Society of Endocrinology, and Americal Association for Clinical Chemistry reviewed drafts of the guidelines. Conclusions: The Task Force recommends that initial biochemical testing for PPGLs shou...
1,858 citations
TL;DR: This evidence-based guideline addresses important clinical issues regarding the evaluation and management of acromegaly, including the appropriate biochemical assessment, a therapeutic algorithm, including use of medical monotherapy or combination therapy, and management during pregnancy.
Abstract: Objective: The aim was to formulate clinical practice guidelines for acromegaly. Participants: The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), five experts in the field, and a methodologist. The authors received no corporate funding or remuneration. This guideline is cosponsored by the European Society of Endocrinology. 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. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society and the European Society of Endocrinology reviewed drafts of the guidelines. Conclusions: Using an evidence-based approach, this acromegaly guideline addresses impor...
1,263 citations
TL;DR: In this article, the authors distill an update of current information about diagnostics, clinical features, and management of primary hyperparathyroidism into a set of revised guidelines.
Abstract: Objective:
Asymptomatic primary hyperparathyroidism (PHPT) is routinely encountered in clinical practices of endocrinology throughout the world. This report distills an update of current information about diagnostics, clinical features, and management of this disease into a set of revised guidelines.
822 citations
TL;DR: Vitamin D supplementation has a small positive impact on muscle strength, but additional studies are needed to define optimal treatment modalities, including dose, mode of administration, and duration.
Abstract: Context: There is growing evidence that vitamin D plays a role on several tissues including skeletal muscle. Objective: The aim was to summarize with a meta-analysis, the effects of vitamin D supplementation on muscle function. Data Sources: A systematic research of randomized controlled trials, performed between 1966 and January 2014 has been conducted on Medline, Cochrane Database of Systematics Reviews, Cochrane Central Register of Controlled and completed by a manual review of the literature and congressional abstracts. Study Selection: All forms and doses of vitamin D supplementation, with or without calcium supplementation, compared with placebo or control were included. Out of the 225 potentially relevant articles, 30 randomized controlled trials involving 5615 individuals (mean age: 61.1 years) met the inclusion criteria. Data Extraction: Data were extracted by two independent reviewers. Data Synthesis: Results revealed a small but significant positive effect of vitamin D supplementation on global...
484 citations
TL;DR: This meta-analysis provides extensive data on the prevalence and incidence of thyroid dysfunction in Europe and categorizes results into 3 categories: prevalence of undiagnosed thyroid dysfunction, prevalence of Thyroid dysfunction, and incidence.
Abstract: Context: Thyroid dysfunction is one of the leading endocrine disorders. Previous data show that about half of the population with thyroid dysfunction remains undiagnosed. Objective: Our objective was to estimate epidemiologic data on thyroid dysfunction in Europe. Data Sources: PubMed, EMBASE, and SCOPUS databases were searched to identify studies that evaluated the prevalence and/or incidence of thyroid dysfunction in Europe published between 1975 and 2012. Study Selection: Of the 541 identified abstracts examined, 178 were considered for evaluation and 17 were included. Studies were excluded if they included participants with an underlying disease or were limited by age or gender. Data Extraction: Results were grouped into 3 categories: 1) prevalence of undiagnosed thyroid dysfunction, 2) prevalence of thyroid dysfunction, and 3) incidence of thyroid dysfunction. Extraction was conducted independently by 2 investigators. Data Synthesis: An empirical Bayesian random-effects model was used. The prevalence...
464 citations
TL;DR: TERT promoter mutations are an indicator of clinically aggressive tumors, being correlated with worse outcome and disease-specific mortality in DTC and, notably, in PTC, where they have an independent prognostic value.
Abstract: Context: Telomerase promoter mutations (TERT) were recently described in follicular cell-derived thyroid carcinomas (FCDTC) and seem to be more prevalent in aggressive cancers. Objectives:Weaimed to evaluate the frequency of TERT promoter mutations in thyroid lesions and to investigate the prognostic significance of such mutations in a large cohort of patients with differentiated thyroid carcinomas (DTCs). Design: This was a retrospective observational study. Setting and Patients: We studied 647 tumors and tumor-like lesions. A total of 469 patients with FCDTC treated and followed in five university hospitals were included. Mean follow-up (±SD) was 7.8 ± 5.8 years. Main Outcome Measures: Predictive value of TERT promoter mutations for distant metastasization, disease persistence at the end of follow-up, and disease-specific mortality. Results: TERT promoter mutations were found in 7.5% of papillary carcinomas (PTCs), 17.1% of follicular carcinomas, 29.0% of poorly differentiated carcinomas, and 33.3% of anaplastic thyroid carcinomas. Patients with TERT-mutated tumors were older (P < .001) and had larger tumors (P = .002). In DTCs, TERT promoter mutations were significantly associated with distant metastases (P< .001) and higher stage (P < .001). Patients with DTC harboring TERT promoter mutations were submitted to more radioiodine treatments (P = .009) with higher cumulative dose (P = .004) and to more treatment modalities (P=.001). At the end of follow-up, patients with TERT-mutated DTCs were more prone to have persistent disease (P=.001). TERT promoter mutations were significantly associated with disease-specific mortality [in the whole FCDTC (P < .001)] in DTCs (P < .001), PTCs (P = .001), and follicular carcinomas (P < .001). After adjusting for age at diagnosis and gender, the hazard ratio was 10.35 (95% confidence interval 2.01-53.24; P = .005) in DTC and 23.81 (95% confidence interval 1.36-415.76; P = .03) in PTCs. Conclusions: TERT promoter mutations are an indicator of clinically aggressive tumors, being correlated with worse outcome and disease-specific mortality in DTC. TERT promoter mutations have an independent prognostic value in DTC and, notably, in PTC. © 2014 by the Endocrine Society.
425 citations
TL;DR: In this paper, a systematic literature search was conducted to identify key articles relating to the screening, diagnosis, and management of congenital hypothyroidism (CH) and the evidence-based guidelines were developed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, describing both the strength of recommendations and the quality of evidence.
Abstract: Objective: The aim was to formulate practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). Evidence: A systematic literature search was conducted to identify key articles relating to the screening, diagnosis, and management of CH. The evidence-based guidelines were developed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. Consensus Process: Thirty-two participants drawn from the European Society for Paediatric Endocrinology and five other major scientific societies in the field of pediatric endocrinology were allocated to working groups with assigned topics and specific questions. Each group searched the literature, evaluated the evidence, and developed a draft document. These papers were debated and finalized by each group before presentation to the full assembly for further discussion and agreement. Recommendations: The recommendations include: worldwide neonatal screening, approaches to assess the cause (including genotyping) and the severity of the disorder, the immediate initiation of appropriate L-T4 supplementation and frequent monitoring to ensure dose adjustments to keep thyroid hormone levels in the target ranges, a trial of treatment in patients suspected of transient CH, regular assessments of developmental and neurosensory functions, consulting health professionals as appropriate, and education about CH. The harmonization of diagnosis, management, and routine health surveillance would not only optimize patient outcomes, but should also facilitate epidemiological studies of the disorder. Individuals with CH require monitoring throughout their lives, particularly during early childhood and pregnancy.
374 citations
TL;DR: Diffuse pituitary enlargement was observed exclusively in all cases of IH and, upon retrospective review of magnetic resonance imaging scans, this finding preceded the clinical diagnosis of hypophysitis in eight patients.
Abstract: Context: Ipilimumab (Ipi) is approved by the Food and Drug Administration for the treatment of unresectable or metastatic melanoma. Little is known about Ipi-induced hypophysitis (IH), an important treatment complication. Objective: The objectives of the study were as follows: 1) to examine the prevalence of IH, 2) to characterize the clinical course and treatment outcomes in IH, 3) to identify the risk factors for the development of IH, and 4) to determine optimal strategies for the management of IH. Design: This was a retrospective review. Setting: The study was conducted at a tertiary referral center. Subjects: One hundred fifty-four adult patients with metastatic melanoma were evaluated at Massachusetts General Hospital and were treated with Ipi between March 2008 and December 2013. Intervention(s): The intervention included treatment with Ipi. Main Outcome Measure(s): Pituitary magnetic resonance imaging, pituitary hormone assessment, and patient survival were measured. Results: IH was diagnosed in 1...
357 citations
TL;DR: The prevalence of NAFLD is much higher than previously believed in overweight/obese patients with T2DM and normal aminotransferases and many are at increased risk of NASH.
Abstract: Context and Objective: Nonalcoholic fatty liver disease (NAFLD) and its more severe form with steatohepatitis (NASH) are common in patients with type 2 diabetes mellitus (T2DM). However, they are usually believed to largely affect those with elevated aminotransferases. The aim of this study was to determine the prevalence of NAFLD by the gold standard, liver magnetic resonance spectroscopy (1H-MRS) in patients with T2DM and normal aminotransferases, and to characterize their metabolic profile. Participants and Methods: We recruited 103 patients with T2DM and normal plasma aminotransferases (age, 60 ± 8 y; body mass index [BMI], 33 ± 5 kg/m2; glycated hemoglobin [A1c], 7.6 ± 1.3%). We measured the following: 1) liver triglyceride content by 1H-MRS; 2) systemic insulin sensitivity (homeostasis model assessment-insulin resistance); and 3) adipose tissue insulin resistance, both fasting (as the adipose tissue insulin resistance index: fasting plasma free fatty acids [FFA] × insulin) and during an oral glucose...
351 citations
TL;DR: Low- to moderate-quality evidence suggests that individual ultrasound features are not accurate predictors of thyroid cancer and two features, cystic content and spongiform appearance, might predict benign nodules, but this has limited applicability to clinical practice due to their infrequent occurrence.
Abstract: Context: Significant uncertainty remains surrounding the diagnostic accuracy of sonographic features used to predict the malignant potential of thyroid nodules. Objective: The objective of the study was to summarize the available literature related to the accuracy of thyroid nodule ultrasound (US) in the prediction of thyroid cancer. Methods: We searched multiple databases and reference lists for cohort studies that enrolled adults with thyroid nodules with reported diagnostic measures of sonography. A total of 14 relevant US features were analyzed. Results: We included 31 studies between 1985 and 2012 (number of nodules studied 18 288; average size 15 mm). The frequency of thyroid cancer was 20%. The most common type of cancer was papillary thyroid cancer (84%). The US nodule features with the highest diagnostic odds ratio for malignancy was being taller than wider [11.14 (95% confidence interval 6.6–18.9)]. Conversely, the US nodule features with the highest diagnostic odds ratio for benign nodules was ...
339 citations
TL;DR: An increasing age at diagnosis and greater detection of smaller-sized intrathyroidal PTCs are found and Sharply rising percentages of the follicular variant histology and RAS mutations after 2000 suggest new and more recent etiologic factors.
Abstract: Context: Thyroid cancer incidence rates in the United States and globally have increased steadily over the last 40 years, primarily due to a tripling of the incidence of papillary thyroid carcinoma (PTC). Objective: The purpose of this study was to analyze trends in demographic, clinical, pathologic, and molecular characteristics of PTC from 1974 to 2009. Design and Setting: We identified and histologically reviewed 469 consecutive cases of PTC from one US institution from 4 preselected periods (1974 to 1985, 1990 to 1992, 2000, and 2009) and assessed BRAF and RAS point mutations and RET/PTC rearrangements among 341 tumors ≥0.3 cm in size. Changes over time were analyzed using polytomous and binary logistic regression; all analyses were adjusted for age and sex. Results: During this period, the median age of patients at diagnosis increased from 37 to 53 years (P < .001) and the percentage of microcarcinomas (≤1.0 cm) increased from 33% to 51% (P < .001), whereas extrathyroidal extension and advanced tumor...
University of São Paulo1, Columbia University2, Peking Union Medical College Hospital3, National Defense Medical Center4, Hungkuang University5, Federal University of Rio de Janeiro6, Oregon Health & Science University7, Erasmus University Medical Center8, University of Edinburgh9, Novartis10, University of Birmingham11
TL;DR: Pasireotide LAR demonstrated superior efficacy over octreotide LAR and is a viable new treatment option for acromegaly.
Abstract: Context: Biochemical control reduces morbidity and increases life expectancy in patients with acromegaly. With current medical therapies, including the gold standard octreotide long-acting-release (LAR), many patients do not achieve biochemical control. Objective: Our objective was to demonstrate the superiority of pasireotide LAR over octreotide LAR in medically naive patients with acromegaly. Design and Setting: We conducted a prospective, randomized, double-blind study at 84 sites in 27 countries. Patients: A total of 358 patients with medically naive acromegaly (GH >5 μg/L or GH nadir ≥1 μg/L after an oral glucose tolerance test (OGTT) and IGF-1 above the upper limit of normal) were enrolled. Patients either had previous pituitary surgery but no medical treatment or were de novo with a visible pituitary adenoma on magnetic resonance imaging. Interventions: Patients received pasireotide LAR 40 mg/28 days (n = 176) or octreotide LAR 20 mg/28 days (n = 182) for 12 months. At months 3 and 7, titration to ...
TL;DR: Age- and sex-adjusted reference intervals derived from a uniquely large cohort reflect the age-related pattern of IGF-I secretion: a decline immediately after birth followed by an increase until a pubertal peak (at 15 years of age) later in life, values decrease continuously.
Abstract: Context: Measurement of IGF-I is a cornerstone in diagnosis and monitoring of GH-related diseases, but considerable discrepancies exist between analytical methods. A recent consensus conference defined criteria for validation of IGF-I assays and for establishment of normative data. Objectives: Our objectives were development and validation of a novel automated IGF-I immunoassay (iSYS; Immunodiagnostic Systems) according to international guidelines and establishment of method-specific age- and sex-adjusted reference intervals and analysis of their robustness. Setting and Participants: We conducted a multicenter study with samples from 12 cohorts from the United States, Canada, and Europe including 15 014 subjects (6697 males and 8317 females, 0–94 years of age). Main Outcome Measures: We measured concentrations of IGF-I as determined by the IDS iSYS IGF-I assay. Results: A new IGF-I assay calibrated against the recommended standard (02/254) and insensitive to the 6 high-affinity IGF binding proteins was de...
TL;DR: In vitro experiments showed that irisin facilitates glucose and lipid metabolism in human muscle through AMP kinase phosphorylation, and exercise-induced irisin secretion is independent of age or fitness level.
Abstract: Context: Irisin has been proposed to be a myokine mediating the effect of exercise on adipocyte browning. The physiology of irisin in humans is not completely understood. Objective: To study the physiology of irisin in healthy individuals with different age and fitness levels and to explore the direct effects of irisin on muscle metabolism. Design, Setting, and Subjects: Treadmill exercise studies were conducted to measure circulating irisin at baseline and in response to exercise among old and young, physically active and sedentary individuals. Also, high- and moderate-intensity swimming was performed in adolescent men and women to study the effect of exercise intensity and the time course of irisin induction by acute bouts of exercise. Human myotubes were treated with recombinant irisin, and the effect on gene expression, cell signaling, and metabolism was examined. Results: Baseline circulating irisin was lower in old (vs young) and physically active (vs sedentary) subjects. Despite differences in basa...
TL;DR: In this large cohort, TERT promoter mutations were found to be common, particularly in FTC and BRAF mutation-positive PTC, and associated with aggressive clinicopathological characteristics.
Abstract: Context: Promoter mutations chr5:1,295,228C>T and chr5:1,295,250C>T (termed C228T and C250T, respectively) in the gene for telomerase reverse transcriptase (TERT) have been reported in various cancers and need to be further investigated in thyroid cancer. Objective: The aim of the study was to explore TERT promoter mutations in various thyroid tumors and examine their relationship with BRAF V600E mutation, iodine intake, and clinicopathological behaviors of thyroid cancer. Design: TERT promoter and BRAF mutations were identified by sequencing genomic DNA of primary thyroid tumors from normal- and high-iodine regions in China, and clinicopathological correlation was analyzed. Results: The C228T mutation was found in 9.6% (39 of 408) of papillary thyroid cancer (PTC), C250T was found in 1.7% (7 of 408) of PTC, and they were collectively found in 11.3% (46 of 408) of PTC. C228T was found in 31.8% (7 of 22) and C250T in 4.6% (1 of 22) of follicular thyroid cancer (FTC), and they were collectively found in 36....
TL;DR: In this article, the authors summarized data on traditional and nontraditional manifestations of primary hyperparathyroidism (PHPT) that have been published since the last International Workshop on PHPT.
Abstract: Objective: This report summarizes data on traditional and nontraditional manifestations of primary hyperparathyroidism (PHPT) that have been published since the last International Workshop on PHPT. Participants: This subgroup was constituted by the Steering Committee to address key questions related to the presentation of PHPT. Consensus was established at a closed meeting of the Expert Panel that followed. Evidence: Data from the 5-year period between 2008 and 2013 were presented and discussed to determine whether they support changes in recommendations for surgery or nonsurgical follow-up. Consensus Process: Questions were developed by the International Task Force on PHPT. A comprehensive literature search for relevant studies was undertaken. After extensive review and discussion, the subgroup came to agreement on what changes in the recommendations for surgery or nonsurgical follow-up of asymptomatic PHPT should be made to the Expert Panel. Conclusions: 1) There are limited new data available on the na...
TL;DR: The fetal CAH status was correctly deduced by targeted MPS of DNA in maternal plasma, as early as 5 weeks 6 days of gestation, representing a generic approach for noninvasive prenatal testing for an array of autosomal recessive disorders.
Abstract: Context: Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition that arises from mutations in CYP21A2 gene, which encodes for the steroidogenic enzyme 21-hydroxylase. To prevent genital ambiguity in affected female fetuses, prenatal treatment with dexamethasone must begin on or before gestational week 9. Currently used chorionic villus sampling and amniocentesis provide genetic results at approximately 14 weeks of gestation at the earliest. This means that mothers who want to undergo prenatal dexamethasone treatment will be unnecessarily treating seven of eight fetuses (males and three of four unaffected females), emphasizing the desirability of earlier genetic diagnosis in utero. Objective: The objective of the study was to develop a noninvasive method for early prenatal diagnosis of fetuses at risk for CAH. Patients: Fourteen families, each with a proband affected by phenotypically classical CAH, were recruited. Design: Cell-free fetal DNA was obtained from 3.6 mL of maternal plasma. U...
TL;DR: Evidence supports the short-term efficacy and safety of high physiological doses of T treatment of postmenopausal women with sexual dysfunction due to hypoactive sexual desire disorder and no long-term safety data are lacking.
Abstract: Objective: To update practice guidelines for the therapeutic use of androgens in women. Participants: A Task Force appointed by the Endocrine Society, American Congress of Obestricians and Gynecologists (ACOG), American Society for Reproductive Medicine (ASRM), European Society of Endocrinology (ESE), and International Menopause Society (IMS) consisting of six experts, a methodologist, and a medical writer. Evidence: The Task Force commissioned two systematic reviews of published data and considered several other existing meta-analyses and trials. The GRADE methodology was used; the strength of a recommendation is indicated by a number “1” (strong recommendation, we recommend) or “2” (weak recommendation, we suggest). Consensus Process: Multiple e-mail communications and conference calls determined consensus. Committees of the Endocrine Society, ASRM, ACOG, ESE, and IMS reviewed and commented on the drafts of the guidelines. Conclusions: We continue to recommend against making a diagnosis of androgen defi...
TL;DR: It is demonstrated that daily cold exposure not only increases the volume of metabolically active BAT but also increases its oxidative capacity and thus its contribution to cold-induced thermogenesis.
Abstract: Context: Recent studies examining brown adipose tissue (BAT) metabolism in adult humans have provided convincing evidence of its thermogenic potential and role in clearing circulating glucose and fatty acids under acute mild cold exposure. In contrast, early indications suggest that BAT metabolism is defective in obesity and type 2 diabetes, which may have important pathological and therapeutic implications. Although many mammalian models have demonstrated the phenotypic flexibility of this tissue through chronic cold exposure, little is known about the metabolic plasticity of BAT in humans. Objective: Our objective was to determine whether 4 weeks of daily cold exposure could increase both the volume of metabolically active BAT and its oxidative capacity. Design: Six nonacclimated men were exposed to 10°C for 2 hours daily for 4 weeks (5 d/wk), using a liquid-conditioned suit. Using electromyography combined with positron emission tomography with [11C]acetate and [18F]fluorodeoxyglucose, shivering intens...
TL;DR: Simultaneous measurement of serum T and A represents a useful tool for predicting metabolic risk in PCOS women and HA levels are a sensitive indicator of PCOS-related androgen excess.
Abstract: Context: Polycystic ovary syndrome (PCOS) is a triad of anovulation, insulin resistance, and hyperandrogenism. Androgen excess may correlate with metabolic risk and PCOS consensus criteria define androgen excess on the basis of serum T. Here we studied the utility of the androgen precursor serum androstenedione (A) in conjunction with serum T for predicting metabolic dysfunction in PCOS. Patients and Methods: Eighty-six PCOS patients fulfilling Rotterdam diagnostic consensus criteria and 43 age- and body mass index-matched controls underwent measurement of serum androgens by tandem mass spectrometry and an oral glucose tolerance test with homeostatic model assessment of insulin resistance and insulin sensitivity index calculation. We analyzed 24-hour urine androgen excretion by gas chromatography/mass spectrometry. Results: PCOS patients had higher levels of serum androgens and urinary androgen metabolites than controls (all P < .001). Within the PCOS cohort, both serum A and T were positively correlated ...
TL;DR: LM exerts a greater effect on BMD than FM in men and women combined, which underlines the concept that physical activity is an important component in the prevention of bone loss and osteoporosis in the population.
Abstract: Context: Body weight is the most important anthropometric determinant of bone mineral density (BMD). Body weight is mainly made up of lean mass (LM) and fat mass (FM), and which component is more important to BMD has been a controversial issue. Objective: This study sought to compare the magnitude of association between LM, FM, and BMD by using a meta-analytic approach. Data Source: Using an electronic and manual search, we identified 44 studies that had examined the correlation between LM, FM, and BMD between 1989 and 2013. These studies involved 20 226 men and women (4966 men and 15 260 women) aged between 18 and 92 years. We extracted the correlations between LM, FM, and BMD at the lumbar spine, femoral neck, and whole body. The synthesis of correlation coefficients was done by the random-effects meta-analysis model. Results: The overall correlation between LM and femoral neck BMD (FNBMD) was 0.39 (95% confidence interval, 0.34 to 0.43), which was significantly higher than the correlation between FM an...
TL;DR: Two years of concomitant teriparatide and denosumab therapy increases BMD more than therapy with either medication alone and more than has been reported with any current therapy.
Abstract: Context: Current osteoporosis medications increase bone mineral density (BMD) modestly and reduce, but do not eliminate, fracture risk. Attempts to improve efficacy by administering anabolic agents and bisphosphonates concomitantly have been unsuccessful. Conversely, 12 months of concomitant denosumab and teriparatide therapy increases BMD more than either drug alone. Objective: The purpose of this study was to determine whether 24 months of combined denosumab and teriparatide will increase hip and spine BMD more than either individual agent. Design: Preplanned continuation of the Denosumab and Teriparatide Administration (DATA) randomized controlled trial in which postmenopausal osteoporotic women received teriparatide (20 μg daily), denosumab (60 mg every 6 months), or both medications for 24 months. Participants: Participants were 94 postmenopausal women with osteoporosis. Outcome Measures: Lumbar spine, femoral neck, total hip, and distal radius BMD and serum markers of bone turnover were measured. Re...
TL;DR: A French retrospective multicenter study reviewing data from patients treated by ketoconazole as a single agent for Cushing's disease, with the aim of clarifying efficacy and tolerance to better determine the benefit/risk balance.
Abstract: Background: The use of ketoconazole has been recently questioned after warnings from the European Medicine Agencies and the Food and Drug Administration due to potential hepatotoxicity. However, ketoconazole is frequently used as a drug to lower circulating cortisol levels. Several pharmacological agents have recently been approved for the treatment of Cushing's disease (CD) despite limited efficacy or significant side effects. Ketoconazole has been used worldwide for more than 30 years in CD, but in the absence of a large-scale study, its efficacy and tolerance are still under debate. Patients and methods: We conducted a French retrospective multicenter study reviewing data from patients treated by ketoconazole as a single agent for CD, with the aim of clarifying efficacy and tolerance to better determine the benefit/risk balance. Results: Data from 200 patients were included in this study. At the last follow-up, 49.3% of patients had normal urinary free cortisol (UFC) levels, 25.6% had at least a 50% de...
TL;DR: Evidence from available trials shows no effect of vitamin D3 supplementation on glucose homeostasis or diabetes prevention, and definitive conclusions may be limited in the context of the moderate degree of heterogeneity, variable risk of bias, and short-term follow-up duration of the available evidence.
Abstract: Context: Observational studies report consistent associations between low vitamin D concentration and increased glycemia and risk of type 2 diabetes, but results of randomized controlled trials (RCTs) are mixed. Objective: The objective of the study was to systematically review RCTs that report on the effects of vitamin D supplementation on glucose homeostasis or diabetes prevention. Data Sources: Sources of data for the study were MEDLINE, EMBASE, SCOPUS, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment, and Science Citation Index from inception to June 2013. Study Selection: Study selection was trials that compared vitamin D3 supplementation with placebo or a non-vitamin D supplement in adults with normal glucose tolerance, prediabetes, or type 2 diabetes. Data Extraction and Synthesis: Two reviewers collected data and assessed trial quality using the Cochrane Risk of Bias tool. Random-effects models were used to estimate mean differences...
TL;DR: Evidence is presented for a pivotal role of TLR-induced inflammation in both obesity and MetS and it is speculated that targeting these TLRs can forestall their adverse sequelae of diabetes and cardiovascular disease.
Abstract: Context: The prevalence of both obesity and metabolic syndrome (MetS) is increasing at alarming rates globally. Both predispose to diabetes, cardiovascular disease, fatty liver disease, obstructive sleep apnea, and certain cancers. Understanding the mechanisms contributing to increased cardiometabolic risk in obesity and MetS is of utmost importance. Evidence Acquisition: For this review, we performed a detailed literature search on PubMed of all publications related to Toll-like receptors (TLRs) and obesity and MetS for the last 20 years. Evidence Synthesis: The TLRs are well-characterized immune receptors that enhance inflammation. The recognition of pathogen-associated molecular patterns and endogenous (host-derived) ligands released by various cell types triggers activation and expression of TLRs. TLRs, especially TLR2 and TLR4, induce insulin resistance, which is pivotal in the pathogenesis of obesity and MetS. Both obesity and MetS are characterized by low-grade chronic inflammation, possibly trigge...
TL;DR: It is suggested that women with a more diverse gut microbiome exhibit an elevated urinary ratio of hydroxylated estrogen metabolites to parent estrogen, which has been predictive of postmenopausal breast cancer risk in previous studies.
Abstract: Context: The gut microbiota may influence the risk of breast cancer through effects on endogenous estrogens. Objective: The objective of the study was to investigate whether urinary estrogens and estrogen metabolites are associated with the diversity and composition of the fecal microbiome. Design and Setting: This was a cross-sectional study among women enrolled in Kaiser Permanente of Colorado. Participants: A total of 60 women drawn from a random sample of healthy postmenopausal women (aged 55–69 y), without current or recent use of antibiotics or hormone therapy and no history of cancer or gastrointestinal disease participated in the study. Outcome Measures and Methods: Creatinine-standardized urinary estrogens (estrone and estradiol) and 13 hydroxylated estrogen metabolites were measured in spot urines by liquid chromatography-tandem mass spectrometry. The fecal microbiome was assessed using pyrosequencing of 16S rRNA amplicons. General linear models were used to test for associations of diversity an...
TL;DR: Heart failure is the leading cause of an increased cardiovascular mortality in both overt and subclinical hyperthyroidism andsubclinical hypothyroidism might be associated with a lower risk of all-cause mortality.
Abstract: Context: Thyroid dysfunction has been associated with both increased all-cause and cardiovascular mortality, but limited data are available on mild thyroid dysfunction and cause-specific mortality. Objective: The objective of the study was to examine the risk of all-cause mortality, major adverse cardiovascular events (MACEs), and cause-specific events in subjects with overt and subclinical thyroid dysfunction. Design: This was a retrospective cohort study. Setting and Participants: Participants in the study were subjects who underwent thyroid blood tests, without prior thyroid disease, consulting their general practitioner in 2000–2009 in Copenhagen, Denmark. Main Outcome Measure: All-cause mortality, MACEs, and cause-specific events identified in nationwide registries were measured. Results: A total of 47 327 (8.4%) deaths occurred among 563 700 included subjects [mean age 48.6 (SD ±18.2) y; 39% males]. All-cause mortality was increased in overt and subclinical hyperthyroidism [age adjusted incidence ra...
TL;DR: These multicenter, clinical experience data confirm originally published Afirma GEC test performance and demonstrate its substantial impact on clinical care recommendations, and although nonsignificant site-to-site variation exists, such differences should be anticipated by the practicing clinician.
Abstract: Background: Increasingly, patients with thyroid nodule cytology labeled atypical (or follicular lesion) of undetermined significance (AUS/FLUS) or follicular neoplasm (FN) undergo diagnostic analysis with the Afirma gene expression classifier (GEC). No long-term, multisite analysis of Afirma GEC performance has yet been performed. Methods: We analyzed all patients who had received Afirma GEC testing at five academic medical centers between 2010 and 2013. Nodule and patient characteristics, fine needle aspiration cytology, Afirma GEC results, and subsequent clinical or surgical follow-up were obtained for 339 patients. Results were analyzed for pooled test performance, impact on clinical care, and site-to-site variation. Results: Three hundred thirty-nine patients underwent Afirma GEC testing of cytologically indeterminate nodules (165 AUS/FLUS; 161 FN; 13 suspicious for malignancy) and 174 of 339 (51%) indeterminate nodules were GEC benign, whereas 148 GEC were suspicious (44%). GEC results significantly ...
TL;DR: The frequency of hereditary forms of PHPT may be underappreciated and needs to be assessed with increased vigilance, and surgery is likely to benefit patients due to high cure rates, low complication rates, and the likelihood of reversing skeletal manifestations.
Abstract: Objective: The surgical management of primary hyperparathyroidism (PHPT) has undergone considerable advances over the past two decades. The purpose of this report is to review these advances. Participants: This subgroup was constituted by the Steering Committee of the Fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism to address key questions related to the surgical management of PHPT. Evidence: Data since the last International Workshop were presented and discussed in detail. The topics included improvements in preoperative imaging, intraoperative adjuncts, refinements in local and regional anesthesia, and rapid intraoperative PTH assays. Consensus Process: Questions were developed by the International Task Force on PHPT. A comprehensive literature search for relevant studies was undertaken. After extensive review and discussion, the subgroup agreed on what recommendations should be made to the Expert Panel regarding surgical approaches to parathyroidectomy. Concl...
TL;DR: The risk of developing DM and CVD is increased in metabolically healthy obese and metabolically unhealthy normal weight individuals, and screening for obesity and other metabolic abnormalities should be routinely performed in clinical practice to institute appropriate preventive measures.
Abstract: Context: The risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (DM) associated with obesity appears to be influenced by the coexistence of other metabolic abnormalities. Objective: We examined the risk of developing CVD and DM in metabolically healthy obese (MHO) and metabolically unhealthy normal weight (MUH-NW) individuals. Design and Setting: We analyzed prospective data of the San Antonio Heart Study, a population-based study among Mexican Americans and non-Hispanic whites (median follow-up, 7.4 y). Participants: Incident DM and CVD were assessed in 2814 and 3700 participants aged 25 to 64 years, respectively. Main Measures: MHO was defined as obesity (body mass index ≥ 30 kg/m2) with no more than one metabolic abnormality, and MUH-NW was defined as body mass index <25 kg/m2 with two or more abnormalities. Results: In logistic regression models, BMI was associated with incident DM after controlling for demographics, family history of DM, and fasting glucose (odds ratio × 1 SD, 1.7 [95%...