Showing papers in "The Journal of Clinical Endocrinology and Metabolism in 2007"
TL;DR: Evidence from trials with vitamin D and/or calcium supplementation suggests that combined Vitamin D and calcium supplementation may have a role in the prevention of type 2 DM only in populations at high risk (i.e. glucose intolerance).
Abstract: Context: Altered vitamin D and calcium homeostasis may play a role in the development of type 2 diabetes mellitus (type 2 DM). Evidence Acquisition and Analyses: MEDLINE review was conducted through January 2007 for observational studies and clinical trials in adults with outcomes related to glucose homeostasis. When data were available to combine, meta-analyses were performed, and summary odds ratios (OR) are presented. Evidence Synthesis: Observational studies show a relatively consistent association between low vitamin D status, calcium or dairy intake, and prevalent type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM prevalence, 0.36 (0.16–0.80) among nonblacks for highest vs. lowest 25-hydroxyvitamin D; metabolic syndrome prevalence, 0.71 (0.57–0.89) for highest vs. lowest dairy intake]. There are also inverse associations with incident type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM incidence, 0.82 (0.72–0.93) for highest vs. lowest combined vitamin D an...
1,810 citations
University of Rhode Island1, Favaloro University2, Brigham and Women's Hospital3, University of Colorado Denver4, Icahn School of Medicine at Mount Sinai5, University of Sydney6, University Hospital of Wales7, University of Paris8, University of Pennsylvania9, University of Southern California10, Medical University of South Carolina11
TL;DR: Practice guidelines are presented for diagnosis and treatment of patients with thyroid-related medical issues just before and during pregnancy and in the postpartum interval, including evidence-based approaches to assessing the cause of the condition, treating it, and managing hypothyroidism.
Abstract: Objective: The aim was to update the guidelines for the management of thyroid dysfunction during pregnancy and postpartum published previously in 2007. A summary of changes between the 2007 and 2012 version is identified in the Supplemental Data (published on The Endocrine Society's Journals Online web site at http://jcem.endojournals.org). Evidence: This evidence-based guideline was developed according to the U.S. Preventive Service Task Force, grading items level A, B, C, D, or I, on the basis of the strength of evidence and magnitude of net benefit (benefits minus harms) as well as the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. Consensus Process: The guideline was developed through a series of e-mails, conference calls, and one face-to-face meeting. An initial draft was prepared by the Task Force, with the help of a medical writer, and reviewed and commented on by members of The Endocri...
1,707 citations
TL;DR: AMI rates and cardiovascular risk factors were increased in HIV compared with non-HIV patients, particularly among women, and cardiac risk modification strategies are important for the long-term care of HIV patients.
Abstract: Context: Metabolic changes and smoking are common among HIV patients and may confer increased cardiovascular risk. Objective: The aim of the study was to determine acute myocardial infarction (AMI) rates and cardiovascular risk factors in HIV compared with non-HIV patients in two tertiary care hospitals. Design, Setting, and Participants: We conducted a health care system-based cohort study using a large data registry with 3,851 HIV and 1,044,589 non-HIV patients. AMI rates were determined among patients receiving longitudinal care between October 1, 1996, and June 30, 2004. Main Outcome Measures: The primary outcome was myocardial infarction, identified by International Classification of Diseases coding criteria. Results: AMI was identified in 189 HIV and 26,142 non-HIV patients. AMI rates per 1000 person-years were increased in HIV vs. non-HIV patients [11.13 (95% confidence interval [CI] 9.58–12.68) vs. 6.98 (95% CI 6.89–7.06)]. The HIV cohort had significantly higher proportions of hypertension (21.2 ...
1,475 citations
TL;DR: There seems to be a differential expression of pro- and antiinflammatory factors with increasing adipocyte size resulting in a shift toward dominance of proinflammatory adipokines largely as a result of a dysregulation of hypertrophic, very large cells.
Abstract: Context: Adipocytes are known to release a variety of factors that may contribute to the proinflammatory state characteristic for obesity. This secretory function is considered to provide the basis for obesity-related complications such as type 2 diabetes and atherosclerosis. Objective: To get a better insight into possible underlying mechanisms, we investigated the effect of adipocyte size on adipokine production and secretion. Design, Patients, and Main Outcome Measures: Protein secretion and mRNA expression in cultured adipocytes separated according to cell size from 30 individuals undergoing elective plastic surgery were investigated. Results: The mean adipocyte volume of the four fractions ranged from 205 ± 146 to 1.077 ± 471 pl. There were strong linear correlations for the secretion of adipokines over time. Secretion of leptin, IL-6, IL-8, TNF-α, monocyte chemoattractant protein-1, interferon-γ-inducible protein 10, macrophage inflammatory protein-1β, granulocyte colony stimulating factor, IL-1ra, ...
1,195 citations
TL;DR: Evaluated clinical assays for total and free testosterone showed that laboratory proficiency testing should be based on the ability to measure accurately and precisely samples containing known concentrations of testosterone, not only on agreement with others using the same method.
Abstract: Objective: The objective of the study was to evaluate the current state of clinical assays for total and free testosterone. Participants: The five participants were appointed by the Council of The Endocrine Society and charged with attaining the objective using published data and expert opinion. Evidence: Data were gleaned from published sources via online databases (principally PubMed, Ovid MEDLINE, Google Scholar), the College of American Pathologists, and the clinical and laboratory experiences of the participants. Consensus Process: The statement was an effort of the committee and was reviewed in detail by each member. The Council of The Endocrine Society reviewed a late draft and made specific recommendations. Conclusions: Laboratory proficiency testing should be based on the ability to measure accurately and precisely samples containing known concentrations of testosterone, not only on agreement with others using the same method. When such standardization is in place, normative values for total and ...
1,105 citations
TL;DR: It is suggested that parents receiving a prenatal diagnosis of TS be advised of the broad phenotypic spectrum and the good quality of life observed in TS in recent years and that patients with defined cardiovascular defects be cautioned in regard to pregnancy and certain types of exercise.
Abstract: Objectives: The objective of this work is to provide updated guidelines for the evaluation and treatment of girls and women with Turner syndrome (TS). Participants: The Turner Syndrome Consensus Study Group is a multidisciplinary panel of experts with relevant clinical and research experience with TS that met in Bethesda, Maryland, April 2006. The meeting was supported by the National Institute of Child Health and unrestricted educational grants from pharmaceutical companies. Evidence: The study group used peer-reviewed published information to form its principal recommendations. Expert opinion was used where good evidence was lacking. Consensus: The study group met for 3 d to discuss key issues. Breakout groups focused on genetic, cardiological, auxological, psychological, gynecological, and general medical concerns and drafted recommendations for presentation to the whole group. Draft reports were available for additional comment on the meeting web site. Synthesis of the section reports and final revisi...
823 citations
TL;DR: A nested case-control study of pregnant women followed from less than 16 wk gestation to delivery to assess the effect of maternal 25-hydroxyvitamin D [25(OH)D] concentration on the risk of preeclampsia and the vitamin D status of newborns of preeClamptic mothers.
Abstract: Context: Vitamin D has direct influence on molecular pathways proposed to be important in the pathogenesis of preeclampsia, yet the vitamin D-preeclampsia relation has not been studied. Objectives: We aimed to assess the effect of maternal 25-hydroxyvitamin D [25(OH)D] concentration on the risk of preeclampsia and to assess the vitamin D status of newborns of preeclamptic mothers. Design and Setting: We conducted a nested case-control study of pregnant women followed from less than 16 wk gestation to delivery (1997–2001) at prenatal clinics and private practices. Patients: Patients included nulliparous pregnant women with singleton pregnancies who developed preeclampsia (n = 55) or did not develop preeclampsia (n = 219). Women’s banked sera were newly measured for 25(OH)D. Main Outcome Measure: The main outcome measure was preeclampsia (new-onset gestational hypertension and proteinuria for the first time after 20 wk gestation). Our hypotheses were formulated before data collection. Results: Adjusted seru...
693 citations
TL;DR: Prevalence of symptomatic androgen deficiency in men 30 and 79 yr of age is 5.6% and increases substantially with age, projection of these estimates to the year 2025 suggests that there will be as many as 6.5 million American men ages 30-79 yr with symptomaticandrogen deficiency, an increase of 38% from 2000 population estimates.
Abstract: Context: Despite recognition that androgen deficiency in men should be defined according to biochemical and clinical criteria, most prevalence estimates are based on low testosterone levels alone Objective: The objective of this study was to examine the association between symptoms of androgen deficiency and low total and calculated free testosterone levels and estimate the prevalence of symptomatic androgen deficiency in men Design: This study was a population-based, observational survey Participants: A total of 1475 Black, Hispanic, and white men, between the ages of 30–79 yr, with complete data on testosterone, SHBG, and symptoms of androgen deficiency, and who are not taking medications that impact sex steroid levels were randomly selected from the Boston Area Community Health Survey Outcome: Outcomes were measured as symptomatic androgen deficiency, defined as low total (<300 ng/dl) and free (<5 ng/dl) testosterone plus presence of low libido, erectile dysfunction, osteoporosis or fracture, or tw
620 citations
TL;DR: It is held that the MetS counts as a multiplex cardiovascular risk factor that is clinically useful and will lead to advances in diagnosis and treatment of an important cause of cardiovascular disease.
Abstract: Context: The metabolic syndrome (MetS) is a multiplex risk factor for cardiovascular disease. The syndrome develops through interplay of obesity and metabolic susceptibility. Objective: This article addresses whether the MetS construct has clinical utility. Position: The National Cholesterol Education Program and other organizations have proposed that the MetS can be recognized clinically by a clustering of simple clinical measures including waist circumferences, blood pressure, triglycerides, high-density lipoproteins, and glucose. People with this clustering have most or all of the components of the MetS. Identifying the MetS has several advantages. It discovers persons who are at increased risk for cardiovascular disease. A diagnosis focuses more clinical attention on the underlying causes, notably obesity and other lifestyle factors; it thereby reinforces the utility of lifestyle changes in clinical practice. A diagnosis further informs physicians on choice and intensity of drug therapy for elevated cholesterol, aspirin prophylaxis, and blood pressure and glucose control. The introduction of the MetS has led to a large number of epidemiological, metabolic, and genetic studies that have heightened our understanding of the condition’s prevalence and pathogenesis. It has been a stimulus to the development of new drugs or drug combinations that will modify multiple risk factors simultaneously. Conclusions: This author holds that the MetS counts as a multiplex cardiovascular risk factor that is clinically useful and will lead to advances in diagnosis and treatment of an important cause of cardiovascular disease. (J Clin Endocrinol Metab 92: 399–404, 2007)
617 citations
TL;DR: Management of thyroid diseases during pregnancy requires special considerations because pregnancy induces major changes in thyroid function, and maternal thyroid disease can have adverse effects on the pregnancy and the fetus.
Abstract: Objective: The objective is to provide clinical guidelines for the management of thyroid problems present during pregnancy and in the postpartum. Participants: The Chair was selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society. The Chair requested participation by the Latin American Thyroid Society, the Asia and Oceania Thyroid Society, the American Thyroid Association, the European Thyroid Association, and the American Association of Clinical Endocrinologists, and each organization appointed a member to the task force. Two members of The Endocrine Society were also asked to participate. The group worked on the guidelines for 2 yr and held two meetings. There was no corporate funding, and no members received remuneration. Evidence: Applicable published and peer-reviewed literature of the last two decades was reviewed, with a concentration on original investigations. The grading of evidence was done using the United States Preventive Services Task Force system and, where possible, the GRADE system. Consensus Process: Consensus was achieved through conference calls, two group meetings, and exchange of many drafts by E-mail. The manuscript was reviewed concurrently by the Society’s CGS, Clinical Affairs Committee, members of The Endocrine Society, and members of each of the collaborating societies. Many valuable suggestions were received and incorporated into the final document. Each of the societies endorsed the guidelines. Conclusions: Management of thyroid diseases during pregnancy requires special considerations because pregnancy induces major changes in thyroid function, and maternal thyroid disease can have adverse effects on the pregnancy and the fetus. Care requires coordination among several healthcare professionals. Avoiding maternal (and fetal) hypothyroidism is of major importance because of potential damage to fetal neural development, an increased incidence of miscarriage, and preterm delivery. Maternal hyperthyroidism and its treatment may be accompanied by coincident problems in fetal thyroid function. Autoimmune thyroid disease is associated with both increased rates of miscarriage, for which the appropriate medical response is uncertain at this time, and postpartum thyroiditis. Fine-needle aspiration cytology should be performed for dominant thyroid nodules discovered in pregnancy. Radioactive isotopes must be avoided during pregnancy and lactation. Universal screening of pregnant women for thyroid disease is not yet supported by adequate studies, but case finding targeted to specific groups of patients who are at increased risk is strongly supported. (J Clin Endocrinol Metab 92: S1–S47, 2007)
608 citations
TL;DR: TSH distribution progressively shifts toward higher concentrations with age, and the prevalence of subclinical hypothyroidism may be significantly overestimated unless an age-specific range for TSH is used.
Abstract: Context: Measurements from all age groups defined the upper limit of the TSH reference range in National Health and Nutrition Examination Survey III. The TSH median, 97.5 centile and prevalence of subclinical hypothyroidism (SCH), normal serum T4 and TSH greater than 4.5 mIU/liter, increased progressively with age. Age-adjusted reference ranges would include many people with TSH greater than 4.5 mIU/liter. Objective: We determined whether increasing 50 and 97.5 centiles with age resulted from more patients with SCH in populations with normal TSH distribution or whether age-specific population shifts to higher serum TSH might account for these findings. Design/Setting/Patients: We analyzed TSH, antithyroid antibodies, and TSH frequency distribution curves for specific age deciles in populations without thyroid disease, with or without antithyroid antibodies. Results: Without thyroid disease, 10.6% of 20- to 29-yr-olds had TSH greater than 2.5 mIU/liter, increasing to 40% in the 80+ group, 14.5% of whom had...
TL;DR: The diagnosis of SGA should be based on accurate anthropometry at birth including weight, length, and head circumference and early neurodevelopment evaluation and interventions are warranted in at-risk children.
Abstract: Objective: Low birth weight remains a major cause of morbidity and mortality in early infancy and childhood. It is associated with an increased risk of health problems later in life, particularly coronary heart disease and stroke. A meeting was convened to identify the key health issues facing a child born small for gestational age (SGA) and to propose management strategies.
TL;DR: Serum 25-OHD concentrations below 20 ng/ml are associated with poorer physical performance and a greater decline in physical performance in older men and women and public health strategies should be aimed at this group.
Abstract: Context: Vitamin D deficiency is common among older people and can cause mineralization defects, bone loss, and muscle weakness. Objective: The aim of this study was to investigate the association of serum 25-hydroxyvitamin D (25-OHD) concentration with current physical performance and its decline over 3 yr among elderly. Design: The study consisted of a cross-sectional and longitudinal design (3-yr follow-up) within the Longitudinal Aging Study Amsterdam. Setting: An age- and sex-stratified random sample of the Dutch older population was used. Other Participants: Subjects included 1234 men and women (aged 65 yr and older) for cross-sectional analysis and 979 (79%) persons for longitudinal analysis. Main Outcome Measure(s): Physical performance (sum score of the walking test, chair stands, and tandem stand) and decline in physical performance were measured. Results: Serum 25-OHD was associated with physical performance after adjustment for age, gender, chronic diseases, degree of urbanization, body mass i...
TL;DR: The relationship between obesity and osteoporosis is reevaluate by accounting for the mechanical loading effects of total body weight on bone mass and the phenotypic correlation between fat mass and fat mass was negative, suggesting increasing fat mass may not have a beneficial effect on bonemass.
Abstract: Context: The relationship between obesity and osteoporosis has been widely studied, and epidemiological evidence shows that obesity is correlated with increased bone mass. Previous analyses, however, did not control for the mechanical loading effects of total body weight on bone mass and may have generated a confounded or even biased relationship between obesity and osteoporosis. Objective: The objective of this study was to reevaluate the relationship between obesity and osteoporosis by accounting for the mechanical loading effects of total body weight on bone mass. Methods: We measured whole body fat mass, lean mass, percentage fat mass, body mass index, and bone mass in two large samples of different ethnicity: 1988 unrelated Chinese subjects and 4489 Caucasian subjects from 512 pedigrees. We first evaluated the Pearson correlations among different phenotypes. We then dissected the phenotypic correlations into genetic and environmental components with bone mass unadjusted or adjusted for body weight. T...
TL;DR: US elastography has great potential as an adjunctive tool for the diagnosis of thyroid cancer, especially in indeterminate nodules on cytology, and an US elastographic score of 4-5 was observed in six of seven patients with carcinoma on histology.
Abstract: Background: Elastography is a newly developed dynamic technique that uses ultrasound (US) to provide an estimation of tissue stiffness by measuring the degree of distortion under the application of an external force. US elastography has been applied to differentiate malignant from benign lesions. Patients: This study included 92 consecutive patients with a single thyroid nodule who underwent surgery for compressive symptoms or suspicion of malignancy on fine needle aspiration cytology. Tissue stiffness on US elastography was scored from one (greatest elastic strain) to five (no strain). Results: On US elastography: scores 1 and 2 were found in 49 cases, all benign lesions; score 3 in 13 cases, one carcinoma and 12 benign lesions; and scores 4 and 5 in 30 cases, all carcinomas. Thus, the elasticity scores 4–5 were highly predictive of malignancy (P < 0.0001), with a sensitivity of 97%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 98%. In 32 patients with an...
TL;DR: Preerential macrophage infiltration into OM fat is a general phenomenon exaggerated by central obesity, potentially linking central adiposity with increased risk of diabetes and coronary heart disease.
Abstract: Context: Macrophage infiltration into adipose tissue has been demonstrated to accompany obesity, with a potential preferential infiltration into intraabdominal vs. sc fat. Objective: Our objective was to determine whether this occurs across different populations with a range of body mass indexes and to assess the relationship with regional adiposity and comorbidity of obesity. Setting and Patients: In two independent cohorts, we used paired omental (OM) and sc fat biopsies from lean controls or predominantly sc or intraabdominally obese persons with minimal comorbidity (n = 60, cohort 1), or from severely obese women with a significant rate of comorbidity (n = 29, cohort 2). Results: Elevated macrophage infiltration into OM vs. sc fat was observable in lean subjects and exaggerated by obesity, particularly if predominantly intraabdominal. This was paralleled by increased monocyte chemoattractant protein-1 (MCP1) and colony-stimulating factor-1 (CSF1) mRNA levels. Level of CSF1 and MCP1 mRNA correlated wit...
TL;DR: It is suggested that oral vitamin D appears to reduce the risk of hip fractures only when calcium supplementation is added.
Abstract: Purpose: The purpose of this study was to extend the metaanalysis of Bischoff-Ferrari et al., which found that 700–800 IU/d vitamin D reduced hip fracture risk in elderly individuals by 25%, by defining the need for additional calcium supplementation in individuals receiving vitamin D for the prevention of hip fractures. Data Sources: MEDLINE and EMBASE.com (search terms: “vitamin D” and “hip fracture”), bibliographies of articles retrieved, and the authors’ reference files were used as data sources. Study Selection: Selected studies were randomized controlled trials (RCTs) of oral vitamin D with or without calcium supplementation vs. placebo/no treatment in postmenopausal women and/or older men (≥50 yr) specifically reporting a risk of hip fracture. Data Extraction: Independent extraction was performed by two authors using predefined criteria, including study quality indicators. Data Synthesis: All pooled analyses are based on random-effects models. Based on four RCTs (9083 patients), the pooled relative...
TL;DR: FT4 was significantly related to four of five components of the metabolic syndrome (abdominal obesity, triglycerides, high-density lipoprotein cholesterol, and blood pressure), independent of insulin resistance, and low normal FT4 levels were significantly associated with increased insulin resistance.
Abstract: Context: Thyroid disease and the metabolic syndrome are both associated with cardiovascular disease. Objective: The aim of this study was to explore the hypothesis that thyroid function, in euthyroid subjects, is associated with components of the metabolic syndrome, including serum lipid concentrations and insulin resistance. Methods: A total of 2703 adult inhabitants of a middle-sized city in The Netherlands participated in this cross-sectional study. Subjects who were not euthyroid were excluded, as were subjects taking thyroid medication, medication for diabetes, and subjects for whom medication data were not available (n = 1122). Homeostasis model assessment for insulin resistance (HOMA-IR) (mU∗mmol/liter2) was calculated as fasting insulin (mU/liter) times fasting glucose (mmol/liter) divided by 22.5. The metabolic syndrome was defined according to National Cholesterol Education Program’s Adult Treatment Panel III criteria. Results: After adjustment for age and sex, free T4 (FT4) was significantly as...
TL;DR: The following clinical scenario and discussion aim to enhance the knowledge of the physician regarding the behavior of pheochromocytoma and to outline current approaches to comprehensive preoperative management of patients suffering from this tumor.
Abstract: Pheochromocytomas are rare neuroendocrine tumors with a highly variable clinical presentation, but they most commonly present as spells of headaches, sweating, palpitations, and hypertension. Patients with pheochromocytoma may develop complicated and potentially lethal cardiovascular and other complications, especially in the setting of diagnostic or interventional procedures (e.g. upon induction of anesthesia or during surgery). The serious and potentially lethal nature of such complications is due to the potent effect of paroxysmal release of catecholamines. Because this warrants prompt diagnosis and treatment, the physician should be aware of the clinical manifestations and complications of catecholamine excess and be able to provide proper preoperative management to minimize catecholamine-related pre-, intra-, and postoperative adverse events. The following clinical scenario and discussion aim to enhance the knowledge of the physician regarding the behavior of pheochromocytoma and to outline current approaches to comprehensive preoperative management of patients suffering from this tumor.
TL;DR: The reduction of AMH in follicles greater than 9 mm from normal ovaries appears to be an important requirement for the selection of the dominant follicle in women with polycystic ovary syndrome.
Abstract: Context: There has been renewed interest in anti-Mullerian hormone (AMH) because of its role in the ovary. Data on its actions are sparse, but it appears to inhibit follicle growth. Interestingly, serum AMH is two to three times higher in women with polycystic ovary (PCO) syndrome than women with normal ovaries. Objective: We examined the production of AMH by cells from a range of follicle sizes from normal ovaries and compared this with production by ovulatory and anovulatory (anov) PCOs. Design: Granulosa cells (GCs) and theca and follicular fluid (ff) were isolated from intact follicles. Cells were cultured for 48 h ± FSH or LH, and AMH was measured in ff and cell-conditioned media (CM). Results: AMH levels in ff and GC-CM ranged from 42 to 2240 and 0.025 to 1.7 ng/ml, respectively, and were low or undetectable in ff and GC-CM from follicles greater than 9 mm, luteinized cells, and theca and stroma. The mean level of AMH was four times higher in GC-CM from ovulatory PCOs [mean (range) 1.56 (0.025–7)] a...
TL;DR: PPARγ is highly expressed in adipose tissue, where its activation with thiazolidinediones alters fat topography and links to improvements in insulin resistance and the progression to type 2 diabetes and atherosclerosis.
Abstract: Context: Adipose tissue is a metabolically dynamic organ, serving as a buffer to control fatty acid flux and a regulator of endocrine function. In obese subjects, and those with type 2 diabetes or the metabolic syndrome, adipose tissue function is altered (i.e. adipocytes display morphological differences alongside aberrant endocrine and metabolic function and low-grade inflammation). Evidence Acquisition: Articles on the role of peroxisome proliferator-activated receptor γ (PPARγ) in adipose tissue of healthy individuals and those with obesity, metabolic syndrome, or type 2 diabetes were sourced using MEDLINE (1990–2006). Evidence Synthesis: Articles were assessed to provide a comprehensive overview of how PPARγ-activating ligands improve adipose tissue function, and how this links to improvements in insulin resistance and the progression to type 2 diabetes and atherosclerosis. Conclusions: PPARγ is highly expressed in adipose tissue, where its activation with thiazolidinediones alters fat topography and...
TL;DR: Liver fat content is significantly increased in subjects with the metabolic syndrome as compared with those without the syndrome, independently of age, gender, and body mass index.
Abstract: Background: The liver, once fatty, overproduces components of the metabolic syndrome, such as glucose and lipids. The amount of liver fat in subjects with and without the metabolic syndrome has not been determined. It is unknown which clinically available markers best reflect liver fat content. Measurements: Components of the metabolic syndrome as defined by the International Diabetes Federation and liver fat content by proton magnetic resonance spectroscopy were measured in 271 nondiabetic subjects (162 women, 109 men). In addition, other features of insulin resistance (serum insulin, C-peptide), intraabdominal and sc fat by magnetic resonance imaging, and liver enzymes (serum alanine aminotransferase and serum aspartate aminotransferase) were measured. Results: Liver fat was 4-fold higher in subjects with [n = 116; median 8.2% (interquartile range 3.2–18.7%)] than without [n = 155; 2.0% (1.0–5.0%); P < 0.0001] the metabolic syndrome. This increase in liver fat remained significant after adjusting for ag...
TL;DR: Cystic appearance, hyperechoic punctuations, loss of hilum, and peripheral vascularization can be considered as major ultrasound criteria of LN malignancy in patients with differentiated thyroid cancer.
Abstract: Context: Neck ultrasonography (US) has become a keystone in the follow-up of patients with differentiated thyroid cancer. Objective: The aim of this study was to determine specificity and sensitivity of ultrasound criteria of malignancy for cervical lymph nodes (LNs) in patients with differentiated thyroid cancer. Design: We prospectively studied 19 patients referred to the Institut Gustave Roussy for neck LN dissection. All patients underwent a neck US within 4 d prior to surgery. Only LNs that were unequivocally matched between US and pathology were taken into account for the analysis. Results: One hundred three LNs were detected on US, 578 LNs were surgically removed, and 56 LNs were analyzed (28 benign and 28 malignant). Sensitivity and specificity were 68 and 75% for the long axis (≥1 cm), 61 and 96% for the short axis (>5 mm), 46 and 64% for the round shape (long to short axis ratio < 2), 100 and 29% for the loss of fatty hyperechoic hilum, 39 and 18% for hypoechogenicity, 11 and 100% for cystic app...
TL;DR: Data suggest that variable responsiveness to UVB radiation is evident among individuals, causing some to have low vitamin D status despite abundant sun exposure, and it seems prudent to use this value as an upper limit when prescribing vitamin D supplementation.
Abstract: Context: Lack of sun exposure is widely accepted as the primary cause of epidemic low vitamin D status worldwide. However, some individuals with seemingly adequate UV exposure have been reported to have low serum 25-hydroxyvitamin D [25(OH)D] concentration, results that might have been confounded by imprecision of the assays used. Objective: The aim was to document the 25(OH)D status of healthy individuals with habitually high sun exposure. Setting: This study was conducted in a convenience sample of adults in Honolulu, Hawaii (latitude 21°). Participants: The study population consisted of 93 adults (30 women and 63 men) with a mean (sem) age and body mass index of 24.0 yr (0.7) and 23.6 kg/m2 (0.4), respectively. Their self-reported sun exposure was 28.9 (1.5) h/wk, yielding a calculated sun exposure index of 11.1 (0.7). Main Outcome Measures: Serum 25(OH)D concentration was measured using a precise HPLC assay. Low vitamin D status was defined as a circulating 25(OH)D concentration less than 30 ng/ml. Re...
TL;DR: Both time (chronological aging) and ovarian aging contributed to substantial changes in body composition (fat and skeletal muscle mass) and waist circumference, which have important ramifications for establishing a metabolic environment that can be healthy or unhealthy.
Abstract: Context: Understanding the menopause association with body weight is important because excess weight increases risk for stroke, incident cardiovascular disease, cardiovascular mortality, and all-cause mortality among the middle-aged. Objective: The objective of this study was to examine chronological age and ovarian age and consider how these could influence body size and composition in midlife women. Design and Setting: The Study of Women’s Health Across the Nation is a longitudinal, community-based study. This report uses data from the Michigan Study of Women’s Health Across the Nation site. Participants: Participants were 543 premenopausal or early perimenopausal African-American and Caucasian women aged 42–52 yr at baseline examination. Main Outcome Measures: Waist circumference, fat mass and skeletal muscle mass, from bioelectrical impedance, were assessed in seven annual serial measures. Annual FSH values were assayed by ELISA. The final menstrual period was defined retrospectively after 12 months o...
TL;DR: SCH treated by L-thyroxine leads to a significant improvement in CV risk factors and symptoms of tiredness, and the CV risk factor reduction is related to the increased level of achieved free T(4) concentration.
Abstract: Context: Subclinical hypothyroidism (SCH) is defined as raised serum TSH levels with circulating thyroid hormones within the reference range. It is uncertain whether treatment of SCH with l-thyroxine improves cardiovascular (CV) risk factors and quality of life. Objective: The objective of the study was to assess CV risk factors and patient-reported outcomes after treatment. Design: This was a randomized, double-blind, crossover study of l-thyroxine and placebo. Setting: The study was conducted with community-dwelling patients. Patients: One hundred patients [mean age (sd) 53.8 (12) yr, 81 females] with SCH [mean TSH 6.6 (1.3) mIU/liter] without previously treated thyroid or vascular disease. Intervention: Intervention consisted of 100 μg l-thyroxine or placebo daily for 12 wk each. Measurements: Primary parameters were total cholesterol (TC) and endothelial function [brachial artery flow-mediated dilatation (FMD)], an early marker of atherosclerosis. Patient-reported outcomes were also assessed. Results:...
TL;DR: To determine whether rosiglitazone, a thiazolidinedione, inhibits bone formation, a 14-wk randomized, double-blind, placebo-controlled trial was conducted in the general community.
Abstract: Context: Thiazolidinediones, which are peroxisome proliferator-activated receptor-γ agonists, are widely prescribed to patients with disorders characterized by insulin resistance. Preclinical studies suggest that peroxisome proliferator-activated receptor-γ signaling negatively regulates bone formation and bone density. Human data on the skeletal effects of thiazolidinediones are currently available only from observational studies. Objective: The objective of the study was to determine whether rosiglitazone, a thiazolidinedione, inhibits bone formation. Design: The study was a 14-wk randomized, double-blind, placebo-controlled trial. Setting: The study was conducted in the general community. Patients: Fifty healthy, postmenopausal women participated in the study. Intervention: Intervention was rosiglitazone 8 mg/d. Main Outcome Measures: The primary end point was biochemical markers of bone formation, and secondary end points were a bone resorption marker and bone mineral density. Results: The osteoblast ...
TL;DR: The data suggest that BRAF V600E mutation is associated with high-risk PTC and in particular in follicular variant with invasive tumor growth.
Abstract: Context: Because very few studies have examined the correlation between BRAF mutations and clinicopathological features of papillary thyroid carcinoma (PTC), we analyzed here a large and homogeneous cohort of patients with PTC for the presence of the BRAF mutation. Objective: We examined BRAF mutations in a consecutive series of 500 PTC patients who underwent surgery in the Department of Surgery of the University of Pisa, and we correlated the presence of the mutation with clinicopathological parameters of the patients: age, gender, tumor size, presence of tumor capsule, extrathyroidal invasion, multicentricity, presence of node metastases, and tumor class. Design: BRAF (exon 15) mutation was examined by PCR-single strand conformational polymorphism followed by DNA sequencing in laser-capture microdissected tissue samples. Results: In this study, BRAF mutation was found in 219 of 500 cases (43.8%). In particular, we found the most common BRAF V600E mutation in 214 cases (42.8%), BRAF K601E mutation in thr...
TL;DR: SDHB mutations, frequent in patients with malignant pheochromocytomas or paragangliomas, are associated with shorter survival, and genetic testing may be of prognostic value for such patients, even those with an apparent sporadic and/or benign presentation at diagnosis.
Abstract: Context: Pheochromocytomas and paragangliomas may be malignant either at presentation or during recurrence, but the clinical course of malignant tumors is unpredictable. Objective: The objective was to analyze survival according to clinical characteristics at diagnosis of malignancy and the presence or absence of SDHB mutations. Design: This was a retrospective cohort study. Setting and Participants: A total of 54 patients with malignant tumors were included. Malignancy was scored according to the presence of metastases or histologically documented lymph node invasion. Main Outcome Measures: The main outcome was the specific survival after the diagnosis of the first metastasis. Results: Germline mutations were identified in SDHB (n = 23, including 21 patients with apparent sporadic tumors) and VHL (n = 1) genes, and two patients had neurofibromatosis 1. Patients were followed up from the diagnosis of primary tumor and from the diagnosis of the first metastasis to the present or to death with medians of 79...
TL;DR: Both chronological aging and changes in health and lifestyle factors are associated with declines in serum T, and the possibility that age-related hormone decline may be decelerated through the management of health andifestyle factors is suggested.
Abstract: Context: Although it is known that serum testosterone (T) concentrations decline with age, the relative contributions of changes in health and lifestyle to that decline have not been adequately assessed. Objective: The objective of this study was to establish the relative importance of aging, health, and lifestyle in contributing to male T decline. Design: A prospective cohort study of health and endocrine functioning in randomly selected men with a baseline visit (T1, 1987–1989) and two follow-up visits (T2, 1995–1997; T3, 2002–2004) was conducted. Setting: An observational study of men residing in greater Boston, Massachusetts, was conducted. Participants: Participants included 1667 men aged 40 to 70 at baseline; follow-up was conducted on 947 (57%) and 584 (35%) at T2 and T3, respectively. Main Outcome Measures: Main outcome measures included total serum T, calculated free T (FT), and SHBG. Results: There were substantial declines in total serum T and FT levels associated with aging alone. However, man...