Showing papers in "The Journal of Clinical Endocrinology and Metabolism in 2010"

Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline.

Abstract: Objective: Our objective was to update the guidelines for the evaluation and treatment of androgen deficiency syndromes in adult men published previously in 2006. Participants: The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, five additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration. Conclusions: We recommend making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels. We suggest the measurement of morning total testosterone level by a reliable assay as the initial diagnostic test. We recommend confirmation of the diagnosis by repeating the measurement of morning total testosterone and, in some men in whom total testosterone is near the lower limit of normal or in whom SHBG abnormality is suspected by measurement of free or bioavailable testosterone level, using validated assays. We recommend testos...

Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline

Abstract: Objective: We developed clinical practice guidelines for congenital adrenal hyperplasia (CAH). Participants: The Task Force included a chair, selected by The Endocrine Society Clinical Guidelines Subcommittee (CGS), ten additional clinicians experienced in treating CAH, a methodologist, and a medical writer. Additional experts were also consulted. The authors received no corporate funding or remuneration. Consensus Process: Consensus was guided by systematic reviews of evidence and discussions. 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: We recommend universal newborn screening for severe steroid 21-hydroxylase deficiency followed by confirmatory tests. We recommend that prenatal treatment of CAH continue to be regarded as experimental. The diagnosis rests on clinical and hormonal data; genotyping is reserved for equivocal cases and genetic counseling. Glucocorticoid dosage should be minimized to avoid iatrogenic Cushing’s syndrome. Mineralocorticoids and, in infants, supplemental sodium are recommended in classic CAH patients. We recommend against the routine use of experimental therapies to promote growth and delay puberty; we suggest patients avoid adrenalectomy. Surgical guidelines emphasize early single-stage genital repair for severely virilized girls, performed by experienced surgeons. Clinicians should consider patients’ quality of life, consulting mental health professionals as appropriate. At the transition to adulthood, we recommend monitoring for potential complications of CAH. Finally, we recommend judicious use of medication during pregnancy and in symptomatic patients with nonclassic CAH.

Update in Vitamin D

Abstract: The past decade, particularly the last 18 months, witnessed a vigorous increase in interest in vitamin D from both the lay and biomedical worlds. Much of the growing interest in vitamin D is powered by new data being extracted from the National Health and Nutrition Examination Survey (NHANES). The newest statistics demonstrate that more than 90% of the pigmented populace of the United States (Blacks, Hispanics, and Asians) now suffer from vitamin D insufficiency (25-hydroxyvitamin D <30 ng/ml), with nearly three fourths of the white population in this country also being vitamin D insufficient. This represents a near doubling of the prevalence of vitamin D insufficiency seen just 10 yr ago in the same population. This review attempts to provide some explanation for: 1) the rapid decline in vitamin D status in the United States; 2) the adverse impact of vitamin D insufficiency on skeletal, infectious/inflammatory, and metabolic health in humans; and 3) the therapeutic rationale and reliable means for vigorous supplementation of our diets with vitamin D.

Assessment of Cardiovascular Risk and Prevention of Cardiovascular Disease in Women with the Polycystic Ovary Syndrome: A Consensus Statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society

Abstract: Objective: Women with polycystic ovary syndrome (PCOS) often have cardiovascular disease (CVD) risk factors. The Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society created a panel to provide evidence-based reviews of studies assessing PCOS-CVD risk relationships and to develop guidelines for preventing CVD. Participants: An expert panel in PCOS and CVD reviewed literature and presented recommendations. Evidence: Only studies comparing PCOS with control patients were included. All electronic databases were searched; reviews included individual studies/databases, systematic reviews, abstracts, and expert data. Articles were excluded if other hyperandrogenic disorders were not excluded, PCOS diagnosis was unclear, controls were not described, or methodology precluded evaluation. Inclusion/exclusion criteria were confirmed by at least two reviewers and arbitrated by a third. Consensus Process: Systematic reviews of CVD risk factors were compiled and submitted for approval to the AE-PCOS Society B...

The product of triglycerides and glucose, a simple measure of insulin sensitivity. Comparison with the euglycemic-hyperinsulinemic clamp

Abstract: Context To meet the worldwide challenge of emerging diabetes, accessible and inexpensive tests to identify insulin resistance are needed. Objective To evaluate the sensitivity and specificity of the product of fasting, we compared the triglycerides and glucose (TyG) index, a simple measure of insulin resistance, with the euglycemic-hyperinsulinemic clamp test. Design and setting We conducted a cross-sectional study of the general population and outpatients of the Internal Medicine Department at the Medical Unit of High Specialty of the Specialty Hospital at the West National Medical Center in Guadalajara, Mexico. Patients Eleven nonobese healthy subjects, 34 obese normal glucose tolerance individuals, 22 subjects with prediabetes, and 32 diabetic patients participated in the study. Intervention We performed a euglycemic-hyperinsulinemic clamp test. Main outcome measures Sensitivity and specificity of the TyG index [Ln(fasting triglycerides) (mg/dl) x fasting glucose (mg/dl)/2] were measured, as well as the area under the curve of the receiver operating characteristic scatter plot and the correlation between the TyG index and the total glucose metabolism (M) rates. Results Pearson's correlation coefficient between the TyG index and M rates was -0.681 (P Conclusions The TyG index has high sensitivity and specificity, suggesting that it could be useful for identification of subjects with decreased insulin sensitivity.

A Consensus on Criteria for Cure of Acromegaly

Abstract: Objective: The Acromegaly Consensus Group met in April 2009 to revisit the guidelines on criteria for cure as defined in 2000. Participants: Participants included 74 neurosurgeons and endocrinologists with extensive experience of treating acromegaly. Evidence/Consensus Process: Relevant assays, biochemical measures, clinical outcomes, and definition of disease control were discussed, based on the available published evidence, and the strength of consensus statements was rated. Conclusions: Criteria to define active acromegaly and disease control were agreed, and several significant changes were made to the 2000 guidelines. Appropriate methods of measuring and achieving disease control were summarized.

Adverse Effects of Testosterone Therapy in Adult Men: A Systematic Review and Meta-Analysis

Abstract: Context: The risks of testosterone therapy in men remain poorly understood. Objective: The aim of this study was to conduct a systematic review and meta-analyses of testosterone trials to evaluate the adverse effects of testosterone treatment in men. Data Sources: We searched MEDLINE, EMBASE, and Cochrane CENTRAL from 2003 through August 2008. Review of reference lists and contact with experts further identified candidate studies. Study Selection: Eligible studies were comparative, randomized, and nonrandomized and reported the effects of testosterone on outcomes of interest (death, cardiovascular events and risk factors, prostate outcomes, and erythrocytosis). Reviewers, working independently and in duplicate, determined study eligibility. Data Extraction: Reviewers working independently and in duplicate determined the methodological quality of studies and collected descriptive, quality, and outcome data. Data Synthesis: The methodological quality of the 51 included studies varied from low to medium, and...

Postmenopausal Hormone Therapy: An Endocrine Society Scientific Statement

Abstract: Objective: Our objective was to provide a scholarly review of the published literature on menopausal hormonal therapy (MHT), make scientifically valid assessments of the available data, and grade the level of evidence available for each clinically important endpoint. Participants in Development of Scientific Statement: The 12-member Scientific Statement Task Force of The Endocrine Society selected the leader of the statement development group (R.J.S.) and suggested experts with expertise in specific areas. In conjunction with the Task Force, lead authors (n = 25) and peer reviewers (n = 14) for each specific topic were selected. All discussions regarding content and grading of evidence occurred via teleconference or electronic and written correspondence. No funding was provided to any expert or peer reviewer, and all participants volunteered their time to prepare this Scientific Statement. Evidence: Each expert conducted extensive literature searches of case control, cohort, and randomized controlled tria...

Effects of Testosterone on Muscle Strength, Physical Function, Body Composition, and Quality of Life in Intermediate-Frail and Frail Elderly Men: A Randomized, Double-Blind, Placebo-Controlled Study

Abstract: Context: Physical frailty is associated with reduced muscle strength, impaired physical function, and quality of life. Testosterone (T) increases muscle mass and strength in hypogonadal patients. It is unclear whether T has similar effects in intermediate-frail and frail elderly men with low to borderline-low T. Objective: Our objective was to determine the effects of 6 months T treatment in intermediate-frail and frail elderly men, on muscle mass and strength, physical function, and quality of life. Design and Setting: We conducted a randomized, double-blind, placebo-controlled, parallel-group, single-center study. Participants: Participants were community-dwelling intermediate-frail and frail elderly men at least 65 yr of age with a total T at or below 12 nmol/liter or free T at or below 250 pmol/liter. Methods: Two hundred seventy-four participants were randomized to transdermal T (50 mg/d) or placebo gel for 6 months. Outcome measures included muscle strength, lean and fat mass, physical function, and...

Long-term use of bisphosphonates in osteoporosis.

Abstract: Context: Bisphosphonates have been widely used in the treatment of osteoporosis. Uncommon side effects have emerged in postapproval use. Because bisphosphonates accumulate in bone and are released for months or years after treatment is stopped, it is reasonable to consider the clinical question of how long to treat. Objective: In this personal perspective, we review the pharmacology and mechanism of action of bisphosphonates and the clinical studies that support their efficacy. We then review the literature for longer-term studies and reports of possible side effects that were not seen in clinical trials. Results: Bisphosphonates have demonstrated antifracture efficacy in randomized, placebo-controlled trials of 3 and 4 yr duration and have been widely used since the initial release of alendronate in 1995. For zoledronic acid and risedronate, an early effect (fractures reduced within 6–12 months of starting therapy) has been shown. A sustained effect for risedronate has been shown through 5 yr and suggest...

Characteristics of Secondary, Primary, and Compensated Hypogonadism in Aging Men: Evidence from the European Male Ageing Study.

Abstract: Context: The diagnosis of late-onset hypogonadism (LOH) in older men with age-related declines in testosterone (T) is currently not well characterized. Objective: Our objective was to investigate whether different forms of hypogonadism can be distinguished among aging men. Design: The study was a cross-sectional survey on 3369 community-dwelling men aged 40-79 yr in eight European centers. Methods: Four groups of subjects were defined: eugonadal (normal T and normal LH), secondary (low T and low/normal LH), primary (low T and elevated LH), and compensated (normal T and elevated LH) hypogonadism. Relationships between the defined gonadal status with potential risk factors and clinical symptoms were investigated by multilevel regression models. Results: Among the men, 11.8, 2.0, and 9.5% were classified into the secondary, primary, and compensated hypogonadism categories, respectively. Older men were more likely to have primary [relative risk ratio (RRR) = 3.04; P < 0.001] and compensated (RRR = 2.41; P < 0.001) hypogonadism. Body mass index of 30 kg/m(2) or higher was associated with secondary hypogonadism (RRR = 8.74; P < 0.001). Comorbidity was associated with both secondary and primary hypogonadism. Sexual symptoms were more prevalent in secondary and primary hypogonadism, whereas physical symptoms were more likely in compensated hypogonadism. Conclusions: Symptomatic elderly men considered to have LOH can be differentiated on the basis of endocrine and clinical features and predisposing risk factors. Secondary hypogonadism is associated with obesity and primary hypogonadism predominately with age. Compensated hypogonadism can be considered a distinct clinical state associated with aging. Classification of LOH into different categories by combining LH with T may improve the diagnosis and management of LOH.

Endocrine and Nutritional Management of the Post-Bariatric Surgery Patient: An Endocrine Society Clinical Practice Guideline

Abstract: Objective: We sought to provide guidelines for the nutritional and endocrine management of adults after bariatric surgery, including those with diabetes mellitus The focus is on the immediate postoperative period and long-term management to prevent complications, weight regain, and progression of obesity-associated comorbidities The treatment of specific disorders is only summarized Participants: The Task Force was composed of a chair, five additional experts, a methodologist, and a medical writer It received no corporate funding or remuneration Conclusions: Bariatric surgery is not a guarantee of successful weight loss and maintenance Increasingly, patients regain weight, especially those undergoing restrictive surgeries such as laparoscopic banding rather than malabsorptive surgeries such as Roux-en-Y bypass Active nutritional patient education and clinical management to prevent and detect nutritional deficiencies are recommended for all patients undergoing bariatric surgery Management of potent

Health Status of Adults with Congenital Adrenal Hyperplasia: A Cohort Study of 203 Patients

Abstract: Context: No consensus exists for management of adults with congenital adrenal hyperplasia (CAH) due to a paucity of data from cohorts of meaningful size. Objective: Our objective was to establish the health status of adults with CAH. Design and Setting: We conducted a prospective cross-sectional study of adults with CAH attending specialized endocrine centers across the United Kingdom. Patients: Participants included 203 CAH patients (199 with 21-hydroxylase deficiency): 138 women, 65 men, median age 34 (range 18–69) years. Main Outcome Measures: Anthropometric, metabolic, and subjective health status was evaluated. Anthropometric measurements were compared with Health Survey for England data, and psychometric data were compared with appropriate reference cohorts. Results: Glucocorticoid treatment consisted of hydrocortisone (26%), prednisolone (43%), dexamethasone (19%), or a combination (10%), with reverse circadian administration in 41% of patients. Control of androgens was highly variable with a normal serum androstenedione found in only 36% of patients, whereas 38% had suppressed levels suggesting glucocorticoid overtreatment. In comparison with Health Survey for England participants, CAH patients were significantly shorter and had a higher body mass index, and women with classic CAH had increased diastolic blood pressure. Metabolic abnormalities were common, including obesity (41%), hypercholesterolemia (46%), insulin resistance (29%), osteopenia (40%), and osteoporosis (7%). Subjective health status was significantly impaired and fertility compromised. Conclusions: Currently, a minority of adult United Kingdom CAH patients appear to be under endocrine specialist care. In the patients studied, glucocorticoid replacement was generally nonphysiological, and androgen levels were poorly controlled. This was associated with an adverse metabolic profile and impaired fertility and quality of life. Improvements in the clinical management of adults with CAH are required.

Impact of Abdominal Visceral and Subcutaneous Adipose Tissue on Cardiometabolic Risk Factors: The Jackson Heart Study

Abstract: Objective: Obesity is a major driver of cardiometabolic risk. Abdominal visceral adipose tissue (VAT) and sc adipose tissue (SAT) may confer differential metabolic risk profiles. We investigated the relations of VAT and SAT with cardiometabolic risk factors in the Jackson Heart Study cohort. Methods: Participants from the Jackson Heart Study (n = 2477; 64% women; mean age, 58 yr) underwent multidetector computed tomography, and the volumetric amounts of VAT and SAT were assessed between 2007 and 2009. Cardiometabolic risk factors were examined by sex in relation to VAT and SAT. Results: Men had a higher mean volume of VAT (873 vs. 793 cm3) and a lower mean volume of SAT (1730 vs. 2659 cm3) than women (P = 0.0001). Per 1-sd increment in either VAT or SAT, we observed elevated levels of fasting plasma glucose and triglyceride, lower levels of high-density lipoprotein-cholesterol, and increased odds ratios for hypertension, diabetes, and metabolic syndrome. The effect size of VAT in women was larger than tha...

High-Resolution Peripheral Quantitative Computed Tomographic Imaging of Cortical and Trabecular Bone Microarchitecture in Patients with Type 2 Diabetes Mellitus

Abstract: Context: Cross-sectional epidemiological studies have found that patients with type 2 diabetes mellitus (T2DM) have a higher incidence of certain fragility fractures despite normal or elevated bone mineral density (BMD). Objective: In this study, high-resolution peripheral quantitative computed tomography was applied to characterize cortical and trabecular microarchitecture and biomechanics in the peripheral skeleton of female patients with T2DM. Design and Setting: A cross-sectional study was conducted in patients with T2DM recruited from a diabetic outpatient clinic. Participants: Elderly female patients (age, 62.9 ± 7.7 yr) with a history of T2DM (n = 19) and age- and height-matched controls (n = 19) were recruited. Outcome Measures: Subjects were imaged using high-resolution peripheral quantitative computed tomography at the distal radius and tibia. Quantitative measures of volumetric (BMD), cross-sectional geometry, trabecular and cortical microarchitecture were calculated. Additionally, compressive mechanical properties were determined by micro-finite element analysis. Results: Compared to the controls, the T2DM cohort had 10% higher trabecular volumetric BMD (P +50%; P < 0.05), whereas pore volume approached significance in the tibia (+118%; P = 0.1). Conclusion: The results of this pilot investigation provide a potential explanation for the inability of standard BMD measures to explain the elevated fracture incidence in patients with T2DM. The findings suggest that T2DM may be associated with impaired resistance to bending loads due to inefficient redistribution of bone mass, characterized by loss of intracortical bone offset by an elevation in trabecular bone density.

The Predictive Value of Different Measures of Obesity for Incident Cardiovascular Events and Mortality

Abstract: 1.74(0.84–3.6),1.71(0.91–3.22),and0.74(0.35–1.57),respectively;all-causemortality,1.86(1.25–2.76), 1.62 (1.22–2.38), 1.36 (0.93–1.69), and 0.77 (0.53–1.13), respectively; and composite endpoint, 2.16 (1.39–3.35), 1.59 (1.04–2.44), 1.49 (1.07–2.07), and 0.57 (0.37–0.89), respectively. Separate analyses of sex and age groups yielded comparable results. Receiver operating characteristics analysis yielded the highest areas under the curve for WHtR for predicting these endpoints. Conclusions:WHtR represents the best predictor of cardiovascular risk and mortality, followed by WC and WHR. Our results discourage the use of the BMI. (J Clin Endocrinol Metab 95: 0000–0000, 2010)

Shear Wave Elastography: A New Ultrasound Imaging Mode for the Differential Diagnosis of Benign and Malignant Thyroid Nodules

Abstract: Context: Elastography uses ultrasound (US) to assess elasticity. Shear wave elastography (SWE) is a new technique that estimates tissue stiffness in real time and is quantitative and user independent. Objectives: The aim of the study was to assess the efficiency of SWE in predicting malignancy and to compare SWE with US. Design: Ninety-three patients and 39 control subjects were included in the study. Predictive value of SWE was assessed by correlation between elasticity, US parameters, and histology. Elasticity index (EI) was first analyzed alone. Scores have been constructed with echographic parameters, i.e. vascularity, hypoechogenicity, and microcalcifications (Score 1 = US Score), and with the same parameters plus EI (Score 2 = US+SWE Score). For statistical analysis, univariate and multivariate analysis and receiver operating characteristic curves were used. Results: A total of 146 nodules from 93 patients were analyzed. Twenty-nine nodules (19.9%) were malignant. Mean (±sd) EI was 150 ± 95 kPa (ran...

Neck Circumference as a Novel Measure of Cardiometabolic Risk: The Framingham Heart Study

Abstract: Background: Neck circumference, a proxy for upper-body sc fat, may be a unique fat depot that confers additional cardiovascular risk above and beyond central body fat. Methods and Results: Participants with neck circumference measures who underwent multidetector computed tomography to assess visceral adipose tissue (VAT) were included [n = 3307, 48% women; mean age = 51 yr; mean body mass index (BMI) = 27.8 kg/m2; mean neck circumference = 40.5 cm (men) and 34.2 cm (women)]. Sex-specific linear regression models were used to assess the association between sd increase in neck circumference and cardiovascular disease (CVD) risk factors (systolic and diastolic blood pressure; total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglycerides; and fasting plasma glucose, insulin, proinsulin, and homeostasis model assessment of insulin resistance). Neck circumference was correlated with VAT [r = 0.63 (men); r = 0.74 (women); P < 0.001] and BMI [r = 0.79 (men); r = 0.80 (women); P < 0.001]. After further adjustment for VAT, neck circumference was positively associated with systolic blood pressure, diastolic blood pressure in men only, triglycerides, fasting plasma glucose in women only, insulin, proinsulin, and homeostasis model assessment of insulin resistance and was inversely associated with high-density lipoprotein (all P values <0.01). Similar results were observed in models that adjusted for both VAT and BMI. In a secondary analysis of incident CVD as an outcome, there was no statistically significant association observed for neck circumference in multivariable-adjusted models. Conclusions: Neck circumference is associated with CVD risk factors even after adjustment for VAT and BMI. These findings suggest that upper-body sc fat may be a unique, pathogenic fat depot.

Increased Pregnancy Loss Rate in Thyroid Antibody Negative Women with TSH Levels between 2.5 and 5.0 in the First Trimester of Pregnancy

Abstract: Context: The definition of what constitutes a normal TSH during pregnancy is in flux. Recent studies suggested that the first trimester upper limit of normal for TSH should be 2.5 mIU/liter. Objective: The objective of the study was to evaluate the pregnancy loss and preterm delivery rate in first-trimester thyroid peroxidase antibody-negative women with TSH values between 2.5 and 5.0 mIU/liter. Design: The present study is a component of a recently published large-scale prospective trial that evaluated the impact of levothyroxine treatment on maternal and neonatal complications in thyroid peroxidase-positive women with TSH levels above 2.5 mIU/liter. The present study evaluated 4123 thyroid peroxidase antibody-negative women with TSH levels at or below 5.0 mIU/liter. Women were divided into two groups based on their initial TSH: group A, TSH level below 2.5 mIU/liter, excluding hyperthyroid women defined as an undetectable TSH with an elevated free T4, and group B, TSH level between 2.5 and 5.0 mIU/liter...

Maternal Thyroid Function during Early Pregnancy and Cognitive Functioning in Early Childhood: The Generation R Study

Abstract: Context: Thyroid hormones are essential for neurodevelopment from early pregnancy onward. Yet population-based data on the association between maternal thyroid function in early pregnancy and children’s cognitive development are sparse. Objective: Our objective was to study associations of maternal hypothyroxinemia and of early pregnancy maternal TSH and free T4 (FT4) levels across the entire range with cognitive functioning in early childhood. Design and Setting: We conducted a population-based cohort in The Netherlands. Participants: Participants included 3659 children and their mothers. Main Measures: In pregnant women with normal TSH levels at 13 wk gestation (sd = 1.7), mild and severe maternal hypothyroxinemia were defined as FT4 concentrations below the 10th and 5th percentile, respectively. Children’s expressive vocabulary at 18 months was reported by mothers using the MacArthur Communicative Development Inventory. At 30 months, mothers completed the Language Development Survey and the Parent Repo...

Height adjustment in assessing dual energy x-ray absorptiometry measurements of bone mass and density in children

Abstract: Context: In children, bone mineral content (BMC) and bone mineral density (BMD) measurements by dual-energy x-ray absorptiometry (DXA) are affected by height status. No consensus exists on how to adjust BMC or BMD (BMC/BMD) measurements for short or tall stature. Objective: The aim of this study was to compare various methods to adjust BMC/BMD for height in healthy children. Design: Data from the Bone Mineral Density in Childhood Study (BMDCS) were used to develop adjustment methods that were validated using an independent cross-sectional sample of healthy children from the Reference Data Project (RDP). Setting: We conducted the study in five clinical centers in the United States. Participants: We included 1546 BMDCS and 650 RDP participants (7 to 17 yr of age, 50% female). Intervention: No interventions were used. Main Outcome Measures: We measured spine and whole body (WB) BMC and BMD Z-scores for age (BMC/BMDage), height age (BMC/BMDheight age), height (BMCheight), bone mineral apparent density (BMADag...

Insulin Resistance in Children: Consensus, Perspective, and Future Directions

Abstract: Objective: Emerging data indicate that insulin resistance is common among children and adolescents and is related to cardiometabolic risk, therefore requiring consideration early in life. However, there is still confusion on how to define insulin resistance, how to measure it, what its risk factors are, and whether there are effective strategies to prevent and treat it. A consensus conference was organized in order to clarify these points. Participants: The consensus was internationally supported by all the major scientific societies in pediatric endocrinology and 37 participants. Evidence: An independent and systematic search of the literature was conducted to identify key articles relating to insulin resistance in children. Consensus Process: The conference was divided into five themes and working groups: background and definition; methods of measurement and screening; risk factors and consequences; prevention; and treatment. Each group selected key issues, searched the literature, and developed a draft document. During a 3-d meeting, these papers were debated and finalized by each group before presenting them to the full forum for further discussion and agreement. Conclusions: Given the current childhood obesity epidemic, insulin resistance in children is an important issue confronting health care professionals. There are no clear criteria to define insulin resistance in children, and surrogate markers such as fasting insulin are poor measures of insulin sensitivity. Based on current screening criteria and methodology, there is no justification for screening children for insulin resistance. Lifestyle interventions including diet and exercise can improve insulin sensitivity, whereas drugs should be implemented only in selected cases.

Universal Screening Versus Case Finding for Detection and Treatment of Thyroid Hormonal Dysfunction During Pregnancy

Abstract: Context: Thyroid disease during pregnancy has been associated with multiple adverse outcomes. Whether all women should be screened for thyroid disease during pregnancy is controversial. Objective: The objective of the study was to determine whether treatment of thyroid disease during pregnancy decreases the incidence of adverse outcomes and compare the ability of universal screening vs. case finding in detecting thyroid dysfunction. Design: Women in the first trimester were randomly assigned to the universal screening group or case-finding group. Women in both groups were stratified as high risk or low risk based on risk factors for thyroid disease. All women in the universal screening group, and high-risk women in the case-finding group, were immediately tested for free T4, TSH, and thyroid peroxidase antibody. Low-risk women in the case-finding group had their sera tested postpartum. Setting: The study was conducted at two ambulatory clinics of community hospitals in southern Italy. Patients: A total of...

A Single Night of Partial Sleep Deprivation Induces Insulin Resistance in Multiple Metabolic Pathways in Healthy Subjects

Abstract: Background: Subsequent nights with partial sleep restriction result in impaired glucose tolerance, but the effects on insulin sensitivity have not been characterized. Objective: The aim of this study was to evaluate the effect of a single night of partial sleep restriction on parameters of insulin sensitivity. Research Design and Methods: Nine healthy subjects (five men, four women) were studied once after a night of normal sleep duration (sleep allowed from 2300 to 0730 h), and once after a night of 4 h of sleep (sleep allowed from 0100 to 0500 h). Sleep characteristics were assessed by polysomnography. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp studies (from 1130 to 1430 h) with infusion of [6,6-2H2]glucose. Results: Sleep duration was shorter in the night with sleep restriction than in the unrestricted night (226 ± 11 vs. 454 ± 9 min; P< 0.0001). Sleep restriction did not affect basal levels of glucose, nonesterified fatty acids, insulin, or endogenous glucose production. Sle...

Incidence of Pituitary Adenomas in Northern Finland in 1992–2007

Abstract: Context: Data on the incidence of pituitary adenomas (PAs) are scant and outdated. A population-based regional cohort with thorough case identification was used to evaluate the incidence of clinically detected PAs in the era of magnetic resonance imaging. Objective: The objective of the study was to describe the age- and sex-specific incidence of all PA subgroups, with data on incidentally found PAs, pituitary apoplexies, and time trends. Design, Settings, and Patients: This was a retrospective descriptive analysis of PA patients diagnosed during 1992–2007 in Northern Finland (NFi). Main Outcome Measure: World Health Organization 2000-standardized incidence rates (SIRs) of PAs per 100,000 were measured. Results and Conclusion: The final cohort consisted of 355 PAs. The incidence rates of the Oulu University Hospital regional district were used as a reference to assess the applicability of our case finding over the rest of NFi. Incidence rates of all PA subgroups except microprolactinomas were statisticall...

Recent Changes in Pubertal Timing in Healthy Danish Boys: Associations with Body Mass Index

Abstract: Context: In the 1990s, the American population-based study NHANES III renewed the focus on possible secular trends in male puberty. However, no conclusions could be made on pubertal onset due to the lack of compatible data. Objective: The aim of the study was to evaluate secular trends in pubertal onset during the recent 15 yr and their relation to body mass index (BMI) in boys. Design and Setting: We conducted a cross-sectional study in 1991–1993 and a combined cross-sectional and longitudinal study in 2006–2008 (The Copenhagen Puberty Study) at a tertiary center for pediatric endocrinology. Participants: A total of 1528 boys aged 5.8 to 19.9 yr participated (n = 824 in 1991–1993, and n = 704 in 2006–2008). Genital and pubic hair stages as well as testicular volume by orchidometry were evaluated. Blood samples were analyzed for LH, FSH, testosterone, and SHBG. Main Outcome Measures: We measured age at onset of pubertal markers. Results: Onset of puberty, defined as age at attainment of testicular volume ...

Serum levels of anti-Müllerian hormone as a marker of ovarian function in 926 healthy females from birth to adulthood and in 172 Turner syndrome patients.

Abstract: Context: In adult women, anti-Mullerian hormone (AMH) is related to the ovarian follicle pool. Little is known about AMH in girls. Objective: The objective of the study was to provide a reference range for AMH in girls and adolescents and to evaluate AMH as a marker of ovarian function. Setting: The study was conducted at a tertiary referral center for pediatric endocrinology. Main Outcome Measures: We measured AMH in 926 healthy females (longitudinal values during infancy) as well as in 172 Turner syndrome (TS) patients according to age, karyotype (A: 45,X; B: miscellaneous karyotypes; C: 45,X/46,XX), and ovarian function (1: absent puberty; 2: cessation of ovarian function; 3: ongoing ovarian function). Results: AMH was undetectable in 54% (38 of 71) of cord blood samples (<2; <2–15 pmol/liter) (median; 2.5th to 97.5th percentile) and increased in all (37 of 37) infants from birth to 3 months (15; 4.5–29.5 pmol/liter). From 8 to 25 yr, AMH levels were stable (19.9; 4.7–60.1 pmol/liter), with the lower l...

Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy

Abstract: Context: For patients on T4 replacement, the dose is guided by serum TSH concentrations, but some patients request higher doses due to adverse symptoms. Objective: The aim of the study was to determine the safety of patients having a low but not suppressed serum TSH when receiving long-term T4 replacement. Design: We conducted an observational cohort study, using data linkage from regional datasets between 1993 and 2001. Setting: A population-based study of all patients in Tayside, Scotland, was performed. Patients: All patients taking T4 replacement therapy (n = 17,684) were included. Main Outcome Measures: Fatal and nonfatal endpoints were considered for cardiovascular disease, dysrhythmias, and fractures. Patients were categorized as having a suppressed TSH (≤0.03 mU/liter), low TSH (0.04–0.4 mU/liter), normal TSH (0.4–4.0 mU/liter), or raised TSH (>4.0 mU/liter). Results: Cardiovascular disease, dysrhythmias, and fractures were increased in patients with a high TSH: adjusted hazards ratio, 1.95 (1.73–...

Clinical Characteristics and Therapeutic Responses in Patients with Germ-Line AIP Mutations and Pituitary Adenomas: An International Collaborative Study

Abstract: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively.

Mutations of the KISS1 gene in disorders of puberty

Abstract: Context: Kisspeptin, encoded by the KISS1 gene, is a key stimulatory factor of GnRH secretion and puberty onset. Inactivating mutations of its receptor (KISS1R) cause isolated hypogonadotropic hypogonadism (IHH). A unique KISS1R-activating mutation was described in central precocious puberty (CPP). Objective: Our objective was to investigate KISS1 mutations in patients with idiopathic CPP and normosmic IHH. Patients: Eighty-three children with CPP (77 girls) and 61 patients with IHH (40 men) were studied. The control group consisted of 200 individuals with normal pubertal development. Methods: The promoter region and the three exons of KISS1 were amplified and sequenced. Cells expressing KISS1R were stimulated with synthetic human wild-type or mutant kisspeptin-54 (kp54), and inositol phosphate accumulation was measured. In a second set of experiments, kp54 was preincubated in human serum before stimulation of the cells. Results: Two novel KISS1 missense mutations, p.P74S and p.H90D, were identified in th...