Showing papers in "The Journal of Clinical Endocrinology and Metabolism in 2006"
University of California, Los Angeles1, University of Palermo2, Lille University of Science and Technology3, National and Kapodistrian University of Athens4, University of Alcalá5, Icahn School of Medicine at Mount Sinai6, University of Duisburg-Essen7, Pennsylvania State University8, University of Adelaide9, Pfizer10, University of Pittsburgh11
TL;DR: It is the view of the AES Task Force on the Phenotype of PCOS that there should be acceptance of the original 1990 National Institutes of Health criteria with some modifications, taking into consideration the concerns expressed in the proceedings of the 2003 Rotterdam conference.
Abstract: Objective: The Androgen Excess Society (AES) charged a task force to review all available data and recommend an evidence-based definition for polycystic ovary syndrome (PCOS), whether already in use or not, to guide clinical diagnosis and future research. Participants: Participants included expert investigators in the field. Evidence: Based on a systematic review of the published peer-reviewed medical literature, by querying MEDLINE databases, we tried to identify studies evaluating the epidemiology or phenotypic aspects of PCOS. Consensus Process: The task force drafted the initial report, following a consensus process via electronic communication, which was then reviewed and critiqued by the AES Board of Directors. No section was finalized until all members were satisfied with the contents and minority opinions noted. Statements that were not supported by peer-reviewed evidence were not included. Conclusions: Based on the available data, it is the view of the AES Task Force on the Phenotype of PCOS that...
1,877 citations
TL;DR: Thyroxine treatment is highly effective in younger patients with (131)I uptake and with small metastases and should be treated until the disappearance of any uptake or until a cumulative activity of 22 GBq has been administered.
Abstract: Aim: The goal of this study was to estimate the cumulative activity of 131I to be administered to patients with distant metastases from thyroid carcinoma. Methods: A total of 444 patients were treated from 1953–1994 for distant metastases from papillary and follicular thyroid carcinoma: 223 had lung metastases only, 115 had bone metastases only, 82 had both lung and bone metastases, and 24 had metastases at other sites. Treatment consisted of the administration of 3.7 GBq (100 mCi) 131I after withdrawal of thyroid hormone treatment, every 3–9 months during the first 2 yr and then once a year until the disappearance of any metastatic uptake. Thyroxine treatment was given at suppressive doses between 131I treatment courses. Results: Negative imaging studies (negative total body 131I scans and conventional radiographs) were attained in 43% of the 295 patients with 131I uptake; more frequently in those who were younger, had well-differentiated tumors, and had a limited extent of disease. Most negative studies...
1,300 citations
TL;DR: The Task Force recommends testosterone therapy for symptomatic men with androgen deficiency, who have low testosterone levels, to induce and maintain secondary sex characteristics and to improve their sexual function, sense of well-being, muscle mass and strength, and bone mineral density.
Abstract: Objective: The objective was to provide guidelines for the evaluation and treatment of androgen deficiency syndromes in adult men 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 professional writer The Task Force received no corporate funding or remuneration Evidence: The Task Force used systematic reviews of available evidence to inform its key recommendations The Task Force used consistent language and graphical descriptions of both the strength of recommendation and the quality of evidence, using the recommendations of the Grading of Recommendations, Assessment, Development, and Evaluation group Consensus Process: Consensus was guided by systematic reviews of evidence and discussions during three group meetings, several conference calls, and e-mail communications The drafts prepared by the panelists with the help of a professional writer were reviewed successively by Th
1,029 citations
TL;DR: Assessment of risk for diabetes or cardiovascular disease stratified by body mass index and the presence or absence of metabolic syndrome (MetS) or insulin resistance (IR) found people with normal weight and MetS or IR or with obesity but no MetS and IR were not uncommon in this sample.
Abstract: Context: Metabolic risk conferred by adiposity may be due to associated risk factor clustering. Objective: The objective of this study was to assess risk for diabetes or cardiovascular disease (CVD) stratified by body mass index (BMI) and the presence or absence of metabolic syndrome (MetS) or insulin resistance (IR). Design, Setting, and Participants: This was a community-based, longitudinal study of 2902 people (55% women, mean age 53 yr) without diabetes or CVD in 1989–1992 followed for up to 11 yr. We categorized subjects by normal weight (BMI 25 kg/m 2 ), overweight (25–29.9 kg/m 2 ), or obese (30 kg/m 2 ) and by the National
956 citations
TL;DR: GH therapy offers benefits in body composition, exercise capacity, skeletal integrity, and quality of life measures and is most likely to benefit those patients who have more severe GHD, and the risks associated with GH treatment are low.
Abstract: Growth hormone treatment can provide benefits in body composition, bone, and quality of life in adults with confirmed growth hormone deficiency.
881 citations
TL;DR: The prevalence of pituitary adenomas in the study population (one case in 1064 individuals) was more than 3.5-5 times that previously reported, which may have important implications when prioritizing funding for research and treatment of Pituitary Adenomas.
Abstract: Context: Prevalence data are important for assessing the burden of disease on the health care system; data on pituitary adenoma prevalence are very scarce. Objective: The objective of the study was to measure the prevalence of clinically relevant pituitary adenomas in a well-defined population. Design: This was a cross-sectional, intensive, case-finding study performed in three regions of the province of Liege, Belgium, to measure pituitary adenoma prevalence as of September 30, 2005. Setting: The study was conducted in specialist and general medical practitioner patient populations, referral hospitals, and investigational centers. Methods: Three demographically and geographically distinct districts of the province of Liege were delineated precisely using postal codes. Medical practitioners in these districts were recruited, and patients with pituitary adenomas under their care were identified. Diagnoses were confirmed after retrieval of clinical, hormonal, radiological, and pathological data; full demogr...
860 citations
TL;DR: Treatments aimed at reducing insulin resistance have had some success, but larger placebo-controlled studies are needed to fully establish the efficacy of these interventions and possibly others in reducing the deleterious effects of fat accumulation in the liver.
Abstract: Context: Insulin resistance is an almost universal finding in nonalcoholic fatty liver disease (NAFLD). This review outlines the evidence linking insulin resistance and NAFLD, explores whether liver fat is a cause or consequence of insulin resistance, and reviews the current evidence for treatment of NAFLD. Evidence Acquisition: Evidence from epidemiological, experimental, and clinical research studies investigating NAFLD and insulin resistance was reviewed. Evidence Synthesis: Insulin resistance in NAFLD is characterized by reductions in whole-body, hepatic, and adipose tissue insulin sensitivity. The mechanisms underlying the accumulation of fat in the liver may include excess dietary fat, increased delivery of free fatty acids to the liver, inadequate fatty acid oxidation, and increased de novo lipogenesis. Insulin resistance may enhance hepatic fat accumulation by increasing free fatty acid delivery and by the effect of hyperinsulinemia to stimulate anabolic processes. The impact of weight loss, metfo...
744 citations
TL;DR: Future advances in the management of ACC will mainly depend on a better understanding of the molecular pathogenesis facilitating the use of modern cancer treatments (e.g. tyrosine kinase inhibitors).
Abstract: Context: Adrenocortical carcinoma (ACC) is a rare and heterogeneous malignancy with incompletely understood pathogenesis and poor prognosis Patients present with hormone excess (eg virilization, Cushing’s syndrome) or a local mass effect (median tumor size at diagnosis > 10 cm) This paper reviews current diagnostic and therapeutic strategies in ACC Evidence Acquisition: Original articles and reviews were identified using a PubMed search strategy (http://wwwncbinlmnihgov/entrez/queryfcgi) covering the time period up until November 2005 The following search terms were used in varying combinations: adrenal, adrenocortical, cancer, carcinoma, tumor, diagnosis, imaging, treatment, radiotherapy, mitotane, cytotoxic, surgery Evidence synthesis: Tumors typically appear inhomogeneous in both computerized tomography and magnetic resonance imaging with necroses and irregular borders and differ from benign adenomas by their low fat content Hormonal analysis reveals evidence of steroid hormone secretion b
695 citations
TL;DR: Euthyroid pregnant women who are positive for TPOAb develop impaired thyroid function, which is associated with an increased risk of miscarriage and premature deliveries, and Substitutive treatment with LT(4) is able to lower the chance of miscarriages and premature delivery.
Abstract: Context: Euthyroid women with autoimmune thyroid disease show impairment of thyroid function during gestation and seem to suffer from a higher rate of obstetrical complications. Objective: We sought to determine whether these women suffer from a higher rate of obstetrical complications and whether levothyroxine (LT4) treatment exerts beneficial effects. Design: This was a prospective study. Setting: The study was conducted in the Department of Obstetrics and Gynecology. Patients: A total of 984 pregnant women were studied from November 2002 to October 2004; 11.7% were thyroid peroxidase antibody positive (TPOAb+). Intervention: TPOAb+ patients were divided into two groups: group A (n = 57) was treated with LT4, and group B (n = 58) was not treated. The 869 TPOAb− patients (group C) served as a normal population control group. Main Outcome Measures: Rates of obstetrical complications in treated and untreated groups were measured. Results: At baseline, TPOAb+ had higher TSH compared with TPOAb−; TSH remaine...
691 citations
TL;DR: Results indicate that visfatin may play a role in the pathogenesis of type 2 diabetes mellitus and multiple logistic regression analysis revealed visFatin as an independent association factor for T2DM, even after full adjustment of known biomarkers.
Abstract: Context: Visfatin (also known as pre-B cell colony-enhancing factor or PBEF) is a cytokine that is highly expressed in visceral fat and whose blood levels correlate with obesity. Originally isolated as a secreted factor that promotes the growth of B cell precursors and recently found to act as an insulin analog on the insulin receptor, its pathophysiological role in humans remains largely unknown. Objectives: In this study we investigated whether plasma visfatin level is altered in patients with type 2 diabetes mellitus (T2DM). Design and Patients: Plasma visfatin as well as adiponectin and resistin concentrations were measured through ELISA in type 2 diabetic and nondiabetic subjects. Results: A total of 61 patients with T2DM and 59 sex- and age-matched nondiabetic subjects were studied. Plasma visfatin was found to be elevated in patients with T2DM (31.9 ± 31.7 vs. 15.8 ± 16.7 ng/ml, P = 0.002). In contrast, adiponectin was decreased (4.3 ± 2.5 vs. 30.8 ± 10.3 μg/ml, P < 0.001), whereas plasma resistin ...
673 citations
TL;DR: The notion that n-3 fatty acids may be beneficial in patients affected by diseases characterized by active inflammation is supported, as well as the fact that PUFAs were independently associated with lower levels of proinflammatory markers and higher levels of antiinflammatory markers independent of confounders.
Abstract: Aims: Persons with high intake of polyunsaturated fatty acids (PUFAs) have lower cardiovascular morbidity and mortality. The protective effect of PUFAs is mediated by multiple mechanisms, including their antiinflammatory properties. The association of physiological PUFA levels with pro- and antiinflammatory markers has not been established. Methods and Results: In 1123 persons (aged 20–98 yr), we examined the relationship between relative concentration of fatty acids in fasting plasma and level of inflammatory markers. Adjusting for age, sex, and major confounders, lower arachidonic and docosahexaenoic acids were associated with significantly higher IL-6 and IL-1ra and significantly lower TGF. Lower -linolenic acid was associated with higherC-reactiveproteinandIL-1ra,andlowereicosapentaenoicacid was associated with higher IL-6 and lower TGF. Lower docosahexaenoic acid was strongly associated with lower IL-10. Total n-3 fatty acids were associated with lower IL-6 (P 0.005), IL-1ra (P 0.004), and TNF (P 0.040) and higher soluble IL-6r (P 0.001), IL-10 (P 0.024), and TGF (P 0.0012). Lower n-6 fatty acid levels weresignificantlyassociatedwithhigherIL-1ra(P0.026)andlower TGF(P0.014).Then-6ton-3ratiowasastrong,negativecorrelate of IL-10. Findings were similar in participants free of cardiovascular diseases and after excluding lipids from covariates. Conclusions: In this community-based sample, PUFAs, and especially total n-3 fatty acids, were independently associated with lower levels of proinflammatory markers (IL-6, IL-1ra, TNF, C-reactive protein) and higher levels of antiinflammatory markers (soluble IL6r, IL-10, TGF) independent of confounders. Our findings support the notion that n-3 fatty acids may be beneficial in patients affected by diseases characterized by active inflammation. (J Clin Endocrinol Metab 91: 439–446, 2006)
TL;DR: The metabolic syndrome and its individual components are common in PCOS, particularly among women with the highest insulin levels and BMI, and Hyperinsulinemia is a likely common pathogenetic factor for both PCOS and the metabolic syndrome.
Abstract: Context: Polycystic ovary syndrome (PCOS) and the metabolic syndrome have many features in common and may share the same pathogenesis. Objective: This study was performed to determine the prevalence and predictors of the metabolic syndrome in PCOS. Design: The clinical, hormonal, and oral glucose tolerance test results were analyzed in 394 PCOS women who were screened for participation in a multicenter trial to evaluate the effects of troglitazone on ovulation and hirsutism. Setting: A multicenter clinical trial is presented. Patients or Other Participants: The subjects were women with PCOS who had or lacked the metabolic syndrome. Main Outcome Measures: Waist circumference, fasting glucose, high-density lipoprotein cholesterol and triglyceride concentrations, and blood pressure were the main outcome measures. Results: Twenty-six (6.6%) subjects had diabetes; among the 368 nondiabetics, the prevalence for individual components comprising the metabolic syndrome were: waist circumference greater than 88 cm ...
TL;DR: Peripheral endocannabinoid overactivity might explain why CB(1) blockers cause weight-loss independent reduction of lipogenesis, of hypoadiponectinemia, and of hyperinsulinemia in obese animals and humans.
Abstract: Context: Cannabinoid CB1 receptor blockade decreases weight and hyperinsulinemia in obese animals and humans in a way greatly independent from food intake. Objective: The objective of this study was to investigate the regulation and function of the endocannabinoid system in adipocytes and pancreatic β-cells. Design, Setting, and Patients: Mouse 3T3-F442A adipocytes and rat insulinoma RIN-m5F β-cells, pancreas and fat from mice with diet-induced obesity, visceral and sc fat from patients with body mass index equal to or greater than 30 kg/m2, and serum from normoglycemic and type 2 diabetes patients were studied. Main Outcome Measure: Endocannabinoid enzyme and adipocyte protein expression, and endocannabinoid and insulin levels were measured. Results: Endocannabinoids are present in adipocytes with levels peaking before differentiation, and in RIN-m5F β-cells, where they are under the negative control of insulin. Chronic treatment of adipocytes with insulin is accompanied by permanently elevated endocanna...
TL;DR: In a patient with one or more thyroid nodules larger than 10 mm in diameter, the likelihood of thyroid cancer per patient is independent of the number of nodules, whereas the likelihood per nodule decreases as the numberof nodules increases.
Abstract: Context: Controversy remains as to the optimal management of patients with multiple thyroid nodules. Objective: The objective of this study was to determine the prevalence, distribution, and sonographic features of thyroid cancer in patients with solitary and multiple thyroid nodules. Design: We describe a retrospective observational cohort study that was carried out from 1995 to 2003. Setting: The study was conducted in a tertiary care hospital. Patients: Patients with one or more thyroid nodules larger than 10 mm in diameter who had ultrasound-guided fine needle aspiration (FNA) were included in the study. Main Outcome Measures: The main outcome measures were prevalence and distribution of thyroid cancer and the predictive value of demographic and sonographic features. Results: A total of 1985 patients underwent FNA of 3483 nodules. The prevalence of thyroid cancer was similar between patients with a solitary nodule (175 of 1181 patients, 14.8%) and patients with multiple nodules (120 of 804, 14.9%) (P ...
TL;DR: Patients with TS and especially the karyotypes 45,X and isoXq have a higher mortality compared with the background population, and there was a steady increase in prevalence, but incidence was unchanged.
Abstract: Aim: Our aim was to study prevalence, incidence, age at diagnosis, and mortality in Turner syndrome (TS) in Denmark. Methods: Using the Danish Cytogenetic Register, we identified all cases (n = 781) of TS alive in Denmark during 1970–2001. Sixty-nine deceased women with TS were identified in the Causes of Death Register. We divided the cohort into women having the karyotype 45,X, karyotypes including an isochromosome Xq, and all other karyotypes associated with TS. We describe the number of patients diagnosed in Denmark yearly, incidence rates, and the age at diagnosis. Standardized mortality ratios (SMR) were calculated. Results: A total of 349 women had a 45,X karyotype, 86 had a karyotype including an isochromosome Xq (isoXq), and 346 had another TS karyotype. Mortality was increased in TS with an SMR of 2.86 (95% confidence interval, 2.18–3.55). SMR was increased for coronary diseases, congenital malformations, endocrine diseases, and other causes. The mortality was increased for all types of karyotyp...
TL;DR: Low serum SHBG, low total testosterone, and clinical AD are associated with increased risk of developing MetS over time, particularly in nonoverweight, middle-aged men (BMI, <25).
Abstract: Lower levels of total testosterone and SHBG were predictive of MetS, particularlyamongmenwithabodymassindex(BMI)below25kg/m 2 with adjusted RRs for a decrease in 1 SD of 1.41 (95% CI, 1.06–1.87) and 1.65 (95% CI, 1.12–2.42). Results were similar for the AD and MetS association, with RRs of 2.51 (95% CI, 1.12–5.65) among men with a BMI less than 25 compared with an RR of 1.22 (95% CI, 0.66–2.24) in men with a BMI of 25 or greater. Conclusions: Low serum SHBG, low total testosterone, and clinical AD are associated with increased risk of developing MetS over time, particularly in nonoverweight, middle-aged men (BMI, 25). Together, these results suggest that low SHBG and/or AD may provide early warning signs for cardiovascular risk and an opportunity for early intervention in nonobese men. (J Clin Endocrinol Metab 91: 843–850, 2006)
University of Sydney1, University of Paris2, Royal Hobart Hospital3, University of Texas Health Science Center at San Antonio4, Waikato Hospital5, Martin Luther University of Halle-Wittenberg6, Sir Charles Gairdner Hospital7, University of Calgary8, University of Angers9, University of New South Wales10, French Institute of Health and Medical Research11, Royal North Shore Hospital12
TL;DR: SDHB mutation carriers were more likely than SDHD mutation carriers to develop extraadrenal pheochromocytomas and malignant disease, whereas SD HD mutation carriers had a greater propensity to develop head and neck paragangliomas and multiple tumors.
Abstract: Context: The identification of mutations in genes encoding peptides of succinate dehydrogenase (SDH) in pheochromocytoma/paraganglioma syndromes has necessitated clear elucidation of genotype-phenotype associations. Objective: Our objective was to determine genotype-phenotype associations in a cohort of patients with pheochromocytoma/paraganglioma syndromes and succinate dehydrogenase subunit B (SDHB) or subunit D (SDHD) mutations. Design, Setting, and Participants: The International SDH Consortium studied 116 individuals (83 affected and 33 clinically unaffected) from 62 families with pheochromocytoma/paraganglioma syndromes and SDHB or SDHD mutations. Clinical data were collected between August 2003 and September 2004 from tertiary referral centers in Australia, France, New Zealand, Germany, United States, Canada, and Scotland. Main Outcome Measures: Data were collected on patients with pheochromocytomas and/or paragangliomas with respect to onset of disease, diagnosis, genetic testing, surgery, patholo...
TL;DR: Women with type 2 diabetes are at increased risk for fractures, seen among black and non-Hispanic white women after adjustment for multiple risk factors including frequent falls and increased BMD (in a subset).
Abstract: Context: Some but not all studies have shown higher rates of fracture in individuals with type 2 diabetes. Objective: The objective of the study was to determine the risk of fracture in postmenopausal women with type 2 diabetes and determine whether risk varies by fracture site, ethnicity, and baseline bone density. Design, Setting, and Participants: Women with clinically diagnosed type 2 diabetes at baseline in the Women’s Health Initiative Observational Cohort, a prospective study of postmenopausal women (n = 93,676), were compared with women without diagnosed diabetes and risk of fracture overall and at specific sites determined. Main Outcome Measures: All fractures and specific sites separately (hip/pelvis/upper leg; lower leg/ankle/knee; foot; upper arm/shoulder/elbow; lower arm/wrist/hand; spine/tailbone) were measured. Bone mineral density (BMD) in a subset also was measured. Results: The overall risk of fracture after 7 yr of follow-up was higher in women with diabetes at baseline after controllin...
TL;DR: Postprandial, but not fasting, blood glucose is an independent risk factor for cardiovascular events in type 2 diabetes, with a stronger predictive power in women than in men, suggesting that more attention should be paid to postprandials hyperglycemia, particularly in women.
Abstract: Objective: The influence of postprandial blood glucose on diabetes complications is intensively debated. We aimed to evaluate the predictive role of both fasting and postprandial blood glucose on cardiovascular events in type 2 diabetes and the influence of gender. Methods: In a population of 529 (284 men and 245 women) consecutive type 2 diabetic patients attending our diabetes clinic, we evaluated the relationships, corrected for cardiovascular risk factors and type of treatment, between cardiovascular events in a 5-yr follow-up and baseline values of hemoglobin A1c (HbA1c) and blood glucose measured: 1) after an overnight fast, 2) after breakfast, 3) after lunch, and 4) before dinner. Continuous variables were categorized into tertiles. Results: We recorded cardiovascular events in 77 subjects: 54 of 284 men (19%) and 23 of 245 women (9.4%). Univariate analysis indicated that cardiovascular events were associated with increasing age, longer diabetes duration, and higher HbA1c and fibrinogen in men, and...
TL;DR: FDG-PET scanning is a simple, expensive, but powerful means to restage thyroid cancer patients who develop subsequent metastases, assigning them to groups that are either at low ( FDG negative) or high (FDG positive) risk of cancer-associated mortality.
Abstract: Context/Objective: Approximately 15% of thyroid cancer patients develop subsequent metastases. The clinical course of patients with metastatic thyroid carcinoma is highly variable. We hypothesized that the metabolic activity of metastatic lesions, as defined by retention of 2-[18F]fluoro-2-deoxyglucose (FDG), would correlate with prognosis. Design/Patients: The initial FDG-positron emission tomography (PET) scans from 400 thyroid cancer patients were retrospectively reviewed and compared with overall survival (median follow-up, 7.9 yr). We examined the prognostic value of clinical information such as gender, age, serum thyroglobulin, American Joint Committee on Cancer (AJCC) stage, histology, radioiodine avidity, FDG-PET positivity, number of FDG-avid lesions, and the glycolytic rate of the most active lesion. Results: Age, initial stage, histology, thyroglobulin, radioiodine uptake, and PET outcomes all correlated with survival by univariate analysis. However, only age and PET results continued to be str...
TL;DR: In aging male patients, psychosomatic complaints and metabolic risk relate to testosterone in a symptom-specific manner, and there is no evidence that a uniform structure of testosterone concentrations and complaints exists within the cohort of elderly male patients.
Abstract: Context: Although attention and concern about health disorders in aging men have been growing, the structure of psychological and somatic complaints of actual patients, not population-based cohorts, has not been elucidated in relation to sex hormone patterns and metabolism. Objective: The objective of the study was investigation of factors influencing complaint structures in aging male patients. Design: This was a cross-sectional cohort study. Setting: The study was conducted in an andrological outpatient department. Patients: Subjects included 434 consecutive male patients aged 50–86 yr. Main Outcome Measures: The following hypotheses were measured: 1) psychosomatic complaints and metabolic factors in aging male patients are related to sex hormone levels in a symptom-specific manner, and 2) patients form subcohorts. Results: A clear-cut threshold for late-onset hypogonadism was not found; rather, prevalence of psychosomatic symptoms and metabolic risk factors accumulated with decreasing androgen levels. ...
TL;DR: A trivariate genetic analysis of oligomenorrhea, acne, and hirsutism confirmed that the familial component in PCOS is due to genetic factors, justifying the search for susceptibility genes.
Abstract: Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. There is evidence for a genetic component in PCOS based on familial clustering of cases. Objective: In the present study, the heritability of PCOS was estimated. Design/Participants: Data from 1332 monozygotic twins (genetically identical) and 1873 dizygotic twins/singleton sisters of twins (whoshareonaverage50%oftheirsegregatinggenes)registeredwith The Netherlands Twin Register were used. PCOS was defined as less than nine menstrual cycles and acne or hirsutism in agreement with the 2003 Rotterdam consensus. Results: Results point to a strong contribution of familial factors to PCOS. The resemblance in monozygotic twin sisters (tetrachoric correlation 0.71) for PCOS was about twice as large as in dizygotic twin and other sisters (tetrachoric correlation 0.38). Univariate analyses point to strong contributions of genetic factors to the variance in PCOS. Next, a trivariate genetic analysis of oligomenorrhea, acne, and hirsutism was carried out. This analysis confirmed that the familial component in PCOS is due to genetic factors. Conclusions: This study demonstrated a large influence of genetic factors to the pathogenesis of PCOS, justifying the search for susceptibility genes. (J Clin Endocrinol Metab 91: 2100–2104, 2006)
TL;DR: The variability of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is described for promoting recognition and adequate follow-up of patients and consideration of AIRE mutation assay.
Abstract: Context: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is known as a rare hereditary disease with classic triad of mucocutaneous candidiasis, hypoparathyroidism, and adrenocortical failure, two of which, diagnostic dyad, are required for the diagnosis. Evidently many patients suffer unrecognized because the condition is more variable and complex. Objective: The objective of the study was to describe the variability of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy for promoting recognition and adequate follow-up of patients. Setting: The Finnish series of patients is the largest internationally. Patients: The study population was all 91 known Finnish patients. Results: Besides the classical triad, a dozen autoimmune endocrine and other components occurred variably, several of them dangerous. The initial manifestation appeared within the age range of 0.2–18 yr, mucocutaneous candidiasis being part of it in 60% of the patients, hypoparathyroidism in 32%, and adrenocortical f...
TL;DR: Consequent to catch-up weight gain between birth and 2 yr, SGA children showed a dramatic transition toward central adiposity and insulin resistance between ages 2 and 4 yr, indicating predisposition to adverse future health.
Abstract: Context and Objective: Low birth weight followed by rapid postnatal weight gain is associated with long-term risks for central obesity and insulin resistance. However, the timing of these changes is unclear. Setting, Design, and Patients: This was a longitudinal cohort study in low birth weight (SGA; birth weight < −2 sd; n = 29) and normal birth weight (AGA; n = 22) children from Barcelona. Main Outcome Measures: Body composition, by dual-energy x-ray absorptiometry scan, and insulin sensitivity, assessed longitudinally at ages 2, 3, and 4 yr, were measured. Results: Mean height, weight, and body mass index at ages 2, 3, and 4 yr were not different between SGA and AGA children. At age 2 yr, SGA children had similar body composition but were more insulin sensitive than AGA children and had lower serum IGF-I levels and lower neutrophil counts. Between ages 2 and 4 yr, despite similar gains in weight and body mass index, SGA children gained more abdominal fat and body adiposity and less lean mass than AGA c...
TL;DR: In patients with type 2 diabetes, near maximal glucose-lowering efficacy of sitagliptin after single oral doses was associated with inhibition of plasma DPP-4 activity of 80% or greater, corresponding to a plasma sitgliptin concentration of 100 nm or greater and an augmentation of active GLP-1 and GIP levels of 2-fold or higher after an OGTT.
Abstract: Context: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4) DPP-4 inhibitors are a novel class of oral antihyperglycemic agents in development for the treatment of type 2 diabetes The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test (OGTT) were evaluated Objective: The objective of the study was to examine the pharmacodynamics, pharmacokinetics, and tolerability of sitagliptin Design: This was a randomized, double-blind, placebo-controlled, three-period, single-dose crossover study Setting: The study was conducted at six investigational sites Patients: The study population consisted of 58 patients with type 2 diabetes who were not on antihyperglycemic agents Interventions: Interventions included sitagliptin 25 mg, sitaglipti
TL;DR: It is proposed that these simple clinical and biochemical factors can serve as an adjunct to FNAB in predicting risk of malignancy in individual patients, taking into account their gender, age, goiter type determined clinically, and serum TSH, was calculated.
Abstract: Context: Thyroid nodules and goiter are common, and fine-needle aspiration biopsy (FNAB) is the first investigation of choice in distinguishing benign from malignant disease. Objective: The objective of the study was to assess whether simple clinical and biochemical parameters can predict the likelihood of thyroid malignancy in subjects undergoing FNAB. Design: The design was a prospective cohort. Setting: The study was conducted at a single secondary/tertiary care clinic. Participants: One thousand five hundred consecutive patients without overt thyroid dysfunction (1304 females and 196 males, mean age 47.8 yr) presenting with palpable thyroid enlargement between 1984 and 2002 were evaluated by FNAB of the thyroid. Intervention(s): There were no interventions. Main Outcome Measures: Goiter type was assessed clinically and classified as diffuse in 183, multinodular in 456, or solitary nodule in 861 cases. Serum TSH concentration at presentation was measured in a sensitive assay in patients presenting afte...
TL;DR: AMH levels measured through a full menstrual cycle did not show consistent fluctuation patterns in contrast to levels of FSH, LH, and estradiol, but random fluctuations were small, indicating that AMH can be relied on as a cycle-independent marker for ovarian reserve.
Abstract: Context: Anti-Mullerian hormone (AMH), a quantitative marker for ovarian reserve, has been suggested to be independent of the classical endocrine fluctuations of the menstrual cycle. Objective: The objective of the study was to determine whether AMH levels are constant throughout the menstrual cycle, compared with those of FSH, LH, and estradiol. Design/Patients: Frequent blood sampling was performed in 44 fertile, regularly cycling, female volunteers during one full menstrual cycle. Setting: The study was conducted at a university hospital. Main Outcome Measures: AMH, FSH, LH, and estradiol measurements were allocated to one of seven cycle phases, and a multilevel analysis was performed. Consistent fluctuation patterns were tested by fitting sine patterns to the data. Finally, the frequency in which randomly selected individual samples would remain in one of five preset level categories (quintiles) for each of the variables was studied. Results: A sine pattern fitted to the AMH data was not statistically...
TL;DR: These observational results suggest that TZDs may cause bone loss in older women, and these results need to be tested in a randomized trial.
Abstract: Context: Activation of peroxisome proliferator-activated receptor-γ by thiazolidinediones (TZDs) results in lower bone mass in mice. Objective: The objective of the study was to determine whether TZD use is associated with changes in bone mineral density (BMD) in older adults with type 2 diabetes. Design: We analyzed 4-yr follow-up data from the Health, Aging, and Body Composition observational study. Setting: The study was conducted in a general community. Patients: White and black, physically able men and women, aged 70–79 yr at baseline with diabetes defined by self-report, use of hypoglycemic medication, elevated fasting glucose (≥126 mg/dl), or elevated 2-h glucose tolerance test (≥200 mg/dl) participated in the study. Main Outcome Measures: Whole-body, lumbar spine (derived from whole body), and hip BMD were measured by dual-energy x-ray absorptiometry at 2-yr intervals. Results: Of 666 diabetic participants, 69 reported TZD use at an annual visit, including troglitazone (n = 22), pioglitazone (n = ...
TL;DR: Short-term treatment with leuprolide and bicalutamide significantly increased fat mass and decreased insulin sensitivity in men with prostate cancer and suggest that GnRH agonists may increase the risk of diabetes mellitus and cardiovascular disease in older men.
Abstract: Context: GnRH agonists markedly increase fat mass in men with prostate cancer, but little is known about the effects of treatment on insulin sensitivity. Objective: The objective of the study was to assess the effects of short-term GnRH agonist treatment on insulin sensitivity. Design: This was a prospective 12-wk study. Setting: The study was conducted at a general clinical research center. Patients or Other Participants: We studied 25 men with locally advanced or recurrent prostate cancer, no radiographic evidence of metastases, no history of diabetes mellitus, and no evidence of diabetes mellitus at baseline visit. Intervention: Leuprolide depot and bicalutamide were used in the study. Main Outcome Measures: Oral glucose tolerance tests and body composition assessment by dual-energy x-ray absorptiometry were performed at baseline and wk 12. The primary study outcome was change in insulin sensitivity index. Results: Mean (± se) percentage fat body mass increased by 4.3 ± 1.3% from baseline to wk 12 (P =...
TL;DR: Significant concentrations of C-3 epimers of 25O HD(2) or 25OHD(3) are commonly found in infants, which can lead to overestimation of 25-OHD levels.
Abstract: Context: We have recently introduced liquid chromatography-tandem mass spectrometry (LC-MS/MS) for 25-hydroxyvitamin D2 (25OHD2) and 25OHD3 testing. During subsequent clinical use, we identified significantly elevated results in some infants. We hypothesized this might represent assay interference caused by C-3 epimers of 25OHD2 or 25OHD3. Objective: Our aims were to 1) determine the prevalence of C-3 epimers of 25OHD2 or 25OHD3 in human serum, and 2) identify the patient populations that might be affected. Study Design: We modified our LC-MS/MS method to allow detection of C-3 epimers. We retested specimens from four patient groups with the new method and an extracted RIA: 1) children less than 1 yr old, 2) children 1–18 yr old, 3) adults aged 20–87 yr with liver disease, and 4) adults aged 19–91 yr without liver disease. Results: In 172 children from group 1 with detectable 25OHD2 or 25OHD3, we identified C-3 epimers in 39 (22.7%). The epimers contributed 8.7–61.1% of the total 25-OHD. There was an inve...