The Journal of Clinical Endocrinology & Metabolism最新文献

{"title":"Low-Dose Aspirin and Sporadic Anovulation in the EAGeR Randomized Trial","authors":"Rose G. Radin, L. Sjaarda, N. Perkins, R. Silver, Zhen Chen, Laurie L. Lesher, N. Galai, J. Wactawski‐Wende, S. Mumford, E. Schisterman","doi":"10.1210/jc.2016-2095","DOIUrl":"https://doi.org/10.1210/jc.2016-2095","url":null,"abstract":"Context Among women with a single, recent pregnancy loss, daily preconception low-dose aspirin (LDA) increased the live birth rate with no effect on pregnancy loss. Ovulation is a potential mechanism underlying this effect. Objective We estimated the effect of LDA on the per-cycle risk of anovulation among eumenorrheic women. Design Multicenter, randomized, double-blind, placebo-controlled trial of daily LDA on reproductive outcomes. Preconception follow-up lasted 1 to 6 menstrual cycles (ClinicalTrials.gov, NCT00467363). Setting Four US medical centers during 2007 to 2011. Patients or Other Participants Healthy women (n = 1214), age 18 to 40, were attempting pregnancy, had regular menstrual cycles (21 to 42 days), and had a history of 1 to 2 documented pregnancy losses, ≤2 live births, and no infertility. All participants completed at least 1 menstrual cycle of follow-up; none withdrew due to adverse events. Intervention Aspirin (81 mg) daily for 1 to 6 menstrual cycles. Main Outcome Measure Per-cycle risk of anovulation, defined as the absence of both a positive spot-urine pregnancy test and a luteinizing hormone (LH) peak (2.5-fold increase in daily urinary LH). Hypothesis formulation preceded data collection. Results Among 4340 cycles, LDA was not associated with anovulation (LDA: 13.4%, placebo: 11.1%; risk ratio = 1.16, 95% confidence interval, 0.88 to 1.52). Results were similar among women with a single, recent loss. Conclusions Daily LDA had no effect on anovulation among women with a history of 1 to 2 pregnancy losses. LDA may affect fertility via other pathways, and these warrant further study.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"17 1","pages":"86–92"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84465948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulinlike Growth Factor Binding Protein-1 and Ghrelin Predict Health Outcomes Among Older Adults: Cardiovascular Health Study Cohort.","authors":"Robert C Kaplan, Garrett Strizich, Chino Aneke-Nash, Clara Dominguez-Islas, Petra Bužková, Howard Strickler, Thomas Rohan, Michael Pollak, Lewis Kuller, Jorge R Kizer, Anne Cappola, Christopher I Li, Bruce M Psaty, Anne Newman","doi":"10.1210/jc.2016-2779","DOIUrl":"10.1210/jc.2016-2779","url":null,"abstract":"<p><strong>Context: </strong>Multiple diseases may explain the association of the growth hormone/insulinlike growth factor-I (GH/IGF-I) axis with longevity.</p><p><strong>Objective: </strong>To relate circulating GH/IGF-I system protein levels with major health events.</p><p><strong>Design and setting: </strong>This is a cohort study set in 4 US communities.</p><p><strong>Participants: </strong>Adults (N = 2268) 65 years and older free of diabetes and cardiovascular disease.</p><p><strong>Measurements: </strong>We assessed insulinlike growth factor binding protein-1 (IGFBP-1) and ghrelin in fasting and 2-hour oral glucose tolerance test (OGTT) blood samples, as well as fasting IGF-I and IGFBP-3. Hazard ratios for mortality and a composite outcome for first incident myocardial infarction, stroke, heart failure, hip fracture, or death were adjusted for sociodemographic, behavioral, and physiological covariates.</p><p><strong>Results: </strong>During 13,930 person-years of follow-up, 48.1% of individuals sustained one or more components of the composite outcome and 31.8% died. Versus the lowest quartiles, the highest quartiles of fasting and 2-hour ghrelin were associated with 27% higher (95% confidence interval [CI]: 6%, 53%) and 39% higher (95% CI: 14%, 71%) risks of the composite outcome, respectively. The highest quartile of 2-hour IGFBP-1 was associated with 35% higher (95% CI: 1%, 52%) risk of the composite end point. Similarly, higher mortality was significantly associated with higher fasting and 2-hour ghrelin levels and with 2-hour IGFBP-1 level. When examined together, 2-hour post-OGTT levels of IGFBP-1 and ghrelin tended to predict outcomes better than fasting levels.</p><p><strong>Conclusions: </strong>Circulating IGFBP-1 and ghrelin measured during an OGTT predicted major health events and death in older adults, which may explain the influence of the GH/IGF-I axis on lifespan and health.</p>","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"40 1","pages":"267-278"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75457832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum 1,25-Dihydroxyvitamin D as a Biomarker of the Absence of Hypercalciuria in Postsurgical Hypoparathyroidism","authors":"L. García-Pascual, M. Barahona, V. Perea, R. Simó","doi":"10.1210/jc.2016-2987","DOIUrl":"https://doi.org/10.1210/jc.2016-2987","url":null,"abstract":"Context Hypercalciuria is an adverse event of postsurgical hypoparathyroidism treatment that can lead to renal complications. The collection of 24-hour urine to detect hypercalciuria is often considered unreliable. Objective The purpose of this study was to find useful predictive biomarkers of hypercalciuria in patients with permanent postsurgical hypoparathyroidism receiving treatment with oral calcium and calcitriol supplements. Design and Setting The investigation was designed as a prospective cross-sectional study. An outpatient hospital clinic served as the study setting. Patients Fifty-four consecutive observations were made of 34 stable outpatients with postsurgical hypoparathyroidism taking oral calcium and calcitriol supplements, and 17 adult controls without hypoparathyroidism. Intervention There were no interventions. Main Outcome Measure Hypercalciuria was defined as 24-hour urine calcium >300 mg. Results Patients without hypercalciuria (n = 21) vs those with hypercalciuria (n = 33) had lower levels of serum 1,25-dihydroxyvitamin D (33.5 ± 11.9 pg/mL vs 45.8 ± 9.5 pg/mL; P < 0.001), similar albumin-corrected serum calcium (8.3 ± 0.5 vs 8.6 ± 0.5 mg/dL; P = nonsignificant), and serum parathyroid hormone (12.5 ± 5.7 vs 10.7 ± 6.8 pg/mL; P = nonsignificant). Multiple linear regression analysis showed an independent relationship between 1,25-dihydroxyvitamin D and urinary calcium excretion (B = 6.2 ± 1.423; P < 0.001). A cutoff value of 33.5 pg/mL for serum 1,25-dihydroxyvitamin D to predict the absence of hypercalciuria had 100% sensitivity and 63.6% specificity, and the area under the receiver operating characteristic curve was 0.797. No patients with serum 1,25-dihydroxyvitamin D levels of <33.5 pg/mL presented with hypercalciuria, regardless of the level of albumin-corrected serum calcium. Conclusions Routine measurement of serum 1,25-dihydroxyvitamin D may be useful as a biomarker to predict the absence of hypercalciuria in patients with permanent postsurgical hypoparathyroidism who are receiving treatment with oral calcium and calcitriol supplements.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"4 1","pages":"259–266"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78499751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Testosterone, Dihydrotestosterone, Sex Hormone-Binding Globulin, and Incident Diabetes Among Older Men: The Cardiovascular Health Study.","authors":"Katherine E Joyce, Mary L Biggs, Luc Djoussé, Joachim H Ix, Jorge R Kizer, David S Siscovick, Molly M Shores, Alvin M Matsumoto, Kenneth J Mukamal","doi":"10.1210/jc.2016-2623","DOIUrl":"10.1210/jc.2016-2623","url":null,"abstract":"<p><strong>Context: </strong>Although sex hormone-binding globulin (SHBG) and testosterone (T) have been inversely associated with risk of diabetes, few studies have examined dihydrotestosterone (DHT), a more potent androgen than T, in older adults, whose glycemic pathophysiology differs from younger adults.</p><p><strong>Objective: </strong>To determine the associations of SHBG, T, and DHT with insulin resistance and incident diabetes in older adult men.</p><p><strong>Design: </strong>In a prospective cohort study, we evaluated baseline levels of SHBG, T, and DHT using liquid chromatography-tandem mass spectrometry among 852 men free of diabetes and cardiovascular disease in the Cardiovascular Health Study in 1994.</p><p><strong>Main outcome: </strong>Insulin resistance estimated by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and insulin sensitivity estimated by the Gutt index in 1996, and incident diabetes (n = 112) ascertained over a mean follow-up of 9.8 years.</p><p><strong>Results: </strong>In linear regression models adjusted for demographics, alcohol consumption, current smoking, body mass index, and other androgens, SHBG [HOMA-IR 0.30 units lower per doubling; 95% confidence interval (CI), 0.08 to 0.52; P = 0.01] and total DHT (HOMA-IR 0.18 units lower per doubling; 95% CI, 0.06 to 0.30; P = 0.01), but not free T (P = 0.33), were inversely associated with insulin resistance. In corresponding Cox proportional hazards models, total DHT was again inversely associated with risk of diabetes (adjusted hazard ratio per doubling, 0.69; 95% CI, 0.52 to 0.92; P = 0.01), but SHBG (hazard ratio, 1.09; 95% CI, 0.74 to 1.59; P = 0.66) and free T (hazard ratio, 1.15; 95% CI, 0.92 to 1.43; P = 0.23) were not.</p><p><strong>Conclusions: </strong>Among older men, higher levels of DHT were inversely associated with insulin resistance and risk of diabetes over the ensuing 10 years, whereas levels of T were not. Future studies are still needed to clarify the role of SHBG in risk of diabetes in this population.</p>","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"4 1","pages":"33-39"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74548644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Familial Multiplicity of Estrogen Insensitivity Associated With a Loss-of-Function ESR1 Mutation.","authors":"Valérie Bernard, Sakina Kherra, Bruno Francou, Jérôme Fagart, Say Viengchareun, Jérôme Guéchot, Asmahane Ladjouze, Anne Guiochon-Mantel, Kenneth S Korach, Nadine Binart, Marc Lombès, Sophie Christin-Maitre","doi":"10.1210/jc.2016-2749","DOIUrl":"10.1210/jc.2016-2749","url":null,"abstract":"<p><strong>Context: </strong>Estrogens influence many physiological processes in mammals, including reproduction. Estrogen peripheral actions are mainly mediated through estrogen receptors (ERs) α and β, encoded by ESR1 and ESR2 genes, respectively.</p><p><strong>Objective: </strong>The study's aim was to describe a family in which 3 members presented with estrogen insensitivity.</p><p><strong>Design and setting: </strong>Clinical evaluation and genetic and mutational analysis were performed in an academic medical center.</p><p><strong>Patients and interventions: </strong>An ESR1 mutation was identified in 2 sisters and 1 brother, originating from a consanguineous Algerian family, who did not enter puberty and presented with delayed bone maturation consistent with estrogen insensitivity. The 2 sisters had enlarged multicystic ovaries. Hormonal evaluation as well as genetic and mutational analysis were performed.</p><p><strong>Results: </strong>Hormonal evaluation revealed extremely high plasma 17β-estradiol (>50-fold normal range) associated with elevated gonadotropin levels (greater than threefold normal range), highly suggestive of estrogen resistance. The 3 affected patients carried a homozygous mutation of a highly conserved arginine 394 for which histidine was substituted through an autosomal recessive mode of transmission. Structural and functional analysis of the mutant ERα revealed strongly reduced transcriptional activity and the inability to securely anchor the activating hormone, estradiol, compared with wild-type ERα. A group of other potential ER activating ligands were tested, but none overcame the estrogen insensitivity in these patients.</p><p><strong>Conclusion: </strong>Description and analysis of this family of patients with mutant ERα provide additional clinical findings toward identification and characterization of what was previously thought to be a highly rare clinical condition.</p>","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"93 1","pages":"93-99"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83869688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Differences in Associations of Adiposity Measures and Insulin Resistance in US Hispanic/Latino Youth: The Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth).","authors":"Qibin Qi, Simin Hua, Krista M Perreira, Jianwen Cai, Linda Van Horn, Neil Schneiderman, Bharat Thyagarajan, Alan M Delamater, Robert C Kaplan, Carmen R Isasi","doi":"10.1210/jc.2016-2279","DOIUrl":"10.1210/jc.2016-2279","url":null,"abstract":"<p><strong>Context: </strong>US Hispanic/Latino youth are disproportionally affected by the obesity and diabetes.</p><p><strong>Objective: </strong>We examined associations of adiposity measures with insulin resistance (IR) and hyperglycemia and the influences of sex and pubertal development on these associations.</p><p><strong>Design, setting, and participants: </strong>We performed a cross-sectional analysis of 1223 8- to 16-year-old Hispanic/Latino youth from a community-based study in the United States (SOL Youth).</p><p><strong>Main outcome measures: </strong>We measured IR (≥75th percentile of sex-specific Homeostatic Model Assessment of Insulin Resistance) and hyperglycemia (fasting glucose ≥100 mg/dL or hemoglobin a1c ≥5.7%).</p><p><strong>Results: </strong>In boys, body mass index (BMI) showed the strongest association with IR [prevalence ratio (PR), 2.10; 95% confidence interval (CI), 1.87 to 2.36 per standard deviation], which was not statistically different compared with body fat percentage (%BF) (PR, 2.03; 95% CI, 1.81 to 2.29) and waist circumference (WC) (PR, 1.89; 95% CI, 1.67 to 2.13) but was significantly stronger compared with fat mass index (FMI) (PR, 1.79; 95% CI, 1.63 to 1.96), waist-to-hip ratio (WHR) (PR, 1.32; 95% CI, 1.21 to 1.44), and waist-to-height ratio (WHtR) (PR, 1.76; 95% CI, 1.54 to 2.01) (P for difference, <0.05). In girls, %BF (PR, 2.73; 95% CI, 2.34 to 3.20) showed a significantly stronger association with IR compared with BMI (PR, 1.48; 95% CI, 1.29 to 1.70), FMI (PR, 1.71; 95% CI, 1.49 to 1.95), WC (PR, 1.96; 95% CI, 1.70 to 2.27), WHR (PR, 1.95; 95% CI, 1.70 to 2.23), and WHtR (PR, 1.79; 95% CI, 1.53 to 2.09) (P for difference, <0.003). Associations between adiposity measures and IR were generally stronger among children in puberty versus those who had completed puberty, with significant interactions for WC and WHtR in boys and for BMI in girls (P for interaction, <0.01). Adiposity measures were modestly associated with hyperglycemia (PR, 1.14 to 1.25), with no interactions with sex or pubertal status.</p><p><strong>Conclusions: </strong>Sex and puberty may influence associations between adiposity measures and IR in US Hispanic/Latino youth. Multiple adiposity measures are needed to better assess IR risk between boys and girls according to pubertal status.</p>","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"27 1","pages":"185-194"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88772661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of LHX4 Mutations to Pituitary Deficits in a Cohort of 417 Unrelated Patients","authors":"Enzo Cohen, M. Maghnie, N. Collot, J. Léger, F. Dastot, M. Polak, S. Rose, P. Touraine, P. Duquesnoy, M. Tauber, B. Copin, A. Bertrand, F. Brioude, D. Larizza, T. Edouard, Laura G González Briceño, I. Netchine, I. Oliver-Petit, M. Sobrier, S. Amselem, M. Legendre","doi":"10.1210/jc.2016-3158","DOIUrl":"https://doi.org/10.1210/jc.2016-3158","url":null,"abstract":"Context LHX4 encodes a LIM-homeodomain transcription factor that is implicated in early pituitary development. In humans, only 13 heterozygous LHX4 mutations have been associated with congenital hypopituitarism. Objective The aims of this study were to evaluate the prevalence of LHX4 mutations in patients with hypopituitarism, to define the associated phenotypes, and to characterize the functional impact of the identified variants and the respective role of the 2 LIM domains of LHX4. Design and Patients We screened 417 unrelated patients with isolated growth hormone deficiency or combined pituitary hormone deficiency associated with ectopic posterior pituitary and/or sella turcica anomalies for LHX4 mutations (Sanger sequencing). In vitro studies were performed to assess the functional consequences of the identified variants. Results We identified 7 heterozygous variations, including p.(Tyr131*), p.(Arg48Thrfs*104), c.606+1G>T, p.Arg65Val, p.Thr163Pro, p.Arg221Gln, and p.Arg235Gln), that were associated with variable expressivity; 5 of the 7 were also associated with incomplete penetrance. The p.(Tyr131*), p.(Arg48Thrfs*104), p.Ala65Val, p.Thr163Pro, and p.Arg221Gln LHX4 variants are unable to transactivate the POU1F1 and GH promoters. As suggested by transactivation, subcellular localization, and protein-protein interaction studies, p.Arg235Gln is probably a rare polymorphism. Coimmunoprecipitation studies identified LHX3 as a potential protein partner of LHX4. As revealed by functional studies of LIM-defective recombinant LHX4 proteins, the LIM1 and LIM2 domains are not redundant. Conclusion This study, performed in the largest cohort of patients screened so far for LHX4 mutations, describes 6 disease-causing mutations that are responsible for congenital hypopituitarism. LHX4 mutations were found to be associated with variable expressivity, and most of them with incomplete penetrance; their contribution to pituitary deficits that are associated with an ectopic posterior pituitary and/or a sella turcica defect is ∼1.4% in the 417 probands tested.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"48 1","pages":"290–301"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79093831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of Functional Osteoprotegerin: More Than a Skeletal Problem","authors":"C. Grasemann, N. Unger, M. Hövel, D. Arweiler-Harbeck, R. Herrmann, Michael M. Schündeln, O. Müller, B. Schweiger, E. Lausch, T. Meissner, C. Kiewert, B. Hauffa, N. Shaw","doi":"10.1210/jc.2016-2905","DOIUrl":"https://doi.org/10.1210/jc.2016-2905","url":null,"abstract":"Introduction Juvenile Paget's disease (JPD), an ultra-rare, debilitating bone disease due to loss of functional osteoprotegerin (OPG), is caused by recessive mutations in TNFRFSF11B. A genotype-phenotype correlation spanning from mild to very severe forms is described. Aim This study aimed to describe the complexity of the human phenotype of OPG deficiency in more detail and to investigate heterozygous mutation carriers for clinical signs of JPD. Patients We investigated 3 children with JPD from families of Turkish, German, and Pakistani descent and 19 family members (14 heterozygous). Results A new disease-causing 4 bp-duplication in exon 1 was detected in the German patient, and a microdeletion including TNFRFSF11B in the Pakistani patient. Skeletal abnormalities in all affected children included bowing deformities and fractures, contractures, short stature and skull involvement. Complex malformation of the inner ear and vestibular structures (2 patients) resulted in early deafness. Patients were found to be growth hormone deficient (2), displayed nephrocalcinosis (1), and gross motor (3) and mental (1) retardation. Heterozygous family members displayed low OPG levels (12), elevated bone turnover markers (7), and osteopenia (6). Short stature (1), visual impairment (2), and hearing impairment (1) were also present. Conclusion Diminished OPG levels cause complex changes affecting multiple organ systems, including pituitary function, in children with JPD and may cause osteopenia in heterozygous family members. Diagnostic and therapeutic measures should aim to address the complex phenotype.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"2 1","pages":"210–219"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89959121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of 17OHPreg and DHEAS by LC-MS/MS: Impact of Age, Sex, Pubertal Stage, and BMI on the &Dgr;5 Steroid Pathway","authors":"A. Kulle, T. Reinehr, G. Šimić-Schleicher, N. Hornig, P. Holterhus","doi":"10.1210/jc.2016-2849","DOIUrl":"https://doi.org/10.1210/jc.2016-2849","url":null,"abstract":"Background Dehydroepiandrosterone sulfate (DHEAS) and 17-hydroxypregnenolone (17OHPreg) are important for understanding the Δ5 pathway (e.g., in adrenarche and obesity). Although mass spectrometry has become the state-of-the-art method for quantifying steroids, there are few comprehensive age-, sex-, and pubertal stage-specific reference ranges for children. Aims To develop a sensitive and reliable ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for simultaneous quantification of DHEAS and 17OHPreg and to establish entire age-, sex- and pubertal stage-specific reference ranges in children. Methods A total of 684 children, 453 (243 female, 210 male) with normal body mass index (BMI; <90th) and 231 (132 female, 99 male) obese subjects (>97th), were categorized into 11 age groups, and age- and Tanner stage (PH)-specific reference ranges were determined. Results The limit of detection was 0.05 nmol/L for 17OHPreg and 0.5 nmol/L for DHEAS. Levels of both steroids declined after the neonatal period. Comparisons with RIA assays (Siemens, Munich, Germany) (DHEAS) and an in-house kit (17OHPreg) revealed 0.95 and 0.93, respectively, as coefficients of determination. Although DHEAS-generally higher in boys-increased continuously starting at 3 to 6 years, 17OHPreg remained largely constant. In obese patients, both were significantly elevated, also in part after alignment to Tanner stages (PH). Conclusions UPLC-MS/MS is sensitive and reliable for quantifying DHEAS and 17OHPreg. Our data support differential maturation of CYP17 during adrenarche with successively increasing 17,20-lyase activity but largely constant 17α-hydroxylation activity. Endocrine interpretation of 17OHPreg and DHEAS must consider differential patterns for age, sex, pubertal stage, and BMI.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"12 1","pages":"232–241"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90509508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Localization of Insulinoma Using 68Ga-DOTATATE PET/CT Scan","authors":"P. Nockel, Bruna Babic, C. Millo, P. Herscovitch, Dhaval Patel, N. Nilubol, S. Sadowski, Craig S. Cochran, P. Gorden, E. Kebebew","doi":"10.1210/jc.2016-3445","DOIUrl":"https://doi.org/10.1210/jc.2016-3445","url":null,"abstract":"Context Reliable localization of insulinoma is critical for successful treatment. Objective This study compared the accuracy of 68Gallium DOTA-(Tyr3)-octreotate (Ga-DOTATATE) positron emission tomography (PET)/computed tomography (CT) to anatomic imaging modalities, selective arterial secretagogue injection (SASI), and intraoperative ultrasound (IO ultrasound) and palpation for localizing insulinoma in patients who were biochemically cured. Design, Setting, and Patients We conducted a retrospective analysis of 31 patients who had an insulinoma. The results of CT, magnetic resonance imaging (MRI), ultrasound, IO ultrasound, 68Ga-DOTATATE PET/CT, SASI, and operative findings were analyzed. Intervention, Main Outcome Measures, and Results The insulinomas were correctly localized in 17 out of 31 (55%) patients by CT, in 17 out of 28 (61%) by MRI, in 6 out of 28 (21%) by ultrasound, and in 9 out of 10 (90%) by 68Ga-DOTATATE. In 29 of 31 patients (93.5%) who had IO ultrasound, an insulinoma was successfully localized. Thirty patients underwent SASI, and the insulinoma was regionalized in 28 out of 30 patients (93%). In 19 out of 23 patients (83%), manual palpation identified insulinoma. In patients who had all 4 noninvasive imaging studies, CT was concordant with 68Ga-DOTATATE in 6 out of 9 patients (67%), MRI in 8 out of 9 (78%), ultrasound in 0 out of 9; the lesion was only seen by 68Ga-DOTATATE in 1 out of 9 (11%). Conclusions 68Ga-DOTATATE PET/CT identifies most insulinomas and may be considered as an adjunct imaging study when all imaging studies are negative and when a minimally invasive surgical approach is planned.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"26 1","pages":"195–199"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81092364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}