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Background: Total 25-OH-vitamin D (25(OH)D) levels are decreased in patients with obesity, but few data exist regarding free-vitamin D3 (f25(OH)D3) concentrations. We aimed to evaluate the effect of bariatric surgery on 25(OH)D and f25(OH)D3 in a cohort of patients with morbid obesity., Methods: Twenty-four patients submitted to sleeve gastrectomy (SG) (mean age 48 years, body mass index (BMI) 48.16±10.73k/m 2 ) were evaluated before and 1 year after surgery. Anthropometric data, parathormone (PTH), calcium, alkaline phosphatase, 25(OH)D, and f25(OH)D3 were recorded., Results: 25(OH)D and f25(OH)D3 correlated well before and after SG. Baseline determinations did not correlate with BMI, but they inversely correlated with BMI 1 year after surgery (r s =-0.46, p=0.02 and r s =-0.60, p=0.002, respectively). Post-surgery % total body weight loss (%TBWL) was 27.4±13.8 %; f25(OH)D3 concentrations increased significantly (5.28±2.29 pg/mL vs 6.64±2.25 pg/mL; p=0.03), whereas 25(OH)D did not change. Patients who achieved a BMI <35 kg/m 2 1 year after surgery had significantly higher concentrations of f25(OH)D3 (7.9±1 pg/mL vs 4.8±1.1, p<0.001) and 25(OH)D (30.9±9.4 ng/mL vs 22.3±13.4; p=0.03) compared to those who remained with BMI >35 kg/m 2 ., Conclusion: There is a significant inverse relationship between BMI and both f25(OH)D3 and 25(OH)D 1 year after surgery. Only f25(OH)D3 concentrations increased 1 year after surgery, which could be explained by a greater f25(OH)D3 sequestration before SG in the adipose tissue, potentially due to the more liposoluble nature of f25(OH)D3 than the protein-bound form 25(OH)D., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The development of female or male sex characteristics occurs during fetal life, when the genetic, gonadal, and internal and external genital sex is determined (female or male). Any discordance among sex determination and differentiation stages results in differences/disorders of sex development (DSD), which are classified based on the sex chromosomes found on the karyotype., Content: This chapter addresses the physiological mechanisms that determine the development of female or male sex characteristics during fetal life, provides a general classification of DSD, and offers guidance for clinical, biochemical, and genetic diagnosis, which must be established by a multidisciplinary team. Biochemical studies should include general biochemistry, steroid and peptide hormone testing either at baseline or by stimulation testing. The genetic study should start with the determination of the karyotype, followed by a molecular study of the 46,XX or 46,XY karyotypes for the identification of candidate genes., Summary: 46,XX DSD include an abnormal gonadal development (dysgenesis, ovotestes, or testes), an androgen excess (the most frequent) of fetal, fetoplacental, or maternal origin and an abnormal development of the internal genitalia. Biochemical and genetic markers are specific for each group., Outlook: Diagnosis of DSD requires the involvement of a multidisciplinary team coordinated by a clinician, including a service of biochemistry, clinical, and molecular genetic testing, radiology and imaging, and a service of pathological anatomy., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2021 Maria Luisa Granada and Laura Audí, published by De Gruyter, Berlin/Boston.)

Objectives: 46,XY differences/disorders of sex development (DSD) involve an abnormal gonadal and/or genital (external and/or internal) development caused by lack or incomplete intrauterine virilization, with or without the presence of Müllerian ducts remnants., Content: Useful biochemical markers for differential diagnosis of 46,XY DSD include hypothalamic-pituitary-gonadal hormones such as luteinizing and follicle-stimulating hormones (LH and FSH; in baseline or after LHRH stimulation conditions), the anti-Müllerian hormone (AMH), inhibin B, insulin-like 3 (INSL3), adrenal and gonadal steroid hormones (including cortisol, aldosterone, testosterone and their precursors, dihydrotestosterone and estradiol) and the pituitary ACTH hormone. Steroid hormones are measured at baseline or after stimulation with ACTH (adrenal hormones) and/or with HCG (gonadal hormones)., Summary: Different patterns of hormone profiles depend on the etiology and the severity of the underlying disorder and the age of the patient at diagnosis. Molecular diagnosis includes detection of gene dosage or copy number variations, analysis of candidate genes or high-throughput DNA sequencing of panels of candidate genes or the whole exome or genome., Outlook: Differential diagnosis of 46,XX or 46,XY DSD requires a multidisciplinary approach, including patient history and clinical, morphological, imaging, biochemical and genetic data. We propose a diagnostic algorithm suitable for a newborn with DSD that focuses mainly on biochemical and genetic data., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2021 Maria Luisa Granada and Laura Audí, published by De Gruyter, Berlin/Boston.)

Background: Recent guidelines recommend establishing a local reference interval (RI) for thyroid function. We aimed to establish trimester-specific RIs for thyrotropin (TSH) and free thyroxine (FT4) in a cohort of healthy pregnant women in Catalonia (Spain)., Methods: A prospective observational study was conducted with 332 healthy pregnant women, from the first trimester (1T) to delivery. TSH was measured using an Architect ® immunoassay (Abbott) and FT4 by two immunoassays, Architect ® (Abbott) and Cobas ® (Roche), in the three trimesters. FT4 was also measured by liquid chromatography mass spectrometry (LC/MS/MS) in the 1T., Results: TSH (µUI/mL) increased throughout pregnancy (1T: 0.03-3.78; 2T: 0.51-3.53; 3T: 0.50-4.32; p < 0.0001) and FT4 (pmol/L) progressively decreased (Architect ® 1T: 10.42-15.96; 2T: 8.37-12.74; 3T: 8.24-12.49; p < 0.0001; and Cobas ® : 1T: 11.46-19.05; 2T: 9.65-14.67; 3T: 8.88-14.54; p < 0.0067). The FT4 RI during 1T determined LC/MS/MS was 8.75-18.27. Despite the 1T FT4 results measured by LC/MS/MS and with the two immunoassays being significantly correlated, the results obtained by the three methods were found to be non-interchangeable., Conclusions: We established trimester-specific RIs for TSH and for FT4 with immunoassays in our population. We also validated the 1T FT4 using LC/MS/MS to confirm the results of FT4 lower than the 2.5th percentile or higher than the 97.5th percentile.

Objetivos: El desarrollo sexual anómalo o diferente (DSD) con cariotipo 46,XY incluye anomalías en el desarrollo gonadal y/o genital (externo y/o interno)., Contenido: Los marcadores bioquímicos útiles para el diagnóstico diferencial de los DSD con cariotipo 46,XY incluyen las hormonas del eje hipotálamo-hipófiso gonadal como son las gonadotropinas LH y FSH (en condiciones basales o tras la estimulación con LHRH), la hormona anti-Mülleriana, la inhibina B, el factor insulinoide tipo 3 y las hormonas esteroideas de origen suprarrenal (se incluirá la hormona hipofisaria ACTH) y testicular (cortisol, aldosterona y sus precursores, testosterona y sus precursores, dihidrotestosterona y estradiol). Las hormonas esteroideas se analizarán en condiciones basales o tras la estimulación con ACTH (hormonas adrenales) y/o con HCG (hormonas testiculares). Los patrones de variación de las distintas hormonas dependerán de la causa y la edad de cada paciente. El diagnóstico molecular debe incluir el análisis de un gen candidato, un panel de genes o el análisis de un exoma completo., Perspectivas: El diagnóstico diferencial de los DSD con cariotipos 46,XX ó 46,XY debe ser multidisciplinar, incluyendo los antecedentes clínicos, morfológicos, de imagen, bioquímicos y genéticos. Se han elaborado numerosos algoritmos diagnósticos., (© 2021 Maria Luisa Granada and Laura Audí, published by De Gruyter, Berlin/Boston.)

Objective: To investigate whether variations in thyroglobulin autoantibodies (TgAb) are related to the recurrence or persistence of differentiated thyroid carcinoma (DTC) and may therefore be useful as surrogate tumor markers. Design and Methods . We retrospectively studied 98 subjects (83 women, 47 ± 15 years old) from an initial cohort of 1017 patients treated for DTC in five hospitals, with positive TgAb at any time during the follow-up. Patients presented five different patterns of evolution of serum TgAb concentrations: (1) stable positive TgAb, (2) de novo appearance, (3) an increase of more than 50%, (4) TgAb levels from positive to negative, and (5) a decrease of more than 50%., Results: In the group of 11 patients with stable TgAb, four cases presented persistence of the disease with structural incomplete response. In the group of 22 patients with sustained increasing trend rising more than 50% or de novo detectable TgAb levels, three patients were diagnosed with structural incomplete response. There was no evidence of recurrence or persistence of the disease in any of the 65 patients who showed a significant decrease in ( n  = 35) or disappearance of ( n  = 30) TgAb., Conclusions: Our results suggest that not only the appearance of a significant increase in TgAb but also stable concentrations of TgAb should be regarded as a sufficient risk condition for an active search for recurrent or persistent disease. Conversely, a significant decrease in TgAb levels can represent a good prognostic sign., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2020 Jordi L. Reverter et al.)

Background & Aims: Peripheral white blood cells (PWBC) may allow for the development of obesity biomarkers. We aimed to investigate the existence of gene expression and DNA methylation changes in PWBC after a very low calorie diet (VLCD) followed by a laparoscopic sleeve gastrectomy (LSG), and its correlation with surgical outcomes., Methods: From July 2013 to June 2014, 35 consecutive bariatric patients and 33 healthy lean volunteers were recruited. Molecular data was obtained once on the control group and at 3 different times on the LSG group: 1) at baseline; 2) after 2 weeks of VLCD, right before LSG; and 3) 6 months after LSG. The expression of 12 genes in PWBC was analyzed by quantitative real-time polymerase chain reaction: ghrelin (GHRL), visfatin (NAMPT), insulin receptor substrate 1 (IRS1), fat mass and obesity-related gene (FTO), leptin (LEP), peroxisome proliferator-activated receptor gamma (PPARG), adiponectin (ADIPOQ), fatty acid synthase (FASN), melanocortin 4 receptor (MC4R), fas cell surface death receptor (FAS), tumor necrosis factor alpha (TNF) and chemokine (C-C motif) ligand 2 (CCL2). Moreover, DNA methylation of GHRL, NAMPT and FAS promoters was analyzed in PWBC by bisulfite pyrosequencing., Results: Seven genes (GHRL, NAMPT, IRS1, FTO, FAS, TNF and CCL2) had detectable expression in PWBC. FTO expression at baseline was lower in patients than in controls (p = 0.042), equalizing after LSG. In patients, FAS expression decreased after VLCD (p = 0.01) and stayed low after LSG (p = 0.015). Also, CCL2 expression decreased 50% after LSG compared to pre-surgical levels (p = 0.016). All studied CpG sites in the GHRL gene promoter followed a consistent pattern of DNA methylation/demethylation. No direct correlation between these molecular changes and surgical outcomes was found at 1-year follow-up., Conclusions: FTO expression increased and FAS and CCL2 expression decreased in PWBC after LSG. Molecular changes did not correlate with surgical outcomes., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Carballeira, E, Morales, J, Fukuda, DH, Granada, ML, Carratalá-Deval, V, López Díaz de Durana, A, and Stout, JR. Intermittent cooling during Judo training in a warm/humid environment reduces autonomic and hormonal impact. J Strength Cond Res 33(8): 2241-2250, 2019-The purpose of this study was to identify the effects of superficial cooling on physiological responses while training in a warm, humid environment during an international Judo training camp. Sixteen judokas (8 women and 8 men) participated in the experiment. Four high-level women and 4 men were randomly assigned to wear a cooling vest (vest group [VG]) during the recovery periods within a training session (i.e., 8 bouts of 5-minute fighting with 5-minute rest) and up to 10 minutes after the session, whereas the remaining athletes in the control group (CG) trained without the use of any cooling aids. No differences between groups were reported in well-being before the session or in perceived fatigue after the session. The temperature was increased after the training session (p = 0.02) without significant differences between groups; however, CG demonstrated a moderate effect size (ES = 0.95, 90% confidence interval [CI] = 0.09-1.82; probability of superiority [PS] = 74.9%) in contrast to the small effect for VG (ES = 0.28, 90% CI = -0.55 to 1.11; PS = 57.9%). There were time × group interactions for heart rate variability (lnRMSSD) (p = 0.006; VG vs. CG, PS = 79.0%) and the dehydroepiandrosterone-cortisol ratio (DHEA/C ratio) (p = 0.04; VG vs. CG, PS = 99.9%). Vest group preserved the cardiac autonomic control (p > = 0.05; ES = -0.06, 90% CI = -0.88 to 0.76; PS = 51.7%) compared with the large decrement of CG (p < 0.05; ES = -1.18, 90% CI = -2.07 to -0.29; PS = 74.9%). Furthermore, VG showed an increase of DHEA/C (p = 0.002) from presession to postsession based on a moderate decrease of cortisol (p > = 0.05; ES = -0.67, 90% CI = -1.52 to 0.17; PS = 68.2%) with a concomitant small increase of DHEA (p > = 0.05; ES = 0.46, 90% CI = -0.38 to 1.29; PS = 62.7%). Conversely, the CG showed a moderate effect for increased DHEA and a small effect for increased cortisol after training. No significant interactions or main effects were shown for isometric handgrip values. Cooling vests diminished the cardiovascular strain and hormonal impact of the Judo training session in high-level athletes and may be considered for recovery purposes during exercise in warm/humid environments.

Acromegaly is a rare disease caused by excess growth hormone (GH) secretion leading to an insulin-like growth factor-1 (IGF-I) which is the major mediator of GH action. Biochemical diagnosis of GH excess is accomplished by the combined measurement of baseline serum IGF-I concentration and the response of GH on an oral glucose tolerance test (OGTT). Several drawbacks regarding the interpretation of biochemical tests that include measurement of GH have been widely described in the literature, including different protocols for obtaining serum samples, great differences in the results obtained by different immunoassays, different cut-off points used to differentiate the normal status of the hypersecretion of GH. Clinical guidelines related to the diagnosis and management of patients with acromegaly state that "normal" IGF-I concentrations, (within an established age- and sex- reference range), excludes the diagnosis of active acromegaly, and mean disease control in patients who have received treatment. But many factors may exert influence over IGF-I measurement or interpretation and limit its value as a biological marker of disease activity. Major drawbacks of IGF-I measurements derive both from its own physiology, to the divergences in results obtained from different biochemical methods used for their quantification, to the heterogeneous ways of expressing the results obtained and to the lack of uniformity of the cut-offs to define treatment effectiveness. All these issues make it difficult to compare the results obtained by different authors. We will focus on the issues regarding the measurement and interpretation of IGF-I concentrations in the management of acromegaly patients.

Background: vitamin D deficiency in children is still a global health problem. Measuring free 25-hydroxyvitamin D concentrations could provide a better estimate of the vitamin D status than total 25-hydroxyvitamin D (25(OH)D) levels., Objective: To assess the relationship between measured free vitamin D (m-f25(OH)D) and calculated free 25(OH)D (c-f25(OH)D), total 25(OH)D, intact parathyroid hormone (iPTH) and other markers of phosphocalcic metabolism. To establish serum m-f25(OH)D concentrations corresponding to a total 25(OH)D > 50 nmol/L which is accepted as vitamin D-sufficiency status in children., Design: Prospective cohort study., Setting: January and February 2017 in a Mediterranean population., Patients: healthy children., Measurements: m-f25(OH)D and vitamin D binding protein (VDBP) by ELISA. Free 25(OH)D was calculated using the formula described by Bikle., Results: m-f25(OH)D directly correlated with total 25(OH)D (r:0.804,p < .001), serum calcium (r:0.26,p:0.035), and c-f25(OH)D (r:0.553,p:0.016); and inversely with iPTH (r:-0.374, p:0.002), alkaline phosphatase (r:-0.28, p:0.026), and age (r:-0.289, p:0.018). Total 25(OH)D correlated with the same parameters as m-f25(OH)D except for serum calcium. However, c-f25(OH)D correlated only with total 25(OH)D and VDBP, both included in the calculation formula. Multiple regression analysis showed that m-f25(OH)D variations were independently explained by calcium (β:0.156, p:0.026) and total 25(OH)D (β:0.043, p < .001). The optimal m-f25(OH)D cut-off for discriminating between insufficient and sufficient total 25(OH)D was >9.8 pmol/L (Area Under Curve (AUC): 0.897 (95% confidence interval (CI): (0.798-0.958); p < .001; sensitivity:72.7% (95%CI: 49.8-89.3); specificity: 95.5% (95%CI: 84.5-99.4))., Conclusions: Directly measured free vitamin D correlated better with markers of phosphocalcic metabolism than total 25(OH)D and c-f25(OH)D in a population of healthy children., (Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Scientific knowledge to understand the biological basis of sex development was prompted by the observation of variants different from the 2 most frequent body types, and this became one of the fields first studied by modern pediatric endocrinology. The clinical observation was supported by professionals working in different areas of laboratory sciences which led to the description of adrenal and gonadal steroidogenesis, the enzymes involved, and the different deficiencies. Steroid hormone measurements evolved from colorimetry to radioimmunoassay (RIA) and automated immunoassays, although gas and liquid chromatography coupled to mass spectrometry are now the gold standard techniques for steroid measurements. Peptide hormones and growth factors were purified, and their measurement evolved from RIA to automated immunoassays. Hormone action mechanisms were described, and their specific receptors were characterized and assayed in experimental materials and in patient tissues and cell cultures. The discovery of the genetic basis for variant sex developments began with the description of the sex chromosomes. Molecular technology allowed cloning of genes coding for the different proteins involved in sex determination and development. Experimental animal models aided in verifying the roles of proteins and also suggested new genes to be investigated. New candidate genes continue to be described based on experimental models and on next-generation sequencing of patient DNAs., (© 2017 S. Karger AG, Basel.)

Background: Nutritional deficiencies are common after bariatric surgery, but data are scarce after sleeve gastrectomy (SG) at long term., Methods: We performed a prospective nutritional status evaluation before and at 2 and 5 years after SG in morbid obese patients receiving mulvitamin and mineral supplementation at a Spanish university hospital. One hundred seventy-six patients (49.3 ± 9.1 years and 46.7 ± 7.4 kg/m 2 ) were evaluated; 51 of them were followed during 5 years. Anthropometric, compliance supplementation intake, and micronutrient evaluation were performed., Results: Baseline concentrations were below normal values for 25(OH) vitamin D (73%), folic acid (16.5%), cobalamin (6.9%), pyridoxine (12%), thiamine (3.4%), and copper (0.5%). Anemia was found in 23%. In 49% of the subjects, at least one micronutrient deficiency was found at 2 years after SG. Vitamin D deficiency persisted at 2 and 5 years higher than 30% of patients. Frequencies of deficiencies for folic acid, B12, B6, and B1 vitamins decreased significantly after 2 years with normalization at 5 years. Copper deficiency increased between 1 and 2 years and it persisted at 5 years after SG. Vitamin supplementation compliance decreased progressively from the first year after surgery (94.8 to 81% at 2 years and to 53% 5 years after surgery)., Conclusions: Vitamin D deficiency is the most prevalent long-term nutritional deficiency after SG. About half of patients show some micronutrient deficiency at medium long term, despite supplementation. A proactive follow-up is required to ensure a personalized and adequate supplementation in all surgically treated obese patients including those in which SG has been performed.

Background: Chronic use of proton pump inhibitors (PPIs) leads to increases in gastrin and pepsinogen-I serum concentrations., Aim: To asses if chronic treatment with PPIs has an effect on serum gastrin and pepsinogen-I concentrations for the diagnosis of pernicious anaemia (PA)., Materials and Methods: Serum gastrin and pepsinogen-I were measured in 38 patients with PA and 74 without PA (controls); 17/38 PA patients and 36/74 controls were treated with PPIs. Receiver Operating Curves (ROC) were used to compare diagnostic accuracy of gastrin and pepsinogen-I for PA in patients under chronic treatment with PPIs and in untreated patients., Results: PPI treatment increased pepsinogen-I in patients and in controls, while gastrin increased only in controls. In untreated patients, a pepsinogen-I <8.3ng/mL had 95.2% sensitivity and 100% specificity, whereas a gastrin >115pg/mL had 100% sensitivity and 92.11% specificity for PA diagnosis. In PPI-treated patients, a pepsinogen I<24.1ng/mL had a lower sensitivity (82.4%) but retained 100% specificity, however the best cut-off point for gastrin, 610pg/mL, had a very low sensitivity (58%)., Conclusions: PPI chronic treatment decreased the diagnostic accuracy for the studied biomarkers, particularly of gastrin. In PPI-treated patients, serum pepsinogen-I concentrations >24.1ng/mL allowed rejecting a PA diagnosis with 100% specificity., (Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Context: Cushing's syndrome (CS) is challenging to diagnose. Increased prevalence of CS in specific patient populations has been reported, but routine screening for CS remains questionable. To decrease the diagnostic delay and improve disease outcomes, simple new screening methods for CS in at-risk populations are needed., Objective: To develop and validate a simple scoring system to predict CS based on clinical signs and an easy-to-use biochemical test., Design: Observational, prospective, multicenter., Setting: Referral hospital., Patients: A cohort of 353 patients attending endocrinology units for outpatient visits., Interventions: All patients were evaluated with late-night salivary cortisol (LNSC) and a low-dose dexamethasone suppression test for CS., Main Outcome Measures: Diagnosis or exclusion of CS., Results: Twenty-six cases of CS were diagnosed in the cohort. A risk scoring system was developed by logistic regression analysis, and cutoff values were derived from a receiver operating characteristic curve. This risk score included clinical signs and symptoms (muscular atrophy, osteoporosis, and dorsocervical fat pad) and LNSC levels. The estimated area under the receiver operating characteristic curve was 0.93, with a sensitivity of 96.2% and specificity of 82.9%., Conclusions: We developed a risk score to predict CS in an at-risk population. This score may help to identify at-risk patients in non-endocrinological settings such as primary care, but external validation is warranted.

Objectives: Primary hyperaldosteronism (PHA) is one of the most common endocrine forms of secondary hypertension. Among the most used confirmatory tests for PHA is urinary aldosterone determination after oral sodium loading test. The primary aim of our study was to investigate if sodium concentrations interfere with urinary aldosterone in an automated competitive immunoassay (Liaison®) as well as to verify the manufacturer's specifications., Design and Methods: 24-hr urine samples were collected and stored frozen until assayed. Two pools at low and high aldosterone concentrations were prepared. Verification of performance for precision was tested according to Clinical and Laboratory Standards Institute (CLSI) document EP15-A2 and interference with increasing concentrations of NaCl according to CLSI EP7-A2., Results: The assay met the quality specifications according to optimal biological variation. Our results show that sodium concentrations up to 200mmol/L do not interfere on urinary aldosterone quantification, but sodium concentrations above 486mmol/L negatively interfere with the test., Conclusions: The Liaison® automated method is useful for aldosterone determination in the PHA confirmatory test, but interferences with NaCl may occur. It is therefore recommended to determine urinary NaCl before measuring urinary aldosterone to avoid falsely low results., (Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: In children with growth disorders, mean final height is associated to poor adherence to Growth Hormone therapy. The primary goal of this study is to identify patients who do not adhere to GH therapy and determine the influence of adherence in response to the treatment. The role of serum IGF-I and influence of socio-economic factors on the therapeutic adherence will also be evaluated., Methods: 158 children under treatment with rhGH were included in the study. Age, gender, etiology, Tanner stage, duration of treatment, growth rate, IGF-I serum values, daily dose, and annual rhGH dose data were collected. Adherence to therapy was defined as moderate-to-poor when the patient had taken less than 92% of the prescribed medication. A subgroup of 106 patients completed a questionnaire to assess social and environmental effects., Results: Moderate-to-poor adherence to rhGH treatment was determined in 33.5% of study patients. A decrease in adherence was associated to treatment duration (p=0.001). A significant correlation was determined between adherence and height velocity (p=0.002) and IGF-I (p<0.0001) levels. Adherence rates were associated to the mother's educational level (p=0.007)., Conclusion: Poor adherence to GH therapy was observed in one-third of study patients, resulting in suboptimal growth. IGF-I levels can be helpful to identify patients with poor adherence to GH medication. Physicians should pay special attention to certain characteristics of the patient and their environment, and encourage desirable therapeutic compliance., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background and Objective: The cause of the anemia in anorexia nervosa (AN) has not been fully ascertained. Ferritin, folate and cobalamin values are usually within normal ranges. Anemia does not have a relationship with bone marrow changes and erythropoietin (EPO) levels have not been investigated. The objective of this study was to evaluate the EPO response in a small group of AN patients., Patients and Methods: EPO levels were measured in serum samples of 41 female AN patients (11 with anemia, and 30 with normal blood cell count). The adequacy of EPO response was assessed by comparing the increase observed in a group of normal weight patients with anemia., Results: EPO concentrations in anemic AN patients were higher than in non-anemic: 20.63mU/mL (4.04-28.46) vs 8.7mU/mL (3.9-20.93), P=.0088, but the increase in EPO was lower than expected (27.85mU/mL [17.7-118.9]), P=.014. BMI and the difference between actual and expected EPO were inversely correlated., Conclusions: Inadequate EPO response may partly explain anemia in AN, but further studies are necessary., (Copyright © 2015 Elsevier España, S.L.U. All rights reserved.)

Background: Metabolic syndrome (MetS) has been associated with higher resistance to clot lysis at 24 hours after tissue plasminogen activator (tPA) administration in patients with acute ischemic stroke. We aimed to test this hypothesis at earlier time points, when neurointerventional rescue procedures may still be indicated to achieve arterial recanalization., Methods: This is a prospective and observational study in consecutive stroke patients with MCA occlusion treated with IV tPA. MetS was diagnosed following the unified criteria of the last Joint Interim Statement 2009 participating several major organizations. The primary outcome variable was resistance to thrombolysis, defined as the absence of complete middle cerebral artery recanalization 2 hours after tPA bolus assessed by transcranial color-coded duplex or when rescue mechanical thrombectomy after IV tPA was required. Secondary outcome variables were dramatic neurological improvement (decrease in ≥10 points, or a National Institutes of Health Stroke Scale [NIHSS] score of 0-1 at 24 hours), symptomatic intracerebral hemorrhage following European-Australasian Acute Stroke Study II criteria, infarct volume at 24 hours (calculated by using the formula for irregular volumes, ABC/2), and good outcome (modified Rankin Scale score < 3) at 3 months., Results: A total of 234 patients (median baseline NIHSS score 16 [10-20]) were included and 146 (62.4%) fulfilled MetS criteria. After multivariate analysis, MetS emerged as an independent predictor of resistance to thrombolysis (odds ratio = 2.2 [1.3-4.2], P = .01) and absence of dramatic neurological improvement (odds ratio = .5 [.28-.97], P = .04). In addition, MetS conferred poorer functional outcome, higher symptomatic intracerebral hemorrhage rate, and increased infarct volume, although these associations disappeared after adjustment for covariates., Conclusions: MetS predicts patients with middle cerebral artery occlusion refractory to early clot dissolution after IV tPA. This finding may help in acute clinical decision-making., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: The glycoprotein YKL-40 is a new marker of early inflammation and endothelial dysfunction. Adiponectin is a collagen-like protein with anti-atherogenic and anti-inflammatory effects. Increased concentrations of both markers have been reported in patients with type 1 diabetes (T1D)., Aim: To assess the possible role of YKL-40 and adiponectin as a marker of subclinical cardiovascular disease in asymptomatic patients with type 1 diabetes with no history of ischemic or macrovascular heart disease and its relationship with other classic inflammatory biomarkers., Methods: Concentrations of YKL-40, adiponectin, IL-6, IL-1β, TNF-α, hsCRP and homocysteine were determined in 150 T1D patients (58% men, age: 38.6 ± 8.1 years, 20.4 ± 8.1 years of evolution, BMI: 25.1 ± 3.6 kg/m(2); HbA1c 8.1 ± 2.3%, 4% smokers; 26% retinopathy, microalbuminuria 9%) and 50 controls age, sex and smoke condition matched. Subclinical atherosclerosis was assessed by a carotid ultrasonography and a computed tomography for evaluation of calcium artery calcification score (CACS)., Results: 82% of T1D patients and 92% of controls had a calcium score of 0. T1D patients showed a significantly higher mean common carotid artery intima media thickness (CIMT) compared to controls (0.55 ± 0.14 vs 0.48 ± 0.14 mm, p = 0.01). Concentrations of YKL-40 and adiponectin were significantly higher in T1D [42.6 (10.4-195.0) vs ±28.7 (11.0-51.2) ng/ml, p = 0.001 and 15.8 ± 9.1 vs. 12.4 ± 5.3 mg/ml, p = 0.008], with no differences when compared to other inflammatory parameters. In T1D patients no association was found between YKL-40 and adiponectin and screening test for subclinical arterial disease (neither CACS nor CIMT). A positive correlation was found between levels of YKL-40 and age and duration of disease (r = 0.28, p = 0.003; r = 0.35, p = 0.001). There were no differences in the YKL-40 in relation to the presence or absence of retinopathy or nephropathy. Levels of adiponectin were higher in patients with nephropathy (21.84 ± 8.15 vs. 14.88 ± 8.27 mg/ml, p = 0.008)., Conclusions: Type 1 diabetes patients from a Mediterranean area with a longer disease evolution, although a lower degree of subclinical disease, showed significatively higher concentrations of YKL-40 and adiponectin compared with the controls. Therefore, we conclude that YKL-40 and adiponectin are early inflammatory markers in diabetic subjects even in the presence of a low atherosclerotic background.

Aims: Several studies linked vitamin D deficiency with coronary artery disease (CAD). The aim of this study was to evaluate the relationship between the concentrations of 25-hydroxyvitamin D (25OHD) and the presence of early atherosclerosis in asymptomatic Type 1 Diabetes (T1D) patients with no previous history of ischemic heart disease., Methods: One hundred and forty-five patients with T1D (age 37.8 ± 8 years, 57 % male, all Caucasian, disease duration 20.6 ± 8.3 years, HbA1c 7.6 ± 1.4 % (60.2 ± 11.1 mmol/mol), body mass index (BMI) 25.2 ± 3.5 kg/m2, 52.4 % smokers, 23 % retinopathy, 10 % nephropathy) and 48 controls matched for age, sex, BMI and smoking habit were studied. 25OHD deficiency was defined for values ≤20 ng/mL. A sun exposure questionnaire, carotid ultrasonography to determine carotid intima-media thickness (CIMT) and the presence of atheroma plaques and cardiac computed tomography for evaluation of calcium artery calcification (CACS) were performed., Results: T1D subjects showed a high proportion of 25OHD deficiency (43.2 % vs. 21.7 %, p = 0.032). Of all, 82 % of T1D patients and 92 % of controls had a calcium score of 0. CIMT was greater in patients with T1D (0.55 ± 0.14 mm vs 0.48 ± 0.15, p = 0.01) compared with controls. T1D subjects showed no differences in the results of CACS or CIMT according to the vitamin D concentrations., Conclusions: T1D patients have lower concentrations and twice more prevalence of 25OHD deficiency than controls. There was no association between 25OHD concentrations and subclinical CAD.

Background: Predictors of weight loss (WL) or weight regain (WR) after Roux-en-Y gastric bypass (RYGBP) are not established. The aim of this study was to analyze the usefulness of some baseline peptides (leptin, insulin, and ghrelin) as biomarkers of WL and WR in morbid obese patients after RYGBP at long term., Methods: Seventy-six morbid obese (47 women, age 41.6 ± 9.6 years, body mass index [BMI] 52.1 ± 8 kg/m(2)) patients were evaluated at baseline and at 1, 2, and 6 years after surgery., Results: Excess body weight loss after 6 years was of 63.9%. Age, BMI, and studied hormones at baseline or their changes over time did not predict long-term excess body weight loss. WR greater than 10% was observed in 36.8% of patients between 2 and 6 years of follow-up, but it was not correlated with BMI, age, or baseline peptide concentrations., Conclusion: Measurement of ghrelin, insulin, and leptin before surgery is not useful as predictors of WL or WR at long term after RYGBP., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Type 2 diabetes (T2D) exists in 25-40% of hospitalized patients. Therapeutic inertia is the delay in the intensification of a treatment and it is frequent in T2D. The objectives of this study were to detect patients admitted to surgical wards with hyperglycaemia (HH; fasting glycaemia > 140 mg/dL) as well as those with T2D and suboptimal chronic glycaemic control (SCGC) and to assess the midterm impact of treatment modifications indicated at discharge. A total of 412 HH patients were detected in a period of 18 months; 86.6% (357) had a diagnosed T2D. Their preadmittance HbA1c was 7.7 ± 1.5%; 47% (189) had HbA1c ≥ 7.4% (SCGC) and were moved to the upper step in the therapeutic algorithm at discharge. Another 15 subjects (3.6% of the cohort) had T2D according to their current HbA1c. Ninety-four of the 189 SCGC patients were evaluated 3-6 months later. Their HbA1c before in-hospital-intervention was 8.6 ± 1.2% and 7.5 ± 1.2% at follow-up (P < 0.004). Active detection of hyperglycaemia in patients admitted in conventional surgical beds permits the identification of T2D patients with SCGC as well as previously unknown cases. A shift to the upper step in the therapeutic algorithm at discharge improves this control. Hospitalization is an opportunity to break therapeutic inertia.

Background: IGF-I is a clinically relevant protein in the diagnosis and monitoring of treatment of growth disor- ders. The Growth Hormone Research Society and the International IGF Research Society have encouraged the adoption of a universal calibration for immunoassays to improve standardization of IGF-I measurements, but currently commercial assays are calibrated either against the old WHO IRR 87/518 or the new WHO 02/254. We compared two IGF-I immunochemiluminescent assays: IMMULITE® 2000 (Siemens) and LIAISON® (DiaSorin), which differ in their standardization, and verified their precision according to quality specifications based on biological variation and their linear range., Methods: 62 patient serum samples were analyzed for both assays and compared according to standards of the Clinical and Laboratory Standards Institute (CLSI), EP9-A2-IR. Precision was verified according to CLSI EP15- A2. Optimal coefficient of variation (CVo) and desirable coefficient of variation (CVd) for IGF-I assays were calculated as quality specifications based on the biological variability, in order to assess if the interassay analytical CV (CVa1) in the two methods were appropriate. Two dilution series using the 1st WHO International Standard (WHO IS) for IGF-I 02/254 were used to verify and compare the linearity range., Results: The regression analysis showed constant and proportional differences for serum samples (slope b = 0.8115 (CI 95% CI; 0.7575-0.8556); intercept a = 33.6873 (95% CI: 23.3613-44.0133) between assays and similar pro- portional differences for WHO IS 02/254 standard dilutions series (slope b = 0.8024 (CI 95% CI; 0.7560-0.8616); intercept a = 6.9623 (95% CI: -2.0819-18.4383) between assays. Within-laboratory coefficients of variation for low and high levels were 2.82% and 3.80% for IMMULITE® 2000 and 3.58% and 2.14% for LIAISON®, respecttively., Conclusions: IGF-I concentrations measured by both assays are not transferable. The results emphasize the need to express IGF-I concentrations in standard deviation score (SDS) according to a matched normal population of the same age and gender. Within-laboratory precision in both methods met quality specifications derived from biological variation.

Objective: To evaluate the presence of early carotid and coronary atherosclerosis in asymptomatic patients with type 1 diabetes with no history of ischemic heart disease., Research Design and Methods: One hundred and fifty patients with type 1 diabetes (58% males; 38.6 ± 8.1 years, 20.4 ± 8.1 years of evolution; HbA1c 8.1 ± 2.3%; 52% nonsmokers; 26% retinopathy; 9% microalbuminuria) and 50 nondiabetic control subjects age and sex matched were studied. Carotid ultrasonography to determine common carotid artery intima-media thickness (c-IMT) and the presence of atheroma plaques and cardiac computed tomography for calcium analysis and quantification (coronary artery calcium score [CACS]) were performed., Results: Most patients with type 1 diabetes and control subjects displayed a CACS of 0 (82 vs. 92%). Patients with type 1 diabetes with CACS ≥1 were older and had higher HbA1c (44.5 ± 5.1 vs. 36.7 ± 8.1 years [P < 0.001] and 8.5 ± 1.1 vs. 7.8 ± 1.0% [P < 0.003], respectively) and longer evolution of diabetes (25.4 ± 9.2 vs. 19.3 ± 7.4 years, P < 0.005) and mean c-IMT (0.67 ± 0.18 vs. 0.53 ± 0.11 mm, P < 0.001) compared with patients with CACS of 0. Smoking (P < 0.02), nephropathy (P < 0.05), retinopathy (P < 0.05), and male sex (P < 0.03) were significantly and positively associated with CACS ≥1. Mean c-IMT was significantly higher in patients with type 1 diabetes (0.55 ± 0.14 vs. 0.48 ± 0.14 mm, P < 0.01), and 11% of them presented atheroma plaques (8% of control subjects). Multivariant logistic regression analysis showed that c-IMT was related to CACS (β = 6.87, P < 0.001)., Conclusions: A small percentage of patients with type 1 diabetes showed data suggestive of subclinical atherosclerosis. Universal screening of coronary disease in this population is not justified. Carotid ultrasonography may be useful for screening in the subset of patients with cardiovascular risk factors and long disease evolution.

Obestatin has been proposed to have anorexigenic and anti-ghrelin actions. The objective was to study obestatin concentrations in relation to handgrip strength, functional capacity and cognitive state in old women. The prospective study included 110 women (age, 76.93 ± 6.32) from the Mataró Ageing Study. Individuals were characterized by anthropometric variables, grip strength, Barthel and assessment of cognitive impairment [Mini Cognoscitive Examination (MCE) Spanish version], depressive status by the Geriatric Depression Scale (GDS) and frailty by the Fried criteria. Obestatin was measured by IRMA. Obestatin showed negative correlation to handgrip at basal time point (r = -0.220, p = 0.023) and at 2-year follow-up (r = -0.344, p = 0.002). Obestatin, divided into quartiles, showed a negative lineal association with handgrip: 11.03 ± 4.88 kg in first, 8.75 ± 4.08 kg in second, 8.11 ± 3.66 kg in third and 7.61 ± 4.08 kg in fourth quartile (p = 0.018). Higher obestatin levels were associated to increased weakness (categorized by handgrip of frailty criteria): 2.24 ± 0.42 ng/ml in weak vs. 1.87 ± 0.57 ng/ml in non-weak (p = 0.01). The decrease of either MCE or Barthel scores at 2-year follow-up was significantly higher in individuals in the fourth quartile of obestatin in comparison with individuals in the first quartile (p = 0.046 and p = 0.019, respectively). No association was found between obestatin and GDS score and neither with frailty as a condition. Obestatin is associated to low muscle strength, and impaired functional and cognitive capacity in old women participating in the Mataró Ageing Study.

Background: There is no consensus about the usefulness of postoperative intact parathyroid hormone (iPTH) determination to predict permanent hypoparathyroidism (pHPP). We evaluated the value of calcium (Ca2+) and iPTH concentration at 24 hours after total thyroidectomy (TT) for predicting pHPP., Methods: Ca2+ and iPTH levels from 70 consecutive patients who underwent TT were measured at 24 hours and 6 months after TT., Results: Five patients (7.1%) developed pHPP. An iPTH concentration ≤5.8 pg/mL at 24 hours after TT identified patients at risk for pHPP (sensitivity, 100%; specificity, 81.5%), but it was not accurate enough to predict its development (positive predictive value, 30%). Conversely, an iPTH level >5.8 pg/mL predicted normal parathyroid function at 6 months (negative predictive value, 100%). Compared with iPTH, a postoperative Ca2+ level ≤1.95 mmol/L was 60% sensitive and 78.5% specific to predict pHPP., Conclusions: An iPTH concentration >5.8 pg/mL on the first postoperative day rules out pHPP with much better diagnostic accuracy than Ca2+. Postoperative iPTH could be helpful in identifying patients at risk for developing pHPP., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: IGF1 is decreased in morbidly obese (MO) patients and its changes after bariatric surgery weight loss (WL) are not well known. The aim of this study was to analyse IGF1 modifications in MO patients after WL and its relationship to ghrelin and to different types of surgeries., Design: Retrospective follow-up study at the University Medical Center., Methods: One hundred and nine MO patients (age 44.19.3, BMI 51.748.75KG/M(2)) were evaluated at baseline and 1 year after surgery: 28 sleeve gastrectomy (SG), 31 distal modified (m), and 50 ringed (r) Roux-en-Y gastric bypass (RYGBP) surgery. Changes in IGF1, IGFBP3, ratio IGF1:IGFBP3, and ghrelin were evaluated 1 year after surgery., Results: Baseline prevalence of low IGF1 (defined by s.d. IGF1<-2) was 22%, and %WL 1 year after surgery was 34.9±8.9%. There was a significant decrease in IGFBP3 in all the procedures, an increase in IGF1:IGFBP3 ratio in rRYGBP and SG, but total IGF1 only increased significantly in SG. Albumin concentrations decreased in mRYGBP, did not change in rRYGBP, but increased in SG after surgery. Total ghrelin concentrations increased after both RYGBPs and decreased after SG (P<0.05 in all cases). The prevalence of low IGF1 decreased in SG (28.6 vs 10.1%, P=0.03) and did not change in RYGPBP techniques. The %albumin change was the only dependent variable associated with the % total IGF1 change., Conclusions: Recovery of low IGF1 after bariatric surgery was specifically related to the albumin modifications induced by surgery and was not related to ghrelin modifications.

Background: The relationship between thyrotropin (TSH) concentrations and body mass index (BMI) in euthyroid subjects has been demonstrated only in some studies. Leptin regulates TSH secretion and TSH stimulates leptin secretion. The main aims of our study were to assess the relationship between leptin, the thyroid axis, and thyroid autoimmunity in a representative sample of a nonhospitalized euthyroid adult population of Catalonia and to determine whether smoking status could influence this relationship., Methods: This cross-sectional population-based study includes 894 euthyroid iodine-sufficient adults (390 men, 44.87±15.03 years old) with BMI 26.19±4.61 kg/m(2), representative of people living in Catalonia. The study analyzes the relationship between TSH, free thyroxine (FT4), leptin, thyroperoxidase and/or thyroglobulin antibodies (thyroid autoimmunity), smoking status, and BMI. Measurements also include glycemia and insulinemia to calculate homeostasis model assessment of insulin resistance (HOMA-IR) index as a measure of insulin sensitivity., Results: In the univariate analysis and in the overall group, TSH correlated directly with BMI, leptin, and HOMA-IR (p=0.039, p<0.001, and p=0.010, respectively). In all men, TSH correlated directly with leptin (p=0.004), and in all women, directly with leptin (p=0.002) and HOMA-IR (p=0.031) and inversely with FT4 (p=0.024). Only in men who smoke, TSH correlated directly with leptin (p=0.010) and HOMA-IR (p=0.024). In women, TSH correlated directly with leptin (p=0.004) and in nonsmoking women, inversely with FT4 (p=0.047). In the multiple regression analysis, age (β=-0.00310, p=0.0265), smoking status (β=-0.24085, p=0.0202), and thyroid autoimmunity (β=0.20652, p=0.0075) were independent predictors of TSH variations. Leptin was a significant independent predictor of TSH variations only in smokers (β=0.16451, p=0.047)., Conclusions: Leptin is an independent predictor of TSH concentration variations only in euthyroid smoker subjects of both sexes at all ranges of BMI, but not in nonsmokers. Age, smoking status, and positive thyroid autoimmunity also influenced TSH variability.

Objective: Ghrelin and obestatin have apparent opposite orexigenic and anorexigenic effects, although the latter has not been firmly demonstrated in humans. So far, little data have been reported in relation to its potential association with metabolic syndrome (MS). The objective was to study obestatin concentrations in relation to nutritional parameters and eating behaviours in old women., Design, Patients and Measurements: Prospective study; a total of 110 women (age: 76.93 ± 6.32) from the Mataró Ageing Study were included. Individuals were characterized by anthropometric variables, lipids, glucose, blood pressure, MS components (Adult Treatment Panel III criteria), anorexia and nutritional status by Mini Nutritional Assessment Short Form (MNA-SF) and re-evaluated at 2-year follow-up. Obestatin was measured by IRMA., Results: 58.2% of the subjects had MS; at 2-year follow-up 24.1% had a weight loss >5%, 7.2% >10%, and 26.4% changed their MNA-SF score to risk of malnutrition category. Anorexia was present in 38.4%. Obestatin levels were not related to either change of weight, MNA-SF or anorexia, but a positive correlation was found with the absolute difference between basal and 2-year waist circumference (WC) (r = 0.429; P < 0.001) and relative difference between basal and 2-year WC (r = 0.420; P < 0.001); both remained significant after adjusting for age and body mass index. When obestatin was divided into quartiles, a significant lineal trend was observed in relation to WC (P = 0.049), absolute and relative difference between basal and 2-year WC (both P < 0.001). Obestatin was associated with glucose impairment (69.0% in 4th quartile vs 47.5% in 1st to 3rd, P = 0.047; after adjustment, P = 0.098) and MS (77.8% in 4th vs 51.3% in 1st to 3rd, P = 0.017; after adjustment, P = 0.046, OR 2.90 (1.02-8.25) 4th vs 1st to 3rd)., Conclusions: Obestatin is elevated in aged women bearing MS but is otherwise not associated with other nutritional parameters, weight loss or anorexia., (© 2012 John Wiley & Sons Ltd.)

Objective: Pregnancy-associated plasma protein-A (PAPP-A) is a protease promoting IGF1 tissue availability and considered as a new biomarker of cardiovascular disease., Aim: To evaluate the relationship between PAPP-A concentrations and anthropometric variables, physical activity, smoking status, glucose homoeostasis and adipocytokines in healthy adults., Design and Methods: One hundred and forty-nine subjects (77 women; mean age 39·7 ± 14 years; mean BMI 23·7 ± 1·9 kg/m(2) ) were randomly selected from 8000 adults of The Health Survey of Catalonia. Possible effects of gender, age, body composition, smoking status, physical activity, glucose homoeostasis and adipocytokines on PAPP-A concentrations were assessed., Results: Pregnancy-associated plasma protein-A was significantly higher in men than in women [1·04 (0·61-0·44) vs 0·61 (0·41-0·90) μIU/ml; P < 0·0001]; there were no differences in relation to physical activity or smoking status. PAPP-A showed a negative correlation with leptin in men (P = 0·01) and women (P = 0·05), and a positive correlation with adiponectin (P = 0·006) in women and a trend (P = 0·073) in men. Homoeostasis model assessment of insulin resistance (HOMA-IR) showed a negative correlation with PAPP-A only in women (P = 0·019). No association was found with blood pressure, IGF1, lipids or glucose in either gender. When a multiple regression analysis was performed including gender, age, BMI, waist-hip ratio, HOMA-IR, adiponectin and leptin as confounders, PAPP-A was independently correlated with adiponectin (β = 0·23; P = 0·02) and leptin (β = -0·33; P = 0·04)., Conclusions: Our study shows a sexual dimorphism of PAPP-A, and a possible influence of leptin and adiponectin on its concentrations in healthy subjects. The mechanisms responsible for this relationship remain to be determined., (© 2012 Blackwell Publishing Ltd.)

Context: One of the side effects of interferon-alpha therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT melanoma patients remains to be defined., Objective: Our objective was to assess different peripheral blood lymphocyte subpopulations, mainly regulatory T cells (Tregs), in melanoma patients who developed IIT., Design, Patients and Methods: From 30 melanoma patients receiving high-dose interferon (HDI)-alpha 2b (IFN-α2b) treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-MM) and healthy controls (Co-H). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment and at appearance of IIT (TT)., Results: Nine patients developed IIT (30%): four Hashimoto's thyroiditis and five destructive thyroiditis. An increase in Tregs was observed in both melanoma groups during HDI treatment. A decrease in CD3(+) , NKT lymphocyte subpopulations and Bcl2 expression on B cells was also observed in both groups. However, no changes were observed in the percentage of CD4(+) , CD8(+) , CD3(+) γδ(+) , CD19(+) , transitional B cells (CD24(high) CD38(high) CD19(+) CD27(-) ), natural killer (NK), invariant NKT (iNKT) lymphocytes and Th1/Th2 balance when BT was compared with ET. At TT, IIT patients had a higher Tregs percentage than Co-MM (P = 0·012) and Co-H (P = 0·004), a higher iNKT percentage than Co-MM (P = 0·011), a higher transitional B cells percentage than Co-H (P = 0·015), a lower CD3(+) percentage than Co-H (P = 0·001) and a lower Bcl2 expression on B cells than Co-H (P < 0·001)., Conclusions: Our results point to the immunomodulatory effects of IFN-α on different lymphocyte subpopulations and a possible role of Tregs in melanoma patients who developed IIT., (© 2012 Blackwell Publishing Ltd.)

Background: The effect of weight loss by bariatric surgery on gonadal hormones in morbidly obese males is not entirely known. The main objective of the study was to analyze gonadal hormonal changes after weight loss., Methods: An observational study was conducted before and after 12 months of weight loss at a clinical research center. Thirty-three men [age 40.5 ± 9.9, body mass index (BMI) 50.3 ± 6.1 kg/m(2)] undergoing bariatric surgery were included. The main outcome measures were as follows: changes in total (TT) and free testosterone (FT), estradiol (E2), sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), inhibin B, and prolactin (PRL)., Results: Baseline prevalence of hypogonadism (defined by TT < 300 ng/dl or FT < 65 pg/ml) was 78.8 and 51.5%, respectively. Hypogonadal patients were older and showed inhibin B and AMH significantly lower than those with normal TT. BMI correlated negatively with TT, LH, and SHBG. Regression analyses showed a significant and independent association of hypogonadism with age (OR = 1.2, p = 0.01), BMI (OR = 1.3, p = 0.03), and AMH (OR = 0.4, p = 0.03) after adjustments. After 1 year, percentage of weight loss (%WL) was 18.8 ± 5.2%, and there was a significant increase of TT, FT, SHBG, and FSH and a decrease of E2 and PRL. Prevalence of persistent hypogonadism after surgery was 6% (low TT) and 15% (low FT). %WL was significantly associated with percent changes in SHBG (r = -0.4, p = 0.04), inhibin B (r = -0.4, p = 0.03), and AMH (r = -0.4, p = 0.01). Age and %WL were the only significant and independent parameters associated with %TT change., Conclusions: Obesity-associated hypogonadism is very prevalent in males with morbid obesity and is mostly reversed after sustained weight loss by bariatric surgery.

Background: Low levels of plasma 25-hydroxyvitaminD (25(OH)D) are associated with a higher incidence of multiple sclerosis (MS) due to the immune suppressive properties of vitamin D.The aim of this study was to determine the correlation between plasma 25(OH)D concentrations and clinical and immunological variables in a cohort of multiple sclerosis patients., Methods: Plasma 25(OH)D concentrations were evaluated in summer and winter in 15 primary progressive MS (PPMS) patients, 40 relapsing- remitting MS (RRMS) patients and 40 controls (HC). Protocol variables included demographic and clinical data, radiological findings and immunological variables (oligoclonal bands, HLADR15 and T-lymphocyte proliferation to a definite mix of 7 myelin peptides)., Results: During the winter, plasma concentrations were significantly lower in RRMS patients compared to HC, whereas no differences were found in summer. No relationships were found between plasma 25(OH)D concentrations and clinical or radiological variables. RRMS patients with a positive T-cell proliferation to a mix of myelin peptides (n = 31) had lower 25(OH)D concentrations., Conclusions: 25(OH)D is an immunomodulatory molecule that might have a regulatory role in T-cell proliferation to myelin peptides in RRMS patients.

Unlabelled: The aim of this study was to analyze the relationship between pre-transplant adiponectin (pre-ADP), abnormalities in glucose homeostasis (AGH) at three months post-transplantation, and preclinical atherosclerosis in non-diabetic patients prior to kidney transplantation (KT)., Methods: We carried out a multicenter study in 157 non-diabetic KT patients (66.5% men; age: 50±13 yr). Pre-ADP levels were analyzed using radioimmunoassay. Carotid ultrasound was performed to determine carotid intima-media thickness (c-IMT). Oral glucose tolerance test was carried out to classify patients according ADA criteria., Results: Of the patients, 52.8% had AGH. Median pre-ADP was 19.5 (14-27) μg/mL. An inverse correlation was found between ADP and HOMA index (r=-0.432; p<0.001). Median c-IMT was 0.6 (0.48-0.71) mm. Significant inverse correlation existed between ADP and c-IMT on both sides (p<0.05). Patients with c-IMT >0.6 mm had more AGH (p=0.012) and lower ADP levels (p=0.02). We performed a logistic regression analysis using preclinical atherosclerosis (c-IMT ≥0.6 mm) as dependent variable and sex, age, BMI, ADP, AGH, and HOMA index as independent variables of altered c-IMT. Age, pre-ADP, and AGH were independent risk factors for elevated c-IMT., Conclusions: Patients with AGH have a greater presence of preclinical atherosclerosis. ADP has an inverse relationship with AGH and is an independent marker of preclinical atherosclerosis., (© 2011 John Wiley & Sons A/S.)

One hundred and forty-six index patients with 46,XY DSD in whom gonads were confirmed as testes were consecutively studied for a molecular diagnosis during the period 2002-2010. AR gene was analysed in all patients as the first candidate gene, yielding a mutation in 42.5% of cases and SRD5A2 gene was analysed as the second candidate gene, resulting in the characterization of 10 different mutations (p.Y91D, p.G115D, p.Q126R, p.R171S, p.Y188CfsX9, p.N193S, p.A207D, p.F219SfsX60, p.R227Q and p.R246W) in nine index patients (6.2% of the total number of 46,XY DSD patients). One of the mutations (p.Y188CfsX9) has never been reported. In addition, we genotyped SRD5A2 gene p.V89L and c.281+15T>C polymorphisms in 46,XY DSD and in 156 normal adult males and found that patients with SRD5A2 mutations or without a known molecular diagnosis presented a higher frequency of homozygous p.L89, homozygous TT and combined CCTT genotypes compared with controls. This result suggests that 46,XY DSD patient phenotypes may be influenced by SRD5A2 polymorphism genotypes. SRD5A2 gene mutations may not be as infrequent as previously considered in 46,XY DSD patients with variable degrees of external genitalia virilization at birth and normal T production and appears to be the second aetiology in our series., (© 2011 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.)

Objective: One of the side effects of interferon-alpha (IFN-α) therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT remains to be defined. The aim of this study was to assess different peripheral blood lymphocyte subpopulations, mainly CD4(+) CD25(+) CD127low/-FoxP3(+) regulatory T cells (Tregs), in patients with chronic hepatitis C virus (HCV) infection who developed IIT., Design, Patients and Methods: From 120 patients with chronic HCV who started antiviral treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-HCV). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment (PT) and at appearance of IIT (TT)., Results: Eleven patients developed IIT: three Hashimoto's thyroiditis, one Graves'disease, one positive antithyroidal antibodies, one nonautoimmune hypothyroidism and five destructive thyroiditis. During antiviral treatment, an increase in CD8(+) and in Tregs was observed in both groups. A decrease in CD3(+) , CD19(+) and NKT lymphocyte subpopulations was also observed (all P < 0·05). However, no changes were observed in the percentage of CD4(+) , CD3(+) γδ(+) and iNKT lymphocytes, Th1/Th2 balance and Bcl2 expression on B cells when BT was compared with ET. At the appearance of IIT (TT), IIT patients had a higher Th1 response (CCR5(+) CCR7(-) ) (P < 0·01) and a higher Tregs percentage (P < 0·05) than Co-HCV., Conclusions: Our results point to the immunomodulatory effects of IFN-α on different lymphocyte subpopulations and a possible role of Th1 response and Tregs in patients with HCV who developed IIT., (© 2011 Blackwell Publishing Ltd.)