Leydig and Sertoli cell function in individuals with genital ambiguity, 46,XY karyotype, palpable gonads and normal testosterone secretion: a case-control study.

BACKGROUND: Because normal male sexual differentiation is more complex than normal female sexual differentiation, there are more cases of disorders of sex development (DSDs) with 46,XY karyotype that have unclear etiology. However, Leydig and Sertoli cell markers are rarely used in distinguishing such individuals. OBJECTIVES: To evaluate the function of Leydig and Sertoli cells in individuals with genital ambiguity, 46,XY karyotype, palpable gonads and normal testosterone secretion. STUDY DESIGN AND SETTING: Case-control study with 77 patients, including eight with partial androgen insensitivity syndrome, eight with 5α-reductase deficiency type 2 (5ARD2) and 19 with idiopathic 46,XY DSD, and 42 healthy controls, from the Interdisciplinary Study Group for Sex Determination and Differentiation (GIEDDS), at the State University of Campinas (UNICAMP), Campinas, Brazil. METHODS: Baseline levels of gonadotropins, anti-Müllerian hormone (AMH), inhibin B, insulin-like 3 (INSL3), testosterone and dihydrotestosterone in cases, and AMH, inhibin B, and INSL3 levels in controls, were assessed. RESULTS: There was no significant difference in age between cases and controls (P = 0.595). AMH and inhibin B levels were significantly lower in cases than in controls (P = 0.031 and P < 0.001, respectively). INSL3 levels were significantly higher in cases than in controls (P = 0.003). Inhibin B levels were lower in 5ARD2 patients (P = 0.045) and idiopathic patients (P = 0.001), in separate comparisons with the controls. CONCLUSION: According to our findings, we can speculate that inhibin B levels may be used to differentiate among DSD cases.

Leydig and Sertoli cell function in individuals with genital ambiguity, 46,XY karyotype, palpable gonads and normal testosterone secretion: a case-control study

Abstract BACKGROUND: Because normal male sexual differentiation is more complex than normal female sexual differentiation, there are more cases of disorders of sex development (DSDs) with 46,XY karyotype that have unclear etiology. However, Leydig and Sertoli cell markers are rarely used in distinguishing such individuals. OBJECTIVES: To evaluate the function of Leydig and Sertoli cells in individuals with genital ambiguity, 46,XY karyotype, palpable gonads and normal testosterone secretion. STUDY DESIGN AND SETTING: Case-control study with 77 patients, including eight with partial androgen insensitivity syndrome, eight with 5α-reductase deficiency type 2 (5ARD2) and 19 with idiopathic 46,XY DSD, and 42 healthy controls, from the Interdisciplinary Study Group for Sex Determination and Differentiation (GIEDDS), at the State University of Campinas (UNICAMP), Campinas, Brazil. METHODS: Baseline levels of gonadotropins, anti-Müllerian hormone (AMH), inhibin B, insulin-like 3 (INSL3), testosterone and dihydrotestosterone in cases, and AMH, inhibin B, and INSL3 levels in controls, were assessed. RESULTS: There was no significant difference in age between cases and controls (P = 0.595). AMH and inhibin B levels were significantly lower in cases than in controls (P = 0.031 and P < 0.001, respectively). INSL3 levels were significantly higher in cases than in controls (P = 0.003). Inhibin B levels were lower in 5ARD2 patients (P = 0.045) and idiopathic patients (P = 0.001), in separate comparisons with the controls. CONCLUSION: According to our findings, we can speculate that inhibin B levels may be used to differentiate among DSD cases.

Adipokines in young survivors of childhood acute lymphocytic leukemia revisited: beyond fat mass.

PURPOSE: This cross-sectional study evaluated the relationship between adipokines (leptin, adiponectin, visfatin, and resistin) and adiposity indexes regarding sex and cranial radiotherapy exposure among young acute lymphocytic leukemia survivors. METHODS: A multivariate analysis of covariance (MANCOVA) was used to evaluate the joint effect of sex, cranial radiotherapy, and body mass index (BMI) z-score (model 1) or fat mass index (FMI) (model 2) on adipokines. RESULTS: This study included 55 survivors of childhood acute lymphocytic leukemia between 15 and 23 years of age from both sexes (56.4% female); 43.6% of the sample had undergone cranial radiotherapy (18-24 Gy). The BMI z-score, the FMI, and sex (P<0.050 for all) influenced at least one adipokine, while cranial radiotherapy exposure was marginal in model 2. Parameter estimates from the MANCOVA's final model showed that the BMI z-score (ß=-0.437, P=0.010) and the FMI (ß=-0.209, P=0.004) negatively influenced adiponectin, while the FMI positively affected resistin (ß=0.142, P=0.020). The relationship between leptin, visfatin, and the adiposity ndexes could not be established. In model 1, females presented with increased adiponectin (ß=-1.014, P=0.011) and resistin (ß=-1.067, P=0.002) levels; in model 2, female sex positively affected adiponectin (ß=-1.515, P=0.001) and marginally influenced resistin (ß=-0.707, P=0.054) levels. Cranial radiotherapy negatively determined visfatin levels in both final models (P<0.050). CONCLUSION: Changes in body fat may be associated with adipose tissue dysfunction and should be carefully evaluated in survivors of acute lymphocytic leukemia, considering both sex and cranial radiotherapy exposure, to treat disorders that may possibly aggravate their risk for early cardiovascular disease.

Comparison between two inhibin B ELISA assays in 46,XY testicular disorders of sex development (DSD) with normal testosterone secretion.

BACKGROUND: Inhibin B is a hormone produced by the Sertoli cells that can provide important information for the investigation of disorders of sex development (DSD) with 46,XY karyotype. The aim of this study is to compare two enzyme-linked immunosorbent assay (ELISA) assays for dosage of serum inhibin B in patients with 46,XY DSD with normal testosterone secretion. METHODS: Twenty-nine patients with 46,XY DSD and normal testosterone secretion (partial androgen insensitivity syndrome [PAIS] [n=8]; 5α-reductase deficiency [n=7] and idiopathic 46,XY DSD [n=14]) were included. Molecular analysis of the AR and SRD5A2 genes were performed in all patients and the NR5A1 gene analysis in the idiopathic group. Measurements of inhibin B were performed by two second-generation ELISA assays (Beckman-Coulter and AnshLabs). Assays were compared using the interclass correlation coefficient (ICC) and the Bland-Altman method. RESULTS: ICC was 0.915 [95% confidence interval (CI): 0.828-0.959], however, a discrepancy was observed between trials, which is more evident among higher values when analyzed by the Bland-Altman method. CONCLUSIONS: It is recommended to perform the inhibin B measurement always using the same ELISA kit when several evaluations are required for a specific patient.

Changes in serum levels of lipopolysaccharides and CD26 in patients with Crohn's disease.

BACKGROUND/AIMS: Lipopolysaccharide (LPS) is a molecule formed by lipids and polysaccharides and is the major cell wall component of gram-negative bacteria. High LPS levels are known to block CD26 expression by activating Toll-like receptor 4. The aim of this study was to correlate the serum levels of LPS and CD26 in Crohn's disease (CD) patients with serum levels of C-reactive protein (CRP), interleukins, CD activity index, and tumor necrosis factor-α (TNF-α). METHODS: Serum samples were collected from 27 individuals (10 with active CD, 10 with inactive CD, and 7 controls) and the levels of LPS, CD26, TNF-α, interleukin-1ß (IL-1ß), IL-6, IL-17, and CRP were determined by enzyme-linked immunosorbent assay. The levels of LPS and CD26 were then tested for correlation with TNF-α, IL-1ß, IL-6, IL-17, and CRP. RESULTS: Serum levels of LPS were significantly elevated in the active CD group (P=0.003). Levels of IL-1ß (P=0.002), IL-6 (P=0.003), and IL-17 (P<0.001) were lower in the CD groups. Serum TNF-α levels were increased in the active CD group. The CRP levels were elevated in the CD groups when compared to controls (P<0.001). The CD26 levels were lower in the CD groups than in the control group (P<0.001). Among the variables analyzed, there was a correlation between LPS and CRP (r=-0.53, P=0.016) in the CD groups. CONCLUSIONS: Individuals with CD exhibited higher serum levels of LPS varying from a 2- to 6-fold increase depending on disease activity, when compared with healthy controls. CD26 levels were lower in the CD groups. Both LPS and CD26 correlated with disease severity and serve as potential CD biomarkers.

Visfatin is a positive predictor of bone mineral density in young survivors of acute lymphocytic leukemia.

Bone mass acquisition may be compromised in survivors of childhood acute lymphocytic leukemia due to various factors, including adiposity. Fat accumulation can affect bone through the direct effect of adipokines or indirectly through the state of chronic inflammation. The aim of this study was to evaluate the effect of body composition and adipokines on bone mass in survivors of acute lymphocytic leukemia. This was a cross-sectional study of 56 survivors aged between 15 and 24 years, 44.6 % of whom received cranial radiotherapy (18-24 Gy), assessed according to body fat, lean mass, and bone mineral density (dual energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, and adipokines by a multiple regression analysis. Both lumbar spine L1-L4 (trabecular bone) and total body (cortical bone) bone mineral density were positively correlated with visfatin (p < 0.050). Lean mass index was positively correlated, while waist-to-height ratio was negatively correlated with cortical bone (p < 0.010). Low bone mineral density for chronological age was detected in 5.4 % of patients in total body, and 8.9 % at the lumbar spine. In survivors of acute lymphocytic leukemia, visfatin may play an important role in the complex relationship between body composition and bone. At present, visfatin may represent a model for further study of bone metabolism, and could possibly explain the unknown mechanisms linking bone metabolism and cancer.

Subcutaneous adipose tissue plays a beneficial effect on subclinical atherosclerosis in young survivors of acute lymphocytic leukemia.

PURPOSE: The aim of this study was to evaluate the relationship between body composition, metabolic profile, adipokines, and carotid intima-media thickness (cIMT) in young survivors of childhood acute lymphocytic leukemia (ALL). PATIENTS AND METHODS: This cross-sectional study compared 55 ALL survivors, of chronological age between 15 years and 24 years, assigned into two groups according to the exposure to cranial radiation therapy (CRT; 25 irradiated and 30 nonirradiated) with 24 leukemia-free controls, and assessed body fat mass (dual-energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, lipid profile, blood pressure (BP), adipokines, and cIMT by a multiple regression analysis. RESULTS: Treatment with CRT had an effect on all of the variables derived from the computed tomography scan: visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) (P<0.050). In a multiple linear regression model, cIMT positively correlated with exposure to CRT (P=0.029), diastolic BP (P=0.016), and leptin-to-adiponectin ratio (P=0.048), while negatively related to SAT (P=0.007). CONCLUSION: In young survivors of childhood ALL, CRT modified the distribution of fat and played a critical role in determining cIMT. Leptin-to-adiponectin ratio, a biomarker of abdominal obesity and metabolic syndrome, and diastolic BP also influenced cIMT, a marker of subclinical atherosclerosis. Nonetheless, adiposity-associated vascular disease might be attenuated by SAT. Changes in body fat must be evaluated in this group of patients in the early course of survivorship in order to avoid premature cardiovascular disease associated with atherosclerosis. Yet, further research as regards the possible protective effect of SAT on vascular disease is warranted.

Polymorphism in LEP and LEPR May Modify Leptin Levels and Represent Risk Factors for Thyroid Cancer.

Purpose. To understand the role of polymorphisms in the LEP (rs7799039 and rs2167270) and LEPR (rs1137101 and rs1137100) genes in DTC susceptibility and their effect on leptin levels. Methods. We studied 153 patients with DTC and 234 controls through TaqMan SNP Genotyping and ELISA, comparing these data to the clinicopathological data of patients with DTC. Results. Patients with AA genotype of rs7799039 had higher levels of serum leptin (9.22 ± 0.98 ng/mL) than those with AG genotype (10.07 ± 0.60 ng/mL; P = 0.005). Individuals with AG genotype of rs2167270 also produced higher serum leptin levels (10.05 ± 0.59 ng/mL) than the subjects with GG genotype (9.52 ± 0.79 ng/mL; P < 0.05). A multivariate logistic regression adjusted for gender, age, and BMI showed that the AG genotype of rs7799039 was an independent risk for DTC (OR, 11.689; P = 0.0183; 95% CI, 1.516-90.119). Similarly, AG and GG genotypes of rs1137101 increased the susceptibility to DTC (OR, 3.747; P = 0.027; 95% CI, 1.161-12.092 and OR, 5.437; P = 0.013; 95% CI, 1.426-20.729). Conclusions. We demonstrated that rs7799039 and rs2167270 polymorphisms modify the serum leptin concentrations in patients with DTC. Furthermore, polymorphisms rs7799039 and rs1137101 increase the risk of DTC development, although they do not correlate with tumor aggressiveness.

Serum levels of retinol binding protein 4 in women with different levels of adiposity and glucose tolerance.

OBJECTIVE: Retinol-binding protein 4 (RBP4) is an adipokine responsible for vitamin A (retinol) transportation. Studies associated RBP4 increased levels with severity of type 2 diabetes mellitus (T2DM) and insulin resistance (IR). The study aimed to quantify RBP4 serum standards in women with a wide range of body mass index (BMI) and glucose tolerance level. SUBJECTS AND METHODS: Cross-sectional study was performed with 139 women divided into three groups: Group 1 (lean-control, n = 45) and Group 2 (obese, n = 53) with normal glucose tolerance and group 3 (obese with T2DM, n = 41), called G1, G2 and G3. Were assessed clinical, biochemical, anthropometric and body composition parameters. RESULTS: According to data analysis, we obtained in G1 higher RBP4 levels (104.8 ± 76.8 ng/mL) when compared to G2 (87.9 ± 38 ng/mL) and G3 (72.2 ± 15.6 ng/mL) levels. Also, were found: in G1 positive correlations of RBP4 with BMI (r = 0.253), glycated hemoglobin (r = 0.378) and fasting insulin (r = 0.336); in G2 with glycated hemoglobin (r = 0.489); in G3 with glycated hemoglobin (r = 0.330), fasting glucose (r = 0.463), HOMA-IR (r = 0.481). CONCLUSIONS: Although RBP4 have shown lower levels in diabetic and obese, a strong correlation with HOMA-IR index highlights that, in our study, there is growing IR when there is an increasing in RBP4 levels.

Serum levels of retinol binding protein 4 in women with different levels of adiposity and glucose tolerance / Níveis séricos da proteína carreadora do retinol 4 em mulheres com diferentes níveis de adiposidade e tolerância à glicose

Objective Retinol-binding protein 4 (RBP4) is an adipokine responsible for vitamin A (retinol) transportation. Studies associated RBP4 increased levels with severity of type 2 diabetes mellitus (T2DM) and insulin resistance (IR). The study aimed to quantify RBP4 serum standards in women with a wide range of body mass index (BMI) and glucose tolerance level. Subjects and methods: Cross-sectional study was performed with 139 women divided into three groups: Group 1 (lean-control, n = 45) and Group 2 (obese, n = 53) with normal glucose tolerance and group 3 (obese with T2DM, n = 41), called G1, G2 and G3. Were assessed clinical, biochemical, anthropometric and body composition parameters. Results According to data analysis, we obtained in G1 higher RBP4 levels (104.8 ± 76.8 ng/mL) when compared to G2 (87.9 ± 38 ng/mL) and G3 (72.2 ± 15.6 ng/mL) levels. Also, were found: in G1 positive correlations of RBP4 with BMI (r = 0.253), glycated hemoglobin (r = 0.378) and fasting insulin (r = 0.336); in G2 with glycated hemoglobin (r = 0.489); in G3 with glycated hemoglobin (r = 0.330), fasting glucose (r = 0.463), HOMA-IR (r = 0.481). Conclusions Although RBP4 have shown lower levels in diabetic and obese, a strong correlation with HOMA-IR index highlights that, in our study, there is growing IR when there is an increasing in RBP4 levels. .

Objetivo A proteína carreadora do retinol 4 (RBP4) é uma adipocina responsável pelo transporte de vitamina A (retinol). Estudos associam os níveis aumentados de RBP4 com a gravidade do diabetes melito tipo 2 (DM2) e resistência à insulina (RI). O objetivo deste estudo foi investigar como esses níveis se comportam em mulheres com ampla variação do índice de massa corporal (IMC) e tolerância à glicose. Sujeitos e métodos: Estudo transversal realizado com 139 mulheres, divididas em três grupos: Grupo 1 (controles-magras; n = 45) e Grupo 2 (obesas; n = 53), com tolerância normal à glicose; Grupo 3 (obesas DM2; n = 41), denominados G1, G2 e G3. Foram avaliados parâmetros clínicos, bioquímicos, antropométricos e composição corporal. Resultados De acordo com a análise dos dados, obtivemos em G1 maiores níveis de RBP4 (104,8 ± 76,8 ng/mL) em comparação ao G2 (87,9 ± 38 ng/mL) e G3 (72,2 ± 15,6 ng/mL). Também foram encontradas correlações positivas entre RBP4 e IMC (r = 0,253), hemoglobina glicada (r = 0,378) e insulinemia de jejum (r = 0,336); em G2 com hemoglobina glicada (r = 0,489); G3 com hemoglobina glicada (r = 0,330), insulinemia de jejum (r = 0,463) e HOMA-IR (r = 0,481). Conclusões Embora a RBP4 tenha apresentado níveis menores em pacientes diabéticas e obesas, a forte correlação com o índice HOMA-IR deixa claro que, em nosso estudo, há crescente RI quando os níveis dessa proteína também são crescentes. .