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The aim of this study was to investigate for first time the thyroid function in patients with inflammatory bowel disease (IBD) and the potential effect of anti-TNF (tumor necrosis factor) therapy. We evaluated 41 patients with IBD (25M/16F, 36.5 ± 11.3 y, 27 with Crohn's disease and 14 with ulcerative colitis), without any known thyroid disorder. Eighteen patients (9M/9F, 33.6 ± 8.8 y) were on anti-TNF therapy, while 23 patients (16M/7F, 38.7 ± 12.5 y) were treated with Azathioprine and Mesalazine (Aza/Mes) for more than 1 year. Twelve patients from the second group were then treated with anti-TNF and studied 6 months later. We assessed thyroid function by measuring thyroid stimulating hormone (TSH), free thyroxine (FT4), triiodothyronine (T3), thyroid peroxidase autoantibodies (TPOAb) and thyroglobulin autoantibodies (TgAb) levels. One patient presented with overt and one with subclinical hyperthyroidism. Thyroid auto-antibodies were positive in 12.2%. Patients from the anti-TNF group had lower levels of FT4 (1.09 ± 0.15 vs. 1.38 ± 0.9 ng/dL, p = 0.042), while TSH and T3 were comparable. The percentage of patients with positive thyroid auto-antibodies was lower in the anti-TNF group (5.6% vs. 17.4%). In the subgroup of patients who changed to anti-TNF, we found statistically significant reduction in FT4 after 6 months (1.26 ± 0.24 vs. 1.08 ± 0.15 ng/dL, p = 0.044), without changes in TSH and T3 levels. There was no change regarding thyroid auto-antibodies. In conclusion, patients with IBD showed a quite high percentage of thyroid autoimmunity. After treatment with anti-TNF, FT4 levels were found to be reduced, while no changes in TSH, T3 levels and thyroid auto-antibodies were noted.
Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Glândula Tireoide/efeitos dos fármacos , Adalimumab/farmacologia , Adulto , Anti-Inflamatórios não Esteroides/farmacologia , Azatioprina/farmacologia , Azatioprina/uso terapêutico , Feminino , Fármacos Gastrointestinais/farmacologia , Humanos , Doenças Inflamatórias Intestinais/sangue , Infliximab/farmacologia , Masculino , Mesalamina/farmacologia , Mesalamina/uso terapêutico , Pessoa de Meia-Idade , Testes de Função Tireóidea , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
OBJECTIVE: The aim of this study was to investigate the impact of adrenal hyperandrogenism on insulin resistance and lipid profile in women with polycystic ovary syndrome (PCOS). PATIENTS AND METHODS: We studied 372 women with PCOS according to the NIH criteria. 232 age- and BMI-matched women served as controls in order to define adrenal hyperandrogenism (DHEA-S >95th percentile). Then, patients with PCOS were classified into two groups: with adrenal hyperandrogenism (PCOS-AH, n = 108) and without adrenal hyperandrogenism (PCOS-NAH, n = 264). Anthropometric measurements were recorded. Fasting plasma glucose, insulin, lipid profile, sex hormone-binding globulin (SHBG) and androgen (TT, Δ4A, DHEA-S) concentrations were assessed. Free androgen index (FAI) and homeostatic model assessment-insulin resistance (HOMA-IR) index were calculated. RESULTS: Women with PCOS-AH were younger than PCOS-NAH (P < 0.001), but did not differ in the degree and type of obesity. No differences were found in HOMA-IR, total cholesterol, HDL-c, LDL-c and triglyceride concentrations (in all comparisons, P > 0.05). These metabolic parameters did not differ between the two groups even after correction for age. Women with PCOS-AH had lower SHBG (29.2 ± 13.8 vs 32.4 ± 11.8 nmol/L, P = 0.025) and higher TT (1.0 ± 0.2 vs 0.8 ± 0.4 ng/mL, P = 0.05) and Δ4A (3.9 ± 1.2 vs 3.4 ± 1.0 ng/mL, P = 0.007) concentrations, as well as FAI (14.1 ± 8.0 vs 10.2 ± 5.0, P < 0.001). These results were confirmed by a multiple regression analysis model in which adrenal hyperandrogenism was negatively associated with age (P < 0.001) and SHBG concentrations (P = 0.02), but not with any metabolic parameter. CONCLUSIONS: Women with PCOS and adrenal hyperandrogenism do not exhibit any deterioration in insulin resistance and lipid profile despite the higher degree of total androgens.
RESUMO
Advanced glycation end products (AGEs) constitute a complex group of compounds produced endogenously during the aging process and under conditions of hyperglycemia and oxidative stress. AGEs also have an emerging exogenous origin. Cigarette smoke and diet are the two main exogenous sources of AGEs (glycotoxins). Modern Western diets are rich in AGEs which have been implicated in the pathogenesis of several metabolic and degenerative disorders. Accumulating evidence underlies the beneficial effect of the dietary restriction of AGEs not only in animal studies but also in patients with diabetic complications and metabolic diseases. This article reviews the evidence linking dietary glycotoxins to several disorders from diabetic complications and renal failure to liver dysfunction, female reproduction, eye and cognitive disorders as well as cancer. Furthermore, strategies for AGE reduction are discussed with a focus on dietary modification.
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BACKGROUND/AIMS: Advanced glycation end products (AGEs) have been related to a wide range of liver disorders including hyperandrogenic states such as the Polycystic Ovary Syndrome (PCOS). The aim of the present study is to evaluate the potential impact of dietary glycotoxins exposure and androgen excess on hepatic histology and biochemistry in an androgenized female rat model. METHODS: The study population consisted of 80 female Wistar rats, divided in 3 groups, a group of prepubertal (Group A, n=30) and adult rats (Group B, n=20) that were androgenized via subcutaneous implantation of dihydrotestosterone-containing pellets as well as a group of adult non-androgenized rodents (Group C, n=30). All groups were randomly assigned either to a high-AGE or low-AGE diet for 3 months. RESULTS: Rats fed with a high-AGE diet exhibited significantly elevated levels of gamma-glutamyl transferase (x03B3;GT) (p≤0.0002) and indices of AGE immunostaining in liver tissue (p<0.01) when compared to the respective low-AGE group, while aspartate aminotransferase (AST) levels were affected only in non-androgenized animals (p=0.0002). Androgenization per se constitutes an aggravating factor as demonstrated by the elevated x03B3;GT levels in adult androgenized animals compared to non-androgenized, independent of diet content (p=0.0002) and by the elevated AST and alanine aminotransferase (ALT) levels in low-AGE subgroups (adult androgenized vs. non-androgenized, p=0.0002) followed by increased immunohistochemical AGE deposition in hepatocytes of the latter categories (p=0.0007). CONCLUSION: The present study suggests that androgens and glycotoxins may contribute synergistically to distort hepatic physiology and function as observed in hyperandrogenic conditions.
Assuntos
Androgênios/efeitos adversos , Produtos Finais de Glicação Avançada/efeitos adversos , Fígado/efeitos dos fármacos , Síndrome do Ovário Policístico/induzido quimicamente , gama-Glutamiltransferase/metabolismo , Androgênios/farmacologia , Animais , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Produtos Finais de Glicação Avançada/farmacologia , Humanos , Fígado/metabolismo , Síndrome do Ovário Policístico/enzimologia , Ratos , Ratos WistarRESUMO
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of unclear etiopathogenesis that is likely to involve genetic and environmental components synergistically contributing to its phenotypic expression. Endocrine disrupting chemicals (EDCs) and in particular Bisphenol A (BPA) represent a group of widespread pollutants intensively investigated as possible environmental contributors to PCOS pathogenesis. Substantial evidence from in vitro and animal studies incriminates endocrine disruptors in the induction of reproductive and metabolic aberrations resembling PCOS characteristics. In humans, elevated BPA concentrations are observed in adolescents and adult PCOS women compared to reproductively healthy ones and are positively correlated with hyperandrogenemia, implying a potential role of the chemical in PCOS pathophysiology, although a causal interference cannot yet be established. It is plausible that developmental exposure to specific EDCs could permanently alter neuroendocrine, reproductive and metabolic regulation favoring PCOS development in genetically predisposed individuals or it could accelerate and/or exacerbate the natural course of the syndrome throughout life cycle exposure.
Assuntos
Compostos Benzidrílicos/sangue , Disruptores Endócrinos/sangue , Hiperandrogenismo/sangue , Fenóis/sangue , Síndrome do Ovário Policístico/sangue , Adolescente , Feminino , HumanosRESUMO
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of unknown etiology that may arise from a combination of a number of underlying genetic interactions and predispositions with environmental factors. Endocrine disruptors and, in particular, Bisphenol A may represent one of the many underlying causes of the syndrome as they are experimentally linked to metabolic and reproductive derangements resembling PCOS-related disorders. Exposure to endocrine-disrupting chemicals may act as an environmental modifier to worsen symptoms of PCOS in affected females or to contribute to the final phenotype of the syndrome in genetically predisposed individuals.
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Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Síndrome do Ovário Policístico/induzido quimicamente , Animais , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/metabolismo , Feminino , Humanos , Sistemas Neurossecretores/efeitos dos fármacos , Sistemas Neurossecretores/fisiopatologia , Obesidade/induzido quimicamente , Obesidade/metabolismo , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/fisiopatologia , Reprodução/efeitos dos fármacosRESUMO
Glyoxalase detoxification system composed of glyoxalase (GLO)-I and GLO-II is ubiquitously expressed and implicated in the protection against cellular damage because of cytotoxic metabolites such as advanced glycation end products (AGEs). Recently, ovarian tissue has emerged as a new target of excessive AGE deposition and has been associated with either a high AGE diet in experimental animals or hyperandrogenic disorders such as polycystic ovarian syndrome (PCOS) in humans. This study was designed to investigate the impact of dietary AGEs and androgens in rat ovarian GLO-I activity of normal nonandrogenized (NAN, group A, n = 18) and androgenized prepubertal (AN) rats (group B, n = 29). Both groups were further randomly assigned, either to a high-AGE (HA) or low-AGE (LA) diet for 3 months. The activity of ovarian GLO-I was significantly reduced in normal NAN animals fed an HA diet compared with an LA diet (p = 0.006). Furthermore, GLO-I activity was markedly reduced in AN animals compared with NAN (p ≤ 0.001) when fed with the corresponding diet type. In addition, ovarian GLO-I activity was positively correlated with the body weight gain (r(s) = 0.533, p < 0.001), estradiol (r(s) = 0.326, p = 0.033) and progesterone levels (r(s) = 0.500, p < 0.001). A negative correlation was observed between GLO-I activity and AGE expression in the ovarian granulosa cell layer of all groups with marginal statistical significance (r(s) = -0.263, p = 0.07). The present data demonstrate that ovarian GLO-I activity may be regulated by dietary composition and androgen levels. Modification of ovarian GLO-I activity, observed for the first time in this androgenized prepubertal rat model, may present a contributing factor to the reproductive dysfunction characterizing PCOS.
Assuntos
Androgênios/farmacologia , Dieta , Produtos Finais de Glicação Avançada/toxicidade , Lactoilglutationa Liase/metabolismo , Ovário/enzimologia , Síndrome do Ovário Policístico/enzimologia , Animais , Estradiol/metabolismo , Feminino , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Imuno-Histoquímica , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/patologia , Ovário/efeitos dos fármacos , Ovário/patologia , Síndrome do Ovário Policístico/patologia , Ratos , Ratos Wistar , Receptores de Progesterona/metabolismo , Testosterona/metabolismoRESUMO
CONTEXT: Bisphenol A (BPA) is a widespread industrial compound used in the synthesis of polycarbonate plastics. In experimental animals, neonatal exposure to BPA results in a polycystic ovary-like syndrome (PCOS) in adulthood. A bidirectional interaction between androgens and BPA levels has been disclosed. OBJECTIVE: To determine BPA levels in PCOS women as well as the association between BPA and hormonal/metabolic parameters compared to a control group. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of 71 PCOS (National Institutes of Health criteria) and 100 normal women, age- and body mass index-matched, in a University hospital setting. MAIN OUTCOME MEASURES: Anthropometric, hormonal, metabolic parameters and BPA blood levels were determined. Patients (PCOS) and controls (C) were further subdivided according to body mass index into lean and overweight subgroups, respectively. RESULTS: BPA levels were significantly higher in the total PCOS group compared with the controls (1.05±0.56 vs. 0.72±0.37 ng/ml, P < 0.001). PCOS women, lean (PCOS-L) and overweight (PCOS-OW), had higher BPA levels compared to the corresponding control group lean (C-L) and overweight (C-OW): (PCOS-L = 1.13±0.63 vs. C-L = 0.70±0.36, P < 0.001) (PCOS-OW = 0.96 ± 0.46 vs. C-OW = 0.72 ± 0.39, P < 0.05). A significant association of testosterone (r = 0.192, P < 0.05) and androstenedione (r = 0.257, P < 0.05) with BPA was observed. Multiple regression analysis for BPA showed significant correlation with the existence of PCOS (r = 0.497, P < 0.05). BPA was also positively correlated with insulin resistance (Matsuda index) in the PCOS group (r = 0.273, P < 0.05). CONCLUSIONS: Higher BPA levels in PCOS women compared to controls and a statistically significant positive association between androgens and BPA point to a potential role of this endocrine disruptor in PCOS pathophysiology.
Assuntos
Disruptores Endócrinos/sangue , Estrogênios não Esteroides/sangue , Fenóis/sangue , Síndrome do Ovário Policístico/sangue , Adulto , Antropometria , Compostos Benzidrílicos , Índice de Massa Corporal , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Teste de Tolerância a Glucose , Humanos , Hiperandrogenismo/sangue , Resistência à Insulina , Sobrepeso/sangue , Adulto JovemRESUMO
OBJECTIVE: To investigate liver enzymes in a cohort of women with Polycystic Ovary Syndrome (PCOS) and controls divided according to body mass index (BMI) and their association with features of the syndrome. DESIGN: Eighty-three PCOS women and 64 healthy women were studied. Patients and controls were subdivided into two groups, a lean subgroup (BMI <25kg/m(2)) and an overweight/obese subgroup (BMI >25kg/m(2)). Clinical history, height and weight were obtained and metabolic and hormonal parameters were determined. RESULTS: Serum fasting insulin, fasting glucose, HOMA-IR, triglycerides and total cholesterol were significantly higher (p<0.05) in women with PCOS compared to controls. No significant difference in serum liver enzymes levels between PCOS women and controls was detected. However, serum levels of alanine aminotransferase (ALT) (17.7 vs. 14.1 U/L, p<0.05) and gamma-glutamyl transpeptidase (gammaGT) (17.9 vs. 13.4 U/L, p<0.05) were significantly higher in overweight/obese PCOS women compared with overweight/obese controls. In overweight/obese PCOS patients and controls, ALT levels were positively correlated with free androgen index (FAI) (r=0.25 p<0.05) and total testosterone levels (r=0.33 p<0.01). CONCLUSIONS: The finding of elevated liver enzymes in overweight/obese PCOS women raises the question of screening for non-alcoholic fatty liver disease in this group.
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Fígado/enzimologia , Obesidade/enzimologia , Sobrepeso/enzimologia , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/enzimologia , Adulto , Alanina Transaminase/sangue , Glicemia/metabolismo , Estudos de Coortes , Fígado Gorduroso/enzimologia , Feminino , Humanos , Insulina/sangue , Obesidade/sangue , Triglicerídeos , gama-Glutamiltransferase/sangueRESUMO
Polycystic Ovary Syndrome (PCOS), the most frequent endocrinopathy in reproductive-aged women, represents a multifactorial nosologic entity considering its pathogenesis and clinical repercussions. PCOS is characterized mainly by hyperandrogenemia and anovulation, while insulin resistance has been established as a key player in the pathophysiology of the syndrome. The natural course of PCOS appears to originate in fetal life and factors of the intrauterine environment have been incriminated in the early pathogenesis of the syndrome. The clinical picture of PCOS becomes manifest in the peripubertal period, unfolds as patients enter later stages of life and may change over time.