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1.
Lancet Diabetes Endocrinol ; 8(9): 773-781, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32711725

RESUMO

BACKGROUND: Cross-sectional imaging regularly results in incidental discovery of adrenal tumours, requiring exclusion of adrenocortical carcinoma (ACC). However, differentiation is hampered by poor specificity of imaging characteristics. We aimed to validate a urine steroid metabolomics approach, using steroid profiling as the diagnostic basis for ACC. METHODS: We did a prospective multicentre study in adult participants (age ≥18 years) with newly diagnosed adrenal masses. We assessed the accuracy of diagnostic imaging strategies based on maximum tumour diameter (≥4 cm vs <4 cm), imaging characteristics (positive vs negative), and urine steroid metabolomics (low, medium, or high risk of ACC), separately and in combination, using a reference standard of histopathology and follow-up investigations. With respect to imaging characteristics, we also assessed the diagnostic utility of increasing the unenhanced CT tumour attenuation threshold from the recommended 10 Hounsfield units (HU) to 20 HU. FINDINGS: Of 2169 participants recruited between Jan 17, 2011, and July 15, 2016, we included 2017 from 14 specialist centres in 11 countries in the final analysis. 98 (4·9%) had histopathologically or clinically and biochemically confirmed ACC. Tumours with diameters of 4 cm or larger were identified in 488 participants (24·2%), including 96 of the 98 with ACC (positive predictive value [PPV] 19·7%, 95% CI 16·2-23·5). For imaging characteristics, increasing the unenhanced CT tumour attenuation threshold to 20 HU from the recommended 10 HU increased specificity for ACC (80·0% [95% CI 77·9-82·0] vs 64·0% [61·4-66.4]) while maintaining sensitivity (99·0% [94·4-100·0] vs 100·0% [96·3-100·0]; PPV 19·7%, 16·3-23·5). A urine steroid metabolomics result indicating high risk of ACC had a PPV of 34·6% (95% CI 28·6-41·0). When the three tests were combined, in the order of tumour diameter, positive imaging characteristics, and urine steroid metabolomics, 106 (5·3%) participants had the result maximum tumour diameter of 4 cm or larger, positive imaging characteristics (with the 20 HU cutoff), and urine steroid metabolomics indicating high risk of ACC, for which the PPV was 76·4% (95% CI 67·2-84·1). 70 (3·5%) were classified as being at moderate risk of ACC and 1841 (91·3%) at low risk (negative predictive value 99·7%, 99·4-100·0). INTERPRETATION: An unenhanced CT tumour attenuation cutoff of 20 HU should replace that of 10 HU for exclusion of ACC. A triple test strategy of tumour diameter, imaging characteristics, and urine steroid metabolomics improves detection of ACC, which could shorten time to surgery for patients with ACC and help to avoid unnecessary surgery in patients with benign tumours. FUNDING: European Commission, UK Medical Research Council, Wellcome Trust, and UK National Institute for Health Research, US National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.


Assuntos
Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/urina , Metabolômica/métodos , Esteroides/urina , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
2.
Diabetes Metab Res Rev ; 35(2): e3098, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30447052

RESUMO

PURPOSE: To investigate the association of leptin, resistin, and tumour necrosis factor α (TNF-α) with prognosis in type 2 diabetes (T2D). METHODS: Analysis included 284 T2D patients. Apart from routine laboratory parameters, baseline leptin, resistin, and TNF-α concentrations were measured. Patients were followed for a median of 5.4 years. The primary endpoint was all-cause death at follow-up. The secondary endpoint was a composite of death, acute coronary syndrome, and stroke or transient ischemic attack. RESULTS: At baseline, median age was 68 years, and 48% of patients were female. Data on the primary endpoint were obtained for all patients: 32 (11%) died during follow-up. Data on the secondary endpoint were available for 230 patients, of whom 45 (20%) reached the secondary endpoint. In univariate analyses, older age, heart failure, lower-glomerular filtration rate, and higher resistin, TNF-α and NT-proBNP concentrations were predictors of the study endpoints. Of these variables, only resistin remained an independent predictor of both study endpoints in multivariate models. In receiver-operating characteristic analysis, area under the curve for resistin was 0.7. Resistin concentration of greater than or equal to 11.4 ng/mL had sensitivity of 41% and specificity of 91% for prediction of death at follow-up (Youden's index). CONCLUSIONS: Higher resistin is associated with reduced survival in T2D, irrespectively of TNF-α. Resistin concentration of above 11 ng/mL indicates T2D patients at an increased risk of unfavourable outcomes. Leptin was not a prognostic factor. These results suggest that in T2D, association of resistin with unfavourable outcomes might, at least in part, result from its pro-inflammatory properties.


Assuntos
Biomarcadores/metabolismo , Diabetes Mellitus Tipo 2/mortalidade , Leptina/metabolismo , Resistina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Idoso , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
3.
Medicine (Baltimore) ; 97(37): e12372, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30212999

RESUMO

Successful risk stratification is necessary for optimum management of patients after acute coronary syndrome (ACS). The aim of the study was to evaluate the role of novel biochemical markers in the prediction of adverse cardiovascular events in stable patients several years after ACS.The study group was randomly selected from all ACS patients treated with reperfusion therapy between 2002 and 2003 at 1st Department of Cardiology, Medical University of Warsaw, Poland. All patients were readmitted to hospital between 2010 and 2011 for clinical and biochemical cardiovascular risk factors assessment and were prospectively observed for 30-months follow-up. The primary endpoint was all-cause death or hospital readmissions due to a cardiovascular condition at 30 months. The secondary endpoint was a composite of all-cause death or hospitalization-related noncardiovascular condition during the follow-up.The study population consisted of 146 patients (mean age 66.6 ±â€Š9.8 years; 60 female). The primary and secondary endpoints occurred in 49 and 65 patients, respectively. Univariate analysis demonstrated that out of 17 analyzed biomarkers only high-sensitive C-reactive protein (hsCRP), Soluble Fms-Like Tyrosine kinase-1 (sFlt-1), and endothelin-1 (ET-1) were significantly associated with primary end-point and N-Terminal pro-B-type natriuretic peptide (NT-proBNP), hsCRP, ET-1, sFlt-1, and procalcitonin (PCT)-with secondary end-point. Multivariate analysis demonstrated that concentration of sFlt-1 was the only independent factor associated with primary end-point (P = .007 and P = .025, respectively), whereas NT-proBNP and hsCRP levels were only associated with secondary end-point (P = .004 and P = .001, respectively).sFlt-1, NT-proBNP, and hsCRP are associated with adverse outcomes in stable patients several years after ACS and may emerge as useful clinical biomarkers to enhance stratify patient's risk.


Assuntos
Síndrome Coronariana Aguda/sangue , Proteína C-Reativa/análise , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Síndrome Coronariana Aguda/mortalidade , Idoso , Biomarcadores/sangue , Calcitonina/sangue , Causas de Morte , Endotelina-1/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco
4.
J Obstet Gynaecol Res ; 44(6): 1118-1125, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29517119

RESUMO

AIM: The diagnosis of biochemical hyperandrogenism is still challenging because a set of appropriate, recommended diagnostic tests has not been established. In our study, we aimed to answer the question of whether salivary testosterone is a reliable test to establish the diagnosis of biochemical hyperandrogenism as compared to serum total testosterone (TT) measured either by liquid chromatography-tandem mass spectrometry (LC-MS/MS) or immunoassay and to assess which set of biochemical tests would be the most appropriate for the identification of biochemical hyperandrogenism. METHODS: A total of 39 women, aged 18-45 years, with clinical or biochemical hyperandrogenism and 41 healthy individuals, aged 19-45 years, were enrolled in the study. Salivary testosterone was measured using the Salimetrics test. Serum TT was measured either using the LC-MS/MS method or immunoassay, and dehydroepiandrosterone sulphate (DHEA-S) and androstenedione were measured using LC-MS/MS. RESULTS: In 15 of 17 (88%) patients with elevated serum TT measured by LC-MS/MS and in 14 of 16 (87%) measured with immunoassay, salivary testosterone showed normal levels. In 11 of 39 women (28%) with normal serum testosterone levels, DHEA-S was elevated. All patients with elevated androstenedione presented with an elevated concentration of either serum testosterone or DHEA-S. CONCLUSION: Salivary testosterone measurement may lead to the underdiagnosis of biochemical hyperandrogenism. Both serum testosterone and DHEA-S should be measured in the endocrine work-up toward biochemical hyperandrogenism.


Assuntos
Sulfato de Desidroepiandrosterona/metabolismo , Hiperandrogenismo/diagnóstico , Hiperandrogenismo/metabolismo , Saliva/metabolismo , Testosterona/metabolismo , Adolescente , Adulto , Cromatografia Líquida , Sulfato de Desidroepiandrosterona/sangue , Feminino , Humanos , Hiperandrogenismo/sangue , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem , Testosterona/sangue , Adulto Jovem
5.
Endokrynol Pol ; 69(2): 200-204, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29442351

RESUMO

Milk-alkali syndrome (MAS), characterized by renal failure, metabolic alkalosis and hypercalcemia, is a severe and life-threatening complication of the treatment of hypoparathyroidism. The clinical course is often sudden and is not preceded by any prodromal symptoms. Occurrence does not depend on the duration of hypoparathyroidism treatment, although it is closely related to the applied therapy, especially the dose of calcium carbonate and active vitamin D preparations. Drugs influencing the glomerular filtration rate (angiotensin receptor blockers, sartans, aldosterone receptor antagonists, thiazide diuretics), lack of adequate routine control, changing the calcium carbonate supplementation, dehydration, a diet rich in pH-basic foods (i.e. vegetarian diet), pregnancy and other associated conditions are listed among the factors triggering MAS. A higher calcium carbonate dose is directly associated with an increased risk of milk-alkali syndrome. In case of a high calcium demand it is necessary to control renal function and monitor the level of calcium in the serum more frequently, aiming for the lower end of the reference range. If MAS has been confirmed or if there are alarming neurological symptoms suggestive of hypercalcemia, the patient must be sent to the hospital immediately. Treatment of MAS involves: discontinuation of calcium and vitamin D supplementation, and intravenous infusion of normal saline solution to eliminate volume deficiencies and to achieve forced diuresis while maintaining proper fluid balance. As soon as there is improvement in the patient's clinical condition, it is necessary to begin the treatment of comorbidities increasing the risk of renal failure or alkalosis (i.e. vomiting, diarrhea).


Assuntos
Carbonato de Cálcio/efeitos adversos , Hipercalcemia/induzido quimicamente , Hipoparatireoidismo/tratamento farmacológico , Vitamina D/efeitos adversos , Carbonato de Cálcio/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Vitamina D/uso terapêutico
6.
Cent Eur J Immunol ; 43(4): 405-412, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30799988

RESUMO

Introduction: Thyroid stimulating hormone (TSH) receptor antibodies (TRAB) play a role in the development of Graves' orbitopathy (GO), and measurements of the TRAB level may be helpful in monitoring GO treatment. Aim of the study: To assess the correlation of TRAB levels measured with two different assays: third-generation TRAB assay (TRAB Cobas) and novel Immulite assay (TRAB Immulite), in patients with moderate-to-severe GO treated with intravenous glucocorticoid pulse therapy (ivGCs). Material and methods: Forty patients with active, moderate-to-severe GO underwent clinical and laboratory evaluation before, in the middle, and after ivGCs therapy. The correlation of TRAB levels with GO signs was evaluated. Laboratory and clinical findings were compared according to the response to ivGCs. TRAB concentration was measured with Immulite TSI assay and with Elecsys IMA. Results: All patients were TRAB positive in both assays at the beginning of the treatment. The decrease of both TRAB Immulite and Cobas levels in serum during ivGCs was statistically significant. We observed strong correlation between both TRAB levels before and after ivGCs. There was no statistically significant difference in antibody levels between patients with good response and no response to the treatment. We did not find any correlation between antibody levels and GO features before the therapy, but measurements during ivGCs showed comparable correlation of both TRAB levels with GO activity. Conclusions: We found similarity between Immulite assay and third-generation TRAB assay in the assessment of patients with GO treated with ivGCs. Both TRAB levels showed comparable correlation with GO activity during ivGCs therapy.

7.
Psychiatr Pol ; 51(2): 231-246, 2017 Apr 30.
Artigo em Inglês, Polonês | MEDLINE | ID: mdl-28581534

RESUMO

OBJECTIVES: We attempted to assess bone mineralization and the frequency of fractures occurrence in women with a history of treatment of anorexia nervosa (AN) in adolescence. METHODS: 47 women (age 20-36.8 years) were re-examined 6.33-21,2 years after the onset of AN symptoms. Bone mineral density (BMD) of total body, lumbar spine, femoral neck, total hip (DXA) and densitometric Vertebral Fracture Assessment (VFA) were performed on 46 of women and BAP, P1NP, CTX, estradiol, testosterone, cortisol, IGF-1, leptin, DHEA-S on 45 of women entered for the current study. Current BMD results were compared with available baseline results from the time of hospitalization. RESULTS: Currently BMD Z-score <-1 examined at any location occurred in 28 from 46 women (including Z-score <-2 in 5 women). In 11 from 12 women with reduced BMD at the time of hospitalization current total body BMD was within the normal range. Lumbar spine BMD was normalized or improved respectively in 5 and 6 from 15 women. Currently increased levels/activity of bone formation markers: P1NP in 27 (60%) and BAP in 28 women (62.2%) were observed. In 7 women (15.6%) increased values of bone formation markers with increased marker of bone resorption (CTX) occurred. Osteoporotic fractures and fractures in the spine in VFA were not observed during the observation period. CONCLUSIONS: Despite early treatment of adolescent-onset AN and good outcomes of the treatment, decreased BMD was currently present in 60.9% of women. During follow-up normalization or significant improvement in BMD results (total body, lumbar spine) were observed in majority of cases.


Assuntos
Anorexia Nervosa/complicações , Anorexia Nervosa/fisiopatologia , Desmineralização Patológica Óssea/etiologia , Densidade Óssea/fisiologia , Vértebras Lombares/lesões , Fraturas por Osteoporose/etiologia , Absorciometria de Fóton , Adulto , Desmineralização Patológica Óssea/diagnóstico por imagem , Densitometria , Difosfonatos/uso terapêutico , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Pessoa de Meia-Idade , Fraturas por Osteoporose/diagnóstico por imagem
8.
Ginekol Pol ; 88(1): 5-8, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28157253

RESUMO

OBJECTIVES: Total testosterone/dihydrotestosterone ratio (TT/DHT) was found to determine metabolic risk in polycystic ovary syndrome (PCOS). The aim of this study was to analyze whether (TT/DHT) may be helpful in predicting metabolic risk not only in PCOS patients but also in healthy women. MATERIAL AND METHODS: Total testosterone (TT), dihydrotestosterone (DHT), androstendione and dehydroepiandrosterone sulphate (DHEA-S) were measured by LC-MS/MS in 36 women with PCOS and in 29 age-matched controls without clinical hyperandrogenism. In all participants, anthropometric data, lipids, adipose tissue percent (%fat), HOMA-IR were also assessed. RESULTS: The studied groups were not different in terms of age, BMI, waist circumference, %fat and HOMA-IR. In the patients group, mean TT and androstendione levels were significantly higher as compared to controls (1.4 nmol/L vs. 1.0 nmol/L, P < 0.001) and (6.6 nmol/L vs. 4.9 nmol/L, P < 0.01), respectively. In the patients group, mean TT/DHT ratio was significantly higher compared to controls (3.6 vs. 2.7, P < 0.01) and correlated with BMI (r = 0.37, P < 0.05), waist circumference (r = 0.44, P < 0.01), %fat (r = 0.30, P < 0.05), as well as with insulin levels (r = 0.38, P < 0.05) and HOMA-IR (r = 0.44, P < 0.05). The association between TT/DHT ratio and unfavorable metabolic parameters was also seen in controls. CONCLUSION: Total testosterone/dihydrotestosterone ratio assessed by LC-MS/MS correlates with a worse metabolic profile not only in PCOS patients, but also in healthy women.


Assuntos
Tecido Adiposo , Androstenodiona/sangue , Sulfato de Desidroepiandrosterona/sangue , Di-Hidrotestosterona/sangue , Resistência à Insulina , Insulina/sangue , Síndrome do Ovário Policístico/sangue , Testosterona/sangue , Adolescente , Adulto , Composição Corporal , Índice de Massa Corporal , Estudos de Casos e Controles , Cromatografia Líquida , Feminino , Humanos , Prognóstico , Espectrometria de Massas em Tandem , Circunferência da Cintura , Adulto Jovem
9.
Clin Endocrinol (Oxf) ; 83(6): 774-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26173372

RESUMO

OBJECTIVES: The diagnosis of adrenal dysfunction in pregnancy and in women taking oral contraceptives remains a diagnostic challenge. Salivary cortisol seems to be a useful tool for the diagnosis of Cushing's syndrome and adrenal insufficiency. However, the changes in salivary cortisol concentration in healthy pregnancy are not clearly defined. DESIGN: The aim of our study was to compare diurnal changes in salivary cortisol in healthy pregnant women, healthy controls and women on oral contraceptives. PATIENTS: The study groups consisted of (i) 41 healthy pregnant women, (ii) 42 healthy women and (iii) 12 healthy women on oral contraceptives. MEASUREMENTS: Serum and salivary cortisol in the morning and salivary late-night cortisol were measured with Roche ECLIA cortisol test (Elecsys 2010) in each trimester and postpartum. RESULTS: Despite the elevation of morning serum cortisol in the second and third trimesters of pregnancy, the morning salivary values as well as late-night salivary cortisol throughout all trimesters were not significantly different from control values (P > 0·5). In the postpartum period, the morning and late-night salivary cortisol values were significantly lower than in late pregnancy. The morning and late-night salivary cortisol values in women on contraceptives were also not different from those in the healthy women group. CONCLUSION: The results of our study suggest that reference values for salivary cortisol established for a healthy adult population can be used for pregnant women and women on oral contraceptives in the initial diagnostic testing for Cushing's syndrome and adrenal insufficiency.


Assuntos
Hidrocortisona/análise , Hidrocortisona/sangue , Saliva/química , Insuficiência Adrenal/sangue , Insuficiência Adrenal/diagnóstico , Adulto , Anticoncepcionais Orais , Síndrome de Cushing/sangue , Síndrome de Cushing/diagnóstico , Feminino , Humanos , Gravidez , Estudos Prospectivos
10.
Endocr Pract ; 21(9): 993-1000, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26121457

RESUMO

OBJECTIVE: The diagnosis of celiac disease (CD) in patients with different autoimmune diseases including Graves disease (GD) remains a challenge. The aims of our study were to: (1) assess the prevalence of CD in Polish patients with GD and (2) evaluate the prevalence of CD in the subgroups of patients with GD divided on the basis of clinical and human leukocyte antigen (HLA) typing criteria. METHODS: The prospective study was conducted at an academic referral center. The study groups consisted of consecutive, euthyroid patients with GD (n = 232) and healthy volunteers without autoimmune thyroid diseases (n = 122). The diagnosis of CD was based on elevated immunoglobulin A autoantibodies to the enzyme tissue transglutaminase (IgA-TTG) and small intestine biopsy findings. RESULTS: CD was diagnosed in 8 patients with GD (3.4%) and 1 healthy volunteer (0.8%). The development of CD in patients with GD was strongly associated with HLA-DQ2 haplotype (as predicted from linkage disequilibria, 14.6% vs. 1.5%, P = .009; odds ratio [OR] = 11.3; 95% confidence interval [CI] 1.3-252.7): 6 patients with CD carried HLA-DRB1(*)03, 1 carried an HLA-DRB1(*)04 allele, and 1 had an HLA-DRB1(*)07/(*)11 genotype. Multivariate analysis showed independent associations between CD and early GD onset (P = .014, OR = 9.6), autoimmunity in family (P = .029, OR = 6.3) and gastroenterologic symptoms (P = .031, OR = 8.1). CONCLUSIONS: The results of our study suggest that serologic screening for CD may be considered in GD patients (1) with the HLA alleles typical for CD, (2) with an early onset of GD, or (3) a family history of autoimmunity. Moreover, the diagnosis of CD should be explored in euthyroid GD patients with nonspecific gastrointestinal symptoms.


Assuntos
Doenças Autoimunes/genética , Doença Celíaca/genética , Doença de Graves/genética , Antígenos HLA-DQ/genética , Haplótipos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Celíaca/complicações , Feminino , Predisposição Genética para Doença , Doença de Graves/complicações , Cadeias HLA-DRB1 , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
11.
Pol Arch Med Wewn ; 125(6): 414-23, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25978118

RESUMO

INTRODUCTION: Data regarding the effect of certain adipokines on lipid metabolism are equivocal. OBJECTIVES: The aim of this study was to evaluate the association of lipid control with adipokines and inflammatory markers in patients with type 2 diabetes. PATIENTS AND METHODS: The analysis included 195 patients with type 2 diabetes. The achievement of treatment targets in terms of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides was assessed in accordance with the current guidelines. Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) index as well as concentrations of highmolecular-weight (HMW) adiponectin, leptin, resistin, high-sensitivity C-reactive protein, interleukin 6, and tumor necrosis factor α (TNF-α) were measured in all patients. Logistic regression analyses were performed to determine the risk factors for inadequate lipid control. RESULTS: Optimal control in terms of total cholesterol, LDL, HDL, and triglycerides was achieved in 61%, 43%, 53%, and 68% of the patients, respectively. In multivariate analyses, female sex, lower resistin concentrations, and the absence of statin treatment were predictors of total cholesterol levels above the treatment target; older age and lower statin dose--of LDL cholesterol levels above the treatment targets; female sex, higher HOMA-IR index, lower HMW adiponectin concentrations, and higher TNF-α concentration-o-f HDL levels below the treatment targets; and higher HOMA-IR, lower HMW adiponectin concentration, and the absence of statin treatment--of triglycerides above the treatment target. CONCLUSIONS: In type 2 diabetes, lower HMW adiponectin concentrations are associated with inadequate triglyceride and HDL control; higher TNF-α, with inadequate HDL control, and lower resistin concentrations, with inadequate total cholesterol control.


Assuntos
Adipocinas/sangue , Proteína C-Reativa/análise , Diabetes Mellitus Tipo 2/sangue , Metabolismo dos Lipídeos , Fator de Necrose Tumoral alfa/sangue , Idoso , Biomarcadores/sangue , Colesterol/sangue , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Inflamação , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Pessoa de Meia-Idade , Fatores de Risco , Triglicerídeos/sangue
12.
Gynecol Endocrinol ; 31(4): 296-300, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25539143

RESUMO

Basal serum 17OHP measurement remains the first screening step for nonclassic congenital adrenal hyperplasia (NCCAH) and the accuracy of the test is of high value. The aim of this study was to compare the accuracy of immunoassays to LC-MS/MS in the assessment of serum 17OHP and androgens concentration in women with hyperandrogenism and controls. 17OHP, total testosterone, androstendione and DHEA-S were measured in 39 women with clinically and/or biochemically evident hyperandrogenism and in 29 age-matched controls without clinical hyperandrogenism. 17OHP and androgens were measured by immunoassays and by LC-MS/MS. In patients group median 17OHP level measured by immunoassays was significantly higher compared to LC-MS/MS (5.49 nmol/l-ELISA NovaTec® and 3.57 nmol/l-ELISA DRG® versus 1.56 nmol/l-LC-MS/MS p < 0.0001) as well as in the control group (2.58 nmol/l-ELISA DRG® versus 1.14 nmol/l-LC-MS/MS p < 0.0001). Additional, unnecessary diagnostic procedures explaining elevated 17OHP level were undertaken in 85% of patients when NovaTec® test was used, in 50% when ELISA DRG® and in none when LC-MS/MS method was applied. Total testosterone, androstendione and DHEA-S concentrations in the patients and the controls assessed by the immunoassays were also significantly higher compared to LC-MS/MS. LC-MS/MS is more reliable diagnostic tool in the measurement of serum 17OHP and androgens concentrations compared to immunoassays in women with hyperandrogenism.


Assuntos
17-alfa-Hidroxiprogesterona/sangue , Hiperplasia Suprarrenal Congênita/diagnóstico , Adolescente , Hiperplasia Suprarrenal Congênita/sangue , Adulto , Androstenodiona/sangue , Cromatografia Líquida de Alta Pressão , Sulfato de Desidroepiandrosterona/sangue , Diagnóstico Diferencial , Reações Falso-Positivas , Feminino , Hospitais Universitários , Humanos , Imunoensaio , Polônia , Kit de Reagentes para Diagnóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem , Testosterona/sangue , Adulto Jovem
13.
Cardiovasc Diabetol ; 13: 112, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-25123549

RESUMO

BACKGROUND: Evidence from the literature suggests diminished acetylsalicylic acid (ASA) treatment efficacy in type 2 diabetes (DM2). High on-aspirin platelet reactivity (HAPR) in DM2 has been linked to poor glycemic and lipid control. However, there are no consistent data on the association between HAPR and insulin resistance or adipose tissue metabolic activity. The aim of this study was to assess the relationship between laboratory response to ASA and metabolic control, insulin resistance and adipokines in DM2. METHODS: A total of 186 DM2 patients treated with oral antidiabetic drugs and receiving 75 mg ASA daily were included in the analysis. Response to ASA was assessed by measuring serum thromboxane B2 (TXB2) concentration and expressed as quartiles of TXB2 level. The achievement of treatment targets in terms of glycemic and lipid control, insulin resistance parameters (including Homeostatic Model Assessment-Insulin Resistance, HOMA-IR, index), and serum concentrations of high-molecular weight (HMW) adiponectin, leptin and resistin, were evaluated in all patients. Univariate and multivariate logistic regression analyses were performed to determine the predictive factors of serum TXB2 concentration above the upper quartile and above the median. RESULTS: Significant trends in age, body mass index (BMI), HOMA-IR, HMW adiponectin concentration, C-reactive protein concentration and the frequency of achieving target triglyceride levels were observed across increasing quartiles of TXB2. In a multivariate analysis, only younger age and higher BMI were independent predictors of TXB2 concentration above the upper quartile, while younger age and lower HMW adiponectin concentration were predictors of TXB2 concentration above the median. CONCLUSIONS: These results suggest that in DM2, the most important predictor of HAPR is younger age. Younger DM2 patients may therefore require total daily ASA doses higher than 75 mg, preferably as a twice-daily regimen, to achieve full therapeutic effect. Higher BMI and lower HMW adiponectin concentration were also associated with less potent ASA effect. This is the first study to demonstrate an association of lower adiponectin concentration with higher serum TXB2 level in patients treated with ASA.


Assuntos
Adiponectina/sangue , Aspirina/uso terapêutico , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Tromboxano B2/sangue , Fatores Etários , Idoso , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Resultado do Tratamento
14.
Arch Med Sci ; 10(6): 1198-205, 2014 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-25624859

RESUMO

INTRODUCTION: The objective of this study was to investigate the effect of common single nucleotide genomic polymorphisms in the cyclooxygenase-1 (COX-1) gene on the thromboxane A2 (TxA2) metabolite concentrations in serum and urine, as well as on prostaglandin F2α (PGF2α) urinary excretion in the diabetic population on acetylsalicylic acid (ASA) therapy. MATERIAL AND METHODS: The study cohort consisted of 284 Caucasians with diabetes type 2 who had been taking ASA tablets at the dose of 75 mg/day for at least 3 months. Genotyping for the 4 selected SNPs within the COX-1 gene (two nonsynonymous-coding variants, rs3842787 [C50T, P17L] and rs5789 [C174A, L237M]; and two other synonymous SNPs, rs3842788 [G128A, Q41Q] and rs5788 [C644A]) was performed using the Sequenom iPLEX platform. RESULTS: No statistically significant results were observed for the investigated SNPs and measured metabolites in the investigated cohort of patients. Statistically significant differences in S-TxB2 could however be observed for rs5788 in the subgroup of patients with very high S-TxB2 concentrations. In particular, more patients who were carriers of the minor allele for this polymorphism were observed in the group with S-TxB2 levels > 95(th) percentile, when compared with similar carriers in the group with S-TxB2 < 95(th) percentile (20% vs. 1.1%, respectively, p < 0.001, Mann-Whitney test). CONCLUSIONS: The results of our study suggest that the four investigated common SNPs in the COX1 gene are not associated with obviously altered TxA2 metabolism and PGF2α synthesis in the investigated diabetic cohort treated with ASA.

15.
Kardiol Pol ; 71(9): 893-902, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24065375

RESUMO

BACKGROUND: Diabetes mellitus type 2 (DM2) is associated with high platelet reactivity both in patients who do not receive antiplatelet drugs and in those treated with acetylsalicylic acid (ASA). The pathomechanism of this phenomenon has not been fully understood. AIM: 1. To evaluate variability of platelet reactivity in patients with DM2 treated with oral antidiabetic drugs and receiving chronic ASA therapy. 2. To identify independent predictors of high platelet reactivity during ASA therapy in patients with DM2. METHODS: We studied 171 patients with DM2 treated with oral antidiabetic drugs and receiving long-term treatment with 75 mg of ASA daily, selected among the participants of the prospective AVOCADO study. Platelet function was simultaneously evaluated using 4 methods: 1. measurement of serum thromboxane B2 (TXB2) concentration; 2. measurement of urinary 11-dehydrothromboxane B2 (11-dhTXB2) concentration; 3. VerifyNow® automated analyser; 4. PFA-100® automated analyser.High platelet reactivity was defined as at least 3 of the following criteria: 1. serum TXB2 concentration in the upper quartile;2. urinary 11-dhTXB2 concentration in the upper quartile; 3. value ≥ 550 aspirin reaction units (ARU) by VerifyNow®;4. collagen-epinephrine closure time (CEPI-CT) below median of readings other than 300 s by PFA-100®. In all patients, DM2 control was evaluated, insulin resistance was measured using HOMA-IR, and routine laboratory tests were performed, including full blood count, renal function parameters, and inflammation markers. RESULTS: Mean patient age was 67.8 years, and median duration of DM2 was 5 years. We found poor agreement between different tests of platelet function. ARU ≥ 550 (VerifyNow®) was found in 14.0% of patients, and CEPI-CT below median of readings other than 300 s (PFA-100®) was found in 32.8% of patients. Our criteria of high platelet reactivity were met by 9.9% of patients. In multivariate logistic regression analysis, independent predictors of high platelet reactivity despite ASA therapy included chronic heart failure, current smoking, and higher leukocyte count. CONCLUSIONS: 1. Patients with DM2 are characterised by large variability of platelet reactivity, with little agreement between various methods. 2. Smoking, chronic heart failure, and subclinical inflammation may be associated with high platelet reactivity in patients with DM2 treated with ASA.


Assuntos
Aspirina/administração & dosagem , Plaquetas/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Inibidores da Agregação de Plaquetas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores/urina , Transtornos Plaquetários/sangue , Transtornos Plaquetários/tratamento farmacológico , Transtornos Plaquetários/etiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/urina , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/urina , Cardiomiopatias Diabéticas/sangue , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/prevenção & controle , Cardiomiopatias Diabéticas/urina , Quimioterapia Combinada , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Agregação Plaquetária/efeitos dos fármacos , Estudos Prospectivos , Tromboxano B2/análogos & derivados , Tromboxano B2/sangue , Tromboxano B2/urina
16.
Mol Med Rep ; 8(3): 853-60, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23828562

RESUMO

The aim of the present study was to investigate the effect of genetic polymorphisms in candidate genes within the leukotriene (LT) pathway on platelet reactivity and the concentration of selected LTs in diabetic patients treated with acetylsalicylic acid (ASA). The study cohort consisted of 287 Caucasians with type 2 diabetes who had received treatment with ASA tablets (75 mg/day) for at least three months. Platelet reactivity analyses were performed using VerifyNow aspirin and PFA­100 assays. The measured LTs included leukotriene B4 (LTB4) and leukotriene E4 (LTE4). Genotyping for the selected 25 single nucleotide polymorphisms (SNPs) within six genes of the LT pathway was performed using a Sequenom iPLEX platform. No statistically significant association was observed between the investigated SNP genotypes, platelet reactivity and measured LTs in the patient cohort. The results of our study suggest that certain polymorphisms of the LT pathway are not associated with altered platelet reactivity and the measured LTs in diabetic patients treated with ASA.


Assuntos
Proteínas Ativadoras de 5-Lipoxigenase/genética , Araquidonato 12-Lipoxigenase/genética , Araquidonato 15-Lipoxigenase/genética , Araquidonato 5-Lipoxigenase/genética , Plaquetas/metabolismo , Diabetes Mellitus Tipo 2/genética , Epóxido Hidrolases/genética , Glutationa Transferase/genética , Idoso , Alelos , Aspirina/uso terapêutico , Estudos de Coortes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Frequência do Gene , Genótipo , Humanos , Leucotrieno B4/metabolismo , Leucotrieno E4/metabolismo , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
17.
Endokrynol Pol ; 64(3): 238-45, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23873430

RESUMO

Increased interest in vitamin D measurements in clinical studies has contributed to the development in recent years of several new immunochemical assays (manual and for automatic analyzers). New methods, including HPLC (high performance liquid chromatography), and LC-MS/MS (liquid chromatography coupled with tandem mass spectrometry) have also been introduced into routine diagnostic laboratories. Because of the variety of assays and methods used, the question arises which one is the most accurate for the measurement of vitamin D metabolites concentration. In this review, we summarise the advantages and disadvantages of these methods, describe the complexity of vitamin D metabolites pattern in the circulation, and discuss the problem of accurate measuring its concentration.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Vitamina D/sangue , Cromatografia Líquida/métodos , Humanos , Vitamina D/análise
18.
Ginekol Pol ; 84(5): 363-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23819402

RESUMO

BACKGROUND/OBJECTIVES: Ensuring the optimal level of 25-hydroxy-vitamin D (250HD) in serum (concentration above 30 ng/ml) is essential for protecting the health of the mother and the developing fetus. Vitamin D plays an important role in maintaining proper bone structure, preventing infections, reducing the risk of premature birth and gestational diabetes. The aim of the study was to verify whether healthy pregnant residents of Warsaw were deficient in vitamin D. MATERIAL AND METHODS: The material consisted of 150 serum samples of 50 healthy women in 1st, 2nd and 3rd trimester of pregnancy 72.7% of the sera were from women who reported taking multivitamin supplements containing vitamin D3 (71% out of that group was taking 400 IU daily). The concentration of 250HD was measured using the vitamin D total assay on Elecsys 2010 automatic analyzer (Roche Diagnostics). RESULTS: The average serum 250HD concentrations of 50 women in 1st, 2nd and 3rd trimester of pregnancy were respectively: 23.1 ng/ml, 24.8 ng/ml, and 25.1 ng/ml, with no statistically significant differences. The optimal levels of 250HD (30-80 ng/ml) were found in 30.0% of samples, hypovitaminosis (20-30 ng/ml) occurred in 38.7%, deficiency (10-20 ng/ml) in 24.0% and severe deficiency (less than 10 ng/ml) in 7.3% of cases. Mean concentration of 250HD in winter season (October 1 - March 31) was 23.6 ng/ml and in summer season (April 1 - September 30) was 25.5 ng/ml, with no statistically significant difference. On the basis of the BMI in 1st trimester two subgroups were distinguished from the studied subjects: BMI <21 (13 patients, 39 samples) and BMI >25 (14 patients, 42 samples). Mean 250HD concentration in these groups were 27.3 and 23.5 ng/ml respectively (p<0.05). High statistical significance (p<0.001) was found among the total number of samples with 250HD deficiency and severe deficiency (<20 ng/ml) and samples with hypovitaminosis and optimal 250HD level (>20 ng/ml) in these groups. CONCLUSIONS: Regardless of trimester and season, vitamin D below the optimal level is a common occurrence during pregnancy and the current level of supplementation among Polish pregnant women appears to be insufficient. Our data suggest that special attention should be paid to the problem of vitamin D insufficiency in overweight pregnant women.


Assuntos
Nível de Saúde , Complicações na Gravidez/epidemiologia , População Urbana/estatística & dados numéricos , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Saúde da Mulher , Adulto , Índice de Massa Corporal , Comorbidade , Feminino , Humanos , Bem-Estar Materno/estatística & dados numéricos , Obesidade/epidemiologia , Polônia/epidemiologia , Gravidez , Complicações na Gravidez/sangue , Cuidado Pré-Natal/métodos , Prevalência , Estações do Ano , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Adulto Jovem
19.
Pol Merkur Lekarski ; 34(202): 200-4, 2013 Apr.
Artigo em Polonês | MEDLINE | ID: mdl-23745325

RESUMO

UNLABELLED: Iodine deficiency and thyroid gland disorders are especially harmful for pregnant women and normal fetal development. After initiation in 1997 of obligatory iodine prophylaxis, Poland has been found since 2003 a country with sufficient delivery of this microelement. However, in the population of pregnant women, slight deficiency of this element still exists. Insufficient iodine supply results in abnormalities of thyroid hormones'biosynthesis. Simultaneously, adaptive changes, occurring in pregnancy, make the proper interpretation of hormone's assays difficult. Lack of normative data for the thyroid hormones concentration in the each pregnancy trimester for Polish population cause additional difficulties in the interpretation of these results. The aim of the study was prospective observation of iodine intake and thyroid function in healthy pregnant women supplemented with 150 pg of iodine daily MATERIALS AND METHODS: 62 healthy pregnant women living in Warsaw in the early weeks of pregnancy, confirmed by ultrasonographic examination, were included to this study. Pregnancies were singleton resulting in birth of healthy neonates. Urinary iodine concentrations (UIC), serum TSH, fT4, fT3, antyTPO, thyroid volume and morphology by the ultrasonography examination were assessed in consecutive trimesters of pregnancy. TSH level was measured in the each newborn. RESULTS: Low urinary iodine concentrations (UIC)-median 96 microg/l was found at the beginning of pregnancy Only in 14% of pregnant women UIC exceeded 150 microg/l. In spite of intended supplementation of at least 150 microg of extra iodine per day, medians of UIC in the next trimesters were 122 microg/l and 129 microg/l, respectively. TSH levels kept reference values for the 1st trimester of pregnancy in 86% of participants and in the next trimesters in 85% and 95%, respectively. Levels of fT4 were within reference range for the women in the 1st trimester. In 2nd trimester 12% and in 3rd trimester 33% of pregnant women had fT4 level below the reference value. Concentrations of fT3 were within reference values during whole pregnancy. Median thyroid volume was respectively 11.12 ml; 13.0 ml and 15.75 ml (range: 6.8-26.8 ml) in subsequent trimesters.Median neonatal' TSH level on the 3rd day of life, as a screening of thyroid insufficiency, was 1.34 mlU/l (range: 0.01-6.6 mlU/l) and in 4.41 % of newborns TSH concentrations were higher than 5 mlU/I. CONCLUSION: Despite the sufficient supply of iodine in the whole population, iodine consumption among the pregnant women is still not satisfactory. The increase of TSH values above the upper reference level for pregnant women in 15% of patients may be related to iodine deficiency. It is important to educate pregnancy planning women about this problem. Our observations confirm the importance of the recommendations that during the pregnancy every woman should receive supplementation of iodine at the minimal amount of 150 microg daily.


Assuntos
Iodo/administração & dosagem , Iodo/urina , Glândula Tireoide/diagnóstico por imagem , Hormônios Tireóideos/sangue , Adulto , Suplementos Nutricionais , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Valores de Referência , Testes de Função Tireóidea , Ultrassonografia Pré-Natal , Adulto Jovem
20.
Med Sci Monit ; 19: 394-408, 2013 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-23715170

RESUMO

BACKGROUND: Platelet reactivity in patients on acetylsalicylic acid (ASA) therapy can be influenced by physiological or pathological conditions affecting ASA pharmacokinetics or pharmacodynamics. The mechanism of such variability in the therapeutic response to ASA, particularly in diabetic patients, is poorly understood. The rate of elimination of ASA and its metabolite, salicylic acid (SA), is likely a major factor determining drug efficacy. The objective of this study was to investigate the effect of genetic polymorphisms in the selected candidate genes within the ASA metabolic pathway on the platelet reactivity and concentration of ASA and thromboxane A(2) (TxA(2)) metabolites in a population of patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: The study cohort consisted of 287 Caucasians with T2DM who had been taking ASA tablets at the dose of 75 mg per day for at least 3 months. Platelet reactivity analyses were performed using VerifyNow Aspirin and PFA-100 assays. The measured ASA metabolite included salicylic acid (ASA), and TxA(2) metabolites included serum TxB(2) and urinary 11-dh-TxB(2). Genotyping for the selected 18 single-nucleotide polymorphisms (SNPs) within 5 genes of the ASA metabolic pathway was performed using a Sequenom iPLEX platform. RESULTS: No statistically significant association was observed between the investigated SNPs genotypes, platelet reactivity, and measured metabolites in the investigated cohort of patients. CONCLUSIONS: The results of our study failed to confirm that the selected variants in the genes within the ASA metabolic pathway might contribute to platelet reactivity in a diabetic population treated with ASA.


Assuntos
Aspirina/metabolismo , Plaquetas/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Redes e Vias Metabólicas/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Demografia , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino
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