RESUMO
AIM: To assess serum chemerin levels and investigate the association of chemerin with the hyperandrogenic and normoandrogenic phenotypes of Polycystic Ovary Syndrome (PCOS) and with the metabolic status of the analyzed population. MATERIAL AND METHODS: A cross-sectional study was conducted on 106 women with PCOS and 60 healthy controls from Argentina. Patients were classified as showing a hyperandrogenic or normoandrogenic phenotype. Participants underwent anthropometric and clinical evaluation and markers of cardiovascular risk, insulin resistance, metabolic syndrome (MS), and serum chemerin levels were assessed. RESULTS: PCOS patients showed increased levels of chemerin. In adjusted models for age and body mass index (BMI), chemerin was associated with markers of metabolic status. The analysis of chemerin levels considering the cutoff values of BMI, homeostatic model of insulin sensitivity (HOMA-IR) and TG/HDL marker showed that PCOS patients always presented higher levels of chemerin than controls. PCOS group showed increased chemerin levels independently of the presence of MS. CONCLUSION: PCOS patients always showed increased levels of chemerin independently of their phenotype and presence of overweight, as well as higher levels of chemerin than controls when considering the cutoff values of HOMA-IR and TG/HDL. Therefore, argentine women with PCOS display increased chemerin levels independently of their metabolic or androgenic status.
Assuntos
Quimiocinas/sangue , Hiperandrogenismo/sangue , Síndrome Metabólica/sangue , Síndrome do Ovário Policístico/sangue , Adulto , Argentina , Índice de Massa Corporal , Estudos de Casos e Controles , HDL-Colesterol/sangue , Feminino , Humanos , Resistência à Insulina , Triglicerídeos/sangue , Circunferência da Cintura , Adulto JovemRESUMO
CONTEXT: 21-hydroxylase deficiency is the most common cause of Congenital Adrenal Hyperplasia. It presents as severe or classical forms-salt wasting and simple virilizing-and a mild or nonclassical (NC). Several studies have reported the frequency of pathogenic variants in different populations, although few of them included a large number of NC patients. OBJECTIVE: To analyse the CYP21A2 gene defects in a large cohort of Argentine patients. DESIGN: Molecular characterization of 628 patients (168 classical, 460 nonclassical, representing 1203 nonrelated alleles), 398 relatives, 126 partners. METHODS: Genetic variants were assessed by allele-specific PCR, PCR-RFLP or direct sequencing. Deletions, duplications and large gene conversions (LGC) were studied by Southern blot/MLPA or long-range PCR. Biological implications of novel variants were analysed by structure-based in silico studies. RESULTS: The most frequent pathogenic variants were p.V282L (58%) in NC alleles and c.293-13C>G (31.8%) and p.I173N (21.1%) in classical. Deletions and LGC were found at low frequency (6.2%), 57 alleles had rare pathogenic variants, and 3 had novel variants: p.(S166F); p.(P189R), p.(R436L). Genotype-phenotype correlation was observed in 98.6% of the cases, 11 asymptomatic first-degree relatives had pathogenic variants in both alleles, and 21/126 partners were carriers. CONCLUSIONS: We conducted a comprehensive genetic characterization of the largest cohort of 21-hydroxylase patients from the region. In particular, we add to the molecular characterization of a large number of NC patients and to the estimation of the disease carrier's frequency in our population.
Assuntos
Hiperplasia Suprarrenal Congênita , Hiperplasia Suprarrenal Congênita/genética , Alelos , Genótipo , Humanos , Mutação , Fenótipo , Esteroide 21-Hidroxilase/genéticaRESUMO
The premutation state of FMR1 (Fragile X Mental Retardation 1) has been associated with primary ovarian insufficiency (POI), and is the most common known genetic cause for 46,XX patients. Nevertheless, very few studies have analyzed its frequency in Latin American populations. Additionally, a relationship between alleles carrying a cryptic microdeletion in the 5'UTR of FMR2 and the onset of POI has only been studied in one population. Our aim was to analyze the incidence of FMR1 premutations and putative microdeletions in exon 1 of FMR2 in a cohort of Argentinean women with POI. We studied 133 patients and 84 controls. Fluorescent PCR was performed, and the FMR2 exon 1 was further sequenced in samples presenting less than 11 repeats. We found the frequency of FMR1 premutations to be 6.7% and 2.9% for familial and sporadic patients, respectively. Among controls, 1/84 women presented a premutation. In addition, although we did not find microdeletions in FMR2, we observed a change (T >C) adjacent to the repeats in two sisters with POI. Given the repetitive nature of the sequence involved, we could not ascertain whether this represents a single nucleotide polymorphism (SNP) or a deletion. Therefore, a relationship between FMR2 and POI could not be established for our population.
RESUMO
Polycystic ovary syndrome (PCOS) is an endocrine disorder. PCOS women are at high risk of developing insulin resistance (IR) and cardiovascular disorders since young age. We aimed to study the reliability of lipid accumulation product (LAP) and visceral adiposity index (VAI) as markers of metabolic disturbances (MD) associated with IR in young reproductive aged PCOS patients. We also evaluated the association between LAP and VAI and the presence of hyperandrogenism. In a cross-sectional study, 110 PCOS patients and 88 control women (18-35 years old) were recruited. PCOS patients were divided into 2 groups, as hyperandrogenic and non-hyperandrogenic considering the signs of hyperandrogenism (clinical or biochemical). Anthropometric measurements were taken and blood samples collected. Metabolic and anthropometric characteristics and their association with IR and associated MD were evaluated and LAP and VAI were calculated. LAP and VAI were compared with TC/HDL-c and TG/HDL-c to define the best markers of MD in this population. Independently of the phenotype, young PCOS patients showed high IR and dyslipidemia. Both LAP and VAI showed to be more effective markers to assess MD and IR in these young women than TG/HDL-c or TC/HDL-c [cut-off values: LAP: 18.24 (sensitivity: 81.43% specificity: 73.49%), positive predictive value (PPV): 75.0%, negative predictive value (NPV): 77.27%, VAI: 2.19 (sensitivity: 81.16% specificity: 72.15% PPV: 74.65% NPV: 72.22%)]. LAP and VAI are representative markers to assess MD associated with IR in young PCOS patients. All PCOS patients, independently of their androgenic condition, showed high metabolic risk.
Assuntos
Biomarcadores , Resistência à Insulina , Gordura Intra-Abdominal/patologia , Produto da Acumulação Lipídica , Doenças Metabólicas/complicações , Síndrome do Ovário Policístico/complicações , Adiposidade/fisiologia , Adolescente , Adulto , Argentina , Biomarcadores/metabolismo , Estudos Transversais , Feminino , Humanos , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/etiologia , Doenças Metabólicas/patologia , Obesidade Abdominal/complicações , Obesidade Abdominal/diagnóstico , Obesidade Abdominal/metabolismo , Obesidade Abdominal/patologia , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Diâmetro Abdominal Sagital , Adulto JovemRESUMO
Introducción: El síndrome de ovario poliquístico (SOP) es una endocrinopatía que afecta a mujeres en edad reproductiva, frecuentemente asociado a insulinorresistencia (IR) y riesgo cardiovascular (RCV). El criterio de Rotterdam distingue 4 fenotipos: 3 presentan hiperandrogenismo clínico y/o bioquímico (HA) y uno es normo-androgénico (NHA). Por ser un síndrome heterogéneo, es necesario identificar a las pacientes con mayor RCV. Dos nuevos marcadores han sido propuestos para evaluarlo: el índice de adiposidad abdominal (VAI) y el producto de acumulación lipídica (LAP). Objetivo: Evaluar los marcadores LAP y VAI como predictores de IR y su correlación con los parámetros de RCV en relación con los fenotipos SOP. Metodología: Se estudió a 130 pacientes con SOP entre 18 y 36 años, clasificadas en 2 grupos: HA y NHA según la presencia de hiperandrogenismo clínico y/o bioquímico. Se evaluaron parámetros de RCV según ATP III: circunferencia de cintura (CC), glucemia, HDL, triglicéridos (TG) y presión arterial. Se calcularon: LAP = (CC [cm] - 58) * TG (mmol/l) y VAI = (CC [cm]/[36,58 + (1,89 * IMC [kg/m²]] * [TG [mg/dl]/0,81] * [1,52/HDL-c [mg/dl]]). Se realizaron curvas ROC/área bajo la curva para establecer valores de corte de LAP y VAI para la identificación de IR, análisis de correlación con parámetros de RCV y de las diferencias entre fenotipos, tomando como significativo p < 0,05. Resultados: Los valores de corte establecidos para definir IR fueron de 14,02 para LAP (especificidad: 93,22%; sensibilidad: 93,94%) y de 2,17 para VAI (especificidad: 91,38%; sensibilidad: 87,88). Dichos marcadores correlacionaron con marcadores de IR (HOMA-IR, QUICKI e índice glucosa/insulina) y presentaron una correlación positiva con TG, CC y negativa con HDL. El análisis entre fenotipos no reveló diferencias en la presencia de SM, IR o factores de RCV. Conclusión: LAP y VAI serían buenos predictores de IR y RCV asociado en pacientes jóvenes con SOP. El análisis de los parámetros entre fenotipos HA y NHA indica que ambos presentan similar riesgo metabólico y de desarrollar enfermedad cardiovascular.
Introduction: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. It is associated with insulin resistance (IR) and high cardiovascular risk (CVR). According to the Rotterdam consensus, four PCOS phenotypes could be established: three with clinical and/or biochemical hyperandrogenism (HA), and one non-hyperandrogenic (NHA). It is necessary to identify which of these patients are at risk of metabolic disturbances and CVR. Two indexes: lipid accumulation product (LAP) and visceral adiposity index (VAI) have been suggested as reliable markers of IR and CVR in PCOS. Objective: The present study aims to assess the reliability of LAP and VAI as IR markers in a young local population of PCOS patients. Their association with CVR parameters is also evaluated. Methodology: LAP and VAI were calculated in 130 PCOS patients. The PCOS patients were divided in two groups as HA and NHA, taking into account the signs of hyperandrogenism (clinical or biochemical). An evaluation was also made of the metabolic and anthropometric characteristics of the population and their association with CVR and IR. Results: Both LAP and VAI showed to be effective markers to asses CVR and IR in these PCOS women (cutoff values: LAP: 14.02 (sensitivity: 93.94% specificity: 93.22%) VAI: 2.17 (sensitivity: 87.88% specificity: 91.38%). There was a positive correlation of both markers with abdominal circumference and triglycerides (TG), and negative with HDL-cholesterol. The risk of IR and metabolic disturbances was similar in both phenotypes (NHA versus HA). Conclusion: Our data show that both LAP and VAI are representative markers for assessing IR and associated CVR in PCOS patients. These results also suggest that the NHA phenotype in the population studied shows the same risk of metabolic disturbances and cardiovascular disease when compared to HA phenotypes.
RESUMO
Objectives Primary aldosteronism (PA) is characterized by the autonomous overproduction of aldosterone. Its prevalence has increased since the use of the aldosterone (ALD)/plasma renin activity (PRA) ratio (ARR). The objective of this study is to determine ARR and ARC (ALD/plasma renin concentration ratio) cut-off values (COV) and their diagnostic concordance (DC%) in the screening for PA in an Argentinian population.Design multicenter prospective study.Subjects and methods We studied 353 subjects (104 controls and 249 hypertensive patients). Serum aldosterone, PRA and ARR were determined. In 220 randomly selected subjects, 160 hypertensive patients and 60 controls, plasma renin concentration (PRC) was simultaneously measured and ARC was determined.Results According to the 95th percentile of controls, we determined a COV of 36 for ARR and 2.39 for ARC, with ALD ≥ 15 ng/dL. In 31/249 hypertensive patients, ARR was ≥ 36. PA diagnosis was established in 8/31 patients (23/31 patients did not complete confirmatory tests). DC% between ARR and ARC was calculated. A significant correlation between ARR and ARC (r = 0.742; p < 0.0001) was found only with PRA > 0.3 ng/mL/h and PRC > 5 pg/mL. DC% for ARR and ARC above or below 36 and 2.39 was 79.1%, respectively.Conclusion This first Argentinian multicenter study determined a COV of 36 for ARR and 2.39 for ARC. Applying an ARR ≥ 36 in the hypertensive group, we confirmed PA in a higher percentage of patients than the previously reported one in our population. As for ARC, further studies are needed for its clinical application, since DC% is acceptable only for medium range renin values.
Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Hiperaldosteronismo/diagnóstico , Hipertensão/epidemiologia , Programas de Rastreamento/normas , Aldosterona/sangue , Argentina/epidemiologia , Hiperaldosteronismo/complicações , Hiperaldosteronismo/epidemiologia , Hipertensão/complicações , Prevalência , Estudos Prospectivos , Potássio/sangue , Radioimunoensaio , Padrões de Referência , Renina/sangue , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: Primary aldosteronism (PA) is characterized by the autonomous overproduction of aldosterone. Its prevalence has increased since the use of the aldosterone (ALD)/plasma renin activity (PRA) ratio (ARR). The objective of this study is to determine ARR and ARC (ALD/plasma renin concentration ratio) cut-off values (COV) and their diagnostic concordance (DC%) in the screening for PA in an Argentinian population.Design multicenter prospective study. SUBJECTS AND METHODS: We studied 353 subjects (104 controls and 249 hypertensive patients). Serum aldosterone, PRA and ARR were determined. In 220 randomly selected subjects, 160 hypertensive patients and 60 controls, plasma renin concentration (PRC) was simultaneously measured and ARC was determined. RESULTS: According to the 95th percentile of controls, we determined a COV of 36 for ARR and 2.39 for ARC, with ALD ≥ 15 ng/dL. In 31/249 hypertensive patients, ARR was ≥ 36. PA diagnosis was established in 8/31 patients (23/31 patients did not complete confirmatory tests). DC% between ARR and ARC was calculated. A significant correlation between ARR and ARC (r = 0.742; p < 0.0001) was found only with PRA > 0.3 ng/mL/h and PRC > 5 pg/mL. DC% for ARR and ARC above or below 36 and 2.39 was 79.1%, respectively. CONCLUSION: This first Argentinian multicenter study determined a COV of 36 for ARR and 2.39 for ARC. Applying an ARR ≥ 36 in the hypertensive group, we confirmed PA in a higher percentage of patients than the previously reported one in our population. As for ARC, further studies are needed for its clinical application, since DC% is acceptable only for medium range renin values.
Assuntos
Hiperaldosteronismo/diagnóstico , Hipertensão/epidemiologia , Programas de Rastreamento/normas , Adolescente , Adulto , Idoso , Aldosterona/sangue , Argentina/epidemiologia , Feminino , Humanos , Hiperaldosteronismo/complicações , Hiperaldosteronismo/epidemiologia , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Potássio/sangue , Prevalência , Estudos Prospectivos , Radioimunoensaio , Padrões de Referência , Renina/sangue , Sensibilidade e Especificidade , Adulto JovemRESUMO
Neuroendocrine tumors (NET) include a spectrum of malignancies arising from neuroendocrine cells throughout the body. The objective of this clinical investigation of retrospectively and prospectively collected data was to describe the prevalence, demographic data, clinical symptoms and methods of diagnosis of NET and the treatment and long-term follow-up of patients with NET. Data were provided by the participating centers and assessed for consistency by internal reviewers. All the cases were centrally evaluated (when necessary) by the pathologists in our group. The tissue samples were reviewed by hematoxylin and eosin and immunohistochemical staining techniques to confirm the diagnosis of NET. In total, 532 cases were documented: 461 gastroenteropancreatic-NET (GEP-NET) and 71 bronchial NET (BNET). All the tumors were immunohistochemically defined according to the World Health Organization (WHO) and European Neuroendocrine Tumor Society criteria. The most common initial symptoms in GEP-NET were abdominal pain, diarrhea, bowel obstruction, flushing, gastrointestinal bleeding and weight loss. The most common tumor types were carcinoid (58.0%), non-functional pancreatic tumor (23.0%), metastatic NET of unknown primary (16.0%) and functional pancreatic tumor (3.0%). Of the BNET, 89.0% were typical and 11.0% atypical carcinoids. Of the patients with GEP-NET, 59.2% had distant metastasis at diagnosis. The locations of the primary tumors in GEP-NET were the small bowel (26.9%), pancreas (25.2%), colon-rectum (12.4%), appendix (7.6%), stomach (6.9%), esophagus (2.8%), duodenum (2.0%) and unknown primary (16.3%). The histological subtypes based on the WHO classification were well-differentiated NET (20.1%), well-differentiated neuroendocrine carcinomas (66.5%) and poorly differentiated neuroendocrine carcinomas (10.3%). Overall, 67.3% of the patients underwent surgery, 41.2% with curative intent and 26.1% for palliative purposes. The 5-year survival rates were 65.1% (95% confidence interval, 58.0-71.4%) in GEP-NET and 100.0% in typical carcinoid of the lung. This observational, non-interventional, longitudinal study aimed to accumulate relevant information regarding the epidemiology, clinical presentation and current practices in the treatment of NET patients in Argentina, providing insight into regional differences and patterns of care in this heterogeneous disease.
RESUMO
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency accounts for 90%-95% of cases. This autosomal recessive disorder has a broad spectrum of clinical forms, ranging from severe or classical, which includes the salt-wasting and simple virilizing forms, to the mild late onset or nonclassical form. Most of the disease-causing mutations described are likely to be the consequence of nonhomologous recombination or gene conversion events between the active CYP21A2 gene and its homologous CYP21A1P pseudogene. Nevertheless, an increasing number of naturally occurring mutations have been found. The change p.H62L is one of the most frequent rare mutations of the CYP21A2 gene. It was suggested that the p.H62L represents a mild mutation that may be responsible for a more severe enzymatic impairment when presented with another mild mutation on the same allele. In this report, a 20-year-old woman carrying an isolated p.H62L mutation in compound heterozygosity with c.283-13A/C>G mutation is described. Although a mildly nonclassical phenotype was expected, clinical signs and hormonal profile of the patient are consistent with a more severe simple virilizing form of 21-hydroxylase deficiency. The study of genotype-phenotype correlation in additional patients would help in defining the role of p.H62L in disease manifestation.
RESUMO
OBJECTIVE: The aim of this study was to explore ß2-adrenoceptor (ADRB2) haplotype associations with phenotypes and quantitative traits related to insulin resistance (IR) and the metabolic syndrome (MS) in a polycystic ovary syndrome (PCOS) population. A secondary purpose was to assess the association between ADRB2 haplotype and PCOS. DESIGN: Genetic polymorphism analysis. Cross-sectional case-control association study. SETTING: Medical University Hospital and research laboratory. PATIENTS: One hundred and sixty-five unrelated women with PCOS and 116 unrelated women without PCOS (control sample). MEASUREMENTS: Clinical and biochemical measurements, and ADRB2 genotyping in PCOS patients and control subjects. METHODS: ADRB2 haplotypes (comprising rs1042711, rs1801704, rs1042713 and rs1042714 in that order), genotyping and statistical analysis to evaluate associations with continuous variables and traits related to IR and MS in a PCOS population. Associations between ADRB2 haplotypes and PCOS were also assessed. RESULTS: We observed an age-adjusted association between ADRB2 haplotype CCGG and lower insulin (P = 0·018) and HOMA (P = 0·008) in the PCOS sample. Interestingly, the expected differences in surrogate measures of IR between cases and controls were not significant in CCGG/CCGG carriers. In the case-control study, genotype CCGG/CCGG was associated with a 14% decrease in PCOS risk (P = 0·043), taking into account confounding variables. CONCLUSIONS: Haplotype I (CCGG) has a protective role for IR and MS in PCOS.